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Background: NSAIDs are the most widely prescribed medications worldwide for their anti-inflammatory, antipyretic, and analgesic effects. However, their chronic use can lead to several adverse drug events including GI toxicity. The selective COX-2 inhibitors developed as gastrosparing NSAIDs also suffer from serious adverse effects which limit their efficacy. Objective: Local generation of reactive oxygen species is implicated in NSAID-mediated gastric ulceration and their combination with H2 antagonists like famotidine reduces the risk of ulcers. The objective of this work was to design and synthesize novel methanesulphonamido isoxazole derivatives by hybridizing the structural features of NSAIDs with those of antiulcer drugs (ranitidine, famotidine, etc.) to utilize a dual combination of anti-inflammatory activity and reducing (antioxidant) potential. Method: The designing process utilized three dimensional similarity studies and utilized an isoxazole core having a potential for anti-inflammatory as well as radical scavenging antioxidant activity. The compounds were assayed for their anti-inflammatory activity in established in vivo models. The in vitro antioxidant activity was assessed in potassium ferricyanide reducing power (PFRAP) assay employing ascorbic acid as the standard drug. Results: Compounds 5, 6, 9 and 10 showed antiinflammatory activity comparable to the standard drugs and were also found to be non-ulcerogenic at the test doses. Compounds 6-10 exhibited good antioxidant effect in the concentration range of 1.0- 50.0 μmol/ml. The test compounds were also found to comply with the Lipinski rule suggesting good oral absorption. Conclusion: A new series of isoxazole based compounds is being reported with good antiinflammatory activity coupled with antioxidant potential as gastro-sparing anti-inflammatory agents.

Background: Coronavirus disease 2019 (COVID-19) barrier box is being used by health-care workers for protection against aerosol-transmitted infection. Usually, a Macintosh laryngoscope (MC) or a video laryngoscope (VL) is used for endotracheal intubation (ETI). We aimed to determine the most suitable laryngoscope blade in terms of time to ETI, ease of ETI, and the first-pass success rate. Methods: American Society of Anesthesiologists Grade I and II patients undergoing surgery under general anesthesia were randomized into the MC and the King Vision VL groups in a 1:1 ratio. ETI was performed using either the MC (the MC group) or the King Vision VL (the VL group) with a COVID-19 barrier box. The first-pass intubation success rate, intubation time, and ease of ETI were analyzed. Results: The first-pass success rate was higher in the MC group (P = 0.43). The mean duration of ETI was 33 s and 47 s in the MC group and VL group, respectively. The difference was statistically significant between the groups (P = 0.002). The ease of ETI was comparable between the groups (P = 0.57), and the Cormack–Lehane grade was significantly different between the groups (P = 0.0025). Conclusion: ETI duration was shorter in the MC group than in the VL group. Hence, a MC can be used along with a COVID-19 barrier box by experienced operators for the prevention of aerosol spread.

Purpose of the Study: Reversible proximal tubular dysfunction associated with distal renal tubular acidosis (dRTA) mimics type 3 RTA, a condition classically associated with features of both proximal RTA (pRTA) and dRTA. Proximal tubulopathy has been reported in children with primary dRTA, but the data in adults are lacking. Study Design: In this hospital record-based retrospective study, data from 66 consecutive cases of RTA, between January 2016 to December 2018, were retrieved and analyzed. Results: Mean age of the study population was 25.3 years (range: 3 months to 73 years). Six (9.1%) of them had pRTA, 58 (87.9%) had dRTA, 1 (1.5%) had type 3 RTA, and the remaining 1 (1.5%) had type 4 RTA. Ten patients (17.2%) with dRTA and 3 patients of pRTA (50%) had underlying secondary etiologies. Data on proximal tubular dysfunction were available for 30 patients with dRTA, of whom 1 had isolated dRTA, and the rest 29 patients had accompanying completely reversible proximal tubular dysfunction. Among the 10 cases of secondary dRTA, 6 were not evaluated for proximal tubular dysfunction. Of the remaining 4, 3 had reversible form of proximal tubular abnormality. Fifty-two patients with dRTA came from a population, indigenous to the “Rarh” region of India. Conclusions: Proximal tubular dysfunction often accompanies dRTA; 75% of the children with primary dRTA, at least 29% of adults with primary dRTA, and at least 30% of adults with secondary dRTA manifest such completely reversible form of proximal tubulopathy. “Rarh' region of India probably is a hotspot for endemic dRTA.

After a period of rapidly declining U.S. COVID-19 incidence during January-March 2021, increases occurred in several jurisdictions (1,2) despite the rapid rollout of a large-scale vaccination program. This increase coincided with the spread of more transmissible variants of SARS-CoV-2, the virus that causes COVID-19, including B.1.1.7 (1,3) and relaxation of COVID-19 prevention strategies such as those for businesses, large-scale gatherings, and educational activities. To provide long-term projections of potential trends in COVID-19 cases, hospitalizations, and deaths, COVID-19 Scenario Modeling Hub teams used a multiple-model approach comprising six models to assess the potential course of COVID-19 in the United States across four scenarios with different vaccination coverage rates and effectiveness estimates and strength and implementation of nonpharmaceutical interventions (NPIs) (public health policies, such as physical distancing and masking) over a 6-month period (April-September 2021) using data available through March 27, 2021 (4). Among the four scenarios, an accelerated decline in NPI adherence (which encapsulates NPI mandates and population behavior) was shown to undermine vaccination-related gains over the subsequent 2-3 months and, in combination with increased transmissibility of new variants, could lead to surges in cases, hospitalizations, and deaths. A sharp decline in cases was projected by July 2021, with a faster decline in the high-vaccination scenarios. High vaccination rates and compliance with public health prevention measures are essential to control the COVID-19 pandemic and to prevent surges in hospitalizations and deaths in the coming months.

Introduction: Chronic total occlusions (CTO) of the superficial femoral artery (SFA) are generally managed by an endovascular retrograde contralateral “crossover” or ipsilateral antegrade common femoral artery (CFA) approach. In cases with flush occlusion or a very short SFA stump at common CFA bifurcation, antegrade recanalization frequently fails due to an inability to engage the true ostium of the SFA. The purpose of this study was to evaluate the efficacy and safety of retrograde popliteal approach for endovascular revascularization of flush SFA CTO. Materials and Methods: We retrospectively investigated 18 patients (14 males and 4 females, mean age 61 ± 14 years) with flush SFA CTO undergoing retrograde popliteal artery (PA) revascularization at two endovascular centers in North India between January 2017 and December 2018. All the patients had critical limb ischemia (CLI) and flush SFA CTO with ostial involvement. Hemostasis was achieved by the manual compression only. Study endpoints were technical success rate, puncture site complications, and limb salvage. Results: CLI with Rutherford category 5 dominated the clinical presentation (56%) with most of the patients presenting late after disease onset. Majority were Trans-Atlantic Inter-Society Consensus-C (72%) chronic SFA occlusions (mean lesion length 185 ± 52 mm). Doppler-guided popliteal puncture and sheath placement were successful in 100%. Technical success rate of retrograde revascularization was 83%. Intraluminal recanalization was possible in 56% from the popliteal access, and subintimal recanalization was done in 28%. There was no major access site-related complication or mortality in the follow-up period. The primary patency rates at 6 months and 1 year postintervention were 93% and 80%, respectively. Conclusions: Retrograde PA approach under Doppler guidance was effective in terms of technical success rate of popliteal puncture as well as retrograde revascularization of flush SFA CTO. The approach was safe with no major access site complications.

Background:NSAIDs are used as first-line drugs for the treatment of various inflammatory disorders. Chronic use of NSAIDs is known to be associated with gastrointestinal and renal toxicity. Local generation of reactive oxygen species finally resulting in cellular apoptosis is one of the accepted mechanisms for NSAID-induced toxicity.Objective:The objective of the present study was to design and synthesize a series of 2-methane sulfonamido substituted arylthiazole derivatives by including structural features of combined antiulcer and anti-inflammatory activity utilizing as the structural core, thiazole nucleus with potential for antioxidant effect.Methods:Compounds were designed based on three dimensional and field similarity studies. The synthesized compounds were evaluated for their anti-inflammatory activity in carrageenan-induced rat paw edema model. Rofecoxib and indomethacin were taken as standard drugs for comparison. The in vitro antioxidant activity was assessed in potassium ferricyanide reducing power (PFRAP) assay employing ascorbic acid as the standard drug.Results:The compounds 6 and 7 showed good anti-inflammatory activity comparable to the standard group and were also non ulcerogenic at the test doses. Compounds 1-7 displayed varying degrees of reducing power in the PFRAP) assay and the methanesulphonamido derivatives 4-7 showed the highest antioxidant activity (EC50 values 3.7-5.1 μmol/ml vs ascorbic acid 7.4 μmol/ml). Theoretical ADME profiling of the compounds based on selected physicochemical properties showed excellent compliance with Lipinski’s rule.Conclusion:A series of compounds have been designed and synthesized having dual antioxidant and anti-inflammatory activity with activities comparable to standard drugs.

Introduction: The term “chronic dermatophytosis” can be described as patients who have suffered tinea infections for more than 6 months, with or without recurrence. Since last few years we are facing an onslaught of chronic and recurrent dermatophytosis. These infections are increasingly becoming debilitating with severe symptoms like itching and increasingly showing lack of response to traditional treatment, hence it has become utmost important to assess impact of dermatophytosis today on quality of life of patients. Objectives: To determine quality of life in patients with chronic dermatophytosis using Dermatology Life Quality Index (DLQI). Materials and Methods: Adult literate patients having chronic dermatophytosis which was confirmed by KOH mount were included in the study. History, clinical features and other relevant details were included in a proforma. All patients were asked to fill DLQI questionnaire in Hindi. Controls having disease for less than six months were also included. Data thus obtained was collected and tabulated. The data was analysed using SPSS software and relevant statistical tests were used. Results: Total number of cases collected were 263, 137 controls were also included. In gender distribution, cases had 71.86% males and 28.14% female while controls had 63.5% males and 36.5% females. Mean DLQI of cases was 14.28+/-5.16 and controls was 11.56+/-3.60. DLQI distribution of cases -162(61.6%) had very large effect, 64(24.33%) had moderate effect, and 32(12.17%) had extremely large effect on DLQI. Domains of Symptoms and feelings (72.67%), work and school related activities (69%) and treatment related problems (67.67%) posed maximum impairment. Quality of life derangement increased significantly with presence of lesions on both exposed and non exposed sites and increase in body surface area. Conclusion: While superficial dermatophytosis affects quality of life (QoL) in all patients, chronic dermatophytosis has a significantly more derogatory effect on the QoL of a person with some of the patient also showing extremely large effect on QoL.

Diabetic kidney disease (DKD) occurs in approximately 20–40% of patients with type 2 diabetes mellitus. Patients with DKD have a higher risk of cardiovascular and all-cause mortality. Angiotensin-converting enzyme inhibitors or angiotensin receptor blockers and antihyperglycemic drugs form the mainstay of DKD management and aim to restrict progression to more severe stages of DKD. Sodium-glucose cotransporter 2 inhibitors (SGLT2i) control hyperglycemia by blocking renal glucose reabsorption in addition to preventing inflammation, thereby improving endothelial function and reducing oxidative stress; consequently, this class of prescription medicines is emerging as an important addition to the therapeutic armamentarium. The EMPA-REG OUTCOME, DECLARE TIMI 58, and CANVAS trials demonstrated the renoprotective effects of SGLT2i, such as restricting decline in glomerular filtration rate, in the progression of albuminuria, and in death due to renal causes. The renoprotection provided by SGLT2i was further confirmed in the CREDENCE study, which showed a 30% reduction in progression of chronic kidney disease, and in the DELIGHT study, which demonstrated a reduction in albuminuria with dapagliflozin compared with placebo (− 21.0%, confidence interval [CI] − 34.1 to − 5.2, p = 0.011). Furthermore, a meta-analysis demonstrated a reduced risk of dialysis, transplantation, or death due to kidney disease (relative risk 0.67; 95% CI 0.52–0.86; p = 0.0019) and a 45% risk reduction in worsening of renal function, end-stage renal disease, or renal death (hazard ratio 0.55, CI 0.48–0.64, p

The human pathogen Mycobacterium tuberculosis (Mtb) harbors a well-orchestrated Clp (caseinolytic protease) proteolytic machinery consisting of two oligomeric segments, a barrel-shaped heterotetradecameric protease core comprising the ClpP1 and ClpP2 subunits, and hexameric ring-like ATP-dependent unfoldases composed of ClpX or ClpC1. The roles of the ClpP1P2 protease subunits are well-established in Mtb, but the potential roles of the associated unfoldases, such as ClpC1, remain elusive. Using a CRISPR interference–mediated gene silencing approach, here we demonstrate that clpC1 is indispensable for the extracellular growth of Mtb and for its survival in macrophages. The results from isobaric tags for relative and absolute quantitation–based quantitative proteomic experiments with clpC1- and clpP2-depleted Mtb cells suggested that the ClpC1P1P2 complex critically maintains the homeostasis of various growth-essential proteins in Mtb, several of which contain intrinsically disordered regions at their termini. We show that the Clp machinery regulates dosage-sensitive proteins such as the small heat shock protein Hsp20, which exists in a dodecameric conformation. Further, we observed that Hsp20 is poorly expressed in WT Mtb and that its expression is greatly induced upon depletion of clpC1 or clpP2. Remarkably, high Hsp20 protein levels were detected in the clpC1(−) or clpP2(−) knockdown strains but not in the parental bacteria, despite significant induction of hsp20 transcripts. In summary, the cellular levels of oligomeric proteins such as Hsp20 are maintained post-translationally through their recognition, disassembly, and degradation by ClpC1, which requires disordered ends in its protein substrates.

SummaryWhat is already known about this topic?The highly transmissible SARS-CoV-2 Delta variant has begun to cause increases in cases, hospitalizations, and deaths in parts of the United States. With slowed vaccination uptake, this novel variant is expected to increase the risk of pandemic resurgence in the US in July—December 2021.What is added by this report?Data from nine mechanistic models project substantial resurgences of COVID-19 across the US resulting from the more transmissible Delta variant. These resurgences, which have now been observed in most states, were projected to occur across most of the US, coinciding with school and business reopening. Reaching higher vaccine coverage in July—December 2021 reduces the size and duration of the projected resurgence substantially. The expected impact of the outbreak is largely concentrated in a subset of states with lower vaccination coverage.What are the implications for public health practice?Renewed efforts to increase vaccination uptake are critical to limiting transmission and disease, particularly in states with lower current vaccination coverage. Reaching higher vaccination goals in the coming months can potentially avert 1.5 million cases and 21,000 deaths and improve the ability to safely resume social contacts, and educational and business activities. Continued or renewed non-pharmaceutical interventions, including masking, can also help limit transmission, particularly as schools and businesses reopen.

The 4th epiDAMIK@SIGKDD workshop is a forum to discuss new insights into how data mining can play a bigger role in epidemiology and public health research. While the integration of data science methods into epidemiology has significant potential, it remains under studied. We aim to raise the profile of this emerging research area of data-driven and computational epidemiology, and create a venue for presenting state-of-the-art and in-progress results-in particular, results that would otherwise be difficult to present at a major data mining conference, including lessons learnt in the 'trenches'. The current COVID-19 pandemic has only showcased the urgency and importance of this area. Our target audience consists of data mining and machine learning researchers from both academia and industry who are interested in epidemiological and public-health applications of their work, and practitioners from the areas of mathematical epidemiology and public health.

Background: Polycystic ovary syndrome (PCOS) is associated with insulin resistance and elevated risk of cardiovascular disease and diabetes. Chronic inflammation has been observed in PCOS in several studies but there is also opposing evidence and a dearth of research in Indians. Objective: To estimate chronic inflammation in PCOS and find its relationship with appropriate anthropometric and biochemical parameters. Materials and Methods: Chronic inflammation was assessed in 30 women with PCOS (Group A) and 30 healthy controls (Group B) with highly sensitive C-reactive protein (hsCRP), interleukin-6 (IL-6), tumour necrosis factor alpha (TNFα), and platelet microparticles (PMP). In group A, the relationship of chronic inflammation with insulin resistance, waist hip ratio (WHR) serum testosterone, and serum glutamate pyruvate transaminase (SGPT) were examined. Results: In group A, the hsCRP, TNFα, and PMP were significantly elevated compared to group B. However, IL-6 level was similar between the groups. In group A, PMP showed a significant positive correlation with waist-hip ratio and serum testosterone. IL-6 showed a significant positive correlation with insulin sensitivity and significant negative correlation with insulin resistance and serum glutamate pyruvate transaminase. Conclusion: PCOS is associated with chronic inflammation and PMP correlates positively with central adiposity and biochemical hyperandrogenism in women with PCOS. Key words: Polycystic ovary syndrome, Inflammation, C-reactive protein, Interleukin-6, Tumor necrosis factor, Microparticles.

Background Pycnodysostosis is an autosomal recessive skeletal dysplasia with easily recognizable clinical features and marked molecular heterogeneity. In this study, we explored the clinical and molecular spectrum of 25 Indian patients with pycnodysostosis from 20 families. Methods Clinical information was collected on a predesigned clinical proforma. Sanger method was employed to sequence all the exons and exon/intron boundaries of the CTSK gene. Novel variants were systematically assessed by prediction softwares and protein modelling. The pathogenicity of variant was established based on ACMG-AMP criteria. An attempt was also made to establish a genotype-phenotype correlation and devise a diagnostic scoring system based on clinical and radiological findings. Results Consanguinity and positive family history were present in 65% (13/20) and 45% (9/20) of the families respectively. Short stature and fractures were the predominant presenting complaints and was evident in 96% (24/25) and 32% (8/25) of affected individuals respectively. Gestalt facial phenotype and acro-osteolysis were present in 76% (19/25) and 82.6% (19/23) of the individuals respectively. Hepatosplenomegaly was present in 15% (3/20) of the individuals with one of them having severe anaemia. Causative sequence variations were identified in all of them. A total of 19 variants were identified from 20 families amongst which 10 were novel. Homozygous variants were identified in 90% (18/20) families. Amongst the novel variants, there was a considerable proportion (40%) of frameshift variants (4/10). No significant genotype-phenotype correlation was noted. Scoring based on clinical and radiological findings led to the proposal that a minimum of 2 scores in each category is required in addition to high bone density to diagnose pycnodysostosis with certainty. Conclusion This study delineated the genotypic and phenotypic characterisation of Indian patients with pycnodysostosis with identification of 10 novel variants. We also attempted to develop a clinically useful diagnostic scoring system which requires further validation.

Introduction Polymerase chain reaction (PCR) testing of cerebrospinal fluid (CSF) is a sensitive and specific method in diagnosing herpes simplex virus (HSV) encephalitis. However there are increasing reports of false negative HSV PCR. Case description We present a patient in the 9th decade of life with abnormal behavior and focal seizures with MRI showing a right temporal T2 hyperintense non-enhancing lesion with electrographic evidence of right lateralized periodic discharges. CSF analysis and PCR for HSV-1 and 2 yielded negative results twice, and therefore acyclovir was discontinued. Patient initially improved following correction of hyponatremia. Patient however deteriorated and imaging revealed a new right parietal lesion. Third CSF sample showed lymphocytic pleocytosis with positive HSV-1 PCR. Patient improved following antiviral treatment. Discussion Acyclovir treatment should continue in high clinical suspicion scenarios despite negative HSV PCR. We further discuss causes of PCR false negatives and challenges it poses for patient care., Neuroscience; Nervous System; Viral Disease; Neurology; Diagnostics; neurovirology, MRI, infectious disease, EEG

Recent aggressive scientific and technological developments all these focus on a global environmental issue considering air quality system, reveals the fact that India is facing severe health hazards. In recent reports, more than 10 cities in India are listed on top. The air quality index (AQI) in India launched in 2014 under Swachh Bharat Abhiyan monitors air pollution on 10 scales ranging from low (green) to moderate (yellow) to serious (red) through data analysis of various air contaminating matters like pm 2.5, O3, NO2, SO2, CO. The present paper develops an Internet of Things (IoT) that enabled air quality monitoring system mobile in nature analyzing real-time surrounding data measuring Carbon Monoxide, Smoke and PM level. The system can measure local area air contamination and generate analyzed data based on which it alerts the people through a buzzer device integrated into the system. The user-friendly and easy handling of the system technology is such that it can be installed in houses and in small places.

Dengue virus is an important prevalent mosquito-borne, single positive-stranded RNA virus of the family Flaviviridae (Flavivirus), which is transmitted by infected Aedes female mosquitoes and causes dengue fever. The challenge to control the transmission of these diseases and prompt sight of this virus is an international health problem at present. As a result of the scientific significance of its recognition, recently, the use of biosensors to sense and measure the disease with quick detection is one of the best methods, which is comparatively simple and practical, with high sensibility, accuracy, and selectivity rather than the traditional techniques such as immunology and molecular-based approaches. The electrochemical biosensor-based recognition method from biomolecules using transducers is a simple method, with the possibility of commercialization, inexpensiveness, simplicity, and convenience. Hence, several types of biosensing methods using different biosensors with transducers such as voltammetric, potentiometric, amperometric, and impedimetric are used for the detection of dengue NS1 protein. In this study, we aimed to find out the best biosensing method for the detection and diagnosis of dengue virus. We expect that dengue NS1-based electrochemical diagnostic techniques will open the horizons for growth in the coming times, with thrilling new opportunities for the advancement of commercial design of electrochemical biosensors.

Introduction: Since the late 1980s, critical illness myopathy (CIM) and polyneuropathy (CIP) have been increasingly recognized in the intensive care unit (ICU). We explored whether these causes of ICU weakness were now more likely to lead to electrodiagnostic studies (EDX) at our institution than they were 19-20 years earlier. Methods: We reviewed 100 consecutive ICU patients who underwent EDX from 2009-2015 and compared them to a previously reported study population from 1990-1995.10 Results: Thirty-seven (39%) had CIM, CIP, or both versus 55% in the previous study (p=0.04). Thirty-four (36%) were diagnosed with “traditional” pre-ICU causes of weakness, such as motor neuron disease or Guillain-Barre syndrome, versus 29% in the earlier study (p=0.3). Discussion: CIM and CIP continue to be common disorders that lead to ICU EDX, but their proportion declined compared to 19-20 years earlier, possibly due to the perceived role and selective use of EDX in the ICU. This article is protected by copyright. All rights reserved.

Objective: 17-α-Hydroxylase deficiency (17-OHD) is a very rare disorder of adrenal and gonadal steroidogeneis. The patient usually presents as a phenotypic female with hypertension, hypokalemia, and delayed puberty due to hypergonadotropic hypogonadism. Karyotype may be 46,XX or 46,XY. Timely diagnosis leads to effective management of the patient and appropriate screening of family members.Methods: Case report and review of the literature.Results: A 24-year-old woman presented with primary amenorrhea and poor development of secondary sexual characters along with persistent hypokalemia and hypertension of several years duration. Examination did not show any stigma of Turner syndrome, features of any pituitary hormone deficiency, or hypothyroidism. Further evaluation revealed hypergonadotropic hypogonadism with persistent hypokalemia and refractory hypertension. The karyotype was 46,XX. Possible diagnosis of 17-OHD was considered, which was supported by low serum cortisol, high adrenocorticotropic hormone, and very high serum progesterone level and suppressed plasma renin activity. The patient had a younger sister (11 years old) whom we called for evaluation. She was found to have diffuse skin and mucosal hyperpigmentation along with hypertension. Analysis of the CYP17A1 gene of these two patients revealed a homozygous mutation, p.R362C (c.1084C>T), which has been shown to completely abolish the activity of both 17-α-hydroxylase and 17,20-lyase.Conclusion: The p.R362C (c.1084C>T) mutation led to 17-OHD in two sisters. One sister was diagnosed as a result of family screening. This is the first report of this mutation in India.Abbreviations: 17-OHD 17-α-hydroxylase deficiency; ACTH adrenocorticotropic hormone; CYP17A1 cytochrome P450 17-α-1; PRA plasma renin activity

Progressive multifocal leukoencephalopathy (PML) is a life-threatening central nervous system (CNS) disorder, most commonly described in patients infected with the human immunodeficiency virus (HIV). Limited data exist on its natural history and treatment in solid organ transplant (SOT) recipients. A complication of PML is the immune reconstitution inflammatory syndrome (IRIS), which develops after T cell reconstitution and can have severe consequences when it occurs in the CNS. While well described in HIV-infected individuals, its clinical features, diagnosis, and treatment after SOT are largely unknown. We report a case of a kidney transplant recipient who was diagnosed with PML and developed significant worsening of her symptoms upon reduction of immunosuppression. Thallium SPECT showed avid uptake suggestive of lymphoma, but the diagnosis of PML-IRIS was ultimately established by brain biopsy. She survived with nearly complete restoration of her functional status after a prolonged steroid taper.

Isolated FSH deficiency due to mutations in the gene for β-subunit of FSH is an extremely rare autosomal recessive disease of which only eleven cases have been reported so far. The clinical features include absent breast development and primary amenorrhea in females and azoospermia with normal testosterone levels in males. In this study we report two Kashmiri sisters born to native Kashmiri consanguineous parents with failure of onset of puberty. Hormonal evaluation revealed undetectable serum FSH and estradiol and high LH. Genetic analysis of FSH β-gene identified one nonsense mutation (c.343C > T:p. Arg115Stop) in exon 3. The two sisters were homozygous for this nonsense mutation while the parents were heterozygous. Incorporation of a stop codon at 115 codon position is predicted to result in the formation of truncated FSH β protein, lacking 14 amino acid from the carboxy-terminus (p.Arg115Stop). Very recently, this same mutation was reported for the first time in a Chinese male. Ours is the first ever report of any FSH β-subunit mutation from the Indian sub-continent and this particular mutation in any female from anywhere in the world. We conclude and emphasize that this diagnosis should be considered in girls with delayed puberty and selective deficiency of FSH.

Neurological emergencies are a significant source of morbidity and mortality in immunocompromised patients. Immunodeficiency can be attributed to congenital and acquired causes. Congenital immunodeficiencies can either be combined with involvement of both cellular and humoral immunity or restricted to impairment of either type. Common combined immunodeficiency syndromes include ataxia telangiectasia, Wiskott Aldrich syndrome, and DiGeorge syndrome whereas X linked agammaglobulinemia and common variable immunodeficiency are characterized by isolated impaired humoral immunity. As opposed to rare patients with congenital immunodeficiencies, acquired immunodeficiencies are much more common. Acquired immunodeficiency is seen in HIV patients, diabetics, and in various patients treated with immunosuppressive, cytotoxic, and antirejection medications (e.g., transplant recipients, patients with autoimmune disorders, and cancer). These people are at increased risk of various neurologic emergencies including opportunistic CNS infections, posterior reversible encephalopathy syndrome (PRES), immune reconstitution inflammatory syndrome (IRIS), epilepsy, and stroke.

Osteolysis, caused by active resorption of bone matrix by osteoclasts, can be primary or can develop secondary to a variety of disease processes. An elevated level of inflammatory cytokines in the local milieu and increased blood flow secondary to infection or autonomic neuropathy stimulate the osteoclasts and cause bone loss in the diabetic foot. Charcot's neuroarthropathy and osteomyelitis are well-known foot complications of diabetes, and secondary osteolysis has largely been underappreciated and, hence, underreported. Plain radiographs, an initial component in the evaluation of the diabetic foot, may not successfully differentiate secondary osteolysis from osteomyelitis. We describe a patient with phalangeal osteolysis secondary to soft-tissue infection in whom a correct and timely diagnosis helped avoid unnecessary surgical interventions.

Background There is a constant search for an ideal treatment for vitiligo. Platelet-rich plasma (PRP) is a novel modality for treating stable vitiligo. Presently, literature regarding the efficacy of combining either PRP or platelet-poor plasma (PPP) with psoralen+sunlight (PUVASOL) in vitiligo does not exist. Objective This study compares the safety and efficacy of combining PUVASOL with either PRP or PPP against PUVASOL alone in patients with stable nonsegmental vitiligo. Patients and methods This prospective, open-labeled, comparative study was done in 20 patients with stable nonsegmental vitiligo, each having at least three vitiligo patches of similar shape and size. All the patients received PUVASOL as standard treatment modality. PRP or PPP was injected into two separate study patches as an adjuvant treatment with PUVASOL; however, the third patch acted as a control and was treated by PUVASOL alone. These patients were followed up for 4 weeks after the end of four treatment sessions. Results Compared with control areas (exposed to PUVASOL only), statistically significant more repigmentation was seen in areas treated with a platelet preparation (either PRP or PPP) along with PUVASOL. However, there was no significant difference between PRP and PPP arm (P=0.824) as per qualitative and quantitative assessment. Conclusion Addition of a platelet preparation (either PRP or PPP) had an additive beneficial effect on the response of PUVASOL therapy in patients with stable vitiligo at the study end point of 16 weeks. However, PRP and PPP showed comparable efficacy at the study end point in terms of repigmentation when used in conjunction with PUVASOL.

Introduction Critical hand ischemia with advancing gangrene of digits requires urgent intervention to salvage as much tissue as possible. The purpose of this study was to evaluate the efficacy of “palmar arch loop” technique for endovascular management of critical hand ischemia by establishing inline flow to the palmar arch via both radial artery and ulnar artery, in patients with failed antegrade recanalization. To the best of our knowledge, this is the first case series evaluating the efficacy of “palmar arch loop” technique, with retrograde percutaneous transluminal angioplasty of the involved radial artery and/or ulnar artery. Material and methods We retrospectively investigated 10 patients (60% female; mean age 42 ± 18 years; mean time of presentation post-acute event 24 ± 11 days) with critical hand ischemia undergoing endovascular intervention using “palmar arch loop” technique at a single center in northern India between April 2017 and March 2019. All patients were followed up at regular intervals (weekly for a month, fortnightly for 3 months, and then at 6 and 12 months) with clinical assessment and SpO2 measurement. Study end points were technical success rate, hand healing, and primary patency rate at one year. Results Causes for critical hand ischemia were iatrogenic injuries due to inadvertent intra-arterial injection in 50% ( n = 5) and thromboembolic events in 50% patients ( n = 5). Vessels involved were: both radial artery and ulnar artery along with the PA in 50%; radial artery and palmar arch in 30%; ulnar artery and palmar arch in 20%. All of them had total occlusion of the involved vessel (>2/3rd of total length) with occlusion/diffuse disease of palmar arch as well; 70% technical success rate was achieved ensuring inflow to palmar arch via both the arteries with improved flow distally to the common and proper digital arteries. Retrograde percutaneous transluminal angioplasty of radial artery in 50% ( n = 5) and ulnar artery in 20% ( n = 2) was done successfully by looping the guidewire across the palmar arch; 90% showed subjective improvement in pain with healing of the lesions and/or formation of clear line of demarcation with reversal of pregangrenous changes proximally. Out of the eight patients with gangrene of fingers, three underwent minor amputation of the gangrenous digits and five underwent auto-amputation of the gangrenous tissue with complete healing of the stump. Primary patency rate was 85.7% at one year. There was no access site-related complication or mortality in the follow-up period. Conclusions Endovascular management of critical hand ischemia by “palmar arch loop” technique is an efficient technique to deal with occluded forearm vessels, particularly when antegrade recanalization fails. This technique, with good technical success and patency rates, is potentially a unique tool in the endovascular armamentarium for salvaging hand.

Background: Postoperative nausea and vomiting (PONV) was termed “the big little problem” nearly a quarter century ago in an editorial .The past decade has witnessed the introduction of several significant innovations to combat PONV, but it still remains as big a problem as before because newer choices and confusions over standardization added side by side . The aim of this study is to compare the efficacy of palonosetron with that of granisetron and ondansetron in the treatment and prevention of postoperative nausea and vomiting after laparoscopic cholecystectomy. Methods: This randomized prospective comparative clinical study was carried out in the NIMS Medical College & Hospital, NIMS University, Jaipur, during the period of January 2013 to December 2013 amongst female patients of ASA grade I and II (ASA = American Society of anesthesiology) , scheduled for laparoscopic cholecystectomy under general anesthesia. A total number of 90 patients were selected and randomized into three groups of 30 patients each. Group-I was given inj. palonosetron (0.25 mg), Group-II was given inj. granisetron (1 mg) and Group–III was given inj. ondansetron (8 mg). One way analysis of variance (ANOVA) and Pearson’s Chi-square test were done as the tests of significance whenever applicable to compare the mean of different groups. Results: The incidence of nausea was 10% in Palonosetron-group while it was found to be 60% in Ondansetron-group. The incidence of vomiting was 6.7% in group-I, 26.6% in group-II & 53.3% in group-III respectively. The difference was statistically significant between group I vs group II (p

The case study relates to firearm suicide by a security personal and such incidents are very common among armed forces Incident of firearm cases are often reported to forensic science laboratory for reconstruction to establish the crime There are various reasons contributed for such incidents among security forces It is observed either head or chest is the most common site for self inflicted firearm wound in almost all suicide cases In one case a security personal was on sentry duty with Indian Small Arms System INSAS rifle and committed suicide by his service firearm The deceased was lying in a pool of blood along with firearm and one fired cartridge case near the body The autopsy surgeon reported having entry wound on the back side situated in occipital bone cm above cervical vertebra and exit wound over the forehead of the deceased The observation was controversial since the presence of entry wound was at uncommon place showing absence of singeing blackening burning tattooing and devoid of impression of the muzzle In addition it was also difficult for the shooter to fire from back side Moreover such type of incident has never been reported in literature in suicide cases by firearm Further bullet wound study along with spot analysis could confirm the entry wound to be on forehead and exit on the back The mystery of origin of entry exit wound could be established by wound ballistics study

Introduction: Glycated hemoglobin (HbA1c) can be altered in different conditions. We hypothesize that HbA1c levels may change due to altered thyroid status, possibly due to changes in red blood cell (RBC) turnover. Objectives: The objective of this study was to determine the effects of altered thyroid status on HbA1c levels in individuals without diabetes, with overt hyper- and hypo-thyroidism, and if present, whether such changes in HbA1c are reversed after achieving euthyroid state. Methods: Euglycemic individuals with overt hypo- or hyper-thyroidism were selected. Age- and sex-matched controls were recruited. Baseline HbA1c and reticulocyte counts (for estimation of RBC turnover) were estimated in all the patients and compared. Thereafter, stable euthyroidism was achieved in a randomly selected subgroup and HbA1c and reticulocyte count was reassessed. HbA1c values and reticulocyte counts were compared with baseline in both the groups. Results: Hb A1c in patients initially selected was found to be significantly higher in hypothyroid group. HbA1c values in hyperthyroid patients were not significantly different from controls. HbA1c reduction and rise in reticulocyte count were significant in hypothyroid group following treatment without significant change in glucose level. Hb A1c did not change significantly following treatment in hyperthyroid group. The reticulocyte count, however, decreased significantly. Conclusion: Baseline HbA1c levels were found to be significantly higher in hypothyroid patients, which reduced significantly after achievement of euthyroidism without any change in glucose levels. Significant baseline or posttreatment change was not observed in hyperthyroid patients. Our study suggests that we should be cautious while interpreting HbA1c data in patients with hypothyroidism.

Background: Pain is one of the most frequent reasons for visiting a doctor. Large-scale studies in Western countries have shown that a fifth of the adult population suffer from chronic pain. Treatment of pain, still a major problem in clinical practice. Despite several available analgesics, unrelieved pain remains a major health care issue. Amitriptyline is a tricyclic antidepressant drug, which is regarded as adjuvant analgesic. There is a common consensus among the researchers on analgesic effect of amitriptyline which is mediated by central pathway but for the peripheral mechanism no conclusive evidence exists till now.Methods: To establish the analgesic mechanism of amitriptyline we tried to evaluate the analgesic activity on different mice models for central (Radiant heat tail flick test and Haffner’s tail clip method) and peripheral analgesia (Writhing test). We also compare the effects of amitriptyline with standard drugs for central and peripheral analgesia.Results: Both in Radiant heat tail flick test and Haffner’s tail clip method we found that the amitriptyline showed significant (p

Introduction: Short penile length is a commonly encountered problem in clinical practice. Detection of abnormal stretched penile length (SPL) warrants appropriate endocrine evaluation. Ethnicity-specific SPL data are required to detect these abnormalities. There is a dearth of such data in India. This study aims to establish normative values of SPL in boys from West Bengal. Materials and Methods: This is a cross-sectional study. SPL, testicular volume (TV), height/length, and weight were measured in 460 boys aged 1 to 13 years from the schools located at urban, suburban, and rural areas in the state of West Bengal, India. Similar data were collected from 36 healthy neonates within 1–3 days of full-term delivery at IPGME and R and SSKM Hospital, Kolkata, West Bengal, India. Results: The 5th percentile, median, and 95th percentile of SPL were 1.7, 2.0, and 2.7 cm for neonates; 3.5, 4.4, and 6.4 cm for the children aged 1 Y–2 Y 11 M; 4.0, 5.5, and 7.0 cm for the age group 3 Y–4 Y 11 M; 4.2, 6.0, and 7.2 cm for the age group 5 Y–6 Y 11 M; 4.3, 6.0, and 7.6 cm for the age group 7 Y–8 Y 11 M; 4.4, 6.5, and 9.0 cm for the age group 9 Y–10 Y 11 M; and 4.8, 7.0, and 11.0 cm for the age group 11 Y–12 Y 11 M, respectively. SPL showed significant positive correlation with TV [r = 0.365, P < 0.0005] and height of the children [r = 0.516, P < 0.0005], but not with BMI. Conclusion: Our study provides normative data of SPL in neonate and children aged 1 to 13 years from the eastern part of India. SPL value correlated positively with TV and height of children.

B ecause type 2 diabetes is a progressive disease, its natural course requires initiation of insulin in a significant proportion of patients, especially when oral agents fail to achieve glycemic targets. Most practicing physicians and endocrinologists acknowledge that neither the transition to nor the journey with insulin treatment is often as smooth as one would hope. Most have occasionally met with patients who plead for help in controlling their blood glucose levels with oral drugs alone. Often, doctors struggle to persuade such patients to start insulin. In this article, we share some of our experiences—some common throughout the world and others unique to our country—in caring for patients who are prescribed insulin. It is important to learn from these experiences with insulin because it represents, more often than not, the last arrow in our treatment quiver. The patient was a 45-year-old man who has had type 2 diabetes for the past 6 years and had been taking insulin for the past 2 years. His body weight was 50 kg (BMI 24 kg/m2). He presented with uncontrolled and recently increased blood glucose levels and a dramatic increase in insulin dose during the past 5 months without any apparent cause. He had no history of fever, infections, or steroid use. He had had multiple hospital visits during the past few months. Figure 1. Discoloration with hypertrophy on medial aspects of both thighs on the site where the patient described in Case Study 1 was injecting insulin. The patient appeared to be well educated and concerned about this situation. To our surprise, however, we found he was injecting insulin on the medial aspect of his thighs. Examination showed lipohypertrophy with swelling in that region (Figure 1). The crowded clinic with its lack of trained diabetes educators and nurses was the perfect setting for this …

Background and objective: Metformin is often used as a first-line therapy for Type 2 diabetes mellitus (T2DM), but the glycemic response to metformin is variable in patients. Here, we aimed to assess the inter-patient variability in terms of glycemic response to metformin in the state of West Bengal, India. Material and methods: We enrolled newly diagnosed treatment naive 113 patients with T2DM. Patients were subjected to assay of glycated hemoglobin (HbA1c), fasting blood glucose (FBG), postprandial blood glucose (PP) and measurement of body mass index (BMI), waist circumstances (WC) before and after the end of 3 months of immediate release metformin (2000mg/day) therapy. Results: Out of 113 patients, 111 (58 male and 53 female; average age 43.13 years) were provided with 3 months of metformin therapy. 102 individuals responded to metformin, but HbA1c levels of 9 patients did not improve after 3 months of drug therapy. Conclusions: In the present study, metformin lead to improvements in glycemic control in 92% of newly diagnosed T2DM patients but in 8% does not which is much less in this part of India.

The XX male syndrome, first reported in 1964, is an unusual cause of male factor infertility. Its relative rarity coupled with the presence of unambiguous male external genitalia in most patients with this syndrome makes clinicians overlook the condition in the differential diagnosis of primary infertility. We report five genetically proven XX males, who all presented with azoospermia and primary infertility (four out of five), and discuss their phenotypic characteristics and hormonal profiles to make treating physicians aware of this diagnosis in appropriate settings.

Pseudoacromegaly or acromegaloidism is a clinical condition characterised by physical signs suggestive of excess growth hormone (GH) but with normal functioning of the GH—insulin-like growth factor-1 (IGF-1) axis. A number of disease entities, such as pachydermoperiostitis, severe insulin resistance, familial mandibular prognathism, acromegaloid facial appearance and chronic intake of phenytoin and minoxidil, are known to be associated with pseudoacromegaly. When clinical features of acromegaly are associated with normal baseline and dynamic GH and IGF1 levels, ‘burned out’ or ‘silent’ acromegaly due to spontaneous infarction of a GH-secreting pituitary adenoma should also be considered. Long-standing severe primary hypothyroidism rarely present with skin and soft tissue changes suggestive of acromegaly and the scenario gets further complicated by the radiological evidence of pituitary enlargement potentially culminating in diagnostic …

There are conflicting opinions on whether postural tachycardia syndrome predisposes to syncope. We investigated this relationship by comparing the frequency of syncope in postural tachycardia syndrome and orthostatic hypotension.We queried our autonomic laboratory database of 3700 patients. Orthostatic hypotension and postural tachycardia syndrome were defined in standard fashion, except that postural tachycardia syndrome required the presence of orthostatic symptoms and a further increase in heart rate beyond 10 minutes. Syncope was defined as an abrupt decrease in blood pressure and often, heart rate, requiring termination of the tilt study. Statistical analysis utilized Fisher's exact test and Student's t test, as appropriate.Of 810 patients referred for postural tachycardia syndrome, 185 met criteria while another 328 patients had orthostatic hypotension. Of the postural tachycardia syndrome patients, 38% had syncope on head-up tilt, compared with only 22% of those with orthostatic hypotension (P.0001). In the postural tachycardia group, syncope on head-up tilt was associated with a clinical history of syncope in 90%, whereas absence of syncope on head-up tilt was associated with a clinical history of syncope in 30% (P.0001). In contrast, syncope on head-up tilt did not bear any relationship to clinical history of syncope in the orthostatic hypotension group (41% vs 36%; P=.49).Our results demonstrate that syncope (both tilt table and clinical) occurs far more commonly in patients who have postural tachycardia syndrome than in patients with orthostatic hypotension. These findings suggest that one should be clinically aware of the high risk of syncope in patients with postural tachycardia syndrome, and the low-pressure baroreceptor system that is implicated in postural tachycardia syndrome might confer more sensitivity to syncope than the high pressure system implicated in orthostatic hypotension.

Testicular metastasis from a solid malignancy of the distant organ is a rare entity and prostate, gastrointestinal tract, lungs, skin, and kidneys are the common primaries. Gastric carcinoma with testicular metastasis is an extremely rare entity with only few cases reported in the literature. Most of the testicular metastases are unilateral. Synchronous bilateral testicular metastasis is an extremely rare situation in gastric primary. We report a first case of synchronous bilateral testicular metastasis in a treated case of gastric carcinoma in India.

Acral metastasis is rare in incidence with poor prognosis due to presence of widespread metastases during presentation. Lung is the most common primary for acral metastases followed by breast and kidney. Acrometastasis with head and neck primary is an extremely rare situation with only few cases reported in the literature. Here, we present a case of acral metastases in a 40-year-old male. The patient was previously diagnosed as a case of squamous cell carcinoma of gingivobuccal sulcus on the left side, and for which, he had undergone radical surgery followed by adjuvant concurrent chemoradiation 6 months back. The patient had local recurrence with multiple metastatic pleural nodules during diagnosis of acral metastasis. The patient was treated with one cycle of palliative chemotherapy followed by amputation of the metastatic finger. However, after 2 months of treatment, the patient was died due to the disease progression.

Renal tubular disorders are an important cause of refractory rickets. Wilson′s disease, an inherited disorder of copper metabolism has varied presentations. We present a case of refractory rickets due to Fanconi′s syndrome attributable to Wilson′s disease. An adolescent girl presented with pain in the hip and knee joints and a knock-knee deformity since six years. She had received multiple doses of cholecalciferol with little improvement. There was no history of seizures, polyuria, jaundice, intake of drugs, or similar complaints in the family. Examination revealed a severely short stature with widening of the wrist joint and genu valgum. Examination of the central nervous system (CNS) was normal. Skeletal radiographs showed features suggestive of rickets at the hip and knee joints. Routine biochemistry was normal, 25-hydroxyvitamin D [25(OH)D] was adequate (57.1 ng/dL), with normal corrected calcium (9.24 mg/dL), low phosphate (2.76 mg/dL), elevated bone-specific alkaline phosphatase, and normal renal functions. Twenty-four-hour urine revealed phosphaturia, kaliuresis, and glucosuria with normal blood sugars and aminoaciduria. Blood gas analysis revealed normal anion gap metabolic acidosis with a urine pH of 7. Ammonium chloride (NH 4 CL) challenge test revealed proximal tubular acidosis. A search for causes revealed Kayser-Fleischer rings. The diagnosis of Wilson′s disease was confirmed by low serum ceruloplasmin levels (6.5 mg/dL; normal: 18-35 mg/dL) with high 24-hour urine copper levels (433 mcg; normal: 20-50 mcg). She was started on a replacement of alkali, phosphate, calcium, and vitamin D, with zinc acetate for Wilson′s disease. Rickets as a presenting feature of Wilson′s disease has been reported rarely. Recognition of this entity is important, as treatment of the primary condition may improve tubular function as well.

Ectopic neurohypophysis (EN) is found in nearly half of children with growth hormone deficiency (GHD). Rathke′s cyst (RC) is uncommon in children and when present, hypopituitarism is found in nearly half of them. We present a fourteen and half-year-old girl with severe short stature and delayed puberty who on evaluation was found to have GHD, secondary hypocortisolism, and hypogonadism. Imaging revealed hypoplastic anterior pituitary, stalk agenesis, EN at tuber cinereum and intrapituitary RC. This is perhaps the first report of simultaneous occurrence of EN and RC, which was seen in a girl with multiple pituitary hormone deficiency. A primary defect in pituitary development may explain this simultaneous occurrence of EN and RC and hence this severe anterior pituitary function deficit.