Mesenteric panniculitis does not confer an increased risk for cancers: A systematic review and meta-analysis

Background:Mesenteric panniculitis (MP) is a non-specific, localized inflammation at the mesentery of small intestines which often gets detected on computed tomography. An association with malignant neoplasms remains unclear. We performed a systematic review and meta-analysis to examine the association of malignancy with MP.Methods:MEDLINE, EMBASE, Web of Science, and Cochrane databases were searched for articles published from inception to 2020 that evaluated the association of malignant neoplasms with MP in comparison with control groups. Using random-effects method, a summary odds ratio (OR) estimate with 95% confidence intervals for malignant neoplasms in MP was estimated.Results:Four case-control studies reporting data on 415 MP patients against 1132 matched-controls met inclusion criteria and were analyzed. The pooled OR for finding a malignant neoplasm in patients with MP was 0.907 (95% CI: 0.688–1.196; P = .489). The heterogeneity was mild and non-significant. Also, there was no heightened risk of any specific type of malignancy with MP. Three more case-series with unmatched-control groups (MP: 282, unmatched-controls: 17,691) were included in a separate analysis where the pooled OR of finding a malignant neoplasm was 2.963 (95% CI: 1.434–6.121; P = .003). There was substantial heterogeneity in this group.Conclusion:This meta-analysis of matched controlled studies proves absence of any significant association of malignant neoplasms with MP. Our study also demonstrates that the putative association of malignancy with MP is mainly driven by uncontrolled studies or case-series.     

Conformational dynamics of superoxide dismutase (SOD1) in osmolytes: a molecular dynamics simulation study

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease caused by the misfolding of Cu, Zn superoxide dismutase (SOD1). Several earlier studies have shown that monomeric apo SOD1 undergoes significant local unfolding dynamics and is the predecessor for aggregation. Here, we have employed atomistic molecular dynamics (MD) simulations to study the structure and dynamics of monomeric apo and holo SOD1 in water, aqueous urea and aqueous urea–TMAO (trimethylamine oxide) solutions. Loop IV (zinc-binding loop) and loop VII (electrostatic loop) of holo SOD1 are considered as functionally important loops as they are responsible for the structural stability of holo SOD1. We found larger local unfolding of loop IV and VII of apo SOD1 as compared to holo SOD1 in water. Urea induced more unfolding in holo SOD1 than apo SOD1, whereas the stabilization of both the form of SOD1 was observed in ternary solution (i.e. water/urea/TMAO solution) but the extent of stabilization was higher in holo SOD1 than apo SOD1. The partially unfolded structures of apo SOD1 in water, urea and holo SOD1 in urea were identified by the exposure of the hydrophobic cores, which are highly dynamic and these may be the initial events of aggregation in SOD1. Our simulation studies support the formation of aggregates by means of the local unfolding of monomeric apo SOD1 as compared to holo SOD1 in water.

Change in conformations of apo and holo SOD1 in water and in osmolytes in terms of configurational entropy (S).     

Association of FcγRIIa Polymorphism with Clinical Outcome of Dengue Infection: First Insight from Pakistan

Dengue illness has been a major health concern in Pakistan during the last decade. Dengue infection can result in a spectrum of clinically distinct outcomes, ranging from asymptomatic infection to potentially life-threatening forms of dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS). A single-nucleotide polymorphism in FcγRIIa (rs1801274) results in altered affinity of the receptor for different subclasses of immunoglobulin G, and is a key player in determining the susceptibility to or protection from severe clinical infection of dengue. In this study, we analyzed the allelic and genotypic distribution of rs1801274 in subjects of Pakistani origin with subclinical dengue infection (n = 40), dengue fever (DF) (n = 40), and DHF/DSS (n = 30). We found that HH homozygotes and heterozygotes were significantly more likely to develop clinical dengue (odds ratio [OR] = 3.21, 95% confidence interval [CI] = 1.29–7.97, P = 0.009), either DF (OR = 2.82, 95% CI = 1.00–7.97, P = 0.045) or DHF/DSS (OR = 3.90, 95% CI = 1.13–13.07, P = 0.024) than the asymptomatic dengue infection. Results of allelic distribution comparisons and logistic regression analysis also supported the same relationship. The results suggest complex nature of interacting factors in determining the course for severe dengue illness.     

Macrosomic infants of nondiabetic and diabetic mothers: The challenges for obstetric practices in low resource community

To estimate and compare the obstetric outcome of fetal macrosomia in both diabetic and non-diabetic mothers as challenges in obstetrics practice Karachi, Pakistan. Study Design: comparative cross sectional, Study duration: From June 2008-May 2009, Study population: All singleton pregnant women, Sample size: 229. Neonates with birth weight of 3,500?gms or greater born to diabetic and non-diabetic mother. Babies with 3,500?gms birth weight and more were considered as macrosomic. The major outcome measures were obstetrics outcome: live births, perinatal mortality, mode of delivery and APGAR scores of both groups. We compared demographic, obstetric and neonatal outcomes on diabetic & non-diabetic mothers delivering macrosomic babies. Data were entered and analyzed using SPSS windows version 15. Significance of difference was calculated using t test, Chi square test as applicable. There were 72 diabetic and 157 non-diabetic pregnant women. Uncomplicated diabetic and non-diabetic women of single index pregnancy had age range of 19?C35?years. Overall incidence of macrosomia (????3,500?gms) in this study was 72(31.4%). In this study there were significantly more macrosomic newborns in diabetic women; (52.8%) compared to (47.2%). Fetal macrosomia in our study was 31.4% in both diabetic and non-diabetic mothers. The obstetric challenges of diagnosis and management of fetal macrosomia in low resource country like Pakistan require screening for macrosomia as an integral part of antenatal care.     

Repurposing verapamil for prevention of cognitive decline in sporadic Alzheimer's disease

Dementia is currently the only leading cause of death that is still on the rise,with its overall costs already surpassing those of cancer and heart disease combined,it has developed into a worldwide crisis.In response to its serious and far-reaching effects,the US government has established the"National Alzheimer's Project Act"(Public Law 111-375).     

Characterization of neuromedin U effects in canine smooth muscle

Two endogenous receptors for the potent smooth muscle-stimulating peptide neuromedin U (NmU) have recently been identified and cloned. Pharmacological, binding, and expression studies were conducted in an attempt to determine the receptor(s) involved in the smooth muscle-stimulating effects of NmU. The NmU peptides caused a concentration-dependent contraction of canine isolated urinary bladder. NmU did not have this same effect in the urinary bladder from rat, guinea pig, rabbit, mouse, or ferret. Although NmU had no effect on canine uterus it did cause contraction of canine stomach, ileum, and colon. As well as causing contraction of canine bladder in vitro, NmU administered systemically resulted in a significant increase in urinary bladder pressure in vivo. High-affinity binding sites for NmU were identified in canine bladder. The four NmU peptides porcine NmU-8, rat NmU-23, human NmU-25, and porcine NmU-25 displaced (125)I-NmU-25 binding with similar K(i) values (0.08-0.24 nM). A different binding profile was revealed in human embryonic kidney-293 cells transiently expressed with the canine NmU-2 receptor where porcine NmU-8 (K(i) = 147.06 nM) was much less potent than the other NmU peptides. Using TaqMan, expression of NmU-1 was detected in human urinary bladder, small intestine, colon, and uterus. Expression of NmU-2 was much lower or absent in these human tissues and undetectable in canine bladder and stomach. The results of this study reveal significant species differences in the activity of NmU. The contractile activity in human and canine smooth muscle seems to be mediated by the recently cloned NmU-1 receptor.     

Patient preferences for managing asthma: results from a discrete choice experiment

Effective control of asthma requires regular preventive medication. Poor medication adherence suggests that patient preferences for medications may differ from the concerns of the prescribing clinicians. This study investigated patient preferences for preventive medications across symptom control, daily activities, medication side-effects, convenience and costs, using a discrete choice experiment embedded in a randomized clinical trial involving patients with mild-moderate persistent asthma. The present data were collected after patients had received 6 weeks' treatment with one of two drugs. Three choice options were presented, to continue with the current drug, to change to an alternative, hypothetical drug, or to take no preventive medication. Analysis used random parameter multinomial logit. Most respondents chose to continue with their current drug in most choice situations but this tendency differed depending on which medication they had been allocated. Respondents valued their ability to participate in usual daily activities and sport, preferred minimal symptoms, and were less likely to choose drugs with side-effects. Cost was also significant, but other convenience attributes were not. Demographic characteristics did not improve the model fit. This study illustrates how discrete choice experiments may be embedded in a clinical trial to provide insights into patient preferences.     

A Comparative Study of the Beneficial Effects of Ipratropium and Beclomethasone against Insulin-Induced Tracheal Tissue Contraction in a Guinea Pig Model

Objective

To evaluate the acute effects of insulin on airway reactivity and the protective effects of beclomethasone and ipratropium against insulin-induced airway hyperresponsiveness on isolated tracheal smooth muscle in a guinea pig model.

Materials and Methods

The trachea of each guinea pig was excised; one end of the tracheal strip was attached to the hook of the oxygen tube of a tissue bath and the other end was connected to a research-grade isometric force displacement transducer. The effects of varying concentrations of insulin (10⁻⁷ to 10⁻³M) and insulin pretreated with a fixed concentration of beclomethasone (10⁻⁶M) and ipratropium (10⁻⁶M) on the isolated tracheal tissue were studied by constructing cumulative concentration-response curves. Changes in tracheal smooth muscle contractions were recorded on a 4-channel oscillograph.

Results

The means ± standard error of the mean of the maximum amplitude of contraction with increasing concentrations of insulin and of insulin pretreated with fixed concentrations of beclomethasone and ipratropium were 35 ± 1.13, 22 ± 1.15 and 27.8 ± 1.27 mm, respectively.

Conclusion

The data showed that beclomethasone inhibited the contractile response of insulin to a greater extent than ipratropium. Thus we suggest that inhalational insulin pretreated with beclomethasone may be more efficacious than with ipratropium for the amelioration of potential respiratory adverse effects such as bronchoconstriction.Key Words: Airway hyper-reactivity, Inhaled insulin, Beclomethasone, Ipratropium, Tracheal muscle     

Effects of late coronary artery reperfusion on left ventricular remodeling persist for 10 weeks after experimental rat myocardial infarction and are associated with improved survival

Objective: To test the hypothesis that coronary artery reperfusion performed too late to reduce infarct size improves survival by altering left ventricular remodeling and preventing progressive left ventricular dilation.Background: Several clinical trials have suggested that late coronary artery reperfusion without infarct size reduction is associated with a survival benefit. Although the mechanism is not known, survival benefits could be related to decreased infarct expansion associated with late coronary artery reperfusion. Decreased infarct expansion results in decreased left ventricular volume, and the resulting decreased wall stress could prevent or attenuate progressive left ventricular dilation and improve survival.Methods: Rats (n=84) were randomized to undergo sham operation, permanent left coronary artery ligation, or 2 hours of left coronary artery ligation followed by reperfusion. Ten weeks later, hemodynamic measurements were made before and after volume loading. The rats were killed, the hearts were removed, and passive pressurevolume curves were obtained. The hearts were fixed at a constant pressure and analyzed morphometrically.Results: When examined 10 weeks after experimental myocardial infarction, late reperfusion's effects on left ventricular remodeling resulted in reduced left ventricular volume when compared to hearts with infarcts supplied by a permanently occluded coronary artery (1.9 ± 0.1 ml/kg vs. 2.1 ± 0.2 ml/ kg; p < 0.01). Although there was a trend toward less thinning (0.95 ± 0.13 mm vs. 1.00 ± 0.10 mm; p=NS) and less expansion (2.3 ± 0.4 vs. 2.8 ± 0.9; p=NS) in reperfused hearts compared to hearts with a permanently occluded coronary artery, changes in infarct shape 10 weeks after infarction were not significantly different. Reperfusion's beneficial effects on remodeling of noninfarcted myocardium were associated with improved survival. Mortality was higher in the permanently occluded rats than in the reperfused rats (35% vs. 12%; p < 0.05).Conclusion: Late coronary artery reperfusion has a beneficial effect on remodeling of noninfarcted myocardium that results in reduced left ventricular volume in rat hearts examined 10 weeks after infarction. These beneficial effects on left ventricular remodeling are associated with improved survival.     

Label‐free mass spectrometry‐based quantification of hemagglutinin and neuraminidase in influenza virus preparations and vaccines

Please cite this paper as: Getie‐Kebtie et al. (2012) Label‐free mass spectrometry‐based quantification of hemagglutinin and neuraminidase in influenza virus preparations and vaccines. Influenza and Other Respiratory Viruses 7(4), 521–530. Background Influenza vaccination is the primary method for preventing influenza and its severe complications. An accurate rapid method to determine hemagglutinin (HA) concentration would facilitate reference antigen preparation and consequently expedite availability of seasonal as well as pandemic vaccines. Objective The goal of this study was to develop a label‐free mass spectrometry (MS) based method that enables simultaneous identification and quantification of HA, neuraminidase (NA), and other viral proteins and protein contaminations in influenza vaccine or virus preparations. Methods The method presented is based on LC/MSE analysis of vaccine or virus preparations tryptic digests spiked with a known amount of protein standard from which a universal response factor is generated and applied to calculate the concentration of proteins identified in the mixture. Results We show that, with the use of an appropriate internal standard, the label‐free MS‐based protein quantification method is applicable for simultaneous identification and absolute quantification of HA and identification and relative quantification of other influenza proteins as well as protein impurities in influenza vaccines and virus preparations. We show that different subtype recombinant HA is preferred internal standard that provides the most accurate results in absolute quantification of HAs and other influenza proteins. We applied this method to measure the absolute quantity of HA as well as relative quantities of other viral proteins and impurities in preparations of whole virus and monovalent vaccine, providing data to demonstrate strain‐dependent differences in the amount of NA. Conclusion The label‐free MS method presented here is ideally suited for timely preparation of reference material needed for potency testing of seasonal and pandemic vaccines.