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pubmed_75_17613
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From January 1982 through December 1983, 83 severely injured and hypovolemic patients were immediately resuscitated with uncrossmatched packed red cells. Seventy-four patients received 250 units (3.3 units/pt) of Group O red blood cells (TOB), and nine patients received 27 units of type-specific blood (TSB) (3.0 units/pt). Additionally, 53 units of TSB were transfused to the TOB group in the interval between TOB immediate transfusion and the availability of fully crossmatched blood. A total of 880 units (10.6 units/pt) were transfused without instance of transfusion reaction or subsequent crossmatching difficulty. The protocol called for two units of TOB (Rh positive for males, Rh negative for females) to be delivered to the resuscitation area before patient arrival. The decision to transfuse TOB was left to the surgeon in charge and was based on the clinical impression of severe shock. Thirty-eight per cent (31 patients) met the criteria of requiring a 'massive transfusion' (greater than 10 units within 24 hours). Overall, 28 patients (31%) died, 22 within hours of arrival. No death was attributable to transfusion reaction or blood incompatibility. Complications included one dysrhythmia, six patients developed ARDS (7.2%), and ten patients (12%) had 'DIC'. Two patients developed positive hepatitis screens, and there was one clinical case of hepatitis observed. None of the 'DIC' cases were related to incompatible blood transfusion. We conclude that for immediate trauma resuscitation, TOB is safe and TOB has additional advantages over TSB or Type O whole blood transfusion.(ABSTRACT TRUNCATED AT 250 WORDS)
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10.1097/00005373-198610000-00006
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pubmed_358_13635
|
Using whole blood sample, we examined the correlation between concentration of granulocyte elastase (GEL) in granulocyte obtained by immunoassay and white blood cell counts. The correlation between concentration of GEL and granulocyte cell counts was also examined. The correlation coefficient between concentration of GEL and white blood cell counts was R = 0.87, and that between concentration of GEL and granulocyte cell counts was R = 0.91. The correlation coefficients of outpatients and patients with diseases accompanied by inflammation except for tumors were better than those of inpatients. The GEL concentration in granulocyte using whole blood sample well responded to the white blood cell counts against the tolerance for a short time, such as after operations. Especially on screening tests of diseases accompanied by inflammation and primary care, analysis of GEL in whole blood is not only useful for observation of inflammation and its progress but also suggests possibility of converting GEL to white blood cell counts or granulocyte. Furthermore, because it can be measured by easy-operative latex agglutination turbidimetric method, an easy measurement system can be built. Extended usage of the system as a rapid diagnostic tool on emergency tests in general clinics and hospitals are expected.
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pubmed_358_13635
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pubmed_291_2298
|
BACKGROUND
Hip osteoarthritis (OA) is a common condition leading to pain, disability and reduced quality of life. There is currently limited evidence to support the use of conservative, non-pharmacological treatments for hip OA. Exercise and manual therapy have both shown promise and are typically used together by physiotherapists to manage painful hip OA. The aim of this randomised controlled trial is to compare the efficacy of a physiotherapy treatment program with placebo treatment in reducing pain and improving physical function.
METHODS
The trial will be conducted at the University of Melbourne Centre for Health, Exercise and Sports Medicine. 128 participants with hip pain greater or equal to 40/100 on visual analogue scale (VAS) and evidence of OA on x-ray will be recruited. Treatment will be provided by eight community physiotherapists in the Melbourne metropolitan region. The active physiotherapy treatment will comprise a semi-structured program of manual therapy and exercise plus education and advice. The placebo treatment will consist of sham ultrasound and the application of non-therapeutic gel. The participants and the study assessor will be blinded to the treatment allocation. Primary outcomes will be pain measured by VAS and physical function recorded on the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) immediately after the 12 week intervention. Participants will also be followed up at 36 weeks post baseline.
CONCLUSIONS
The trial design has important strengths of reproducibility and reflecting contemporary physiotherapy practice. The findings from this randomised trial will provide evidence for the efficacy of a physiotherapy program for painful hip OA.
|
10.1186/1471-2474-11-238
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pubmed_767_3906
|
Electric activity of brain gets disturbed prior to epileptic seizure onset. Early prediction of an upcoming seizure can help to increase effectiveness of antiepileptic drugs. The scalp electroencephalogram signals contain information about the dynamics of brain and have been used to predict an upcoming seizure and localise its zone. The objective of this paper is to localise the epileptogenic region and predict an upcoming seizure at the earliest. To localise epileptogenic region, Electroencephalogram signals are categorised into four regions of brain (Frontal, Temporal, Parietal and Central). For each signal seventy-two (72) parameters in frequency domain have been extracted by using ten minute non overlapping window. Four prominent ratio parameters, γ1/γ5, γ3/γ1, θ/γ2 and γ4/θ have been identified as best parameters based on relative fisher score. Zone 2 shows the highest change in all the parameters as compared to the other zones. So, temporal region is identified as the epileptogenic region in this work. For prediction of the epileptic seizure machine learning algorithm artificial neural network (ANN) is proposed. The proposed machine learning algorithm has an accuracy of 92.3%, sensitivity of 100% and specificity of 83.3%.
|
10.1080/03091902.2018.1464074
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pubmed_958_9692
|
INTRODUCTION AND OBJECTIVES
Hearts exposed to reversible ischemia stand a subsequent prolonged episode of coronary artery occlusion (ischemic preconditioning) better. The reduction of infarct size by means of preconditioning has been amply demonstrated, but the relationship between preconditioning and contractile function remains less well defined. In this study we assess the effect of a later ischemia on the regional contractility in a stunned-preconditioned myocardium.
METHODS
We analyze the shortening fraction in the ischemic (dependent on the left anterior descending coronary artery), periischemic and control zone (dependent on the left circumflex coronary artery), using chronic implants of ultrasonic crystals in 17 adult mongrel dogs. In the control series, we quantified the effects of partial (30-60% reduction of coronary flow from the basal) and transitory (15 minutes) ischemic episode in the regional myocardial function in a "virgin" myocardium. In two other series, the myocardium was previously stunned-preconditioned through brief and repeated ischemias. Afterwards, at 5th day (series B) and at 15th day (series C), the dogs were subjected to ischemic episode similar to control ones.
RESULTS
After comparing the results with the control series, we observed that the shortening fraction of the ischemic zone was decreased by 107% (p < 0.01) during partial ischemic episode when it was induced on the 5th day of the stunning-preconditioning (series B).
CONCLUSIONS
In dogs, the brief and repeated episodes of ischemia could condition the contractile function so that a later partial and transitory reduction of coronary flow could induce a severe affectation of contractility expressed as a diskinetic area.
|
10.1016/s0300-8932(99)74941-9
|
pubmed_21_12419
|
The clinical relevance of Acinetobacter species, other than A. baumannii, as human pathogens has not been sufficiently assessed owing to the insufficiency of simple phenotypic clinical diagnostic laboratory tests. Infections caused by these organisms have different impacts on clinical outcome and require different treatment and management approaches. It is therefore important to correctly identify Acinetobacter species. Matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) has been introduced to identify a wide range of microorganisms in clinical laboratories, but only a few studies have examined its utility for identifying Acinetobacter species, particularly those of the non-Acinetobacter baumannii complex. We therefore evaluated MALDI-TOF MS for identification of Acinetobacter species by comparing it with sequence analysis of rpoB using 123 isolates of Acinetobacter species from blood. Of the isolates examined, we identified 106/123 (86.2%) to species, and 16/123 (13.0%) could only be identified as acinetobacters. The identity of one isolate could not be established. Of the 106 species identified, 89/106 (84.0%) were confirmed by rpoB sequence analysis, and 17/106 (16.0%) were discordant. These data indicate correct identification of 89/123 (72.4%) isolates. Surprisingly, all blood culture isolates were identified as 13 species of Acinetobacter, and the incidence of Acinetobacter pittii was unexpectedly high (42/123; 34.1%) and exceeded that of A. baumannii (22/123; 17.9%). Although the present identification rate using MALDI-TOF MS is not acceptable for species-level identification of Acinetobacter, further expansion of the database should remedy this situation.
|
10.1111/1469-0691.12376
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pubmed_977_19155
|
INTRODUCTION
Ex-preterm infants with severe bronchopulmonary dysplasia (BPD) sometimes require long-term ventilation (LTV) to facilitate weaning from respiratory support. There are however limited data characterizing this cohort. We aim to describe the background characteristics, neonatal comorbidities, characteristics at the initiation of ventilation, and outcomes of neonatal unit graduates with BPD established on LTV.
METHODS
A retrospective cohort study of infants born <32 weeks gestation with BPD referred to a regional LTV service between January 2015 and December 2020.
RESULTS
Twenty-five infants were referred during the study period. Median birth gestation was 26 + 1 weeks (24 + 0-30 + 4) and birth weight 645 g (430-1485). At 36 weeks postmenstrual age (PMA), median FiO<sub>2</sub> was 0.45 (0.24-0.80) and one-quarter of infants remained on invasive ventilation. Twenty (80%) infants were established on noninvasive ventilation (NIV), with the smallest weighing 2085 g, and five (20%) required tracheostomy invasive ventilation (TIV). At initiation of NIV/TIV, median PMA was 41 + 1 weeks and median FiO<sub>2</sub> 0.40 (0.29-0.80). Infants established on TIV spent almost five times longer in hospital before discharge compared to those on NIV (p = 0.003). By March 2022, 18 (72%) infants had discontinued ventilation, spending a median total time of 113 days (18-1792) on ventilation.
CONCLUSION
Due to advances in interfaces, headgear, and ventilator technology, NIV is an attractive and practically achievable option for infants with severe BPD as small as 2 kg. Initiation and weaning should take place in a facility with the required multidisciplinary expertize.
|
10.1002/ppul.26072
|
pubmed_174_1770
|
Although responses of BALB/c mice to TNP-Ficoll or TNP-Brucella abortus are usually decreased by injection of allo anti-IgD (anti-Igh-5a) given 1 day before antigen, increased responses are obtained if a lymphokine mixture (SN) containing IL 2 is also injected. Simultaneous injection of anti-IgD and SN 4 days after priming with TNP-KLH induces an increase in antibody production similar to that induced by a second antigen injection. Injected together with a second injection of TNP-KLH at that time, anti-IgD and SN cause a synergistic enhancement of the secondary response. In allotype heterozygous (BALB/c X SJL)F1 mice injected with anti-IgD directed against one allotype, this enhancement of the secondary response is seen predominantly in the alternate allotype, because the IgG response of linked allotype specificity is slightly suppressed by the anti-IgD alone and is less enhanced than the alternate allotype by anti-IgD plus SN. Cells from unprimed heterozygous mice, incubated with anti-Igh-5a in vitro and transferred, together with antigen, to TNP-KLH-primed recipients, cause a much greater enhancement of the IgG responses of the Igb than of the Iga allotype in recipients. If, however, SN is also injected into the recipients, the anti-TNP response of both IgG allotypes is greatly enhanced.
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pubmed_174_1770
|
pubmed_959_22949
|
INTRODUCTION
The outbreak of the coronavirus disease 2019 (COVID-19) poses an unprecedented challenge to healthcare workers (HCWs) globally. This study investigated potential factors related to depression, anxiety, and stress in a sample of Chinese HCWs during the peak of the COVID-19 epidemic.
METHODS
An online survey was distributed to Chinese HCWs using respondent-driven sampling. Data were collected between February 13th and February 20th, 2020, immediately following the COVID-19 contagion peak in Hubei. A total of 1208 respondents were eligible for analysis. Mental health problems and social support were measured by the Depression Anxiety Stress Scales-21 (DASS-21) and the Perceived Social Support Scale (PSS).
RESULTS
The prevalence rates of depression, (DASS-depression > 9) anxiety (DASS-anxiety > 7) and stress (DASS-stress > 14) were 37.8%, 43.0% and 38.5%, respectively. Multivariate logistic regressions revealed that stress, anxiety, and depression were positively related to lower levels of social support, longer working hours, discrimination experience and workplace violence. The scarcity of medical equipment was correlated with increased stress and depression. Chinese HCWs working at COVID 19 designated hospitals were more likely to report anxiety. Additionally, volunteering to work in the frontline health facilities was inversely associated with depression.
CONCLUSION
Mental health problems among Chinese HCWs were alarming during the peak of the COVID-19 epidemic. Health facilities require appropriate and standing services that address the mental health of healthcare workers, particularly during epidemic outbreaks.
|
10.2147/PRBM.S290931
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pubmed_795_13982
|
Notch receptors are single transmembrane receptors that contain a large number of epidermal growth factor-like repeats (EGF repeats) in their extracellular domains. Mutations in the EGF repeats of the human Notch 3 receptor lead to the vascular dementia disease Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL). The vast majority of CADASIL mutations are missense mutations removing or inserting cysteine residues in the EGF repeats, but it is not yet clear whether these mutations primarily affect receptor trafficking, maturation, andor signaling. To address this issue, we have generated and analyzed stable cell lines expressing either wild-type murine Notch 3 (mNotch 3) or the mutant mNotch 3(R142C), which corresponds to the prevalent CADASIL form of Notch 3, Notch 3(R141C) in humans. We find that a lower proportion of mNotch 3(R142C) is expressed in the site 1-cleaved configuration, and that reduced amounts of mNotch 3(R142C) appear at the cell surface, as compared with wild-type mNotch 3. This observation is accompanied by a higher propensity for mNotch 3(R142C) to form intracellular aggregates, which may be a result of increased accumulation or slowed transport in the secretory pathway. In contrast to the impaired cell surface expression, mNotch 3(R142C) signals equally well in response to Delta 1 and Jagged 1 as wild-type mNotch 3. Taken together, these data suggest that trafficking and localization rather than signaling of mNotch 3 are affected in mNotch 3(R142C).
|
10.1073/pnas.252624099
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pubmed_1125_23423
|
Image charge detection has been used to measure the charge and velocity of individual electrosprayed water droplets. With a positive bias on the electrospray needle the majority of the droplets are, as expected, positively charged. However, a small fraction, surprisingly, carry a negative charge. Plausible explanations for the presence of the negatively charged droplets are discussed. In particular, we consider the possibility of the negatively charged droplets resulting from a bipolar fission process where the incorporation of a small negatively charged droplet between two larger positively charged progeny lowers the energy barrier for symmetric fission.
|
10.1021/jp064581b
|
pubmed_289_18297
|
BACKGROUND
Exaggerated and prolonged inflammation after myocardial infarction (MI) accelerates left ventricular remodeling. Inflammatory pathways may present a therapeutic target to prevent post-MI heart failure. However, the appropriate magnitude and timing of interventions are largely unknown, in part because noninvasive monitoring tools are lacking. Here, we used nanoparticle-facilitated silencing of CCR2, the chemokine receptor that governs inflammatory Ly-6C(high) monocyte subset traffic, to reduce infarct inflammation in apolipoprotein E-deficient (apoE(-/-)) mice after MI. We used dual-target positron emission tomography/magnetic resonance imaging of transglutaminase factor XIII (FXIII) and myeloperoxidase (MPO) activity to monitor how monocyte subset-targeted RNAi altered infarct inflammation and healing.
METHODS AND RESULTS
Flow cytometry, gene expression analysis, and histology revealed reduced monocyte numbers and enhanced resolution of inflammation in infarcted hearts of apoE(-/-) mice that were treated with nanoparticle-encapsulated siRNA. To follow extracellular matrix cross-linking noninvasively, we developed a fluorine-18-labeled positron emission tomography agent ((18)F-FXIII). Recruitment of MPO-rich inflammatory leukocytes was imaged with a molecular magnetic resonance imaging sensor of MPO activity (MPO-Gd). Positron emission tomography/magnetic resonance imaging detected anti-inflammatory effects of intravenous nanoparticle-facilitated siRNA therapy (75% decrease of MPO-Gd signal; P<0.05), whereas (18)F-FXIII positron emission tomography reflected unimpeded matrix cross-linking in the infarct. Silencing of CCR2 during the first week after MI improved ejection fraction on day 21 after MI from 29% to 35% (P<0.05).
CONCLUSION
CCR2-targeted RNAi reduced recruitment of Ly-6C(high) monocytes, attenuated infarct inflammation, and curbed post-MI left ventricular remodeling.
|
10.1161/CIRCULATIONAHA.112.000116
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pubmed_553_11941
|
Eight boys aged 10-12 years performed three tests on each of three treadmill protocols. Each test was a continuous, progressively graded performance to exhaustion, but protocols differed in speed--(walk: 90 m . min-1, jog: 110 m . min-1, run: 130 m . min-1). The walk protocol was found inappropriate for VO2 max determination in children. Compared to the faster speeds, the walk test elicited a lower VO2 at exhaustion, and had lower reliability (0.56) and a high coefficient of variation (8%). For the Vo2 at exhaustion on the jog and run protocols the coefficient of variation was 3-5% and the reliability coefficient averaged 0.90, comparable to values seen for repeated trials in adults. The usually accepted VO2 max criterion of a plateau of VO2 with increasing work levels was inappropriate for use with children. Attempts to derive plateau criteria suitable for use with children proved unsuccessful. Plateau criteria may be difficult to achieve with children in light of their apparently weaker glycolytic energy capacity. Nevertheless, the highest VO2 measured at jog or run speeds has a consistency similar to that found for Vo2 max measurement in adults.
|
10.1007/BF00421663
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pubmed_33_3683
|
This is an interesting paper of a 4 cm posttraumatic pseudolipoma on the back of the neck of an adult man who has participated in "tar barrel rolling" since adolescence. To the best of our knowledge, this is the first case of a pseudolipoma to be reported in the literature in association with tar barreling.
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10.1155/2012/130973
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pubmed_18_19296
|
Given the high proportion of water used for agriculture in certain regions, the economic value of agricultural water can be an important tool for water management and policy development. This value is quantified using economic demand curves for irrigation water. Such demand functions show the incremental contribution of water to agricultural production. Water demand curves are estimated using econometric or optimisation techniques. Calibrated agricultural optimisation models allow the derivation of demand curves using smaller datasets than econometric models. This paper introduces these subject areas then explores the effect of spatial aggregation (upscaling) on the valuation of water for irrigated agriculture. A case study from the Rio Grande-Rio Bravo Basin in North Mexico investigates differences in valuation at farm and regional aggregated levels under four scenarios: technological change, warm-dry climate change, changes in agricultural commodity prices, and water costs for agriculture. The scenarios consider changes due to external shocks or new policies. Positive mathematical programming (PMP), a calibrated optimisation method, is the deductive valuation method used. An exponential cost function is compared to the quadratic cost functions typically used in PMP. Results indicate that the economic value of water at the farm level and the regionally aggregated level are similar, but that the variability and distributional effects of each scenario are affected by aggregation. Moderately aggregated agricultural production models are effective at capturing average-farm adaptation to policy changes and external shocks. Farm-level models best reveal the distribution of scenario impacts.
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10.1016/j.scitotenv.2009.08.013
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pubmed_390_5733
|
The interaction of DNA and poly(A) with bis-(2-guanidoethyl)disulfide (GED) which is the most simple model of arginine containing proteins has been investigated by means of ultrasonic velocimetry. It has been shown that the association of GED with nucleic acids proceeds by two stages. The stoichiometric relationships and association constants for each of these stages are estimated. A mechanism of the binding is proposed.
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pubmed_390_5733
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pubmed_455_2503
|
OBJECTIVE
We explored the usefulness of intraoperative measurement of hypogastric artery (HGA) stump pressure (HGA-SP) and postoperative near infrared spectroscopy (NIRS) in evaluating buttock claudication (BC) after abdominal aortic aneurysm (AAA) repair.
DESIGN
Retrospective clinical study.
PATIENTS AND METHODS
Twenty patients who were undergoing AAA repair were enrolled. The HGA was ligated bilaterally in 5 patients, unilaterally in 12, and preserved in 3. The HGA-SP was measured intraoperatively. Postoperatively, NIRS was used to evaluate buttock muscle ischemia during walking.
RESULTS
Six patients had unilateral and 1 bilateral BC after AAA repairs. The median HGA-SP brachial pressure index (HBI) was 0.62 (range: 0.45-0.64) in 8 claudicating buttocks and 0.76 (range: 0.63-0.90) in 13 asymptomatic buttocks (p < 0.0005). The HBI was <0.65 in all claudicating buttocks, whereas it was >0.63 in asymptomatic buttocks. In all 8 claudicating buttocks, NIRS showed the ischemic pattern with recovery time lasting more than 240 s.
CONCLUSIONS
An HBI below 0.65 may be a predictor of BC after AAA repair. NIRS appears to be a useful noninvasive method for evaluating BC after AAA.
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10.1053/ejvs.2002.1870
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pubmed_187_15397
|
A 61-year-old-male with local advanced inoperable cervical esophageal cancer (squamous cell carcinoma, T4N1M0 stage III) was treated by concurrent radiochemotherapy. A dose of 50.6 Gy/46 Fr/36 days and one course each of CDDP-5-FU and nedaplatin-5-FU were delivered safely. Radical surgery could be performed thereafter because of the good tumor response. Pathological CR was obtained in metastatic cervical lymph nodes and almost total necrosis in primary cancer. Concurrent radiochemotherapy produced a significant improvement in this case of advanced cervical esophageal cancer.
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pubmed_187_15397
|
pubmed_1110_19303
|
Arteriovenous fistula is the preferred option for vascular access in hemodialysis patients. The aim of this study was to assess different follow-up methods for hemodialysis patients in our hemodialysis center in China. A cohort of 124 patients with stage 3 chronic kidney disease was recruited and double-blind randomly assigned into two groups. Patients in Group A received phone calls to schedule their next consultation a week in advance. Patients in Group B scheduled their next appointment at the end of each visit. A total of 116 patients were included in the study and eight dropped out. Twenty-seven patients (46.4%) in Group A and 13 patients (22.4%) in Group B had an AVF prior to hemodialysis (P = 0.006), and 44.8% of patients in Group A and 15.5% of patients in Group B were using AVFs at the initiation of dialysis (P = 0.003). Sixteen patients (27.6%) in Group A and 24 patients (41.3%) in Group B required central venous catheters due to acute on chronic kidney disease and 13 patients (22.4%) in Group A and 21 patients (36.2%) in Group B required central venous catheters due to patient-related delays (P = 0.02). At the end of the study, seven patients in Group A died and 17 patients in Group B died (P = 0.027). The patients who received phone calls to schedule appointments in advance had a higher rate of arteriovenous fistulas prior to dialysis and at hemodialysis initiation had a reduced incidence of acute on chronic kidney disease and patient-related delays, and had an improved prognosis.
|
10.1111/1744-9987.12646
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pubmed_6_9479
|
Recently, accumulating preclinical findings suggest the possibility that functional abnormalities of tripartite synaptic transmission play important roles in the pathophysiology of schizophrenia and affective disorder. Therefore, to explore the novel mechanisms of mood-stabilizing effects associated with tripartite synaptic transmission, the present study determined the effects of mood-stabilizing antipsychotics, clozapine (CLZ), quetiapine (QTP) and brexpiprazole (BPZ), on the astroglial l-glutamate release and expression of connexin43 (Cx43) in the astroglial plasma membrane using cortical primary cultured astrocytes. Neither acute (for 120 min) nor subchronic (for 7 days) administrations of CLZ, QTP and BPZ affected basal astroglial l-glutamate release, whereas both acute and subchronic administration of CLZ, QTP and BPZ concentration-dependently enhanced astroglial l-glutamate release through activated hemichannels. Subchronic administration of therapeutic-relevant concentration of valproate (VPA), a histone deacetylase inhibiting mood-stabilizing antiepileptic drug, enhanced the stimulatory effects of therapeutic-relevant concentration of CLZ, QTP and BPZ on astroglial l-glutamate release through activated hemichannel. Subchronic administration of therapeutic-relevant concentration of CLZ, QTP and BPZ did not affect Cx43 protein expression in the plasma membrane during resting stage. After subchronic administration of VPA, acute and subchronic administration of therapeutic-relevant concentrations of CLZ increased Cx43 protein expression in the plasma membrane. Both acute administrations of therapeutic-relevant concentrations of QTP and BPZ did not affect, but subchronic administrations enhanced Cx43 protein expression in the astroglial plasma membrane. Furthermore, protein kinase B (Akt) inhibitor suppressed the stimulatory effects of CLZ and QTP, but did not affect Cx43 protein expression in the astroglial plasma membrane. These results suggest that three mood-stabilizing atypical antipsychotics, CLZ, QTP and BPZ enhance tripartite synaptic glutamatergic transmission due to enhancement of astroglial Cx43 containing hemichannel activities; however, the Cx43 activating mechanisms of these three mood-stabilizing antipsychotics were not identical. The enhanced astroglial glutamatergic transmission induced by CLZ, QTP and BPZ is, at least partially, involved in the actions of these three mood-stabilizing antipsychotics.
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10.3390/ijms22115623
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pubmed_554_16992
|
The stability of molecular radicals containing main-group elements usually hinges on the presence of bulky substituents that shield the reactive radical center. We describe a family of Group 14 formazanate complexes whose chemical reduction allows access to radicals that are stabilized instead by geometric and electron-delocalization effects, specifically by the square-pyramidal coordination geometry adopted by the Group 14 atom (Si, Ge, Sn) within the framework of the heteroatom-rich formazanate ligands. The reduction potentials of the Si, Ge, and Sn complexes as determined by cyclic voltammetry become more negative in that order. Examination of the solid-state structures of these complexes suggested that their electron-accepting ability decreases with increasing size of the Group 14 atom because a larger central atom increases the nonplanarity of the ligand-based conjugated π-electron system of the complex. The experimental findings were supported by density-functional calculations on the parent complexes and the corresponding radical anions.
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10.1002/anie.201806097
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pubmed_720_4107
|
Objective: To understand the characteristics of adulthood weight change through the analysis on data from China Kadoorie Biobank (CKB) Study of 0.5 million adults from ten areas in China. Methods: An electronic questionnaire was used to collect the information about the body weight at age 25 years, social-demographic characteristics and lifestyle of the study subjects and their body weight were measured. After excluding the adults with self-reported histories of coronary heart disease, stroke, cancer or diabetes and those who had no data of body weight at age 25 years and those aged outside of 35-70 years, a total of 360 903 adults were included in the analysis. Adulthood weight change were defined as difference value between current body weight and body weight at age 25 years. Results: The mean adulthood weight change of the participants was 4.9 kg. The adults living in urban area showed more body weight increase compared with those living in rural area, so did the adults in northern area compared with those in southern area. Among the ten areas in China, Qingdao reported the highest adulthood weight increase (9.3 kg), and Gansu reported the lowest adulthood weight increase (1.5 kg). Older adults had higher BMI at early adulthood (25 years old), but the adults aged 45-50 years had the highest adulthood body weight increase. Adults with higher educational level, higher household income level, but lower physical activity level had more body weight increase, while current smokers, farmers and workers had less body weight increase. BMI at age 25 years was negatively associated with adulthood body weight change, but current BMI was positively associated with adulthood body weight change (P<0.001). Conclusion: Adulthood body weight change varied greatly among population with different demographic characteristics and lifestyle and in ten areas in China.
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10.3760/cma.j.issn.0254-6450.2019.05.004
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pubmed_263_22375
|
INTRODUCTION AND OBJECTIVES
Facial nerve monitoring is fundamental in the preservation of the facial nerve in vestibular schwannoma surgery. Our objective was to analyse the usefulness of facial nerve monitoring under partial neuromuscular blockade.
METHODS
This was a retrospective analysis of 69 patients operated in a tertiary hospital.
RESULTS
We monitored 100% of the cases. In 75% of the cases, we could measure an electromyographic response after tumour resection. In 17 cases, there was an absence of electromyographic response. Fifteen of them had an anatomic lesion with loss of continuity of the facial nerve and, in 2 cases, there was a lesion with preservation of the nerve. Preoperative facial palsy (29% 7%; P=.0349), large tumour size (88 vs. 38%; P=.0276), and a non-functional audition (88 vs. 51%; P=.0276) were significantly related with an absence of electromyographic response.
CONCLUSIONS
Facial nerve monitoring under neuromuscular blockade is possible and safe in patients without previous facial palsy. If the patient had an electromyographic response after tumour excision, they developed better facial function in the postoperative period and after a year of follow up.
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pubmed_263_22375
|
pubmed_32_17443
|
Restriction fragment analysis of mitochondrial DNA (mtDNA) was used to examine genetic variation and population structure in 13 species of banded-winged grasshoppers (subfamily Oedipodinae). Total DNA of 246 individuals was digested with 11 restriction enzymes and probed with three cloned EcoRI fragments representing the entire mitochondrial genome of Melanoplus sanguinipes. On average, members of this subfamily were five times more variable than those in another subfamily, Melanoplinae, previously examined. This would appear to lend support to Vickery's claim that the time of origin of Nearctic oedipodines is more ancient than that of melanoplines. With respect to population structure, a few different patterns were exhibited. Species such as Camnula pellucida had populations containing a mixture of haplotypes, some widespread and some geographically restricted. In contrast, Chortophaga viridifasciata populations were characterized by unique assemblages of diverse haplotypes. Phylogeographic hypotheses are advanced to account for these observations.
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10.1007/BF00554553
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pubmed_639_5385
|
Hyperspectral light detection and ranging (HSL) can acquire the spatial and spectral information simultaneously, which can provide more information than hyperspectral imaging and single band lidar. However, the echo intensity from targets is influenced by incident angle, and relative studies were still limited which result in the effect of incident angle on HSL not being completely understood. In this study, the incident angle effect in the whole band of HSL was analyzed and corrected. Then, five types of vegetation sample with different spectral characteristics were collected at the leaf level. Spectral range changing from 550 to 830 nm with a 1 nm spectral resolution was obtained. Lambert-Beckman model was applied to analyze the effect of the incident angle on the echo intensity. The experimental results demonstrated that the Lambert-Beckman model can efficiently apply in fitting the changing of echo intensity with incidence angle and efficiently eliminate the specular effect of target. In addition, the coefficient of variation ratio is significantly improved compared to the reference target-based model. The results illustrated that, compared to reference target-based model, the Lambert-Beckman model can efficiently explain and correct the incident angle effect with specular reflection in HSL. In addition, it was found that the specular fraction Ks, which is reduced with the increasing of reflectance, is dominating the incident angle effect in the whole band, while roughness m keeps stable at different wavelengths. Thus, this research will provide notably advanced insight into correcting the echo intensity of HSL.
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10.1364/OE.420468
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pubmed_431_15859
|
Termination translation in Saccharomyces cerevisiae is controlled by two interacting polypeptide chain release factors, eRF1 and eRF3. Two regions in human eRF1, position at 281-305 and position at 411-415, were proposed to be involved on the interaction to eRF3. In this study we have constructed and characterized yeast eRF1 mutant at position 410 (correspond to 415 human eRF1) from tyrosine to serine residue resulting eRF1(Y410S). The mutations did not affect the viability and temperature sensitivity of the cell. The stop codons suppression of the mutant was analyzed in vivo using PGK-stop codon-LACZ gene fusion and showed that the suppression of the mutant was significantly increased in all of codon terminations. The suppression on UAG codon was the highest increased among the stop codons by comparing the suppression of the wild type respectively. In vitro interaction between eRF1 (mutant and wild type) to eRF3 were carried out using eRF1-(His)6 and eRF1(Y410S)-(His)6 expressed in Escherichia coli and indigenous Saccharomyces cerevisiae eRF3. The results showed that the binding affinity of eRF1(Y410S) to eRF3 was decreased up to 20% of the wild type binding affinity. Computer modeling analysis using Swiss-Prot and Amber version 9.0 programs revealed that the overall structure of eRF1(Y410S) has no significant different with the wild type. However, substitution of tyrosine to serine triggered the structural change on the other motif of C-terminal domain of eRF1. The data suggested that increasing stop codon suppression and decreasing of the binding affinity of eRF1(Y410S) were probably due to the slight modification on the structure of the C-terminal domain.
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10.7150/ijbs.4.87
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pubmed_65_4345
|
In eukaryotic cells, the inactivation of the cyclic nucleotide signal depends on a complex array of cyclic nucleotide phosphodiesterases (PDEs). Although it has been established that multiple PDE isoenzymes with distinct catalytic properties and regulations coexist in the same cell, the physiological significance of this remarkable complexity is poorly understood. To examine the role of a PDE in cAMP signaling in vivo, we have inactivated the type 4 cAMP-specific PDE (PDE4D) gene, a mammalian homologue of the Drosophila dunce. This isoenzyme is involved in feedback regulation of cAMP levels. Mice deficient in PDE4D exhibit delayed growth as well as reduced viability and female fertility. The decrease in fertility of the null female is caused by impaired ovulation and diminished sensitivity of the granulosa cells to gonadotropins. These pleiotropic phenotypes demonstrate that PDE4D plays a critical role in cAMP signaling and that the activity of this isoenzyme is required for the regulation of growth and fertility.
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10.1073/pnas.96.21.11998
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pubmed_76_22571
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A study of the prevalence and intensity of malaria transmission in the lagunar area of Benin was carried out by means of repeated cross-sectional surveys of the child population. Six areas were selected: two urban areas of Cotonou, three lagunar villages and one savanna village. Slide positive rates and prevalence of antibodies to P. falciparum sporozoites were examined in June-July 1989 (long rainy season), October-November 1989 (short rainy season) and March-April 1990 (short dry season). Parasite rates in children 2 to 9 year-old showed holoendemic malaria, in the savanna village (89.4-94.2%) and hyperendemic malaria in the lagunar zone (60.7-83.5%). Levels of P. falciparum antisporozoite antibodies were higher in the sample from the periurban sector of Ladji compared with the nearby traditional lagunar villages and lowest in children living in the central urban sector. Cotonou had higher levels of malaria transmission compared with other West African cities.
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pubmed_76_22571
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pubmed_734_3014
|
Catalysts derived from pyrolysis of metal organic frameworks (MOFs) are promising candidates to replace expensive and scarce platinum-based electrocatalysts commonly used in polymer electrolyte membrane fuel cells. MOFs contain ordered connections between metal centers and organic ligands. They can be pyrolyzed into metal- and nitrogen-doped carbons, which show electrocatalytic activity toward the oxygen reduction reaction (ORR). Furthermore, metal-free heteroatom-doped carbons, such as N-F-Cs, are known for being active as well. Thus, a carbon material with Co-N-F doping could possibly be even more promising as ORR electrocatalyst. Herein, we report the mechanochemical synthesis of two polymorphs of a zeolitic imidazole framework, Co-doped zinc 2-trifluoromethyl-1H-imidazolate (Zn0.9Co0.1(CF3-Im)2). Time-resolved in situ X-ray diffraction studies of the mechanochemical formation revealed a direct conversion of starting materials to the products. Both polymorphs of Zn0.9Co0.1(CF3-Im)2 were pyrolyzed, yielding Co-N-F containing carbons, which are active toward electrochemical ORR.
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10.3389/fchem.2022.840758
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pubmed_166_4472
|
OBJECTS
Meningioma is the most common intracranial neoplasm, comprising approximately 30% of all primary intracranial tumors (Claus et al., 2005) [1]. Treatment options include observation, microsurgical resection, stereotactic radiosurgery (SRS), and whole brain radiation therapy (WBRT). Gamma knife radiosurgery (GKRS) is a very effective treatment for intracranial meningiomas; previous studies showed the tumor control rate at 5-10 years of follow-up as 84.3%-100% in all cases (Feigl et al., 2005; Linskey et al., 2005; Malik et al., 2005; Aichholzer et al., 2000; Hakim et al., 1998; Chang and Adler 1997; Lunsford, 1994; Ganz et al., 1993) [2-9]. Many studies have discussed issues like optimal dose, conformal configurations, and adverse effects to improve the treatment result with GKRS (Malik et al., 2005; Kenai et al., 2005; Rowe et al., 2004; Shrieve et al., 2004) [4,10-12]. There are some cases in which the radiosurgery result is unfavorable and perhaps further treatment is needed. In these cases, re-radiosurgery can be an option. However, there have not been comprehensive studies discussing the issues of re-radiosurgery. Therefore, we analyzed the result of re-radiosurgery for recurrent meningiomas and their impact on clinical outcomes.
METHODS
From 1995 to 2015, we retrospectively reviewed 1163 patients who underwent GKRS for intracranial meningioma at the Asan Medical Center. Patients with multiple meningiomas or a follow-up with a period of less than a year were excluded from this study. Finally, 865 patients were enrolled in this study. Clinical symptoms and brain magnetic resonance imaging (MRI) scans were assessed by neurosurgeons. When tumor size increased together with newly developed neurologic symptoms, further management, such as microsurgical resection or SRS, was considered. Histologic analysis of the resected tumors was performed by neuropathologists. Clinical data, including patient's sex, age, and tumor locations were recorded. Treatment data included tumor volume, tumor grade, radiation dose, and presence of edema. Final outcome data including follow-up period, time to progression, interval between first and second radiosurgery courses and interval between microsurgery and radiosurgery were obtained.
RESULTS
Among 865 patients, tumor recurrence was found in 63 patients (7.28%). Seven patients showed transient tumor growth after GKRS. These patients have been under close observation without any further treatments. Fifty-six patients (6.47%) showed permanent tumor growth on follow-up MRI. Thirty-three patients from this group underwent repeated radiosurgery owing to tumor growth, resulting in a re-irradiation rate of 3.82% at our radiosurgery center. The other 23 patients were treated using methods other than re-radiosurgery. Among the 33 patients, 25 underwent microsurgical resection prior to their initial course of GKRS, and the other 8 were treated with re-radiosurgery only. An analysis was performed to determine factors that may have a role in treatment results. Of the many variables, tumor grade (p=0.004, Fisher's exact test) was the only significant factor for progression-free survival (PFS). Thirteen patients with unbiopsied or benign meningioma showed stable tumor size, while there was tumor growth in 8 patients. Among high-grade meningioma patients, 3 and 9 showed stable disease and tumor growth, respectively. As a result of re-radiosurgery, 11 out of 17 patients showed tumor growth and needed further treatments; this involved a third GKRS for 4 patients, microsurgical resection for 6 patients, and cyber knife radiosurgery (CKRS) for 1 patient. Four patients from this group were also treated with WBRT.
CONCLUSION
We analyzed the results of re-radiosurgery for recurrent meningiomas and observed that World Health Organization (WHO) grade II and III was significantly associated with a lower PFS rate compared with low-grade meningiomas (p=0.004). Conversely, patients with benign meningioma or unbiopsied tumors had much better results. Hence, re-radiosurgery is recommended for patients with unknown or benign meningiomas if their first GKRS result is unsatisfactory. However, re-radiosurgery should be considered carefully for recurrent high-grade tumors. Owing to the small number of recurrent meningioma patients treated with re-radiosurgery, further studies are required to delineate the role of this treatment.
|
10.1016/j.clineuro.2016.12.014
|
pubmed_225_15716
|
Malignant hyperthermia (MH) is an acute syndrome that occurs in genetically susceptible persons who have been exposed to certain anesthetic agents. It can also be induced by catecholamines activated by stress. One in 200 people is at risk for developing malignant hyperthermia. The mortality rate may be as high as 15%. A thorough history obtained before surgery is of extreme importance to prevent an MH crisis and in the management of those susceptible to the disorder. If MH is suspected a diagnosis, which can be confirmed by muscle biopsy, should be ruled out before surgery.
|
10.1097/00006416-199101000-00008
|
pubmed_239_20869
|
Essentials Reversal of anticoagulant effects of dabigatran may occur despite application of idarucizumab. Monitoring of dabigatran level after antidote application is crucial to detect rebound. Repeated doses of idarucizumab may be necessary in cases of massive dabigatran accumulation. Combination of antidote application and renal replacement therapy may offer additional benefit.
SUMMARY
Idarucizumab is a monoclonal antibody fragment designed for reversing the anticoagulant effects of dabigatran. Administration is recommended as two intravenous boluses of 2.5 g within 15 min of each other or as a single 5 g bolus. However, in certain situations a second dose of the drug could be necessary. We report the case of a 77-year-old man, treated with dabigatran for paroxysmal atrial fibrillation. He presented at our department with acute renal failure, concomitant massive dabigatran accumulation and subsequent acute gastrointestinal bleeding. Fifty minutes after the administration of idarucizumab, the dabigatran plasma concentration decreased from a peak of 1630 ng ml-1 to a level below the detection limit of 30 ng ml-1 and bleeding stopped. Eight hours after administration, the dabigatran plasma level started to increase up to 1560 ng ml-1 (96% of the maximum value obtained), accompanied by a further drop in hemoglobin. Concomitant hemodialysis and hemofiltration led to a continuous decrease in dabigatran plasma levels. However, sepsis and multiorgan failure ensued, which led to death. With this case report we raise the question of whether massive dabigatran accumulation requires repeated doses of idarucizumab, or alternatively, if the combination of antidote with hemodialysis/renal replacement therapy is advisable in order to remove circulating levels of dabigatran.
|
10.1111/jth.13706
|
pubmed_948_9661
|
Scratch tests (SCT) with powdered commercial spices were performed in 70 patients with positive skin tests to birch and/or mugwort pollens and celery. Positive SCT to aniseed, fennel, coriander and cumin--all from the same botanical family (Apiaceae) as celery--were observed in more than 24 patients. Spices from unrelated families (red pepper, white pepper, ginger, nutmeg, cinnamon) elicited positive immediate skin test reactions only in three of 11 patients. Specific serum IgE to spices (determined in 41 patients with positive RAST to celery) up to class 3 were seen especially in patients with celery-mugwort or celery-birch-mugwort association, and concerned various botanical families. Celery-birch association pattern was linked to positive reactions (RAST classes 1-2) to spices from the Apiaceae family only.
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10.1111/j.1398-9995.1991.tb04228.x
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pubmed_648_12090
|
Inactivating mutations in the copper transporter Atp7b result in Wilson's disease. The Atp7b-/- mouse develops hallmarks of Wilson's disease. The activity of several nuclear receptors decreased in Atp7b mice, and nuclear receptors are critical for maintaining metabolic homeostasis. Therefore, we anticipated that Atp7b mice would exhibit altered progression of diet-induced obesity, fatty liver, and insulin resistance. Following 10 wk on a chow or Western-type diet (40% kcal fat), parameters of glucose and lipid homeostasis were measured. Hepatic metabolites were measured by liquid chromatography-mass spectrometry and correlated with transcriptomic data. Atp7b-/- mice fed a chow diet presented with blunted body-weight gain over time, had lower fat mass, and were more glucose tolerant than wild type (WT) littermate controls. On the Western diet, Atp7b mice exhibited reduced body weight, adiposity, and hepatic steatosis compared with WT controls. Atp7b mice fed either diet were more insulin sensitive than WT controls; however, fasted Atp7b-/- mice exhibited hypoglycemia after administration of insulin due to an impaired glucose counterregulatory response, as evidenced by reduced hepatic glucose production. Coupling gene expression with metabolomic analyses, we observed striking changes in hepatic metabolic profiles in Atp7b mice, including increases in glycolytic intermediates and components of the tricarboxylic acid cycle. In addition, the active phosphorylated form of AMP kinase was significantly increased in Atp7b mice relative to WT controls. Alterations in hepatic metabolic profiles and nuclear receptor signaling were associated with improved glucose tolerance and insulin sensitivity as well as with impaired fasting glucose production in Atp7b mice.
|
10.1073/pnas.1914267117
|
pubmed_195_22414
|
OBJECTIVE
This research aims to assess apprentices' and trainees' work conditions, psychosocial factors at work, as well as health symptoms after joining the labor force.
BACKGROUND
Despite the fact that there are over 3.5 million young working students in Brazil,this increasing rate brings with it difficult working conditions such as work pressure, heavy workloads,and lack of safety training.
METHOD
This study was carried out in a nongovernmental organization (NGO) with 40 young members of a first job program in the city of São Paulo, Brazil. They filled out a comprehensive questionnaire focused on sociodemographic variables, working conditions,and health symptoms. Individual and collective semi-structured interviews were conducted. Empirical data analysis was performed using analysis of content.
RESULTS
The majority of participants mentioned difficulties in dealing with the pressure and their share of responsibilities at work. Body pains, headaches, sleep deprivation during the workweek, and frequent colds were mentioned. Lack of appropriate task and safety training contributed to the occurrence of work injuries.
CONCLUSION
Having a full-time job during the day coupled with evening high school attendance may jeopardize these people's health and future.
APPLICATION
This study can make a contribution to the revision and implementation of work training programs for adolescents. It can also help in the creation of more sensible policies regarding youth employment.
|
10.1177/0018720812463146
|
pubmed_554_23850
|
Spermatogenesis is a finely regulated process of germ cell multiplication and differentiation leading to the production of spermatozoa in the seminiferous tubules. Spermatogenesis can be divided into three parts: spermatocytogenesis, meiosis and spermiogenesis. During spermatocytogenesis, germ cells engage in a cycle of several mitotic divisions that increases the yield of spermatogenesis and to renew stem cells and produce spermatogonia and primary spermatocytes. Meiosis involves duplication and exchange of genetic material and two cell divisions that reduce the chromosome number and yield four haploid round spermatids. Spermiogenesis involves the differentiation of round spermatids into fully mature spermatozoa released into the lumin of seminiferous tubules. The seminiferous epithelium is composed of several generations of germ cells due to the fact that new generations of sperm cells engage in the spermatogenic process without waiting for the preceding generations to have completed their evolution and to have disappeared as spermatozoa into the lumen of the tubules. In bulls, the duration of the seminiferous epithelium cycle is 13.5 days. The total duration of spermatogenesis is 61 days, that is 4.5 times the duration of the cycle of the seminiferous epithelium. The spermatogenetic wave is used to describe the spatial arrangement of cell associations along the tubules. Several theories have been described to explain the renewal of spermatogonia. Depending on the model, there are five or six spermatogonial mitoses explaining the renewal of stem cells and the proliferation of spermatogonia. Daily sperm production and germ cell degeneration can be quantified from numbers of germ cells in various steps of development throughout spermatogenesis. Bulls have a lower efficiency of spermatogenesis than most species examined, but higher than that of humans.
|
10.1017/S1751731118000435
|
pubmed_950_23299
|
OBJECTIVE
To elucidate the impact of hearing loss on patient health literacy.
STUDY DESIGN
Prospective, cross-sectional study.
SETTING
Academic otology practice at a university hospital.
PATIENTS
Consecutive, adult, English-speaking patients.
MAIN OUTCOME MEASURES
Inadequate health literacy, defined as a composite score of less than or equal to nine on the brief health literacy screen (BHLS), was compared with patient hearing data utilizing the American Academy of Otolaryngology-Head and Neck Surgery (AAO-HNS) hearing classification. Secondary outcome measures included comparisons of inadequate BHLS scores according to patient demographic and clinical information.
RESULTS
There were 300 consecutive adult (>18 years old) patients evaluated with the BHLS at a university otology practice between February and March 2019. The median patient age was 60-years (range, 18-91 yr), a slight majority (160, 53.3%) were women, and most patients were White (241, 86.7%) and non-Hispanic (260, 91.6%). Overall, 9.7% of patients were found to have inadequate health literacy. Men had higher rates of inadequate health literacy as compared with women (13.6% versus 6.3%, odds ratio [OR] = 2.35, 95% confidence interval [CI] 1.06-5.25). Audiometric data was available for 284 (95%) patients, of which 235 (82.7%) had class A or B hearing and 49 (17.3%) had class C or D hearing. Patients with Class C or D hearing had a lower median composite BHLS score compared with patients with Class A or B hearing (11.6 versus 13.6, p < 0.0001) and an increased rate of inadequate health literacy (28.6% versus 4.7%, OR = 8.15, 95% CI 3.42-19.37). Increased age, female sex, and better hearing were independent predictors of higher BHLS scores on multivariable analysis.
CONCLUSIONS
Hearing loss is an independent risk factor for inadequate health literacy. Providers should be aware of this risk and consider implementing strategies to improve counseling for this at-risk group of patients.
|
10.1097/MAO.0000000000002713
|
pubmed_866_15742
|
Background
Teaching anatomy is an important but expensive part of the medical curriculum, potentially more than many countries can afford. In the search for efficient methods, cost-effectiveness is of utmost importance for such countries. The aim of this contribution is to provide a review of the literature on anatomy teaching methods, evaluating these for feasibility in resource-deprived countries.
Methods
A literature review was carried out to identify distinct approaches to anatomy teaching published in the period 2000-2014, using the databases of PubMed, Wiley Online Library, Elsevier, HINARI, Springer, and ERIC. The approaches found were compared against their conceptual, operational, technical, and economic feasibility and Mayer's principles of effective instruction.
Results
Our search yielded 432 papers that met the inclusion criteria. We identified 14 methods of teaching anatomy. Based on their conceptual feasibility, dissection and technology enhanced learning approaches appeared to have more benefits than others. Dissection has, besides benefits, many specific drawbacks. Lectures and peer teaching showed better technical and economic feasibility. Educational platforms, radiological imaging, and lectures showed the highest operational feasibility. Dissection and surgery were found to be less feasible with regard to operational, technical, and economic characteristics.
Discussion
Based on our findings, the most important recommendations for anatomy teaching in seriously resource-deprived countries include a combination of complementary strategies in 3 different moments, lecturing at the beginning, using virtual learning environment (for self-study), and at the end, using demonstration through prosected specimens and radiological imaging. This provides reasonable insights in anatomy through both dead and living human bodies and their virtual representations.
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10.4103/efh.EfH_272_17
|
pubmed_43_22576
|
Background: Helicobacter pylori (H. pylori), an important human pathogen, is classified as a human carcinogen. It is known to cause dyspepsia, peptic ulcers, and gastric cancer. Awareness regarding H. pylori infections in Saudi Arabia awaits investigation to reduce or even eliminate the infection that would ease the substantial burden of managing H. pylori among both malignant and non-malignant diseases. Aims: The study aims were to (1) assess the knowledge of H. pylori infection, testing, and management among undergraduate students in Saudi Arabia and (2) compare the H. pylori knowledge among health science and non-health science students. Methods: This study involved a cross-sectional online survey among 334 undergraduate students in health science and non-health science colleges at King Saud University, Saudi Arabia, using a valid and reliable author-developed survey. The survey had two sections: the socio-demographic factors and knowledge items regarding H. pylori. Data were collected during the 2019-2020 academic year. Data analysis included descriptive statistics, Chi-square, and Mann-Whitney U test. The knowledge scores were categorized as poor, fair, and good. Results: Less than 10% of the students in both groups had a good knowledge level about H. pylori. The comparison of the overall mean between both groups was non-significant. Moreover, the level of knowledge of the respondents was significantly associated with their university level (p < 0.001), family monthly income (p < 0.007), having heard about H. pylori infection (p < 000.1), and a previous history of H. pylori infection (p < 000.1). Conclusion: The overall knowledge level of Saudi undergraduate students about H. pylori infection was low. Thus, health awareness interventions through educational programs are recommended for improving their knowledge about H. pylori infection and its prevention.
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10.3390/ijerph18158173
|
pubmed_1104_14828
|
Phase variation through slippage-like mechanisms involving homopolymeric tracts depends in part on the absence of Dam-methylase in several pathogenic isolates of Neisseria meningitidis. In Dam-defective strains drg (dam-replacing gene), flanked by pseudo-transposable small repeated elements (SREs), replaced dam. We demonstrate that drg encodes a restriction endonuclease (NmeBII) that cleaves 5'-GmeATC-3'. drg is also present in 50% of Neisseria lactamica strains, but in most of them it is inactive because of the absence of an SRE-providing promoter. This is associated with the presence of GATmeC, suggesting an alternative restriction-modification system (RM) specific for 5'-GATC-3', similar to Sau3AI-RM of Staphylococcus aureus 3A, Lactococcus lactis KR2 and Listeria monocytogenes.
|
10.1016/s0014-5793(01)02388-2
|
pubmed_333_7298
|
Inadequately aerated Escherichia coli B/r cultures did not shut their respiration off 60 min after ultraviolet light (52 M/m2 at 254 nm) as they did when well supplied with oxygen. Since cessation of respiaration is associated with cell death, the result suggested that oxygen toxicity by superoxide radicals generated by cell metabolism might be responsible for cell death. The specific activity of superoxide dismutase, which scavenges O2- radicals, increased twofold after 90 min of adequate aeration, but the specific activity of catalase remained constant. Respiration and viability of irradiated cells were affected not at all by the presence of superoxide dismutase and only slightly by the presence of catalase. Metal ions such as Mn2+ and Fe2+ inducers of superoxide dismutase, had no effect on respiration and viability. When irradiated cells were incubated under N2 for 90 min, the respiration, growth, and viability time-course responses were the same as for the cells not exposed to anareobiosis. We conclude that superoxide anions generated at the time of irradiation play no part in cessation delays the ultraviolet light-induced synthesis of proteins responsible for the irreversible cessation of respiration.
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10.1128/jb.129.2.714-717.1977
|
pubmed_83_22259
|
Introduction
Direct-acting oral anticoagulant (DOAC) prescriptions have increased steadily since the first, dabigatran, was Food and Drug Administration-approved in 2010. They have multiple advantages over vitamin K antagonists including fixed dosing without coagulation lab monitoring, rapid onset and offset of action, and fewer drug and food interactions. Patient-specific dosing, administration education, adherence, and monitoring are critically important. Many providers are unfamiliar with these concepts and too often use DOACs for off-label indications or at off-label dosing. A DOAC workshop was created to address knowledge gaps and improve internal medicine resident prescribing confidence.
Methods
One author (Irsk Anderson) conducted four 1-hour DOAC workshops with 49 total internal medicine residents rotating on their outpatient clinical rotation between October 2018 and November 2019. Residents performed small-group learning around four DOAC-specific cases, followed by a large-group report-out session. The residents completed pre- and postworkshop multiple-choice questions (MCQs) to assess knowledge as well as a postworkshop DOAC confidence self-assessment.
Results
Resident knowledge, assessed by percentage of residents answering correctly, improved significantly for all four MCQs after completing the workshop (all p <.003). Resident confidence, assessed on a 5-point Likert scale, improved significantly for all five themes (p <.001). Overall resident satisfaction was high (M = 4.2 on a 5-point Likert scale) and 85% desired further DOAC training.
Discussion
A 1-hour DOAC workshop was feasible and improved internal medicine resident knowledge and self-confidence. Future work should assess behavior change and patient clinical outcomes.
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10.15766/mep_2374-8265.10981
|
pubmed_474_2340
|
It was found in the experiments with rats that in response to carminomycin administration in a single LD50 and the therapeutic doses during the treatment course the intracellular fond of the amino acids in the liver tissue increased, the autolytic processes activated, the activity of the transamination enzymes, histidine and ammonia lyases increased. The level of the residual nitrogen increased mainly at the expense of increased ammonia production and urea levels. These changes were more pronounced when the antibiotic was administered in LD50. Independent of the administration multiplicity and the antibiotic dosage they were of reversible nature and mainly disappeared by the end of the observation.
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pubmed_474_2340
|
pubmed_584_15322
|
Acetylcholine has long been known to excite sympathetic neurons via M1 muscarinic receptors through an inhibition of M-currents. Nevertheless, it remained controversial whether activation of muscarinic receptors is also sufficient to trigger noradrenaline release from sympathetic neurons. In primary cultures of rat superior cervical ganglia, the muscarinic agonist oxotremorine M inhibited M-currents with half-maximal effects at 1 microM and induced the release of previously incorporated [3H]noradrenaline with half-maximal effects at 10 microM. This latter action was not affected by the nicotinic antagonist mecamylamine which, however, abolished currents through nicotinic receptors elicited by high oxotremorine M concentrations. Ablation of the signalling cascades linked to inhibitory G proteins by pertussis toxin potentiated the release stimulating effect of oxotremorine M, and the half-maximal concentration required to stimulate noradrenaline release was decreased to 3 microM. Pirenzepine antagonized the inhibition of M-currents and the induction of release by oxotremorine M with identical apparent affinity, and both effects were abolished by the muscarinic toxin 7. These results indicate that one muscarinic receptor subtype, namely M1, mediates these two effects. Retigabine, which enhances M-currents, abolished the release induced by oxotremorine M, but left electrically induced release unaltered. Moreover, retigabine shifted the voltage-dependent activation of M-currents by about 20 mV to more negative potentials and caused 20 mV hyperpolarisations of the membrane potential. In the absence of retigabine, oxotremorine M depolarised the neurons and elicited action potential discharges in 8 of 23 neurons; in its presence, oxotremorine M still caused equal depolarisations, but always failed to trigger action potentials. Action potential waveforms caused by current injection were not affected by retigabine. These results indicate that the inhibition of M-currents is the basis for the stimulation of transmitter release from sympathetic neurons via M1 muscarinic receptors.
|
10.1113/jphysiol.2003.052449
|
pubmed_894_17428
|
Ca-activated K-currents (IC) in sympathetic neurones have been triggered by intracellular Ca-injection or by activating ICa. IC is strongly voltage-dependent, with a peak slope of 11 mV/e-fold depolarization above -50 mV. Relaxation, fluctuation and single channel analysis suggests this to result from voltage-dependent opening and closing rates. Time-constants for channel opening and closing are about 15 msec near zero mV. Single channel conductance is about 100 pS. Currents can be blocked by TEA. IC is activated very rapidly (less than or equal to 5 msec) and sometimes transiently by a depolarizing voltage-step. It is suggested that IC contributes to both spike repolarization and spike after-hyperpolarization. Spontaneous miniature ICs have also been recorded, probably activated by the release of packets of intracellular Ca.
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10.1016/0143-4160(83)90017-9
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pubmed_672_2462
|
Physical and clinicopathologic findings from six cows with proximal duodenal obstruction (PDO) and 58 cows with abomasal volvulus (AV) were compared retrospectively. Many of the physical signs were similar in cows with PDO and cows with AV, but the two conditions differed in the type of abdominal distention, and in the findings from rectal examination and abdominal auscultation. Cows with PDO had significantly lower mean values for serum sodium (Na+) and chloride ion (Cl-), and higher mean values for plasma bicarbonate [HCO3-], base excess, carbon dioxide pressure (pCO2), serum phosphate, urea nitrogen, and total protein than AV affected cattle. Cows with PDO showed hyperglycemia (range, 263-990 mg/dl; mean, 618 mg/dl) of unexplained etiology that was significantly higher than blood-glucose concentrations in AV cows (mean, 178 mg/dl). Although all AV cows with anion gap values greater than 32 mEq/l died;PDO cows with equally elevated anion gap survived. The anion gap elevations in PDO and AV cows resulted from accumulation of different anions. Although the site of obstruction of aborad flow of ingesta is similar in both disease conditions, the differences in physical and clinicopathologic findings appear to reflect differences in the degree of reticulo-omasal orifice obstruction and the degree of abomasal vascular compromise.
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10.1111/j.1532-950x.1988.tb01002.x
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pubmed_379_434
|
The levels of neurotrophin mRNA in sensory ganglia, sciatic nerve, and skeletal muscle were measured in the streptozotocin-diabetic rat using northern blotting. Periods of diabetes of 4, 6, and 12 weeks significantly elevated brain-derived neurotrophic factor (BDNF) mRNA levels in soleus muscle compared with age-matched controls, the increase being highest at 6 weeks. At all time periods studied, the levels of nerve growth factor (NGF) mRNA in soleus muscle were decreased by 21-47%. Following 12 weeks of diabetes, BDNF mRNA levels were increased approximately two- to threefold in L4 and L5 dorsal root ganglia (DRG), and in sciatic nerve, NGF mRNA levels were raised 1.65-fold. Intensive insulin treatment of diabetic rats for the final 4 weeks of the 12-week period of diabetes reversed the up-regulation of BDNF mRNA in DRG and muscle and NGF mRNA in sciatic nerve. All diabetes-induced changes in neurotrophin mRNA were not paralleled by similar alterations in the levels of beta-actin mRNA in muscle and nerve, or of GAP-43 mRNA in DRG and nerve. It is proposed that the up-regulation of neurotrophin mRNA is an endogenous protective and/or repair mechanism induced by insult and, as such, appears as an early marker of peripheral nerve and muscle damage in experimental diabetes.
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10.1046/j.1471-4159.1995.64031231.x
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pubmed_11_10066
|
BACKGROUND
Low plasma 25-hydroxyvitamin D (25[OH]D) concentration and high BMI have been associated with increased risk of diabetes. We tested the hypotheses that genetic variants associated with low concentrations of 25(OH)D are associated with diabetes, and that the effect on diabetes of genetic variants associated with high BMI is partly mediated through reduced plasma 25(OH)D concentration.
METHODS
In this mendelian randomisation study, we genotyped 96 423 white Danes aged 20-100 years from three studies. 5037 of these participants had type 2 diabetes. All individuals were surveyed for diabetes from 1977 to 2011. 31 040 participants had their plasma 25(OH)D concentration measured and 90 169 had their BMI measured. We assessed the effects of genetic variation in DHCR7 (related to endogenous production) and CYP2R1 (related to liver conversion) on plasma 25(OH)D concentration, and the effects of variation in FTO, MCR4, and TMEM18 on BMI. We then assessed the effect of genetic variation in these genes on risk of type 2 diabetes, and the association of measured plasma 25(OH)D concentration and BMI with risk of type 2 diabetes. We did a mediation analysis to assess how much of the effect of BMI genotype on risk of diabetes was mediated through plasma 25(OH)D concentration.
FINDINGS
The odds ratios for type 2 diabetes for participants who had a 20 nmol/L reduction in plasma 25(OH)D concentration as determined by genetics were 1·51 (95% CI 0·98-2·33) for DHCR7 and 1·02 (0·75-1·37) for CYP2R1. The DHCR7 allele score was significantly associated with increased risk of type 2 diabetes (p for trend=0·04), whereas the allele score for CYP2R1 was not. For participants who had a measured 20 nmol/L reduction in plasma 25(OH)D concentration, the adjusted odds ratio for type 2 diabetes was 1·16 (1·08-1·25). For participants who had a 10 kg/m(2) increase in BMI as determined by genetics, the odds ratio for type 2 diabetes was 19·4 (6·4-59·1); this was associated with an 11·1 nmol/L (2·6-19·6) lower plasma 25(OH)D concentration. For a 10 kg/m(2) increase in measured BMI, the adjusted odds ratio for type 2 diabetes was 4·33 (3·70-5·07); this was associated with a 9·1 nmol/L (8·4-9·7) lower plasma 25(OH)D concentration. Mediation analysis showed that 3% (1-5) of the effect of BMI on risk of type 2 diabetes was mediated through lowered plasma 25(OH)D concentrations.
INTERPRETATION
Genetic variants associated with low plasma 25(OH)D concentrations are associated with type 2 diabetes and low plasma 25(OH)D concentrations might be a modest mediator between obesity and increased risk of diabetes. Genetic variants associated with endogenous production of 25(OH)D might partially explain this increased risk; however, as findings for DHCR7 were not statistically significant, our results require independent confirmation.
FUNDING
Danish Heart Foundation, Copenhagen University Hospital.
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10.1016/S2213-8587(13)70200-6
|
pubmed_720_13114
|
BACKGROUND
Neuraxial ultrasound might improve the efficacy of spinal anaesthesia but this has not been tested for the paramedian approach in the elderly.
OBJECTIVE
The current study aims to assess whether the ultrasound-assisted paramedian technique can decrease the number of needle passes required for success compared with the landmark-guided paramedian technique in the elderly.
DESIGN
Randomised controlled study.
SETTING
Single-institution, tertiary-level hospital in Seoul, Republic of Korea from October 2017 to January 2018.
PATIENTS
Eighty patients aged at least 60 years undergoing orthopaedic surgery.
INTERVENTION
All received paramedian spinal anaesthesia by either the landmark-guided or preprocedural ultrasound-assisted technique.
MAIN OUTCOME MEASURES
The number of needle passes required for successful dural puncture.
RESULTS
The number of needle passes (median [interquartile range]) was significantly lower (1.0 [1.0 to 2.0] vs. 4.5 [2.0 to 7.0]) and the success rate at first pass significantly higher at 65.0 vs. 17.5% in the ultrasound compared with the landmark group (both P < 0.001). The ultrasound-assisted technique required a longer time for establishing landmarks (117.5 s [85.5 to 150.7 s] vs. 17.5 s [14.0 to 23.0 s]) and for total procedure (181.5 s [133.5 to 212.5 s] vs. 92.5 s [62.5 to 176.5 s]) but a shorter time for administering spinal anaesthesia (39.5 s [31.5 to 71.3 s] vs. 77.0 s [45.8 to 136.5 s]; all, P < 0.001) than the palpation-guided technique. The ultrasound group showed lower periprocedural pain scores (3 [2 to 4] vs. 4 [4 to 6]; P = 0.009) and discomfort scores (2 [0 to 3] vs. 5 [2 to 6]; P = 0.003) than the landmark group.
CONCLUSION
Compared with the landmark-guided paramedian technique, the ultrasound-assisted paramedian technique decreases the number of needle manipulations and periprocedural pain and discomfort scores in the elderly. Our results suggest that neuraxial ultrasonography facilitates the performance of spinal anaesthesia in the elderly.
TRIAL REGISTRATION
NCT03316352.
|
10.1097/EJA.0000000000001029
|
pubmed_813_19825
|
OBJECTIVES
The purpose of this study was to confirm earlier reports that low-dose vasopressin (LDVP) analogues promote urine output in patients with hepatorenal syndrome (HRS) and to check whether this mode of therapy could also be effective in renal shutdown due to nonhepatic conditions.
DESIGN
A prospective, open, interventional study.
SETTING
An intermediate-level (step-down) medical intensive care unit within a general medical ward of a large university-affiliated hospital.
SUBJECTS
Eighteen successive hospitalized patients with HRS (mean age 65 +/- 13 years) and 11 patients with end-stage congestive heart failure (CHF) (mean age 81 +/- 5 years) who failed to restore urine output with conventional treatment (fluids, dopamine, and diuretics) given for at least 24 h.
INTERVENTIONS
The patients received LDVP (1 IU h-1) continuously in addition to the conventional treatment.
MAIN OUTCOME MEASURES
Urine output and creatinine clearance every 24 h.
RESULTS
In the HRS group, before treatment the urine output was 155 +/- 9 mL 24 -1h (mean +/- SD). After treatment with LDVP for 24, 48, and 72 h, urine output improved to 1067 +/- 87, 1020 +/- 501, and 1311 +/- 988 mL 24 -1h, respectively (P < 0.0001 for all measures; two-tailed paired t-test). In the CHF group, before treatment the urine output was 99 +/- 99 mL 24 -1h. After treatment with LDVP for 24, 48, and 72 h, this improved to 1125 +/- 994 mL 24 -1h (P = 0.0028), 1821 +/- 1300 mL 24 -1h (P = 0.004), and 2920 +/- 2423 mL 24 -1h (P = 0.0012), respectively. The improvement in urine output was not accompanied by a parallel improvement in creatinine clearance. The overall outcome did not change, and all patients except two in each group succumbed to their end-stage disease, due to nonrenal causes.
CONCLUSIONS
LDVP is effective in restoring urine output both in HRS and in CHF. This suggests that LDVP affects mechanisms not specifically related to liver disease. LDVP may be useful in critical patients with renal shutdown whilst awaiting liver or heart transplantation.
|
10.1046/j.1365-2796.1999.00556.x
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pubmed_885_5146
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Weissella confusa and Weissella cibaria isolated from wheat sourdoughs produce, from sucrose, linear dextrans due to a single soluble dextransucrase. In this study, the first complete gene sequence encoding dextransucrase from a W. confusa strain (LBAE C39-2) along with the one from a W. cibaria strain (LBAE K39) were reported. Corresponding gene cloning was achieved using specific primers designed on the basis of the draft genome sequence of these species. Deduced amino acid sequence of W. confusa and W. cibaria dextransucrase revealed common structural features of the glycoside hydrolase family 70. Notably, the regions located in the vicinity of the catalytic triad (D, E, D) are highly conserved. However, comparison analysis also revealed that Weissella dextransucrases form a distinct phylogenetic group within glucansucrases of other lactic acid bacteria. We then cloned the W. confusa C39-2 dextransucrase gene and successfully expressed the mature corresponding enzyme in Escherichia coli. The purified recombinant enzyme rDSRC39-2 catalyzed dextran synthesis from sucrose with a K m of 8.6 mM and a V max of 20 μmol/mg/min. According to (1)H and (13)C NMR analysis, the polymer is a linear class 1 dextran with 97.2 % α-(1→6) linkages and 2.8 % α-(1→3) branch linkages, similar to the one produced by W. confusa C39-2 strain. The enzyme exhibited optimum catalytic activity for temperatures ranging from 35 to 40 °C and a pH of 5.4 in 20 mM sodium acetate buffer. This novel dextransucrase is responsible for production of dextran with predominant α-(1→6) linkages that could find applications as food hydrocolloids.
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10.1007/s00253-012-4447-8
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pubmed_44_10839
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Reactive oxygen and nitrogen species have been implicated in the pathogenesis of pulmonary diseases. The goal of this study was to measure the response of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 enzymes (COX-2) in lung with moderate zinc deficiency. Adult male Wistar rats were divided into two groups receiving (1) a zinc-deficient diet (ZD) or (2) a zinc-adequate control diet. After 2 months of treatment, the zinc-deficient group showed a significant pulmonary edema. This was associated to a reduction of protein thiols and to a significant increase of metallothionein and glutathione disulfide levels. In addition, a higher serum and lung NO production in ZD group was positively related to the higher activity and expression of iNOS and COX-2 found in lungs. Western blot analysis revealed increased IkappaBalpha degradation, an indicator of NF-kappaB activation in ZD lungs. Anatomopathologic analysis of ZD lungs showed an increase of connective tissue fibers with an influx of polymorphonuclear cells. These cells and type II cells from the alveoli showed specific immunohistochemical signals for iNOS. The conclusion is that, during the development of zinc-deficiency, iNOS activity increases in lung and contributes to lung injury. Zinc deficiency implications must be taken into account to design therapies and public health interventions involving targeted zinc supplementation for high-risk subjects or certain diseases, such as asthma.
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10.1016/j.niox.2005.09.001
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pubmed_686_14525
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The purpose of this article is to introduce our notion of epistemic space and to demonstrate its utility for understanding the origins and trajectories of nursing theory in the 20th century using multidimensional scaling (MDS). A literature review was conducted on primary and secondary sources written by and about 20 nurse theorists to investigate whether or not they cited 129 different scholars in the fields of anthropology, biology, nursing, philosophy, psychology, and sociology. Seventy-four scholars were identified as having been cited by at least two nurse theorists (319 citations total). Proximity scores, quantifying the similarity among nurse theorists based on proportions of shared citations, were calculated and analyzed using MDS. The emergent model of epistemic space that accommodated these similarities among nurse theorists revealed the systematic influence of scholars from various fields, notably psychology, biology, and philosophy. We believe that this schema and resulting taxonomy will prove useful for furthering our understanding of the relationships among nursing theories and theories in other fields of science.
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10.1016/j.ijnurstu.2004.09.021
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pubmed_33_893
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Very high takeoff of the left main coronary artery in the absence of another coronary anomaly is a rare finding. The pathologic consequences of this anomaly are unclear, and the literature on this subject does not agree on whether the condition is dangerous. We present our findings in 2 patients who were discovered to have this anomaly upon noninvasive computed tomographic coronary angiography, and we discuss our analysis of the literature and our management of these patients.
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pubmed_33_893
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pubmed_947_7985
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Determination of the nutritional condition, including estimation of amounts of total body fat (tBF), at routine postmortem examination of cats is typically based on subjective visual assessment. Subjective assessment may result in uncertainties regarding degree of overweight, and objective methods that provide a numerical value reflecting the tBF could be valuable to accurately judge excess body fat. We investigated if the falciform fat pad weight (FFPW) was correlated to tBF and could be used to detect overweight and obesity in cats. The FFPW and the femur length (FL) were recorded at postmortem examination in 54 cats and the FFPW:FL ratio (FFR) calculated. Each cat was additionally assigned to a fat category (FC) according to subjective assessment. Computed tomography was used to determine tBF as the body fat percentage (%BF), the body fat volume (BFV), and BFV normalized to animal size (nBFV) in 39 cats. There was strong correlation between the FFPW and the BFV (r = 0.888) and between the FFR and the nBFV (r = 0.897). The correlation between the nBFV and %BF was very strong (r = 0.974). Using a lower FFR cutoff value of 3.5 for obesity and 1.6 for overweight, there was a discrepancy in FC between using the FFR and subjective assessment in 6 of 54 cats (11%). We conclude that the FFPW increases proportionally with tBF and that the FFR provides a method for objective tBF estimation. We suggest introducing the FFR to feline postmortem examination protocols as an objective estimate of tBF.
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10.1177/10406387211071078
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pubmed_781_8192
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In previous studies, mebudipine, a dihydropyridine calcium channel blocker, showed a considerable potential to be used in cardiovascular diseases. The aim of the current study was to develop a valid method using reversed-phase high performance liquid chromatography coupled with electrospray ionization mass spectrometry to assay mebudipine in the human plasma. Separation was achieved on a Zorbax Eclipse(®) C18 analytical column using a mobile phase consisted of methanol/water (90:10, v/v). The flow rate was 0.6 mL/min and carbamazepine was used as an internal standard (IS). This method involved the use of [M +Na](+) ions of mebudipine and IS at m/z 411 and 259, respectively with the selected ion monitoring (SIM) mode. There were no interfering peaks from endogenous components in blank plasma chromatograms. Standard curves were linear (r(2)>0.99) between 5 to 100 ng/mL. The mean extraction efficiency was about 84% and the limit of quantification for mebudipine was 5 ng/mL in plasma. The coefficient of variation and error at all of the intra-day and inter-day assessments were less than 11%. The results indicated that this method is a fast, accurate, sensitive, selective and reliable method for the determination of mebudipine in the human plasma. The assay method has been successfully used to estimate plasma concentration of mebudipine after the oral administration of 2.5 mg tablet in healthy adults.
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pubmed_781_8192
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pubmed_714_15035
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Studies of the effect of parathyroidectomy (PTX) on bone turnover in patients with the combination of primary hyperparathyroidism (PHPT) and Paget's disease (PD) are largely limited to case reports. The etiology of the combination is disputed. We report 30 patients and their biochemical (n = 17) and histomorphometric (n = 4) responses to PTX in 18. All 18 patients except one had a post-PTX fall in plasma alkaline phosphatase (pAP). There was a significant positive correlation between the degree of post-PTX fall in pAP and both the preoperative plasma total corrected calcium (CaC) (P < 0.01) and serum ionized calcium (P < 0.05). For the patients with CaC levels >3.0 mmol/liter, the mean % fall in pAP was 68% of pretreatment (to 32%). For those with CaC levels >/=2.68 mmol/liter the fall in pAP was >18%. Of 12 literature cases treated by PTX and followed up, 11 had a postoperative fall in pAP (range 6-83%). Pretreatment bone biopsies (n = 6) could not be distinguished from uncomplicated PD. No significant histomorphometric changes were documented postoperatively in the four patients studied; however, % fibrotic surfaces declined in each of the four. Of the 18 patients, only one had radiologic subperiosteal erosions preoperatively; none had clinical tetany postoperatively-thus distinguishing this combination of diseases from severe PHPT bone disease-a situation easily biochemically confused with this combination. The sex distribution of 2.75:1 F/M in this series resembles reported ratios in pure PHPT of 2.37:1, unlike the ratios found in pure PD (0.49-1.01:1). The prevalence of PHPT in PD is 2.2-6.0% (mean 4.4%) in 1836 patients. In our series, 73% of patients with both diseases were females >60 years of age. In population studies >60 years, PHPT was present in 3% of women and 1% of men. Hypercalcemia in PD is frequently attributed to immobilization. As part of this study, we examined 184 patients referred with PD for the existence of, and cause of hypercalcemia. Of this group, 21 were hypercalcemic, 19 (90%) of whom had PHPT; none had immobilization hypercalcemia. In patients with both disorders, the indications for PTX should include the potential post-PTX improvement in pagetic biochemistry and symptoms. The sex distribution (resembling pure PHPT) and the similar prevalence of PHPT in Paget's, and in the elderly population, support the likelihood, in most cases, that these two common diseases are associated by chance.
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10.1007/s002239900728
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pubmed_426_817
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A 50-kDa polypeptide was obtained from photosynthetically active phycobilisome-photosystem II preparations from the red alga Porphyridium cruentum after removal of phycobiliproteins. Removal of phycobiliproteins caused destabilization of the structure of the phycobilisome-photosystem II preparations and was accompanied by a decline in photosystem II activity (oxygen-evolution and dichlorophenol-indophenol (DPIP) reduction). The treatments in increasing relative effectiveness were: addition of EDTA (10 mM), lowering the pH (6.8----4.4), and lowering the ionic strength (to ca. 1 mM phosphate). The lowering of the ionic strength by dialysis resulted in a preparation highly enriched in a 50-kDa polypeptide (apparent molecular mass on SDS-PAGE). This preparation retained photosystem II activity as evidenced by the photoreduction of DPIP in the presence of diphenylcarbazide (222 mumol DPIP/mg chlorophyll/h). Also it had a 698-nm (77K) fluorescence emission maximum, as compared to a 668-nm emission in the unfractionated preparation, which indicates enrichment of the photosystem II reaction center. Comparing our results with those obtained from green plants and a cyanobacterium leads us to suggest that the reaction center II polypeptides are highly similar in all chlorophyll alpha-containing plants.
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10.1016/0003-9861(86)90729-0
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pubmed_723_11051
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Molecularly imprinted polymers (MIPs) mimic the binding sites of antibodies by substituting the amino acid-scaffold of proteins by synthetic polymers. In this work, the first MIP for the recognition of the diagnostically relevant enzyme butyrylcholinesterase (BuChE) is presented. The MIP was prepared using electropolymerization of the functional monomer o-phenylenediamine and was deposited as a thin film on a glassy carbon electrode by oxidative potentiodynamic polymerization. Rebinding and removal of the template were detected by cyclic voltammetry using ferricyanide as a redox marker. Furthermore, the enzymatic activity of BuChE rebound to the MIP was measured via the anodic oxidation of thiocholine, the reaction product of butyrylthiocholine. The response was linear between 50 pM and 2 nM concentrations of BuChE with a detection limit of 14.7 pM. In addition to the high sensitivity for BuChE, the sensor responded towards pseudo-irreversible inhibitors in the lower mM range.
|
10.3390/polym11121970
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pubmed_171_4375
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A 42-year-old woman presenting to an academic medical center with low back pain radiating down her left leg was deemed to be a good candidate for a lumbar epidural steroid injection after undergoing a thorough evaluation. The procedure along with all the possible attendant side effects were thoroughly explained to the patient who readily signed the consent form. The patient was prepped and positioned, but, upon seeing that a resident rather than her attending doctor would be doing the procedure, she objected, insisting that the attending do the procedure. The attending explained that she was in a teaching hospital, where residents commonly do procedures under close supervision of attending physicians. Nevertheless, the patient still insisted on whom she wanted to do the procedure and became visibly agitated. How do you accommodate the training needs of medical students, residents, and fellows while maintaining adequate care for patients? Does the "see one, do one, teach one" principle commonly practiced in academic settings compromise the bioethical principles of nonmaleficence and beneficence? What should the attending do in this case with the patient on the table? What are the patient's rights here versus the needs of the training setting?
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10.1111/j.1526-4637.2004.4030_1.x
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pubmed_598_9080
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Metallothioneins (MTs) are low-molecular-weight proteins with high Cys content and high metal-chelating ability. CdMT and CuMT subfamilies present different characteristics in Tetrahymena. To explore the effect of the cysteine arrangement and sequence length of MTs for binding different metal ions, MTT1, truncated MTT1 (TM1), MTT2, and truncated MTT2 (TM2) were expressed in E. coli. The half-maximal inhibiting concentrations (IC50) of Cd2+ and Cu+ for the recombinant strains were different. Furthermore, E. coli cells expressing MTT1 and TM1 exhibited higher accumulating ability for Cd2+ than cells expressing MTT2 and TM2. However, the opposite is true for Cu+. The binding ability of the different recombinant proteins to Cd2+ and Cu+ were also different. MTT1 and truncated mutant TM1 were the preference for Cd2+, whereas MTT2 and truncated mutant TM2 were the preference for Cu+ coordination. These results showed that metal ion tolerance and accumulation ability not only depended on cysteine arrangement pattern but also on sequence length of MT in Tetrahymena.
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10.1080/09168451.2018.1431517
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pubmed_774_8114
|
In the last decade, innovative therapeutic strategies against inherited retinal degenerations (IRDs) have emerged. In particular, chemical- and opto-genetics approaches or a combination of them have been identified for modulating neuronal/optical activity in order to restore vision in blinding diseases. The 'chemical-genetics approach' (optopharmacology) uses small molecules (exogenous photoswitches) for restoring light sensitivity by activating ion channels. The 'opto-genetics approach' employs light-activated photosensitive proteins (exogenous opsins), introduced by viral vectors in injured tissues, to restore light response. These approaches offer control of neuronal activities with spatial precision and limited invasiveness, although with some drawbacks. Currently, a combined therapeutic strategy (optogenetic pharmacology) is emerging. This review describes the state of the art and provides an overview of the future perspectives in vision restoration.
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10.4155/fmc-2018-0315
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pubmed_443_2534
|
To substitute for exocrine pancreatic insufficiency, patients with cystic fibrosis (CF) take pancreatic enzymes (PE) originating from porcine pancreas. Five different pancreatic enzyme preparations used by our patients contained 0.5-1.4 microg selenium per g tablet. In patients taking PE in doses that were gradually increased to improve fat absorption during a 48-month period, the effects of PE dose on erythrocyte selenium-dependent glutathione peroxidase (SeGSH-Px) activities and plasma selenium concentrations were studied. At baseline, erythrocyte SeGSH-Px activities were significantly lower in patients (p=.01), while plasma selenium concentrations did not differ between patients and healthy subjects. When PE dose and, consequently, selenium intake from PE was increased, erythrocyte SeGSH-Px activities (p < .001) and plasma selenium concentrations (p=.02) increased. Changes in SeGSH-Px activities during the initial 8 months correlated with those in selenium intake from PE (r=0.67, p < .001). Plasma selenium concentrations plateaued at 12 months and erythrocyte SeGSH-Px activities did so at 36 months, when patients had reached SeGSH-Px activities similar to those of healthy subjects. At 48 months, patients took an average lipase dose of 17400 U x kg(-1) x d(-1) and selenium dose from PE of 0.53 microg x kg(-1) x d(-1). We conclude that selenium content of PE preparations has a significant effect on SeGSH-Px activity in patients with CF. This form of selenium supply needs to be taken into account when selenium supplements are given to patients with CF.
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10.1016/s0891-5849(98)00061-6
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pubmed_1114_15973
|
Cereal powdery mildews caused by Blumeria graminis and cereal rusts caused by Puccinia spp. are constant disease threats that limit the production of almost all important cereal crops. Rice is an intensively grown agricultural cereal that is atypical because of its immunity to all powdery mildew and rust fungi. We analyzed the nonhost interactions between rice and the wheat powdery mildew fungus B. graminis f. sp. tritici (Bgt) and the wheat leaf rust fungus Puccinia triticina (Ptr) to identify the basis of nonhost resistance (NHR) in rice against cereal powdery mildew and rust fungi at cytological and molecular levels. No visible symptoms were observed on rice leaves inoculated with Bgt or Ptr. Microscopic observations showed that both pathogens exhibited aberrant differentiation and significantly reduced penetration frequencies on rice compared to wheat. The development of Bgt and Ptr was also completely arrested at early infection stages in cases of successful penetration into rice leaves. Attempted infection of rice by Bgt and Ptr induced similar defense responses, including callose deposition, accumulation of reactive oxygen species, and hypersensitive response in rice epidermal and mesophyll cells, respectively. Furthermore, a set of defense-related genes were upregulated in rice against Bgt and Ptr infection. Rice is an excellent monocot model for genetic and molecular studies. Therefore, our results demonstrate that rice is a useful model to study the mechanisms of NHR to cereal powdery mildew and rust fungi, which provides useful information for the development of novel and durable strategies to control these important pathogens.
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10.1007/s00709-014-0750-9
|
pubmed_835_7149
|
CONTEXT
Autosomal recessive hypophosphatemic rickets (ARHR) are rare, heritable renal phosphate-wasting disorders that arise from overexpression of the bone-derived phosphaturic hormone fibroblast growth factor 23 (FGF23) leading to impaired bone mineralization (rickets and osteomalacia). Inactivating mutations of Dentin matrix protein 1 (DMP1) give rise to ARHR type 1 (ARHR1). Short stature, prominent bowing of the legs, fractures/pseudofractures, and severe enthesopathy are prominent in this patient population. Traditionally, treatment consists of oral phosphate replacement and the addition of calcitriol but this approach is limited by modest efficacy and potential renal and gastrointestinal side effects.
OBJECTIVE
The advent of burosumab (Crysvita), a fully humanized monoclonal antibody to FGF23 for the treatment of X-linked hypophosphatemia and tumor-induced osteomalacia, offers a unique opportunity to evaluate its safety and efficacy in patients with ARHR1.
RESULTS
Monthly administration of burosumab to 2 brothers afflicted with the disorder resulted in normalization of serum phosphate, healing of pseudofracture, diminished fatigue, less bone pain, and reduced incapacity arising from the extensive enthesopathy and soft tissue fibrosis/calcification that characterizes this disorder. No adverse effects were reported following burosumab administration.
CONCLUSION
The present report highlights the beneficial biochemical and clinical outcomes associated with the use of burosumab in patients with ARHR1.
|
10.1210/clinem/dgac433
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pubmed_234_20676
|
The prognosis of primary lung cancer associated with hypertrophic osteopulmonary arthropathy is not well known. Between July 1973 adn August 1995, we cared for 53 consecutive patients with resectable non-small-cell lung cancer associated with osteoplumonary arthropathy. There were 51 men and 2 women, mean age 56 years. In 83% of the cases the lung cancer was revealed by hypertrophic osteopulmonary arthropathy. The tumor generally involved the right lung (n = 38) and the upper lobe (n = 35). There was no peripheral or central predominance. Complete tumoral resection was performed in 47 patients, incomplete resection in 4 and exploratory thoracotomy in 2. The main histologies were adenocarcinoma (50%) and squamous cell carcinoma (40%). Among the 51 resected tumors, 27 were grade I, 5 grade II, 17 grade III and 2 grave IV. Overall 5-year survival was 39%, reaching 51% for grade I, 40% for grade II, 27% for grade III and 0% for grade IV. The pulmonary manifestations of hypertrophic osteopulmonary arthropathy regressed within the first postoperative hours in all the patients whose tumor was resected and in 1 of the 2 patients who underwent exploratory thoracotomy. AT follow-up, the hypertropic pulmonary arthropathy had disappeared in all resected patients except 1 with a grade I tumor. Tumor recurrence was proven in 18 resected patients, 5 of whom also had recurrent osteopulmonary arthropathy. Our results suggest that primary lung cancer associated with hypertrophic pulmonary arthropathy has characteristic features and that prognosis is comparable with primary lung cancer alone.
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pubmed_234_20676
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pubmed_314_8765
|
BACKGROUND
Recent studies have shown that aggressive preoperative radiation increases the likelihood of limb salvage in sarcoma patients.
METHOD
The Surveillance, Epidemiology and End Results database was used to run an adjusted logistic regression for the receipt of cancer-directed treatment modalities.
RESULTS
Of patients with specific surgical procedures recorded (n = 2,104), 86.0% had undergone a limb-sparing procedure. On bivariate analysis, African American patients were less likely to receive a limb-sparing procedure than white patients (80.4% vs 86.9%; P = .02). On multivariate analysis, African Americans were significantly more likely to receive preoperative radiation (odds ratio [OR], 2.31; 95% confidence interval [CI], 1.22-4.40; P = .011), yet this did not translate into an increase in limb salvage (OR, .67; 95% CI, .42-1.08; P = .10). Limb salvage significantly increased for all groups in 2001 and after (OR, 2.75; 95% CI, 1.55-4.88; P = .001) without a decrease in survival. For those with tumors greater than 4 cm, there was a trend away from limb salvage for African Americans (OR, .59; 95% CI, .32-1.07; P = .08).
CONCLUSIONS
Our results of an increase in limb-salvage surgeries after 2001 without a decrease in survival support previous studies. The trend away from limb salvage for African Americans cannot be answered by this study.
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10.1016/j.amjsurg.2009.12.003
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pubmed_326_18084
|
A clone containing the H1 histamine receptor (H1HR)-encoding gene was isolated from a human genomic DNA library. The 5'-UTR of the H1HR gene reported here differs upstream from bp -142 from that reported previously [Fukui et al., Biochem. Biophys. Res. Comm. 201 (1994) 894-901]. PCR amplification utilizing primer pairs derived from the 5'-UTR reported herein amplified a DNA fragment of the expected size from human genomic DNA whereas 5'-UTR primers derived from the Fukui et al. sequence did not yield a PCR product. The 5'-UTR of H1HR contains potential TATA and CCAAT boxes, a CACCC sequence, potential GREs and other DNA-binding motifs.
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10.1016/0378-1119(96)00036-4
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pubmed_796_23234
|
The dopamine (DA) D-2 receptor agonists quinpirole (threshold dose, 0.01 mg/kg IP), pergolide (0.025 mg/kg), B-HT 920 (0.003 mg/kg) and (-)-3-PPP (4 mg/kg) produced dose-dependent locomotor depression (immobility) in mice as assessed by a subjective scoring system, with the immobility being characterized by a frozen posture. The animals were still but had their eyes open. The immobility was accompanied by reductions in sniffing, rearing and grooming. The depression (and the associated reduction in the various behaviours) produced by quinpirole (0.1 mg/kg), pergolide (0.1 mg/kg) and B-HT 920 (0.1 mg/kg) was substantially (but not always completely) reversed by the selective D-1 receptor agonist SKF38393 (up to 12 mg/kg) and the non-selective D-1 receptor agonist CY208243 (up to 3 mg/kg). The immobility induced by (-)-3-PPP (16 mg/kg) was also reversed by CY208243 and SKF38393, but the reversal was due to an increase in grooming behaviour in mice challenged with the D-1 receptor agonists, whether or not the animals had also received (-)-3-PPP. There was no reversal of the depression of rearing or sniffing. In contrast, CY208243 and SKF38393 also antagonized the immobility induced by B-HT 920, but the reversal was accompanied by at least partial reversals of the depression of sniffing, rearing and grooming. The reversal of quinpirole-induced immobility by SKF38393 and CY208243 was antagonized by SCH23390 (0.1 mg/kg). The selective D-2 receptor antagonist raclopride (0.025 to 0.4 mg/kg) could not reverse quinpirole-induced immobility. High doses of either raclopride (0.4 mg/kg) or SCH23390 (greater than 0.1 mg/kg) significantly increased immobility. Although raclopride itself (0.2 mg/kg) produced a substantial increase in DOPAC and homovanillic acid (HVA) levels in the striatum, it did not antagonize the autoreceptor mediated effects of quinpirole (0.1 mg/kg) in reducing the striatal dihydroxyphenylacetic acid (DOPAC) to DA ratio. However, the same dose of raclopride was partly effective in reducing the effects of lower doses of quinpirole (0.01 and 0.03 mg/kg) on the striatal DOPAC to DA ratio. Raclopride (0.2 mg/kg) also partially but significantly reduced the locomotor stimulant effects of d-amphetamine in reserpinized mice. Biochemical analyses in the striata indicated that CY208243 slightly retarded DA turnover (as assessed by the DOPAC/DA ratio). SKF38393 itself also slightly reduced DA turnover. In automated activity cages, using mice depleted of DA with reserpine and alpha-methyltyrosine, all the D-2 receptor agonists tested, in combination with SKF38393, produced an increase in activity.(ABSTRACT TRUNCATED AT 400 WORDS)
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10.1007/BF00167035
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pubmed_852_17404
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This paper describes a new procedure for extracting polychlorinated biphenyls (PCBs) from marine samples using subcritical 1,1,1,2-tetrafluoroethane (R134a). The extraction procedure was optimized at temperatures varying from 20 to 70°C and pressures ranging from 3 to 15 MPa. The volume of the co-solvent was then optimized using 1,1,1,2-tetrafluoroethane (R134a) as the subcritical phase. PCBs were characterized by GC-MS using the optimized conditions of 3 MPa, 30°C, and a co-solvent volume of 6 mL. The average yields of PCBs from subcritical fluid extraction of spiked oyster samples were measured and found to be greater than 90%, with relative standard deviations (RSD) of less than 10%. Detection limits of this method were in the range of 0.045-0.108 ng/g of dry mass. The method was compared to Soxhlet extraction and then applied for monitoring PCBs in oysters from Qingdao, Shandong, China.
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pubmed_852_17404
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pubmed_367_10224
|
Steroid hormones regulate gene expression in organisms by binding to receptor proteins. These hormones include the androgens, which signal through androgen receptors (ARs). Endocrine disrupters (EDCs) are chemicals in the environment that adversely affect organisms by binding to nuclear receptors, including ARs. Vinclozolin, a fungicide used on fruit and vegetable crops, is a known anti-androgen, a type of EDC that blocks signals from testosterone and its derivatives. In order to better understand the effects of EDCs, further research on androgen receptors and other hormone signaling pathways is necessary. In this study, we demonstrate the evolutionary conservation between the genomic structure of the human and zebrafish ar genes and find that ar mRNA expression increases in zebrafish embryos exposed to vinclozolin, which may be evolutionarily conserved as well. At 48 and 72 h post-fertilization, vinclozolin-treated embryos express ar mRNA 8-fold higher than the control level. These findings suggest that zebrafish embryos attempt to compensate for the presence of an anti-androgen by increasing the number of androgen receptors available.
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10.1016/j.cbpc.2009.10.001
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pubmed_505_18306
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Explants of mature vigorous donor trees of wych elm ( Ulmus glabra Huds.) that had not been previously exposed to Dutch elm disease were investigated for the influence of phytohormones and media on shoot multiplication rates and organogenic capacity. The regenerates were micropropagated from cultures that originated from 15-year-old progeny of plus trees. Two plus trees aged over 70 years showed recalcitrant responses. Thidiazuron in combination with 6-benzylaminopurine (BAP) induced a significantly higher number of shoots per explant than the most optimal BAP treatment (5.88 vs. 3.05 shoots). Woody plant medium and Dubovský minimal medium had no significant effects on shoot formation and multiplication rates. All plantlets raised in vitro were phenotypically normal and successfully hardened to ex vitro conditions. Two experimental field plots with 3-year-old in vitro-propagated trees were established.
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10.1007/s00299-003-0749-8
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pubmed_475_2729
|
CLINICAL QUESTION
Is acupuncture associated with reduced pain outcomes for patients with chronic pain compared with sham-acupuncture (placebo) or no-acupuncture control?
BOTTOM LINE
Acupuncture is associated with improved pain outcomes compared with sham-acupuncture and no-acupuncture control, with response rates of approximately 30% for no acupuncture, 42.5% for sham acupuncture, and 50% for acupuncture.
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10.1001/jama.2013.285478
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pubmed_36_21429
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In 2010, the Management Stream of the Australasian Child and Adolescent Obesity Research Network (ACAORN) undertook a Delphi survey asking 'What research questions remain to be addressed in the effective management of child and adolescent obesity?' Members of ACAORN, the Child and Adolescent Obesity Clinics of Australasia Network (CAOCOA-Net) and attendees at the Child Obesity symposium at the annual scientific meeting for the Australian and New Zealand Obesity Society (ANZOS) contributed to three rounds of survey development. Although reasonable concordance in ratings was evident for all 10 questions, 'determining the best strategies for long-term weight management' and 'how best to support the primary healthcare system to achieve these strategies' were clearly identified as the highest research priorities. Other priorities included 'how best to identify the right children with whom to intervene' and 'managing factors which impact on service delivery'. Identifying priority research areas from those working in the field offers the opportunity to stimulate research collaboration and provide justification for funding applications.
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10.1111/cob.12014
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pubmed_6_17595
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Renal and hepatic functions are often mingled through both the existence of associated primary organ diseases and hemodynamic co-relationship. The primary objective of this study was to sum up the relationship between autoimmune hepatitis (AIH) on renal tubular acidosis (RTA) and the stages of the disease. A systematic review was performed for 24 trials. A total of 3687 patients were included. The incidence of RTA occurring and short-term mortality reduction was seen in two groups; for an overall effect: Z = 2.85 (P = 0.004) a total 95% CI of 0.53 [0.34, 0.82]. Only one patient with alcoholic liver cirrhosis was found to have an incomplete type of RTA. Test for overall effect: Z = 2.28 (P = 0.02) 95% CI of 2.83 [1.16, 6.95]. A reduction in fatal infections with dual therapy of corticosteroid plus N-acetylcysteine (NAC) test for overall effect: Z = 3.07 (P = 0.002) with 95% CI of 0.45 [0.27, 0.75]. Autoimmune diseases are the most frequent underlying cause of secondary RTA in adults. The primary renal disease must be actively excluded in all patients with hepatic failure by aggressive clinical and laboratory evaluations.
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10.7759/cureus.15287
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pubmed_1066_25309
|
BACKGROUND
We have hypothesized that Parkinson's disease (PD) comprises two subtypes. Brain-first, where pathogenic α-synuclein initially forms unilaterally in one hemisphere leading to asymmetric nigrostriatal degeneration, and body-first with initial enteric pathology, which spreads through overlapping vagal innervation leading to more symmetric brainstem involvement and hence more symmetric nigrostriatal degeneration. Isolated REM sleep behaviour disorder has been identified as a strong marker of the body-first type.
OBJECTIVE
To analyse striatal asymmetry in [18F]FDOPA PET and [123I]FP-CIT DaT SPECT data from iRBD patients, de novo PD patients with RBD (PD+RBD) and de novo PD patients without RBD (PD-RBD). These groups were defined as prodromal body-first, de novo body-first, and de novo brain-first, respectively.
METHODS
We included [18F]FDOPA PET scans from 21 iRBD patients, 11 de novo PD+RBD, 22 de novo PD-RBD, and 18 controls subjects. Also, [123I]FP-CIT DaT SPECT data from iRBD and de novo PD patients with unknown RBD status from the PPPMI dataset was analysed. Lowest putamen specific binding ratio and putamen asymmetry index (AI) was defined.
RESULTS
Nigrostriatal degeneration was significantly more symmetric in patients with RBD versus patients without RBD or with unknown RBD status in both FDOPA (p = 0.001) and DaT SPECT (p = 0.001) datasets.
CONCLUSION
iRBD subjects and de novo PD+RBD patients present with significantly more symmetric nigrostriatal dopaminergic degeneration compared to de novo PD-RBD patients. The results support the hypothesis that body-first PD is characterized by more symmetric distribution most likely due to more symmetric propagation of pathogenic α-synuclein compared to brain-first PD.
|
10.3233/JPD-212761
|
pubmed_597_20190
|
OBJECTIVE
The National Quality Forum has endorsed a quality metric concerning the use of adjuvant chemotherapy administration in stage III colon cancer, yet a substantial treatment gap exists. Our objective was to evaluate the association of postoperative complications on the use of adjuvant therapy after colectomy for cancer.
PATIENTS AND METHODS
Data from the American College of Surgeons National Surgical Quality Improvement Program and National Cancer Data Base were linked to augment cancer registry information with robust clinical data on comorbidities and postoperative complications (2006-2008). The association of complications on adjuvant chemotherapy use was assessed using hierarchical multivariable regression models.
RESULTS
From 126 hospitals, 2368 patients underwent resection for stage III colon adenocarcinoma. Overall utilization of adjuvant chemotherapy was 63.2% (1497/2368). Of the 871 patients who did not receive chemotherapy, 652 met National Quality Forum exclusion criteria: death, severe comorbidity, refusal of care, advanced age (≥80 years), or prior malignancy. Of the remaining 219 patients, 19.1% (42/219) had 1 or more serious postoperative complications (eg, pneumonia, pulmonary failure). After accounting for the aforementioned potential explanations, the utilization rate was 87.2% (1497/1716). The strongest predictors of adjuvant chemotherapy omission were prolonged postoperative ventilation, renal failure, reintubation, and pneumonia (all Ps < 0.05). Superficial surgical site infection did not decrease adjuvant therapy receipt but delayed the time to its use by 3-fold. Serious complications increased time to chemotherapy by 65%. Abscess/anastomotic leak increased time to adjuvant chemotherapy by more than 5-fold.
CONCLUSIONS
Serious postoperative complications explained nearly 20% of the adjuvant chemotherapy treatment gap for patients with stage III colon cancer. The use of clinical data remains important when judging provider performance.
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10.1097/SLA.0000000000000312
|
pubmed_1019_5653
|
PURPOSE
Jagged1, a Notch ligand, is expressed on both tumor epithelial and endothelial cells and therefore may be amenable to dual targeting of the tumor stroma and malignant cell compartments of the tumor microenvironment.
EXPERIMENTAL DESIGN
We describe in vitro effects of targeting of Jagged1 on ovarian cancer cells and in vivo effects of independent targeting of stromal and malignant cell Jagged1 using species-specific human or murine siRNA constructs incorporated into chitosan nanoparticles and delivered intravenously in an orthotopic mouse model.
RESULTS
Jagged1 expression was prominent in SKOV3ip1 and IGROV-AF1, and significantly overexpressed in SKOV3TRip2, a taxane-resistant SKOV3 subclone. Jagged1 silencing with siRNA decreased cell viability and reversed taxane chemoresistance. In two different orthotopic ovarian cancer models, treatment with anti-human Jagged1 siRNA-CH reduced growth by 54.4% to 58.3% and with anti-murine Jagged1 siRNA-CH reduced growth by 41.7% to 48.8%. The combination of both species-specific constructs reduced tumor weight by 87.5% to 93.1% and sensitized SKOV3TRip2 tumors to docetaxel in vivo. Tumors showed reduced microvessel density with anti-murine Jagged1 constructs and decreased proliferation with anti-human Jagged1 siRNAs-CH. In addition, we show that Jagged1 downregulation does not sensitize cells to taxanes through a reduction in MDR1 expression, but at least in part by cross-talk with the GLI2 mediator of the Hedgehog pathway.
CONCLUSIONS
Jagged1 plays dual roles in cancer progression through an angiogenic function in tumor endothelial cells and through proliferation and chemoresistance in tumor cells. Dual inhibition represents an attractive therapeutic strategy for ovarian and potentially other malignancies.
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10.1158/1078-0432.CCR-11-0432
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pubmed_585_6596
|
Retroviruses are useful tools for the efficient delivery of genes to mammalian cells, owing to their ability to stably integrate into the host cell genome. Over the past few decades, retroviral vectors have been used in gene therapy clinical trials for the treatment of a number of inherited diseases and cancers. The earliest retrovirus vectors were based on simple oncogenic gammaretroviruses such as Moloney murine leukemia virus (MMLV) which, when pseudotyped with envelope proteins from other viruses such as the gibbon ape leukemia virus envelope protein (GALV) or vesicular stomatitis virus G protein (VSV-G), can efficiently introduce genes to a wide range of host cells. However, gammaretroviral vectors have the disadvantage that they are unable to efficiently transduce nondividing or slowly dividing cells. As a result, specific protocols have been developed to activate cells through the use of growth factors and cytokines. In the case of hematopoietic stem cells, activation has to be carefully controlled so that pluripotency is maintained. For many applications, gammaretroviral vectors are being superseded by lentiviral vectors based on human immunodeficiency virus type-1 (HIV-1) which has additional accessory proteins that enable integration in the absence of cell division. In addition, retroviral and lentiviral vector design has evolved to address a number of safety concerns. These include separate expression of the viral genes in trans to prevent recombination events leading to the generation of replication-competent viruses. Further, the development of self-inactivating (SIN) vectors reduces the potential for transactivation of neighboring genes and allows the incorporation of regulatory elements that may target gene expression more physiologically to particular cell types.
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10.1016/B978-0-12-386509-0.00003-X
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pubmed_15_13389
|
Very low density lipoproteins (VLDL) are a major secretory product of the liver. They serve to transport endogenously synthesized lipids, mainly triglycerides (but also some cholesterol and cholesteryl esters) to peripheral tissues. VLDL is also the precursor of LDL. ApoB100 is absolutely required for VLDL assembly and secretion. The amount of VLDL triglycerides secreted by the liver depends on the amount loaded onto each lipoprotein particle, as well as the number of particles. Each VLDL has one apoB100 molecule, making apoB100 availability a key determinant of the number of VLDL particles, and hence, triglycerides, that can be secreted by hepatic cells. Surprisingly, the pool of apoB100 in the liver is typically regulated not by its level of synthesis, which is relatively constant, but by its level of degradation. It is now recognized that there are multiple opportunities for the hepatic cell to intercept apoB100 molecules and to direct them to distinct degradative processes. This mini-review will summarize progress in understanding these processes, with an emphasis on autophagy, the most recently described pathway of apoB100 degradation, and the one with possibly the most physiologic relevance to common metabolic perturbations affecting VLDL production. This article is part of a Special Issue entitled Triglyceride Metabolism and Disease.
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10.1016/j.bbalip.2012.02.001
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pubmed_614_2775
|
BACKGROUND
Indoleamine 2,3-dioxygenase (IDO), which degrades tryptophan (Trp) to kynurenine (Kyn), has been demonstrated to contribute to modulation of allergic responses. However, the role of IDO in food allergy has not yet been elucidated.
METHODS
Serum Trp and Kyn concentrations were analyzed by high-pressure liquid chromatography. Expression of IDO gene was measured by real-time PCR. The levels of interleukin (IL)-4, IL-10, and interferon (IFN)-γ in cell culture supernatants were measured by ELISA.
RESULTS
Kyn/Trp (IDO activity) was significantly lower in subjects with food allergy (n = 100) than in aged-matched healthy controls (n = 112) (P = 0.004). Kyn/Trp was decreased from healthy through completely tolerant, partially tolerant, and reactive ones [LN transformation (mean ± SEM) healthy: 3.9 ± 0.02 μM/mM; completely tolerant: 3.83 ± 0.04; partially tolerant: 3.8 ± 0.06; reactive: 3.7 ± 0.04] (P = 0.008). The frequency of genetic polymorphisms of IDO did not reveal a significant association with Trp, Kyn, and Kyn/Trp in healthy and food-allergic cases. Culture of PBMC experiments yielded that IDO mRNA expression was not different between tolerant and reactive groups. IL-4 synthesis when stimulated with casein increased significantly in subjects who are reactive and tolerant to foods (P = 0.042, P = 0.006, respectively). Increase in IL-10 synthesis was observed only in children tolerant to milk, but not in reactive ones. IFN-γ synthesis, when stimulated with IL-2 and β-lactoglobulin in cell culture, was significantly higher in subjects tolerant to milk than in the reactive ones (P = 0.005 and P = 0.029, respectively).
CONCLUSION
Our results imply the probability of involvement of IDO in development of tolerance process, and we presume that high IDO activity is associated with nonresponsiveness to food allergens despite allergen sensitization.
|
10.1111/all.12785
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pubmed_407_23409
|
A 19-year old male who had a pectus excavatum deformity and recurrent primary spontaneous pneumothorax was admitted to our clinic. An intervention simultaneously combining a videothoracoscopic apical wedge resection and minimally invasive repair of the pectus excavatum deformity was successfully performed.
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10.1093/icvts/ivs283
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pubmed_437_9569
|
We report Raman spectra measurements on a MoS(2) monolayer supported on SiO(2) as a function of temperature. Unlike in previous studies, the positions of the two main Raman modes, E(2g)(1) and A(1g) exhibited nonlinear temperature dependence. Temperature dependence of phonon shifts and widths is explained by optical phonon decay process into two acoustic phonons. On the basis of Raman measurements, local temperature change under laser heating power at different global temperatures is derived. Obtained results contribute to our understanding of the thermal properties of two-dimensional atomic crystals and can help to solve the problem of heat dissipation, which is crucial for use in the next generation of nanoelectronic devices.
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10.1021/am502359k
|
pubmed_864_21355
|
INTRODUCTION AND HYPOTHESIS
Since the first reported laparoscopic sacrocolpopexy in 1991, a limited number of single-center studies have attempted to assess the procedure's effectiveness and safety. Therefore, we analyzed a national Medicare database to compare real-world short-term outcomes of open and laparoscopically assisted (including robotic) sacrocolpopexy in a United States sample of patients.
METHODS
Public Use File data for a 5% random national sample of all Medicare beneficiaries aged 65 and older were obtained from the Centers for Medicare and Medicaid Services for the years 2004-2008. Women with pelvic organ prolapse were identified using ICD-9 diagnosis codes. CPT-4 procedure codes were used to identify women who underwent open (code 57280) or laparoscopic (code 57425) sacrocolpopexy. Individual subjects were followed for 1 year post-operatively. Outcomes measured, using ICD-9 and CPT-4 codes, included medical and surgical complications and re-operation rates.
RESULTS
Seven hundred and ninety-four women underwent open and 176 underwent laparoscopic (including robotic) sacrocolpopexy. Laparoscopic sacrocolpopexy was associated with a significantly increased rate of re-operation for anterior vaginal wall prolapse (3.4% vs 1.0%, p = 0.018). However, more medical (primarily cardiopulmonary) complications occurred post-operatively in the open group (31.5% vs 22.7%, p = 0.023). When sacrocolpopexy was performed with concomitant hysterectomy, mesh-related complications were significantly higher in the laparoscopic group (5.4% vs 0%, p = 0.026).
CONCLUSION
Laparoscopic sacrocolpopexy resulted in an increased rate of reoperation for prolapse in the anterior compartment. When hysterectomy was performed at the time of sacrocolpopexy, the laparoscopic approach was associated with an increased risk of mesh-related complications.
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10.1007/s00192-013-2088-9
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pubmed_510_5053
|
We have shown, by analyzing serial serum samples from a chronic hepatitis B virus (HBV) carrier, the emergence of HBV DNA molecules with nucleotide rearrangements in the pre-S/S and pre-C/C genes. Serum samples were obtained at four different times (1983, 1985, 1988, and 1989) from an HBsAg- and HBeAg-positive carrier with chronic hepatitis. The polymerase chain reaction was used to amplify the pre-S/S and pre-C/C genes. The amplified products were cloned, and 8 to 10 independent clones were sequenced. In 1983 and 1985 only one type of HBV DNA molecule was observed. Nucleotide divergence relative to the adw2 subtype was 4.7, 7.2, and 1.6%, for the pre-S1, pre-S2, and S regions, respectively, and 2.2 and 3.9% for the pre-C and C regions, respectively. In 1988 and 1989, HBV DNA forms with marked rearrangements of both the pre-S/S and pre-C/C regions were evidenced. In the pre-S/S region, they comprised two distinct HBV DNA molecules. The first showed nucleotide divergence of 20.4, 14.8, and 3.3% for the pre-S1, pre-S2, and S regions when compared with the adw2 sequence. In addition, nucleotide deletions in the pre-S1 region led to the appearance of a stop codon. The second was created by recombination between the original and mutated HBV DNA. In the pre-C/C region, the mutated viral DNA showed 11.7% divergence when compared with the adw2 sequence. A point mutation led to the creation of a stop codon in the pre-C region, together with an insertion of 36 nucleic acids in the core gene. Most of this DNA insertion was identical to that reported in an independent HBV isolate but showed no significant homology with known sequences. Semiquantitative estimation of the proportion of wild-type and mutated HBV DNA molecules showed a marked increase in the mutated forms during the period of follow-up. Sucrose gradient analysis indicated that the defective HBV DNA molecules were present in circulating virions. Western immunoblot analysis showed the appearance of modified translation products. Our findings thus indicate the emergence of and gradual takeover by mutated HBV DNA forms during the HBV chronic carrier state. The rearrangements we observed in the pre-S/S and pre-C/C genes might lead to changes in the immunogenicity of the viral particles and thus affect the clearance of the virus by the immune system.
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10.1128/JVI.65.7.3566-3574.1991
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pubmed_713_11639
|
BACKGROUND
Emerging evidence implicates the gut microbiome in liver inflammation and hepatocellular carcinoma (HCC) development. We aimed to characterize the temporal evolution of gut dysbiosis, in relation to the phenotype of systemic and hepatic inflammatory responses leading to HCC development. In the present study, Mdr2 -/- mice were used as a model of inflammation-based HCC. Gut microbiome composition and function, in addition to serum LPS, serum cytokines/chemokines and intrahepatic inflammatory genes were measured throughout the course of liver injury until HCC development.
RESULTS
Early stages of liver injury, inflammation and cirrhosis, were characterized by dysbiosis. Microbiome functional pathways pertaining to gut barrier dysfunction were enriched during the initial phase of liver inflammation and cirrhosis, whilst those supporting lipopolysaccharide (LPS) biosynthesis increased as cirrhosis and HCC ensued. In parallel, serum LPS progressively increased during the course of liver injury, corresponding to a shift towards a systemic Th1/Th17 proinflammatory phenotype. Alongside, the intrahepatic inflammatory gene profile transitioned from a proinflammatory phenotype in the initial phases of liver injury to an immunosuppressed one in HCC. In established HCC, a switch in microbiome function from carbohydrate to amino acid metabolism occurred.
CONCLUSION
In Mdr2 -/- mice, dysbiosis precedes HCC development, with temporal evolution of microbiome function to support gut barrier dysfunction, LPS biosynthesis, and redirection of energy source utilization. A corresponding shift in systemic and intrahepatic inflammatory responses occurred supporting HCC development. These findings support the notion that gut based therapeutic interventions could be beneficial early in the course of liver disease to halt HCC development.
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10.1186/s12866-021-02171-9
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pubmed_1110_15264
|
Epithelial cell dynamics can be difficult to study in intact animals or tissues. Here we use the medusa form of the hydrozoan Clytia hemisphaerica, which is covered with a monolayer of epithelial cells, to test the efficacy of an orientation-independent differential interference contrast microscope for in vivo imaging of wound healing. Orientation-independent differential interference contrast provides an unprecedented resolution phase image of epithelial cells closing a wound in a live, nontransgenic animal model. In particular, the orientation-independent differential interference contrast microscope equipped with a 40x/0.75NA objective lens and using the illumination light with wavelength 546 nm demonstrated a resolution of 460 nm. The repair of individual cells, the adhesion of cells to close a gap, and the concomitant contraction of these cells during closure is clearly visualized.
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10.1111/jmi.12682
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pubmed_242_3422
|
IgA nephropathy (IgAN) is the most common form of primary glomerulonephritis in the world. IgAN is characterized by the mesangial accumulation of immune complexes containing IgA1, usually with co-deposits of complement C3 and variable IgG and/or IgM. Although more than 40 years have passed since IgAN was first described, the mechanisms underlying the disease development are not fully understood. Small-animal experimental models of IgAN can be very helpful in studies of IgAN, but development of these models has been hindered by the fact that only humans and hominoid primates have IgA1 subclass. Thus, multiple models have been developed, that may be helpful in studies of some specific aspects of IgAN. These models include a spontaneous animal model of IgAN, the ddY mouse first reported in 1985. These mice show mild proteinuria without hematuria, and glomerular IgA deposits, with a highly variable incidence and degree of glomerular injury, due to the heterogeneous genetic background. To obtain a murine line consistently developing IgAN, we intercrossed an earlyonset group of ddY mice, in which the development of IgAN includes mesangial IgA deposits and glomerular injury. After selective intercrossing for >20 generations, we established a novel 100% early-onset grouped ddY murine model. All grouped ddY mice develop proteinuria within eight weeks of age. The grouped ddY mouse model can be a useful tool for analysis of multiple aspects of the pathogenesis of IgAN and may aid in assessment of some approaches for the treatment of IgAN.
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10.1016/j.ddmod.2014.07.002
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pubmed_795_12584
|
Synthesis of river-monitoring data reveals that the average annual discharge of fresh water from the six largest Eurasian rivers to the Arctic Ocean increased by 7% from 1936 to 1999. The average annual rate of increase was 2.0 +/- 0.7 cubic kilometers per year. Consequently, average annual discharge from the six rivers is now about 128 cubic kilometers per year greater than it was when routine measurements of discharge began. Discharge was correlated with changes in both the North Atlantic Oscillation and global mean surface air temperature. The observed large-scale change in freshwater flux has potentially important implications for ocean circulation and climate.
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10.1126/science.1077445
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pubmed_848_16825
|
On computed tomograms obtained during a seven-year period, 27 patients were found to have high-density bile in the gallbladder. Serial computed tomography (CT) examinations showed that gradual narrowing of common bile duct is a causative factor. This has not been reported previously. The density of the bile in the gallbladder of patients with such obstruction was almost equal to that of normal liver on CT. In some of the patients in whom obstruction of the cystic duct was the factor of high-density bile and continued for a long time, the density of the bile decreased and hydrops developed.
|
10.1007/BF01888727
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pubmed_163_15042
|
Scattering and correlation properties of a two-photon (TP) pulse are studied in a four-terminal waveguide system, i.e., two one-dimensional waveguides connected by a Jaynes-Cummings emitter (JCE). The wave function approach is utilized to exactly calculate the real-time dynamic evolution of the TP transport. When the width of the incident TP Gaussian pulse is much larger than the photon wavelength, the TP transmission spectra approach that of the corresponding single photon cases and are almost independent of the pulse width. On the contrary, as the pulse width is comparable to the photon wavelength, the TP transmission and correlation both show strong dependence on the pulse width. The resonant scattering due to the JCE and the photon interference together determine the TP correlation. When the distance between the TPs is small, the TP correlations between any two terminals for the scattered TP pulse are much different from those for the incident TP pulse and therefore, such a four-terminal waveguide system provides a way to control the TP correlation.
|
10.1364/OE.438840
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pubmed_214_852
|
On March 15, 2019, Cyclone Idai made landfall near the port city of Beira in central Mozambique causing significant casualties and serious damage to infrastructure. The Emergency Medical Team Type 2 - Italy Regione Piemonte (EMT2-ITA) was deployed approximately two weeks after the disaster to support the country in need, providing essential medical and surgical care.The EMT2-ITA staff was composed of 77 team members including two rotations and integrating local staff. A total of 1,121 patients (1,183 triage admissions) were treated during the 27 days of field hospital activity; among all the admissions, only few cases (17; 1%) were directly or indirectly attributed to the disaster event. Only three cases of cholera were confirmed and transferred to one of the treatment centers set up in Beira. The EMT2-ITA performed a total of 62 surgical operations (orthopedic, gynecological, general, and plastic surgery), of which more than one-half were elective procedures.The objective of this manuscript is to report the mission of the EMT2-ITA in Mozambique, raising interesting points of discussion regarding the impact of timing on the mission outcomes, the operational and clinical activities in the field hospital, and the great importance to integrate local staff into the team.
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10.1017/S1049023X22000772
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pubmed_197_24781
|
Optical phase conjugation in methylene blue sensitized gelatin film has been obtained with 514.5-nm radiation from an argon-ion laser with power levels as low as 50 mW/cm(2) for the pump beam in a degenerate four-wavemixing configuration. The film with a thickness of 110-120 microm prepared from a solution of a 1.8-mmol concentration of methylene blue sensitized gelatin shows a good phase-conjugate reflectivity of 0.5% for this power level at 514.5 nm, which is well away from its absorption peak at ~ 650 nm.
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10.1364/AO.31.004905
|
pubmed_749_22802
|
Enhancement of brain-derived neurotrophic factor (BDNF) signalling has great potential in therapy for neurological and psychiatric disorders. This neurotrophin not only attenuates cell death but also promotes neuronal plasticity and function. However, an important challenge to this approach is the persistence of aberrant neurotrophic signalling due to a defective function of the BDNF high-affinity receptor, tropomyosin-related kinase B (TrkB), or downstream effectors. Such changes have been already described in several disorders, but their importance as pathological mechanisms has been frequently underestimated. This review highlights the relevance of an integrative characterization of aberrant BDNF/TrkB pathways for the rational design of therapies that by combining BDNF and TrkB targets could efficiently promote neurotrophic signalling.
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10.3390/ijms18020268
|
pubmed_319_6021
|
OBJECTIVE
Attention-deficit/hyperactivity disorder (ADHD) is one of the most prevalent mental disorders in children in the United States and often persists into adulthood with associated symptomatology and impairments. This article comprehensively reviews studies reporting ADHD-related incremental (excess) costs for children/adolescents and adults and presents estimates of annual national incremental costs of ADHD.
METHOD
A systematic search for primary United States-based studies published from January 1, 1990 through June 30, 2011 on costs of children/adolescents and adults with ADHD and their family members was conducted. Only studies in which mean annual incremental costs per individual with ADHD above non-ADHD controls were reported or could be derived were included. Per-person incremental costs were adjusted to 2010 U.S. dollars and converted to annual national incremental costs of ADHD based on 2010 U.S. Census population estimates, ADHD prevalence rates, number of household members, and employment rates by age group.
RESULTS
Nineteen studies met the inclusion criteria. Overall national annual incremental costs of ADHD ranged from $143 to $266 billion (B). Most of these costs were incurred by adults ($105 B-$194 B) compared with children/adolescents ($38 B-$72 B). For adults, the largest cost category was productivity and income losses ($87 B-$138 B). For children, the largest cost categories were health care ($21 B-$44 B) and education ($15 B-$25 B). Spillover costs borne by the family members of individuals with ADHD were also substantial ($33 B-$43 B).
CONCLUSION
Despite a wide range in the magnitude of the cost estimates, this study indicates that ADHD has a substantial economic impact in the United States. Implications of these findings and future directions for research are discussed.
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pubmed_319_6021
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pubmed_892_21681
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Progression of eukaryotic cells through the cell cycle is governed by the sequential formation, activation, and subsequent inactivation of a series of cyclin-dependent kinase (Cdk) complexes. p27(Kip1) (p27) is a Cdk inhibitor that blocks, in vitro, the activity of cyclin D-Cdk4, cyclin D-Cdk6, cyclin E-Cdk2 as well as cyclin A-Cdk2, a complex active during S phase. The level of p27 protein expression, usually high in G0/G1 resting cells, declines as cells progress toward S phase and enforced expression of p27 in fibroblasts causes G1 arrest. This situation prevails in CCL39, a Chinese hamster lung fibroblast cell line (this report). However, in addition to p27, several other Cdk inhibitors known to alter G1 progression coexist in most mammalian cells. To investigate the specific contribution of p27 in the control of the mitogen-sensitive G0/G1 arrest, we specifically reduced its synthesis by expressing a full-length p27 antisense cDNA in CCL39 cells. Interestingly, reduction of up to 90% of p27 protein expression increased both basal and serum-stimulated gene transcription of cyclin D1, cyclin A, dihydrofolate reductase, and DNA synthesis reinitiation. Moreover, overexpression of this antisense allows cells to grow for several generations in a serum-free medium supplemented with insulin and transferrin only, thus suggesting that p27-depleted cells cannot exit the cell cycle. These effects were fully reversed by coexpression of a plasmid encoding p27 sense. We conclude that p27, by setting the level of growth factor requirement, plays a pivotal role in controlling cell cycle exit, a fundamental step in growth control.
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10.1074/jbc.271.31.18337
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pubmed_213_13214
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Immunoreactive atrial natriuretic peptide (ANP) has been detected in retinal tissue by radioimmunoassay, although it is unclear whether it was in retinal cells or represented residual peptide from blood and/or ocular fluids. We report here, using the immunoperoxidase method and a highly specific anti-rat ANP, that the peptide was localized consistently in the outer and inner plexiform layers of retinas of rats and rabbits. This information raises important issues: what are the implications for retinal function and, since blood-borne radioligands do not reveal retinal 'receptors', what is the endogenous target of retinal ANP?
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10.1016/0006-8993(89)91612-0
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pubmed_1118_3114
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Osteoporosis is a significant health problem, with skeletal fractures increasing morbidity and mortality. Excess glucocorticoids (GC) represents the leading cause of secondary osteoporosis. The first phase of glucocorticoid-induced osteoporosis is increased bone resorption. In this Chapter, in vitro studies of the direct glucocorticoid receptor (GR) mediated cellular effects of GC on osteoclasts to affect bone resorption and indirect effects on osteoblast lineage cells to increase the RANKL/OPG ratio and stimulate osteoclastogenesis and bone resorption are reviewed in detail, together with detailed descriptions of in vivo effects of GC in different portions of the skeleton in research animals and humans. Brief sections are devoted to contrasting functions of GC in osteonecrosis, vitamin D formation, in vitro and in vivo bone resorptive actions dependent on vitamin D receptor and vitamin D toxicity, as well as the molecular basis of GR action. Included are also more detailed assessments of the interactions of GC with the major calcium regulating hormones, 1,25(OH)2-vitamin D3 and parathyroid hormone, describing the in vitro increases in RANKL/OPG ratios, osteoclastogenesis and synergistic bone resorption that occurs when GC is combined with either 1,25(OH)2-vitamin D3 or parathyroid hormone. Additionally, a molecular basic for the synergistic interaction of GC with 1,25(OH)2-vitamin D3 is provided along with a suggested molecular basic for the interaction between GC and parathyroid hormone.
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10.1016/bs.vh.2022.04.005
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pubmed_1102_11139
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Keloid fibroblasts (KFs) undergo reprogramming of the metabolic phenotype from oxidative phosphorylation to the Warburg effect. However, more studies are needed to demonstrate whether there is a Warburg effect in KFs and to determine whether there is a similar phenomenon in other types of scars or in the proliferative stage of scars. In our study, the mRNA and protein expression of key glycolytic enzymes, glucose consumption and lactate production in KFs, normal skin fibroblasts (NFs), atrophic scar fibroblasts (ASFs), proliferative stage scar fibroblasts (PSSFs), and hypertrophic scar fibroblasts (HSFs) were detected. In addition, the effects of 2-deoxy-d-glucose (2-DG, a glycolysis inhibitor) on cell proliferation in KFs and NFs were studied. We found that the mRNA and protein expression of key glycolytic enzymes in KFs were significantly upregulated compared with those in NFs. Glucose consumption and lactate production in KFs were also higher than that in NFs. However, we found no similar phenomenon in ASFs, PSSFs, or HSFs. When treated with 2mmol/l 2-DG, the cell viability of KFs decreased more than that of NFs. What's more, treatment with increasing concentrations of 2-DG could inhibit cell viability and migration of KFs in a dose-dependent manner. In conclusion, the Warburg effect in KFs is a feature different from ASFs, PSSFs, or HSFs. Keloids are essentially different from other types of scars in terms of energy metabolism. This characteristic of KFs could provide new hope for the early diagnosis and treatment of keloids.
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10.1016/j.burns.2021.03.003
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pubmed_1098_163
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The aim of this study was to evaluate the electrocardiographic responses of Colossoma macropomum exposed to short-term baths using the essential oil of Piper divaricatum (EOPD) as an anaesthetic-like agent in different doses (40, 60, and 80 μL L-1). Cardiac responses throughout and after exposure to EOPD were monitored and evaluated through mean heart rate (HR), duration and amplitude of the QRS complex (ventricular depolarization), and Q-T (ventricular contraction) and R-R (time between two successive QRS complexes) wave intervals. Across all doses, there was a marked depression of the HR, mainly at 80 μL L-1 EOPD. Mean amplitudes recorded for the QRS complex and Q-T interval at 40 μL L-1 EOPD were indistinguishable from the control, which could reinforce this concentration as sufficient and safe to promote fast anaesthesia without affecting cardiac function. Recovery from bradycardia, duration of the R-R interval, and QRS complex were similar at 60 and 80 μL L-1 EOPD; however, the Q-T interval at 80 μL L-1 EOPD revealed a more pronounced cardiac depression in relation to the controls and fish exposed to 60 μL L-1 EOPD. Thus, we conclude that 40 μL L-1 EOPD should suffice to induce fast, deep, and safe anaesthesia in tambaqui juveniles, whereas the concentration of 80 μL L-1 led to a greater depression of the cardiac function, albeit showing effect reversibility.
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10.1007/s10695-022-01132-x
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