Pharmacology for National Board Examination

This pharmacology study guide is designed to provide students preparing for the National Boards exam with a clear and concise visual aid in the form of systemic flow charts. Each flow chart is organized by drug class and includes information on the mechanism of action, indications, contraindications, dosages, and common adverse effects for each drug within the class. By using this study guide, students can easily navigate through the complex world of pharmacology and feel confident in their ability to succeed on the pharmacology section of the National Board exam. The study guide for pharmacology is significant in several ways. Firstly, it serves as a valuable resource for students who are preparing for the national board exam. This study guide helps students master the material in a structured and organized manner. Secondly, the study guide can also be used by instructors as a teaching aid to supplement their pharmacology curriculum and enhance their students\u27 learning experience

Expiry Prediction and Reducing Food Wastage using IoT and ML

This paper details development of a low-cost, small-size, and portable electronic nose (E-nose) for the prediction of the expiry date of food products. The Sensor array is composed of commercially available metal oxide semiconductors sensors like MQ2 sensor, temperature sensor, and humidity sensor, which were interfaced with the help of ESP8266 and Arduino Uno for data acquisition, storage, and analysis of the dataset consisting of the odor from the fruit at different ripening stages. The developed system is used to analyze gas sensor values from various fruits like bananas and tomatoes. Responding signals of the e-nose were extracted and analyzed. Based on the obtained data we applied a few machine learning algorithms to predict if a banana is stale or not. Logistic regression, Decision Tree Classifier, Support Vector Classifier (SVC) & K-Nearest Neighbours (KNN) classifiers were the binary classification algorithms used to determine whether the fruit became stale or not. We achieved an accuracy of 97.05%. These results prove that e-nose has the potential of assessing fruits and vegetable freshness and predict their expiry date, thus reducing food wastage

Gabapentin for chronic pelvic pain in women (GaPP2):a multicentre, randomised, double-blind, placebo-controlled trial

BackgroundChronic pelvic pain affects 2–24% of women worldwide and evidence for medical treatments is scarce. Gabapentin is effective in treating some chronic pain conditions. We aimed to measure the efficacy and safety of gabapentin in women with chronic pelvic pain and no obvious pelvic pathology.MethodsWe performed a multicentre, randomised, double-blind, placebo-controlled randomised trial in 39 UK hospital centres. Eligible participants were women with chronic pelvic pain (with or without dysmenorrhoea or dyspareunia) of at least 3 months duration. Inclusion criteria were 18–50 years of age, use or willingness to use contraception to avoid pregnancy, and no obvious pelvic pathology at laparoscopy, which must have taken place at least 2 weeks before consent but less than 36 months previously. Participants were randomly assigned in a 1:1 ratio to receive gabapentin (titrated to a maximum dose of 2700 mg daily) or matching placebo for 16 weeks. The online randomisation system minimised allocations by presence or absence of dysmenorrhoea, psychological distress, current use of hormonal contraceptives, and hospital centre. The appearance, route, and administration of the assigned intervention were identical in both groups. Patients, clinicians, and research staff were unaware of the trial group assignments throughout the trial. Participants were unmasked once they had provided all outcome data at week 16–17, or sooner if a serious adverse event requiring knowledge of the study drug occurred. The dual primary outcome measures were worst and average pain scores assessed separately on a numerical rating scale in weeks 13–16 after randomisation, in the intention-to-treat population. Self-reported adverse events were assessed according to intention-to-treat principles. This trial is registered with the ISRCTN registry, ISCRTN77451762.FindingsParticipants were screened between Nov 30, 2015, and March 6, 2019, and 306 were randomly assigned (153 to gabapentin and 153 to placebo). There were no significant between-group differences in both worst and average numerical rating scale (NRS) pain scores at 13–16 weeks after randomisation. The mean worst NRS pain score was 7·1 (standard deviation [SD] 2·6) in the gabapentin group and 7·4 (SD 2·2) in the placebo group. Mean change from baseline was −1·4 (SD 2·3) in the gabapentin group and −1·2 (SD 2·1) in the placebo group (adjusted mean difference −0·20 [97·5% CI −0·81 to 0·42]; p=0·47). The mean average NRS pain score was 4·3 (SD 2·3) in the gabapentin group and 4·5 (SD 2·2) in the placebo group. Mean change from baseline was −1·1 (SD 2·0) in the gabapentin group and −0·9 (SD 1·8) in the placebo group (adjusted mean difference −0·18 [97·5% CI −0·71 to 0·35]; p=0·45). More women had a serious adverse event in the gabapentin group than in the placebo group (10 [7%] of 153 in the gabapentin group compared with 3 [2%] of 153 in the placebo group; p=0·04). Dizziness, drowsiness, and visual disturbances were more common in the gabapentin group.InterpretationThis study was adequately powered, but treatment with gabapentin did not result in significantly lower pain scores in women with chronic pelvic pain, and was associated with higher rates of side-effects than placebo. Given the increasing reports of abuse and evidence of potential harms associated with gabapentin use, it is important that clinicians consider alternative treatment options to off-label gabapentin for the management of chronic pelvic pain and no obvious pelvic pathology.FundingNational Institute for Health Research

New genetic loci link adipose and insulin biology to body fat distribution.

Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms

Genome-wide association identifies nine common variants associated with fasting proinsulin levels and provides new insights into the pathophysiology of type 2 diabetes.

OBJECTIVE: Proinsulin is a precursor of mature insulin and C-peptide. Higher circulating proinsulin levels are associated with impaired β-cell function, raised glucose levels, insulin resistance, and type 2 diabetes (T2D). Studies of the insulin processing pathway could provide new insights about T2D pathophysiology. RESEARCH DESIGN AND METHODS: We have conducted a meta-analysis of genome-wide association tests of ∼2.5 million genotyped or imputed single nucleotide polymorphisms (SNPs) and fasting proinsulin levels in 10,701 nondiabetic adults of European ancestry, with follow-up of 23 loci in up to 16,378 individuals, using additive genetic models adjusted for age, sex, fasting insulin, and study-specific covariates. RESULTS: Nine SNPs at eight loci were associated with proinsulin levels (P < 5 × 10(-8)). Two loci (LARP6 and SGSM2) have not been previously related to metabolic traits, one (MADD) has been associated with fasting glucose, one (PCSK1) has been implicated in obesity, and four (TCF7L2, SLC30A8, VPS13C/C2CD4A/B, and ARAP1, formerly CENTD2) increase T2D risk. The proinsulin-raising allele of ARAP1 was associated with a lower fasting glucose (P = 1.7 × 10(-4)), improved β-cell function (P = 1.1 × 10(-5)), and lower risk of T2D (odds ratio 0.88; P = 7.8 × 10(-6)). Notably, PCSK1 encodes the protein prohormone convertase 1/3, the first enzyme in the insulin processing pathway. A genotype score composed of the nine proinsulin-raising alleles was not associated with coronary disease in two large case-control datasets. CONCLUSIONS: We have identified nine genetic variants associated with fasting proinsulin. Our findings illuminate the biology underlying glucose homeostasis and T2D development in humans and argue against a direct role of proinsulin in coronary artery disease pathogenesis

Pharmacology for National Board Examination

This pharmacology study guide is designed to provide students preparing for the National Boards exam with a clear and concise visual aid in the form of systemic flow charts. Each flow chart is organized by drug class and includes information on the mechanism of action, indications, contraindications, dosages, and common adverse effects for each drug within the class. By using this study guide, students can easily navigate through the complex world of pharmacology and feel confident in their ability to succeed on the pharmacology section of the National Board exam. The study guide for pharmacology is significant in several ways. Firstly, it serves as a valuable resource for students who are preparing for the national board exam. This study guide helps students master the material in a structured and organized manner. Secondly, the study guide can also be used by instructors as a teaching aid to supplement their pharmacology curriculum and enhance their students\u27 learning experience

ROS-Mediated Oxidative Stress Influence Anti-Apoptotic Genes and Cyt c Release in Hyperglycemic Mouse Kidneys to Initiate Late Nephropathic Complications

Decades of intense research has shown that hyperglycemiainduced ROS production can lead to a redox-imbalance causing oxidative stress (OS) in a variety of target organs in vivo. In the absence of an efficient antioxidant counteracting system, massive OS often leads to activation of stress-responsive signaling pathways resulting in deregulated expression of pro-survival and/or pro-death genes. Persistent deregulation of such pathways eventually masterminds late complications of diabetes. Most studies hold hyperglycemia-induced OS as the ‘cause’, and premature onset of apoptosis as the ‘effect’. This ‘cause and effect’ axis ultimately initiates the development and progression of macro and microvascular complications including diabetic nephropathy. This acute in vivo study was designed to investigate: (i) whether streptozotocin (STZ)-induced hyperglycemia can cause OS in kidneys; and if so (ii) whether acute OS can influence anti-apoptotic genes and Cyt c release, and contribute to kidney-injury. Mice (8 mo old; ♀B6C3F1) were treated with STZ (dissolved in citrate buffer pH 4.0; 100 mg/kg, ip) for six consecutive days and all the animals were sacrificed on day-7. Control animals received vehicle alone (Citrate buffer). Blood and kidneys were collected for tissue biochemistry and pathology. All the STZ-exposed animals showed massive hyperglycemia (average blood glucose in mg/dl: Cont- 120±10; STZ- 395.5±50), elevated BUN (in mg/dl: Cont- 30±2; STZ121±11), increased lipid peroxidation (nmol/gm. Protein: Cont8.3±1; STZ- 19.1±2), increased DNA fragmentation (%Control100±11; STZ-330±18), and presence of apoptotic nuclei were found scattered throughout the tissues. In contrast, glutathione peroxidase (U/gm. protein: Cont 431±19; STZ- 291±15) and SOD activity (Cont 414±9; STZ- 183±10) declined in kidneys. Along with the antioxidant team, expression of anti-death Bcl-2 and BclXL proteins decreased and Cyt c (cytosolic) release dramatically increased. In summary, this study showed that even a short-term hyperglycemia-induced OS may perturb the tissue biochemistry favorable for apoptosis and long-term impact of this may translate into serious nephrotoxic complications

A cross-sectional study of clinical, histopathological and direct immmunofluorescence diagnosis in autoimmune bullous diseases

Background: Immunobullous diseases are morphologically heterogeneous and the differentiation between various subtypes is essential for proper treatment and prognosis. Aim of our study was to analyze and correlate clinical, histopathological and immunofluorescence findings in autoimmune bullous diseases. Materials and Methods: A cross-sectional study was done over a period of two years (2010-2012) after approval of the ethics committee. Sixty patients, who met the inclusion criteria of immunobullous disease, were included in the study. Skin biopsy for histopathology and direct immunofluorescence (DIF) examination was taken. DIF using salt-split technique was done in few of the cases. The final diagnosis was based on clinical, histopathology and DIF findings. Pearson′s coefficient of correlation (r) was calculated. Statistical Analysis was done using Epi info version. 7.0. Results: Fifty-three cases with clinical diagnosis of autoimmune bullous diseases were evaluated. In 88.6% of cases, histopathology diagnosis was consistent with clinical diagnosis and in 75.5% of cases, DIF findings were consistent with clinical diagnosis. A positive relation was seen between clinical and DIF findings with r = 0.65 and between histopathology and DIF findings with r = 0.75. DIF positivity was seen in 100% cases of bullous pemphigoid (BP) and pemphigus foliaceous and 94.7% cases of pemphigus vulgaris, which was statistically significant with p < 0.05. In DIF salt-split test, deposition was seen on roof of blister in BP whereas on floor in epidermolysis bullosa acquisita. Conclusion: Our study provides evidence-based guidance for the diagnosis and classification of various immunobullous disorders. DIF test should be done in conjunction with histopathology for definitive diagnosis and to minimize both: False-positive and false-negative results

Primary plasma cell leukemia: autologous stem cell transplant in an era of novel induction drugs

Primary plasma cell leukemia (pPCL) is a rare and aggressive variant of multiple myeloma (MM) with poor long-term survival after cytotoxic chemotherapy. Many novel drugs have revolutionized the treatment algorithms for MM. The impact of targeted therapy, both pre- and post-autologous stem cell transplant (auto-HCT) remains an area of ongoing interest. In this study, we report outcomes post auto-HCT for pPCL and the impact of maintenance therapy posttransplant with novel agents