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pubmed_949_16210 | Contradictory results have been published about the relation between copper, zinc and selenium and blood pressure (BP). To evaluate the role of these trace elements in BP regulation, we analysed the correlations between BP and copper, zinc and selenium, measured from serum, diet and hair among 3596 healthy children in a 6-year follow up. Fasting blood samples were used in serum copper, zinc and selenium analyses. The dietary intake of trace elements and energy were determined by the 48-h recall method. The hair copper and zinc analyses were performed from the naturally coloured hair samples. Correlation analysis was used to show the relation between BP and copper, zinc or selenium in each study year and during a 3- or 6-year follow-up period. The zinc-to-copper ratio in serum, diet and hair was calculated. In the correlation analyses the data was adjusted for weight and the daily intake of energy. Neither serum and diet copper or zinc, nor the zinc-to-copper ratio correlated uniformly with BP measured in the same year (correlation coefficients varying from -0.12 to 0.18) or in the subsequent years. Hair copper and zinc correlated weakly negatively with BP (correlation coefficients varying from -0.17 to -0.01). Serum selenium correlated weakly positively with systolic and diastolic BP measured in the same year (correlation coefficients varying from 0.03 to 0.14), but not with subsequent BP measured in the second or third survey. Dietary selenium had an inconsistent effect on BP (correlation coefficients varying from -0.14 to 0.26). In conclusion, copper, zinc, their ratio or selenium did not associate with BP, nor did they have any effect on subsequent BP. | 10.1038/sj.jhh.1000466 |
pubmed_158_20296 | Few basic nursing education programs provide the student nurse with courses in business and finance. Those skills were most often acquired by nurse managers when they were promoted from a staff position to a management position and they were acquired on the job. As the health care environment becomes more complex, so too does the scope of business and financial skills. Today's nurse manager must develop a wider range of skills to survive. Among the most important is an ability to connect unit level needs to the overall goals of the organization. | 10.1016/s1089-9472(96)90056-8 |
pubmed_83_7212 | In this work, a detection and classification method for sleep apnea and hypopnea, using photopletysmography (PPG) and peripheral oxygen saturation (SpO 2) signals, is proposed. The detector consists of two parts: one that detects reductions in amplitude fluctuation of PPG (DAP)and one that detects oxygen desaturations. To further differentiate among sleep disordered breathing events (SDBE), the pulse rate variability (PRV) was extracted from the PPG signal, and then used to extract features that enhance the sympatho-vagal arousals during apneas and hypopneas. A classification was performed to discriminate between central and obstructive events, apneas and hypopneas. The algorithms were tested on 96 overnight signals recorded at the UZ Leuven hospital, annotated by clinical experts, and from patients without any kind of co-morbidity. An accuracy of 75.1% for the detection of apneas and hypopneas, in one-minute segments,was reached. The classification of the detected events showed 92.6% accuracy in separating central from obstructive apnea, 83.7% for central apnea and central hypopnea and 82.7% for obstructive apnea and obstructive hypopnea. The low implementation cost showed a potential for the proposed method of being used as screening device, in ambulatory scenarios. | 10.1109/TBME.2020.3028041 |
pubmed_205_11457 | OBJECTIVE
To review the outcomes of transcatheter closure of atrial septal defects using the Cardio-Seal implant.
DESIGN
A prospective interventional study.
SETTING
Tertiary referral centre.
PATIENTS
The first 50 patients (median age 9.7 years) who underwent attempted percutaneous occlusion.
INTERVENTIONS
Procedures were done under general anaesthesia and transoesophageal guidance between December 1996 and July 1998.
MAIN OUTCOME MEASURES
Success of deployment, complications, and assessment of right ventricular end diastolic diameter, septal wall motion, and occlusion status by echocardiography.
RESULTS
The median balloon stretched diameter was 14 mm. Multiple atrial septal defects were present in 11 patients (22%) and a deficient atrial rim (< 4 mm) in 19 (38%). In four patients (8%), a second device was implanted after removal of an initially malpositioned first implant. There were no significant immediate complications. All patients except one were discharged within 24 hours. At the latest follow up (mean 9.9 months) a small shunt was present in 23 patients (46%), although right ventricular end diastolic dimensions (mean (SD)) corrected for age decreased from 137 (29)% to 105 (17)% of normal, and septal motion abnormalities normalised in all but one patient. No predictors for a residual shunt were identified. Supporting arm fractures were detected in seven patients (14%) and protrusion of one arm through the defect in 16 (32%), the latter being more common in those with smaller anterosuperior rims. No untoward effects resulted from arm fractures or protrusion. There were no complications during follow up, although five patients (10%) experienced transient headaches.
CONCLUSIONS
The implantation of the Cardio-Seal device corrects the haemodynamic disturbances secondary to the right ventricular volume overload, with good early outcome. | 10.1136/heart.84.3.320 |
pubmed_849_11734 | BACKGROUND
To our knowledge, a systematic comparison of predictors of mortality in middle-aged to elderly individuals has not yet been done. We investigated predictors of mortality in UK Biobank participants during a 5 year period. We aimed to investigate the associations between most of the available measurements and 5 year all-cause and cause-specific mortality, and to develop and validate a prediction score for 5 year mortality using only self-reported information.
METHODS
Participants were enrolled in the UK Biobank from April, 2007, to July, 2010, from 21 assessment centres across England, Wales, and Scotland with standardised procedures. In this prospective population-based study, we assessed sex-specific associations of 655 measurements of demographics, health, and lifestyle with all-cause mortality and six cause-specific mortality categories in UK Biobank participants using the Cox proportional hazard model. We excluded variables that were missing in more than 80% of the participants and all cardiorespiratory fitness test measurements because summary data were not available. Validation of the prediction score was done in participants enrolled at the Scottish centres. UK life tables and census information were used to calibrate the score to the overall UK population.
FINDINGS
About 500,000 participants were included in the UK Biobank. We excluded participants with more than 80% variables missing (n=746). Of 498,103 UK Biobank participants included (54% of whom were women) aged 37-73 years, 8532 (39% of whom were women) died during a median follow-up of 4·9 years (IQR 4·33-5·22). Self-reported health (C-index including age 0·74 [95% CI 0·73-0·75]) was the strongest predictor of all-cause mortality in men and a previous cancer diagnosis (0·73 [0·72-0·74]) was the strongest predictor of all-cause mortality in women. When excluding individuals with major diseases or disorders (Charlson comorbidity index >0; n=355 043), measures of smoking habits were the strongest predictors of all-cause mortality. The prognostic score including 13 self-reported predictors for men and 11 for women achieved good discrimination (0·80 [0·77-0·83] for men and 0·79 [0·76-0·83] for women) and significantly outperformed the Charlson comorbidity index (p<0·0001 in men and p=0·0007 in women). A dedicated website allows the interactive exploration of all results along with calculation of individual risk through an online questionnaire.
INTERPRETATION
Measures that can simply be obtained by questionnaires and without physical examination were the strongest predictors of all-cause mortality in the UK Biobank population. The prediction score we have developed accurately predicts 5 year all-cause mortality and can be used by individuals to improve health awareness, and by health professionals and organisations to identify high-risk individuals and guide public policy.
FUNDING
Knut and Alice Wallenberg Foundation and the Swedish Research Council. | pubmed_849_11734 |
pubmed_756_1062 | BACKGROUND
Autoimmune hepatitis (AIH) after liver transplantation has been defined histologically as a "hepatitic" pattern of injury, characterized by lymphoplasmacytic inflammation with necroinflammatory activity (NIA), comparable with findings seen in native livers. This definition, however, is difficult to apply in practice because specific histologic criteria are not clearly delineated. This study aimed to determine which histologic features correlated best with clinical and serologic features of dAIH.
METHODS
Index liver biopsies from patients with autoimmune-like hepatitis transplanted for non-AIH in two centers (n=35 and 20) were reviewed. Histologic features were correlated with the clinical diagnosis of AIH based on a retrospective review of clinical and serologic data, including therapeutic response.
RESULTS
A clinical diagnosis of AIH was retrospectively assigned to 24 of 35 (68%) and 18 of 20 (90%) patients, respectively (P=0.10). In multivariate analysis, centrilobular NIA and centrilobular plasma cell (PC) ratio of 30% to 50% were independently discriminating for a clinical diagnosis of AIH (P=0.04 and 0.05, respectively). The best level of predictability (99.6%) was mathematically achieved when severe centrilobular NIA and centrilobular PC ratio of 30% to 50% were both present.
CONCLUSION
A histologic pattern of centrilobular injury including increased NIA and increased PC infiltration correlates with measurements of autoimmunity in liver recipients. It could be used to segregate cases for further study and introduced into the AIH scoring systems when applied in the context of liver transplantation. | 10.1097/TP.0b013e31829eda7f |
pubmed_30_17196 | Electrophysiological, mechanical, dimensional and coronary flow characteristics were studied on papillary strips and on isolated hearts, from spontaneously hypertensive (SHR) and normotensive (WKY) rats respectively, which from 5 to 15 weeks of age had been on either 'low' (LNa, 0.5 mmol 100 g-1 food), control (CNa, 5) 'high' (HNa, 50) or 'very high' (vHNa, 120) sodium diets. With respect to cardiac electrophysiological characteristics, contractility, and maximal stroke volume capacity only minor, if any, differences were observed between the various Na diet groups, both in WKY and SHR. This is in accordance with our earlier findings concerning vascular smooth muscle, where a largely unchanged sensitivity and responsiveness to, for example, noradrenaline was noted. Further, only to the extent that the various Na diets had also caused changes in average blood pressure levels, adaptations of cardiac and coronary resistance vessel design were observed, in general agreement with our earlier findings in other preparations and experimental designs. The largely unaffected functional characteristics of cardiac as well as vascular effector cells, despite 240-fold long-term variations in sodium intake, are in sharp contrast to the marked changes that have been shown to affect the adrenergic nerves, as here chronic low-Na intakes cause reductions of transmitter release/impulse, and vice versa at high Na intakes. This latter type of change seems to be by far the most important functional deviation affecting cardiovascular control during long-term alterations of sodium intake, as it can markedly affect both cardiac and vascular influences on haemodynamics, even though the respective effector functions seem to be surprisingly little influenced directly.(ABSTRACT TRUNCATED AT 250 WORDS) | 10.1111/j.1748-1716.1989.tb08582.x |
pubmed_405_16116 | Excitation-contraction coupling (ECC) is the physiological mechanism whereby an electrical signal detected by the dihydropyridine receptor, is converted into an increase in [Ca2+], via activation of ryanodine receptors (RyRs). Mutations in RYR1, the gene encoding RyR1, are the underlying cause of various congenital myopathies including central core disease, multiminicore disease (MmD), some forms of centronuclear myopathy (CNM) and congenital fibre-type disproportion. Interestingly, patients with recessive, but not dominant, RYR1 mutations show a significant reduction in RyR protein in muscle biopsies as well as ophthalmoplegia. This specific involvement of the extraocular muscles (EOMs) indicates that this group of muscles may express different amounts of proteins involved in ECC compared with limb muscles. In the present paper, we report that this is indeed the case; in particular the transcripts encoding RyR3, cardiac calsequestrin (CSQ2) and the α1 subunit of the cardiac dihydropyridine receptor are up-regulated by at least 100-fold, whereas excitation-coupled Ca2+ entry is 3-fold higher. These findings support the hypothesis that EOMs have a unique mode of calcium handling. | 10.1042/BJ20140970 |
pubmed_788_2311 | The mechanisms underlying gamma-amino butyric acid (GABA(B)) receptor-mediated inhibition of exocytosis have been characterized in a variety of synapses. Using patch-clamp recording methods, we attempted to clarify the intracellular mechanisms underlying presynaptic inhibition in autaptic synapses of isolated mouse hippocampal neurons. Baclofen, a selective GABA(B) receptor agonist, decreased the frequency of glutamatergic miniature excitatory postsynaptic currents (mEPSCs) without changing their amplitude in Ca(2+)-free extracellular solution, suggesting that baclofen inhibits exocytosis downstream of Ca(2+) entry. Syntaxin 1A is known to modulate exocytosis and suppress neuronal sprouting. Antisense oligonucleotide-mediated knockdown of syntaxin 1A increased the frequency of mEPSCs under Ca(2+)-free condition. Estimation of the number of functional release sites by staining with FM1-43 indicated that the increased frequency of mEPSCs was induced by facilitation of exocytosis at each site, rather than by an increased number of release sites due to neuronal sprouting. Baclofen reduced mEPSC frequency in syntaxin 1A-knockdown neurons to the same level as that in nonsense oligonucleotide transfected neurons under Ca(2+)-free condition. These results suggest that the GABA(B) receptor- and syntaxin 1A-induced inhibitions of exocytosis occlude one another and that the GABA(B) receptor shares a common intracellular pathway with syntaxin 1A in inhibiting transmitter release downstream of Ca(2+) entry. | 10.1016/j.neulet.2007.01.062 |
pubmed_786_21361 | OBJECTIVE
Prominent pediatric organizations agree that young physicians need to be trained for the role of patient advocate in the community. However, information on the community site administrators' perspective on such training is limited. Therefore, the objective of this study was to explore community site administrators' perceptions of the advantages and disadvantages to pediatric resident training at their centers. Understanding these perspectives may lead to better partnerships and experiences for both the residents and the community sites.
METHODS
Twenty-eight community site administrators participating in 2 residency community rotations located in Ohio and Florida were surveyed with a semistructured questionnaire. A qualitative data analysis methodology was used to explore the entire set of responses. Research team members reviewed the responses, coded them for emerging themes, and generated three themes: 1) awareness, 2) knowledge exchange, and 3) organizational issues.
RESULTS
Fifty-seven percent of site administrators responded. These administrators consistently indicated that they valued the opportunity to increase residents' awareness of the services their sites provided to the community. The administrators and families served by the agencies appeared to benefit from the medical knowledge exchange, and this was a significant advantage from the community site administrators' perspective. Finally, community sites identified organizational issues of complex scheduling as an area for improvement.
CONCLUSIONS
These findings demonstrate the value community sites place on active, early involvement of pediatric residents with community agencies. We have also identified key points to improve the experiences for both community sites and residents during a community pediatric rotation. | 10.1367/1539-4409(2004)004<0121:llfcsa>2.0.co;2 |
pubmed_715_21762 | Penetrating middle ear injury can result in hearing loss, vertigo, and facial nerve injury. We describe the cases of 2 children with penetrating trauma to the right ear that resulted in ossicular chain disruption; one injury was caused by cotton-tipped swabs and the other by a wooden matchstick. Symptoms in both children included hearing loss and otalgia; in addition, one child experienced ataxia and the other vertigo. Physical examination in both cases revealed a perforation in the posterosuperior quadrant of the tympanic membrane and visible ossicles. Audiometry identified a moderate conductive hearing loss in one child and a mild sensorineural hearing loss in the other. Both children underwent middle ear exploration and reduction of a subluxed stapes. We discuss the diagnosis, causes, and management of penetrating middle ear trauma. To reduce the morbidity associated with these traumas, otologic surgeons should act promptly and be versatile in choosing methods of repairing ossicular chain injuries. | pubmed_715_21762 |
pubmed_334_23850 | Growth of the yeast Saccharomyces cerevisiae deficient as to superoxidedismutase (SOD) genes in the media containing ethanol or glycerol has been investigated. It was shown that the role of the two isoforms of SOD was different under conditions used in this study. The strain which has only mitochondrial Mn-SOD demonstrated higher velocity of culture growth on ethanol compared with the other strains investigated. In contrast to that, cytosolic Cu, Zn-SOD played more important role under growth on glycerol than Mn-SOD. The levels of carbonyl proteins in SOD-deficient strains grown on glycerol and in the cells of strain producing only Cu, Zn-SOD exposed to inhibitor diethyldithiocarbamate were investigated. The strains lacking Mn-SOD and Cu, Zn-SOD demonstrated virtually the same levels of carbonyl proteins. It is supposed that Cu, Zn-SOD can compensate Mn-SOD and vice versa. Nonlinear correlation between SOD activity and the level of carbonyl proteins was found that indicates to the uncertain role of SOD in protein oxidation. | pubmed_334_23850 |
pubmed_852_6456 | Transient network hydrogels cross-linked through histidine-divalent cation coordination bonds were studied by conventional rheologic methods using histidine-modified star poly(ethylene glycol) (PEG) polymers. These materials were inspired by the mussel, which is thought to use histidine-metal coordination bonds to impart self-healing properties in the mussel byssal thread. Hydrogel viscoelastic mechanical properties were studied as a function of metal, pH, concentration, and ionic strength. The equilibrium metal-binding constants were determined by dilute solution potentiometric titration of monofunctional histidine-modified methoxy-PEG and were found to be consistent with binding constants of small molecule analogs previously studied. pH-dependent speciation curves were then calculated using the equilibrium constants determined by potentiometric titration, providing insight into the pH dependence of histidine-metal ion coordination and guiding the design of metal coordination hydrogels. Gel relaxation dynamics were found to be uncorrelated with the equilibrium constants measured, but were correlated to the expected coordination bond dissociation rate constants. | 10.1021/ma301791n |
pubmed_282_6967 | Patients with penetrating head trauma with retained projectiles develop intracranial abscesses as a common complication. The most common presentation is a suddenly worsening headache. The most common pathogen identified is staphylococcus. Outcomes are related to adherence of Matson's tenets. This case study details the presentation of a 19-year-old patient that presented to the neurological surgery clinic without neurologic deficits. Further questioning revealed complaints of intermittent diffuse headaches with bilateral upper extremity shock-like sensation for two weeks. Eight weeks prior he had undergone right craniotomy, after a gunshot wound, for debridement and watertight dural closure. The patient denied symptoms of fever, chills, nausea, vomiting, diarrhea, or seizure. The patient presented with a noncontrast head computed tomography (CT) which revealed retained projectile fragments without clear evidence of abscess. On physical exam, the patient was without any neurological deficit. Laboratory investigation revealed normal white blood cell count, erythrocyte sedimentation rate, C-reactive protein, and negative blood cultures. Head CT with contrast revealed a large intracerebral abscess adjacent to the thalamus. The patient was taken to the operating room for repeat craniotomy with resection of the abscess and removal of the intracranial projectile fragments. Post-operatively, the patient remained neurology intact. Intraoperative cultures were not significant for the growth of any bacteria. In eight weeks time, the patient returned to his employment and his baseline level of activity. This case underscores the importance of thorough assessment in patients with retained intracranial projectiles as well as the need to routine follow-up. The unique presentation of this patient prompted further investigation which elucidated a lesion which correlated to his symptoms although laboratory assessment was without abnormality. | 10.7759/cureus.1328 |
pubmed_508_14342 | The Src family of nonreceptor tyrosine kinases regulates numerous cellular processes, including proliferation, differentiation, migration, survival and angiogenesis. In solid tumors, Src is frequently aberrantly active, and promotes tumor progression and metastasis. Although multiple Src functions may contribute to metastasis, recently Src has been shown to play a role in epithelial to mesenchymal transition. Increased Src activity promotes this process and inhibition of Src suppresses epithelial to mesenchymal transition. Although the molecular events causing epithelial to mesenchymal transition are becoming well defined, the processes in tumor cells that trigger the onset of this phenotype remain unclear. Recent studies have associated epithelial to mesenchymal transition with the development of chemoresistance. Src has also been shown to be involved in chemoresistance of cancer cells. The activation of Src in chemoresistant cells is related to an increase in motility, invasiveness and detachment, all phenotypes characteristic both of Src activation and of epithelial to mesenchymal transition. This review focuses on upregulation of Src in cancer as it relates to chemoresistance and epithelial to mesenchymal transition. | 10.1097/CAD.0b013e32801265d7 |
pubmed_675_5649 | OBJECTIVE
To assess the status of intestinal schistosomiasis among preschool-aged (PSAC) and school-aged children (SAC) and to compare the efficacy of praziquantel (PZQ) in both groups.
METHODS
The study was conducted on 400 children; 103 PSAC and 297 SAC. Diagnosis of Schistosoma mansoni was based on triplicate Kato-Katz thick smears from a single stool sample. To identify the missed cases by Kato-Katz, 120 randomly selected negative cases (38 PSAC and 82 SAC) were screened by real-time PCR. All S. mansoni-positive cases by Kato-Katz were treated by crushed PZQ tablets. Four weeks after treatment, the cure rate was assessed by Kato-Katz smears and real-time PCR.
RESULTS
The prevalence of S. mansoni with Kato-Katz was 7.8% among PSAC and 7.4% among SAC. Most of children (63.3%) had light-intensity infection. The cure rate was 100% among PSAC by both techniques, and 91%, and 77.2% among SAC by Kato-Katz and real-time PCR, respectively. In the 120 stool samples screened by real-time PCR, S. mansoni prevalence was 25%; 15.8% and 29.3% were among PSAC and SAC respectively. Treated cases showed a lower range of Ct values than untreated cases. Two melting temperature ranges (Tm = 83-87°C and 89-93°C) were recognised among uncured cases which may point to S. mansoni genetic variability.
CONCLUSION
Continuous monitoring and inclusion of PSAC in schistosomiasis control programmes are crucial. Real-time PCR and other molecular tools are recommended for evaluation of the true prevalence, assessment of cure and further studies on genetic diversity. | 10.1111/tmi.13562 |
pubmed_625_6017 | OBJECTIVES
To describe the relationship between the proximity of miniscrew implants (MSIs) to the periodontal ligament (PDL) and stress in the PDL under different load magnitudes and different bone properties.
MATERIALS AND METHODS
Sixteen subject-specific finite element models of the region of the maxillary first molar and second premolar were developed using computed tomography images of four patients. For each patient, an MSI surface model derived from micro-computed tomography was placed at four different distances from the premolar PDL. Finite element analysis was conducted with mesial load on the MSI, increasing from 1 N to 4 N. Peak absolute compression stress (CS) was calculated at each 1 N step. Stepwise multiple regression modeling was conducted to explain compressive stress by proximity, load magnitude, and bone properties.
RESULTS
The multiple regression model explained 83.47% of the variation of CS and included all three factors: proximity, load magnitude, and bone properties. The model expected significant interaction between the bone properties and load magnitude, implying that strong bone properties could be associated with significant increases in CS at small increases in load.
CONCLUSIONS
To ensure the safety of adjacent roots, MSIs should be placed at least 1 mm from the roots. Assessment of alveolar bone properties is recommended when the use of MSI is intended, as some patients may present with strong bone properties and thereby a high risk of MSI-induced root resorption. | 10.2319/122017-873.1 |
pubmed_812_10309 | The elastic coefficients of anisotropic solids are often evaluated from measurements of phase or group velocities of ultrasonic bulk waves by the usage of inverse optimizing procedures. This paper discusses the effects of various factors on such procedures results for transversely isotropic solids with considerably strong anisotropy. First, the inverse determination of all elastic coefficients of unidirectional CFRP composite is briefly outlined. Then the results of the optimization are treated as exact values and the sensitivity of the optimizing process versus main considered sources of inaccuracies is analyzed. Results of extensive simulations are presented to illustrate the effect of input data distortion, input data incompleteness, and geometrical conversion from experimentally obtained group velocities into corresponding phase velocities used as input data for the optimizing procedure. The paper takes note of how information about the elastic coefficients can be extracted from the different segments of the phase velocity surface. The stability versus input data distortion for inversion from group velocities and phase velocities is compared and the importance of reliable geometrical converting from group into phase velocities is illustrated. An novel method for geometrical conversion of distorted group velocity data into corresponding phase velocities based on affine combinations of low-order polynomials is presented and compared with piecewise or high-order polynomial fitting. | 10.1016/j.ultras.2004.07.004 |
pubmed_973_18951 | Headspace single-drop microextraction has been investigated for the determination of chloride in conjunction with fibre optic-based cuvetteless micro-spectrophotometry which accommodates sample volume of 1 microL placed between the two ends of optical fibres. Method has been evolved for the determination of 0.025-4 mg L(-1) of chloride involving its oxidation with permanganate in sulphuric acid medium, and reaction of chlorine with 2 microL drop of starch-iodide reagent suspended at the tip of microsyringe needle in the headspace of the reaction mixture. The limit of detection was found to be 2.8 microg L(-1) of chloride which was better than obtained by existing methods. The method was highly selective and a number of ions which interfered severely in other methods did not affect the results. The method has been used to analyze water samples, inorganic compounds and cement when the overall recovery of chloride was 94.9% with a relative standard deviation of 3.9%. | 10.1016/j.talanta.2009.10.027 |
pubmed_1072_21724 | OBJECTIVE
In order to assess the current status of temperature management during cardiopulmonary bypass (CPB) in China and, thereby, implement standardized management protocols, the authors carried out a national survey about institutions performing CPB.
METHOD
The survey was carried out from September 2015 to February 2016 and was supported by the Chinese Society of ExtraCorporeal Circulation. A total of 114 institutions participated, accounting for 15.64% (114/729) of the total of germane Chinese institutions, whereby, 80.85% (38/47) of the institutions had an annual surgical volume of more than 1000 cases.
RESULTS
The most common sites of temperature measurement were nasopharyngeal (NP) (99.12%) and rectal (92.98%) while oxygenator blood temperature was less popular (28%). Rectal temperature as the core temperature was chosen by 78.95% of the institutions; 92.11% of the institutions chose nasopharyngeal temperature to represent the cerebral temperature. During deep hypothermia circulatory arrest (DHCA) when there was no cerebral perfusion, 18 to 22℃ was the most common indication of circulatory arrest. However, with cerebral perfusion, more than 40% of the institutions maintained a lowest temperature of 22 to 25℃ for adult and pediatric patients. A NP temperature of 36 to 37℃ was chosen by 70.18% of the institutions while 81.79% chose a rectal temperature of 35 to 36.5℃ as the indication to wean from CPB. The majority of the institutions chose a difference of 10℃ between the water tank and core temperatures as the temperature gradient during rewarming. Auxiliary heat preservation techniques and equipment were used in 91.23% of the institutions, whereas 35.58% of them would lower the indications to wean from CPB.
CONCLUSIONS
This survey accurately reflects the current situation of temperature management during CPB in institutions with an annual surgical volume of >500 cases, but has, hereby, failed to properly represent the institutions with a lower annual surgical volume. | 10.1177/0267659117736119 |
pubmed_491_6750 | Endocytosis, which encompasses the internalization and sorting of plasma membrane (PM) lipids and proteins to distinct membrane-bound intracellular compartments, is a highly regulated and fundamental cellular process by which eukaryotic cells dynamically regulate their PM composition. Indeed, endocytosis is implicated in crucial cellular processes that include proliferation, migration, and cell division as well as maintenance of tissue homeostasis such as apical-basal polarity. Once PM constituents have been taken up into the cell, either via clathrin-dependent endocytosis (CDE) or clathrin-independent endocytosis (CIE), they typically have two fates: degradation through the late-endosomal/lysosomal pathway or returning to the PM via endocytic recycling pathways. In this review, we will detail experimental procedures that allow for both qualitative and quantitative assessment of endocytic recycling of transmembrane proteins internalized by CDE and CIE, using the HeLa cervical cancer cell line as a model system. | pubmed_491_6750 |
pubmed_241_5842 | Different attempts have been made to improve the health status of humans and animals by increasing the intestinal production of short-chain fatty acids (SCFA) derived from non-digestible carbohydrates fermentation. In this paper we investigate the in vitro production of short-chain fatty acids (SCFA) after addition of inulin, propionibacteria or a combination of both in an experimental model of mice cecal slurries. The development of bacterial genera which are usually stimulated by inulin addition was also investigated. According to our experimental data, acetic acid and butyric acids concentrations increased after incubation in slurries that had no supplements. By contrast, butyric acid concentrations remained in the basal value when supplements were used. Fermentation of only inulin did not increase the concentration of total SCFA. Propionibacterium acidipropionici CRL1198 improved the production of propionic acid in cecal slurries when it was added alone, but the effect was more noticeable in the combination with inulin. A modulation of the global fermentative activity of the cecal microbiota was evidenced by the increase on the ratio propionic acid/SCFA in supplementations with propionibacteria. Statistical analysis of data demonstrated that samples from homogenates with propionibacteria alone or combined with inulin belong to the same cluster. The presence of propionibacteria limited the growth of Bacteroides fragilis and Clostridium hystoliticum groups in slurries with and without inulin. The growth of Bifidobacterium was not modified and the stimulating effect of inulin on lactobacilli disappeared in the presence of propionibacteria. In conclusion, dairy propionibacteria are potential candidates to develop new functional foods helpful to ensure the intestinal production of SCFA during inulin supplementation and to control the overgrowth of bacteria belonging to Bacteroides and Clostridium genera. | 10.1016/j.anaerobe.2010.04.006 |
pubmed_1102_11587 | OBJECTIVE
This is the first double-blind randomized controlled trial evaluating the efficacy and safety of IV immunoglobulin (IVIG) vs placebo in patients with idiopathic small fiber neuropathy (I-SFN).
METHODS
Between July 2016 and November 2018, 60 Dutch patients with skin biopsy-proven I-SFN randomly received a starting dose of IVIG (2 g/kg body weight) or matching placebo (0.9% saline). Subsequently, 3 additional infusions of IVIG (1 g/kg) or placebo were administered at 3-week intervals. The primary outcome was a 1-point change in Pain Intensity Numerical Rating Scale score at 12 weeks compared to baseline.
RESULTS
Thirty patients received IVIG, and 30 received placebo. In both groups, 29 patients completed the trial. In 40% of patients receiving IVIG, the mean average pain was decreased by at least 1 point compared to 30% of the patients receiving placebo (p = 0.588, odds ratio 1.56, 95% confidence interval 0.53-4.53). No significant differences were found on any of the other prespecified outcomes, including general well-being, autonomic symptoms, and overall functioning and disability.
CONCLUSIONS
This randomized controlled trial showed that IVIG treatment had no significant effect on pain in patients with painful I-SFN.
TRIAL REGISTRATION INFORMATION
ClinicalTrials.gov Identifier: NCT02637700, EudraCT 2015-002624-31.
CLASSIFICATION OF EVIDENCE
This study provides Class I evidence that for patients with painful I-SFN, IVIG did not significantly reduce pain compared to placebo. | 10.1212/WNL.0000000000011919 |
pubmed_232_8495 | BACKGROUND/AIMS
When advanced hepatobiliary malignancy involves the major veins that are requisite for draining venous flow from the remnant liver after hepatectomy, it may be unresectable, unless the hepatic vein involved by the tumor can be reconstructed after combined resection with hepatectomy.
METHODOLOGY
Seven patients with hepatobiliary malignancy underwent hepatic vein resection and reconstruction using autologous vein grafts in our study. Five patients had patch repairs of the hepatic vein, with the gonadal vein used in 2 cases, the umbilical vein in 2, and the inferior mesenteric vein in 1. Two other patients underwent segmental reconstruction of the hepatic vein, using the inferior mesenteric vein for reconstruction of the middle hepatic vein, and the internal iliac vein for reconstruction of the right hepatic vein. Operative results and postoperative outcome, including liver function, patency, and survival, were evaluated. Literatures reporting hepatic vein reconstruction in hepatic resection, including this study, are also reviewed.
RESULTS
In 6 of 7 patients, autologous vein grafts were obtained from the upper abdominal operative field without making an additional skin incision. The right internal iliac vein was used in segmental reconstruction of the right hepatic vein, and the inferior mesenteric vein was used in segmental reconstruction of the middle hepatic vein, based on caliber matching. Patch repairs of the right hepatic vein were successfully performed in 2 cases, the middle hepatic vein in 2, and the left hepatic in 1, using the umbilical vein, the gonadal vein and the inferior mesenteric vein. During hepatic vein reconstruction, total hepatic vascular exclusion was required in 2 cases, and Pringle's inflow clamp with selective clamp of reconstructed hepatic vein in 5, in order to avoid massive bleeding, congestion, and air embolism. Postoperatively, there were no remarkable complications of liver dysfunction or other organ damage encountered in any of the patients. Reconstructed hepatic veins were revealed to be patent postoperatively in all cases. Six patients survived for 60-1035 days after surgery, and 1 patient died of cancer recurrence 550 days after surgery.
CONCLUSIONS
We conclude that hepatic vein reconstruction using an autologous vein graft can be safely and effectively performed with a suitable vascular control method for appropriately selected patients with advanced hepatobiliary cancer. | pubmed_232_8495 |
pubmed_655_9066 | Bacterial fructans with a high degree of polymerisation cause a very large increase in surface pressure of lipid monolayers at the air-water interface with a broad range of lipids, including phosphatidylethanolamine and several types of phosphatidylcholines. The surface active effect of fructans contrasts strongly with the maximal effects observed for trehalose, sucrose and glucose under comparable conditions (20 and 0.6 mN/m for fructans and the other sugars, respectively). The results demonstrate a profound and specific membrane interaction of the fructans which is probably very different from the effect of the smaller carbohydrates. The fructan concentrations used in this study are within the physiological range observed in fructan-accumulating plants. The suggested water-stress protective effect of fructans may be induced by membrane-fructan interaction which prevent lipid condensation and phase transitions to take place. | 10.1016/s0005-2736(98)00138-2 |
pubmed_822_374 | Highly accurate coupled-cluster (CC) calculations with large basis sets have been performed to study the binding energy of the (CH)12, (CH)16, (CH)20, and (CH)24 polyhedral hydrocarbons in two, cage-like and planar, forms. We also considered the effect of other minor contributions: core-correlation, relativistic corrections, and extrapolations to the limit of the full CC expansion. Thus, chemically accurate values could be obtained for these complicated systems. These nearly exact results are used to evaluate next the performance of main approximations (i.e., pure, hybrid, and double-hybrid methods) within density functional theory (DFT) in a systematic fashion. Some commonly used functionals, including the B3LYP model, are affected by large errors, and only those having reduced self-interaction error (SIE), which includes the last family of conjectured expressions (double hybrids), are able to achieve reasonable low deviations of 1-2 kcal/mol especially when an estimate for dispersion interactions is also added. | 10.1021/ct200198z |
pubmed_633_14850 | In complex organisms, caspase proteases mediate a variety of cell behaviors, including proliferation, differentiation, and programmed cell death/apoptosis. Structural homologs to the caspase family (termed metacaspases) engage apoptosis in single-cell eukaryotes, yet the molecular mechanisms that contribute to nondeath roles are currently undefined. Here, we report an unexpected role for the Saccharomyces cerevisiae metacaspase Yca1 in protein quality control. Quantitative proteomic analysis of Deltayca1 cells identified significant alterations to vacuolar catabolism and stress-response proteins in the absence of induced stress. Yca1 protein complexes are enriched for aggregate-remodeling chaperones that colocalize with Yca1-GFP fusions. Finally, deletion and inactivation mutants of Yca1 accrue protein aggregates and autophagic bodies during log-phase growth. Together, our results show that Yca1 contributes to the fitness and adaptability of growing yeast through an aggregate remodeling activity. | 10.1073/pnas.1006610107 |
pubmed_206_8080 | AIM
Maternal disease can cause prematurity and neonatal complications, notably feeding problems. To determine the relationship between maternal disease and the nature and severity of neonatal feeding problems, we compared feeding profiles, time to demand feeding and length of hospital stay between preterm infants of preeclamptic mothers, mothers with amniotic infection and mothers with other disease causing prematurity.
METHODS
The retrospective study used labour ward data collected from 2002 to 2005 in a tertiary university centre to analyse three groups of singletons born at <32 completed gestational weeks to mothers with preeclampsia (n = 61), amniotic infection (n = 55) and non-preeclamptic non-amniotic infection controls (n = 55). The groups were similar in gestational age, birthweight and sex ratio; all infants received enteral feeding according to departmental guidelines. Feeding profiles and enteral/oral nutrition were compared.
RESULTS
Feeding problems occurred in 46% of the preeclamptic group, 11% of the amniotic infection group and 13% of controls. Full oral demand feeding was established at 36 0/7 weeks postmenstrual age, 35 3/7 weeks (P = 0.03) and 35 2/7 weeks (P < 0.0001), respectively. Feeding problems were the main cause of delay (7-10 days) in hospital discharge in the preeclamptic group (P = 0.0002).
CONCLUSIONS
Feeding problems are greater, and hospital stay longer, in preterm infants of preeclamptic mothers than in other preterm infants. | 10.1111/j.1440-1754.2008.01375.x |
pubmed_561_419 | Bcl-2 family proteins regulate programmed cell death, and may play an important role in the selection of lymphocytes. We investigated the expression of Bcl-2, Bcl-x, Bax, Bak and Bim in human lymphocytes using flow-cytometry. Bcl-2 was down-regulated in CD4(+)8(+) (DP) thymocytes and CD19(+)38(+) tonsillar lymphocytes (GC B cells). Among DP thymocytes, cells co-expressing CD69 up-regulated Bcl-2, suggesting that the role of Bcl-2 is promoting survival of positively selected DP cells. Unexpectedly, the expression level of Bcl-x was higher in DP cells than in Single Positive (SP) cells and in CD69(+) DP thymocytes it was lower than in CD69(+) DP thymocytes. Expression of Bim was low in DP thymocytes but high in a subset of GC B cells. Bim and Bax were expressed more highly in SP than in DP thymocytes. Among peripheral blood lymphocytes (PBL), CD8(+) T cells expressed an approximately ten-fold higher level of Bcl-x than CD4(+) T cells while both subsets expressed similar levels of Bcl-2. Bak expression was low and Bim expression was absent in PBL. These results suggest that not only Bcl-2 but other members of the Bcl-2 family are involved in T cell development in the thymus and affinity maturation of B cells in the germinal center. | 10.1016/s0165-2478(02)00003-2 |
pubmed_616_22481 | Keloids negatively impact the health and quality of life of many affected dermatologic patients. Treating keloids is often difficult, and suboptimal responses are frequent. Fortunately, there are many treatment options available to the clinician that may lead to improved clinical outcomes. We present a review of currently available therapeutic options. Intralesional steroid injection remains the first-line treatment for keloids. Imiquimod, direct interferon therapy, or intralesional 5-flurouracil may alleviate the need for excessive corticosteroid therapy. Radiation and laser therapy are emerging therapeutic options that have demonstrated efficacy in reviewed studies. Given the unsatisfactory outcomes associated with pressure dressings, vitamin E, ablative laser, and surgical excision, these options should be avoided in keloid management. Further research is needed to evaluate the efficacy and recurrence associated with the reviewed therapeutics. | pubmed_616_22481 |
pubmed_497_4533 | This article explores the potential effects of visualism (a prejudice in favor of the seen) on the perceived legitimacy of telephone work in community nursing. It discusses data from an exploratory study on telephone work, which used guided interviews with a purposive sample of 14 community nurses. Interviewees expressed both positive and negative ideas about telephone work and had particular concerns about the assessment of people, context, problems, and comprehension by telephone. These issues are discussed with reference to publications on visualism, metaphor, communication, and nursing work. The authors conclude that an awareness of the possible effects of visualism on ideas and practice could lead to improvements in both communication and assessment, whether carried out by telephone or face to face. | 10.1177/104973200129118606 |
pubmed_868_18479 | BACKGROUND
Hepatocellular carcinoma (HCC) is a leading cause of cancer-related death worldwide, mainly due to its high rates of postoperative recurrence and metastasis. Please remove, it currently ranks as the third most common cause of cancer-related deaths. MiRNAs are a set of small, single-stranded, non-coding RNA molecules that negatively regulate gene expression at the post-transcriptional level. In this study, we demonstrated the down-regulation of miR-148a in HCC and non-cancerous tissues using qRT-PCR.
METHODS
Ninety six HCC samples and their noncancerous normal liver tissues were collected. Total mRNA including miRNA was extracted, and miR-148a expression was determined using qRT-PCR. Furthermore, the correlation between the miR-148a expression and clinicopathological parameters was investigated.
RESULTS
The result showed that reduction of miR-148a expression was associated with TNM stage, metastasis, and number of tumor nodes. Multivariate Cox proportional hazards model analysis showed that low expression of miR-148a was independently associated with recurrence of HCC in the current study. Moreover, our result showed that lower expression in tumor tissues in comparison with corresponding normal control tissues.
CONCLUSION
Down-regulation of miR-148a is related to HCC carcinogenesis and deterioration of HCC. MicroRNA-148a may act as a suppressor miRNA of HCC, and it is therefore a potential prognostic biomarker for HCC patients. | 10.1186/s13000-015-0371-4 |
pubmed_623_7787 | BACKGROUND
The Borrelia burgdorferi sensu lato (s.l.) species complex consists of tick-transmitted bacteria and currently comprises approximately 20 named and proposed genospecies some of which are known to cause Lyme Borreliosis. Species have been defined via genetic distances and ecological niches they occupy. Understanding the evolutionary relationship of species of the complex is fundamental to explaining patterns of speciation. This in turn forms a crucial basis to frame testable hypotheses concerning the underlying processes including host and vector adaptations.
RESULTS
Illumina Technology was used to obtain genome-wide sequence data for 93 strains of 14 named genospecies of the B. burgdorferi species complex and genomic data already published for 18 additional strain (including one new species) was added. Phylogenetic reconstruction based on 114 orthologous single copy genes shows that the genospecies represent clearly distinguishable taxa with recent and still ongoing speciation events apparent in Europe and Asia. The position of Borrelia species in the phylogeny is consistent with host associations constituting a major driver for speciation. Interestingly, the data also demonstrate that vector associations are an additional driver for diversification in this tick-borne species complex. This is particularly obvious in B. bavariensis, a rodent adapted species that has diverged from the bird-associated B. garinii most likely in Asia. It now consists of two populations one of which most probably invaded Europe following adaptation to a new vector (Ixodes ricinus) and currently expands its distribution range.
CONCLUSIONS
The results imply that genotypes/species with novel properties regarding host or vector associations have evolved recurrently during the history of the species complex and may emerge at any time. We suggest that the finding of vector associations as a driver for diversification may be a general pattern for tick-borne pathogens. The core genome analysis presented here provides an important source for investigations of the underlying mechanisms of speciation in tick-borne pathogens. | 10.1186/s12864-016-3016-4 |
pubmed_22_11030 | Wider use and adaptation of microfluidics is hindered by the infrastructure, knowledge, and time required to build prototype systems, especially when multiple fluid operations and measurements are required. As a result, 3D printing of microfluidics is attracting interest, yet cannot readily achieve the feature size, smoothness, and optical transparency needed for many standard microfluidic systems. Herein we present a new approach to the design and construction of high-precision modular microfluidics, using standard injection-molded blocks that are modified using micromilling and assembled via elastically averaged contacts. Desktop micromilling achieves channel dimensions as small as 50 μm depth and 150 μm width and adhesive films seal channels to allow internal fluid pressure of >400 kPa. Elastically averaged connections between bricks result in a mechanical locating repeatability of ∼1 μm, enabling fluid to pass between bricks via an O-ring seal with >99.9% reliability. We demonstrated and tested block-based systems for generating droplets at rates above 9000 min-1 and COV <3%, and integrated optical sensors. We also show how blocks can be used to build easily reconfigurable interfaces with glass microfluidic devices and imaging hardware. Microfluidic bricks fabricated by FDM and SLA 3D printing cannot achieve the dimensional quality of molded bricks, yet 3D printing allows customized bricks to be integrated with standard LEGOs. Our approach enables a wide variety of modular microfluidic units to be built using a widely available, cost-effective platform, encouraging use in both research and education. | 10.1039/c7lc00951h |
pubmed_826_12511 | The presence of a foreign body in the periapical tissues can cause endodontic failure by triggering an inflammatory response and a subsequent foreign body reaction. This inflammatory response, which can occur to varying degrees, appears radiographically as a radiolucency that can remain asymptomatic for many years. A foreign object can reach the apical region by accident or iatrogenic procedures during dental procedures. The aim of the present case report is to describe the endodontic surgical treatment of an iatrogenic displacement of a foreign body (a metal fragment) into the periapical tissues and to describe its clinical and radiographic follow-up over a period of 52 months. | 10.1155/2014/698538 |
pubmed_1045_3278 | We investigated chondrogenesis of cell-mediated sox9 gene therapy as a new treatment regimen for cartilage regeneration. pIRES2-EGFP vector containing a full-length mouse sox9 cDNA was transfected into bone marrow-derived mesenchymal stem cells (MSCs) by lipofection and chondrogenic differentiation of these cells was evaluated. In vitro high density micromass culture of these sox9 transfected MSCs demonstrated that a matrix-rich micromass aggregate with EGFP expressing MSCs was positively stained by Alcian blue and type II collagen. Next, sox9 transfected MSCs were loaded into the diffusion chamber and transplanted into athymic mice to analyze in vivo chondrogenesis. A massive tissue formation in about 2mm diameter was visible in the chamber after 4 weeks transplantation. Histological examinations demonstrated that both Alcian blue and type II collagen were positively stained in the extracellular matrix of the mass while type X collagen was not stained. These results indicated that cell-mediated sox9 gene therapy could be a novel strategy for hyaline cartilage damage. | 10.1016/s0006-291x(02)03026-7 |
pubmed_1125_2556 | Imbalanced plasticity of neural networks in the brain is proposed to underlie deficits in the integration of efferent and afferent processes in schizophrenia. These deficits affect the priming of the behavior implementing systems by prior knowledge, and thus impair both controlled regulation and automatic activation of mental and motor processes. The sense of self as a distinct entity can consequently be undermined. In predominantly reality-distorting patients, hypo-plasticity of neural connectivity may cause the emergence of highly focused but inflexible patterns of activation in their representation and response systems. This may lead to dominance of prepotent patterns of activity in these systems and a relative inability of higher control systems to bias lower level activity towards congruence with the ongoing cognitive and motor context. By contrast, predominantly disorganized patients are characterized by hyper-plastic connectivity. This leads to a weakening of prepotent response tendencies but also, as in reality-distorting patients, to less effective top-down contextual constraining. | 10.1016/j.concog.2006.09.007 |
pubmed_842_15552 | We show how crystallisation of supramolecular isomers of a dynamic coordination system generates a series of isostructural porous materials. These mercury, cobalt and zinc metallocyclic materials show permanent porosity and exhibit single-crystal-to-single-crystal transformations. | 10.1039/c2cc16691g |
pubmed_1005_23140 | BACKGROUND AND AIMS
In children, entropy-guided titration of isoflurane and sevoflurane leads to faster recovery after anaesthesia. However, role of entropy in recovery following desflurane anaesthesia is not known. Hence, we compared laryngeal mask airway (LMA) removal time and desflurane consumption with entropy and minimal alveolar concentration-guided titration in children given low-flow desflurane anaesthesia.
METHODS
After ethics committee approval and parental consent, 80 American Society of Anesthesiologists grade I-II children, age 2-14 years, undergoing elective ophthalmic surgery were randomised into entropy and minimal alveolar concentration-guided groups. After LMA insertion, anaesthesia was maintained using oxygen, air (FiO2 0.5) and desflurane using low fresh gas flow of 0.75 L/min. In the entropy-guided group, desflurane was titrated to maintain state entropy between 40 and 60. In the minimal alveolar concentration-guided group, desflurane was titrated to maintain a minimal alveolar concentration between 1 and 1.3. We recorded LMA removal time (from switching off desflurane at the end of surgery till removal of LMA), haemodynamic parameters, uptake and consumption of desflurane between the groups.
RESULTS
LMA removal time was significantly decreased in the entropy-guided group in comparison to the minimal alveolar concentration-guided group (4.34 ± 2.03 vs 8.8 ± 2.33 min) (P < 0.0001). Consumption of desflurane was significantly less in the entropy-guided group compared with the minimal alveolar concentration-guided group (18.7 ± 5.07 vs 25.3 ± 8.11 mL) (P < 0.0001).
CONCLUSION
Entropy-guided low-flow desflurane anaesthesia is associated with faster LMA removal and reduced consumption of desflurane in children undergoing ophthalmic surgery. | 10.4103/ija.IJA_237_19 |
pubmed_763_6617 | The endoplasmic reticulum (ER) is connected to the plasma membrane (PM) through the plant-specific NETWORKED protein, NET3C, and phylogenetically conserved vesicle-associated membrane protein-associated proteins (VAPs). Ten VAP homologues (VAP27-1 to 27-10) can be identified in the Arabidopsis genome and can be divided into three clades. Representative members from each clade were tagged with fluorescent protein and expressed in Nicotiana benthamiana. Proteins from clades I and III localized to the ER as well as to ER/PM contact sites (EPCSs), whereas proteins from clade II were found only at the PM. Some of the VAP27-labelled EPCSs localized to plasmodesmata, and we show that the mobility of VAP27 at EPCSs is influenced by the cell wall. EPCSs closely associate with the cytoskeleton, but their structure is unaffected when the cytoskeleton is removed. VAP27-labelled EPCSs are found in most cell types in Arabidopsis, with the exception of cells in early trichome development. Arabidopsis plants expressing VAP27-GFP fusions exhibit pleiotropic phenotypes, including defects in root hair morphogenesis. A similar effect is also observed in plants expressing VAP27 RNAi. Taken together, these data indicate that VAP27 proteins used at EPCSs are essential for normal ER-cytoskeleton interaction and for plant development. | 10.1111/nph.13857 |
pubmed_704_20608 | The subversive role of Calcium sensing receptor (CaSR) in cerebral ischemia and traumatic brain injury has been recently reported. Nevertheless, the role of CaSR in early brain injury (EBI) after subarachnoid hemorrhage (SAH) remains unexplored. Using the endovascular perforation model in mice, this study was aimed at investigating the role and potential mechanism of CaSR in EBI after SAH. Gadolinium trichloride (GdCI3), an agonist of CaSR, and NPS-2143, an inhibitor of CaSR, were administered intraperitoneally. The CaMKII inhibitor KN-93 was injected to intracerebroventricular. We found that CaSR expression was increased and widely expressed in neurons, astrocytes, and microglia after SAH. GdCI3 further deteriorated neurological function, brain edema, neurodegeneration, which were alleviated by NPS-2143. Also, GdCI3 increased the level of CaMKII phosphorylation, and upregulated expression of NLRP3, cleaved caspase-1, and IL-1β, which were attenuated by NPS-2143. Besides, CaMKII inhibitor KN-93 down-regulated the upregulated expression of NLRP3, cleaved caspase-1, and IL-1β induced by GdCI3. In conclusion, CaSR activation promotes early brain injury, which may be related to the CaMKII/NLRP3 signaling pathway. | 10.1016/j.bbrc.2020.07.081 |
pubmed_32_10375 | The sinusoidal fetal heart rate pattern has been described in association with severe fetal anaemia, with fetal hypoxaemia, and with the administration of parenteral narcotics. Here, we report a case of decreased fetal movement in which a sinusoidal tracing was recorded. The sonographic diagnosis of a massive fetal intracranial haemorrhage was made. A non-interventive approach was taken and the fetus died soon after in utero. We review 28 previous cases in which the prenatal sonographic diagnosis of fetal intracranial haemorrhage was made, including the underlying maternal and fetal factors and neonatal outcomes. We propose that the sinusoidal tracing in this case was due to the intracranial bleed and suggest that fetal intracranial haemorrhage be considered in the sonographic evaluation of the fetus with a sinusoidal pattern. | 10.1002/pd.1970150306 |
pubmed_330_6946 | Accumulating evidence links prefibrillar oligomeric species of the amyloid beta peptide (Abeta) to cellular toxicity in Alzheimer's disease, potentially via disruption of biological membranes. Congo red (CR) affects protein aggregation. It is known to self-associate into micelle-like assemblies but still reduces the toxicity of Abeta aggregates in cell cultures and model organisms. We show here that CR interacts with Abeta(1-40) in a manner similar to that of anionic detergents. Although CR promotes beta sheet formation and peptide aggregation, it may also solubilize toxic protein species, making them less harmful to critical cellular components and thereby reducing amyloid toxicity. | 10.1021/bi902005t |
pubmed_189_15602 | Inflammation-associated proteinase functions are key determinants of inflammatory stromal tissues deconstruction. As a specialized inflammatory pathological process, dental internal resorption (IR) includes both soft and hard tissues deconstruction within the dentin-pulp complex, which has been one of the main reasons for inflammatory tooth loss. Mechanisms of inflammatory matrix degradation and tissue resorption in IR are largely unclear. In this study, we used a combination of Cre-loxP reporter, flow cytometry, cell transplantation, and enzyme activities assay to mechanistically investigate the role of regenerative cells, odontoblasts (ODs), in inflammatory mineral resorption and matrices degradation. We report that inflamed ODs have strong capabilities of matrix degradation and tissue resorption. Traditionally, ODs are regarded as hard-tissue regenerative cells; however, our data unexpectedly present ODs as a crucial population that participates in IR-associated tissue deconstruction. Specifically, we uncovered that nuclear factor-kappa b (NF-κB) signaling orchestrated Tumor necrosis factor α (TNF-α)-induced matrix metalloproteinases (Mmps) and Cathepsin K (Ctsk) functions in ODs to enhance matrix degradation and tissue resorption. Furthermore, TNF-α increases Rankl/Opg ratio in ODs via NF-κB signaling by impairing Opg expression but increasing Rankl level, which utterly makes ODs cell line 17IIA11 (A11) become Trap+ and Ctsk+ multinucleated cells to perform resorptive actions. Blocking of NF-κB signaling significantly rescues matrix degradation and resorptive functions of inflamed ODs via repressing vital inflammatory proteinases Mmps and Ctsk. Utterly, via utilizing NF-κB specific small molecule inhibitors we satisfactorily attenuated inflammatory ODs-associated human dental IR in vivo. Our data reveal the underlying mechanisms of inflammatory matrix degradation and resorption via proteinase activities in IR-related pathological conditions. | 10.1038/s41368-022-00159-3 |
pubmed_496_521 | Postoperative nausea and vomiting (PONV) are distressing and frequent adverse events of anesthesia and surgery, with a relatively high incidence after laparoscopic cholecystectomy. Numerous antiemetics have been studied for the prevention and treatment of PONV in patients scheduled for laparoscopic cholecystectomy. Traditional antiemetics, including anticholinergics (e.g., scopolamine), antihistamines (e.g., dimenhydrinate), phenothiazines (e.g., promethazine), butyrophenones (e.g., droperidol), and benzamide (e.g., metoclopramide), are used for the control of PONV. The available nontraditional antiemetics for the prophylaxis against PONV are dexamethasone and propofol. Serotonin receptor antagonists (ondansetron, granisetron, tropisetron, dolasetron, and ramosetron), compared with traditional antiemetics, are highly efficacious for PONV. The prophylactic ondansetron, granisetron, tropisetron, and dolasetron in antiemetic efficacy are comparable. Ramosetron is effective for the long-term prevention of PONV. None of the available antiemetics is entirely effective, perhaps because most of them act through the blockade on one type of receptor. There is a possibility that combined antiemetics with different sites of activity would be more effective than one drug alone for the prophylaxis against PONV. Combination antiemetic therapy is often effective for the prevention of PONV following laparoscopic cholecystectomy. The efficacy of a combination of serotonin receptor antagonists (ondansetron and granisetron) and droperidol is superior to monotherapy with a serotonin receptor antagonist or droperidol. Similarly, adding dexamethasone to ondansetron or granisetron improves antiemetic efficacy in PONV. Knowledge regarding antiemetics is necessary to completely prevent and treatment of PONV in patients scheduled for laparoscopic cholecystectomy. | 10.2174/1381612054864911 |
pubmed_631_16284 | We report on a rare case of sarcoidosis that developed after chemotherapy for ovarian cancer, and mimicked a cancer metastasis. A 52-year-old female diagnosed with stage III ovarian cancer underwent curative surgery and postoperative chemotherapy. Four months later, her whole-body positron emission tomography and computed tomography (CT) scan showed high uptake in the mediastinal lymph nodes, and ovarian cancer recurrence was suspected. Biopsy of the mediastinal lymph nodes and subcutaneous nodules revealed noncaseating granulomas. These lesions resolved spontaneously without treatment; however, newly developed perilymphatic and centrilobular nodules were observed on follow-up chest CT. Surgical biopsy of these lesions also showed noncaseating granulomas. She was finally diagnosed with sarcoidosis. | 10.4143/crt.2013.45.4.354 |
pubmed_1110_15213 | Lentiviral vectors (LVs) are promising tools for gene therapy. However, scaling up the production methods of LVs in order to produce high-quality vectors for clinical purposes has proven to be difficult. In this article, we present a scalable and efficient method to produce LVs with transient transfection of adherent 293T cells in a fixed-bed bioreactor. The disposable iCELLis bioreactors are scalable with a large three-dimensional (3D) growth area range between 0.53 and 500 m2, an integrated perfusion system, and a controllable environment for production. In this study, iCELLis Nano (2.67-4 m2) was used for optimizing production parameters for scale-up. Transfections were first done using traditional calcium phosphate method, but in later runs polyethylenimine was found to be more reliable and easier to use. For scalable LV production, perfusion rate control by measuring cell metabolite concentrations in the bioreactor leads to higher productivity and reduced costs. Optimization of cell seeding density for targeted cell concentration during transfection, use of low compaction fixed-bed and lowering the culture pH have a positive effect on LV productivity. These results show for the first time that iCELLis bioreactor is scalable from bench level to clinical scale LV production. | 10.1038/gt.2017.91 |
pubmed_1119_20504 | It was the first time that a primer pairs derived from the 190KDa protein antigen gene of R. rickettsii were used to amplify SFGR DNA in ticks, tick ova, larva, tick faeces and rodent organs which were collected in Hebei, Heilongjiang, Hainan and Beijing. A 532bp fragment was respectively amplified from above samples. The results were partially in concordance with data obtained through rickettsiae isolation. It was suggested that PCR is a rapid, specific, sensitive and practical method for detection of SFGR in endemic foci. | pubmed_1119_20504 |
pubmed_1132_1517 | Cell encapsulation in hydrogels is widely used in tissue engineering applications, including encapsulation of islets or other insulin-secreting cells in pancreatic substitutes. Use of adhesive, biofunctionalized hydrogels is receiving increasing attention as cell-matrix interactions in three-dimensional (3-D) environments can be important for various cell processes. With pancreatic substitutes, studies have indicated benefits of 3-D adhesion on the viability and/or function of insulin-secreting cells. As long-term storage of microencapsulated cells is critical for their clinical translation, cryopreservation of cells in hydrogels is being actively investigated. Previous studies have examined the cryopreservation response of cells encapsulated in non-adhesive hydrogels using conventional freezing and/or vitrification (ice-free cryopreservation); however, none have systematically compared the two cryopreservation methods with cells encapsulated within an adhesive 3-D environment. The latter would be significant, as evidence suggests adhesion influences the cellular response to cryopreservation. Thus, the objective of this study was to determine the response to conventional freezing and vitrification of insulin-secreting cells encapsulated in an adhesive biomimetic hydrogel. Recombinant insulin-secreting C2C12 myoblasts were encapsulated in oxidized RGD-alginate and cultured for 1 or 4days post-encapsulation, cryopreserved, and assessed up to 3days post-warming for metabolic activity and insulin secretion, and 1day post-warming for cell morphology. Besides certain transient differences in the vitrified group relative to the fresh control, both conventional freezing and vitrification maintained the metabolism, secretory activity, and morphology of the recombinant C2C12 cells. Thus, due to a simpler procedure and slightly superior results, conventional freezing is recommended over vitrification for the cryopreservation of C2C12 cells encapsulated in oxidized, RGD-modified alginate. | pubmed_1132_1517 |
pubmed_192_17163 | BACKGROUND
Fibromyalgia is characterized by chronic generalized pain, fatigue, sleep disorders and other symptoms. Physical exercise is recommended as the first choice of non-pharmacological therapy. Thus, the aim of this study is to evaluate the effectiveness and cost-effectiveness of modified Pilates exercises compared to aerobic exercises in the treatment of patients with fibromyalgia.
METHODS
In this randomized controlled trial with blinded assessor, 98 patients who meet the fibromyalgia classification criteria of the American College of Rheumatology 2010, aged between 20 and 75 years, and with pain intensity greater than or equal to 3 points in the Pain Numerical Rating Scale, will be randomly divided into Aerobic Group (aerobic exercises on treadmills or stationary bikes) and Pilates Group (modified Pilates exercises), and treated twice a week for eight weeks on the Center for Excellence in Clinical Research in Physical Therapy at Universidade Cidade de São Paulo, Brazil. The following outcomes will be evaluated by a blinded assessor at baseline, eight weeks, six months, and 12 months after randomization: impact of fibromyalgia assessed by the Fibromyalgia Impact Questionnaire, pain intensity by the Pain Numerical Rating Scale, kinesiophobia by the Tampa Scale of Kinesiophobia, specific disability by the Patient-Specific Functional Scale, functional capacity by the 6-min Walk Test, quality of sleep by the Pittsburgh Sleep Quality Index, and health-related quality of life by EQ-5D-3L and SF-6D questionnaires.
DISCUSSION
It is expected that the Pilates exercises will be more effective than aerobic exercises in improving clinical outcomes and that this improvement will be maintained over the medium to long term. This study aims to clarify whether the Pilates method can be incorporated into the clinical practice of physical therapists treating patients with fibromyalgia. The study will also provide information on which exercise will be most cost-effective, information that can be used by insurers and public health systems.
TRIAL REGISTRATION
This study was prospectively registered at the Clinical Trials Registry (NCT03050606) in February 2017. | 10.1186/s41927-018-0051-6 |
pubmed_499_5001 | STUDY QUESTION
What are the downstream endocrine and paracrine consequences of letrozole (LZ) cotreatment during ovarian stimulation and is follicle growth and recruitment affected?
SUMMARY ANSWER
Letrozole cotreatment induces marked changes in both the follicular and luteal phase endocrinology causing potentiation of follicle diameter and an improved corpus luteum function without affecting the secondarily recruited follicle cohort.
WHAT IS KNOWN ALREADY
Letrozole is a third-generation aromatase inhibitor that is well-established as an effective ovulatory agent, while its possible benefits in standard in vitro fertilization protocols are less thoroughly investigated.
STUDY DESIGN, SIZE, DURATION
This study included a double-blinded, placebo-controlled, randomized study with LZ or placebo intervention during ovarian stimulation for IVF treatment, an observational preceding baseline natural cycle and a succeeding follow-up visit. Participants were enrolled between August 2016 and November 2018. Data from the randomized, stimulated cycle were part of a larger RCT, which was previously published.
PARTICIPANTS/MATERIALS, SETTING, METHODS
The study was conducted at a public fertility clinic at Herlev Hospital, Denmark, including 31 healthy, normo-responding women eligible for IVF treatment. They underwent a natural baseline cycle and were subsequently randomized to receive either LZ 5 mg (n = 16) or placebo (n = 15) daily during ovarian stimulation from cycle day (CD) 2-3 until induction of ovulation. Throughout both cycles, monitoring was performed every third day with transvaginal ultrasound for assessment of follicle count and diameter, and blood analyses for the determination of twelve endocrine and paracrine parameters. A follow-up assessment was performed at CD2-3 in the succeeding cycle. In the randomized part of the study, we determined differences in blood parameters, follicle recruitment, and follicle diameter. In the observational part of the study, we assessed follicle recruitment in between cycles and its correlation to endocrine parameters.
MAIN RESULTS AND THE ROLE OF CHANCE
Letrozole cotreatment significantly suppressed oestradiol (E2) concentrations in the follicular phase (area under the curve (AUC) -58% (95% CI [-70%; -43%], P < 0.001)) and luteal phase (AUC -39% [-63%; -1%], P = 0.046). This had a marked effect on the endocrine and paracrine output with increased follicular phase luteinizing hormone (AUC +37% [3%; 82%], P = 0.033), androstenedione (AUC +36% [6%; 74%], P = 0.016), testosterone (AUC +37% [7%; 73%], P = 0.013) and 17-OH-progesterone (AUC +114% [10%; 318%], P = 0.027). Furthermore, follicle-stimulating hormone (FSH) was increased at stimulation day 5 in the LZ group (P < 0.05). In the luteal phase, increased corpus luteum output was reflected by elevated progesterone (AUC +44% [1%; 104%], P = 0.043), inhibin A (AUC +52% [11%; 108%], P = 0.011), androstenedione (AUC +31% [9%; 58%], P = 0.006) and testosterone (AUC +29% [6%; 57%], P = 0.012) in the LZ group. The altered balance between oestrogens and androgens was reflected in a markedly reduced SHBG concentration in the LZ group throughout the luteal phase (AUC -35% [-52%; -11%], P = 0.009). Endocrine and paracrine parameters were similar between groups at the follow-up visit. Letrozole cotreatment significantly increased the mean number of follicles >16 mm at oocyte retrieval (7.2 vs 5.2, difference: 2.0, 95% CI [0.1; 3.8], P = 0.036), while the mean total number of follicles at oocyte retrieval was the same (23.7 vs 23.5, difference: 0.2 [-5.8; 6.1], P = 0.958), and the mean FSH consumption during the stimulated cycle was similar (1500 vs 1520 IU, difference -20 IU [-175; 136], P = 0.794). Between cycles, the mean antral follicle count at CD2-3 was unchanged (natural cycle 19.0, stimulated cycle 20.9, follow-up cycle 19.7, P = 0.692) and there was no effect of LZ cotreatment on the recruitment of the next follicle cohort (test for interaction, P = 0.821).
LIMITATIONS, REASONS FOR CAUTION
This study included a relatively small, selected group of healthy women with an expected normal ovarian function and reserve, and the effects of LZ may therefore be different in other patient groups.
WIDER IMPLICATIONS OF THE FINDINGS
We confirm some previous findings concerning increased follicle growth and increased endogenous FSH and androgen production, which support the rationale for further studies on the use of LZ cotreatment, for example, as a form of endogenous androgen priming sensitizing the follicle to FSH. Letrozole appears to improve the luteal phase with better stimulation of corpus luteum and progesterone secretion.
STUDY FUNDING/COMPETING INTEREST(S)
The authors declare no conflicts of interest relating to the present work.
TRIAL REGISTRATION NUMBER
NCT02939898. | 10.1093/humrep/deac119 |
pubmed_886_11194 | Water complexes involving methanol, ethanol, formaldehyde, formic acid, acetone, ammonia, acetylene, ethylene, chloroethene, trichloroethene, 1,1,1-trichloroethane, hydroxyl radical, and hydroperoxyl radical have been studied. Enthalpies, entropies, and Gibbs free energies of association have been estimated, as well as the concentrations of the complexes under lower-troposphere conditions. The influence of the relative air humidity on the complexation processes has been analyzed. The association processes yielding water complexes of methanol, ethanol, formic acid, ammonia, acetone, hydroxyl radical, and hydroperoxyl radical were found to be more exothermic than that of the water dimer. General trends for the reactivity of the studied water complexes, compared to those of the corresponding free species, are proposed based on global reactivity indexes. The previously reported increased reactivity of the (*)OOH self-reaction, when there is water present, has been explained. The IR spectra of the complexes have been analyzed and compared with those of the free species. | 10.1021/jp101157b |
pubmed_594_3759 | Using an experimental model that enables the effects of alcohol to be distinguished from the effects of the nonalcoholic components present in wine, we determined whether wine has effects other than those of alcohol on the metabolism of cholesterol. Male rats were fed a standard diet and had free access to water and either wine or an equivalent alcohol solution for 45 d or 6 mon. Alcohol intake was similar in the two groups of animals. Consumption of the alcohol solution or wine did not influence plasma cholesterol or high density lipoprotein-cholesterol. At 45 d, the consumption both of wine and of alcohol solution reduced low density lipoprotein (LDL)-cholesterol and very low density lipoprotein cholesterol. At 6 mon, only the rats that consumed wine had reduced LDL-cholesterol. After 45 d of consuming alcohol solution, total cholesterol in the aorta was significantly increased mainly as a result of the rise in free cholesterol. In the aorta, the effect of wine consumption was similar to the effect of alcohol solution consumption, although it was less intense. The only clear effect that could be ascribed to the nonalcoholic components in wine was that the LDL-cholesterol was reduced in the long term, although aortic cholesterol was not. | 10.1007/s11745-001-0732-6 |
pubmed_313_21238 | Efforts are under way to improve the efficacy of subunit malaria vaccines through assessments of new adjuvants, vaccination platforms, and antigens. In this study, we further assessed the Plasmodium falciparum antigen upregulated in infective sporozoites 3 (PfUIS3) as a vaccine candidate. PfUIS3 was expressed in the viral vectors chimpanzee adenovirus 63 (ChAd63) and modified vaccinia virus Ankara (MVA) and used to immunize mice in a prime-boost regimen. We previously demonstrated that this regimen could provide partial protection against challenge with chimeric P. berghei parasites expressing PfUIS3. We now show that ChAd63-MVA PfUIS3 can also provide partial cross-species protection against challenge with wild-type P. berghei parasites. We also show that PfUIS3-specific cellular memory responses could be recalled in human volunteers exposed to P. falciparum parasites in a controlled human malaria infection study. When ChAd63-MVA PfUIS3 was coadministered with the vaccine candidate P. falciparum thrombospondin-related adhesion protein (PfTRAP) expressed in the ChAd63-MVA system, there was no significant change in immunogenicity to either vaccine. However, when mice were challenged with double chimeric P. berghei-P. falciparum parasites expressing both PfUIS3 and PfTRAP, vaccine efficacy was improved to 100% sterile protection. This synergistic effect was evident only when the two vaccines were mixed and administered at the same site. We have therefore demonstrated that vaccination with PfUIS3 can induce a consistent delay in patent parasitemia across mouse strains and against chimeric parasites expressing PfUIS3 as well as wild-type P. berghei; when this vaccine is combined with another partially protective regimen (ChAd63-MVA PfTRAP), complete protection is induced. | 10.1128/IAI.00641-16 |
pubmed_472_14764 | BACKGROUND
Rosacea features increased neurovascular reactivity; migraine is a complex neurologic disorder characterized by recurrent episodes of headache associated with nausea and increased sensitivity to light and sound.
OBJECTIVE
We evaluated the prevalence and risk of new-onset migraine in patients with rosacea.
METHODS
All Danish individuals 18 years of age or older were linked in nationwide registers. Adjusted hazard ratios (HRs) were estimated by Cox regression.
RESULTS
In the total cohort (n = 4,361,688), there were 49,475 patients with rosacea. Baseline prevalence of migraine was 7.3% and 12.1% in the reference population and in patients with rosacea, respectively. The fully adjusted HR of migraine was 1.31 (95% confidence interval 1.23-1.39) for patients with rosacea. Patients with phymatous rosacea (n = 594) had no increased risk of migraine (adjusted HR 0.45; 95% confidence interval 0.11-1.80), whereas patients with ocular rosacea (n = 6977) had a 69% increased risk (adjusted HR 1.69; 95% confidence interval 1.43-1.99). Notably, the risk was higher among patients age 50 years or older than in younger individuals, and the risk was only significant among women.
LIMITATIONS
We were unable to distinguish between migraine subtypes.
CONCLUSION
We found a significantly higher prevalence and risk of incident migraine especially in female patients with rosacea. These data add to the accumulating evidence for a link between rosacea and the central nervous system. | 10.1016/j.jaad.2016.08.055 |
pubmed_739_1217 | Halothane causes an idiosyncratic hepatitis that is thought to result, in part, from immune reactions against one or more lumenal endoplasmic reticulum (ER) proteins that have been covalently modified by the trifluoroacetyl chloride metabolite of halothane. In this study, we have identified a 170 kDa protein target of halothane in the liver of rats. The 170 kDa protein was first detected when proteins in lysates of hepatocytes from halothane-treated rats were immunoprecipitated with antisera against several resident ER proteins. This 170 kDa protein was found to be associated with other protein targets of halothane, including protein disulfide isomerase, a protein disulfide isomerase isoform, a 59 kDa carboxylesterase, and 78 kDa glucose-regulated protein. Immunoblotting with antiserum directed against the trifluoroacetylated hapten indicated that the 170 kDa protein was trifluoroacetylated. Based upon its subcellular localization, molecular mass, N-terminal amino acid sequence, and antigenicity, the trifluoroacetylated 170 kDa protein was identified as UDP-glucose:glycoprotein glucosyltransferase (UGGT), a lumenal ER protein that is thought to have a role in the folding of N-linked glycoproteins. Moreover, treatment of rats with halothane caused a 44% decrease in the activity of liver microsomal UGGT, and at least 36% of the change in the activity of the enzyme could be due to a decrease in the level of the protein. The results suggest that the function of UGGT in folding of N-linked glycoproteins may be affected by other resident ER proteins or xenobiotics such as halothane. | 10.1021/tx9601364 |
pubmed_926_3546 | Reduced blood flow in the coronary arteries can lead to damaged heart tissue (myocardial ischaemia). Although one method for detecting myocardial ischaemia involves changes in the ST segment of the electrocardiogram, the relationship between these changes and subendocardial ischaemia is not fully understood. In this study, we modelled ST-segment epicardial potentials in a slab model of cardiac ventricular tissue, with a central ischaemic region, using the bidomain model, which considers conduction longitudinal, transverse and normal to the cardiac fibres. We systematically quantified the effect of uncertainty on the input parameters, fibre rotation angle, ischaemic depth, blood conductivity and six bidomain conductivities, on outputs that characterise the epicardial potential distribution. We found that three typical types of epicardial potential distributions (one minimum over the central ischaemic region, a tripole of minima, and two minima flanking a central maximum) could all occur for a wide range of ischaemic depths. In addition, the positions of the minima were affected by both the fibre rotation angle and the ischaemic depth, but not by changes in the conductivity values. We also showed that the magnitude of ST depression is affected only by changes in the longitudinal and normal conductivities, but not by the transverse conductivities. | 10.1007/s11517-017-1714-y |
pubmed_509_23022 | Hypokalaemia is a common problem in critically ill patients, which if untreated, can result in dysrhythmia or another adverse outcome. We assessed the safety and efficacy of a continuous infusion of potassium chloride versus an existing intermittent infusion regimen. In this open-label randomised parallel-arm active-controlled pilot study, critically ill adults with plasma potassium concentration between 2.5 and 3.8 mmol/l were randomised to receive either a continuous infusion or intermittent infusions of potassium chloride for establishment and maintenance of normokalaemia. The primary outcome was the mean difference in plasma potassium concentration over time between the two study arms as assessed by a linear mixed-effects model. Although a statistically significant difference was observed (0.22 mmol/l; 95% confidence interval 0.17, 0.27; P <0.0001), this did not reach the pre-determined level indicative of a treatment effect (0.5 mmol/l). The continuous group demonstrated less variance in (mean) plasma potassium as reflected in narrower confidence intervals in a prediction-by-time model. The incidence rate ratio of dysrhythmia, assessed by a mixed-effects Poisson model, was similar in each group (0.62; 95% confidence interval 0.32, 1.21; P=0.16). We recorded no adverse events directly attributable to infusion of potassium chloride in either study arm. Although titrated continuous infusion did not demonstrate a clinically important difference by comparison with intermittent infusions for the maintenance of normokalaemia, there was more consistent control of plasma potassium with no observed complications or adverse events. Therefore, this trial showed an acceptable efficacy and safety profile for the continuous infusion regimen, suggesting scope for further study. | 10.1177/0310057X1204000308 |
pubmed_947_6606 | This Special Issue of Nutrients "Leptin and Metabolic Programming" includes one review article regarding the function of leptin throughout the entire life on cardiometabolic fates and four original articles related to the new function of leptin present in milk and liquid amniotic, its possible relation with other components of breast milk, and how environmental conditions may impact on leptin action and metabolic programming [...]. | 10.3390/nu14010114 |
pubmed_812_22144 | Several lines of evidence indicate that inhibition of butyrylcholinesterase (BuChE) is important in the treatment of certain dementias. Further testing of this concept requires inhibitors that are both BuChE-selective and robust. N-alkyl derivatives (2, 3, 4) of phenothiazine (1) have previously been found to inhibit only BuChE in a mechanism involving pi-pi interaction between the phenothiazine tricyclic ring system and aromatic residues in the active site gorge. To explore features of phenothiazines that affect the selectivity and potency of BuChE inhibition, a series of N-carbonyl derivatives (5-25) was synthesized and examined for the ability to inhibit cholinesterases. Some of the synthesized derivatives also inhibited AChE through a different mechanism involving carbonyl interaction within the active site gorge. Binding of these derivatives takes place within the gorge, since this inhibition disappears when the molecular volume of the derivative exceeds the estimated active site gorge volume of this enzyme. In contrast, BuChE, with a much larger active site gorge, exhibited inhibition that increased directly with the molecular volumes of the derivatives. This study describes two distinct mechanisms for binding phenothiazine amide derivatives to BuChE and AChE. Molecular volume was found to be an important parameter for BuChE-specific inhibition. | 10.1016/j.bmc.2004.09.059 |
pubmed_594_17042 | Subsurface tile drains are a key source of nitrate N (NO3-N) losses to streams in parts of the north central USA. In this study, the Erosion Productivity Impact Calculator (EPIC) model was evaluated by comparing measured vs. predicted tile flow, tile NO3-N loss, soil profile residual NO3-N, crop N uptake, and yield, using 4 yr of data collected at a site near Lamberton, MN, for three crop rotations: continuous corn (Zea mays L.) or CC, corn-soybean [Glycine max (L.) Merr.] or CS, and continuous alfalfa (Medicago sativa L.) or CA. Initially, EPIC was run using standard Soil Conservation Service (SCS) runoff curve numbers (CN2) for CC and CS; monthly variations were accurately tracked for tile flow (r2 = 0.86 and 0.90) and NO3-N loss (r2 = 0.69 and 0.52). However, average annual CC and CS tile flows were underpredicted by -32 and -34%, and corresponding annual NO3-N losses were underpredicted by -11 and -52%. Predicted average annual tile flows and NO3-N losses generally improved following calibration of the CN2; tile flow underpredictions were -9 and - 12%, whereas NO3-N losses were 0.6 and -54%. Adjusting a N parameter further improved predicted CS NO3-N losses. Predicted monthly tile flows and NO3-N losses for the CA simulation compared poorly with observed values (r2 values of 0.27 and 0.19); the annual drainage volumes and N losses were of similar magnitude to those measured. Overall, EPIC replicated the relative impacts of the three cropping systems on N fate. | 10.2134/jeq2001.303822x |
pubmed_650_1905 | Leber hereditary optic neuropathy (LHON) is a maternally inherited disorder characterized by bilateral acute or subacute loss of central vision, primarily in young males. A G----A single base mutation at 11778nt of the mitochondrial genome which eliminates a SfaNI restriction site [Wallace et al., 1988; Holt et al., 1989; Hotta et al., 1989; Singh et al., 1989; Vilkki et al., 1989; Yoneda et al., 1989; Stone et al., 1990; Lott et al., 1990.] has been found in more than 60% of the families with LHON studied. We studied 25 persons from 4 families with LHON using SfaNI and Mae III digestion of a 201 base pair polymerase chain reaction (PCR) product encompassing the 11778nt mutation. The loss of the SfaNI site and the acquisition of a Mae III site at 11778nt were identified in all maternal relatives of the LHON families studied. The mutation was heteroplasmic in all affected individuals, female carriers, and males at-risk. The heteroplasmy of mitochondrial DNA (mtDNA) was also identified by direct DNA sequencing of PCR amplified by direct DNA sequencing of PCR amplified mtDNA digested by SfaNI or Mae III. It appears that the proportion of the mutant mtDNA correlates with the severity of the disease. | 10.1002/ajmg.1320420208 |
pubmed_1051_7156 | Twelve polyphenols from three distinct families (dihydroflavonols, flavan-3-ols, and flavanones) were studied as potential substrates of anthocyanidin synthase from Vitis vinifera (VvANS). Only flavan-3-ols of (2R,3S) configuration having either a catechol or gallol group on ring B are accepted as substrates. Only dihydroflavonols of (2R,3R) configuration are accepted as substrates, but a catechol or gallol group is not mandatory. Flavanones are not substrates of VvANS. HPLC and MS/MS analyses of the enzymatic products showed that the VvANS-catalyzed oxidative transformation of (+)-dihydroflavonols, such as dihydroquercetin, dihydrokaempferol and dihydromyricetin, leads only to the corresponding flavonols. Among the flavan-3-ols recognized as substrates, (+)-gallocatechin was only transformed into delphinidin by VvANS, whereas (+)-catechin was transformed into three products, including two major products that were an ascorbate-cyanidin adduct and a dimer of oxidized catechin, and a minor product that was cyanidin. Data from real-time MS monitoring of the enzymatic transformation of (+)-catechin suggest that its products are all derived from the initial C3-hydroxylation intermediate, i.e., a 3,3-gem-diol, and their most likely formation mechanism is discussed. | 10.3390/molecules27031047 |
pubmed_416_10608 | Retinal pigment epithelial (RPE) cells are constantly exposed to oxidative injury while clearing byproducts of photoreceptor turnover, a circumstance thought to be responsible for degenerative retinal diseases. The mechanisms of hydrogen peroxide (H(2)O(2))-induced apoptosis in RPE cells are not fully understood. We studied signal transduction mechanisms of H(2)O(2)-induced apoptosis in the human RPE cell line ARPE-19. Activation of two stress kinases (JNK and p38) occurs during H(2)O(2) stimulation, and H(2)O(2)-mediated cell death was significantly reduced by their specific inhibition. Exposure to a lethal dose of H(2)O(2) elicited Bax translocation to the mitochondria and release of apoptosis-inducing factor (AIF) from the mitochondria, both of which were abolished by either JNK- or p38-specific inhibitors. Both H(2)O(2)-induced cell death and JNK/p38 phosphorylation were partially inhibited by C. difficile toxin B, inhibitor of Rho, Rac, and cdc42. Use of pull-down assays revealed that the small GTPase activated by H(2)O(2) is Rac1. This study is the first to demonstrate that H(2)O(2) induces a Rac1/JNK1/p38 signaling cascade, and that JNK and p38 activation is important for H(2)O(2)-induced apoptosis as well as AIF/Bax translocation of RPE cells. | 10.1007/s10495-006-9403-6 |
pubmed_732_20939 | Increasing evidence indicates that the Trypanosoma brucei flagellum (synonymous with cilium) plays important roles in host-parasite interactions. Several studies have identified virulence factors and signaling proteins in the flagellar membrane of bloodstream-stage T. brucei, but less is known about flagellar membrane proteins in procyclic, insect-stage parasites. Here we report on the identification of several receptor-type flagellar adenylate cyclases (ACs) that are specifically upregulated in procyclic T. brucei parasites. Identification of insect stage-specific ACs is novel, as previously studied ACs were constitutively expressed or confined to bloodstream-stage parasites. We show that procyclic stage-specific ACs are glycosylated, surface-exposed proteins that dimerize and possess catalytic activity. We used gene-specific tags to examine the distribution of individual AC isoforms. All ACs examined localized to the flagellum. Notably, however, while some ACs were distributed along the length of the flagellum, others specifically localized to the flagellum tip. These are the first transmembrane domain proteins to be localized specifically at the flagellum tip in T. brucei, emphasizing that the flagellum membrane is organized into specific subdomains. Deletion analysis reveals that C-terminal sequences are critical for targeting ACs to the flagellum, and sequence comparisons suggest that differential subflagellar localization might be specified by isoform-specific C termini. Our combined results suggest insect stage-specific roles for a subset of flagellar adenylate cyclases and support a microdomain model for flagellar cyclic AMP (cAMP) signaling in T. brucei. In this model, cAMP production is compartmentalized through differential localization of individual ACs, thereby allowing diverse cellular responses to be controlled by a common signaling molecule. | 10.1128/EC.00019-14 |
pubmed_328_17310 | This work is a continuation of a previous study which described the development of dense and porous chitosan-alginate polyelectrolyte complexes through the addition of different amounts of Pluronic F68 to the polymeric mixture. The present study consisted in the incorporation of an antimicrobial agent, polyhexamethylene biguanide (PHMB), to the previously developed system. PHMB was incorporated at 1 and 10% (w/w) with high incorporation efficiencies, varying from 72 to 86%. Release profiles in phosphate buffered saline were evaluated using the Korsmeyer-Peppas equation, which suggested a quasi-Fickian diffusion mechanism for all obtained formulations. The maximum release percentage was approximately 15% as a result from the high affinity between PHMB and the polysaccharides. The obtained polyelectrolyte complexes were able to prevent the growth of both Staphylococcus aureus and Pseudomonas aeruginosa on their surfaces, being considered potentially effective wound dressings. | 10.1016/j.msec.2018.07.076 |
pubmed_828_3972 | OBJECTIVE
To investigate the expression profile of immune effector molecules in peripheral natural killer cells (NK) in patients with chronic hepatitis virus B.
METHODS
According to the infection status, patients were divided into four experiment groups: normal hepatic function and high HBV DNA level group, normal hepatic function and low HBV DNA level group, abnormal hepatic function and high HBV DNA level group and abnormal hepatic function and low HBV DNA level group. The expression of perforin (PF), granzyme B (Gr B), granulysin (GNLY), tumor necrosis factor alpha (TNFa) and interferon gamma (IFNr) in NK cells were detected by flow cytometer.
RESULTS
Compared with control group (31.50%+/-27.64%), the expression of GNLY was significantly increased in normal hepatic function and high HBV DNA level group (59.74%+/-30.82%) and normal hepatic function and low HBV DNA level group (61.89%+/-33.30%); the expression of IFNr in normal hepatic function and high HBV DNA level group (39.89%+/-21.30%) and abnormal hepatic function and high HBV DNA level group (37.54%+/-18.79%) was lower than that in normal control group (57.38%+/-23.69%); the expression of PF, GrB, GNLY in abnormal hepatic function and high HBV DNA level group (35.47%+/-29.64%, 66.55%+/-22.92%, 42.03%+/-33.17%) was lower than that in normal hepatic function and high HBV DNA level group (56.98%+/-38.34%, 81.53%+/-19.58%, 59.74%+/-30.82%) and normal hepatic function and low HBV DNA level groups (62.95%+/-31.98%, 84.51%+/-14.57%, 61.89%+/-33.3%); there were positive correlations between ef PF, Gr B, GNLY, TNFa, and IFNr.
CONCLUSION
The expression of IFNr in NK cells from patients with high HBV DNA replication level is lower than that in normal control group; the expression of PF, Gr B and GNLY in NK cells from patients with normal hepatic function is higher than that in NK cells from patients with abnormal hepatic function. | pubmed_828_3972 |
pubmed_372_11048 | PURPOSE
This study aimed to investigate the clinical features and treatment outcomes of idiopathic full-thickness macular hole (FTMH) without vitreomacular separation (VMS).
METHODS
Consecutive cases of idiopathic FTMH at one tertiary center from January 2013 to April 2020 were retrospectively recruited. They were separated into two groups according to the findings in optical coherence tomography (OCT): FTMH with VMS and FTMH without VMS. Ophthalmic examinations and OCT were performed pre- and postoperatively. The clinical findings were compared between the two groups.
RESULTS
Of the total 124 cases, 15 (12.1%) were noted as FTMH without VMS with the presence of an attached posterior hyaloid (PH) at macula. The macular hole (MH) size was smaller (276.06 ± 170.10 μm) compared to those with VMS (492.83 ± 209.31 μm) (p < 0.001). The incidence of lamellar hole-associated epiretinal proliferation (LHEP) was much higher in this group (13/15, 86.7%) compared to FTMH with VMS (11/109, 10.1%) (p < 0.001). A higher rate of spontaneous closure of MH (13.3%) was also noted in FMTH without VMS (13.3% vs. 0.9% in FTMH with VMS, p = 0.040). After operation, the MH closure rate was 93.3%. The postoperative best-corrected visual acuity was not significantly different between the two groups (p = 0.098).
CONCLUSIONS
A small percentage (12.1% in this series) of idiopathic FTMH had no VMS. The completely attached PH along with the high incidence of LHEP implied a tangential traction in FTMH without VMS. The MH size was usually small, and the postoperative outcomes were similar to those of conventional FTMH with VMS. | 10.1159/000521731 |
pubmed_871_8407 | The mouse Ig H chain (Igh) complex locus is composed of >100 gene segments encoding the variable, diversity, joining, and constant portions of the Ab H chain protein. To advance the characterization of this locus and to identify all the V(H) genes, we have isolated the entire region from C57BL/6 and C57BL/10 as a yeast artificial chromosome contig. The mouse Igh locus extends approximately three megabases and contains at least 134 V(H) genes classified in 15 partially interspersed families. Two non-Igh pseudogenes (Odc-rs8 and Rpl32-rs14) were localized in the distal part of the locus. This physical yeast artificial chromosome map will provide important structure and guidance for the sequencing of this large, complex, and highly repetitive locus. | 10.4049/jimmunol.168.11.5659 |
pubmed_727_10091 | No mortality was observed in 6 week old male Sprague-Dawley rats subjected to cold at 4 C for 3 weeks and fed either a control diet (Chow) or a semisynthetic diet containing 20% by wt rapeseed oil high in erucic acid (23.6%). All rats fed the Chow diet and 17 of 20 rats fed the rapeseed oil-containing diet survived 4 weeks in the same environment. Three rats on the latter diet died of self-mutilation. Marked myocardial lipidosis as well as a large acumulation of 20:1 and 22:1 was observed in the hearts of rats fed the rapeseed oil-containing diet. Five of 20 rats on the Chow diet and 2 of 20 rats on the rapeseed oil-containing diet had focal necrotic areas in the myocardium. | 10.1007/BF02532577 |
pubmed_437_531 | BACKGROUND
Traditional diagnoses of major depressive disorder (MDD) suggested that the presence or absence of stress prior to onset results in either 'reactive' or 'endogenous' subtypes of the disorder, respectively. Several lines of research suggest that the biological underpinnings of 'reactive' or 'endogenous' subtypes may also differ, resulting in differential response to treatment. We investigated this hypothesis by comparing the gene-expression profiles of three animal models of 'reactive' and 'endogenous' depression. We then translated these findings to clinical samples using a human post-mortem mRNA study.
METHODS
Affymetrix mouse whole-genome oligonucleotide arrays were used to measure gene expression from hippocampal tissues of 144 mice from the Genome-based Therapeutic Drugs for Depression (GENDEP) project. The study used four inbred mouse strains and two depressogenic 'stress' protocols (maternal separation and Unpredictable Chronic Mild Stress) to model 'reactive' depression. Stress-related mRNA differences in mouse were compared with a parallel mRNA study using Flinders Sensitive and Resistant rat lines as a model of 'endogenous' depression. Convergent genes differentially expressed across the animal studies were used to inform candidate gene selection in a human mRNA post-mortem case control study from the Stanley Brain Consortium.
RESULTS
In the mouse 'reactive' model, the expression of 350 genes changed in response to early stresses and 370 in response to late stresses. A minimal genetic overlap (less than 8.8%) was detected in response to both stress protocols, but 30% of these genes (21) were also differentially regulated in the 'endogenous' rat study. This overlap is significantly greater than expected by chance. The VAMP-2 gene, differentially expressed across the rodent studies, was also significantly altered in the human study after correcting for multiple testing.
CONCLUSIONS
Our results suggest that 'endogenous' and 'reactive' subtypes of depression are associated with largely distinct changes in gene-expression. However, they also suggest that the molecular signature of 'reactive' depression caused by early stressors differs considerably from that of 'reactive' depression caused by late stressors. A small set of genes was consistently dysregulated across each paradigm and in post-mortem brain tissue of depressed patients suggesting a final common pathway to the disorder. These genes included the VAMP-2 gene, which has previously been associated with Axis-I disorders including MDD, bipolar depression, schizophrenia and with antidepressant treatment response. We also discuss the implications of our findings for disease classification, personalized medicine and case-control studies of MDD. | 10.1186/1741-7015-12-73 |
pubmed_688_16562 | Recognition of injuries on victims of vehicular fatalities should be performed with the help of means of precise instrumental diagnosis on the basis of information about the etiology of the injury which should be contained in the medical documents. | pubmed_688_16562 |
pubmed_291_15880 | INTRODUCTION
Obesity is an important risk factor for the development of diabetes, hypertension, coronary disease, left ventricular dysfunction, stroke and cardiac arrhythmias. Paradoxically, previous studies in patients undergoing elective coronary angioplasty showed a reduction in hospital and long-term mortality in obese patients. The relation with body mass index (BMI) has been less studied in the context of primary angioplasty.
OBJECTIVES
To evaluate the impact of obesity on the results of ST-segment elevation acute myocardial infarction treated by primary angioplasty.
METHODS
This was a study of 464 consecutive patients with ST-segment elevation acute myocardial infarction undergoing primary angioplasty, 78% male, mean age 61 +/- 13 years. We assessed in-hospital, 30-day and one-year mortality according to BMI. Patients were divided into three groups according to BMI: normal--18-24.9 kg/m2 (n = 171); overweight--25-29.9 kg/m2 (n = 204); and obese-- > 30 kg/m2 (n = 89).
RESULTS
Obese patients were younger (ANOVA, p < 0.001) and more frequently male (p = 0.014), with more hypertension (p = 0.001) and dyslipidemia (p = 0.006). There were no differences in the prevalence of diabetes, previous cardiac history, heart failure on admission, anterior location, multivessel disease, peak total CK or medication prescribed, except that obese patients received more beta-blockers (p = 0.049). In-hospital mortality was 9.9% for patients with normal BMI, 3.4% for overweight patients and 6.7% for obese patients (p = 0.038). Mortality at 30 days was 11 4.4% and 7.8% (p = 0.032) and at one year 12.9%, 4.9% and 9% (p = 0.023), respectively. On univariate analysis, overweight was the only BMI category with a protective effect; however, after multivariate logistic regression analysis, adjusted for confounding variables, none of the BMI categories could independently predict outcome.
CONCLUSIONS
Overweight patients had a better prognosis after primary angioplasty for ST-segment elevation acute myocardial infarction compared with other BMI categories, but this was dependent on other potentially confounding variables. | pubmed_291_15880 |
pubmed_506_5919 | Cold-adapted β-1,3-xylanase (P.t.Xyn26A) from the psychrotrophic bacterium, Psychroflexus torquis, was expressed as a fusion protein with tandem repeats of the N-terminal domain of Protein S from Myxocuccus xanthus (ProS2) in Escherichia coli. After cell lysis in phosphate buffer, most of the ProS2-P.t.Xyn26A was located in the insoluble fraction and aggregated during purification. Arginine hydrochloride (ArgHCl) efficiently solubilized the ProS2-P.t.Xyn26A. The solubilized ProS2-P.t.Xyn26A was purified using immobilized metal affinity chromatography (IMAC) with 500 mM ArgHCl. After cleavage of ProS2-P.t.Xyn26A by human rhinovirus 3C protease, we confirmed that recombinant P.t.Xyn26A maintained its native fold. This is the first report of the expression of a cold-adapted enzyme fused with a ProS2 tag under IMAC purification using a high concentration of ArgHCl. These insights into the expression and purification should be useful during the handling of cold-adapted enzymes. | 10.1007/s10529-014-1666-3 |
pubmed_649_14348 | The authors discuss some defects in the diagnosis and primary treatment tactics in the management of infectious outpatients placed under observation of the district internists. The organizational and methodological measures aimed at the improvement of the diagnosis, polypragmasy control and reduction of the self-treatment hazard are suggested. | pubmed_649_14348 |
pubmed_987_15553 | The genus Bulbophyllum is of scientific interest due to the phytochemical components and diverse biological activities found across species of the genus. Most Bulbophyllum species are epiphytic and located in habitats that range from subtropical dry forests to wet montane cloud forests. In many cultures, the genus Bulbophyllum has a religious, protective, ornamenting, cosmetic, and medicinal role. Detailed investigations into the molecular pharmacological mechanisms and numerous biological effects of Bulbophyllum spp. remain ambiguous. The review focuses on an in-depth discussion of studies containing data on phytochemistry and preclinical pharmacology. Thus, the purpose of this review was to summarize the therapeutic potential of Bulbophyllum spp. biocompounds. Data were collected from several scientific databases such as PubMed and ScienceDirect, other professional websites, and traditional medicine books to obtain the necessary information. Evidence from pharmacological studies has shown that various phytoconstituents in some Bulbophyllum species have different biological health-promoting activities such as antimicrobial, antifungal, antioxidant, anti-inflammatory, anticancer, and neuroprotective. No toxicological effects have been reported to date. Future clinical trials are needed for the clinical confirmation of biological activities proven in preclinical studies. Although orchid species are cultivated for ornamental purposes and have a wide traditional use, the novelty of this review is a summary of biological actions from preclinical studies, thus supporting ethnopharmacological data. | 10.1155/2022/6727609 |
pubmed_422_805 | A high-level expression of a transgene, Ead, encoding the I-Ed alpha-chain is very effective in protection against murine lupus. To investigate the specific contribution of select H-2 haplotypes on the Ead transgene-mediated disease-suppressing effect, we generated H-2 congenic (NZB x BXSB)F1 hybrid mice bearing either H-2b/b, H-2d/b, or H-2d/d haplotype, and compared the transgene-mediated protective effect on the clinical development (autoantibody production and glomerulonephritis) of lupus in these F1 hybrids. The level of protection was most remarkable in mice bearing the I-E- H-2b/b haplotype but was only minimal in I-E+ H-2d/d F1 hybrids. Additional analysis demonstrated a marked suppression of lupus in I-E+ H-2k/k (MRL x BXSB)F1 hybrid mice, indicating that the transgene is able to suppress autoimmune responses even in mice already expressing I-E molecules at a homozygous level. Our results indicate that the level of the transgene-mediated protection is dependent on the host H-2 haplotype. This suggests that the autoimmune suppressive activity of the Ead transgene is likely to be determined through the interaction of the transgene product with the host MHC class II molecules, providing new insight into the role of MHC in lupus-like autoimmunity. | 10.4049/jimmunol.164.1.505 |
pubmed_558_16174 | This study was a follow up investigation of Brawer et al.'s (Prof Psychol Res Pr 33(2):203-206, 2002) survey of education and training of clinical psychologists in religion/spirituality. Directors of clinical training were surveyed to determine whether changes had occurred in the coverage of religion and spirituality through course work, research, supervision, and in the systematic coverage of the content area. Results indicated an increased coverage in the areas of supervision, dedicated courses, inclusion as part of another course, and research. There was no increase in systematic coverage, but significantly more programs provided at least some coverage. The current study also assesses other areas of incorporation as well as directors' opinions regarding the importance of religion/spirituality in the field of psychology. | 10.1007/s10943-009-9272-8 |
pubmed_97_2729 | Reversal of forepaw preference was studied in rats under conditions of peripheral (bracelet) or central (inactivation of contralateral motor cortex and caudate nucleus by intracerebral injection of tetrodotoxin) preferred limb block. Persisting change of the forepaw preferred when reaching for food into a tubular feeder was achieved on the average after 91 (n = 27) and 211 (n = 26) reaches, respectively. When tested in another task (recovering food pellets from a horizontal shelf accessible through a narrow slit below the ceiling of the test box) same rats displayed identical (45%) and opposite (15%) preference or were ambidextrous (40%). Forced change of handedness on the tubular feeder task was accompanied by similar change of preference on the shelf task in only 17% rats. It is concluded that rather independent lateralisation of the two tasks reflects differential contribution of the corticospinal, rubrospinal and ventromedial motor systems. Reversal training proceeds faster with peripheral blockade which establishes not only the new preference but also inhibits the original one. | 10.1016/0304-3940(91)90138-j |
pubmed_885_6575 | Two new methymycin derivatives, 3'-demethylmethymycin (1) and 3'-demethyldeoxymethymycin (2), together with seven known ones (3-9), were obtained from the strain Streptomyces venezuelae ATCC 15439. Their structures were determined on the basis of IR, MS, 1D and 2D NMR data. In addition, the inhibitory effects of all the compounds on human T cell proliferation mediated by PMA/ionomycin were evaluated. The data suggested for the first time that methymycin derivatives have potential anti-inflammatory activity. | 10.1007/s12272-012-0907-z |
pubmed_415_16124 | Predictions of surface water exposure to "down-the-drain" chemicals are presented which employ grid-based spatially-referenced data on average monthly runoff, population density, country-specific per capita domestic water and substance use rates and sewage treatment provision. Water and chemical load are routed through the landscape using flow directions derived from digital elevation data, accounting for in-stream chemical losses using simple first order kinetics. Although the spatial and temporal resolution of the model are relatively coarse, the model still has advantages over spatially inexplicit "unit-world" approaches, which apply arbitrary dilution factors, in terms of predicting the location of exposure hotspots and the statistical distribution of concentrations. The latter can be employed in probabilistic risk assessments. Here the model was applied to predict surface water exposure to "down-the-drain" chemicals in China for different levels of sewage treatment provision. Predicted spatial patterns of concentration were consistent with observed water quality classes for China. | 10.1016/j.envpol.2011.10.035 |
pubmed_6_9831 | Small quantities of lipids accumulate in the white rice grains. These are grouped into non-starch lipid and starch lipid fractions that affect starch properties through association with starch. Lysophosphatidylcholine (LPC) and lysophosphatidylethanolamine (LPE) are two major lipid classes in the two fractions. Using high-oleic rice grains, we investigated the fatty-acid composition in flour and starch by LC-MS and evaluated its impact on starch properties. In the wild-type grain, nearly 50% of fatty acids in LPC and LPE were palmitic acid (C16:0), over 20% linoleic acid (C18:2) and less than 10% oleic acid (C18:1). In the high-oleic rice grain, C18:1 increased at the expense of C18:2 and C16:0. The compositional changes in starch lipids suggest that LPC and LPE are transported to an amyloplast with an origin from endoplasmic reticulum-derived PC and PE during endosperm development. The high-dissociation temperature of the amylose-lipid complex (ALC) and restricted starch swelling power in the high-oleic rice starch indicates that the stability of the ALC involving C18:1 is higher than that of C18:2 and C16:0. This study provides insight into the lipid deposition and starch properties of rice grains with optimized fatty-acid composition. | 10.3390/foods10061169 |
pubmed_834_12238 | To clarify the phenotypes of various classes of human hematopoietic progenitor cells, we used a multicolor staining protocol in conjunction with CD34 and a newly developed mouse antihuman c-kit proto-oncogene product (KIT) monoclonal antibody (MoAb). We characterized three cell fractions in CD34+ cells that express KITlow and KIThigh cells in addition to KIT- cells. A clonogenic assay showed that most granulocyte-macrophage colony-forming cells (GM-CFC) were present in CD34+KIThigh populations, whereas erythroid burst-forming cells (BFU-E) were detected mainly in the CD34+KITlow population. CD34(+)-KIT- fraction contained a small number of BFU-E. Morphologic analysis showed that blast-like cells were more enriched in the CD34+KITlow fraction. KITlow cells contained CD34+CD38- cells that were considered to be very primitive progenitor cells, as determined by a replating assay. To clarify the biologic differences between both fractions, we examined the more primitive progenitor cell functions by assessing long-term culture-initiating cells (LTC-IC) on the stromal cells. At week 2, more CFC recovered from the culture in the fraction initiated with a CD34+KIThigh population. However, more LTC-IC were present during weeks 5 to 9 in the CD34+KITlow population. These results indicate that primitive progenitors are more enriched in the KITlow population and that the KIThigh population contains many GM-committed progenitor cells. We also showed that anti-KIT MoAb inhibited the ability of CD34+ cells to generate CFC on the stromal layer in the LTC system. This suppressive effect was more evident in the generation of BFU-E by CD34+KITlow cells. Moreover, we confirmed that CD34+KIThigh cells emerged from CD34+KITlow cells during coculture with allogeneic stromal cells or from liquid culture in the presence of stem cell factor (SCF), interleukin-6, and erythropoietin. These results emphasize the pivotal role of the KIT and SCF interaction in hematopoiesis and indicate that KITlow cells are more primitive than KIThigh cells. | pubmed_834_12238 |
pubmed_613_24944 | Activation of the translation initiation factor 4E (eIF4E) promotes malignant transformation and metastasis. Signaling through the AKT-mTOR pathway activates eIF4E by phosphorylating the inhibitory 4E binding proteins (4E-BP). This liberates eIF4E and allows binding to eIF4G. eIF4E can then be phosphorylated at serine 209 by the MAPK-interacting kinases (Mnk), which also interact with eIF4G. Although dispensable for normal development, Mnk function and eIF4E phosphorylation promote cellular proliferation and survival and are critical for malignant transformation. Accordingly, Mnk inhibition may serve as an attractive cancer therapy. We now report the identification of a potent, selective and orally bioavailable Mnk inhibitor that effectively blocks 4E phosphorylation both in vitro and in vivo. In cultured cancer cell lines, Mnk inhibitor treatment induces apoptosis and suppresses proliferation and soft agar colonization. Importantly, a single, orally administered dose of this Mnk inhibitor substantially suppresses eIF4E phosphorylation for at least 4 hours in human xenograft tumor tissue and mouse liver tissue. Moreover, oral dosing with the Mnk inhibitor significantly suppresses outgrowth of experimental B16 melanoma pulmonary metastases as well as growth of subcutaneous HCT116 colon carcinoma xenograft tumors, without affecting body weight. These findings offer the first description of a novel, orally bioavailable MNK inhibitor and the first preclinical proof-of-concept that MNK inhibition may provide a tractable cancer therapeutic approach. | 10.1158/0008-5472.CAN-10-3298 |
pubmed_416_8603 | OBJECTIVE
To review the recent literature relevant to genetic research in eating disorders and to discuss unique issues which are crucial for the development of a genetic research project in eating disorders in Brazil.
METHOD
A computer literature review was conducted in the Medline database between 1984 and may 2005 with the search terms "eating disorders", "anorexia nervosa", "bulimia nervosa", "binge eating disorder", "family", "twin" and "molecular genetic" studies.
RESULTS
Current research findings suggest a substantial influence of genetic factors on the liability to anorexia nervosa and bulimia nervosa. Genetic research with admixed populations should take into consideration sample size, density of genotyping and population stratification. Through admixture mapping it is possible to study the genetic structure of admixed human populations to localize genes that underlie ethnic variation in diseases or traits of interest.
CONCLUSIONS
The development of a major collaborative genetics initiative of eating disorders in Brazil and South America would represent a realistic possibility of studying the genetics of eating disorders in the context of inter ethnic groups, and also integrate a new perspective on the biological etiology of eating disorders. | 10.1590/s1516-44462006000300015 |
pubmed_591_16159 | PM10 samples were collected at the top of Jiuxian Mountain in Fujian Province from March 2011 to January 2012 and were analyzed for inorganic water-soluble ions and dicarboxylic acids to investigate their seasonal variations and sources. The results showed that PM10 and its associated species exhibited much higher levels in the spring than those in other seasons but the total contribution of the nine species of dicarboxylic acids to PM10 (0.51%±0.41%) was significantly lower than that of the water-soluble ions (18.07%±8.73%). The water-soluble ions were characterized by the highest concentrations of SO42- and NO3-, followed by Na+ and NH4+. Significant positive correlations were observed between cation and anion equivalents, as well as between NH4+ and SO42- or NO3- equivalents. Individual dicarboxylic acid showed a monotonically decreasing trend with increasing carbon number in which oxalic acid accounted for approximately 75% of the total dicarboxylic acids. Characteristic ratios of malonic acid to succinic acid and adipic acid to azelaic acid, MODIS fire spots, and backward trajectories showed that dicarboxylic acids mainly originated from secondary reactions in the atmosphere and that the direct contributions of open biomass burning to dicarboxylic acid concentrations were negligible. | 10.13227/j.hjkx.201702151 |
pubmed_65_1720 | In order to measure broiler chick hydrogen gas production, a sealed atmosphere chamber was constructed and chicks were intubated with soybean meal (SBM), alpha-galactoside free, ethanol-extracted soybean meal (ESBM), and ESBM with alpha-galactosides added to the levels of SBM (ESBMG). Six male broiler chicks averaging 156 g of weight were deprived of feed for 12 h prior to intubation with 6 g of the test soybean meals. Two chicks were used for each treatment. Following intubation, chicks were placed in the sealed atmosphere chamber for 20 min at 2-h intervals for 28 h. At the end of this 20-min period, a sample of the chamber atmosphere was collected with a gas-tight syringe and analyzed for hydrogen gas by gas-solid chromatography. The hydrogen production of the two chicks intubated with SBM peaked 7 h postintubation at 127 ppm. The ESBM produced a peak at approximately 17 h postintubation at 26 ppm. Intubation with ESBMG resulted in peak hydrogen production at approximately 12 h postintubation at an average of 67 ppm. Results indicate that chicks intubated with SBM produced 3.2 times the amount of total hydrogen gas than those chicks intubated with ESBM. Chicks intubated with ESBMG produced 2.2 times the amount of total hydrogen gas than chicks intubated with ESBM. The research indicates the alpha-galactoside oligosaccharides are a major cause of hydrogen gas production from SBM in poultry. | 10.1093/ps/78.9.1313 |
pubmed_391_4936 | DNA sequences of specific human papillomavirus (HPV) types are found integrated in the cell genome in most invasive genital carcinomas. We have determined the chromosomal localization of integrated HPV type 16 (HPV-16) or HPV-18 genomes in genital cancers by in situ hybridization experiments. In three cancers, HPV sequences were localized in chromosome band 8q24.1, in which the c-myc gene is mapped, and in one cancer HPV sequences were localized in chromosome band 2p24, which contains the N-myc gene. In three of the four cases, the proto-oncogene located near integrated viral sequences was found to be structurally altered and/or overexpressed. These data indicate that HPV genomes are preferentially integrated near myc genes in invasive genital cancers and support the hypothesis that integration plays a part in tumor progression via an activation of cellular oncogenes. | 10.1128/JVI.65.8.4534-4538.1991 |
pubmed_650_12665 | The anti-tumor effect of active specific chemoimmunotherapy, using butanol-extracted tumor-specific transplantation antigen (TSTA), cyclophosphamide (CY), and continuous intrasplenic infusion of interleukin-2 (IS-IL-2), was assessed in a C3H/HeJ murine methylcholanthrene (MCA)-induced fibrosarcoma model. Sole administration of TSTA induced tumor-specific, suppressor T cells in the spleens of mice bearing 3-day established tumors. Concomitant low-dose (20 mg/kg) CY treatment not only inhibited TSTA-mediated suppressor cell induction, but also evoked splenic lymphocytes of tumor-bearing mice to display tumor-specific cytotoxic activity. High-dose (200 mg/kg) CY abrogated the immunotherapeutic benefit. The immune effectors generated by TSTA plus CY bear the Thy 1, L3T4, Lyt 2 phenotype. Continuous IS-IL-2 infusion in combination with TSTA and CY induced tumor-specific Lyt 2+ cytolytic T cells, as well as the activation of L3T4+ cytostatic T cells. Thus, a triple regimen using TSTA, CY, and IS-IL-2 appears to augment CTL induction in tumor-bearing hosts undergoing stimulation of helper elements by TSTA and inhibition of suppressor cells by CY. | pubmed_650_12665 |
pubmed_250_12410 | Nine Virginia soybeans grown in a single location were evaluated and compared for their antioxidant properties and isoflavone profiles. The total phenolic content (TPC) in the soybean extracts was significantly different among different genotypes. The V01-4937, V03-1144, and MFS-511 soybeans had the highest TPC values of 3.89, 3.63, and 3.53 mg of gallic acid equiv/g of seeds, respectively. The isoflavone composition was also different among the different soybean varieties. Malonylgenistin was the major isoflavone in all soybean seeds, accounting for 75-83% of the total measured isoflavones. The V01-4937 variety had the highest total isoflavones and malonylgenistin content followed by the V03-5794. The antioxidant activities of the soybean extracts were also significantly different. V01-4937 and Teejay showed the strongest ORAC values, which were 70% higher than that of the V00-3493 soybean, which had the lowest ORAC value (115.7 micromol of Trolox equiv/g of seeds). However, their ORAC values were correlated with neither TPC nor total isoflavone content. The MFS-511, V01-4937, and Teejay soybeans had the highest DPPH radical scavenging activities of 4.94, 4.78, and 4.64 micromol of Trolox equiv/g of seeds. Overall, the V01-4937 soybean stood out among the tested Virginia soybeans with regard to having the highest TPC, ORAC value, and isoflavone content as well as the second highest DPPH scavenging activity. | 10.1021/jf800468z |
pubmed_402_12344 | The Pax-6 gene encodes a transcriptional master regulator involved in the development of the eye. The quail Pax-6 gene is expressed in the neuroretina from two promoters, P0 and P1, P0 being activated at the onset of neuronal differentiation. In this paper we have identified two regions in the quail Pax-6 gene 5' flanking sequences, located 6 and 2.5 kbp upstream from the P0 promoter that, like the previously characterised intragenic enhancer (EP enhancer), function as neuroretina-specific enhancers whose activity is restricted to the P0 promoter. Moreover, the activity of these 5' enhancers in embryonic neuroretina cells is weaker at day 5 than at day 7, like the EP enhancer, and parallels the level of expression of P0-initiated mRNAs. Footprinting experiments show that neuroretina-specific factors bind to these 5' enhancer elements. In addition we show that these quail Pax-6 enhancer elements, as well as the P0 promoter, are structurally and functionally conserved in humans. These results strongly suggest that these enhancer elements may contribute to the neuroretina-specific transcriptional regulation of the Pax-6 gene in vivo. Thus the complex regulation of the quail Pax-6 gene is also conserved in humans. | 10.1007/s004270050240 |
pubmed_796_3044 | 1. Based on radioligand binding and adenylate cyclase activation, functional receptors to vasoactive intestinal peptide(VIP)/helodermin, were shown to coexist with beta 2-adrenoceptors and prostaglandin receptors in membranes from a cultured cloned BL/VL3 cell line of murine T-cell lymphoma induced by a radiation leukemia virus. 2. The relative potency of VIP-related peptides to stimulate adenylate cyclase activity was: helodermin greater than VIP greater than peptide histidine isoleucinamide. Five VIP analogs inhibited 125I-iodo-VIP binding and stimulated adenylate cyclase activity, their decreasing order of potency being: VIP greater than [D-Asp3]VIP greater than [D-Ser2]VIP greater than [D-Ala4]VIP = [D-His1]VIP = [D-Phe2]VIP. [D-Phe2]VIP acted as a partial agonist (with an intrinsic activity of 0.1 as compared to that of VIP = 1.0) and competitively inhibited helodermin- and VIP-stimulated adenylate cyclase activity with a similar Ki (0.07-0.10 microM). These data suggest the existence, in this murine T-cell lymphoma, of VIP receptors of the 'helodermin-preferring' subtype that are coupled to adenylate cyclase. | 10.1111/j.1432-1033.1989.tb14922.x |
pubmed_245_1751 | Low temperature affects seed germination in plants, and low-temperature germination (LTG) is an important agronomic trait. Natural variation of LTG has been reported in rice, but the molecular basis for this variation is largely unknown. Here we report the phenotypic analysis of LTG in 187 rice natural accessions and a genome-wide association study (GWAS) of LTG in this collection. A total of 53 quantitative trait loci (QTLs) were found to be associated with LTG, of which 20 were located in previously reported QTLs. We further identified Stress-Associated Protein 16 (OsSAP16), coding for a zinc-finger domain protein, as a causal gene for one of the major LTG QTLs. Loss of OsSAP16 function reduces germination while greater expression of OsSAP16 enhances germination at low temperature. In addition, accessions with extremely high and low LTG values have correspondingly high and low OsSAP16 expression at low temperatures, suggesting that variation in expression of the OsSAP16 gene contributes to LTG variation. As the first case of identification of an LTG gene through GWAS, this study indicates that GWAS of natural accessions is an effective strategy in genetically dissecting LTG processes and gaining molecular understanding of low-temperature response and germination. | 10.1093/jxb/erx413 |
pubmed_629_20170 | In the new millennium, indications for splenectomy have expanded. Proper patient selection based on an understanding of the biology of each individual's disease is essential for a favorable outcome. We review the most common diseases for which surgeons may be called on to perform splenectomy and while highlighting potential pitfalls and caveats. | pubmed_629_20170 |
pubmed_217_3388 | Vascular endothelial growth factor (VEGF) and metalloproteinase (MMP) 2 and 9 are useful biomarkers in human lymphoma. During cancerogenesis, transforming growth factor beta (TGF-β) stimulates VEGF and MMPs production. VEGF and TGF-β plasma levels were tested by ELISA, MMP-2 and MMP-9 by gelatine zymography in 37 dogs with lymphoma, 13 of which were also monitored during chemotherapy. Ten healthy dogs served as control. Lymphoma dogs showed higher act-MMP-9 (P < 0.01) and VEGF (P < 0.05), and lower TGF-β than controls, and a positive correlation between act-MMP-9 and VEGF (P < 0.001). Act-MMP-9 and VEGF were significantly higher in T-cell lymphomas, and in stage V compared with stages III-IV disease, regardless of immunophenotype. VEGF was higher in high-grade compared with low-grade T-cell lymphomas. No correlation was found between cytokines levels at presentation and outcome. During chemotherapy, act-MMP-9 and VEGF decreased in B-cell lymphomas (P < 0.01), suggesting a possible predictive role in this group of dogs. | 10.1111/j.1476-5829.2012.00328.x |
pubmed_614_19775 | Ferrisia gilli Gullan (Hemiptera: Pseudococcidae) is a new pest in California pistachios, Pistacea vera L. We conducted a 3-yr field study to determine the type and amount of damage caused by F. gilli. Using pesticides, we established gradients of F. gilli densities in a commercial pistachio orchard near Tipton, CA, from 2005 to 2007. Each year, mealybug densities on pistachio clusters were recorded from May through September and cumulative mealybug-days were determined. At harvest time, nut yield per tree (5% dried weight) was determined, and subsamples of nuts were evaluated for market quality. Linear regression analysis of cumulative mealybug-days against fruit yield and nut quality measurements showed no relationships in 2005 and 2006, when mealybug densities were moderate. However, in 2007, when mealybug densities were very high, there was a negative correlation with yield (for every 1,000 mealybug-days, there was a decrease in total dry weight per tree of 0.105 kg) and percentage of split unstained nuts (for every 1,000 mealybug-days, there was a decrease in the percentage of split unstained of 0.560%), and a positive correlation between the percentage of closed kernel and closed blank nuts (for every 1,000 mealybug-days, there is an increase in the percentage of closed kernel and closed blank of 0.176 and 0.283%, respectively). The data were used to determine economic injury levels, showing that for each mealybug per cluster in May there was a 4.73% reduction in crop value associated with quality and a 0.866 kg reduction in yield per tree (4.75%). | 10.1093/jee/tov223 |
pubmed_556_17321 | Multiple noninvasive imaging modalities are available to measure biventricular function, although limited studies have assessed agreement between modalities in assessing left and right ventricular ejection fraction (LVEF & RVEF) in the same cohort of patients. In this study we prospectively compared the agreement of 2-dimensional echocardiography (2DE), contrast enhanced 2DE, 3-dimensional echocardiography (3DE), and gated heart pool scan (GHPS) measures of LVEF and RVEF in patients with acute ST-elevation myocardial infarction. We recruited 95 consecutive ST-elevation myocardial infarction patients (mean age 61.4 ± 12.0, male: 79.5%) admitted to a major tertiary hospital between July 2016 and May 2018. Despite minimal inter- and intra-observer variability (coefficient of variance < 5% in both categories), substantial discrepancies exist between modalities with Pearson's correlation coefficients ranging from 0.64 to 0.91 for LVEF measurements, and 0.27 to 0.86 for RVEF measurements. Bland-Altman plots demonstrated no systematic bias between modalities. GHPS and 3DE offered the closest agreement for both LVEF and RVEF, demonstrating the greatest correlation coefficient (r = 0.91 and 0.86 respectively), lowest mean absolute differences (4% and 3% respectively), and narrowest Bland-Altman limits of agreement (19% and 18% respectively). Greater than 10% of 2DE and contrast enhanced 2DE scans discordantly showed LVEF values >40% for patients whose LVEF was measured as ≤ 40% by 3DE or GHPS. In conclusion, substantial variation exists between modalities when assessing LVEF and RVEF, although we demonstrate that 3DE and GHPS have the closest agreement. This variability should be considered in clinical management of patients, and modalities should not be used interchangeably in sequential patient follow-up. | 10.1016/j.amjcard.2020.07.057 |
pubmed_675_5157 | Clubfoot describes a congenital condition. If untreated, clubfoot can cause long-term functional issues. The Ponseti method is the gold-standard treatment; it emphasizes casting over surgery. We identified a high rate of major recurrence in patients with isolated clubfoot at our institution. We implemented a quality improvement intervention to address the recurrences.
METHODS
We established a clubfoot program that aimed to (1) develop a standardized treatment pathway; (2) improve care team education; (3) improve coordination of care with families; and (4) improve documentation. The purpose of this study was to outline our quality improvement intervention and evaluate its success. Data were retrospectively collected from isolated clubfeet before (2003-2007, phase I) and after (2012-2014, phase II) implementation of the clubfoot program. We compared the differences in treatment and major recurrence between the 2 phases using generalized logistic or linear mixed models. Modified Poisson regression models were used to evaluate the association between provider nonadherence and recurrence.
RESULTS
The pre- (phase I) and post- (phase II) implementation groups included 91 patients (131 feet) and 68 patients (101 feet), respectively. The incidence of major recurrence (odds ratio: 59.5, 95% confidence interval: 7.8-454.4, P < 0.0001) was lower during phase II compared to phase I. Nonadherence with the care pathway was associated with an increased risk of recurrence (risk ratio: 4.1, 95% confidence interval: 1.2-14.3, P = 0.0274).
CONCLUSIONS
The implementation of a clubfoot program was associated with a decrease in major clubfoot surgery and improved adherence to established guidelines for clubfoot management. | 10.1097/pq9.0000000000000362 |
pubmed_704_23604 | We present DANTE, a novel method for training neural networks using the alternating minimization principle. DANTE provides an alternate perspective to traditional gradient-based backpropagation techniques commonly used to train deep networks. It utilizes an adaptation of quasi-convexity to cast training a neural network as a bi-quasi-convex optimization problem. We show that for neural network configurations with both differentiable (e.g. sigmoid) and non-differentiable (e.g. ReLU) activation functions, we can perform the alternations effectively in this formulation. DANTE can also be extended to networks with multiple hidden layers. In experiments on standard datasets, neural networks trained using the proposed method were found to be promising and competitive to traditional backpropagation techniques, both in terms of quality of the solution, as well as training speed. | 10.1016/j.neunet.2020.07.026 |
pubmed_614_14486 | Germinal matrix hemorrhage (GMH) is the most common and devastating neurological problem of premature infants. Current treatment is largely ineffective and GMH has been nonpreventable. Osteopontin (OPN) is an endogenous protein that has been shown to be neuroprotective, however, it has not been tested in GMH. P7 neonatal rats were subjected to stereotactic ganglionic eminence collagenase infusion. Groups were as follows: (1) sham, (2) GMH + vehicle, (3) GMH + intranasal OPN. Seventy-two hours later, the animals were evaluated using righting reflex, blood-brain barrier (BBB) permeability by Evans blue dye leakage, brain water content, and hemoglobin assay. Intranasal OPN improved outcomes after GMH by attenuation of brain swelling, BBB function, re-bleeding, and neurological outcomes. OPN may play an important role in enhancing neuroprotective brain signaling following GMH. These observed effects may offer novel possibilities for therapy in this patient population. | 10.1007/978-3-319-18497-5_39 |
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