A comparative study of metabolic and hormonal effects of myoinositol vs. metformin in women with polycystic ovary syndrome: a randomised controlled trial

Background: The purpose of the study was to find out which drug is more effective in treatment and improvement of metabolic and hormonal parameters in women with polycystic ovary syndrome (PCOS); Myoinositol or Metformin. This study was conducted since there are very limited studies on the same.Methods: Patients between 15-40 years of age with signs and symptoms of PCOS who attended the outpatient department of obstetrics and gynaecolgy at AVBRH between study period of September, 2012 to August 2014, were subjected to specific investigations to diagnose PCOS. Patients who were diagnosed with PCOS according to the Rotterdam criteria were included in the study group. Patients were randomly allocated to treatment with either myoinositol or metformin. Myoinositol group received 1 g twice daily while Metformin group received 500 mg twice daily for 6 months .The findings and investigations were repeated after 6 months and was compared with the baseline values.Results: Treatment with myoinositol and metformin both decreased body mass index, androgenic features, improved menstrual abnormalities and polycystic ovaries but the Level of insulin resistance as measured by fasting insulin and homeostatic model assessment (HOMA) decreased only on treatment with myoinositol.Conclusions: Myoinositol acts at the level of insulin receptors and is effective in treatment of hyperinsulinemia and insulin resistance, which is the underlying factor leading to the development of polycystic ovary syndrome

Cross-cultural adaptation into Punjabi of the English version of the Hospital Anxiety and Depression Scale

BACKGROUND: We wanted to use a Punjabi version of the Hospital Anxiety and Depression Scale (HADS) to enable non-English speaking patients to participate in a clinical trial. The aim of the study was to translate and validate the Hospital Anxiety and Depression Scale into Punjabi. METHODS: The HADS was translated into Punjabi by a multidisciplinary team, verified against the original version, and administered to 73 bilingual patients attending an outpatient clinic. RESULTS: One sample t-tests and the Bland-Altman plots demonstrated acceptable linguistic agreement between the two versions of the HADS. Spearman's rank-order correlation coefficients (p < 0.0001) demonstrate excellent conceptual agreement between each item and its corresponding subscale score, for both versions. Concordance rates revealed that the Punjabi HADS adequately identified borderline cases of anxiety (80.8%), definite cases of anxiety (91.8%) and depression (91.8%), but was less reliable in identifying borderline cases of depression (65.8%). Cronbach alpha coefficients revealed high levels of internal consistency for both the Punjabi and English versions (0.81 and 0.86 for anxiety and 0.71 and 0.85 for depression, respectively). CONCLUSION: The Punjabi HADS is an acceptable, reliable and valid measure of anxiety and depression among physically ill Punjabi speaking people in the United Kingdom

Accuracy and Reliability of Pallor for Detecting Anaemia: A Hospital-Based Diagnostic Accuracy Study

Anaemia is a common disorder. Most health providers in resource poor settings rely on physical signs to diagnose anaemia. We aimed to determine the diagnostic accuracy of pallor for anaemia by using haemoglobin as the reference standard.In May 2007, we enrolled consecutive patients over 12 years of age, able to consent and willing to participate and who had a haemoglobin measurement taken within a day of assessment of clinical pallor from outpatient and medicine inpatient department of a teaching hospital. We did a blind and independent comparison of physical signs (examination of conjunctivae, tongue, palms and nailbed for pallor) and the reference standard (haemoglobin estimation by an electronic cell counter). Diagnostic accuracy was measured by calculating likelihood ratio values and 95% confidence intervals (CI) at different haemoglobin thresholds and area under the receiver operating characteristic curve. Two observers examined a subset of patients (n = 128) to determine the inter-observer agreement, calculated by kappa statistics. We studied 390 patients (mean age 40.1 [SD 17.08] years); of whom 48% were women. The haemoglobin was <7 g/dL in 8% (95% confidence interval, 5, 10) patients; <9 g/dL in 21% (17, 26) patients and <12 g/dL in 64% (60, 70) patients. Among patients with haemoglobin <7 g/dL, presence of severe tongue pallor yielded a LR of 9.87 (2.81, 34.6) and its absence yielded a LR of 0. The tongue pallor outperformed other pallor sites and was also the best discriminator of anaemia at haemoglobin thresholds of 7 g/dL and 9 g/dL (area under the receiver operating characteristic curves (ROC area  = 0.84 [0.77, 0.90] and 0.71[0.64, 0.76]) respectively. The agreement between the two observers for detection of anaemia was poor (kappa values  = 0.07 for conjunctival pallor and 0.20 for tongue pallor).Clinical assessment of pallor can rule out and modestly rule in severe anaemia

Colistin: recent data on pharmacodynamics properties and clinical efficacy in critically ill patients

Recent clinical studies performed in a large number of patients showed that colistin "forgotten" for several decades revived for the management of infections due to multidrug-resistant (MDR) Gram-negative bacteria (GNB) and had acceptable effectiveness and considerably less toxicity than that reported in older publications. Colistin is a rapidly bactericidal antimicrobial agent that possesses a significant postantibiotic effect against MDR Gram-negative pathogens, such as Pseudomonas aeruginosa, Acinetobacter baumannii, and Klebsiella pneumoniae. The optimal colistin dosing regimen against MDR GNB is still unknown in the intensive care unit (ICU) setting. A better understanding of the pharmacokinetic-pharmacodynamic relationship of colistin is urgently needed to determine the optimal dosing regimen. Although pharmacokinetic and pharmacodynamic data in ICU patients are scarce, recent evidence shows that the pharmacokinetics/pharmacodynamics of colistimethate sodium and colistin in critically ill patients differ from those previously found in other groups, such as cystic fibrosis patients. The AUC:MIC ratio has been found to be the parameter best associated with colistin efficacy. To maximize the AUC:MIC ratio, higher doses of colistimethate sodium and alterations in the dosing intervals may be warranted in the ICU setting. In addition, the development of colistin resistance has been linked to inadequate colistin dosing. This enforces the importance of colistin dose optimization in critically ill patients. Although higher colistin doses seem to be beneficial, the lack of colistin pharmacokinetic-pharmacodynamic data results in difficulty for the optimization of daily colistin dose. In conclusion, although colistin seems to be a very reliable alternative for the management of life-threatening nosocomial infections due to MDR GNB, it should be emphasized that there is a lack of guidelines regarding the ideal management of these infections and the appropriate colistin doses in critically ill patients with and without multiple organ failure

Short interfering RNA against STAT1 attenuates cisplatin-induced ototoxicity in the rat by suppressing inflammation

Cisplatin is widely used for treating various solid tumors. However, this drug produces dose-limiting ototoxicity and nephrotoxicity, which significantly reduce the quality of life of cancer patients. While nephrotoxicity could be alleviated by diuresis, there is currently no approved treatment for hearing loss. Previous studies show that the ROS and inflammation are major contributors to cisplatin-induced hearing loss. In this study, we show that ROS trigger the inflammatory process in the cochlea by activating signal transducer and activator of transcription-1 (STAT1). Activation of STAT1 activation was dependent on ROS generation through NOX3 NADPH oxidase, knockdown of which by siRNA reduced STAT1 activation. Moreover, STAT1 siRNA protected against activation of p53, reduced apoptosis, reduced damage to OHCs and preserved hearing in rats. STAT1 siRNA attenuated the increase in inflammatory mediators, such as TNF-α, inhibition of which protected cells from cisplatin-mediated apoptosis. Finally, we showed that trans-tympanic administration of etanercept, a TNF-α antagonist, protected against OHC damage and cisplatin-induced hearing loss. These studies suggest that controlling inflammation by inhibition of STAT1-dependent pathways in the cochlea could serve as an effective approach to treat cisplatin ototoxicity and improve the overall quality of life for cancer patients

Functional selectivity of adenosine receptor ligands

Adenosine receptors are plasma membrane proteins that transduce an extracellular signal into the interior of the cell. Basically every mammalian cell expresses at least one of the four adenosine receptor subtypes. Recent insight in signal transduction cascades teaches us that the current classification of receptor ligands into agonists, antagonists, and inverse agonists relies very much on the experimental setup that was used. Upon activation of the receptors by the ubiquitous endogenous ligand adenosine they engage classical G protein-mediated pathways, resulting in production of second messengers and activation of kinases. Besides this well-described G protein-mediated signaling pathway, adenosine receptors activate scaffold proteins such as β-arrestins. Using innovative and sensitive experimental tools, it has been possible to detect ligands that preferentially stimulate the β-arrestin pathway over the G protein-mediated signal transduction route, or vice versa. This phenomenon is referred to as functional selectivity or biased signaling and implies that an antagonist for one pathway may be a full agonist for the other signaling route. Functional selectivity makes it necessary to redefine the functional properties of currently used adenosine receptor ligands and opens possibilities for new and more selective ligands. This review focuses on the current knowledge of functionally selective adenosine receptor ligands and on G protein-independent signaling of adenosine receptors through scaffold proteins

A review of data needed to parameterize a dynamic model of measles in developing countries

<p>Abstract</p> <p>Background</p> <p>Dynamic models of infection transmission can project future disease burden within a population. Few dynamic measles models have been developed for low-income countries, where measles disease burden is highest. Our objective was to review the literature on measles epidemiology in low-income countries, with a particular focus on data that are needed to parameterize dynamic models.</p> <p>Methods</p> <p>We included age-stratified case reporting and seroprevalence studies with fair to good sample sizes for mostly urban African and Indian populations. We emphasized studies conducted before widespread immunization. We summarized age-stratified attack rates and seroprevalence profiles across these populations. Using the study data, we fitted a "representative" seroprevalence profile for African and Indian settings. We also used a catalytic model to estimate the age-dependent force of infection for individual African and Indian studies where seroprevalence was surveyed. We used these data to quantify the effects of population density on the basic reproductive number <it>R</it>₀.</p> <p>Results</p> <p>The peak attack rate usually occurred at age 1 year in Africa, and 1 to 2 years in India, which is earlier than in developed countries before mass vaccination. Approximately 60% of children were seropositive for measles antibody by age 2 in Africa and India, according to the representative seroprevalence profiles. A statistically significant decline in the force of infection with age was found in 4 of 6 Indian seroprevalence studies, but not in 2 African studies. This implies that the classic threshold result describing the critical proportion immune (<it>p</it>_c) required to eradicate an infectious disease, <it>p</it>_c= 1-1/<it>R</it>₀, may overestimate the required proportion immune to eradicate measles in some developing country populations. A possible, though not statistically significant, positive relation between population density and <it>R</it>₀for various Indian and African populations was also found. These populations also showed a similar pattern of waning of maternal antibodies. Attack rates in rural Indian populations show little dependence on vaccine coverage or population density compared to urban Indian populations. Estimated <it>R</it>₀values varied widely across populations which has further implications for measles elimination.</p> <p>Conclusions</p> <p>It is possible to develop a broadly informative dynamic model of measles transmission in low-income country settings based on existing literature, though it may be difficult to develop a model that is closely tailored to any given country. Greater efforts to collect data specific to low-income countries would aid in control efforts by allowing highly population-specific models to be developed.</p

Coupling changes in cell shape to chromosome segregation

Animal cells undergo dramatic changes in shape, mechanics and polarity as they progress through the different stages of cell division. These changes begin at mitotic entry, with cell–substrate adhesion remodelling, assembly of a cortical actomyosin network and osmotic swelling, which together enable cells to adopt a near spherical form even when growing in a crowded tissue environment. These shape changes, which probably aid spindle assembly and positioning, are then reversed at mitotic exit to restore the interphase cell morphology. Here, we discuss the dynamics, regulation and function of these processes, and how cell shape changes and sister chromatid segregation are coupled to ensure that the daughter cells generated through division receive their fair inheritance

Lead-Time Trajectory of CA19-9 as an Anchor Marker for Pancreatic Cancer Early Detection

Background & Aims There is substantial interest in liquid biopsy approaches for cancer early detection among subjects at risk, using multi-marker panels. CA19-9 is an established circulating biomarker for pancreatic cancer; however, its relevance for pancreatic cancer early detection or for monitoring subjects at risk has not been established. Methods CA19-9 levels were assessed in blinded sera from 175 subjects collected up to 5 years before diagnosis of pancreatic cancer and from 875 matched controls from the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial. For comparison of performance, CA19-9 was assayed in blinded independent sets of samples collected at diagnosis from 129 subjects with resectable pancreatic cancer and 275 controls (100 healthy subjects; 50 with chronic pancreatitis; and 125 with noncancerous pancreatic cysts). The complementary value of 2 additional protein markers, TIMP1 and LRG1, was determined. Results In the PLCO cohort, levels of CA19-9 increased exponentially starting at 2 years before diagnosis with sensitivities reaching 60% at 99% specificity within 0 to 6 months before diagnosis for all cases and 50% at 99% specificity for cases diagnosed with early-stage disease. Performance was comparable for distinguishing newly diagnosed cases with resectable pancreatic cancer from healthy controls (64% sensitivity at 99% specificity). Comparison of resectable pancreatic cancer cases to subjects with chronic pancreatitis yielded 46% sensitivity at 99% specificity and for subjects with noncancerous cysts, 30% sensitivity at 99% specificity. For prediagnostic cases below cutoff value for CA19-9, the combination with LRG1 and TIMP1 yielded an increment of 13.2% in sensitivity at 99% specificity ( P = .031) in identifying cases diagnosed within 1 year of blood collection. Conclusion CA19-9 can serve as an anchor marker for pancreatic cancer early detection applications

Frequently asked questions about chlorophyll fluorescence, the sequel

[EN] Using chlorophyll (Chl) a fluorescence many aspects of the photosynthetic apparatus can be studied, both in vitro and, noninvasively, in vivo. Complementary techniques can help to interpret changes in the Chl a fluorescence kinetics. Kalaji et al. (Photosynth Res 122: 121-158, 2014a) addressed several questions about instruments, methods and applications based on Chl a fluorescence. Here, additionalChl a fluorescence-related topics are discussed again in a question and answer format. 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