Role of Teplizumab, a Humanized Anti-CD3 Monoclonal Antibody, in Managing Newly Diagnosed Type 1 Diabetes: An Updated Systematic Review and Meta-Analysis.

OBJECTIVE: Teplizumab has emerged as a potential disease-modifying drug in type 1 diabetes (T1D). This meta-analysis sought to summarize the therapeutic effect of teplizumab in newly diagnosed patients with T1D. METHODS: Randomized controlled trials involving patients with T1D receiving teplizumab in the intervention arm and placebo (or no active intervention) in the control arm were searched throughout the electronic databases. The primary outcome was the change in area under the curve of C-peptide levels from baseline. RESULTS: Seven reports from 6 studies involving 834 subjects met the inclusion criteria. Compared to teplizumab, greater reductions in area under the curve of C-peptide from the baseline values were observed in the control group after 6 months (mean difference [MD] 0.07 nmol/L [0.01, 0.13], P = .02), after 12 months (MD 0.07 nmol/L [0.04, 0.11], P = .0001), after 18 months (MD 0.10 nmol/L [0.06, 0.14], P < .00001), and after 24 months (MD 0.07 nmol/L [0.01, 0.14], P = .03) of interventions. Moreover, fewer patients treated with teplizumab had a decreased C-peptide response after 6 months (odds ratio [OR] 0.21), after 12 months (OR 0.17), after 18 months (OR 0.30), and after 24 months (OR 0.12) of treatment. The preservation of endogenous insulin production was supported by reduced use of exogenous insulin with maintenance of comparable glycemic control for up to 18 months post-treatment. Teplizumab imparted higher risks of grade 3 or higher adverse events, adverse events leading to study medication discontinuation, nausea, rash, and lymphopenia. CONCLUSION: The results of the meta-analysis support teplizumab as a promising disease-modifying therapy for newly diagnosed T1D.

Fostering Excellence in Endocrinology Research: The Inaugural Edition of the Yuvaratna Awards of the Endocrine Society of India.

The Endocrine Society of India (ESI) has introduced a new award, the Yuvaratna Awards, for recognizing the best research conducted by recently graduated endocrinologists across the country. This research should be carried out independently and not as part of or as a continuation of work initiated during residency. Two distinct categories were established: one for individuals working in academic institutions and another for those employed in private hospitals. This distinction acknowledges the unique benefits and challenges faced in both settings. This initiative serves as an excellent means to foster and promote research enthusiasm among young endocrinologists. This article elaborates on our firsthand experience as participants in the inaugural session of this award and delves into how it influenced our motivation for further research.

Growth hormone therapy is associated with improved uterine dimensions in girls with Turner syndrome prior to oestrogen replacement.

BACKGROUND: Adult women with Turner syndrome (TS) have high rates of miscarriage, presumably due to the abnormal size and shape of the uterus. There is a paucity of data regarding the determinants of uterine volume (UtVol) in young girls with TS before the initiation of oestrogen replacement therapy (ERT). METHODS: We performed a cross-sectional study on premenarchal girls with TS, aged 5-15 years, pubertal stage B1-B3, not having received ERT (n = 73) and 50 age-matched healthy controls. Anthropometric parameters and a history of growth hormone (GH) therapy (≥1 year) were noted. Uterine length (UtL), UtVol, and mean-ovarian-volume (MOV) standard-deviation scores (SDS) were determined from transabdominal ultrasonography data. RESULTS: Girls with TS had lower median UtVol-SDS (-1.07 vs. 0.86; p < .001), UtL-SDS (-3.72 vs. -0.41; p < .001) and MOV-SDS (-5.53 vs. 1.96; p < .001) compared to age-matched controls. Among TS girls, recipients of GH (n = 38) had higher UtVol-SDS (-0.63 vs. -1.39; p = .0001), UtL-SDS (-1.73 vs. -6.49; p < .0001) but similar MOV-SDS compared to nonrecipients (n = 35). Those with normal uterine volume for age (NUVA, n = 29) had earlier initiation (7.8 vs. 9.3 years; p = .03) and a longer duration of GH (3.71 vs. 2.14 years; p = .002) than those with low UtVol for age (n = 44). UtVol-SDS correlated with duration of GH (ρ = 0.411, p = .01) and negatively with age at GH initiation (ρ = -0.479, p = .003). In a model adjusted for pubertal status, karyotype and height-SDS, GH use could independently predict having NUVA (odds ratio: 5.09, confidence interval: 1.63-15.94, p = .005). CONCLUSION: GH therapy has a stimulatory effect on uterine dimensions in pre-and peripubertal girls with TS. Earlier initiation and longer duration of GH is important in TS girls before ERT.

Hyperprolactinemia Due to Prolactinoma has an Adverse Impact on Bone Health with Predominant Impact on Trabecular Bone: A Systematic Review and Meta-Analysis.

BACKGROUND: No meta-analysis has holistically analysed and summarized the effect of prolactin excess due to prolactinomas on bone mineral metabolism. We undertook this meta-analysis to address this knowledge-gap. METHODS: Electronic databases were searched for studies having patients with hyperprolactinemia due to prolactinoma and the other being a matched control group. The primary outcome was to evaluate the differences in BMD Z-scores at different sites. The secondary outcomes of this study were to evaluate the alterations in bone mineral density, bone mineral content and the occurrence of fragility fractures. RESULTS: Data from 4 studies involving 437 individuals was analysed to find out the impact of prolactinoma on bone mineral metabolism. Individuals with prolactinoma had significantly lower Z scores at the lumbar spine [MD -1.08 (95 % CI: -1.57 - -0.59); P < 0.0001; I2 = 54 % (moderate heterogeneity)] but not at the femur neck [MD -1.31 (95 % CI: -3.07 - 0.45); P = 0.15; I2 = 98 % (high heterogeneity)] as compared to controls. Trabecular thickness of the radius [MD -0.01 (95 % CI: -0.02 - -0.00); P = 0.0006], tibia [MD -0.01 (95 % CI: -0.02 - -0.00); P=0.03] and cortical thickness of the radius [MD -0.01 (95 % CI: -0.19 - -0.00); P = 0.04] was significantly lower in patients with prolactinoma as compared to controls. The occurrence of fractures was significantly higher in patients with prolactinoma as compared to controls [OR 3.21 (95 % CI: 1.64 - 6.26); P = 0.0006] Conclusion: Bone mass is adversely affected in patients with hyperprolactinemia due to prolactinoma with predominant effects on the trabecular bone.

Abnormal Body Composition Increases the Cardiometabolic Risk in Adolescents and Young Adults With Turner Syndrome.

OBJECTIVE: To determine the cardiometabolic risk of adolescents and adults with Turner syndrome (TS) and whether and how anthropometry and body composition predict this risk. METHODS: We compared the anthropometric, biochemical, and dual-energy x-ray absorptiometry-derived body composition parameters of 103 girls and women with TS aged 12 to 30 years and 103 controls of the same age and body mass index: (1) between TS with and without metabolic syndrome (MetS), (2) between the different karyotypes of TS, and (3) between growth hormone recipients and nonrecipients. RESULTS: Individuals with TS had higher prevalence rates of truncal obesity (57.2%), MetS (37.9%), prediabetes (20.4%), dyslipidemia (73.8%), hypertension (9.7%), and hepatic steatosis (15.5%) and a greater total body fat percentage (38.43% vs 34.26%) and fat mass index (9.15 vs 6.71 kg/m2) but a lower lean mass index (11.05 vs 12.49 kg/m2) than controls (P <.001). Individuals with TS and MetS (n = 39) had a higher total body fat percentage (41.74% vs 36.42%, P <.0001), truncal fat percentage (44.66% vs 36.09%, P <.0001), and visceral adipose tissue mass (495.57 vs 276 g, P <.0001) than those with TS but without MetS. Those with classic TS (45,X) had a higher prevalence of prediabetes (32.6% vs 10.5%, P =.01). Growth hormone recipients had a lower prevalence of MetS and lesser truncal obesity. Altered body composition was significantly correlated with metabolic risk. The truncal fat percentage independently predicted MetS (odds ratio, 1.12; 95% confidence interval, 1.003-1.24; P =.04). Waist circumference and waist-hip ratio predicted metabolic risk with good sensitivity and specificity. CONCLUSION: Adverse cardiometabolic risk and altered body composition start early in life in TS. Postpubertal women with TS should be routinely assessed for truncal obesity, dysglycemia, dyslipidemia, and liver steatosis, irrespective of body mass index and karyotype.

PURsuit of Endocrinology (PURE): A National Survey among First-Year Endocrinology Residents Across India.

Background: Endocrinology has been a popular choice of super-specialisation in India in recent years. The PURsuit of Endocrinology (PURE) survey aims to determine the factors that facilitated the selection of endocrinology as the area of super-specialisation among first-year residents across India. Methods: We conducted an electronic questionnaire-based survey among first-year residents across India. The questionnaire evaluated the respondents' demographics, feeder speciality, challenges during preparation, factors influencing endocrinology as a career preference, unappealing aspects of the subject and future career plans. Results: A total of 81 (43 males and 38 females) responses were recorded. The mean age was 31.3 ± 3.3 years, with 63% married. Internal medicine was the feeder speciality in 92.5% of cases. Work-life balance was the critical consideration for pursuing endocrinology in 91.4%, followed by professional satisfaction (64.2%) and the scope of having a solo practice (43.2%). Interestingly, there was less emphasis on monetary satisfaction (12.3%). Almost half of the respondents intended to practice in a government academic institution (46.9%) or in an independent set-up (45.7%). Conclusions: The PURE survey suggests that work-life balance and professional satisfaction are the key driving factors behind the choice of endocrinology. An increasing interest among the residents to join as faculty in academic institutions, apart from having self-owned private clinics, is a welcome finding.

Prevalence and Predictors of Prediabetes in Adolescents and Young Adults with Turner Syndrome: A Cross-Sectional Study from Eastern India.

Background: Individuals with Turner syndrome (TS) have a high risk for prediabetes/type 2 Diabetes Mellitus (T2DM). There is scarce data regarding risk factors for prediabetes in TS, specially from South Asia. Methods: We conducted a cross-sectional study on girls with TS aged 12-30 years who had achieved pubertal stage B3 and above-spontaneously or with oestrogen. Anthropometric measurements and biochemical tests were conducted, and medical records were reviewed for details about pubertal onset and progression, growth hormone (GH) and oestrogen therapy. Results: Out of 129 patients with TS in our database, 99 met the criteria for inclusion, mean age 18.33+/-3.78 years and mean BMI 20.57+/- 3.71 kg/m2. Prevalence of prediabetes was 23.23%. Plasma-glucose measured after 75 g-oral-anhydrous-glucose-load (OGTT-PPG) identified five additional prediabetes cases, who had normal fasting plasma glucose (FPG) or HbA1c%. Compared to those without prediabetes, TS with prediabetes (n = 23) had higher mean body weight, BMI, waist circumference (WC) [42.02+/- 5.83 vs 36.22+/-8.07, 22.77+/-2.78 vs 19.91+/- 3.72, 85.26+/- 3.52 vs 81.08+/- 4.59, pall < 0.03 ], higher median WC-to-height ratio (WHtR) and WC-to-hip ratio (WHR)((0.64 [0.6-0.69] vs 0.59[0.56- 0.66], 0.9[0.84-1.12] vs 0.85[0.75-1.01], pboth < 0.02), and higher LDL-cholesterol, triglycerides, and greater prevalence of hepatosteatosis (47.1% vs 21.1%, P < 0.01). Among GH recipients (n = 36), those with prediabetes had delayed initiation and shorter duration of GH therapy. There were no differences in cardiometabolic parameters or the prevalence of diabetes between different karyotypic variants of TS. BMI, WC and WHR had significant positive correlation with FBG, OGTT-PPG and HbA1c% (pall < 0.004). Delay in oestrogen initiation had a significant correlation with OGTT-PPG (Spearman's-rho = 0.69, P < 0.004). BMI, WHR and pubertal status were independent predictors for prediabetes (OR: 1.27 [1.03-1.57]), 1.18 [1.04-1.34]) and 0.09[0.02-0.38], respectively, pall < 0.02), but karyotype was not. BMI had the highest sensitivity [cut-off: 21.04 kg/m2 (sensitivity: 82.6%, specificity: 62.2%) and WHR had the highest specificity [cut-off: 0.89 (sensitivity: 73.9%, specificity 78.4%)] for predicting prediabetes. Conclusion: Indian girls with TS have a high risk for prediabetes, irrespective of underlying karyotype and should be screened with oral glucose challenge to identify prediabetes. Timely intervention against central obesity and early initiation of GH and oestrogen should be ensured in TS. Late presenting girls should be closely monitored for dysglycaemia before and during treatment with GH and/or oestrogen.

Subacute thyroiditis following recovery from COVID-19 infection: novel clinical findings from an Eastern Indian cohort.

OBJECTIVE: Recent reports have suggested a link between COVID-19 infection and subacute thyroiditis (SAT). We aimed to describe variations in clinical and biochemical parameters in patients developing post-COVID SAT. DESIGN: Ours was a combined retrospective-prospective study on patients presenting with SAT within 3 months of recovery from COVID-19 infection, who were subsequently followed up for a further 6 months since diagnosis of SAT. RESULTS: Out of 670 patients with COVID-19, 11 patients presented with post-COVID-19 SAT (6.8%). Those with painless SAT (PLSAT, n = 5) presented earlier, had more severe thyrotoxic manifestations and exhibited higher C-reactive protein, interleukin 6 (IL-6), neutrophil-lymphocyte ratio and lower absolute lymphocyte count than those with painful SAT (PFSAT, n = 6). There were significant correlations of total and free T4 and total and free T3 levels with serum IL-6 levels (pall <0.04). No differences were observed between patients with post-COVID SAT presenting during the first and second waves. Oral glucocorticoids were needed for symptomatic relief in 66.67% of patients with PFSAT. At 6 months of follow-up, majority (n = 9, 82%) achieved euthyroidism, while subclinical and overt hypothyroidism were found in one patient each. CONCLUSIONS: Ours is the largest single-centre cohort of post-COVID-19 SAT reported until, demonstrating two distinct clinical presentations-without and with neck pain-depending on time elapsed since COVID-19 diagnosis. Persistent lymphopaenia during the immediate post-COVID recovery period could be a key driver of early,painless SAT. Close monitoring of thyroid functions for at least 6 months is warranted in all cases.

Turner Syndrome and Neurofibromatosis 1: Rare Co-Existence with Important Clinical Implications.

A 16.5-year-old Indian female presented with secondary amenorrhoea, cubitus valgus, scoliosis and multiple lentigines on the face. Karyotyping revealed mosaic Turner syndrome (TS) with 45, X/46, X iXq. She also had multiple café-au-lait macules and axillary freckles but no neurofibroma and did not fulfil the classic criteria for diagnosis of Neurofibromatosis-1 (NF1). Many of her macules were smaller than 15 mm in diameter, which might be due to her hypoestrogenic state. However, exome-sequencing found a pathologic variant consistent with NF1. She was started on daily oral estrogen, and oral progesterone for 10 days every month with close monitoring for neurofibroma and/or glioma expansion. Co-occurrence of NF1 and TS is extremely rare, TS and NF1 can both affect growth and puberty, cause different cutaneous and skeletal deformities, hypertension, vasculopathy and learning disabilities. Our case highlights the need for genetic testing in some cases with NF1 who do not strictly fulfil the NIH diagnostic criteria. We also emphasize the need for close monitoring during therapy with growth hormone, estrogen and progesterone due to the potential risk of tumour expansion in NF1.

Diagnostic approach in 46, XY DSD: an endocrine society of bengal (ESB) consensus statement.

OBJECTIVES: 46, XY difference/disorder of sex development (DSD) is a relatively uncommon group of heterogeneous disorders with varying degree of underandrogenization of male genitalia. Such patients should be approached systematically to reach an aetiological diagnosis. However, we lack, at present, a clinical practice guideline on diagnostic approach in 46, XY DSD from this part of the globe. Moreover, debate persists regarding the timing and cut-offs of different hormonal tests, performed in these cases. The consensus committee consisting of 34 highly experienced endocrinologists with interest and experience in managing DSD discussed and drafted a consensus statement on the diagnostic approach to 46, XY DSD focussing on relevant history, clinical examination, biochemical evaluation, imaging and genetic analysis. CONTENT: The consensus was guided by systematic reviews of existing literature followed by discussion. An initial draft was prepared and distributed among the members. The members provided their scientific inputs, and all the relevant suggestions were incorporated. The final draft was approved by the committee members. SUMMARY: The diagnostic approach in 46, XY DSD should be multidisciplinary although coordinated by an experienced endocrinologist. We recommend formal Karyotyping, even if Y chromosome material has been detected by other methods. Meticulous history taking and thorough head-to-toe examination should initially be performed with focus on external genitalia, including location of gonads. Decision regarding hormonal and other biochemical investigations should be made according to the age and interpreted according to age-appropriate norms Although LC-MS/MS is the preferred mode of steroid hormone measurements, immunoassays, which are widely available and less expensive, are acceptable alternatives. All patients with 46, XY DSD should undergo abdominopelvic ultrasonography by a trained radiologist. MRI of the abdomen and/or laparoscopy may be used to demonstrate the Mullerian structure and/or to localize the gonads. Genetic studies, which include copy number variation (CNV) or molecular testing of a candidate gene or next generation sequencing then should be ordered in a stepwise manner depending on the clinical, biochemical, hormonal, and radiological findings. OUTLOOK: The members of the committee believe that patients with 46, XY DSD need to be approached systematically. The proposed diagnostic algorithm, provided in the consensus statement, is cost effective and when supplemented with appropriate genetic studies, may help to reach an aetiological diagnosis in majority of such cases.

Monitoring Endocrine Nursing in South Asia (MENSA).

Background: South Asian countries face the colossal challenge of tackling the massive burden of diabetes and other endocrine disorders. These patients grossly outnumber the specialists trained to deal with these conditions. A trained cadre of diabetes specialist nurses (DSN) and endocrine specialist nurses (ESN) might help bridge this gap. Exploring the perception of DSN/ESN among South Asian doctors will help to understand their role, responsibilities and future prospects. Methods: One hundred and seventy-four endocrinologists from South Asia participated in an online survey on their perception of DSNs and ESNs. Results: Out of the 174 respondents, 61 (35%) were currently working with DSN/ESN, 79 (45.4%) had worked in the past and 131 (75.2%) were willing to start recruiting or employ additional DSN/ESN in the future. The majority considered that the primary function of DSN and ESN is to educate on diabetes (n = 86, 96.6%) and endocrine disorders (n = 34, 57.6%), respectively, followed by anthropometry and initial work-up. Only a small minority felt they could write independent follow-up prescriptions (nurse-led clinics) [DSN - 16 (18%) and ESN - 3 (5.1%)]. Graduation with a certificate course in diabetes and basic endocrinology was considered a sufficient qualification by 68 (39.1%) respondents. Endocrinologists from countries other than India were more willing to recruit ESN/DSN in the future (89.7% vs 72.4%; P < 0.03) and approve a nurse-led clinic (62.1% vs 29.7%; P < 0.03). Upon multiple logistic regression, working in countries other than India was an independent predictor of future willingness to work with DSN/ESN (odds ratio (OR): 4.48, 95% confidence interval (CI) 1.09-18.43, P = 0.03). Conclusion: DSN and ESN could facilitate the management of healthcare-seekers with diabetes and endocrine disorders. A certification course to train nurses on diabetes and basic endocrine disorders following graduation could be helpful. Major hindrances in creating a regular cadre of DSN/ESN were limited opportunities for career progression and lack of additional remuneration for services.

Stress hyperglycemia ratio, rather than admission blood glucose, predicts in-hospital mortality and adverse outcomes in moderate-to severe COVID-19 patients, irrespective of pre-existing glycemic status.

AIM: To compare admission-blood-glucose (ABG) or stress-hyperglycemia-ratio (SHR) performs better in predicting mortality and worse outcomes in COVID-19 patients with (DM) and without known Type 2 Diabetes Mellitus (UDM). METHODS: ABG and SHR were tested for 451 patients with moderate-severe COVID-19 infection [DM = 216,47.9%; pre-diabetes = 48,10.6%, UDM = 187,41.4%],who were followed-up to look for in-hospital-mortality (primary outcome) and secondary outcomes (ICU stay or mechanical ventilation, hospital-acquired-sepsis and multiple organ dysfunction syndrome [MODS]). Those with and without SHR ≥ 1.14 were compared; logistic regression was done to identify predictors of outcomes, with subgroup analysis based on pre-existing DM status and COVID-19 severity. RESULTS: Those who died (n = 131) or developed ≥ 1 secondary outcomes (n = 218) had higher prevalence of SHR ≥ 1.14, ABG ≥ 180 mg/dl and higher median SHR (pall < 0.01). Those with SHR ≥ 1.14 had higher mortality (53.7%), higher incidence of ≥ 1 secondary outcomes (71.3%) irrespective of pre-existing diabetes status. SHR ≥ 1.14, but not ABG ≥ 180 was an independent predictor of mortality in the whole group (OR: 7.81,4.07-14.98), as also the DM (OR:10.51,4.34-25.45) and UDM (5.40 (1.57-18.55) subgroups. SHR ≥ 1.14 [OR: 4.41 (2.49-7.84)] but not ABG ≥ 180 could independently predict secondary outcomes AUROC of SHR in predicting mortality was significantly higher than ABG in all subgroups. CONCLUSION: SHR better predicts mortality and adverse outcomes than ABG in patients with COVID-19, irrespective of pre-existing chronic glycemic status.

Characterizing progressive beta-cell recovery after new-onset DKA in COVID-19 provoked A-ß+ KPD (ketosis-prone diabetes): A prospective study from Eastern India.

BACKGROUND: Recent literature suggests a bi-directional relationship between COVID-19 infection and diabetes mellitus, with an increasing number of previously normoglycemic adults with COVID-19 being admitted with new-onset diabetic ketoacidosis (DKA). However, the possibility of COVID-19 being a potential trigger for A-ß + ketosis-prone diabetes (KPD) in these patients needs elucidation. Our study aimed at analyzing such a cohort of patients and determining their natural course of ß-cell recovery on serial follow-up. METHODS: After initial screening, n = 42 previously non-diabetic patients with new-onset DKA and RT-PCR positive COVID-19, were included in our ten-month follow-up study. Of these, n = 22 were negative (suspected A-ß + KPD) and n = 20 were positive (Type 1A DM) for autoantibodies (GAD/IA-2/ZnT8). Subsequently, n = 19 suspected KPD and n = 18 Type 1A DM patients were followed-up over ten months with serial assessments of clinical, biochemical and ß-cell secretion. Amongst the former, n = 15 (79%) patients achieved insulin independence, while n = 4 (21%) continued to require insulin at ten-months follow-up. RESULTS: On comparison, the suspected KPD patients showed significantly greater BMI, age, Hba1c, IL-6 and worse DKA parameters at presentation. Serial C-peptide estimations demonstrated significant ß-cell recovery in KPD group, with complete recovery seen in the 15 patients who became insulin independent on follow-up. Younger age, lower BMI, initial severity of DKA and inflammation (IL-6 levels), along-with reduced 25-hydroxy-Vitamin-D levels were associated with poorer recovery of ß-cell secretion at ten-month follow-up amongst the KPD patients, CONCLUSIONS: This is the first prospective study to demonstrate progressive recovery of ß-cell secretion in new-onset A-ß + KPD provoked by COVID-19 infection in Indian adults, with a distinctly different profile from Type 1A DM. Given their significant potential for ß-cell recovery, meticulous follow-up involving C-peptide estimations can help guide treatment and avoid injudicious use of insulin.

A trimodular family 16 glycoside hydrolase from the cellulosome of Ruminococcus flavefaciens displays highly specific licheninase (EC 3.2.1.73) activity.

Cellulosomes are highly complex cell-bound multi-enzymatic nanomachines used by anaerobes to break down plant carbohydrates. The genome sequence of Ruminococcus flavefaciens revealed a remarkably diverse cellulosome composed of more than 200 cellulosomal enzymes. Here we provide a detailed biochemical characterization of a highly elaborate R. flavefaciens cellulosomal enzyme containing an N-terminal dockerin module, which anchors the enzyme into the multi-enzyme complex through binding of cohesins located in non-catalytic cell-bound scaffoldins, and three tandemly repeated family 16 glycoside hydrolase (GH16) catalytic domains. The DNA sequence encoding the three homologous catalytic domains was cloned and hyper-expressed in Escherichia coli BL21 (DE3) cells. SDS-PAGE analysis of purified His6 tag containing RfGH16_21 showed a single soluble protein of molecular size ~89 kDa, which was in agreement with the theoretical size, 89.3 kDa. The enzyme RfGH16_21 exhibited activity over a wide pH range (pH 5.0-8.0) and a broad temperature range (50-70 °C), displaying maximum activity at an optimum pH of 7.0 and optimum temperature of 55 °C. Substrate specificity analysis of RfGH16_21 revealed maximum activity against barley ß-d-glucan (257 U mg-1) followed by lichenan (247 U mg-1), but did not show significant activity towards other tested polysaccharides, suggesting that it is specifically a ß-1,3-1,4-endoglucanase. TLC analysis revealed that RfGH16_21 hydrolyses barley ß-d-glucan to cellotriose, cellotetraose and a higher degree of polymerization of gluco-oligosaccharides indicating an endo-acting catalytic mechanism. This study revealed a fairly high, active and thermostable bacterial endo-glucanase which may find considerable biotechnological potentials.

Critical review of bone health, fracture risk and management of bone fragility in diabetes mellitus.

The risk of fracture is increased in both type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM). However, in contrast to the former, patients with T2DM usually possess higher bone mineral density. Thus, there is a considerable difference in the pathophysiological basis of poor bone health between the two types of diabetes. Impaired bone strength due to poor bone microarchitecture and low bone turnover along with increased risk of fall are among the major factors behind elevated fracture risk. Moreover, some antidiabetic medications further enhance the fragility of the bone. On the other hand, antiosteoporosis medications can affect the glucose homeostasis in these patients. It is also difficult to predict the fracture risk in these patients because conventional tools such as bone mineral density and Fracture Risk Assessment Tool score assessment can underestimate the risk. Evidence-based recommendations for risk evaluation and management of poor bone health in diabetes are sparse in the literature. With the advancement in imaging technology, newer modalities are available to evaluate the bone quality and risk assessment in patients with diabetes. The purpose of this review is to explore the pathophysiology behind poor bone health in diabetic patients. Approach to the fracture risk evaluation in both T1DM and T2DM as well as the pragmatic use and efficacy of the available treatment options have been discussed in depth.

Predictors of new-onset diabetic ketoacidosis in patients with moderate to severe COVID-19 receiving parenteral glucocorticoids: A prospective single-centre study among Indian type 2 diabetes patients.

BACKGROUND AND AIM: COVID-19 infection predisposes to diabetic ketoacidosis(DKA); whether glucocorticoids enhances this risk is unknown.We aimed to study the occurrence of DKA after initiating glucocorticoids in patients with type 2 diabetes mellitus(T2DM) and moderate-to-severe COVID-19, and identify predictors for it. METHODS: Patients with T2DM and moderate or severe COVID-19 infection were prospectively observed for development of new-onset DKA for one week following initiation of parenteral dexamethasone. Clinical and biochemical parameters were compared between those who developed DKA (Group A) and those who didnot (Group B). Logistic regression was done to identify independent risk-factors predicting DKA; ROC-curve analysis to determine cut-offs for the parameters in predicting DKA. RESULTS: Amongst 302 patients screened, n = 196 were finally included, of whom 13.2% (n = 26,Group A) developed DKA. Patients in Group A were younger, had lower BMI, increased severity of COVID-19 infection, higher HbA1c%, CRP, IL-6, D-dimer and procalcitonin at admission (pall < 0.02). Further, admission BMI (OR: 0.43, CI: 0.27-0.69), HbA1c % (OR: 1.68, CI: 1.16-2.43) and serum IL-6 (OR: 1.02, CI: 1.01-1.03) emerged as independent predictors for DKA. Out of these, IL-6 levels had the highest AUROC (0.93, CI: 0.89-0.98) with a cut-off of 50.95 pg/ml yielding a sensitivity of 88% and specificity of 85.2% in predicting DKA. CONCLUSION: There is significant incidence of new-onset DKA following parenteral glucocorticoids in T2DM patients with COVID-19, especially in those with BMI <25.56 kg/m2, HbA1c% >8.35% and IL-6 levels >50.95 pg/ml at admission.

Karyotype-Phenotype Correlation in Turner Syndrome at a Single Center in Eastern India.

OBJECTIVE: To describe clinical features in Indian girls with Turner syndrome along with the phenotype-karyotype correlation. METHODS: 103 girls with Turner syndrome were divided into karyotype-groups: Classic (45X), 45,X/46,XX mosaics, isochromosomeXq (46,X,iXq and 45,X/46,X,iXq mosaics), 45,X/46,XYmosaics and structural defects, and analyzed for phenotypic differences. RESULTS: Majority (44.1%) had classic karyotype followed by isochromosome-Xq (26.5%). Classic Turner syndrome had higher prevalence of most skeletal and cutaneous stigmata, cubitus valgus (68.3%) and multiple nevi (68.2%) being the commonest. Bicuspid aortic valve was most common in 45,X/46,XX mosaics (5/15, 33.3%), and aortic coarctation in classic TS (3/42, 7.2%). Congenital renal anomalies occurred mostly in classic TS (6/42,14.3%). Overt hypothyroidism, conductive deafness and recurrent otitis media were commonest in isochromosomes (P<0.03). 45,X/46,XY mosaics had highest IQ (P<0.005). CONCLUSIONS: We report some novel associations of karyotype with non-endocrine parameters in Turner syndrome. In resource-limited settings, underlying karyotype may help prioritize screening investigations in girls with Turner syndrome.