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pubmed_579_2043
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This paper presents the results of microscopic examinations of the yeast cells cultured in yeast extract-peptone-dextrose (YPD) media supplemented with sodium selenite(IV). The analysis of the morphological changes in yeast cells aimed to determine whether the selected selenium doses and culturing time may affect this element accumulation in yeast cell structures in a form of inorganic or organic compounds, as a result of detoxification processes. The range of characteristic morphological changes in yeasts cultivated in experimental media with sodium selenite(IV) was observed, including cell shrinkage and cytoplasm thickening of the changes within vacuole structure. The processes of vacuole disintegration were observed in aging yeast cells in culturing medium, which may indicate the presence of so-called ghost cells lacking intracellular organelles The changes occurring in the morphology of yeasts cultured in media supplemented with sodium selenite were typical for stationary phase of yeast growth. From detailed microscopic observations, larger surface area of the cell (6.03 μm(2)) and yeast vacuole (2.17 μm(2)) were noticed after 24-h culturing in the medium with selenium of 20 mg Se(4+)/L. The coefficient of shape of the yeast cells cultured in media enriched with sodium selenite as well as in the control YPD medium ranged from 1.02 to 1.22. Elongation of cultivation time (up to 48 and 72 h) in the media supplemented with sodium selenite caused a reduction in the surface area of the yeast cell and vacuole due to detoxification processes.
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10.1007/s12011-015-0415-3
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pubmed_856_22070
|
OBJECTIVE
Takotsubo syndrome following cardiac surgery is a rare occurrence. However, early diagnosis is essential to prevent treatment which could increase the left ventricular outflow tract pressure gradient in patients with Takotsubo syndrome, and lead to cardiogenic shock. Therefore, our study aimed to identify the incidence of Takotsubo syndrome after cardiopulmonary bypass and the associated risk factors and prognosis.
METHODS
We retrospectively studied 5773 patients who underwent cardiopulmonary bypass between February 2007 and July 2017. Among these, Takotsubo syndrome was diagnosed in 52 (0.9%). To evaluate the risk factors for Takotsubo syndrome, 104 of the remaining 5721 patient were randomly selected as the control group (1:2 ratio). Univariate and multivariate logistic regression analyses were used for risk factor analysis.
RESULTS
Majority of patients (69.2%) in the Takotsubo syndrome group underwent mitral valve surgery, compared with 32.7% in the control group. The following risk factors of Takotsubo syndrome were identified: atrio-ventricular valve surgery (odds ratio (OR) 10.5; 95% confidence interval (CI), 2.6-42.5; p = 0.001); and the immediate postoperative use of epinephrine (OR, 3.3; 95% CI, 1.0-10.7; p = 0.05) and dobutamine (OR, 4.8; 95% CI, 1.72-13.3; p = 0.003). Hypertension was a significant protective factor against Takotsubo syndrome following cardiac surgery (OR, 0.22; 95% CI, 0.06-0.73; p = 0.01).
CONCLUSION
Takotsubo syndrome following cardiac surgery is rare. Immediate postoperative use of epinephrine and doputamine, as well as atrio-ventricular valve surgery were factors associated with the development of Takotsubo syndrome.
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10.1111/jocs.15626
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pubmed_414_1133
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The radical reaction of TMS-substituted xanthates with 2,2-dichlorovinyl ethyl sulfone afforded TMS-substituted homodichlorovinyl compounds that can be transformed into TMS-substituted propargyl alcohols. Various 2,3-allenols were efficiently prepared from the reaction of these TMS-substituted propargyl alcohols with TBAF.
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10.1021/ol900739x
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pubmed_921_16565
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Familial hypercholesterolaemia (FH) is an autosomal-dominant inherited disorder clinically characterized by high serum cholesterol (low-density lipoprotein--LDL-fraction) concentrations, xanthomas and premature atherosclerosis. Homozygous individuals suffer from vascular disease in childhood or young adolescence since heterozygous persons are usually at ligh risk of premature cardiovascular death. We present a 42-year old female with coronary heart disease and tuber and tendinous xanthomas, which appeared as a consequence of delayed diagnosis of familial hypercholesterolaemia. She was admitted to the hospital due to unstable angina pectoris. On admission the patient was haemodinamically compensated. Cardiac rhythm was regular and heart sounds were of normal intensity. She also presented two systolic murmurs. The first, the ejection murmur had maximal intensity in the second right intercostal space and radiated to the appex. The second murmur was regurgitant, generated at the appex and propagated to the anterior aixllary line. On inspection, we observed xanthomas in Achillis tendons and palmar extensors as well as tuberous xanthomas in the knees and fingers of both hands and feet. We also observed bilateral xantholasms. Arcus corneae was detected by ophthalmological examination. On admittance, the cholesterol serum level was 13.2 mmol/L, and LDL fraction was 7.6 mmol/L. Echocardiography revealed sclerosis of the aortic valve and mitral annulus. Coronarography documented the three-vessel disease. An aggressive medical treatment, which consisted of bile salts and HMGCoA reductase inhibitors, resulted in significant lowering of serum cholesterol--more than 30%. However, due to refractory angina pectorts, she had to be operated on and aorto-coronary by-pass was performed.
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pubmed_921_16565
|
pubmed_558_3183
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Large-conductance calcium and voltage-dependent potassium (BK(Ca)) channel is an important determinant of vascular tone. It is activated by hydrogen peroxide (H(2)O(2)) which occurs in various physiological and pathological processes. However, the regulation mechanism is not fully understood. In the present study, the mSlo in the presence or absence of hbeta1 were cotransfected with the PTEN(wt), PTEN(C124S), PTEN(G129E) in HEK 293 cells. Typical BK(Ca) channel currents could be recorded in cell-attached configurations. We found that PTEN(wt) reduced the H(2)O(2)-induced BK(Ca) channel activation during the initial 10 min treatment. In contrast, coexpression with catalytically inactive PTEN(C124S)/PTEN(G129E) mutants that lack lipid phosphatase activity produced no regulation on the H(2)O(2)-induced BK(Ca) channel activation. These results demonstrated that PTEN regulated the H(2)O(2)-induced BK(Ca) channel activation through phosphatidylinositol 3-phosphatse. However, the inhibitory effect of PTEN on the H(2)O(2)-induced BK(Ca) channel activation was attenuated when cells were treated with H(2)O(2) at concentrations higher than 100 microM or at 100 microM for long-term treatment. In addition, the p-AKT expression level in PTEN(wt) overexpressing cells was lower than that in control cells, and the increase of cytoplasmic free calcium concentration ([Ca(2+)](i)) induced by H(2)O(2) was also inhibited. These findings may elucidate a new mechanism for H(2)O(2)-induced BK(Ca) channel activation and provide some evidences for the role of PTEN on vasodilation induced by H(2)O(2).
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10.1016/j.bbamem.2009.07.016
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pubmed_121_25425
|
Today's science is largely funded by taxpayer dollars, and because of this, scientists have a responsibility to ensure that their research is being effectively communicated back to taxpayers and to the policy makers who determine the distribution of those funds. The importance and impact of effective science communication is compounded when research is used to inform legislative action. Science impacts policy, and policy can impact science. However, the formal education of scientists does not usually include specific training on interacting with science policy. This article describes strategies for engaging with science policy-starting with simple and easy policy actions, and delving into more complex event planning and group organizing tasks. Whether advocating for evidence-based policies or policies that impact the scientific enterprise or STEM education, practicing skills pertinent to science policy can help you gain comfort in translating your experiences and experiments into lasting change.
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10.1002/cpet.37
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pubmed_497_872
|
The supply of medical goods is an important critical success factor in German hospitals. One major managerial area in the procurement concerns the decision between single patient use (SPU) and multiple patient use (MPU) products. Especially laparoscopic instruments which are generally expensive are a field of interest for decision makers. Due to a lack of quantifiable factors describing the two different forms of supply alternatives with their effects on effectivity and efficiency of the procurement process and the final use are often not taken into account. Since it is expected that in the future more and more laparoscopic instruments will be needed there is a necessity for finding a concept allowing the identification of the "right" product. The Center for Hospital Management (CKM) has the aim to develop a corresponding approach but needs the help of the reader.
|
10.1055/s-2000-10608
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pubmed_1092_22832
|
The objective of this study was to estimate the current prevalence of psychiatric disorders in cocaine-dependent patients who attend different treatment centres in the Community of Madrid. A prospective multicentre study was used, and a total of 197 cocaine-dependent subjects were assessed. The assessment instrument used for diagnosis was the Psychiatric Research Interview for Substance and Mental Disorders (PRISM-IV). The main findings of this study were a high prevalence of psychiatric comorbidity in cocaine-dependent patients seeking treatment (64.0%). The most common Non Substance Use Disorders found were attention-deficit/hyperactivity Disorders (34.5%) and depressive disorders (13.7%). The most common Substance Use Disorder was alcohol dependence (28.4%). Cocaine-dependent patients who had a depressive disorder and were alcohol dependent presented a more severe clinical profile and a higher degree of psychopathology, measured using different assessment tools, than the patients who were only cocaine dependent. These data suggest that the presence of psychiatric comorbidity could constitute a risk factor associated with the severity of cocaine dependence. The clinical heterogeneity found also indicates the need to search for individualised treatments that more specifically fit the needs of this population.
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10.20882/adicciones.785
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pubmed_1029_4853
|
To determine the site of action of opiates in humans, we have studied the effect of systemic and inhaled opiates on cough and increase in respiratory resistance (Rrs) caused by inhaled capsaicin. In 13 subjects, a range of doses of capsaicin inhaled in single breaths given in random order produced a reproducible dose-cough response. Inhalation of a dose of capsaicin that caused fewer than two coughs increased Rrs by 28% (21-35, mean 95% confidence interval). Inhaled codeine (50 mg) and morphine (10 mg) did not alter the cough response. In contrast, both drugs increased base-line Rrs by 24% (16-44) and 13% (3-23), respectively, and significantly reduced the increase in Rrs after inhaled capsaicin (P less than 0.05). Oral codeine (60 mg) significantly (P less than 0.05) reduced the number of coughs at 1 and 2 h but did not alter base-line Rrs or its increase after capsaicin. Intravenous morphine (0.15 mg/kg) significantly reduced the sensitivity of the cough response (P less than 0.05), which was reversed by naloxone. However, there was no significant drug effect on either the base-line Rrs or its increase after capsaicin. Systemic dosing of opiates is therefore required to reduce the cough reflex, whereas inhaled opiates may reduce the increase in Rrs after inhaled capsaicin.
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10.1152/jappl.1988.65.3.1125
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pubmed_89_26203
|
BACKGROUND/AIM
The over-expression of P-glycoprotein (P-gp) is a major mechanism underlying multidrug resistance (MDR). Co-treatment with Janus kinase 2 (Jak2) inhibitors sensitizes P-gp-over-expressing drug-resistant cancer cells. In this study, we evaluated pacritinib, a Jak2 inhibitor currently in phase III clinical trials.
MATERIALS AND METHODS
Microscopic observation, cell viability assay, colony forming assay, rhodamine uptake tests, annexin V analyses, fluorescence-activated cell sorting (FACS), and western-blot analysis were performed to further investigate the mechanism of action.
RESULTS
We found that pacritinib reduced cell viability, induced G2 arrest, and upregulated early apoptosis when administered to P-gp-over-expressing resistant KBV20C cells with vincristine (VIC). Moreover, apoptosis and G2 arrest in VIC-pacritinib-treated cells were involved in the upregulation of pH2AX expression. Pacritinib had an approximately 2-fold higher P-gp-inhibitory activity than the dimethyl sulfoxide (DMSO)-treated control, indicating that VIC-pacritinib sensitization involves the P-gp-inhibitory effects of pacritinib. Similar to VIC, other antimitotic drugs (vinorelbine, vinblastine, and eribulin) could also sensitize against KBV20C cells by co-treatment with pacritinib. Furthermore, comparison of pacritinib with previously characterized Jak2 inhibitors revealed that the VIC-pacritinib combination had sensitization effects similar to those of VIC- CEP-33779 or VIC-NVP-BSK805 combinations at lower doses in KBV20C cells. Generally, Jak2 inhibitor and VIC co-treatment sensitized P-gp-over-expressing resistant cancer cells by inducing early apoptosis.
CONCLUSION
Collectively, pacritinib, induced G2 arrest, reduced cell viability, had high P-gp inhibitory activity, and upregulated the expression of pH2AX when used in combination with VIC. As pacritinib is a Jak2 inhibitor currently in phase III clinical trials, our findings may facilitate the application of this co-treatment in patients with MDR cancer.
|
10.21873/anticanres.15722
|
pubmed_1050_5615
|
Miscarriage is a common, complex trait affecting ~15% of clinically confirmed pregnancies. Here we present the results of large-scale genetic association analyses with 69,054 cases from five different ancestries for sporadic miscarriage, 750 cases of European ancestry for multiple (≥3) consecutive miscarriage, and up to 359,469 female controls. We identify one genome-wide significant association (rs146350366, minor allele frequency (MAF) 1.2%, P = 3.2 × 10-8, odds ratio (OR) = 1.4) for sporadic miscarriage in our European ancestry meta-analysis and three genome-wide significant associations for multiple consecutive miscarriage (rs7859844, MAF = 6.4%, P = 1.3 × 10-8, OR = 1.7; rs143445068, MAF = 0.8%, P = 5.2 × 10-9, OR = 3.4; rs183453668, MAF = 0.5%, P = 2.8 × 10-8, OR = 3.8). We further investigate the genetic architecture of miscarriage with biobank-scale Mendelian randomization, heritability, and genetic correlation analyses. Our results show that miscarriage etiopathogenesis is partly driven by genetic variation potentially related to placental biology, and illustrate the utility of large-scale biobank data for understanding this pregnancy complication.
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10.1038/s41467-020-19742-5
|
pubmed_1094_14584
|
INTRODUCTION
Pain is the key concern of women after caesarean delivery that may interfere with breastfeeding.
AIM
The aim of this study was to assess effect of ketofol (ketamine/propofol combination) on pain and complication after caesarean delivery under spinal anaesthesia.
MATERIALS AND METHODS
In this randomized double-blind clinical trial, 92 parturient scheduled for elective caesarean delivery under spinal anaesthesia were included. The simple random sampling method was used to place subjects in four groups of ketamine (0.25 mg/kg), propofol (0.25 mg/kg), ketofol (25 mg ketamine plus 25 mg propofol) and placebo (saline). The drugs were administered intravenously immediately after clamping the umbilical cord. Visual Analog Scale (VAS) was used to determine the intensity of pain. Complications after surgery including shivering, nausea and vomiting as well as onset of breastfeeding were recorded.
RESULTS
The mean score of pain, morphine consumption and time of breastfeeding in the ketofol group were significantly lower than other groups at various intervals (p<0.05, p<0.001). The frequencies of shivering, nausea, vomiting, retention and pruritus in the ketofol group were significantly lower than other groups (p<0.001, p<0.05).
CONCLUSION
The effective role of ketofol on reducing pain and complication after caesarean delivery indicated that it can be considered as a safe and alternative drug in these patients.
|
10.7860/JCDR/2017/21437.9434
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pubmed_692_20070
|
Radiation necrosis (RN) is a serious complication that can occur in up to 10% of brain radiotherapy cases, with the incidence dependent on both dose and brain location. Available medical treatment for RN includes steroids, vitamin E, pentoxifylline, and hyperbaric oxygen. In a significant number of patients, however, RN is medically refractory and the patients experience progressive neurological decline, disabling headaches, and decreased quality of life. Vascular endothelial growth factor (VEGF) is a known mediator of cerebral edema in RN. Recent reports have shown successful treatment of RN with intravenous bevacizumab, a monoclonal antibody for VEGF. Bevacizumab, however, is associated with significant systemic complications including sinus thrombosis, pulmonary embolus, gastrointestinal tract perforation, wound dehiscence, and severe hypertension. Using lower drug doses may decrease systemic exposure and reduce complication rates. By using an intraarterial route for drug administration following blood-brain barrier disruption (BBBD), the authors aim to lower the bevacizumab dose while increasing target delivery. In the present report, the authors present the cases of 2 pediatric patients with cerebral arteriovenous malformations, who presented with medically intractable RN following stereotactic radiosurgery. They received a single intraarterial infusion of 2.5 mg/kg bevacizumab after hyperosmotic BBBD. At mean follow-up duration of 8.5 months, the patients had significant and durable clinical and radiographic response. Both patients experienced resolution of their previously intractable headaches and reversal of cushingoid features as they were successfully weaned off steroids. One of the patients regained significant motor strength. There was an associated greater than 70% reduction in cerebral edema. Intraarterial administration of a single low dose of bevacizumab after BBBD was safe and resulted in durable clinical and radiographic improvements at concentrations well below those required for the typical systemic intravenous route. Advantages over the intravenous route may include higher concentration of drug delivery to the affected brain, decreased systemic toxicity, and a significantly lower cost.
|
10.3171/2014.9.PEDS14198
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pubmed_452_9919
|
Epidermal adult stem cells (EpiASCs) have the potential for unlimited proliferation and differentiation, however, the ability of these stem cells to activate corneal genetic programs in response to corneal stroma stimulation needs to be further validated. Herein, a feasible strategy was developed to reconstruct the damaged corneal surface in a goat model with total limbal stem cell deficiency (LSCD) by transplanting EpiASCs, which had been explanted and cultured from the skin of an adult ram goat and were then purified by selecting single cell-derived clones and cultivating them on a denuded human amniotic membrane (HAM). These artificial tissues were then successfully transplanted into ewe goats with total LSCD. Binding of EpiASCs to the base membrane of an EpiASCs-HAM-Sheet (EHS) indicated their proliferating status. After transplantation, the EpiASCs could survive in the host tissue and they reconstructed the damaged ocular surface of total LSCD. The crystal reconstructed corneal epithelium expressed CK3 and Pax-6 similar to normal corneal epithelium and expressed the Sry gene after transplantation. These results demonstrated that EpiASCs could be induced to differentiate into corneal epithelial cell types in a corneal microenvironment and had the ability to activate corneal genetic programs. This work offer a foundation for promoting tissue-engineered cornea into clinical application.
|
10.1007/s10735-020-09879-4
|
pubmed_648_1402
|
In recent years, climate change and carbon sinks have been widely studied by the academic community, and relevant research results have emerged in abundance. In this paper, a scientometric analysis of 747 academic works published between 1991 and 2018 related to climate change and carbon sinks is presented to characterize the intellectual landscape by identifying and revealing the basic characteristics, research power, intellectual base, research topic evolution, and research hotspots in this field. The results show that ① the number of publications in this field has increased rapidly and the field has become increasingly interdisciplinary; ② the most productive authors and institutions in this subject area are in the USA, China, Canada, Australia, and European countries, and the cooperation between these researchers is closer than other researchers in the field; ③ 11 of the 747 papers analyzed in this study have played a key role in the evolution of the field; and ④ in this paper, we divide research hotspots into three decade-long phases (1991-1999, 2000-2010, and 2011-present). Drought problems have attracted more and more attention from scholars. In the end, given the current trend of the studies, we conclude a list of research potentials of climate change and carbon sinks in the future. This paper presents an in-depth analysis of climate change and carbon sink research to better understand the global trends and directions that have emerged in this field over the past 28 years, which can also provide reference for future research in this field.
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10.1007/s11356-019-07489-6
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pubmed_784_5222
|
Paraquat, a frequently used contact herbicide, produces oxidative stress by undergoing redox cycling and generating reactive oxygen species. Paraquat is also effective at increasing hepatic levels of metallothionein (MT). The mechanism(s) by which agents that induce oxidative stress produce increases in MT concentrations is not yet known. Therefore, the goal of the current study was to characterize the elevation in hepatic MT produced by paraquat administration to mice and to examine potential mechanism(s) of this increase. A dose-response study for increases in MT showed that administration of 0.1 to 0.5 mmol/kg of paraquat, sc, increased hepatic MT with a maximal increase of 36-fold. Subsequent studies were carried out with paraquat at a dose (0.3 mmol/kg, sc) that caused oxidative stress, as shown by a 35-fold increase in the biliary excretion of oxidized glutathione. There were coordinate elevations of both hepatic MT-I and MT-II mRNA of approximately 5-fold with peaks at both 6 and 24 hr after paraquat. The time course for the elevation in hepatic MT protein following paraquat treatment showed that MT levels had a maximal increase of 18-fold obtained at 36 hr. Paraquat appears to be an indirect MT inducer, in that there were no elevations in MT when cultured mouse hepatocytes were exposed to paraquat. No rise in liver Zn was observed prior to the increase in hepatic MT, thus, a Zn redistribution to the liver did not cause the increase in hepatic MT following paraquat administration. Adrenalectomy did not abolish the increase in MT produced by paraquat, suggesting that adrenal gland products are not required for the increase in MT produced by paraquat. In conclusion, the chemical mediator responsible for the increase in hepatic MT after paraquat was not determined, but the elevation in MT concentration appears to be due to increased transcription.
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10.1016/0041-008x(92)90242-k
|
pubmed_871_12449
|
PURPOSE
To evaluate the incidence of residual diplopia and enophthalmos and the possible risk factors leading to their occurrence in patients who had orbital blowout fracture repair.
METHODS
Forty-two patients with pure orbital blowout fracture who had at least 6 months postoperative follow-up were included in the study group. Nineteen (45.2%) patients had orbital floor, two (4.8%) patients had medial orbital wall and 21 (50%) patients had a combination of orbital floor and medial orbital wall fractures. The fracture was reconstructed with porous polyethylene (Medpore) in 22, supramide in 12 and gelatin (Gelfilm) in 8 orbits. Mean postoperative follow-up was 11 months.
RESULTS
Preoperatively, 35 patients (83%) had diplopia and 13 patients (30.9%) had enophthalmos greater than 2 mm. Of 35 patients who had preoperative diplopia, only 7 (17%) patients experienced diplopia postoperatively. Diplopia improved 1 to 4 weeks (mean, 3 weeks) following surgery in 28 patients. Timing of surgery and age of the patient were significant for the development of postoperative diplopia (p < 0.05). Sex, location of the blowout fracture and the alloplast material were not found to be significant for the development of postoperative diplopia (p > 0.05). Enophthalmos persisted in three (7%) patients postoperatively.
CONCLUSION
Old patients were more likely to have residual postoperative diplopia. Surgical repair of blowout fractures within two weeks of trauma decreases the incidence of residual diplopia.
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10.1076/orbi.21.1.27.2598
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pubmed_1142_17350
|
AIMS
Depression and anxiety are the most common and prevalent mental health issues among undergraduate students. This study aimed to investigate the prevalence of anxiety and depression, their associated predictors, and to assess knowledge and use of antidepressant medications among university students in Jordan.
METHODS
A cross-sectional survey-based study was conducted in Jordan among undergraduate students from all levels of study. Istilli et al's questionnaire, the PHQ-9 and generalised anxiety disorder (GAD) scales were used in this study to explore the study objectives. Logistic regression analysis was used to identify predictors of anxiety and depression.
RESULTS
A total of 1582 undergraduate students participated in the study. Prevalence of depression was 22.3% (n = 330), with proportions of minimal, mild, moderate, moderately severe and severe depression to be 15.9%, 32.4%, 29.5%, 14.7% and 7.6%, respectively. Prevalence of anxiety was 15.8% (n = 173), with proportions of mild, moderate and severe anxiety to be 46.4%, 37.8% and 15.8%, respectively. Female students and those with low income (<500 JD) had higher depression mean scores compared with others. Females, arts and engineering students, divorced and those who have four or more children had higher anxiety mean scores compared with others.
CONCLUSION
Findings of this study addressed the importance of taking serious measures and interventions to prevent the development of severe mental illness among university students.
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10.1111/ijcp.14414
|
pubmed_888_19345
|
BACKGROUND
Insulin resistance appears to be an important risk factor for coronary artery disease.
OBJECTIVE
To examine the role of insulin resistance on coronary vasoreactivity in healthy subjects.
PATIENTS AND METHODS
Myocardial blood flow was quantitated using positron emission tomography and oxygen-15-labelled water in 10 healthy, nonobese men. The perfusion measurements were performed basally and during adenosine infusion, which has been used as a measure of coronary vasoreactivity. After perfusion measurements were taken, whole-body glucose uptake was determined using the euglycemic hyperinsulinemic clamp technique.
RESULTS
Basal myocardial blood flow was 0.89+/-0.21 mL.g(-1).min(-1); adenosine significantly increased the flow to 4.00+/-1.13 mL.g(-1).min(-1). Adenosine-stimulated myocardial blood flow was inversely associated with fasting serum insulin concentration (r=-0.69, P<0.05). Concordantly, hyperemic blood flow was associated with whole-body glucose uptake during euglycemic hyperinsulinemic conditions (r=0.64, P<0.05). Basal myocardial blood flow was not affected by insulin resistance.
CONCLUSION
The results of the present study demonstrate the novel finding that insulin resistance is associated with reduced coronary vasoreactivity, even in healthy subjects.
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pubmed_888_19345
|
pubmed_764_10570
|
Due to increased chloroquine resistance, the antifolate/sulpha drug combinations are becoming increasingly important in the chemotherapy of falciparum malaria. However, point mutations in the dihydrofolate reductase gene lead to resistance to the antifolate drugs. We therefore investigated the prevalence of the 6 reported point mutations in this gene among field isolates of Plasmodium falciparum from Kenya, to determine if the mutations correlated with resistance to pyrimethamine and the biguanides cycloguanil and chlorcycloguanil. We used a mutation-specific polymerase chain reaction technique to test for these reported mutations in 21 Kenyan isolates and 4 reference lines. We also amplified and directly sequenced the dihydrofolate reductase coding sequence from these parasites to confirm the results and test for other possible mutations. Of the reported mutations, we found S108N, which is the central mutation of pyrimethamine resistance, and mutations N51I and C59R, which modulate the levels of resistance and may confer decreases in response to cycloguanil that are folate and p-aminobenzoic acid dependent. No isolate possessed the paired point mutations S108T and A16V, or I164L and S108N, which have been associated with cycloguanil resistance in previous studies. These results provided supportive evidence for the combined use of a cycloguanil-class drug (e.g., chlorproguanil) and a sulpha drug (e.g., dapsone) against P.falciparum malaria in Kenya.
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10.1016/s0035-9203(97)90284-4
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pubmed_1066_8946
|
Maternal physiological dyslipidemia (MPD) supports fetal development in human pregnancy. However, some women develop maternal supraphysiological dyslipidemia (MSPD: increased total cholesterol (TC) and triglycerides (TG) levels). MSPH is present in normal and also in gestational diabetes mellitus (GDM) pregnancies. MSPD and GDM associate with fetoplacental endothelial dysfunction, producing alterations in nitric oxide (NO)-L-arginine/arginase metabolism. Nevertheless, the effect of MSPD on GDM, and how this synergy alters fetoplacental endothelial function is unknown. Therefore, the aim of this study was to evaluate in human umbilical vein endothelial cells, the effects of MSPD in GDM and how these pathologies together affect the fetoplacental endothelial function. 123 women at term of pregnancy were classified as MPD (n = 40), MSPD (n = 35), GDM with normal lipids (GDM-MPD, n = 23) and with increased lipids (GDM-MSPD, n = 25). TC ≥291 mg/dL and TG ≥275 mg/dL were considered as MSPD. Endothelial NO synthase (eNOS), human cationic amino acid transporter 1 (hCat1), and arginase II protein abundance and activity, were assayed in umbilical vein endothelial cells. In MSPD and GDM-MSPD, TC and TG increased respect to MPD and GDM-MPD. eNOS activity was reduced in MSPD and GDM-MSPD, but increased in GDM-MPD compared with MPD. However, decreased tetrahydrobiopterin levels were observed in all groups compared with MPD. Increased hCat1 protein and L-arginine transport were observed in both GDM groups compared with MPD. However, the transport was higher in GDM-MSPD compared to GDM-MPD. Higher Arginase II protein and activity were observed in GDM-MSPD compared with MPD. Thus, MSPD in GDM pregnancies alters fetal endothelial function associated with NO metabolism.
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10.1016/j.bbadis.2021.166216
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pubmed_476_4623
|
OBJECTIVE
To explore the accessibility and quality of existing haemodialysis services in an urban setting.
SETTING
The study was conducted in Bangalore city, India.
PARTICIPANTS
A total of 28 stakeholders including 2 nephrologists, 7 duty doctors, 13 dialysis technicians and 6 patients on long-term haemodialysis were selected from 20 dialysis centres in Bangalore city.
DESIGN AND METHODS
Qualitative study using in-depth interviews. A thematic analysis was done using the Availability, Accessibility, Acceptability and Quality Framework of WHO and the Bruce's Quality of Care Framework.
RESULTS
The study found several gaps with regard to the access and quality of existing services for patients with end-stage kidney disease (ESKD). The charges for dialysis sessions across settings displayed a wide variance. Patients often started dialysis services in private and later shifted to government and non-governmental organisations-run centres and reduced the number of weekly dialysis sessions due to financial constraints. Most standalone dialysis centres did not have the facilities to manage any emergencies. Most centres did not admit patients with hepatitis or HIV. The quality of care in dialysis centres seemed to be variable and most centres were managed solely by dialysis technicians. There were no psychosocial interventions available to the patients irrespective of the settings. Cost-cutting practices such as employing underqualified technicians, reusing dialysis equipment and using substandard water for dialysis were common.
CONCLUSION
The study highlights the need for more financial and personnel investments in ESKD care in India to ensure optimal care for the growing patient population. The study points towards the need for comprehensive management practices, including diet counselling and psychosocial support. While there are comprehensive guidelines on the establishment and management of dialysis services, more policy attention needs to be on effective implementation of these, to ensure better accessibility and quality of existing services.
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10.1136/bmjopen-2021-052525
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pubmed_1084_2435
|
The hip arthroscopy develops quickly in the past 20 years. Its use in the diagnosis and treatment of the hip injury get more notably. Many of pathologic conditions previously unrecognized through X-ray, CT or MRI have been diagnosed correctly under hip arthroscopy. The technology has become gradually a golden standard to confirm the hip discords. In the present, the examining path of the hip arthroscopy contains mainly the outside path, the anterior path, the outside-posterior path. The application range of the hip arthroscopy includes the management of labral tears, the femoroacetabular impingement, the ligamentum tear injuries, the chondral lesions, the synovical abnormalities, the intra-articular infection, the loose bodies in the joint etc. The hip arthroscopy is a comprehensive technology. Its superiority can be reflect well if the doctors are familiar with the indication, the contraindication and the operation procedure. And also the thorough physical examination and imaging examination should be made before operation, as well as reasonable and effective postoperative function training should be conducted.
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pubmed_1084_2435
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pubmed_163_22356
|
OBJECTIVE
We examined the cost of lost productivity due to erectile dysfunction (ED) and employer benefit exclusion of penile prosthesis implantation (PPI) among men with employer-sponsored health insurance.
METHODS
A decision-analytic model was developed using administrative claims data, US Bureau of Labor Statistics, and published literature. The economic impact of ED productivity loss and PPi benefit exclusion was reported in2019USD.
RESULTS
Men with ED had an additional 282.7 hours/ year of work impairment compared to men without ED, resulting in annual incremental costs of $7270. US employers excluding PPi benefits could lose $9.3billion/year of work due to additional work impairment from ED.
CONCLUSIONS
Productivity loss due to ED and PPI benefit exclusion have considerable economic impacts on men with ED and their employers. continuous advocacy for benefit exclusion removal is needed to ensure appropriate patient access.
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10.1097/JOM.0000000000002449
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pubmed_1045_18956
|
The proximal promoter of the telomerase RNA gene, hTR, contains four Sp1 sites and one CCAAT box. We have carried out a functional analysis of the role of these sequence elements. Two Sp1 sites downstream of the CCAAT box mediated negative regulation, while the other two Sp1 sites were positive regulators with the strongest effect mediated by the negative regulatory Sp1 site closely flanking the CCAAT box. Basal transcriptional activity is maintained via the CCAAT box even when all four Sp1 sites are mutated, suggesting nuclear factor-Y (NF-Y) is a fundamental regulator of hTR promoter function. Chromatin immunoprecipitation revealed binding of NF-Y, Sp1 and TFIIB to the promoter in vivo. Thus the interaction of NF-Y at the CCAAT box is pivotal to hTR gene transcription and surrounding sequence elements may provide an environment for the regulation of activity through recruitment of additional protein complexes.
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10.1016/s0014-5793(03)00038-3
|
pubmed_60_1727
|
In Mediterranean habitats, temperature affects both ant foraging behaviour and community structure. Many studies have shown that dominant species often forage at lower temperature than subordinates. Yet, the factors that constrain dominant species foraging activity in hot environments are still elusive. We used the dominant ant Tapinoma nigerrimum as a model species to test the hypothesis that high temperatures hinder trail following behaviour by accelerating pheromone degradation. First, field observations showed that high temperatures (> 30°C) reduce the foraging activity of T. nigerrimum independently of the daily and seasonal rhythms of this species. Second, we isolated the effect of high temperatures on pheromone trail efficacy from its effect on worker physiology. A marked substrate was heated during 10 min (five temperature treatments from 25°C to 60°C), cooled down to 25°C, and offered in a test choice to workers. At hot temperature treatments (>40°C), workers did not discriminate the previously marked substrate. High temperatures appeared therefore to accelerate pheromone degradation. Third, we assessed the pheromone decay dynamics by a mechanistic model fitted with Bayesian inference. The model predicted ant choice through the evolution of pheromone concentration on trails as a function of both temperature and time since pheromone deposition. Overall, our results highlighted that the effect of high temperatures on recruitment intensity was partly due to pheromone evaporation. In the Mediterranean ant communities, this might affect dominant species relying on chemical recruitment, more than subordinate ant species, less dependent on chemical communication and less sensitive to high temperatures.
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10.1007/s00114-011-0852-6
|
pubmed_452_16817
|
The real-time vehicle detection and counting plays a crucial role in traffic control. To collect traffic information continuously, the access to information from traffic video shows great importance and huge advantages compared with traditional technologies. However, most current algorithms are not adapted to the effects of undesirable environments, such as sudden changes in illumination, vehicle shadows, and complex urban traffic conditions, etc. To address these problems, a new vehicle detection and counting method was proposed in this paper. Based on a real-time background model, the problem of sudden illumination changes could be solved, while the vehicle shadows could be removed using a detection method based on motion. The vehicle counting was built on two types of ROIs-called Normative-Lane and Non-Normative-Lane-which could adapt to the complex urban traffic conditions, especially for non-normative driving. Results have shown that the methodology we proposed is able to count vehicles with 99.93% accuracy under the undesirable environments mentioned above. At the same time, the setting of the Normative-Lane and the Non-Normative-Lane can realize the detection of non-normative driving, and it is of great significance to improve the counting accuracy.
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10.3390/s20092686
|
pubmed_21_5598
|
BACKGROUND
The majority of deleterious health consequences of coeliac disease (CD) are most likely to be secondary to intestinal inflammation; hence, mucosal recovery is a desirable goal of therapy. Follow-up in CD is controversial and serological response is often used as a surrogate for histological recovery.
AIMS
To inform the clinical management of CD using comparative serological and histological data from a biopsy-driven pathway of care.
METHODS
A retrospective analysis of the Cambridge Coeliac Clinic database of 595 patients routinely followed up by biopsy and serology.
RESULTS
Paired biopsy results were available for 391 patients (15% seronegative). Persisting villous atrophy (VA) occurred in 182 patients (47%). The sensitivity of anti-tissue transglutaminase (TTG) antibody for ongoing VA was only 43.6%. Information on dietetic management and further biopsy to assess response was available for 94 initially unresponsive patients, in whom targeted dietetic intervention by removal of identified gluten sources or avoidance of trace amounts of gluten led to resolution of persistent VA in 50%. The effects of institution of a formal care pathway are analysed in 298 patients. Discharge to primary care and clinical management was facilitated by the information derived from repeat biopsy.
CONCLUSIONS
Serology appears to be a poor surrogate marker for mucosal recovery on a gluten-free diet; dietary assessment fails to identify a potential gluten source in many patients with ongoing villous atrophy. The benefits of re-biopsy on diet include stratification of patients with coeliac disease suitable for early discharge from secondary care or those requiring more intensive clinical management.
|
10.1111/apt.12510
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pubmed_806_17880
|
OBJECTIVES
To evaluate the effects of various chemical surface modifications on adhesion between zirconia and resin adhesive.
MATERIAL AND METHODS
Pre-sintered zirconia discs were sectioned from commercial cylindrical blocks and polished with abrasive papers under running tap water. All the discs were randomly divided into five study groups according to the methods of surface treatment, including: the control group (fully sintered, without any modification), group S (fully sintered and sandblasted with silica coated alumina particles), group HN (fully sintered and etched with a blend of mineral acid solution at 100 °C for 25 min), group HF (fully sintered and etched with 48% hydrofluoric acid solution at 100 °C for 25 min), and group Si (coated with silica particles and then fully sintered). The mean value of surface roughness was evaluated before further treatment. Resin stubs (3.6mm in diameter and 3mm in height) were adhered and light cured on each zirconia disc after the application of a silane coupling agent. In each group, all the samples were further divided into three subgroups with each n=12, one for the measurement of initial adhesion strength (shear bond) value and the other two were tested after thermal cycling for 10,000 and 20,000 cycles, respectively. The results were analyzed with two-way ANOVA and Turkey HSD (p<0.05). XRD technique was utilized in the examination of zirconia surface crystallinity. The morphological appearance of zirconia surface after surface treatment was observed with SEM.
RESULTS
The control group showed the lowest initial shear bond strength (SBS) value (16.8 ± 2.4 MPa) and did not survive the aging treatments. All the investigated surface treatments improved resin zirconia bond strength significantly, the group S displaying the highest initial value of 25.1 ± 2.7 MPa. However, the highest resistance to the aging effects of thermal cycling was found in group Si. It was further shown in the XRD examination that only the grit-blasting caused the crystalline transformation from tetragonal phase to monoclinic phase (T → M). On the other hand, such a phase transformation could not be detected in all the other four groups.
SIGNIFICANCE
Resin zirconia adhesion could be effectively improved by both HF etching and silica coating on zirconia surface, without leading to a T → M crystalline phase transformation.
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pubmed_806_17880
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pubmed_175_26027
|
White-tailed deer (Odocoileus virginianus) serve as a host for cattle fever ticks (Rhipicephalus [Boophilus] microplus and Rhipicephalus [Boophilus] annulatus; CFTs); therefore, deer are a concern for CFT control programs in southern Texas, US. Systemic (oral delivery of ivermectin) and topical (permethrin on pelage) treatment devices have been developed for white-tailed deer; however, the efficacy of these treatment options has not been determined for CFTs in southern Texas. Our objectives were to evaluate the effectiveness of CFT treatment strategies by 1) measuring exposure rates of deer to the acaricides permethrin and ivermectin, 2) determining the relationship between CFTs on deer and exposure to the acaricides, and 3) determining if photos from remote cameras at medicated bait sites can be used as a measure of acaricide treatment. We captured 327 deer at four sites in southern Texas. Deer visitation to medicated bait sites was monitored using remote cameras from March 2010 to February 2012. There was no relationship between the presence of permethrin and the probability of being infested with CFTs (P≥0.336). The probability of infestation with CFTs decreased as serum ivermectin levels increased for male (n=18, P=0.098) and female (n=33, P<0.001) deer. Our results indicate ivermectin may be more effective in treating CFTs than permethrin; thus it would be worthwhile to develop topical acaricides other than permethrin for treating white-tailed deer in southern Texas.
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10.7589/2015-11-304
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pubmed_463_2053
|
BACKGROUND AND OBJECTIVES
Attempts to enhance bond strength of the sealant have been among the most important sides of dental research. The purpose of the present study was to evaluate the effect of using different rinsing angles on the micro-tensile bond strength of the sealant to the etched enamel.
MATERIALS AND METHODS
Sixty first-premolars were randomly assigned to six groups based on the rinsing angle applied (15°, 30°, 45°, 60°, 75° and 90°). Following etching and rinsing, a 4-mm height build-up of sealant material was created. Bonded specimens were sectioned into sticks (1 mm × 1 mm), which were subjected to micro-tensile bond strength, testing at a cross head speed of 0.5 mm/min.
STATISTICAL ANALYSIS USED
The data were analyzed by Kolmogorov-Smirnov and post-hoc Tukey test.
RESULTS
The tensile bond strength in specimens rinsed at 90° were statistically higher compared to those rinsed at 15° and 30° (P < 0.05) and increasing the angle from 15° to 90° was correlated with a reduction in the number of specimens with adhesive failures.
CONCLUSIONS
Rinsing the conditioned enamel surface at 90° may improve the bond strength and retention of the sealant.
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10.4103/0976-237X.114888
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pubmed_789_14516
|
Objective. This study evaluates the bacterial contamination rate of items in the hospital setting that are in frequent contact with patients and/or physicians. By determining the bacterial species and the associated antibiotic resistance that patients are exposed to. Methods. Hospital-based cross-sectional surveillance study of potential bacterial reservoirs. Cultures from 30 computer keyboards, 32 curtains, 40 cell phones, 35 white coats, and 22 ties were obtained. Setting. The study was conducted an urban academic 650-bed teaching hospital providing tertiary care to the city of Medellin, Colombia. Results. In total, 235 bacterial isolates were obtained from 159 surfaces sampled. 98.7% of the surfaces grew positive bacterial cultures with some interesting resistance profiles. Conclusion. There are significant opportunities to reduce patient exposure to frequently pathogenic bacteria in the hospital setting; patients are likely exposed to many bacteria through direct contact with white coats, curtains, and ties. They may be exposed to additional bacterial reservoirs indirectly through the hands of clinicians, using computer keyboards and cell phones.
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10.1155/2012/507640
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pubmed_483_10617
|
FMT has gained enormous momentum in the treatment of acute inflammatory and infectious diseases. Despite an encouraging safety profile, FMT has been met with caution in the oncological setting due to perceived infectious risks in immunocompromised patients. Theoretical risks aside, the application of FMT in oncology may stand to benefit patients, via modulation of treatment efficacy and the mitigation of treatment complications. Here, we summarize most recent safety data of FMT in immunocompromised cohorts, including people with cancer, highlighting that FMT may actually provide protection against bacterial translocation via introduction of a diverse microbiome and restoration of epithelial defenses. We also discuss the emerging translational applications of FMT within supportive oncology, including the prevention and treatment of graft vs. host disease and sepsis, treatment of immunotherapy-induced colitis and restoration of the gut microbiome in survivors of childhood cancer.
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10.1016/j.ebiom.2019.03.070
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pubmed_481_6832
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The effect of emphasizing speed or accuracy on the learning of a high speed-high accuracy skill, the fastpitch softball pitch was investigated. 26 10- and 11-yr.-old girls were randomly assigned to two groups receiving feedback on speed of throwing or accuracy of throwing during a 6-wk. training. Measurements of speed and accuracy were made and recorded on all participants at each practice session and a videotape of their pitching technique was also made at each session. Data were subjected to 2 x 3 (2 groups by 3 testing times) repeated-measures analyses of variance. The speed group threw faster and with better technique during the study and was able to maintain speed and accuracy in the reversed test condition.
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10.2466/pms.1997.85.3.1011
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pubmed_219_16008
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Suicide attacks and terrorism are characterized by cognitive simplicity, which is related to self-deception. In justifying violence in pursuit of ideologically and/or politically driven commitment, people with high religious commitment may be particularly prone to mechanisms of self-deception. Related megalomania and glorious self-perception are typical of self-deception, and are thus crucial in the emergence and expression of (suicide) terrorism.
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10.1017/S0140525X13003385
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pubmed_942_17553
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Six cyclised tetraprenyltoluquinols and five stereoisomers with the previously reported amentol skeleton have been isolated from the lipophilic extract of the South African brown alga Cystophora fibrosa. Structures and relative stereochemistry were determined using spectrometric techniques, particularly 1D and 2D NMR, and molecular modelling experiments. The compounds isolated appear to be enantiomeric to compounds with the same skeleton isolated from brown algae of the genus Cystoseira collected in northern Africa and the Mediterranean Sea. The isolation of tetraprenyltoluquinols with the amentol skeleton from this alga suggests that C. fibrosa should be moved from the genus Cystophora into the Cystoseira.
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10.1016/j.phytochem.2006.03.011
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pubmed_466_10788
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We studied 96 patients subjected to elective proximal gastric vagotomy for intractable duodenal ulceration. Dysphagia was a frequent finding and occurred in 32 percent. It appeared in the immediate postoperative period and usually lasted for 1 to 2 months without any abnormalities in lower esophageal sphincter function. In five patients, dysphagia was severe and, although transient, was associated with changes in lower esophageal function simulating those observed in achalasia. The mechanism of these motor abnormalities is probably due to a reversible neuromuscular dysfunction of the lower esophageal sphincter.
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10.1016/s0002-9610(85)80076-3
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pubmed_240_20961
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We present three cases with juvenile ossifying fibroma. Two occurring in the maxilla, and one in the mandible. All three cases presented with a major swelling in the face. After clinical and radiological evaluation the lesions were surgically excised and sent for histopathological evaluation. Two histological types of juvenile ossifying fibroma were found, the psammatous type in two cases and the trabecular pattern in one case. Although juvenile ossifying fibroma is an uncommon clinical entity, its aggressive local behaviour and high recurrence rate mean that it is important to make an early diagnosis. It is also important to apply the appropriate treatment and to follow-up the patient closely over the long term. This report describes the diagnosis and treatment of juvenile ossifying fibroma in the maxilla and the mandible. It also emphasizes the importance of considering the less aggressive options as a first line of treatment before choosing the aggressive approach when dealing with children.
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10.1007/s12663-010-0027-6
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pubmed_776_7149
|
Pregnant Swiss albino mice were given a priming injection(im) of tritiated water (HTO) at the dose rate of 2.3 and 5 microCi/ml body water (74, 111 or 185 KBq/ml body water) at 0, 6 and 14 day post conception (d.p.c.) and were subsequently maintained on tritiated drinking water ad libitum during preimplantation (0-5 d.p.c.), organogenetic (6-12 d.p.c.) or fetal (14-18 d.p.c.) period, respectively. On day 18 of gestation the females were sacrificed by cervical dislocation to record the implant sites per dam and embryonic/fetal mortality. Significant reduction was observed in average implant sites per dam when the females were exposed to any of the three doses during the preimplantation period due to embryonic resorption before implantation. However, the same was found to be within the normal range when mothers were exposed during the organogenetic or fetal period. Prenatal mortality (embryonic resorption/fetal death) was higher after in utero exposure to different doses during preimplantation period as compared to organogenetic period, but mortality did not occur after exposure to any of the doses during the fetal period. Occurrence of mortality was found to be dose dependent.
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pubmed_776_7149
|
pubmed_21_5790
|
BACKGROUND
During on-pump cardiac surgery, hemorrhagic complications occur frequently. Fresh-frozen plasma (FFP) is widely transfused to provide coagulation factors. Yet, no randomized clinical trial has demonstrated its benefits on mortality. We assessed the relationship between therapeutic transfusion of FFP and 30-day mortality in cardiac surgery patients suffering from excessive bleeding in a prospective cohort study.
STUDY DESIGN AND METHODS
Adult patients who underwent on-pump cardiac surgery and experienced excessive bleeding during the 48-hour perioperative period were recruited from 15 French centers between February 2004 and January 2006. Patients who received a preventive FFP transfusion were excluded. The association between FFP transfusion and all cause 30-day mortality was estimated using a Cox proportional hazards model, adjusted for confounding. A propensity score (PS) sensitivity analysis was also performed.
RESULTS
Among 967 patients included in this study, 58.1% received FFP. The median dose was 11.3 mL/kg (interquartile range, 7.6-19.5). The cumulative 30-day mortality rate was 11.3% (95% confidence interval [CI], 9.5-13.5). FFP transfusion was associated with a higher 30-day mortality (hazard ratio [HR], 3.2; 95% CI, 1.7-6.1) in univariate analysis; however, after adjusting for prognostic factors, there was no longer any association (HR, 1.5; 95% CI, 0.8-3.0, p = 0.20). The results of the PS analysis were consistent with the adjusted analysis.
CONCLUSION
Among on-pump cardiac surgery patients experiencing excessive perioperative bleeding, there is no evidence of a beneficial impact of FFP transfusion on mortality.
|
10.1111/trf.12422
|
pubmed_153_3667
|
PURPOSE
The purpose was to determine the effectiveness of the Tobacco Tactics program in three Veterans Affairs hospitals.
METHODS
In this effectiveness trial, inpatient nurses were educated to provide the Tobacco Tactics intervention in Ann Arbor and Detroit, while Indianapolis was the control site (N = 1,070). Smokers were surveyed and given cotinine tests. The components of the intervention included nurse counseling, brochure, DVD, manual, pharmaceuticals, 1-800-QUIT-NOW card, and post-discharge telephone calls.
RESULTS
There were significant improvements in 6-month quit rates in the pre- to post-intervention time periods in Ann Arbor (p = 0.004) and Detroit (p < 0.001) compared to Indianapolis. Pre- versus post-intervention quit rates were 4 % compared to 13 % in Detroit, were similar (6 %) pre- and post-intervention in Ann Arbor, and dropped from 26 % to 12 % in Indianapolis.
CONCLUSION
The Tobacco Tactics program, which meets the Joint Commission standards that apply to all inpatient smokers, has the potential to significantly decrease smoking among Veterans.
|
10.1007/s12160-014-9605-z
|
pubmed_258_9586
|
Coenzyme Q10 (CoQ10), an endogenous antioxidant, has been reported frequently to exert an outstanding protective effect on multiple organ injury, including acute kidney injury (AKI). In this study, we aim to summarize all the current evidence of the protective action of CoQ10 against AKI as there are presently no relevant reviews in the literature. After a systematic search, 20 eligible studies, either clinical trials or experimental studies, were included and further reviewed. CoQ10 treatment exhibited a potent renal protective effect on various types of AKI, such as AKI induced by drugs (e.g., ochratoxin A, cisplatin, gentamicin, L-NAME, and nonsteroidal anti-inflammatory drug), extracorporeal shock wave lithotripsy (ESWL), sepsis, contrast media, and ischemia-reperfusion injury. The renal protective role of CoQ10 against AKI might be mediated by the antiperoxidative, anti-apoptotic, and anti-inflammatory potential of CoQ10. The molecular mechanisms for the protective effects of CoQ10 might be attributed to the regulation of multiple essential genes (e.g., caspase-3, p53, and PON1) and signaling cascades (e.g., Nrf2/HO-1 pathway). This review highlights that CoQ10 may be a potential strategy in the treatment of AKI.
|
10.1186/s11658-022-00361-5
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pubmed_153_4667
|
Statistical learning is characterized by detection of regularities in one's environment without an awareness or intention to learn, and it may play a critical role in language and social behavior. Accordingly, in this study we investigated the electrophysiological correlates of visual statistical learning in young children with autism spectrum disorder (ASD) using an event-related potential shape learning paradigm, and we examined the relation between visual statistical learning and cognitive function. Compared to typically developing (TD) controls, the ASD group as a whole showed reduced evidence of learning as defined by N1 (early visual discrimination) and P300 (attention to novelty) components. Upon further analysis, in the ASD group there was a positive correlation between N1 amplitude difference and non-verbal IQ, and a positive correlation between P300 amplitude difference and adaptive social function. Children with ASD and a high non-verbal IQ and high adaptive social function demonstrated a distinctive pattern of learning. This is the first study to identify electrophysiological markers of visual statistical learning in children with ASD. Through this work we have demonstrated heterogeneity in statistical learning in ASD that maps onto non-verbal cognition and adaptive social function.
|
10.1111/desc.12188
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pubmed_26_9627
|
Arterial spin labeling (ASL) uses proximally inverted blood water spins as an endogenous contrast agent to measure blood perfusion in tissue. In this work pulsed ASL was used to measure the kinetic curves of cerebral blood flow (CBF) across eight anatomically based regions of interest (ROIs) in five normal healthy subjects. CBF estimates based on these data were compared when obtained using a single inversion time versus fitting a kinetic model to all 10 measured inversion times. CBF estimates were also compared when fitting to the 10 inversion time data using a standard two-parameter approach (CBF and bolus arrival time) or a more recently proposed three-parameter model (CBF, bolus arrival time, and arrival time dispersion). Variations in the shape of the kinetic curve were found across the brain that were consistent across subjects. The arrival time in the occipital ROI was found to be long enough to lead to underestimation of the CBF when using a single inversion time of 1.5 s. In four out of the eight ROIs there was significant underestimation of CBF using the standard two-parameter model compared to the three-parameter approach. These results have important implications for the development of a robust, quantitative ASL protocol.
|
10.1002/mrm.21886
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pubmed_460_8852
|
Reproductive development of female European corn borer, Ostrinia nubilalis (Hübner), was investigated and a classification system proposed. Females collected in a blacklight trap during 1982 and 1983 were dissected and their reproductive system examined. Female reproductive systems were divided into six stages based on ovum development within the ovarioles, ovum depletion, ovariole appearance, and fat body color and shape. The female reproductive systems were also staged on the basis of spermatophore appearance. The time necessary to classify a female is also reported. Based on the classification system, the relationship between female age and stage of ovarian development was quantified under three temperature regimes. Females were found to experience a 3- to 5-d preoviposition period before initiation of egg deposition under optimal temperature conditions. This delay between adult emergence and initiation of egg laying corresponded with more advanced ovarian developmental stages collected in blacklight traps and indicates that actively ovipositing females are primarily being collected in blacklight traps.
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10.1093/jee/97.3.828
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pubmed_2_17163
|
In order to fully characterize the zinc white artists' pigment (ZnO), much used since the mid-nineteenth century, three samples collected in the early 20th century were studied using a combination of synchrotron and macroscopic photoluminescence spectroscopy and imaging. An improved microscope setup based on synchrotron microspectroscopy and microimaging was used to study the powders dispersed onto indium foil. The synchrotron setup offered a diffraction-limited resolution of 153 nm. The PL spectra of individual grains were measured and the distribution of particles' emission spectra was mapped at the nanoscale. The results revealed that while the samples have apparent homogeneous photoluminescence behavior at the macroscale (bulk), their PL signatures are inhomogeneous below 20 μm. At the nanoscale the three powder samples have quite different PL signatures. Different sources, perhaps even different batches, of zinc white might be readily differentiated using this method.
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10.1039/c3an36874b
|
pubmed_2_18465
|
Post-translational modifications can dramatically impact protein activity, but identifying such structure:function relationships, as well as capitalizing on functionally enhanced variants, is a significant challenge. Here, affinity chromatography resins that contained immobilized FcγRIII receptors were used to enrich nonfucosylated antibodies 6- to 9-fold, offering what may be a tractable method for both the identification of post-translational modifications that affect function, as well as a means to enrich variants with enhanced activity.
|
10.1002/btpr.1717
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pubmed_510_3220
|
The purposes of this study were to (1) describe errors in weightbearing at three target levels for patients with neuropathic feet and control subjects, (2) compare the absolute errors at the three target levels between groups, and (3) identify predictor variables of errors in weightbearing by the neuropathic group. The groups of 26 subjects were matched for age and height. Weightbearing was measured with digital scales while subjects attempted to adjust their weight through a designated lower extremity to each target level (25, 50, and 75% of body weight). Analysis of variance indicated no significant difference in the percentage weightbearing between groups at the three target levels. There was a significant difference in errors made in weightbearing by the groups at the three target levels. Mean errors ranged from 8.5 to 9.7% for the neuropathic group and from 2.4 to 6.6% for the control group. The findings cast doubt on the utility (in the absence of feedback) of requesting individuals, particularly those with neuropathic feet, to weightbear at specific target levels.
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10.2466/pms.1991.72.1.19
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pubmed_27_12912
|
The majority of humans deficient in the cytochrome P450 CYP2D6 enzyme, so-called poor metabolizers (PMs), can now be identified by genotyping for several different PM-associated mutations. However, additional null alleles remain to be identified as demonstrated by subjects with the PM phenotype in the absence of a corresponding genotype. The rare 11 kb band on Xba I RFLP analysis, which is distinct from the 13 kb CYP2D6D (CYP2D6*5) allele, has been proposed to constitute such a unique non-functional allele. Here we demonstrate that the 11 kb band represents at least two different nine exon CYP2D7P/CYP2D6 hybrids generated by large deletions in the CYP2D gene cluster due to unequal cross-over or looping-out mechanisms. The total allele frequency was approximately 0.001-0.01 in European and North American Caucasians. The most common variant (CYP2D6*16) had breakpoints lying between the end of exon 7 and the start of exon 9 of the respective genes. The "CYP2D7-like' part of the gene was most homologous to the previously described CYP2D7AP and CYP2D7 (44/11.5) sequences. The other chimeric allele consisted of exon 1 of CYP2D7 and exons 2-9 from CYP2D6, and may be similar to a hybrid gene termed CYP2D6*13 recently described in a French individual. Two different routine PCR assays were developed for rapid and sensitive detection of these alleles, namely amplification of a 8 kb fragment from both CYP2D6*13 and CYP2D6*16, together with a CYP2D6*16-specific method which gave a 1.4 kb PCR product. The 8 kb assay for the CYP2D6*13 and CYP2D6*16 alleles also produced a 9.5 kb fragment in samples positive for the 13 kb CYP2D6*5 allele. Therefore, it is now possible to screen for the large CYP2D gene deletions by a single long PCR method.
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10.1097/00008571-199608000-00005
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pubmed_130_11298
|
Nosocomial infections, termed hospital-acquired infections (HAIs), are acquired from a healthcare or hospital setting. HAI is mainly caused by bacteria, such as Acinetobacter baumannii, Klebsiella pneumoniae, Escherichia coli, Enterococci spp., Methicillin-resistant Staphylococcus aureus (MRSA), and many more. Due to growing antibacterial resistance, nanotechnology has paved the way for more potent and sensitive methods of detecting and treating bacterial infections. Nanoparticles have been used with molecular beacons for identifying bactericidal activities, targeting drug delivery, and anti-fouling coatings, etc. This review addresses the looming threat of nosocomial infections, with a focus on the Indian scenario, and major initiatives taken by medical bodies and hospitals in spreading awareness and training. Further, this review focuses on the potential role nanotechnology can play in combating the spread of these infections.
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10.3390/bioengineering9020051
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pubmed_687_18282
|
OBJECTIVE
To assess heterogeneity in patient and physician preferences for multiple sclerosis treatment features and outcomes via a discrete-choice experiment.
METHOD
Patients with self-reported multiple sclerosis and treating physicians participated in an online discrete-choice experiment. Patients, each considering a better or worse reference condition, and physicians, each considering two patient profiles, chose between hypothetical treatment profiles defined by seven attributes with varying levels: years until disability progression, number of relapses in the decade, mode of administration, dosing frequency, and risks of mild, moderate, and severe side effects. Latent class analysis was used to measure respondent preferences and identify potential subgroups with distinct preferences.
RESULTS
Distinct treatment preferences emerged among subgroups of patients (n = 301) and physicians (n = 308). Patients in class 1 (43% of sample) were most concerned about side effects; chief concerns of class 2 patients (57%) were delaying disability progression and avoiding severe side-effect risks. The most important attributes for physicians (by class) were delaying disability (class 1, 45%), avoiding severe side-effect risks and (class 2, 33%), and avoiding all side-effect risks (class 3, 22%).
CONCLUSION
Patients and physicians have diverse preferences for multiple sclerosis treatments, reflecting heterogeneity in the disease course and available therapies and the need for shared decision making.
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10.1177/2055217320910778
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pubmed_321_19627
|
BACKGROUND
The impact of paravalvular regurgitation (PVR) following transcatheter aortic valve implantation (TAVI) remains uncertain.
OBJECTIVE
To evaluate the impact of PVR on mortality and hospital readmission one year after TAVI.
METHODS
Between January 2009 and June 2015, a total of 251 patients underwent TAVI with three different prostheses at two cardiology centers. Patients were assessed according to PVR severity after the procedure.
RESULTS
PVR was classified as absent/trace or mild in 92.0% (n = 242) and moderate/severe in 7.1% (n = 18). The moderate/severe PVR group showed higher levels of aortic calcification (22% vs. 6%, p = 0.03), higher serum creatinine (1.5 ± 0.7 vs. 1.2 ± 0.4 mg/dL, p = 0.014), lower aortic valve area (0.6 ± 0.1 vs. 0.7 ± 0.2 cm2, p = 0.05), and lower left ventricular ejection fraction (49.2 ± 14.8% vs. 58.8 ± 12.1%, p = 0.009). Patients with moderate/severe PVR had more need for post-dilatation (p = 0.025) and use of larger-diameter balloons (p = 0.043). At one year, all-cause mortality was similar in both groups (16.7% vs. 12%, p = 0.08), as well as rehospitalization (11.1% vs. 7.3%, p = 0.915). PVR grade significantly reduced throughout the first year after the procedure (p < 0.01). The presence of moderate/severe PVR was not associated with higher one-year mortality rates (HR: 0.76, 95% CI: 0.27-2.13, p = 0.864), rehospitalization (HR: 1.08, 95% CI: 0.25-4.69, p=0.915), or composite outcome (HR: 0.77, 95% CI: 0.28-2.13, p = 0.613).
CONCLUSION
In this sample, moderate/severe PVR was not a predictor of long-term mortality or rehospitalization. (Arq Bras Cardiol. 2017; [online].ahead print, PP.0-0).
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10.5935/abc.20170172
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pubmed_302_14292
|
The Asian Forum for Health Research convened in Manila, the Philippines, in February 2000 to determine how best to create a new paradigm for health research in Asia. The forum was organized as an 'open university of research for equity in health development' to define the new paradigm and to identify methods for building a dynamic and collaborative architecture to more effectively link the nations and region of Asia with global stakeholders in health research. It was also to: determine Asian actions required to enhance leadership functions for innovative health research management; develop and disseminate tools and methodologies needed to accomplish essential tasks; establish collaborative networks within developing countries/regions to ensure efforts are not duplicated and international inputs are not monopolized; and use new information and communication technologies to integrate the process and contents of health research with equity in health development. Results of the forum's review of issues were presented and discussed at the International Conference on Health Research for Development, held in October 2000 in Bangkok, Thailand.
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10.1093/heapol/17.2.213
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pubmed_1091_5139
|
BACKGROUND
The interpretation of previous studies on the association of physical activity and sedentary behaviour with psychological health is limited by the use of mostly self-reported physical activity and sedentary behaviour, and a focus on Western populations. We aimed to explore the association of self-reported and devise-based measures of physical activity and sedentary behaviour domains on psychological distress in an urban multi-ethnic Asian population.
METHODS
From a population-based cross-sectional study of adults aged 18-79 years, data were used from an overall sample (n = 2653) with complete self-reported total physical activity/sedentary behaviour and domain-specific physical activity data, and a subsample (n = 703) with self-reported domain-specific sedentary behaviour and accelerometry data. Physical activity and sedentary behaviour data were collected using the Global Physical Activity Questionnaire (GPAQ), a domain-specific sedentary behaviour questionnaire and accelerometers. The Kessler Screening Scale (K6) and General Health Questionnaire (GHQ-12) were used to assess psychological distress. Logistic regression models were used to calculate odds ratios (ORs) and 95% confidence intervals, adjusted for socio-demographic and lifestyle characteristics.
RESULTS
The sample comprised 45.0% men (median age = 45.0 years). The prevalence of psychological distress based on the K6 and GHQ-12 was 8.4% and 21.7%, respectively. In the adjusted model, higher levels of self-reported moderate-to-vigorous physical activity (MVPA) were associated with significantly higher odds for K6 (OR = 1.47 [1.03-2.10]; p-trend = 0.03) but not GHQ-12 (OR = 0.97 [0.77-1.23]; p-trend = 0.79), when comparing the highest with the lowest tertile. Accelerometry-assessed MVPA was not significantly associated with K6 (p-trend = 0.50) nor GHQ-12 (p-trend = 0.74). The highest tertile of leisure-time physical activity, but not work- or transport-domain activity, was associated with less psychological distress using K6 (OR = 0.65 [0.43-0.97]; p-trend = 0.02) and GHQ-12 (OR = 0.72 [0.55-0.93]; p-trend = 0.01). Self-reported sedentary behaviour was not associated with K6 (p-trend = 0.90) and GHQ-12 (p-trend = 0.33). The highest tertile of accelerometry-assessed sedentary behaviour was associated with significantly higher odds for K6 (OR = 1.93 [1.00-3.75]; p-trend = 0.04), but not GHQ-12 (OR = 1.34 [0.86-2.08]; p-trend = 0.18).
CONCLUSIONS
Higher levels of leisure-time physical activity and lower levels of accelerometer-based sedentary behaviour were associated with lower psychological distress. This study underscores the importance of assessing accelerometer-based and domain-specific activity in relation to mental health, instead of solely focusing on total volume of activity.
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10.1186/s12966-018-0669-1
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pubmed_847_25898
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Following predictions of a dramatic drop in the developmental-behavioral healthcare workforce by 2023 due to retirement and/or burnout, much has been written about ways to replenish or sustain needed personnel. To date, we continue to have a crisis of not enough new clinicians being attracted to the field to replenish the third of the workforce that is expected to retire. Recent concerns about increased clinician mental health problems and burnout in the wake of COVID-19 and other societal stressors add further complexity and urgency. This crisis will not be solved solely by a top-down focus on intensive graduate training or marketing to newly licensed professionals. Through the lived experience of three fellows from the Leadership Education in Neurodevelopmental and related Disabilities (LEND) program, this paper offers a "grassroots" approach to supporting people with disabilities (PWD) to weather this rebuilding period by increasing (a) their material wealth through entrepreneurship and (b) capacities for self-determination through thoughtful mentorship and considered changes in institutional culture.
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10.1007/s40737-022-00278-4
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pubmed_205_21847
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Four of 107 samples obtained from hepatitis C virus (HCV) carriers showed lower HCV core antigen levels in a fluorescence enzyme immunoassay (FEIA) than expected from corresponding HCV RNA levels. Nucleotide sequencing revealed a mutation in the HCV core region (Thr49Pro) that appears to have reduced the FEIA sensitivity.
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10.1128/JCM.38.9.3450-3452.2000
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pubmed_753_19981
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In this study thirteen 6-substituted-3(2H)-pyridazinone-2-acetyl-2-(substituted/nonsubstituted benzal)hydrazone V derivatives were synthesized as acetylcholinesterase and butyrylcholinesterase inhibitors. Ten of the synthesized compounds were synthesized for the first time in this study and the rest of them had been synthesized in a previous study. The structures of compounds V were elucidated by IR, 1H-NMR and MASS spectra. The acetylcholinesterase (AChE) and butyrylcholinesterase (BChe) inhibitory activities of V derivatives were measured using Ellman's method. While some of the 6-substituted-3(2H)-pyridazinone-2-propyl-3-(substituted/-nonsubstituted benzal)hydrazone V derivatives exhibited significant AChE inhibitory activity, none of the compoundsshowed BChE inhibitory activity. Theseresults indicate that V derivatives were AChE inhibitors with AChE/ BChE selectivity.
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10.1055/s-0031-1296161
|
pubmed_785_3364
|
BACKGROUND
This study evaluated the effect of infection control interventions on the incidence of carbapenem-resistant Acinetobacter baumannii (CRAB) in a tertiary hospital over a 6-year period.
METHODS
Multiple interventions, including cohorting, promotion of hand hygiene, active surveillance in the intensive care units, and environmental cleaning, were implemented from 2007 through 2009 (period 1). From 2009 through 2012 (period 2), infection control programs were enhanced by the introduction of an onsite education and hand hygiene campaign in preparation for hospital accreditation. To assess the efficacy of the infection control intervention programs, the nosocomial incidence density of CRAB, consumption of alcohol-based hand gel, and consumption of antimicrobials during the study period were measured.
RESULTS
The incidence density of CRAB increased from 0.35 to 0.46 per 1000 patient-days (PD) during period 1, but decreased to 0.06 per 1000 PD in period 2 (P = .011). The consumption of alcohol-based hand gel increased from 5.6 L to 11.9 L per 1000 PD during the study period (P < .001). There was a significant association between the incidence density of CRAB and carbapenem use (P = .008).
CONCLUSIONS
Education for infection control programs, hand hygiene campaign, and the judicious use of carbapenem may decrease the nosocomial incidence of CRAB.
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pubmed_785_3364
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pubmed_177_9835
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Self-fertilisation that is delayed until after opportunities for outcrossing have ceased has been argued to provide both the reproductive assurance benefits of selfing and the genetic advantages of outcrossing. In the Campanulaceae, presentation of pollen on stylar hairs and progressive stigma curvature have been hypothesised to facilitate delayed selfing, but experimental tests are lacking. Stigma curvature is common in Campanula, a genus largely characterised by self-incompatibility, and therefore is unlikely to have initially evolved to promote self-fertilisation. In derived self-compatible species, however, stigma curvature might serve the secondary function of delayed selfing. We investigated delayed selfing in Triodanis perfoliata, a self-compatible relative of Campanula. Using floral manipulation experiments and pollen tube observations, we quantified the extent and timing of self-pollination. Further, we hypothesised that, if stigma curvature provides the benefit of delayed selfing in Triodanis, selection should have favoured retention of self-pollen through the loss of a stylar hair retraction mechanism. Results of a stigma removal experiment indicated that autonomous selfing produces partial seed set, but only some selfing was delayed. Pollen tube observations and a flower senescence assay also supported the finding of partial delayed selfing. Scanning electron microscopy revealed that pollen-collecting hairs retract during anthesis, which may limit the extent of delayed selfing. Delayed selfing appeared to be only partially effective in T. perfoliata. The stylar hair retraction in this species would seem to contradict selection for selfing. We suggest that caution and rigour are needed in interpreting floral traits as adaptive mechanisms for delayed selfing.
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10.1111/plb.12677
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pubmed_159_11916
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The efficacy of current antiviral drugs used to treat influenza has been declining because of mutations and resistance of the virus. Herein, a light-sensitive multiligand architecture is developed consisting of chitosan conjugated to a photosensitizer and 6'-sialyllactose (SL) to develop an antiviral agent against influenza with a different mechanism of action (SL-chitosan-Chlorin e6, SCC). Saturation transfer difference-nuclear magnetic resonance determined that the ability of SCC to bind to viral hemagglutinin is stronger than that of the monomeric substance. Virus recognition is confirmed by immunofluorescence and transmission electron microscope imaging. SCC induces viral inactivation by causing permanent membrane damage through its photoactivity. Viral membrane is oxidized by the photoactivity of SCC, thus, the virus membrane collapses. Furthermore, using the plaque reduction assay to evaluate the inhibitory effect of SCC on influenza A and B, it is found that its antiviral effects are 23% and 50% higher than the conventional antiviral drug. Additionally, SCC prevents infection by influenza in 100% of mice subjected to laser irradiation. These results indicate that this photodynamic multiligand structure can overcome the limitations of existing antiviral agents and suggest a pertinent methodology of prophylaxis and treatment by preemptively attacking the virus before it enters the host cell.
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10.1002/smll.202000556
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pubmed_972_2722
|
Urothelial cell carcinoma (UCC) with musculus detrusor (MD) invasion is treated by cystectomy. Subsequent pathologic evaluation of cystectomies does not reveal MD invasion (<pT2) in a subgroup of patients. Our objective was to identify features at diagnostic transurethral resection (TUR) predicting down-staging (<pT2) at cystectomy. Patients with pathologically confirmed MD invasion at TUR followed by cystectomy for UCC without (neo-) adjuvant therapy were included (N = 106). Slides of both TUR and cystectomy specimens were reviewed, and survival analyses were performed. In total, 27/106 (26 %) tumors were down-staged at cystectomy, of which 13 (12 %) had no residual tumor (pT0). There was no significant difference in age, gender, time interval between TUR and operation, number of slides sampled, and presence of TUR scar between down-staged (<pT2) and pT2 UCC. At review of TUR specimens (N = 52) with UCC initially diagnosed as pT2, MD invasion was not confirmed in eight cases (15 %). One case showed extensive histiocytic reaction misinterpreted as UCC; in four cases, muscularis mucosae had been considered MD, and in three cases, desmoplastic reaction mimicked MD. No histologic parameter at TUR was significantly associated with down-staging at cystectomy. Overall and disease-specific survival was not statistically different in down-staged and pT2 UCC. In conclusion, down-staging of UCC (<pT2) at cystectomy occurred in 26 %. At review of diagnostic TURs, MD invasion was not confirmed in 15 %. No clinical or pathologic parameter was predictive for down-staging at cystectomy. There was no difference in survival between down-staged and pT2-staged UCC.
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10.1007/s00428-012-1277-0
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pubmed_1058_20500
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Four patients with systemic mastocytosis, two men and two women, are presented. Three of them (patients 1, 2, and 4) developed portal hypertension and ascites without histological evidence of cirrhosis in liver biopsy. The remaining patient (patient 3) had severe bone lesions with multiple vertebral fractures. None of the patients had skin or lymph node involvement. Two patients (patients 1 and 2) died 12 and 9 months after diagnosis with acute nonlymphocytic leukemia and overt mastocytic leukemia, respectively, while the other two (patients 3 and 4) are alive 58 and 14 months after diagnosis. Treatment with hydroxyurea or cytosine arabinoside had not any beneficial effect in two patients, while a substantial amelioration of back pain had been obtained by local irradiation and recombinant human interferon-alpha-2b administration in one patient (patient 3). All patients had laboratory findings compatible with autoimmune cholangitis. We concluded that systemic mastocytosis is a rare cause of noncirrhotic portal hypertension often simulating autoimmune cholangitis and leading to the erroneous diagnosis of liver cirrhosis. Diagnosis is based on the presence of mast cells in Giemsa-stained liver histological sections, and it may be confirmed by immunohistochemical detection of tryptase in the cytoplasm of these abnormally proliferating cells.
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10.1111/j.1572-0241.1998.106_c.x
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pubmed_392_23939
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The lack of access to safe and effective antimicrobials for human populations is a threat to global health security and a contributor to the emergence and spread of antimicrobial resistance (AMR). The increasingly common shortages of antimicrobials are an additional threat to the emergence of AMR. While the threat of such drug shortages is most acutely experienced in low-income and middle-income settings, their consequences impact the quality and effectiveness of antimicrobials worldwide. Furthermore, there is a need for robustly conducted studies examining the impact of these increasingly prevalent shortages on patient outcomes and on the emergence and spread of AMR. In this review, we have mapped common drivers for antimicrobial shortages and propose strategies for rethinking the regulation, supply and pricing of antimicrobials to secure their sustainable access across diverse healthcare systems and to help minimise the unintended consequences of weak and ineffective supply chains. Greater government involvement in antimicrobial manufacture and supply is essential to ensure no one is left behind. Dedicated demand systems need to be developed for antimicrobials which take into consideration evolving AMR patterns, burden of diseases, pandemic events and supply and demand issues and facilitate implementation of strategies to address them. Interventions, ranging from advocacy and forecasting to public-private collaborations, new economic models and international consortia working across countries and supply chains, will help assure access to safe and effective antimicrobials to all populations around the globe and ensure that shortages no longer contribute to AMR.
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10.1136/bmjgh-2021-006961
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pubmed_574_9625
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Decisions to admit and discharge patients to and from the intensive care unit (ICU) when resources are scarce should be made according to the triage principle--that is, resources should be allocated based on the patient's ability to benefit from critical care. The ICU organizational structure and the constraints on decision-making processes are discussed in this article along with strategies for improvement in both areas.
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pubmed_574_9625
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pubmed_639_19313
|
BACKGROUND
Distraction osteogenesis using the Ilizarov external circular fixator has been applied in lower limb reconstructive surgery widely. The increasing ankle osteoarthritis (OA) progression and severity are often associated with the period of external fixator and the greater relative instability of the ankle joint, but few studies have quantified risk factors directly during this technique.
METHODS
The study was conducted on 236 patients who underwent bone transport surgery for tibias using the Ilizarov external circular fixator from 2008 to 2018. The cumulative incidence of ankle OA diagnoses in patients after the Ilizarov technique treatment was calculated and stratified by risk factors from preoperative and postoperative management. After the data were significant through the Mann-Whitney U test analyzed, odds ratios were calculated using logistic regression to describe factors associated with the OA diagnosis including gender, age, BMI, location of bone defect, diabetes, hypertension, osteoporosis, the history of metal allergy and glucocorticoid intake, the American Orthopaedic Foot & Ankle Society (AOFAS) ankle-HF scale scores, defect size (DS), the type of bone transport, the bone union time, external fixator time (EFT), and external fixator index (EFI).
RESULTS
There were 199 males and 37 females with a mean age of 47 years (range 28-59 years). Out of 236 patients, 49 had an additional treatment for ankle OA after the Ilizarov technique treatment of bone defects (average follow-up time 2.1 years, range 1.6-4.2 years). The incidence of postoperative ankle OA was 20.8 %, with 19 patients classified as K&L grade 3 and seven patients as grade 4. The top five risk factors included double-level bone transport (OR3.79, P = 0.005), EFI > 50days/cm (OR3.17, P = 0.015), age > 45years (OR2.29, P = 0.032), osteoporosis (OR1.58, P < 0.001), BMI > 25 (OR1.34, P < 0.001). Male, BMI > 25, diabetes, osteoporosis, and AOFAS ankle-HF scale scores are the independent risk factors.
CONCLUSIONS
Ilizarov external circular fixator is a safe and effective method of treatment for critical bone defects. The double level bone transport, EFI > 50days/cm, age > 45years, osteoporosis, BMI > 25 are the top five relevant risk factors of ankle OA. The probability of developing ankle OA among patients having three or more risk factors is 50-70 %.
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10.1186/s12891-021-04214-8
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pubmed_317_19057
|
Pituitary adenomas are among the most prevalent forms of intrinsic brain tumors. Although most pituitary adenomas are benign, some of them may become invasive and cause significant mass effect and hormonal dysfunction. We have previously shown that β-catenin is overexpressed in human pituitary adenomas and its level correlates to tumor grades. In the present study, we further investigated the role of β-catenin in pituitary adenoma cell proliferation and invasion in vitro. Stable β-catenin knockdown pituitary adenoma cell line was created by transfecting mouse growth hormone pituitary adenoma GT1.1 cells with β-catenin shRNA plasmid. Cell proliferation and invasion were assessed using CCK-8 kit and transwell assay, respectively. Our data demonstrated that knockdown of β-catenin with shRNA significantly inhibited the proliferation and invasion of GT1.1 cells. In β-catenin shRNA transfected cells, the expression of AKT, STAT3, cyclin D1 and CDK4 were significantly suppressed, which accounted for the observed growth retardation following β-catenin shRNA transfection. Moreover, β-catenin shRNA transfection led to a drastic reduction in MMP-2/9 secretion into the conditioned media, which might be responsible for the reduced invasiveness of β-catenin shRNA-transfected pituitary adenoma cells. These results indicate that β-catenin may regulate the expression of AKT, STAT3, cyclin D1, CDK4 and MMP-2/9 to promote pituitary adenoma cell proliferation and invasion.
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10.3892/ijo.2015.2862
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pubmed_67_15926
|
Sexually assaulted women represent a particularly high-risk group for developing post-traumatic stress disorder (PTSD). Potentially traumatic events (PTEs) and peritraumatic dissociation (PD) are known risk factors for PTSD. However, little is known about how previous trauma affects PD and how this relationship affects PTSD. We aimed to investigate whether PD acts as a mediator between PTEs and PTSD severity in a sample of recently sexually assaulted women in Sao Paulo, Brazil. Seventy-four sexually assaulted women aged 18-44 completed questionnaires and structured interviews on PTSD, PD, and PTEs. We examined direct and indirect effects of variables using causal mediation analysis. Lifetime exposure to PTEs was a risk factor for PD, but PD was not a risk factor for PTSD symptom severity. Also, PD was not a mediator between PTEs and PTSD severity. We provided recommendations on how to further explore the relationship between lifetime traumatic exposure, PTSD, and peritraumatic dissociation.
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10.1080/15299732.2022.2136326
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pubmed_318_2664
|
Experiments were conducted on rats. The influence of the serum of a burn convalescent on the toxic properties, the level of proteolytic enzymes activity, and morphological changes following burn were studied. After the burn the blood serum and the extracts of the organs acquired toxic properties; there was an increase in the activity of proteolytic enzymes, and marked morphological changes developed Administration of the serum of aburn convalescent promoted detoxication, diminished the activity of proteolytic enzymes distinctly, and decreased the morphological disturbances.
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pubmed_318_2664
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pubmed_984_21849
|
Oxidation products of biogenic volatile organic compounds (BVOCs) (isoprene, monoterpenes, and sesquiterpene) were investigated in the Canadian High Arctic aerosols using gas chromatography-mass spectrometry. Twelve specific secondary organic aerosol (SOA) tracers and two hydroxyacids (glycolic and salicylic acids) were determined. The total concentrations of alpha-/beta-pinene oxidation products (e.g., pinic and 3-hydroxyglutaric acids, 138-5303 pg m(-3), average 1646 pg m(-3)) were much higher than those of isoprene oxidation products (e.g., 2-methyltetrols and 2-methylglyceric acid, 80-567 pg m(-3), 300 pg m(-3)) and sesquiterpene (beta-caryophyllene) oxidation product (beta-caryophyllinic acid, 9-372 pg m(-3), 120 pg m(-3)). Although the mean contribution of isoprene oxidation products to organic carbon (OC) is very low (0.059%) compared to monoterpene oxidation products (0.29%), they increase significantly up to 0.20% in early summer when photochemical activity and atmospheric transport from North America are enhanced. Temporal variations of SOA tracers of monoterpenes and beta-caryophyllene are characterized by a winter/spring maximum and a summer minimum, being similar to those of OC and EC. In contrast, the isoprene oxidation tracers such as 2-methyltetrols showed a peak in early summer. By using a tracer-based method, we found that monoterpenes and beta-caryophyllene are the major contributors to secondary OC from dark winter to late May. However in early June, isoprene was found to be the largest contributor among the three precursors. This study demonstrates that photochemical oxidation of BVOCs also contributes to the formation of OC and WSOC in the Arctic atmosphere during late winter to early summer.
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10.1021/es803669a
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pubmed_1104_1525
|
Medical interviewing is the foundation of medical care and is the clinician's most important activity. A growing body of evidence suggests that clinicians use distinctive, describable behaviors to conduct medical interviews. This article describes four patterns of behavior that we term Habits and reviews the research evidence that links each Habit with both biomedical and functional outcomes of care. The Four Habits are: Invest in the Beginning, Elicit the Patient's Perspective, Demonstrate Empathy, and Invest in the End. Each Habit refers to a family of skills. In addition, the Habits bear a sequential relationship to one another and are thus interdependent. The Four Habits approach offers an efficient and practical framework for organizing the flow of medical visits. It is unique because it concentrates on families of interviewing skills and on their inter-relationships.
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pubmed_1104_1525
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pubmed_711_8346
|
The chloramphenicol resistance gene from pSa was introduced into T-DNA of pTi T37 of Agrobacterium tumefaciens by cointegration with intermediary plasmid based on pBR322. The resulting intermediary vector was mobilized to A. tumefaciens T37 by conjugative plasmid pRK2. The RK2 plasmid also forms contegrates with pTi due to the Tn3 transposon which was used for the mobilization of modified pTi into plasmid-less A. tumefaciens strain. Transconjugants were selected on the basis of their antibiotic resistance markers and tested for agrocin sensitivity as proof of Ti plasmid transfer. Agrocin sensitivity of tranconjugants together with chloramphenicol resistance was shown to be a sufficient and simple criterion of transfer of modified Ti plasmids. Agrobacterium strains with modified Ti plasmids showed decreased virulence in consequence of the presence of additional borderline sequence inside their T-DNA.
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10.1007/BF02926824
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pubmed_1041_7883
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A high-precision half-life measurement for the superallowed β+ emitter 26Al(m) was performed at the TRIUMF-ISAC radioactive ion beam facility yielding T 1/2 6346.54 ± 0.46(stat) ± 0.60 (syst) ms, consistent with, but 2.5 times more precise than, the previous world average. The 26Al(m) half-life and ft value, 3037.53(61) s, are now the most precisely determined for any superallowed β decay. Combined with recent theoretical corrections for isospin-symmetry-breaking and radiative effects, the corrected Ft value for (26)Al(m), 3073.0(12) s, sets a new benchmark for the high-precision superallowed Fermi β-decay studies used to test the conserved vector current hypothesis and determine the V(ud) element of the Cabibbo-Kobayashi-Maskawa quark mixing matrix.
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10.1103/PhysRevLett.106.032501
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pubmed_362_7999
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The present work aimed to study the guest-host complexes of β-hexachlorocyclohexane (β-HCH), a pesticide with high environmental stability that can cause severe health problems, with the most common cyclodextrins (α-, β-, and γ-CDs). The formation reactions of these molecular inclusion complexes were addressed in this research. The multiple minima hypersurface methodology, quantum calculations based on density functional theory and a topological exploration of the electron density based on the quantum theory of atoms in molecules approach were used to characterize the interaction spaces of the pollutant with the three CDs. Additionally, charge distribution, charge transfer and dual descriptor analyses were employed to elucidate the driving forces involved in the formation of these molecular inclusion complexes. Three types of fundamental interactions were observed: total occlusion, partial occlusion and external interaction (non-occlusion). Finally, experiments were performed to confirm the formation of the studied complexes. The most stable complexes were obtained when γ-CD was the host molecule. The interactions between the pesticide and CDs have fundamentally dispersive natures, as was confirmed experimentally by spectroscopic results. All the obtained results suggest the possibility of using CDs for the purification and treatment of water polluted with β-HCH.
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10.1039/c9ra04431k
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pubmed_323_3552
|
BACKGROUND
Despite the increasing pervasiveness of mobile computational technologies, knowledge about psychiatric patients' preferences regarding the design and utility of mobile applications is very poor. This paper reports on a pilot-study that involved 120 psychiatric patients in the development of a mobile application (app) that is being used for data entry into the Signature Project data bank at the Institut universitaire en santé mentale de Montréal (IUSMM), Canada. Participants were invited to comment on the 'look and feel' of the Signature App. Their input also extended the procedures for data collection. These suggestions may contribute to increased mental health literacy and empowerment of persons with mental illness receiving services at the IUSMM.
METHODS
Participants were recruited to fill out a questionnaire on a tablet computer while waiting at the Emergency Room (ER, n = 40), Psychotic Disorders outpatient clinic (n = 40) or Anxiety and Mood Disorders outpatient clinic (n = 40) of IUSMM. Nine patients from each of these sub-groups participated in a focus group to review the results and to discuss how the design and use of the Signature App could be improved to better meet the needs of patients.
RESULTS
This study (n = 120) indicated that psychiatric patients are clearly capable of using a tablet computer to fill out questionnaires for quantitative data entry, and that they enjoyed this experience. Results from the focus groups (n = 27) highlight that the app could also be used by patients to communicate some personal and contextual qualitative information. This would support a holistic and person-centered approach, especially at the ER where people acutely need to describe their recent history and receive emotional support.
CONCLUSIONS
This pilot-study has confirmed the necessity of involving patients not only in the testing of a new mobile application, but also as active contributors in the entire research and development process of a person-centered information and communication technology infrastructure. The input of participants was essential in designing the Signature Project computational procedure and making use of the app a positive and empowering experience. Participants also gave critical feedback remarks that went beyond the initial scope of the pilot-study, for example they suggested the addition of a client-clinician component.
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10.1186/1472-6947-13-78
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pubmed_849_24763
|
AIMS
We sought to determine the association between levels of adiponectin and oxidized low-density lipoprotein (ox-LDL) in patients with diabetic nephropathy as well as their effect on carotid intima-media thickness (cIMT).
METHODS
Adiponectin and ox-LDL were determined in 25 diabetic patients without nephropathy and 94 patients at different stages of diabetic nephropathy including subjects on hemodialysis. cIMT was measured using real-time B-mode ultrasonography.
RESULTS
Plasma adiponectin levels increased significantly with severity of diabetic nephropathy (P = 0.002), on the contrary to ox-LDL which decreased with disease severity (P < 0.001). cIMT was significantly higher at late stages of diabetic nephropathy compared with early stages (P = 0.022). Adiponectin was a significant negative predictor of ox-LDL levels (β = -5.45, P = 0.023), independently of confounding factors. There was no significant correlation between cIMT and adiponectin or ox-LDL either in the total sample population or according to disease staging. Cluster analysis showed that patients with the highest cIMT values, highest levels of adiponectin, and lowest levels of ox-LDL were included in one cluster and all assigned to stage 5 of diabetic nephropathy.
CONCLUSIONS
There was no significant association between adiponectin or ox-LDL and cIMT and, therefore, other factors affecting this surrogate marker of cardiovascular disease in diabetic nephropathy should be sought.
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10.1155/2015/507265
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pubmed_649_2390
|
Treatment of MCF 7 human breast cancer cells with three high affinity hydroxylated antiestrogens (Kd for the estrogen receptor = 0.11-0.45 nM) resulted in biphasic inhibition of cell growth. Administration of 0.1-1.0 nM of each drug caused a concentration-dependent decrease in cell number to a maximum of 30-40% of control but no further change was observed as the drug concentration was increased to 1 microM. Between 1.0 and 10 microM, however, a further concentration-dependent decrease in cell proliferation was observed. Among these compounds relative potencies paralleled their affinities for estrogen receptor in the 0.1-10 nM range but at micromolar concentrations this relationship did not hold. It is concluded that antiestrogens inhibit cell proliferation by two distinct mechanisms one of which involves the estrogen receptor and the other a mechanism yet to be defined. The parallel changes in cell cycle kinetic parameters accompanying growth inhibition in both concentration ranges i.e. accumulation of cells in the G1 phase at the expense of S phase cells, suggests that both mechanisms may converge on common pathways critical to cell cycle progression.
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10.1016/0006-291x(86)90763-1
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pubmed_959_17931
|
In this paper, we construct rogue wave solutions on the periodic background for the fourth-order nonlinear Schrödinger (NLS) equation. First, we consider two types of the Jacobi elliptic function solutions, i.e., dn- and cn-function solutions. Both dn- and cn-periodic waves are modulationally unstable with respect to the long-wave perturbations. Second, on the background of both periodic waves, we derive rogue wave solutions by combining the method of nonlinearization of spectral problem with the Darboux transformation method. Furthermore, by the study of the dynamics of rogue waves, we find that they have the analogs in the standard NLS equation, and the higher-order effects do not have effect on the magnification factor of rogue waves. In addition, when the elliptic modulus approaches 1, rogue wave solutions can reduce to multi-pole soliton solutions in which the interacting solitons form weakly bound states.
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10.1063/5.0030072
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pubmed_608_9599
|
In all eukaryotes, the mechanistic target of rapamycin (mTOR) signaling emerges as a master regulator of homeostasis, which integrates environmental inputs, including nutrients, energy, and growth factors, to regulate many fundamental cellular processes such as cell growth and metabolism. mTOR signaling functions through two structurally and functionally distinct complexes, mTOR complex 1 (mTORC1) and mTOR complex 2 (mTORC2), which correspond to two major branches of signal output. While mTORC1 is well characterized for its structure, regulation, and function in the last decade, information of mTORC2 signaling is only rapidly expanding in recent years, from structural biology, signaling network, to functional impact. Here we review the recent advances in many aspects of the mTORC2 signaling, with particular focus on its involvement in the control of cell metabolism and its physiological implications in metabolic diseases and aging.
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10.1155/2018/7838647
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pubmed_417_3342
|
Limited studies indicate increased free fraction of valproic acid in uremia. One study also described displacement of valproic acid from protein binding by salicylate in children with epilepsy. The authors studied in vitro interaction of valproic acid and salicylate in uremic sera and compared their results with same interactions in normal sera. As expected, the concentrations of free valproic acid were always significantly higher in uremic sera compared with normal sera. When uremic sera were supplemented with both valproic acid and salicylate, a much lower displacement of valproic acid by salicylate was observed, compared with the effects observed in normal sera. Treatment of uremic sera with charcoal removed those uremic compounds, and the concentration of free valproic acid in charcoal-treated uremic sera were comparable to the concentrations observed in normal sera. When uremic compounds were extracted from charcoal with methanol, lyophilized, and added to normal serum, an increase in free valproic acid concentration in normal serum was observed, indicating that uremic compounds, rather than altering albumin structure, are responsible for elevated free valproic acid concentration in uremia. However, uremic extract failed to produce any further displacement of valproic acid in normal serum in the presence of salicylate. The authors concluded that uremic compounds are responsible for elevated free valproic acid concentrations, but the displacement of valproic acid by salicylate in uremic sera are less remarkable compared with such effect in normal sera.
|
pubmed_417_3342
|
pubmed_551_4182
|
AIMS
External beam radiotherapy followed by brachytherapy is the standard treatment for patients with carcinoma cervix. However, for patients who come from peripheral hospitals after incomplete surgery, whole pelvic radiotherapy (WPRT) followed by boost with either vaginal vault brachytherapy if suitable or further external beam radiotherapy is recommended. This study was conducted to evaluate if it was possible to give a higher tumour dose using intensity-modulated radiotherapy for that group of patients who were not suitable for high dose rate vaginal vault brachytherapy because of gross disease after WPRT.
MATERIALS AND METHODS
A prospective study was carried out from 2005 to 2010 in which 25 postoperative patients of cervical carcinoma with gross residual disease after WPRT of 46 Gy/23 fractions/4.5 weeks were included. Nine patients were treated with 20 Gy to the planning target volume and 30 Gy to the clinical target volume in 10 fractions; 16 patients were treated with 30 Gy to the planning target volume and 35 Gy to the clinical target volume in 15 fractions. The end points of this study were local control, survival and treatment-related toxicity.
RESULTS
The median follow-up was 38 months. The 3 year local control, progression-free survival and overall survival rates were 76, 74 and 67%, respectively. Late grade 2 rectal toxicity was seen in 11 patients. Grade 2 bladder toxicity occurred in two patients and grade 3 bowel toxicity in two patients. No other grade 3 or higher toxicity was seen.
CONCLUSION
Inadequate and inappropriate surgery in invasive cervical cancer with resulting gross residual disease is common in India. It is possible to escalate the tumour dose by intensity-modulated radiotherapy boost after WPRT in postoperative cervical carcinoma patients with gross residual disease with low incidence of severe toxicity and excellent local control.
|
pubmed_551_4182
|
pubmed_996_18866
|
We describe a 53-year-old Japanese woman with absence of the posterior arch of the atlas. Computed tomography revealed that the residual posterior fragment which was displaced to the right side does not correspond to a rare ossification center in the midline and that there was no clear mass of the posterior arch except for a small fragment. Moreover, the midline center was not demonstrated as a soft tissue mass. Easy tilting of the posterior fragment on flexion-extension movement suggests that the cartilaginous arch was not present between the lateral masses and the posterior fragment of the atlas. These observations support the hypothesis that hypoplastic development of the arch plays a major role in the pathogenesis of this anomaly rather than incomplete ossification. Abnormal segmentation of the vertebrae may be implicated in the etiology of this condition, since fusion of the anterior vertebral masses between the C5-6 levels, as shown in Klippel-Feil syndrome, is also observed.
|
10.1007/BF00572917
|
pubmed_896_18885
|
OBJECTIVES
The penetration of antiretroviral drugs into deep compartments, such as the CNS, is a crucial component of strategies towards an HIV cure. This study aimed to determine CSF concentrations of bictegravir, emtricitabine and tenofovir in patients with HIV-related CNS impairment (HCI) enrolled in a real-life observational study.
METHODS
Patients with HCI treated by optimized ART, including bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) for at least 1 month were enrolled. Plasma and CSF concentrations were measured by quality control-validated assays (LC-MS/MS). The inhibitory quotient (IQARV) was calculated as the ratio of unbound (bictegravir) or total (emtricitabine and tenofovir) concentration to half (or 90%) maximal inhibitory concentration for bictegravir (or emtricitabine and tenofovir). All numerical variables are expressed as median (range).
RESULTS
Twenty-four patients (nine women) were enrolled. The age was 45 (26-68) years. Unbound bictegravir and total emtricitabine and tenofovir CSF concentrations were 4.4 (1.6-9.6), 84.4 (28.6-337.4) and 1.6 (0.7-4.3) ng/mL, respectively. The unbound bictegravir CSF fraction was 34% (15%-82%) versus 0.33% (0.11%-0.92%) in plasma. Three patients had an IQARV above unity for the three antiretrovirals. Factors positively associated with the CSF concentration (unbound for bictegravir) were age and total plasma concentration for the three antiretrovirals. Patients aged over 51 years had higher CSF concentrations (unbound for bictegravir).
CONCLUSIONS
We observed low CSF exposure to bictegravir, emtricitabine and tenofovir. These results suggest that BIC/FTC/TAF should be used with caution as first-line treatment for people living with HIV with HCI under 51 years of age.
|
10.1093/jac/dkab334
|
pubmed_701_20488
|
The metabolism of terfenadine was studied with a cDNA-expressed/purified recombinant fusion protein containing human liver microsomal cytochrome P4503A4 (CYP3A4) linked to rat NADPH-P450 reductase (rF450[mHum3A4/mRatOR]L1) and was compared with that observed in the presence of human liver microsomes and precision-cut human liver tissue slices. In all three cases, [3H]terfenadine was metabolized to at least three major metabolites. LC/MS (electrospray) analysis confirmed that these metabolites were alpha, alpha-diphenyl-4-piperidinomethanol (M5), t-butyl hydroxy terfenadine (M4), and t-butyl carboxy terfenadine (M3), although the level of M5 detected in the presence of fusion protein was greater than that found with microsomes or tissue slices. Two additional metabolites, M1 (microsomes and tissue slices) and M2 (fusion protein), were also detected, but remain uncharacterized. Consumption of parent drug (microsomes: KM = 9.58 +/- 2.79 microM, Vmax = 801 +/- 78.3 pmol/min/nmol CYP; fusion protein: KM = 14.1 +/- 1.13 microM, Vmax = 1670 +/- 170 pmol/min/nmol CYP) and t-butyl hydroxylation to M4 (microsomes: KM = 12.9 +/-3.74 microM, Vmax = 643 +/- 62.5 pmol/min/nmol CYP, ; fusion protein: KM = 30.0 +/- 2.55 microM, Vmax = 1050 +/- 141 pmol/min/nmol CYP) obeyed Michaelis-Menten kinetics over the terfenadine concentration range of 1-200 microM. Ketoconazole, a well-documented CYP3A inhibitor, effectively inhibited terfenadine metabolism in all three models. The conversion of M4 to M3, studied with human liver microsomes and fusion protein, was NADPH-dependent and inhibited by ketoconazole. It is concluded that cDNA-expressed CYP3A4, in the form of a NADPH-P450 reductase-linked fusion protein, may also serve as a model for studying the metabolism of terfenadine in vitro and many other drugs.
|
pubmed_701_20488
|
pubmed_795_13175
|
Isolated hepatocytes from fed rats were exposed for 120 min to D-glucose (10 mM) and either D-[1-13C]fructose, D-[2-13C]fructose or D-[6-13C]fructose (also 10 mM) in the presence of D2O. The identification and quantification of 13C-enriched D-fructose and its metabolites (D-glucose, L-lactate, L-alanine) in the incubation medium and the measurement of their deuterated isotopomers indicated, by comparison with a prior study conducted in the absence of exogenous D-glucose, that the major effects of the aldohexose were to increase the recovery of 13C-enriched D-fructose, decrease the production of 13C-enriched D-glucose, restrict the deuteration of the 13C-enriched isotopomers of D-glucose to those generated by cells exposed to D-[2-13C]fructose, and to accentuate the lesser deuteration of the C, (as compared to C5) of 13C-enriched D-glucose derived from D-[2-13C]fructose. The ratio between C2-deuterated and C2-hydrogenated L-lactate, as well as the relative amounts of the CH3-, CH2D-, CHD, and CD3- isotopomers of 13C-enriched L-lactate were not significantly different, however, in the absence or presence of exogenous D-glucose. These findings indicate that exogenous D-glucose suppressed the deuteration of the C1 of D-[I-13C]glucose generated by hepatocytes exposed to D-[1-13C]fructose or D-[6-13C]fructose, as otherwise attributable, in part at least, to gluconeogenesis from fructose-derived [3-13C]pyruvate, and apparently favoured the phosphorylation of D-fructose by hexokinase isoenzymes, probably through stimulation of D-fructose phosphorylation by glucokinase.
|
10.1023/a:1020818810935
|
pubmed_805_15975
|
Is there a difference in the numbers of tape injuries, hematomas, and recurrent bleeding episodes associated with the postarteriographic wound between the standard pressure dressing and the pelvic-girdle-type pressure dressing? The answers to these questions can be important to critical care nursing practices.
|
pubmed_805_15975
|
pubmed_1121_12705
|
Fluoroarenes are widely used in medicinal, agricultural, and materials chemistry, and yet their production remains a critical challenge in organic synthesis. Indeed, the nearly identical physical properties of these vital building blocks hinders their purification by traditional methods, such as flash chromatography or distillation. As a result, the Balz-Schiemann reaction is currently employed to prepare fluoroarenes instead of more atom-economical C-H fluorination reactions, which produce inseparable mixtures of regioisomers. Herein, we propose an alternative solution to this problem: the purification of mixtures of fluoroarenes using metal-organic frameworks (MOFs). Specifically, we demonstrate that controlling the interaction of fluoroarenes with adjacent coordinatively unsaturated Mg2+ centers within a MOF enables the separation of fluoroarene mixtures with unparalleled selectivities. Liquid-phase multicomponent equilibrium adsorption data and breakthrough measurements coupled with van der Waals-corrected density functional theory calculations reveal that the materials Mg2(dobdc) (dobdc4- = 2,5-dioxidobenzene-1,4-dicarboxylate) and Mg2(m-dobdc) (m-dobdc4- = 2,4-dioxidobenzene-1,5-dicarboxylate) are capable of separating the difluorobenzene isomers from one another. Additionally, these frameworks facilitate the separations of fluoroanisoles, fluorotoluenes, and fluorochlorobenzenes. In addition to enabling currently unfeasible separations for the production of fluoroarenes, our results suggest that carefully controlling the interaction of isomers with not one but two strong binding sites within a MOF provides a general strategy for achieving challenging liquid-phase separations.
|
10.1021/jacs.0c11530
|
pubmed_363_383
|
Human NK cells are characterized by the expression of surface receptors of the killer cell Ig-like receptor (KIR) family, which are involved in the specific recognition of pathogenic target cells. Each NK cell expresses and maintains an individual subset of inhibitory and stimulatory KIR and in this way contributes to a diversified NK cell repertoire. To date, the molecular basis for generation of clonally distributed KIR expression patterns has been elusive. Here, analyses of DNA methylation patterns of KIR genes in NK cell lines as well as in NK cells, freshly isolated from peripheral blood, demonstrated that a small CpG island surrounding the transcriptional start site of each KIR gene is consistently demethylated in expressed KIR and methylated in unexpressed KIR. DNA-demethylating treatment resulted in a rapid and stable induction of transcription and cell surface expression of all formerly unexpressed KIR in NK cell lines, NK cell clones, and freshly isolated NK cells, but not in other cell types. In vitro methylation of KIR CpG islands repressed reporter gene expression in NK cells. We conclude that clonal patterns of KIR expression are mainly epigenetically determined and maintained through DNA methylation.
|
10.4049/jimmunol.169.8.4253
|
pubmed_547_20843
|
Perianal dermatitis is one of the most common proctological disorders. The anatomy of the anal region provides suitable conditions for the development of dermatitis. In the diagnostic work-up and the management of patients with perianal dermatitis, three types need to be distinguished: irritant contact dermatitis, atopic dermatitis, and allergic contact dermatitis. Each type has its aetiological and pathogenetic factors, which will provide clues to the diagnosis and subsequent management of the condition. In the differential diagnosis of the condition, consideration should be given to inflammatory diseases of the perianal region which may produce eczema-like patterns.
|
10.1007/s10354-004-0046-3
|
pubmed_600_11194
|
BACKGROUND
Evidence suggests that human leukocyte antigen (HLA) alleles influence the host immune response against Mycobacterium leprae. However, the association between HLA alleles and borderline (B) leprosy has not been studied. The aim of this study was to determine whether HLA class I and II molecules are associated with susceptibility or resistance to B leprosy including borderline-tuberculoid (BT), borderline-borderline (BB), and borderline-lepromatous (BL).
METHODS
DNA was obtained by the salting-out technique from the blood samples of 202 patients with B leprosy and 478 control subjects. HLA class I (A*, B*, and C* loci) and class II (DRB1* and DQB1* loci) genotypes were determined by polymerase chain reaction amplification and reverse hybridization with sequence-specific oligonucleotide probes and sequence-specific primers.
RESULTS
The case-controlled analysis results showed a significant association between B leprosy and HLA-C*05 (5.94% vs. 14.02%; p = 0.002, OR = 0.38, 95% CI = 0.20-0.73, pc = 0.032) and HLA-DRB1*07 (16.34% vs. 26.77%; p = 0.003, OR = 0.53, 95% CI = 0.3-0.8, pc = 0.039). A protective association was observed between BL leprosy and HLA-DQB1*02 (18.18% vs. 39.53%; p = 0.005, OR = 0.34, 95% CI = 0.15-0.75, pc = 0.025). In reactional patients, a significant association was observed between HLA-B*15 (28.72% vs. 12.76%; p = 0.011, OR = 2.75, 95% CI = 1.30-5.85, pc = 0.352) and predisposition to reversal reaction. Haplotype analysis showed that A*02-B*07-C*07-DRB1*15-DQB1*06 (2.97% vs. 1.04%; p = 0.015) and A*02-B*40-C*03-DRB1*13-DQB1*06 (1.73% vs. 0.10%; p = 0.0011) were associated with susceptibility to the B form. The presence of the HLA-DRB1*02 or HLA-DRB1*03/HLA-DQB1*01 haplotypes in B patients (22.05% vs. 33.0%; p = 0.005) suggested the involvement of these haplotypes in this clinical form of the disease.
CONCLUSIONS
The results indicate the involvement of HLA class I and class II molecules in B leprosy and reversal reactions; it also suggest a role for HLA in polarization of the disease in this group of patients.
|
10.1186/s12879-015-0751-0
|
pubmed_278_4841
|
In recent years, metabolomic analyses have been increasingly performed in studies with an epidemiological design. Since 2012, the National Cancer Institute has recognized the importance of supporting these efforts by strategically building resources and infrastructure to move this area forward. This review outlines those efforts, including building infrastructure, leveraging existing resources, establishing the COnsortium of METabolomics Studies (COMETS), and improving rigor and reproducibility.
|
10.1007/s11306-021-01791-6
|
pubmed_1138_14630
|
Many chromaffin cell tumors contain somatostatin (SS), and most of them are receptor-positive by in vitro autoradiography and by in vivo administration of radiolabeled SS analogs. We evaluated the effect of a 2-hour infusion of 50 micrograms octreotide on plasma norepinephrine (NE) and epinephrine (E) levels in 6 patients with chromaffin cell tumors. To ascertain the biological activity of octreotide, plasma insulin levels were also measured. Infusion of octreotide was followed in all the patients but 1 by a progressive decrease of plasma NE levels. On the average, plasma NE decreased significantly during octreotide administration, halving its baseline levels at the end of the infusion (51.3 +/- 11.46%, p < 0.05) and rising again slowly thereafter. A slight reduction of plasma E levels was also recorded at the end of octreotide infusion (76.1 +/- 13.77% of baseline, NS) with a prompt return of hormone concentrations to preinfusion values. During octreotide administration, plasma insulin displayed an early and steep fall (49.7 +/- 4.61% of baseline, p < 0.03, at 60 min) with a tendency to escape from inhibition before termination of the infusion. In 5/6 patients, 2 of whom were normotensive before the study and 1 the day of the test, blood pressure did not change during octreotide infusion. In the other patient, blood pressure fell from baseline values of 160/100 to 120/70 mm Hg at 120 min and rebounded to 205/100 mm Hg at 240 min. In conclusion, the short-term administration of low-dose octreotide is capable of lowering NE levels, though with no consistent effect on blood pressure, in patients with chromaffin cell tumors.(ABSTRACT TRUNCATED AT 250 WORDS)
|
10.1159/000183786
|
pubmed_16_8760
|
RNA interference (RNAi) is a natural mechanism for regulating gene expression, which exists in plants, invertebrates, and mammals. We investigated whether non-viral infusion of short interfering RNA (siRNA) by the intracerebroventricular route would enable a sequence-specific gene knockdown in the mouse brain and whether the knockdown translates into disease-relevant behavioral changes. Initially, we targeted enhanced green fluorescent protein (EGFP) in mice overexpressing EGFP. A selective knockdown of both EGFP protein and mRNA was observed throughout the brain, with lesser down-regulation in regions distal to the infusion site. We then targeted endogenous genes, encoding the dopamine (DAT) and serotonin transporters (SERT). DAT-siRNA infusion in adult mice produced a significant down-regulation of DAT mRNA and protein and elicited hyperlocomotion similar, but delayed, to that produced on infusion of GBR-12909, a potent and selective DAT inhibitor. Similarly, SERT-siRNA infusion resulted in significant knockdown of SERT mRNA and protein and elicited reduced immobility in the forced swim test similar to that obtained on infusion of citalopram, a very selective and potent SSRI. Application of this non-viral RNAi approach may accelerate target validation for neuropsychiatric disorders that involve a complex interplay of gene(s) from various brain regions.
|
10.1080/10799890600929663
|
pubmed_446_3403
|
AIMS/HYPOTHESIS
Research on the pathogenesis of type 1 diabetes relies heavily on good animal models. The aim of this work was to study the translational value of animal models of type 1 diabetes to the human situation.
METHODS
We compared the four major animal models of spontaneous type 1 diabetes, namely the NOD mouse, BioBreeding (BB) rat, Komeda rat and LEW.1AR1-iddm rat, by examining the immunohistochemistry and in situ RT-PCR of immune cell infiltrate and cytokine pattern in pancreatic islets, and by comparing findings with human data.
RESULTS
After type 1 diabetes manifestation CD8(+) T cells, CD68(+) macrophages and CD4(+) T cells were observed as the main immune cell types with declining frequency, in infiltrated islets of all diabetic pancreases. IL-1β and TNF-α were the main proinflammatory cytokines in the immune cell infiltrate in NOD mice, BB rats and LEW.1AR1-iddm rats, as well as in humans. The Komeda rat was the exception, with IFN-γ and TNF-α being the main cytokines. In addition, IL-17 and IL-6 and the anti-inflammatory cytokines IL-4, IL-10 and IL-13 were found in some infiltrating immune cells. Apoptotic as well as proliferating beta cells were observed in infiltrated islets. In healthy pancreases no proinflammatory cytokine expression was observed.
CONCLUSIONS/INTERPRETATION
With the exception of the Komeda rat, the animal models mirror very well the situation in humans with type 1 diabetes. Thus animal models of type 1 diabetes can provide meaningful information on the disease processes in the pancreas of patients with type 1 diabetes.
|
10.1007/s00125-013-3125-4
|
pubmed_541_2714
|
A new and still evolving paradigm of a highly dynamic nucleus has emerged in recent years. This paradigm includes an inherently high turnover rate of histone and non-histone protein modifications, targeted turnover and/or displacement of 'stable' core histone proteins, constant flux of macromolecules through chromosomes and nuclear bodies, including transcription factors and co-activators, and an energy-dependent facilitation of nuclear-protein complex formation and disassembly. Also included are fast, local movements of chromosomes, together with slower but long-range movements of chromosomes and nuclear bodies.
|
10.1016/s0955-0674(03)00045-0
|
pubmed_1072_1303
|
BACKGROUND
Flunarizine dihydrochloride is used as a prophylaxis to migraine. Flunarizine dihydrochloride nanoemulsion was fabricated in this research work. Since, it is a low soluble high permeable drug, work was designed to enhance the solubility and the same can be administered as nasal drug delivery for faster onset of action and therapeutic effect.
OBJECTIVE
To fabricate a nanoemulsion of flunarizine dihydrochloride by using surfactant and co-surfactants.
METHODS
The experimental work involved compatibility studies by using FTIR, crystallinity study by XRD. The prepared nanoemulsion was studied by photon correlation spectroscopy by master sizer 2000 for the particle size analysis and characterized for D10, D50 and D90 MPS, span and uniformity. Further studies were conducted by Laser light scattering technique by delsa nano common and TEM.
RESULTS
The study demonstrated that the formulations (FNE 1 -FNE 5) demonstrated the MPS of 14, 22.7, 326.7, 14.3 and 40.73 respectively. The formulae FNE1 and FNE5 demonstrated the MPS of 214.6±179.9 and 2118.6 ±1503.6 with the diameter of 127.8 and 1307, respectively. The zeta potential of FNE1 was -3.84 mV and other parameters such as TEM and drug release studies were also reported.
CONCLUSION
The nanoemulsion of Flunarizine dihydrochloride was prepared successfully by using cremophor and labrafil which was better than the existed formula prepared by tween 80. The optimised formula demonstrated lower droplet size, satisfactory zeta potential, and high drug loading reproducible drug release profile.
|
10.2174/2211738504666160601162604
|
pubmed_206_17329
|
Rheumatoid arthritis (RA) is characterized by proliferation of synoviocytes that produce proinflammatory cytokines, which are implicated in the pathogenesis of RA. When human fibroblast-like synoviocytes line MH7A was treated with cigarette smoke condensate (CSC), either mainstream or sidestream, expression levels of interleukin (IL)-1alpha, IL-1beta, IL-6, IL-8, and CYP1A1 mRNA were upregulated in both time- and dose-dependent manners. The upregulatory effects of CSC on these cytokines were not significantly inhibited by alpha-naphthoflavone, an aryl hydrocarbon receptor (AhR) antagonist, suggesting that the effects of CSC were independent of AhR. Cycloheximide treatment indicated that the augmenting effect of CSC on IL-1alpha, IL-1beta and IL-8, but not IL-6 and CYP1A1, mRNA expression requires de novo protein synthesis. CSC also induced cytokines at protein levels and further augmented the effects of tumor necrosis factor alpha on induction of these cytokines at both mRNA and protein levels. These results support the epidemiological studies indicating a strong association between heavy cigarette smoking and pathogenesis of RA.
|
10.1089/jir.2007.0081
|
pubmed_372_25843
|
This case report describes a 56-year-old female who presented to the emergency department with diffuse facial and bilateral upper extremity swelling. The patient has a past medical history of Superior vena cava (SVC) syndrome secondary to a clot around her port-a-cath, adenocarcinoma of the lungs status post chemotherapy and radiation, hyperlipidemia, rheumatoid arthritis, diverticulitis status post colon resection, and hypothyroidism. Imaging confirmed the presence of a thrombus obstructing the SVC, likely due to her hypercoagulable state. This case report details the successful removal of a thrombus using the FlowTriever device by INARI in a patient with SVC syndrome. Although indicated for treatment of PE, FlowTriever has shown success in other conditions and nearly eliminates the risk of bleeding without the need for administering thrombolytics, as explained below in the setting of SVC syndrome.
|
10.1016/j.radcr.2021.12.032
|
pubmed_800_18134
|
The aim of the study was to evaluate the possible interactions and/or modulations of the serotoninergic system on hormonal parameters and the reproductive axis in amenorrheic subjects. Hypogonadotropic, underweight, amenorrheic patients (n = 8) were studied before and during cyproheptadine clorhydrate administration (4 mg/day for 3 months). A pulsatility study (4 hours, sampling every 10 minutes) and a naloxone test were performed before and after 4 and 12 weeks of treatment. Plasma luteinizing hormone (LH), follicle-stimulating hormone (FSH), growth hormone (GH), estradiol, thryoid-stimulating hormone (TSH), free tri-iodothyronine (fT3), free thyroxine (fT4) and total tri-iodothyonine (total T3), insulin-like growth factor-I (IGF-I) concentrations were determined. Pulse detection analysis was performed using the DETECT program. Serotoninergic receptor blockade affected neither the naloxone-inducted LH response nor the gonadotropin pulsatile parameters. Body mass index (BMI) did not vary; conversely, integrated mean gonadotropins, GH and fT3 concentrations increased during the treatment. In conclusion, cyproheptadine administration affects some of the abnormal endocrine parameters of underweight amenorrheic subjects with no modulation of the opioidergic system. It is likely that the gonadotropin and the fT3 increases take place owing to a change in the metabolic signals modulating hypothalamic function and/or an increased energy availability. Our study suggests a specific central effect of cyproheptadine on the serotonergic pathway controlling food intake at the hypothalamic level.
|
10.1080/gye.15.4.279.285
|
pubmed_372_1351
|
The taxonomic status of Triatomadimidiata (Latreille, 1811) is, by far, the most discussed within Triatominae. Molecular studies have recovered at least three independently evolving lineages in T.dimidiata across its range. The original description of T.dimidiata (as Reduviusdimidiatus) included few taxonomic characters, and no types were assigned. To define and describe the cryptic diversity within T.dimidiata sensu lato (s.l.), a neotype must be designated. For this purpose, all 199 specimens identified as T.dimidiata from the collections of the Smithsonian Institution - National Museum of Natural History and the American Museum of Natural History, ranging from Peru to Mexico, were studied. Only one specimen (from Tumbes, Peru) matched the combination of characters as listed in the original description, and it is herein formally designated as the neotype for T.dimidiata. The neotype is morphologically described and DNA sequences of its whole mitochondrial genome and the nuclear second internal transcribed spacer region (ITS2), commonly used in triatomine molecular systematics studies, are presented and compared to other publicly available sequences of T.dimidiata s.l. in GenBank. Our results suggest that T.dimidiata sensu stricto (s.s.) is somewhat rare and, therefore, unlikely to serve as a major vector of Chagas disease.
|
10.3897/zookeys.1076.72835
|
pubmed_150_7589
|
BACKGROUND
Several risk scores have been developed for predicting cognitive impairment and dementia, but none have been validated in Asian samples. We aimed to produce a risk score that best predicts incident neurocognitive disorder (NCD) among Chinese elderly and to validate this score against the modified risk score derived from the Cardiovascular Risk Factors, Aging and Dementia (CAIDE) study.
METHODS
Data from participants enrolled in the Singapore Longitudinal Ageing Study (SLAS) 1 were analyzed. A total of 957 participants >55 years of age with normal cognition at baseline were included. Incident cases of NCD were measured using the global Clinical Dementia Rating (CDR) and determined by a consensus panel.
RESULTS
The best prediction model from SLAS included age, gender, education, depression, heart disease, social and productive activities and Mini-Mental State Examination score. This model predicted the short-term risk of incident NCD in elderly participants moderately well, with a C statistic (area under the curve) of 0.72. Modified CAIDE models applied to our sample had a C statistic of 0.71.
CONCLUSION
Our risk score performs as well as other available risk scores. It is the only risk score formulated for ethnic Chinese, rendering it valuable for clinical use in Asia; at-risk individuals can be identified for early intervention.
|
10.1159/000447448
|
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