Effect of sustained released metformin therapy on phenotypic and biochemical markers of insulin resistance in polycystic ovary syndrome in South Indian women

Background: Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in young women. Insulin resistance (IR) may play a substantial part in the pathogenesis of PCOS, which leads to type 2 diabetes mellitus (T2DM), cardiovascular disorders and ovarian cancer. Metformin is an insulin sensitizing agent, however its role in PCOS is still controversial.Methods: Sixty women newly diagnosed with PCOS and healthy age matched controls between 18 to 45 years were enrolled after obtaining informed consent. Women in the PCOS group were started on metformin-SR 1gram orally, which was then increased to 1.5 grams after two weeks and continued for 6 months. Fasting blood sugar (FBS), fasting insulin (FI), SHBG, TT, free androgen index (FAI), homeostatic model assessment of Insulin resistance (HOMA-IR), homeostatic model assessment of β- cell function (HOMA-B), homeostatic model assessment of Insulin sensitivity (HOMA-S) and quantitative insulin sensitivity check index (QUICKI) were measured in the control group as well as PCOS group before and after metformin therapy.Results: After six months of metformin-SR therapy, PCOS group showed significant reduction in FI, HOMA-IR, HOMA- β, HOMA-S QUICKI, TT and FAI and significant increase in SHBG levels.Conclusions: Six months of metformin-SR therapy favorably altered markers of IR, TT, SHBG, anovulation and hyperandrogenism in normoglycemic women with PCOS

Formation of quinones by oxidative dealkylation. Part II. Constitution of pedicinin

This article does not have an abstract

Chronic neuropsychiatric sequelae of SARS‐CoV‐2: Protocol and methods from the Alzheimer's Association Global Consortium

Introduction Coronavirus disease 2019 (COVID-19) has caused >3.5 million deaths worldwide and affected >160 million people. At least twice as many have been infected but remained asymptomatic or minimally symptomatic. COVID-19 includes central nervous system manifestations mediated by inflammation and cerebrovascular, anoxic, and/or viral neurotoxicity mechanisms. More than one third of patients with COVID-19 develop neurologic problems during the acute phase of the illness, including loss of sense of smell or taste, seizures, and stroke. Damage or functional changes to the brain may result in chronic sequelae. The risk of incident cognitive and neuropsychiatric complications appears independent from the severity of the original pulmonary illness. It behooves the scientific and medical community to attempt to understand the molecular and/or systemic factors linking COVID-19 to neurologic illness, both short and long term. Methods This article describes what is known so far in terms of links among COVID-19, the brain, neurological symptoms, and Alzheimer's disease (AD) and related dementias. We focus on risk factors and possible molecular, inflammatory, and viral mechanisms underlying neurological injury. We also provide a comprehensive description of the Alzheimer's Association Consortium on Chronic Neuropsychiatric Sequelae of SARS-CoV-2 infection (CNS SC2) harmonized methodology to address these questions using a worldwide network of researchers and institutions. Results Successful harmonization of designs and methods was achieved through a consensus process initially fragmented by specific interest groups (epidemiology, clinical assessments, cognitive evaluation, biomarkers, and neuroimaging). Conclusions from subcommittees were presented to the whole group and discussed extensively. Presently data collection is ongoing at 19 sites in 12 countries representing Asia, Africa, the Americas, and Europe. Discussion The Alzheimer's Association Global Consortium harmonized methodology is proposed as a model to study long-term neurocognitive sequelae of SARS-CoV-2 infection

The impact of surgical delay on resectability of colorectal cancer: An international prospective cohort study

AIM: The SARS-CoV-2 pandemic has provided a unique opportunity to explore the impact of surgical delays on cancer resectability. This study aimed to compare resectability for colorectal cancer patients undergoing delayed versus non-delayed surgery. METHODS: This was an international prospective cohort study of consecutive colorectal cancer patients with a decision for curative surgery (January-April 2020). Surgical delay was defined as an operation taking place more than 4 weeks after treatment decision, in a patient who did not receive neoadjuvant therapy. A subgroup analysis explored the effects of delay in elective patients only. The impact of longer delays was explored in a sensitivity analysis. The primary outcome was complete resection, defined as curative resection with an R0 margin. RESULTS: Overall, 5453 patients from 304 hospitals in 47 countries were included, of whom 6.6% (358/5453) did not receive their planned operation. Of the 4304 operated patients without neoadjuvant therapy, 40.5% (1744/4304) were delayed beyond 4 weeks. Delayed patients were more likely to be older, men, more comorbid, have higher body mass index and have rectal cancer and early stage disease. Delayed patients had higher unadjusted rates of complete resection (93.7% vs. 91.9%, P = 0.032) and lower rates of emergency surgery (4.5% vs. 22.5%, P < 0.001). After adjustment, delay was not associated with a lower rate of complete resection (OR 1.18, 95% CI 0.90-1.55, P = 0.224), which was consistent in elective patients only (OR 0.94, 95% CI 0.69-1.27, P = 0.672). Longer delays were not associated with poorer outcomes. CONCLUSION: One in 15 colorectal cancer patients did not receive their planned operation during the first wave of COVID-19. Surgical delay did not appear to compromise resectability, raising the hypothesis that any reduction in long-term survival attributable to delays is likely to be due to micro-metastatic disease

Multiple novel prostate cancer susceptibility signals identified by fine-mapping of known risk loci among Europeans

Genome-wide association studies (GWAS) have identified numerous common prostate cancer (PrCa) susceptibility loci. We have fine-mapped 64 GWAS regions known at the conclusion of the iCOGS study using large-scale genotyping and imputation in 25 723 PrCa cases and 26 274 controls of European ancestry. We detected evidence for multiple independent signals at 16 regions, 12 of which contained additional newly identified significant associations. A single signal comprising a spectrum of correlated variation was observed at 39 regions; 35 of which are now described by a novel more significantly associated lead SNP, while the originally reported variant remained as the lead SNP only in 4 regions. We also confirmed two association signals in Europeans that had been previously reported only in East-Asian GWAS. Based on statistical evidence and linkage disequilibrium (LD) structure, we have curated and narrowed down the list of the most likely candidate causal variants for each region. Functional annotation using data from ENCODE filtered for PrCa cell lines and eQTL analysis demonstrated significant enrichment for overlap with bio-features within this set. By incorporating the novel risk variants identified here alongside the refined data for existing association signals, we estimate that these loci now explain ∼38.9% of the familial relative risk of PrCa, an 8.9% improvement over the previously reported GWAS tag SNPs. This suggests that a significant fraction of the heritability of PrCa may have been hidden during the discovery phase of GWAS, in particular due to the presence of multiple independent signals within the same regio

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Abstract Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

The neuroendocrinology of love

Romantic love could be considered as a collection of activities associated with the acquisition and retention of emotions needed to survive and reproduce. These emotions change the individual's behavioural strategies in a way that will increase the likelihood of achieving these goals. Love may be defined as an emergent property of an ancient cocktail of neuropeptides and neurotransmitters. It appears that lust, attachment and attraction appear to be distinct but intertwined processes in the brain each mediated by its own neurotransmitters and circuits. These circuits feed on and reinforce each other. Sexual craving is mediated by testosterone and oestrogen and has the amygdala as an important centre. Attraction is mediated by hormones of stress and reward including dopamine, norepinephrine cortisol and the serotinergic system and has the nucleus accumbens the ventral tegmental area as key mediators

Endocrinology and the arts at the feet of the dancing Lord: Parathyroid hormone resistance in an Indian icon

The dance of Siva has a cosmic appeal. Nowhere has this dance been crystallised in its pristine form as in the Nataraja Bronzes from the Chola period. Mysticism surrounds the dancing form of the Nataraja. But does Nataraja dance upon an endocrine mystery. Does the demon under his feet Apasmara literally forgetfulness or epilepsy have an endocrine disorder. The short limbed stocky eye popping dwarf with possible mental retardation with a name that suggests epilepsy throws open a host of endocrine diagnoses. From cretinisim to the original descriptions of pseudohypoparathyroidism here is one view of the medical mystery under Shiva′s dancing feet

Hunches on hunchbacks

The hunchback has long been a symbol of revilement in art and literature. This write up tries to find the cause of the deformity into two iconic hunchbacks in literature, Manthara and Quasimodo

The breasts of Tutankhamun

Despite being an obscure pharaoh who ruled for a very short time, Tutankhamun, the boy king, has reigned popular consciousness since the discovery of his tomb in 1922. To endocrinologists, the depiction of the kings of the 18th dynasty in an androgynous form complete with gynecomastia has been a source of intrigue and academic curiosity. Many explanations abound. But is the depiction just stylized art? Or did the kings indeed have familial gynecomastia, or aromatase excess with craniosynostosis. An inspired team of researchers used molecular genetic tests to truly lay the Tut controversy to rest.