Effects of pain education on disability, pain, quality of life, and self-efficacy in chronic low back pain: A randomized controlled trial.

BACKGROUND: Low back pain stands as a prevalent contributor to pain-related disability on a global scale. In addressing chronic low back pain (CLBP), there is a growing emphasis on incorporating psychological strategies into the management process. Among these, pain education interventions strive to reshape pain beliefs and mitigate the perceived threat of pain. This randomized controlled trial sought to assess the effects of pain education on various aspects, including pain levels, disability, quality of life, self-efficacy, and prognostic characteristics in individuals grappling with CLBP. METHODS: The clinical trial, retrospectively registered with the Clinical Trials Registry of India (CTRI/2021/08/035963), employed a two-arm parallel randomized design. Ninety-two participants with CLBP were randomly assigned to either the standard physiotherapy care with a pain education program or the control group. Both groups underwent a 6-week intervention. Assessment of pain intensity (using NPRS), disability (using RMDQ), self-efficacy (using the general self-efficacy scale), and well-being (using WHO 5I) occurred both before and after the 6-week study intervention. FINDINGS: Post-intervention score comparisons between the groups revealed that the pain education intervention led to a significant reduction in disability compared to the usual standard care at 6 weeks (mean difference 8.2, p < 0.001, effect size Cohen d = 0.75), a decrease in pain intensity (mean difference 3.5, p < 0.001, effect size Cohen d = 0.82), and an improvement in the well-being index (mean difference 13.7, p < 0.001, effect size Cohen d = 0.58). CONCLUSION: The findings suggest that integrating a pain education program enhances the therapeutic benefits of standard physiotherapy care for individuals dealing with chronic LBP. In conclusion, the clinical benefits of pain education become apparent when delivered in conjunction with standard care physiotherapy during the management of chronic low back pain.

Pituitary stalk interruption syndrome due to novel ROBO1 mutation presenting as combined pituitary hormone deficiency and central diabetes insipidus.

OBJECTIVES: The genetic causes of pituitary stalk interruption syndrome (PSIS) remain elusive in 95 % of cases. The roundabout receptor-1 gene (ROBO1) plays critical roles in axonal guidance and cell migration. Recently, mutations in the ROBO1 gene have been reported patients with PSIS. CASE PRESENTATION: We report a 2.9-year-old boy with PSIS who presented with combined pituitary hormone deficiency, central diabetes insipidus, and the classical triad of MRI findings. Through clinical exome sequencing using next-generation sequencing techniques, a previously unidentified novel heterozygous frame shift mutation in the ROBO1 gene was identified. This is the first report of ROBO1 mutation associated with posterior pituitary dysfunction. CONCLUSIONS: We conclude and emphasize that ROBO1 should be investigated in patients with PSIS. Our case is unique in the published literature in that we are first time reporting posterior pituitary dysfunction as manifestation of ROBO1 mutation. The full clinical spectrum of the mutations may not be fully known.

Prevalence of type 2 diabetes among tribal population of india: a multi-centric cross-sectional study.

BACKGROUND: The perception among healthcare workers is that the Indian tribal (indigenous) population are less affected by diabetes. This paper reports the prevalence of type 2 diabetes and its associated factors among tribal populations from six districts across India. METHODOLOGY: Random blood glucose (RBG) and fasting blood glucose (FBG) were measured for 8486 and 3131 adults, respectively, with a glucose meter. FBG ≥ 126 mg/dL (7.0 mmol/L) and RBG ≥ 200 mg/dL (11.1 mmol/L) were used to diagnose diabetes. In addition, blood pressure, anthropometric (height, weight, waist and hip circumferences), socio-demographic (age, gender, education, type of tribe and type of village) and behavioural data (tobacco smoking, non-smoking tobacco use and alcohol consumption) were collected. RESULTS: The overall prevalence of type 2 diabetes, based on RBG, was 4.77% (95% CI: 4.33-5.25). The prevalence of type 2 diabetes and prediabetes, based on FBG, was 6.80% (95% CI: 5.95-7.74) and 8.69% (7.72-9.73), respectively. The prevalence of type 2 diabetes was significantly associated with age (p<0.001), smokeless tobacco use (p < 0.05), hypertension (p < 0.001) and obesity (p < 0.01). CONCLUSION: The prevalence of type 2 diabetes among the Indian tribal population reported in this study is less than the national average of 7.3% for the general population. Hypertension and obesity were the major risk factors. Due to changing behavioural patterns, including dietary behaviour, there is likely to be an increase in the prevalence of hypertension and obesity, which further leads to increased prevalence of type 2 diabetes. Hence, appropriate interventions are to be initiated by the primary healthcare system.

VDR downregulation and promoter hypermethylation as one of the causes for triggering type 2 diabetes mellitus: Clinical and molecular studies.

Background: Our present study was to investigate the methylation and Gene expression of the vitamin D receptor (VDR) gene in the causing T2DM and to determine the inflammatory biomarkers in exaggerating T2DM in Kashmiri population. Methods: In this study, T2DM cases (n = 100) and controls (n = 100) of Kashmiri population were designed. Blood samples were taken from both groups, and serum vitamin D levels, inflammatory biomarkers (TNF-α, IL-6, IL-10, CRP, Leptin and adiponectin) were estimated by ELISA. By using methylation-specific PCR (MS-PCR) and RT-PCR, respectively, the levels of methylation and expression were measured after the extraction of DNA and RNA. Results: Studies using RT-PCR demonstrated that patients with diabetes had a lower degree of VDR expression than control subjects (P > 0.05). The T2DM was shown to be strongly correlated with hypermethylation (p-value < 0.001, OR 2.9; 95%CI 1.6-5.54). When compared to control groups, T2DM patients' levels of vitamin D in their serum were considerably lower (p < 0.01). Pro-inflammatory mediators like TNF-α, CRP, IL-6, and leptin levels were discovered to be higher, and concentrations of anti-inflammatory mediators like IL-10 and adiponectin were observed to be lower in people with T2DM than in people without the condition (p < 0.05). Conclusions: This study suggests the hypermethylation and down expression of VDR as one of the basis for causing T2DM in kashmiri individuals, exaggerated by enhanced degree of TNF-α, CRP, IL-6 and leptin and diminished concentration of IL-10 and adiponectin in T2DM. Supplementary Information: The online version contains supplementary material available at 10.1007/s40200-023-01266-6.

Normative Data on Dehydroepiandrosterone Sulphate (DHEAS) and its Attributes in Healthy Indian Children and Adolescents.

Dehydroepiandrosterone sulphate (DHEAS), the biochemical indicator of adrenarche and pubarche, is of paramount importance in the evaluation of puberty-related disorders. The reference range of DHEAS should be ethnicity, age, sex, pubarche and Tanner stage specific. Anthropometry, puberty assessment and hormonal parameters were estimated using electrochemiluminescence assay. Bone age was estimated using the BoneXpert software. Of 2191 healthy Indian children aged 5-18 y screened at Chandigarh, 1919 were included in the final analysis (994 boys). The median DHEAS levels at pubarche stage P2 were 82.10 (55.0-129.0) g/dl in girls and 132.50 (95.12-205.50) g/dl in boys. By ROC analysis, the level of DHEAS at pubarche was 63.7 g/dl (sensitivity 72.6%, specificity 64.4%) in girls and 82.2 g/dl (sensitivity 81.8%, specificity 68.8%) in boys. The median age at adrenarche was 9.5 y in both sexes. On multivariate regression analysis; bone age, body mass index (BMI), gonadal steroids, and insulin-like growth factor-1 (IGF-1) significantly correlated with serum DHEAS levels in either sex.

Hypertension Prevalence, Awareness, Treatment, Control and Risk Factors in Tribal Population of India: a Multi-Centric Cross-Sectional Study.

The prevalence of hypertension is increasing in the tribal population of India. Lifestyle modifications, including dietary changes and acculturation, are the main reasons for the high prevalence of hypertension among the Indian indigenous (tribal) population. This paper reports hypertension prevalence, awareness, treatment, control and risk factors among tribes in five districts of different geographical zones of India. A cross-sectional study was conducted among the adult tribal population of 7590 from these states. Data related to blood pressure, anthropometry, demographic and behavioural variables were collected with prior consent from the participants. The prevalence of hypertension is 34.0% and 28.3% among men and women, respectively. Of the total hypertensives, 27.5% were aware of their hypertension status; of them, 83.9% were receiving treatment, and blood pressure was in control among 33.5% of patients who were receiving treatment. Age, alcohol intake, sedentary lifestyle, Particularly Vulnerable Tribal Groups status and body mass index are found to be significantly associated with the prevalence of hypertension. The prevalence of hypertension is high among these tribal populations, which could be due to modernization and acculturation. Awareness and treatment-seeking behaviour are poor. Hence, early screening, awareness campaigns for seeking treatment, and health promotion are immediately required. Comprehensive health promotion programs need to promote lifestyle modification and re-orientation of the primary health care system to improve availability and accessibility to hypertension screening and treatment.

Impact of empagliflozin add-on therapy on quality of life in patients of type 2 diabetes mellitus with hypertension: A prospective study.

Background: Diabetes has a negative impact on patient's quality of life (QoL). Comorbidities and polypharmacy further worsen their QoL. Thus, in addition to glycemic control, assessment of QoL is also gaining importance. Objective: The objective of this study was to evaluate QoL in patients of type 2 diabetes mellitus (T2DM) with hypertension after add-on empagliflozin to triple drug therapy (metformin, teneligliptin, and glimepiride). Materials and Methods: A prospective research was done on T2DM patients with hypertension, who visited a tertiary care referral institute's endocrine outpatient clinic. For 3 months, empagliflozin, 25 mg once daily, was administered as an add-on treatment with metformin, teneligliptin, and glimepiride. In addition to clinical assessment, an Urdu-translated QoL instrument for Indian diabetes patients was used to conduct QoL study. The QoL outcomes prior to empagliflozin add-on were compared with those obtained at the conclusion of the 3 months of treatment. Results: Empagliflozin as an add-on therapy significantly improved various aspects of QoL like role limitation due to physical health, physical endurance, general health, symptom botherness, financial worries, emotional/mental health, and diet satisfaction (P < 0.001). It also improved glycemic and blood pressure parameters significantly. Conclusion: QoL is an essential measure with respect to patient-centered treatment approach. Empagliflozin, as an add-on medication, improved QoL, glycemic parameters and blood pressure in T2DM patients with hypertension. It can be recommended as an add-on, but more research with a larger sample size is required.

Biomarkers: Tools for Discriminating MODY from Other Diabetic Subtypes.

Maturity Onset Diabetes of Young (MODY), characterized by the pancreatic b-cell dysfunction, the autosomal dominant mode of inheritance and early age of onset (often ≤25 years). It differs from normal type 1 and type 2 diabetes in that it occurs at a low rate of 1-5%, three-generational autosomal dominant patterns of inheritance and lacks typical diabetic features such as obesity. MODY patients can be managed by diet alone for many years, and sulfonylureas are also recommended to be very effective for managing glucose levels for more than 30 years. Despite rapid advancements in molecular disease diagnosis methods, MODY cases are frequently misdiagnosed as type 1 or type 2 due to overlapping clinical features, genetic testing expenses, and a lack of disease understanding. A timely and accurate diagnosis method is critical for disease management and its complications. An early diagnosis and differentiation of MODY at the clinical level could reduce the risk of inappropriate insulin or sulfonylurea treatment therapy and its associated side effects. We present a broader review to highlight the role and efficacy of biomarkers in MODY differentiation and patient selection for genetic testing analysis.

Role of human organic cation transporter-1 (OCT-1/SLC22A1) in modulating the response to metformin in patients with type 2 diabetes.

BACKGROUND: Organic cation transporter 1 primarily governs the action of metformin in the liver. There are considerable inter-individual variations in metformin response. In light of this, it is crucial to obtain a greater understanding of the influence of OCT1 expression or polymorphism in the context of variable responses elicited by metformin treatment. RESULTS: We observed that the variable response to metformin in the responders and non-responders is independent of isoform variation and mRNA expression of OCT-1. We also observed an insignificant difference in the serum metformin levels of the patient groups. Further, molecular docking provided us with an insight into the hotspot regions of OCT-1 for metformin binding. Genotyping of these regions revealed SNPs 156T>C and 1222A>G in both the groups, while as 181C>T and 1201G>A were found only in non-responders. The 181T>C and 1222A>G changes were further found to alter OCT-1 structure in silico and affect metformin transport in vitro which was illustrated by their effect on the activation of AMPK, the marker for metformin activity. CONCLUSION: Taken together, our results corroborate the role of OCT-1 in the transport of metformin and also point at OCT1 genetic variations possibly affecting the transport of metformin into the cells and hence its subsequent action in responders and non-responders.

Clinical profiling and screening for HNF4α and GCK gene mutations in Kashmiri patients with maturity-onset diabetes of the young (MODY).

AIM: Maturity-onset Diabetes of Young (MODY) is a monogenic form of diabetes affecting 1-5% of young (often ≤25 years) diabetic patients exhibiting an autosomal dominant mode of inheritance. Considering the significance of genetic polymorphisms in a variety of diseases, this study aimed to determine the association between HNF4α and GCK gene polymorphisms and the risk of MODY in the Kashmir community, as well as their clinical differences. METHOD: The study was conducted on clinically confirmed MODY patients (n = 50), and age and gender-matched controls (25 T1DM and 25 non-diabetic) recruited from the endocrinology department of the hospital, for evaluating the HNF4α and GCK mutation. Under standard conditions, PCR-mediated amplification was done to evaluate the respective exons. Preliminary mutations were detected using restriction enzymes (BfaI and HhaI), which were then followed by sequencing of representative samples. The diabetic history, clinical and biochemical data were obtained after proper consent. RESULTS: Our data revealed no association of HNF4α (exon7) and GCK (exon8) gene mutation with MODY disease susceptibility in the Kashmiri population. On diagnosis, no MODY patient was given immediate insulin; instead, metformin (68%) or sulphonyl-urea (28%) and dietary changes (4%) were recommended. Later in life, 54% of MODY patients develop insulin dependency. The MODY probability was calculated to be 73.88% (±4.56). HbA1c levels were lower [7.48% (±1.64)] than in T1DM [9.17(±2.29%)]. CONCLUSIONS: Young early-onset diabetic patients were able to keep their HbA1c and blood glucose levels stable with a modified diet and metformin/sulphonyl-urea, but they may become insulin-dependent in the future, as seen in our study. As a result, prompt diagnosis and management are essential for avoiding complications. Furthermore, no HNF4α (exon7) or GCK (exon 8) mutations were found in MODY patients or T1DM/healthy non-diabetic controls.

Environmental Factors as Diabetic Mediators: A Mechanistic Approach.

Despite substantial investment in research and treatment options, diabetes mellitus remains a pressing public health concern with potential epidemic proportions globally. There are reports that by the end of 2040, 642 million people will be suffering from diabetes. Also, according to an estimation, 1.6 million deaths were caused directly by diabetes in 2016. Diabetes is a metabolic disorder characterized by impaired glucose regulation in the body due to the destruction of pancreatic ß-cells or insulin resistance. Genetic propensity, unhealthy and imbalanced diet, obesity and increasing urbanization are the common risk factors for diabetes. Besides this, it has been reported that environmental pollutants like organic pesticides, heavy metals, and air pollutants act as strong predisposing factors for diabetes owing to their highly bio-accumulative nature. These pollutants disturb glucose homeostasis either by up-regulating or down-regulating the expression of diabetic marker genes like insulin (INS) and glucokinase (GCK). Unfortunately, the molecular mechanism of the role of pollutants in causing diabetes is not very clear. This mechanistic review provides evidence of different environmental determinants, including persistent organic pollutants (POPs), air pollutants, toxic metals, etc., in inducing diabetes and proposes a framework for the possible mechanisms involved. It also illuminates the current status and future challenges, which will not only broaden our understanding but can also be a reasonable platform for further investigation.

Clinical Manifestations of Hyperandrogenism and Ovulatory Dysfunction Are Not Associated with His1058 C/T SNP (rs1799817) Polymorphism of Insulin Receptor Gene Tyrosine Kinase Domain in Kashmiri Women with PCOS.

BACKGROUND: Polycystic ovary syndrome (PCOS) is the most common endocrine metabolic disorder affecting premenopausal women. Besides primary features like anovulation, hyperandrogenism, and polycystic ovaries, women with PCOS present with multiple metabolic, cardiovascular, and psychological disorders. The etiology is multifactorial and the different genetic variants are suggested to play an important role in pathogenesis. Insulin resistance is a ubiquitous finding in PCOS and SNPs in genes involved in the insulin signaling pathway are possible candidates that can explain the development of clinical manifestations of PCOS. AIM: We aimed to investigate the association of INSR His1058 C/T (rs1799817) single nucleotide polymorphism with PCOS in Kashmiri women. The genotypic-phenotypic correlation of the tested SNP with hyperandrogenism, ovulatory dysfunction, and metabolic markers was evaluated. RESULTS: The allele frequency (OR = 1.00, 95% CI = 0.67-1.48, χ 2 = 0.01, P=0.99) and genotype distribution (χ 2 = 3.73, P=0.15) in INSR C/T polymorphism were comparable with controls. No significant association was found with PCOS in dominant (P=0.194), recessive (P=0.442), and homo vs. het. (P=0.5) genotype models. Genotype-phenotype correlation analysis revealed that variant TT genotype had significantly higher HOMA (P=0.029) and reduced insulin sensitivity QUICKI (P=0.037) values. There was no significant variation in the prevalence of hirsutism, acne, alopecia, menstrual disturbances, acanthosis nigricans, and obesity (all P > 0.05) in different INSR C/T genotypes. CONCLUSION: The INSR C/T SNP (rs1799817) does not increase the risk of PCOS in Kashmiri women. This SNP is unlikely to play a significant role in the development and manifestation of clinical symptoms of polycystic ovary syndrome.

Effect of steroid hormone receptor gene variants PROGINS (Alu insertion) and PGR C/T (rs1042839) as a risk factor for recurrent pregnancy loss in Kashmiri population (North India).

AIM: To unveil and evaluate the association and analyze the incidence and pattern of PGR gene polymorphisms (PROGINS insertion and PGR exon 5-C/T polymorphism) in recurrent pregnancy loss (RPL) couples of Kashmir. METHODS: In this study, analyses of PGR gene polymorphisms in RPL couples were genotyped by amplification-refractory mutation system polymerase chain reaction (PCR) and PCR-restriction fragment length polymorphism. RESULTS: Molecular analysis of PGR gene polymorphisms indicated that the genotypic and allelic frequencies of PROGINS insertion and PGR exon 5 C/T polymorphisms of female group in cases and controls to be significantly different and poses risk in predisposition to RPL. Moreover, haplotype analysis in female group revealed that P1P2/CC and P1P2/CT genotype are significantly associated with RPL. CONCLUSION: Our data indicate that the PROGINS insertion and exon 5-C/T polymorphism can act as useful genetic markers in the female group, but needs to be replicated in further studies including various other single nucleotide polymorphisms of PGR gene relevant to pregnancy loss which may contribute to novel therapeutic targets with improved conclusions.

Lactic Acidosis in Diabetic Ketoacidosis: A Marker of Severity or Alternate Substrate for Metabolism.

PURPOSE: The lactate level is being increasingly used as a marker of severity of illness and prognosis in multitude of critical conditions. However, its role in diabetic ketoacidosis (DKA) is not well defined. AIM: To determine the prevalence and clinical importance along with the underlying role of metformin in lactic acidosis (LA) in patients admitted with DKA. METHODS: A 2-year prospective and observational study involving 62 consenting in hospital DKA patients. Plasma lactate level on arrival, its clinical significance and relationship with morbidity and mortality in patients with DKA was evaluated. RESULTS: The prevalence of LA (lactate ≥2.5 mmol/l) among the study cohort was found to be 55% with significant LA (≥5 mmol/l) documented in 16%. The median lactate level was 2.55 mmol/l (interquartile range, 1.70-3.20). No significant difference in the severity of LA was seen with metformin use. Lactate correlated positively with initial plasma glucose (IPG) (P = 0.001) and APACHE-II Score (P = 0.002); correlated negatively with systolic blood pressure (P = 0.003), pH (P = 0.002) and severity of DKA (P = 0.001). After controlling for AKI, APACHE II score and blood pressure, lactate continued to correlate positively with IPG (P = 0.002). No mortality or significant morbidity was documented in the entire cohort. CONCLUSIONS: LA has a significant presence in patients with DKA; however, it is not associated with mortality or significant morbidity. Moreover, there was no significant difference in severity of LA with metformin use. Elevated lactate levels may be an adaptation to provide alternate substrate for metabolism in the presence of hypoinsulinemic state. The study results provide rationale for large well-designed studies evaluating in-depth clinical relationship of lactate in DKA.

Impact of rs2414096 polymorphism of CYP19 gene on susceptibility of polycystic ovary syndrome and hyperandrogenism in Kashmiri women.

Polycystic ovary syndrome (PCOS) is the most common reproductive endocrine disorder in pre-menopausal women having complex pathophysiology. Several candidate genes have been shown to have association with PCOS. CYP19 gene encodes a key steroidogenic enzyme involved in conversion of androgens into estrogens. Previous studies have reported contradictory results with regard to association of SNP rs2414096 in CYP19 gene with PCOS and hyperandrogenism in different ethnic populations. Present study was aimed to investigate the impact of SNP rs2414096 polymorphism of CYP19 gene on susceptibility of PCOS and hyperandrogenism in Kashmiri women. Further we also studied the genotypic-phenotypic association for various clinical and biochemical parameters of this polymorphism. Case control study. 394 PCOS cases diagnosed on the basis of Rotterdam criteria and age matched 306 healthy women. We found a significant differences in genotypic frequency (χ2 = 18.91, p < 0.05) as well as allele frequency (OR 0.63, CI 0.51-0.78, χ2 = 17.66, p < 0.05) between PCOS women and controls. The genotype-phenotype correlation analysis showed a significant difference in FG score (p = 0.047) and alopecia (p = 0.045) between the three genotypes. Also, the androgen excess markers like DHEAS (p < 0.001), Androstenedione (p < 0.001), Testosterone (p < 0.001) and FAI (p = 0.005) were significantly elevated in GG genotype and showed a significant difference in additive model in PCOS women. rs2414096 polymorphism of CYP19 gene is associated with the risk of PCOS as well as with clinical and biochemical markers of hyperandrogenism, hence suggesting its role in clinical manifestations of PCOS in Kashmiri women.

Effects of Single Dose of Dexamethasone on Perioperative Blood Glucose Levels in Patients Undergoing Surgery for Supratentorial Tumors - An Observational Study.

INTRODUCTION: Dexamethasone is commonly administered in intracranial tumors to reduce the cerebral edema. Its administration may be associated with hyperglycemia. The primary objective of this study was to study the magnitude of rise in blood sugar levels following the administration of a single 10 mg dose of dexamethasone. METHODS: Seventy patients who underwent various neurosurgical procedures were enrolled in the study. Group D (n = 35 undergoing surgery for intracranial tumors) were administered injection dexamethasone 10 mg while as Group P (n = 35 undergoing surgery for subarachnoid hemorrhage) received placebo. Blood samples were obtained through the arterial line at baseline (before dexamethasone administration), 60, 120, 180, and 240 min after the dexamethasone administration and blood glucose concentrations noted. RESULTS: Glucose concentrations were significantly increased in patients who received dexamethasone compared with those who received placebo (P < 0.05). Blood glucose concentrations at different time intervals were greater when compared with the baseline blood sugar levels in both the placebo and dexamethasone group (P < 0.05). The arterial blood glucose concentration in those who received 10 mg dexamethasone (n = 35) increased from 95.29 ± 13.69 mg.dl-1 to 139.97 ± 10.34 mg.dl-1 over 4 h, compared with a change from 94.74 ± 10.05 mg.dl-1 to 122.34 ± 10.68 mg.dl-1 in those who received placebo (n = 35) (P < 0.05). CONCLUSION: The administration of a single intravenous dose of 10-mg dose dexamethasone caused a significant increase in the blood glucose concentrations at different point intervals when compared with the placebo over a 4-h period. We recommend intensive monitoring of the blood sugar levels during the intraoperative period to prevent the development of severe hyperglycemia and its associated complications.

Variations in the inhibin gene in Kashmiri women with primary ovarian insufficiency.

Inhibin is a glycoprotein produced by granulosa cells and its main function is the negative feedback control of follicle stimulating hormone (FSH) which has an important role in folliculogenesis. Mutation in the INHα gene leading to decreased bioactive inhibin has been associated with primary ovarian insufficiency (POI). The aim of this study was to investigate the role of variations in the INHα gene in increasing the susceptibility to POI in Kashmiri women. INHα c.769G > A mutation was analysed in 100 POI cases and 100 controls using PCR-RFLP and agarose gel electrophoresis. The INHα c.769G > A mutation was found in 10% of POI cases with 8% having heterozygous mutation and 2% having a homozygous mutation. The frequency of mutation in healthy controls was zero. Statistically, a very significant association was found between INHα c.769G > A mutation and the occurrence of POI (p = 0.0015). Moreover, the mutation was also significantly associated with high levels of FSH in POI patients (p < 0.0001). Given the significant association of INHα c.769G > A mutation with the increased FSH levels and POI in Kashmiri population, we suggest this mutation can be used to identify POI variants for screening of women susceptible to POI before the disease onset and can further facilitate putative therapy for such patients.

RET/PTC Gene Rearrangements in Thyroid Carcinogenesis: Assessment and Clinico-Pathological Correlations.

Rearranged during transfection (RET) is a proto oncogene implicated in thyroid carcinogenesis of papillary type (PTC). The RET proto-oncogene in PTC is constitutively activated by fusion of its tyrosine kinase domain with the 5 ´region of another gene thereby generating chimeric products collectively named RET/PTCs. RET/PTC1 and RET/PTC3 are best characterized among all RET/PTC rearrangements. Kashmir valley has witnessed an alarming increase in thyroid cancer incidence in young women. Therefore, we investigated the occurrence of RET/PTC 1 & 3 rearrangements by semi quantitative and qPCR in thyroid cancer patients (n = 48) of Kashmiri population and interrelated results with various clinicopathological characteristics. We observed that all the RET/PTC rearrangements were confined to PTC cases (10/40). Presence of RET/PTC rearrangement significantly correlated with gender, elevated TSH levels and lymph node metastasis. Overall, our study advocates that RET/PTC3 rearrangement is a frequent event in the carcinogenesis of thyroid gland in Kashmiri population although a study with a larger sample size is needed to get a clear scenario.

Coadministration of metformin or spironolactone enhances efficacy of rosiglitazone in management of PCOS.

The aim of this study was to compare the efficacy and safety of adding metformin or spironolactone to rosiglitazone in women with polycystic ovary syndrome (PCOS). This is a prospective non-randomized study in a tertiary care with at in a tertiary care endocrine clinic. Women (n = 138) diagnosed with PCOS on the basis of Rotterdam criteria 2003 were categorized into three groups on the basis of drug intake as - rosiglitazone (R), rosiglitazone with spironolactone (R + S), and rosiglitazone with metformin (R + M). Clinical, biochemical, hormonal, and insulin sensitivity parameters were assessed at baseline and after six months of follow up. There was a significant improvement in number of menstrual cycles per year and Ferriman Gallwey (FG) score in all three groups after 6 months. Plasma insulin (0, 2 h), HOMA-IR and serum total testosterone levels decreased after six months in all the three groups. The inter group comparison showed higher efficacy of R + S in improving hyperandrogenism whereas R + M was most effective in decreasing body weight and plasma insulin levels compared to R and R + S (p<.05). Treatment of women with PCOS using rosiglitazone alone and in combination with spironolactone or metformin is safe and efficacious with limited adverse events however randomized trials with longer duration of follow up are warranted.

Disorders of Sex Development: A 10 Years Experience with 73 Cases from the Kashmir Valley.

PURPOSE: To present the clinical data, investigative profile, and management of patients with disorders of sex development (DSD) from the endocrine unit of a tertiary care university hospital. MATERIALS AND METHODS: This retrospective study included 73 cases of DSD, evaluated and managed at Department of Endocrinology, Sher-i-Kashmir Institute of Medical Sciences, Srinagar, Kashmir, over a period of 10 years from September 2008 to August 2018. RESULTS: Twenty-nine patients (39.7%) had 46 XY DSD and twenty-nine patients (39.7%) had 46 XX. Sex chromosome DSD was diagnosed in 15 (20.5%) patients. Of 29 patients with 46 XY DSD, 17 (58.6%) had 5α-reductase type-2 deficiency (5α-RD) and 6 (20.7%) had complete androgen insensitivity syndrome. In our patients with 5α-RD, the history of consanguinity was documented in nine (52.9%) patients. Two patients had testosterone biosynthetic defect and one patient had partial androgen insensitivity syndrome. Of 29 patients with 46 XX DSD, 16 (55.1%) had congenital adrenal hyperplasia (CAH). Of 15 patients with sex chromosome DSD, 7 patients had Turner's syndrome, 7 had Klinefelter's syndrome, and 1 patient had mixed gonadal dysgenesis. CONCLUSION: In our study, equal number of patients had 46 XY DSD and 46 XX DSD. We are for the first time reporting from India that the most common cause of 46 XY DSD is 5α-RD, whereas CAH is the most common cause of 46 XX DSD as reported previously.