Exploring the novel duo of Reticulocalbin, and Sideroflexin as future biomarker candidates for Exacerbated Chronic Obstructive Pulmonary Disease.

BACKGROUND: COPD is a complex respiratory disorder with high morbidity and mortality rates. Even with the current conventional diagnostic methods, including circulating inflammatory biomarkers, underdiagnosis rates in COPD remain as high as 70%. Our study was a comparative cross-sectional study that aimed to address the diagnostic challenges by identifying future biomarker candidates in COPD variants. METHODS: This study used a label-free plasma proteomics approach that combined mass spectrometric data with bioinformatics to shed light on the functional roles of differentially expressed proteins in the COPD lung microenvironment. The predictive capacity of the screened proteins was assessed using Receiver Operating Characteristic (ROC) curves, with Western blot analysis validating protein expression patterns in an independent cohort. RESULTS: Our study identified three DEPs-reticulocalbin-1, sideroflexin-4, and liprinα-3 that consistently exhibited altered expression in COPD exacerbation. ROC analysis indicated strong predictive potential, with AUC values of 0.908, 0.715, and 0.856 for RCN1, SFXN4, and LIPα-3, respectively. Validation through Western blot analysis confirmed their expression patterns in an independent validation cohort. CONCLUSIONS: Our study discovered a novel duo of proteins reticulocalbin-1, and sideroflexin-4 that showed potential as valuable future biomarkers for the diagnosis and clinical management of COPD exacerbations.

Management of Hypertension in Patients with Diabetes: A Comprehensive Review of the Perceptions and Practices of Health Care Providers in India.

OBJECTIVES: This study evaluated the perception and practices of health care providers (physicians, diabetologists, and endocrinologists) regarding the treatment of hypertension in patients with diabetes in India. METHODS: Health care providers throughout India who treated patients with diabetes and hypertension were invited to participate in an online survey and periodic 21 virtual meetings. They were questioned about their perception and practices in managing these patients, and strategies to improve blood pressure (BP). RESULTS: The online survey was completed by 2,513 health care providers, and 344 participated in virtual meetings. More than 50% reported that 31-50% of their patients with diabetes also had hypertension. Home BP monitoring was recommended by 88%, and lifestyle modifications were consistently recommended. Choice of antihypertensive treatment varied based on comorbidities, and a renin-angiotensin system blocker plus a calcium channel blocker (CCB) was the most common combination for dual antihypertensive therapy. Suggested strategies to improve BP control included patient awareness/education, lifestyle modifications, better follow-up/monitoring, and optimization of therapy. CONCLUSION: Indian health care providers were aware of clinical recommendations and practices regarding treatment of patients with diabetes and hypertension, and generally make clinical decisions consistent with current guidelines. Optimization of care for these patients is essential to reduce cardiovascular disease risk and improve patient outcomes.

Identification of Novel Serum Proteins Associated with Myelination and Cholesterol Transport in Neuromyelitis Optica Spectrum Disorders by Mass Spectrometry.

Neuromyelitis optica spectrum disorders (NMOSD) is a demyelinating autoimmune disease affecting the central nervous system causing inflammatory lesions in the optic nerves, spinal cord and other vital areas of CNS. The clinical manifestations include acute transverse myelitis with paraplegia and optic neuritis with impaired vision. In the present study we focussed on comparative expression of serum proteins between NMOSD variants and control. The study has identified a plethora of novel and unexplored acute phase proteins involved in lipid transport and myelination in perspective of NMOSD. The serum proteins obtained after albumin globulin depletion were subjected to LC-MS/MS. The commonly altered proteins in all NMOSD variants with respect to control were smaug homolog protein and serum amyloid A. Truncated breast and ovarian cancer susceptibility protein and cystic fibrosis transmembrane conductance regulator protein were specifically upregulated and can act as potential biomarkers for neuromyelitis optica with autoantibody negativity to Aquaporin - 4 (AQP-4) and myelin oligodendrocyte (MOG) immunoglobulins. In addition, the uniquely downregulated proteins such as antithrombin III and histidine rich glycoprotein in NMO/MOG autoantibody negative samples can be accounted for its dysregulated fibrinolysis associated with NMO. The differentially expressed proteins were involved in cholesterol transport, synaptic vesicle mediated transport, neurotransmission and immune regulation which are closely associated with myelin formation and protection. Supplementary Information: The online version contains supplementary material available at 10.1007/s12291-021-01004-w.

Long-acting porcine ACTH stimulated salivary cortisol in the diagnosis of adrenal insufficiency.

BACKGROUND: Synacthen stimulated salivary cortisol has been previously evaluated and found beneficial in the diagnosis of adrenal insufficiency (AI), especially in situations with altered cortisol-binding protein (CBG) levels. Unfortunately, Synacthen is not marketed in many parts of the world whereas porcine sequence corticotrophin (Acton Prolongatum) is readily available. This study aimed to find the diagnostic accuracy of Acton prolongatum stimulated salivary cortisol test (APSST) compared to the short synacthen test (SST). METHODS: Consecutive outpatients with suspected AI underwent SST initially, followed by APSST after 3 days. For APSST, saliva was collected at 0, 60 and 120 minutes after administering 30 units Acton Prolongatum intramuscularly. Serum and salivary cortisol were estimated using electrochemiluminescence assay. (Cobas e 411, Elecsys Cortisol II kits) RESULTS: Sixty-seven patients with clinically suspected AI were enrolled for the study. Based on SST, 35 patients were classified as having AI [primary AI (n=19) and secondary AI (n=16)] whereas 32 had normal glucocorticoid reserve. The area under receiver operator curve of 0.99 and 0.98 was observed for salivary cortisol values at 60 and 120 minutes, respectively, for APSST. A cut-off value of 18.5 nmol/L (0.67 µg/dL) and 29.3 nmol/L (1.06 µg/dL) at 60 and 120 minutes, respectively, had a sensitivity as well as specificity of 93%-100% in diagnosing AI. CONCLUSION: Salivary cortisol estimation following stimulation using intramuscular porcine ACTH (Adrenocorticotrophic hormone) (30 units) is an economical and accurate alternative to SST in the diagnosis of AI, m and its level of 30 nmol/L or more at 2 hours confirms adrenal sufficiency.

Practical use of insulin degludec/insulin aspart in a multinational setting: beyond the guidelines.

Insulin degludec/insulin aspart (IDegAsp) is a fixed-ratio co-formulation of insulin degludec, which provides long-lasting basal insulin coverage, and insulin aspart, which targets postprandial glycaemia. This review provides expert opinion on the practical clinical use of IDegAsp, including: dose timings relative to meals, when and how to intensify treatment from once-daily (OD) to twice-daily (BID) dose adjustments, and use in special populations (including hospitalized patients). IDegAsp could be considered as one among the choices for initiating insulin treatment, preferential to starting on basal insulin alone, particularly for people with severe hyperglycaemia and/or when postprandial hyperglycaemia is a major concern. The recommended starting dose of IDegAsp is 10 units with the most carbohydrate-rich meal(s), followed by individualized dose adjustments. Insulin doses should be titrated once weekly in two-unit steps, guided by individualized fasting plasma glucose targets and based on patient goals, preferences and hypoglycaemia risk. Options for intensification from IDegAsp OD are discussed, which should be guided by HbA1c, prandial glucose levels, meal patterns and patient preferences. Recommendations for switching to IDegAsp from basal insulin, premixed insulins OD/BID, and basal-plus/basal-bolus regimens are discussed. IDegAsp can be co-administered with other antihyperglycaemic drugs; however, sulphonylureas frequently need to be discontinued or the dose reduced, and the IDegAsp dose may need to be decreased when sodium-glucose co-transporter-2 inhibitors or glucagon-like peptide-1 receptor agonists are added. Considerations around the initiation or continuation of IDegAsp in hospitalized individuals are discussed, as well as in those undergoing medical procedures.

Use of Gla-100 in Special Situations.

Insulin therapy is the cornerstone of diabetes management in people with type 2 diabetes mellitus (T2DM). Therefore, its use is recommended even in special populations and situations such as the elderly, pregnant women, obese individuals, people observing religious fasting, and in the presence of comorbidities such as renal insufficiency, and cancer. Since these special situations predispose to complications such as a high risk of hypoglycemia, patients need constant glucose monitoring and insulin dose adjustments, wherever applicable. This review discusses the various considerations that might guide the decision-making process in the special situations alluded to here. It also throws light on how insulin glargine 100 U/mL has emerged as a preferred choice of insulin therapy in most of these situations, on the strength of its inherently low hypoglycemia and weight gain potential, which has found traction even in the recent diabetes guidelines.

Consensus on "Basal insulin in the management of Type 2 Diabetes: Which, When and How?"

INTRODUCTION: Type 2 diabetes mellitus (T2DM) has attained epidemic proportions and continues to increase despite the availability of a number of oral antidiabetic medications and major advances made in insulin delivery since its discovery nearly a hundred years ago. One, amongst many other reasons responsible for the inability to achieve adequate glycaemic control in a substantial proportion of T2DM patients is the delayed initiation and inappropriate intensification of insulin treatment. Appropriate initiation and intensification of insulin is critical for the successful achievement of tight glycaemic control. OBJECTIVE: To provide simple and easily implementable guidelines to primary care physicians on basal insulin initiation and intensification, along with use of basal insulin in special situations (hepatic failure, renal failure and gestational diabetes mellitus). METHODS: Each consensus statement on basal insulin initiation, intensification and use of basal insulin in special situations was evaluated for dosing and titration based on established guidelines, data from approved pack inserts, prescribing information or summary of product characteristics for each insulin type, and published scientific literature. These evaluations were then factored into the national context based not only on the clinical experience of the expert committee representatives' but also based on the common therapeutic practices followed in India to successfully achieve optimal glucose control. RESULTS: Recommendations on initiation and intensification of basal insulin, and its use in special situations, have been developed. The key recommendations are to initiate basal insulin when 2 or 3 oral antidiabetic medications fail to achieve target glycaemic control, or in symptomatic patients with glycated haemoglobin value greater than 9%. Depending upon patient characteristics, any of the four available basal insulins [Neutral protamine Hagedorn (NPH), Glargine (IGlar), Detemir (IDet), Degludec (IDeg)] can be used. However, IDeg has a longer duration of action, comparatively lesser hypoglycaemia (both overall and nocturnal) and more flexibility in administration timing compared to IGlar) and IDet. Inability to maintain glycaemic control should lead to prompt intensification of basal insulin treatment by adding mealtime insulin, consisting of one to three injections of either rapid-acting insulin analog or regular insulin; depending upon patient characteristics, intensification can also be achieved by transition from basal insulin to twice daily premixed insulin analogs/premixed human insulin/insulin co-formulations. IDeg/IDet can be used in all grades of renal and hepatic impairment; and IDet has been approved for use in gestational diabetes mellitus. CONCLUSIONS: We hope that these consensus based recommendations shall be a useful reference tool for health care practitioners and help them in initiating and intensifying insulin therapy in T2DM patients in order to achieve optimal glycaemic control.

Efficacy and safety of canagliflozin in patients with type 2 diabetes mellitus living in hot climates.

AIMS: Patients with type 2 diabetes mellitus (T2DM) have increased risk of adverse events (AEs; e.g. dehydration, hypoglycaemia) in hot weather. This analysis assessed the efficacy and safety of canagliflozin, a sodium glucose co-transporter 2 (SGLT2) inhibitor, in patients with T2DM who live in hot climates. METHODS: This post hoc analysis evaluated patients with T2DM using pooled data from four 26-week, placebo-controlled studies (N=2,313) and data from a 104-week, active-controlled study (add-on to metformin vs glimepiride; N=1,450). Changes in HbA1c, fasting plasma glucose (FPG), body weight and blood pressure (BP) were assessed in subsets of patients living in hot climates (pooled, placebo-controlled studies, n=611; active-controlled study, n=307) and those living in other climates (i.e. other climate subset; pooled, placebo-controlled studies, n=1,702; active-controlled study, n=1,143). Safety was assessed based on AE reports. RESULTS: Canagliflozin 100 and 300 mg lowered HbA1c, FPG, body weight and BP vs placebo over 26 weeks and glimepiride over 104 weeks in the hot climate subsets. Canagliflozin was generally well tolerated in the hot climate subsets, with a higher incidence of AEs related to the mechanism of SGLT2 inhibition (i.e. genital mycotic infections). Volume depletion-related AEs were low across groups. CONCLUSION: Canagliflozin improved glycaemic control, lowered body weight and BP, and was generally well tolerated in patients with T2DM living in hot climates compared with placebo over 26 weeks or glimepiride over 104 weeks. CLINICAL TRIALS REGISTRATION: ClinicalTrials.gov NCT01081834, NCT01106677, NCT01106625, NCT01106690, NCT00968812.

Minimally invasive oesophagectomy in prone versus lateral decubitus position: A comparative study.

BACKGROUND: Thoracoscopic oesophageal mobilisation during a minimally invasive oesophagectomy (MIE) is most commonly performed with the patient placed in the lateral decubitus position (LDP). The prone position (PP) for thoracoscopic oesophageal mobilisation has been proposed as an alternative. MATERIALS AND METHODS: This was a retrospective, comparative study designed to compare early outcomes following a minimally invasive thoracolaparoscopic oesophagectomy for oesophageal cancer in LDP and in PP. RESULTS: During the study period, between January 2011 and February 2014, 104 patients underwent an oesophagectomy for cancer. Of these, 42 were open procedures (transhiatal and transthoracic oesophagectomy) and 62 were minimally invasive. The study group included patients who underwent thoracolaparoscopic oesophagectomy in LDP (n = 23) and in PP (n = 25). The median age of the study population was 55 (24-71) years, and there were 25 males. Twenty-one (21) patients had tumours in the middle third of the oesophagus, 24 in the lower third, and 3 arising from the gastro-oesophageal junction. The most common histology was squamous cell cancer (85.4%). The median duration of surgery was similar in the two groups; however, the estimated median intraoperative blood loss was less in the PP group [200 (50-400) mL vs 300 (100-600) mL; P = 0.01)]. In the post-operative period, 26.1% patients in the LDP group and 8% in the PP group (8%) developed respiratory complications. The incidence of other post-operative complications, including cervical oesophagogastric anastomosis, hoarseness of voice and chylothorax, was not different in the two groups. The T stage of the tumour was similar in the two groups, with the majority (37) having T3 disease. A mean of 8 lymph nodes (range 2-33) were retrieved in the LDP group, and 17.5 (range 5-41) lymph nodes were retrieved in the PP group (P = 0.0004). The number of patients with node-positive disease was also higher in the PP group (19 vs 10, P = 0.037). CONCLUSION: MIE in the PP is an effective alternative to LDP. The exposure obtained is excellent even without the need for a complete lung collapse, thereby obviating the need for a double-lumen endotracheal tube. A more meticulous dissection can be performed resulting in a higher lymph nodal yield.

The evolution of the polycrystalline copper surface, first to Cu(111) and then to Cu(100), at a fixed CO2RR potential: a study by operando EC-STM.

A study based on operando electrochemical scanning tunneling microscopy (EC-STM) has shown that a polycrystalline Cu electrode held at a fixed negative potential, -0.9 V (vs SHE), in the vicinity of CO2 reduction reactions (CO2RR) in 0.1 M KOH, undergoes stepwise surface reconstruction, first to Cu(111) within 30 min, and then to Cu(100) after another 30 min; no further surface transformations occurred after establishment of the Cu(100) surface. The results may help explain the Cu(100)-like behavior of Cu(pc) in terms of CO2RR product selectivity. They likewise suggest that products exclusive to Cu(100) single-crystal electrodes may be generated through the use of readily available inexpensive polycrystalline Cu electrodes. The study highlights the dynamic nature of heterogeneous electrocatalyst surfaces and also underscores the importance of operando interrogations when structure-composition-reactivity correlations are intended.

Sub-pocket-focused designing of tacrine derivatives as potential acetylcholinesterase inhibitors.

Human acetylcholinesterase (hAChE) has a potential role in the management of acetylcholine, one of the neurotransmitters that modulate the overall activity of cholinergic system, AChE inhibitors have a greater impact in the therapeutics. Though the atomic structure of hAChE has been extensively studied, the precise active site geometry upon binding to different ligands are yet to be explored. In the present study, an extensive structural analysis of our recently reported hAChE-tacrine complex has carried out and revealed the presence of two prominent sub-pockets located at the vicinity of the hAChE active site. Structural bioinformatics assisted studies designed 132 putative sub-pockets focused tacrine derivatives (SPFTDs), their molecular docking, free energy estimations revealed that they are stronger than tacrine in terms of binding affinity. Our in vitro studies also supported the in silico findings, all these SPFTDs are having better potencies than tacrine. Cytotoxic nature of these SPFTDs on HepG2 and Neuro-2a cell lines, diminishes the possibilities for future in vivo studies. However, the identification of these sub pockets and the SPFTDs paved a new way to the future drug discovery especially since AChE is one of the promising and approved drug targets in treatment of AD drug discovery.

Intranasal administration of insulin lowers amyloid-beta levels in rat model of diabetes.

Alzheimer's disease (AD) is a neurodegenerative disorder characterized by abnormal accumulation of amyloid beta (A beta) peptide in brain regions subserving memory and other cognitive functions. Hyperglycemia and perturbed insulin signaling have been proposed as pathogenic factors contributing to AD. The aim of the present study is to validate the use of streptozotocin (STZ) injected rats as an experimental model of AD. Using this model, the effect of intranasal administration of insulin on reduction of A beta levels was measured. The current findings strengthen the case for insulin as therapy for AD afflicted individuals with or without diabetes.

Utility of TSH Receptor Antibodies in the Differential Diagnosis of Hyperthyroidism in Clinical Practice.

Graves' disease (GD) is the most common cause of hyperthyroidism in iodine-sufficient areas. It is important to distinguish GD from other causes of hyperthyroidism for optimal management. Thyroid stimulating hormone receptor antibody (TRAb) test is a commonly used test for this purpose. However, the sensitivity for this test in routine clinical practice may be affected by various factors leading to fallacies in diagnosis. Materials and Methods: A retrospective study was performed to assess the utility of an automated electrochemiluminescence TRAb immunoassay (Roche) in differentiating GD from non-Graves' disease (NGD) in routine clinical practice. Results: In 227 subjects, 146 had GD and 81 had NGD. Total T3, Total T4, Free T4, and TRAb were significantly higher in people with GD in comparison to NGD. The area under the receiver operating characteristics (ROC) curve for the assay was 0.96 (95% CI: 0.926 to 0.984, P < 0.0001). The optimal threshold for the test derived from the ROC was 3.37 IU/L, which is more than the cut-off of 1.75 IU/L suggested by the manufacturer. The sensitivity/specificity of TRAb in the diagnosis of GD at presentation was 98.4%/62.9% at 1.75 IU/L and 91.2%/90.12% at 3.37 IU/L, respectively. Conclusion: The TRAb test is a sensitive test to differentiate between subjects with GD and NGD presenting with hyperthyroidism. However, the cutoff (1.75 IU/L) as per the kit manufacturer may lead to a lower specificity for diagnosis. A modified cut-off of 3.37 IU/L should be considered for optimizing the diagnostic efficacy of the test.

Role and importance of high fiber in diabetes management in India.

BACKGROUND & AIMS: India is facing a triple burden of pre-diabetes, diabetes, and obesity. Unhealthy eating habits and physical inactivity have been linked to the onset and progression of type 2 diabetes mellitus (T2DM). Despite dietary recommendations, individuals consume inadequate amounts or unsuitable type of dietary fiber (DF) which needs correction. An Expert group attempted to review and report on the role and importance of high DF in the management of T2DM and offer practical guidance on high fiber use in daily diet. METHODOLOGY: Twelve diabetologists and two expert dietitians from India were chosen to ensure diversity of the members both in professional interest and cultural background. The authors convened virtually for one group meeting and actively participated in a detailed discussion. Multiple reviews of the draft document followed by focused teleconference calls & email helped to reach consensus on final recommendations between Aug 2021 and Dec 2021. RESULTS: Evidence has shown that medical nutrition therapy (MNT) is a valuable approach and an essential component of T2DM prevention and management. Studies have shown that fiber rich diabetes nutrition (FDN) has multi-systemic health benefits, including, improvement in glycemic control, reduction in glucose spikes, decrease in hyperinsulinemia, improvement in plasma lipid concentrations and weight management in T2DM patients. CONCLUSION: A high fiber diet is vital for people with diabetes and associated conditions. Increasing fiber intake, preferably through food or through dietary supplement, may help. Fiber rich diabetes nutrition (FDN) is recommended in order to prevent and manage T2DM.

Cardiovascular risk in newly diagnosed type 2 diabetes patients in India.

BACKGROUND: Type 2 diabetes mellitus (T2DM) worldwide continues to increase, in particular in India. Early T2DM diagnosis followed by appropriate management will result in more cardiovascular event free life years. However, knowledge of the cardiovascular profile of newly diagnosed T2DM patients is still limited. The aim of this study was to understand the extent of cardiovascular disease (CVD) risk of newly diagnosed T2DM patients in India. METHODS: A cross sectional observational study was conducted to evaluate clinical laboratory and socio-demographic parameters of 5,080 newly diagnosed T2DM patients (48.3 ± 12.8 years of age; 36.7% female). In addition, we determined their cardiovascular risk according to the guidelines of the Lipid Association of India (LAI) and the criteria of the QRISK3 score. RESULTS: Of the newly T2DM diagnosed patients in India 2,007(39.5%) were classified as "High risk" and 3,073 (60.5%) were classified as "Very high risk" based on LAI criteria. On average, patients had 1.7 ± 0.9 major atherosclerotic cardiovascular disease (ASCVD) risk factors. Low HDL-C value was the most frequent major risk (2,823; 55.6%) followed by high age (2,502; 49.3%), hypertension (2,141; 42.1%), smoking/tobacco use (1,078; 21.2%) and chronic kidney disease stage 3b or higher (568; 11.2%). In addition, 4,192 (82.5%) patients appeared to have at least one cholesterol abnormality and, if the latest LAI recommendations are applied, 96.5% (4,902) presented with lipid values above recommended targets. Based on the QRISK3 calculation Indian diabetes patients had an average CVD risk of 15.3 ± 12.3%, (12.2 ± 10.1 vs. 17.1 ± 13.5 [p<0.001] for females and males, respectively). CONCLUSIONS: Newly diagnosed Indian T2DM patients are at high ASCVD risk. Our data therefore support the notion that further extension of nationwide ASCVD risk identification programs and prevention strategies to reduce the occurrence of cardiovascular diseases are warranted.

Basal insulin analogues--a review of recent data on efficacy and safety.

Conventional basal insulin preparations have to be resuspended prior to injection and have low therapeutic efficacy and drawbacks like nocturnal hypoglycaemia. There is evidence supporting improved pharmacokinetic and pharmacodynamic profiles of basal insulin analogues, glargine and detemir as compared with NPH. Initiation and titration of basal insulin analogues helps patients to improve compliance due to low injection frequency compared to the conventional basal insulin. The unique protraction mechanism adds advantage to insulin detemir in terms of high predictability. Also these analogues have better patient adherence, improved quality of life and higher treatment satisfaction. So basal insulin analogues particularly are better treatment options for treatment of diabetes.

Testosterone replacement therapy in men with type 2 diabetes mellitus and functional hypogonadism -an Integrated Diabetes and Endocrine Academy (IDEA) consensus guideline.

BACKGROUND: Though testosterone replacement therapy in men with organic hypogonadism is established, its role in men with type 2 diabetes mellitus (T2DM) and functional hypogonadism is unclear. METHODS: Thirteen experts addressed ten topic-specific questions after an in-depth review of literature, where all relevant issues were critically evaluated. RESULTS: Ten recommendations concerning diagnosis and management of men with T2DM and functional hypogonadism have been put forward. CONCLUSION: Routine measurement of serum testosterone in all, and inappropriate replacement of testosterone in asymptomatic T2DM men with functional hypogonadism and borderline low serum testosterone values, is not recommended.

Cardiometabolic vigilance in COVID-19 and resource husbandry in resource-challenged times: Clinical practice- based expert opinion.

BACKGROUND AND AIMS: The ongoing pandemic of coronavirus disease 2019 (COVID-19) is rapidly evolving, thereby posing a profound challenge to the global healthcare system. Cardiometabolic disorders are associated with poor clinical outcomes in persons with COVID-19. Healthcare challenges during the COVID-19 pandemic are linked to resource constraints including shortage of Personal Protective Equipment's (PPE), laboratory tests and medication. In this context, a group of clinical experts discussed the endocrine and cardiology vigilance required in times of COVID-19. Further, the group proposed certain resource husbandry recommendations to be followed during the pandemic to overcome the constraints. METHOD: The clinical experts discussed and provided their inputs virtually. The expert panel included clinical experts comprising endocrinologists, Consultant Physicians and cardiologists from India. The panel thoroughly reviewed existing literature on the subject and proposed expert opinion. RESULTS: The expert panel put forward clinical practice-based opinion for the management of cardiometabolic conditions including diabetes mellitus and hypertension. As these conditions are associated with poor clinical outcomes, the expert panel recommends that these persons be extra-cautious and take necessary precautions during the ongoing pandemic. Further, experts also provided appropriate, affordable, available and accessible solution to the resource constraint situations in times of COVID-19 pandemic. CONCLUSION: The clinical expert opinion put forward in this article will serve as a reference for clinicians treating diabetes and cardiovascular disease during the COVID-19 pandemic.

Design and development of non-fibrillar amyloid beta as a potential Alzheimer vaccine.

Alzheimer's disease (AD) is the most common cause of dementia affecting the elderly. Treatment for effective cure of this complex neurodegenerative disease does not yet exist. In AD, otherwise soluble, monomeric form of amyloid beta (Abeta) peptide converts into toxic, fibrillar form rich in beta-sheet content. Several immunological approaches that prevent this conversion of Abeta into pathological form or that accelerate its clearance are being actively pursued worldwide. As part of these attempts, we report here, the design and characterization of a non-amyloidogenic homologue of Abeta (Abeta-KEK). We demonstrate that this peptide is helical in nature and retains the immunoneutralizing epitopes of native Abeta. More importantly, Fab fragments of the polyclonal anti-Abeta-KEK antibodies interfere with formation of Abeta fibrils as well as dissociate the preformed Abeta aggregates in vitro. These results suggest that non-amyloidogenic Abeta-KEK may serve as a safer alternative vaccine for Alzheimer's disease.

Diagnostic efficacy of midnight cortisol and midnight ACTH in the diagnosis and localisation of Cushing's syndrome.

Classical tests for diagnosis of Cushing's syndrome (CS) like urine free cortisol and dexamethasone suppression tests have limitations in various clinical settings. This study evaluated the usefulness of sleeping midnight serum cortisol (SMNC) as a diagnostic test for hypercortisolemia. A simultaneously done midnight plasma ACTH level was used to classify the disease as ACTH dependent or independent. Standard biochemical tests, SMNC, midnight plasma ACTH and appropriate imaging evaluated patients with a clinical suspicion of Cushing's syndrome. We evaluated 43 patients with CS comprising of 34 patients with Cushing's disease (CD), 2 patients with thymic carcinoid producing ectopic CS, 5 patients with adrenal carcinoma and 2 with adrenal adenoma. Thirteen patients with clinical suspicion were also evaluated with the above tests and CS was ruled out. SMNC, midnight plasma ACTH and dexamethasone suppressed cortisol was collected from patients with a suspicion of CS. SMNC was evaluated against histopathology as the gold standard. SMNC achieved 100% sensitivity in the diagnosis of endogenous CS at cut offs of 138 nmol/l and below. Raising the cut off to 207 nmol/l resulted in a test sensitivity of 90.5%. At a cut off of 1.65 pmol/l, midnight plasma ACTH could distinguish ACTH independent causes of CS with 100% sensitivity. We concluded that a single midnight collection could identify all patients with CS and classify the ACTH status at the proposed cut offs.