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Abstract Introduction Although real-world studies demonstrate that those prescribed nirmatrelvir/ritonavir (and particularly within 5 days of symptom onset) are less likely to experience severe COVID-19 outcomes, prior studies show that only a small fraction of patients with COVID-19 who are eligible for nirmatrelvir/ritonavir receive a prescription. Studies calculating the proportion of nirmatrelvir/ritonavir prescriptions filled and identifying individual- and pharmacy-level correlates of filling nirmatrelvir/ritonavir are lacking. Methods This retrospective cohort study included individuals aged ≥ 12 years with a nirmatrelvir/ritonavir prescription ordered at a large national retail pharmacy (December 22, 2021–August 12, 2023). Those taking contraindicated medications were excluded. For those with only one nirmatrelvir/ritonavir prescription ordered, the outcome was whether the prescription was filled (yes/no). In a subanalysis of these individuals, the outcome was whether the prescription was filled within 5 days of symptom onset (yes/no). For those with multiple prescriptions ordered, the outcome was whether > 1 (vs. 0 or 1) prescriptions were filled. A log-binomial regression with generalized estimating equations was used to identify individual (clinical and demographic) and pharmacy-level (percentage of trade area that is non-Hispanic white, urbanicity, US Census region, and tract-level area deprivation index) correlates. Results A total of 2,103,570 unique nirmatrelvir/ritonavir prescriptions were ordered for 1,985,990 individuals. Among the 95% of individuals prescribed only one nirmatrelvir/ritonavir course, 88% filled their prescription. Among those with > 1 prescription ordered, 77% (82,993/108,411) filled one and 13% (13,662/108,411) filled > 1. Patients ≥ 50 years of age and those with documented high-risk conditions were slightly more likely to fill prescriptions, regardless of whether one or multiple courses were ordered. Individuals with cancer, asthma, or taking corticosteroids or immunosuppressive medications were more likely to fill multiple prescriptions. Conclusions Most patients filled their nirmatrelvir/ritonavir prescriptions. Interventions to improve uptake should focus on increasing patient and provider awareness, reducing nirmatrelvir/ritonavir prescribing disparities, and ensuring treatment initiation within 5 days.

• The efficacy of weekly somatrogon injections was no different from that of daily somatropin injections to treat children who don’t make enough growth hormone to grow adequately. ○ Efficacy refers to how well a drug works in a clinical trial. ○ Children treated with weekly somatrogon had an increased growth rate, similar to that of children treated with daily somatropin . • The safety of weekly somatrogon injections was similar to that of daily somatropin injections. The original scientific article on which this summary is based was published in The Journal of Clinical Endocrinology & Metabolism and can be accessed for free at: https://academic.oup.com/jcem/article/107/7/e2717/6566444 . The details of the original article are as follows: Cheri L. Deal, Joel Steelman, Elpis Vlachopapadopoulou, Renata Stawerska, Lawrence A Silverman, Moshe Phillip, Ho-Seong Kim, CheolWoo Ko, Oleg Malievskiy, Jose F. Cara, Carl L. Roland, Carrie Turich Taylor, Srinivas Rao Valluri, Michael P. Wajnrajch, Aleksandra Pastrak, and Bradley S. Miller. Efficacy and safety of weekly somatrogon vs daily somatropin in children with growth hormone deficiency: a phase 3 study. J Clin Endocrinol Metab 2022; 107(7): e2717–e2728. The purpose of this plain language summary is to help you to understand the findings from recent research. • Somatrogon is used to treat growth hormone deficiency (the condition under study that is discussed in this summary). Approval varies by country; please check with your local healthcare provider for more details. • The results of this study may differ from those of other studies. Physicians/providers should make treatment decisions based on all available evidence and not on the results of a single study.

Although N-ethyl-N’-(3-dimethylaminopropyl) carbodiimide hydrochloride (EDC.HCl) is a common reagent in peptide synthesis, it presents two drawbacks. First of all, it is in a tautomerism equilibrium with cyclic form that it is not productive. Second, it is hydrolysed to the corresponding urea. Furthermore, it is only soluble in water, which limits its use in solid-phase peptide synthesis (SPPS) strategy. Herein, two quaternary carbodiimides (QCD), namely 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide methiodide (EDC.MeI) and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide methotosylate (EDC.MeTos), are described. The presence of the quaternary N prevents the formation of the cyclic form but preserves its solubility in water. However, the QCDs are also soluble in other organic solvents. These QCDs are totally stable at least up to 20 days. They present a level of racemization similar or even slightly better than EDC.HCl and a better performance when used for the Solid-Phase Peptide Synthesis (SPPS) of different peptides. Finally, the preliminary tests indicate that its use is safer than other carbodiimides.

Cardiac dysfunction is a common feature of numerous diseases, ranging from metabolic disorders like Mucopolysaccharidosis Type 1 (MPS I), a.k.a. Hurler syndrome to neuromuscular disorders such as Myotonic Dystrophy type 1 (DM1). The ability to quantify cardiac abnormalities in animal models of these diseases is a valuable translational tool for preclinical testing of novel therapeutic approaches. In contrast to methods that measure the left ventricle (LV) phenotype, we employed ultrasound imaging to assess the ascending aortic diameter and ascending aortic blood velocity. Methods: We imaged two disease models - MPS I Hurler mouse model and DM1 mouse model (DMSXL) - using the Vevo2100 platform. Ascending aortic diameter in the proximal thoracic aortic region and ascending aortic blood velocity just before the branching point of the brachiocephalic artery were measured as rapid imaging readouts. In addition, histopathology was performed on relevant tissue samples. Results: The two mouse models demonstrate opposing aorta phenotypes. Hurler mice had a dilated aorta and slightly increased blood velocity with disease progression, while the aorta diameter in DMSXL mice narrowed and had a blood velocity decrease as the disease progressed. In the Hurler model, we demonstrated that a single dose of adeno-associated virus (AAV) delivered gene therapy provides aortic phenotype improvement. In the DMSXL model, we established aortic phenotype criteria at baseline. Conclusion: Ultrasound imaging of aortic diameter and blood velocity can offer objective and longitudinal assessments of disease progression and treatment efficacy in real time. This method might therefore have noninvasive clinical applicability as phenotype indicator of cardiac dysfunction.

Introduction: Accurate diagnosis of the etiology of thyrotoxicosis in pregnancy is important to guide appropriate treatment. The role of thyroid blood flow velocities by color Doppler to differentiate between Graves' disease (GD) in pregnancy and gestational transient thyrotoxicosis (GTT) is not well explored. This study evaluated inferior thyroid artery (ITA)-peak systolic velocity (PSV) as a marker for differential diagnosis of thyrotoxicosis in pregnancy. Methods: Fifty-six pregnant patients with thyrotoxicosis (30 with GTT and 26 with GD) along with 30 age-matched healthy euthyroid pregnant subjects were enrolled. Thyroid ultrasound examinations and color Doppler was performed by an ultrasound scanner. The studies of the right and left ITAs were performed with Doppler, and the PSV and End diastolic velocity (EDV) values were obtained from the right and left ITA. Results: The mean total T4 value in GD and GTT were almost similar (25.04 ± 2.43 vs 23.25 ± 2.81, P value = 0.14). Beta HCG levels were significantly higher in cases of GTT as compared to GD (152946 ± 26694 vs 120608 ± 21244 mIU/ml, P < 0.0001). The ITA-PSV and EDV in patients with GTT were significantly lower than those of pregnant patients with GD (right: 22.5 ± 6.8 and 8.3 ± 2.3; left: 22.97 ± 6.3 and 8.13 ± 2.01; P < 0.001). receiver-operating-characteristic (ROC) curve demonstrated an optimal cutoff value of mean right ITA-PSV of 35 cm/sec to differentiate GTT from GD during pregnancy, with 84.6% and 93.3% sensitivity and specificity. Conclusion: Thyroid artery velocities can help to differentiate between GD and GTT. The cutoff point of mean ITA-PSV at 35 cm/s had an excellent value in differentiating between the two, with good sensitivity and specificity.

It is important to understand real-world BNT162b2 COVID-19 vaccine effectiveness (VE), especially among racial and ethnic minority groups. We performed a test-negative case-control study to measure BNT162b2 COVID-19 VE in the prevention of COVID-19-associated acute respiratory illness (ARI) hospitalizations at two Atlanta hospitals from May 2021–January 2023 and adjusted for potential confounders by multivariate analysis. Among 5139 eligible adults with ARI, 2763 (53.8%) were enrolled, and 1571 (64.5%) were included in the BNT162b2 analysis. The median age was 58 years (IQR, 44–68), 889 (56.6%) were female, 1034 (65.8%) were African American, 359 (22.9%) were White, 56 (3.6%) were Hispanic ethnicity, 645 (41.1%) were SARS-CoV-2-positive, 412 (26.2%) were vaccinated with a primary series, and 273 (17.4%) had received ≥1 booster of BNT162b2. The overall adjusted VE of the BNT162b2 primary series was 58.5% (95% CI 46.0, 68.1), while the adjusted VE of ≥1 booster was 78.9% (95% CI 70.0, 85.1). The adjusted overall VE of primary series for African American/Black individuals was 64.0% (95% CI 49.9, 74.1) and 82.7% (95% CI 71.9, 89.4) in those who received ≥1 booster. When analysis was limited to the period of Omicron predominance, overall VE of the primary series decreased with widened confidence intervals (24.5%, 95% CI −4.5, 45.4%), while VE of ≥1 booster was maintained at 60.9% (95% CI 42.0, 73.6). BNT162b2 primary series and booster vaccination provided protection against COVID-19-associated ARI hospitalization among a predominantly African American population.

Obesity has been associated with reduced growth hormone (GH) secretion, which might lead to the over diagnosis of adult GH deficiency (GHD) in overweight (OW)/obese hypopituitary patients. Currently, there are no body mass index (BMI)-specific peak GH cut-offs for the glucagon stimulation test (GST) for assessing adult GHD in India, given the BMI cut-offs vary for Asians. The study's main objective was to determine a peak GH cut-off level for the diagnosis of adult GHD in overweight (OW)/obese individuals utilizing the GST. Forty OW/obese subjects were studied in two groups of 20 each. The first group included 20 OW/obese hypopituitary adults and the second group included 20 control subjects. The intervention consisted of a 3 h GST. The main outcome measured was the peak GH level on GST. The mean age of control subjects was lower (33.15 ± 7.67 v/s. 42.10 ± 13.70 years; P = 0.017) in comparison with hypopituitary adults. The mean BMI (27.93 ± 1.63 v/s. 25.81 ± 1.66 kg/m2; P < 0.001), mean IGF1 (272.81 ± 38.57 v/s. 163.75 ± 42.42; P < 0.001, and mean HOMA IR (11.8 ± 9.7 v/s. 6.02 ± 3.14; P = 0.02) was greater in OW/obese controls. The mean GH peak was significantly higher in control subjects (5.41 ± 3.59 ng/mL v/s. 1.49 ± 1.25 ng/mL; P < 0.001) compared to hypopituitary subjects. ROC curve analysis demonstrated a GH cut-off of 3.3 ng/mL with a moderate sensitivity of 70% and high specificity of 95%, with an AUC of 0.838 (P < 0.001; 95% confidence interval [CI] of 0.710–0.965) for the diagnosis of GHD in overweight/obese hypopituitary adults. This study demonstrates that a cut-off of 3.3 ng/mL would diagnose GHD in Indian overweight/obese hypopituitary adults.

Groin hernias are the commonest abdominal wall hernias; these hernias are known to develop various complications. Strangulation is a serious and life-threatening complication. Various surgical procedures like primary tissue repair, mesh repair, keep open with secondary repair, etc. are in practice for strangulated groin hernias. Postoperative infection and recurrence are the main concerns with these procedures. The aim of conducting this study was to compare the outcomes of the mesh hernioplasty with Desarda’s purely tissue hernioplasty in the treatment of strangulated inguinal hernia. A total of one hundred and twenty-four patients were included in the study. These patients were grouped into group A (mesh hernioplasty group) and group B (Desarda’s tissue repair group) and randomization was done. Results of these two techniques were compared with respect to post-operative seroma, surgical site infection, recurrence, and chronic pain. Seroma formation was more in group A, which accounts for 35.48%(22) of patients than in group B patients accounts for 19.35%(12). Operative site infection was more in group A, which accounts for 35.48%(22) patients than in group B 9.67%(6) patients. Recurrence was more in Group A patients which accounts for 22.58%(14) than in Group B patients which accounts for 3.22%(2). More patients account for 19.35%(12) in group A experienced chronic pain than the patients 1.61%(1) in Group B. The current study showed that Desarda’s technique is a safe, effective, and single-sitting technique with a significantly reduced risk of seroma, surgical site infection, chronic pain, and recurrence than mesh hernioplasty for strangulated inguinal hernia.

In Purpose: The fabrication technique can influence the mechanical properties of Cobalt-Chromium (Co-Cr) dental alloys. Hence, the present study aims to determine the corrosion resistance and thermal expansion of alloys manufactured using three contemporary techniques. Material and Methods: A total of nine specimens of Co-Cr alloy were prepared according to ISO 22674 by each one of the three manufacturing processes (three in each process); conventional casting, direct metal laser sintering (DMLS) and milling (MIL). All these specimens were tested for coefficient of thermal expansion and corrosion resistance. The data was tabulated and analyzed statistically. Results: The difference in the thermal expansion of alloys fabricated using three techniques was non-significant at almost all the temperatures from 50 ºC to 950 ºC (p>0.05), except 450 ºC and 600 °C. The polarization resistance of specimens manufactured using the conventional method was more compared to DMLS and MIL at pH 5 (Conventional>MIL>DMLS) (p

Current environmental concerns and expensive infrastructure costs have a significant impact on the adoption of wind turbine technology. Research on the technologies of small wind turbines, which are much smaller in size and capacity, has increased recently. These Small wind turbines have a minimal influence on the environment and require less infrastructure. They have a limited capacity for power generation, necessitating the connection of several turbines to generate usable power. Numerous topologies have been proposed by researchers to combine the power of several wind turbines, but these conventional topologies were primarily developed for high-power wind turbines and cannot be used to connect very small wind turbines because a sizable portion of the generated power would be lost in driving the sophisticated electronic components

Summary: Despite extensive studies on kinematic features of impacting drops, the effect of mechanical stress on desiccated bacteria-laden droplets remains unexplored. In the present study, we unveiled the consequences of the impaction of bacteria-laden droplets on solid surfaces and their subsequent desiccation on the virulence of an enteropathogen Salmonella typhimurium (STM). The methodology elucidated the deformation, cell-cell interactions, adhesion energy, and roughness in bacteria induced by impact velocity and low moisture because of evaporation. Salmonella retrieved from the dried droplets were used to understand fomite-mediated pathogenesis. The impact velocity-induced mechanical stress deteriorated the in vitro viability of Salmonella. Of interest, an uninterrupted bacterial proliferation was observed in macrophages at higher mechanical stress. Wild-type Salmonella under mechanical stress induced the expression of phoP whereas infecting macrophages. The inability of STM ΔphoP to grow in nutrient-rich dried droplets signifies the role of phoP in sensing the mechanical stress and maintaining the virulence of Salmonella.

Introduction. Ventral hernias are the second most common hernia; Onlay and Sublay operating techniques are procedures commonly performed in such cases. There is no consensus on the superiority of these procedures. The aim of this study was to compare the results of both procedures in order to identify the recommended technique between the two options. Materials and Methods. A total of 106 patients with epigastric, umbilical, paraumbilical, incisional hernias were studied. These patients were grouped into group A (onlay) and Group B (sublay). The outcomes of the two techniques were compared with respect to operative time, pain, hospital stay, seroma, infection, recurrence and patient satisfaction. Results. The mean operative time was 81.30 minutes in group A, and 85.85minutes in group B. Twenty-two (42.5%) patients in group A and seven (12.96%) patients in group B developed seroma. Nine (17.3%) patients in group A, 3 (5.55%) patients in group B developed post-operative infection. 30 (57.69%) patients in group A and 47(87.3%) patients in group B reported moderate pain, whereas three (5.76 %) and seven (12.96%) patients in group A and group B were reported severe pain in immediate post-operative period. At 48 hours, 20 (38.46%) and 24 (44.44%) of patients in group A and B were reported moderate pain, whereas 32 (61.53%) and 30 (55.55%) patients in group A and B reported mild pain. The mean hospital stay was 10.11 days in group A and 6.22 in group B. Three (5.76 %) patients of group A has recurrence, none of the patients in sublay group has developed recurrence. Thirty-nine (72.22%) patients of sublay group expressed their satisfaction but only 20 (38.46%) patients in onlay group expressed their satisfaction. Conclusion. With reference to all the study parameters except one, the sub lay technique of mesh placement appears to be better. The exception is pain in the immediate postoperative period.

OBJECTIVE: To study the etiological and clinical profile of children presenting with short stature and to assess growth velocity in children after 6 months of treatment. METHODS: This prospective observational study was conducted between January 2017 to May 2018. One hundred consecutive children attending the outpatient department for short stature were thoroughly evaluated clinically and investigations were done as deemed necessary. The cases were followed up for 6 months to assess the growth velocity. RESULTS: Female to male ratio was 1.56. Nutritional short stature (NSS) and normal variant short stature were the most prevalent, with the equal frequency of 19% each, followed by endocrine and other causes. The significant number of children had Vitamin D deficiency/insufficiency (92%). mid-parental height (MPH) was below-1 standard deviation score (SDS) from the national standard in all the children studied. CONCLUSION: In the present study, normal variants of short stature and NSS were the most common causes of short stature, followed by endocrine disorders. Vitamin D status was low in the majority of the children (92%), with possible contribution to short stature in all groups irrespective of primary diagnosis and needs further exploration. Growth hormone (GH) therapy in select non GH deficiency short stature can be promising. We also noted that maternal, paternal heights, and consequently, MPH was below the national standard in 100% of children. This may implicate ethnic variations and maybe a call for local growth charts. It needs further studies to look for factors responsible for lower MPH in our cohort.

Tumor necrosis factor (TNF) is a pleiotropic cytokine belonging to a family of trimeric proteins with both proinflammatory and immunoregulatory functions. TNF is a key mediator in autoimmune diseases and during the last couple of decades several biologic drugs have delivered new therapeutic options for patients suffering from chronic autoimmune diseases such as rheumatoid arthritis and chronic inflammatory bowel disease. Attempts to design small molecule therapies directed to this cytokine have not led to approved products yet. Here we report the discovery and development of a potent small molecule inhibitor of TNF that was recently moved into phase 1 clinical trials. The molecule, SAR441566, stabilizes an asymmetrical form of the soluble TNF trimer, compromises downstream signaling and inhibits the functions of TNF in vitro and in vivo. With SAR441566 being studied in healthy volunteers we hope to deliver a more convenient orally bioavailable and effective treatment option for patients suffering with chronic autoimmune diseases compared to established biologic drugs targeting TNF.

Introduction: Binge eating disorder (BED) was underdiagnosed, underestimated eating disorder known to be responsible for obesity in both children and adults. Sedentary behavior estimated by measuring the sitting time was one of the major contributing factors in the development of metabolic syndrome in adults. People working in Information Technology (IT) sector possess both of these determinants in a significant capacity and thereby might be at risk for obesity, which in turn can be responsible for various cardio-metabolic events in their life. Methods: A cross-sectional study was conducted on 513 working adults belonging to the IT sector, using a face-to-face interview with a pre-tested questionnaire along with anthropometric measurements to measure BMI for obesity. Binge-eating disorder screener-7 for adults was adopted to assess the disorder, and the Marshall Sitting Questionnaire was used to evaluate their sitting behavior. Results: The study found that the prevalence of BED (23%) was higher in unmarried individuals, and moderate BED is significantly associated with higher BMI among them. Conversely, sitting time (Mean=8.83 hours/day) was seen mostly in married adults, and is also associated with higher BMI. As a risk cluster, both BED and sitting time combined had higher odds of resulting in Obesity than existing separately. Conclusion: Several lifestyle factors such as binge-watching TV, late working hours, higher salaries, etc., have contributed to developing Binge eating disorder and higher sitting time, which pose a significant risk for metabolic disorders like obesity.

This case study deals with a 32-year-old Indian male patient who presented with a traumatic head injury in the hospital, experienced uncontrolled bleeding after conducting surgery, and was eventually diagnosed with Glanzmann thrombasthenia. Glanzmann thrombasthenia is a rare hereditary blood clotting disorder characterised by a lack of platelet aggregation due to the absence of platelet glycoprotein IIb/IIIa. This occurrence is generally triggered by consanguineous marriages and is apparent in approximately one in one million people. Education and raising awareness about consanguinity in communities may help to reduce challenging, unusual genetic diseases.

Abstract Phenylketonuria (PKU) is an autosomal recessive inborn error of l-phenylalanine (Phe) metabolism. It is caused by a partial or complete deficiency of the enzyme phenylalanine hydroxylase (PAH), which is necessary for conversion of Phe to tyrosine (Tyr). This metabolic error results in buildup of Phe and reduction of Tyr concentration in blood and in the brain, leading to neurological disease and intellectual deficits. Patients exhibit retarded body growth, hypopigmentation, hypocholesterolemia and low levels of neurotransmitters. Here we report first attempt at creating a homozygous Pah knock-out (KO) (Hom) mouse model, which was developed in the C57BL/6 J strain using CRISPR/Cas9 where codon 7 (GAG) in Pah gene was changed to a stop codon TAG. We investigated 2 to 6-month-old, male, Hom mice using comprehensive behavioral and biochemical assays, MRI and histopathology. Age and sex-matched heterozygous Pah-KO (Het) mice were used as control mice, as they exhibit enough PAH enzyme activity to provide Phe and Tyr levels comparable to the wild-type mice. Overall, our findings demonstrate that 6-month-old, male Hom mice completely lack PAH enzyme, exhibit significantly higher blood and brain Phe levels, lower levels of brain Tyr and neurotransmitters along with lower myelin content and have significant behavioral deficit. These mice exhibit phenotypes that closely resemble PKU patients such as retarded body growth, cutaneous hypopigmentation, and hypocholesterolemia when compared to the age- and sex-matched Het mice. Altogether, biochemical, behavioral, and pathologic features of this novel mouse model suggest that it can be used as a reliable translational tool for PKU preclinical research and drug development.

Abstract Background Coronavirus disease 2019 (COVID-19) is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a novel coronavirus that was first discovered in December 2019 in Wuhan, China. With the growing numbers of community spread cases worldwide, the World Health Organization (WHO) declared the COVID-19 outbreak as a pandemic on March 11, 2020. Like influenza viruses, SARS-CoV-2 is thought to be mainly transmitted by droplets and direct contact, and COVID-19 has a similar disease presentation to influenza. Here we present a case of influenza A and COVID-19 co-infection in a 60-year-old man with end-stage renal disease (ESRD) on hemodialysis. Case presentation A 60-year-old man with ESRD on hemodialysis presented for worsening cough, shortness of breath, and diarrhea. The patient first developed a mild fever (37.8 °C) during hemodialysis 3 days prior to presentation and has been experiencing worsening flu-like symptoms, including fever of up to 38.6 °C, non-productive cough, generalized abdominal pain, nausea, vomiting, and liquid green diarrhea. He lives alone at home with no known sick contacts and denies any recent travel or visits to healthcare facilities other than the local dialysis center. Rapid flu test was positive for influenza A. Procalcitonin was elevated at 5.21 ng/mL with a normal white blood cell (WBC) count. Computed tomography (CT) chest demonstrated multifocal areas of consolidation and extensive mediastinal and hilar adenopathy concerning for pneumonia. He was admitted to the biocontainment unit of Nebraska Medicine for concerns of possible COVID-19 and was started on oseltamivir for influenza and vancomycin/cefepime for the probable bacterial cause of his pneumonia and diarrhea. Gastrointestinal (GI) pathogen panel and Clostridioides difficile toxin assay were negative. On the second day of admission, initial nasopharyngeal swab came back positive for SARS-CoV-2 by real-time reverse-transcriptase polymerase chain reaction (RT-PCR). The patient received supportive care and resumed bedside hemodialysis in strict isolation, and eventually fully recovered from COVID-19. Conclusions We presented a case of co-infection of influenza and SARS-CoV-2 in a hemodialysis patient. The possibility of SARS-CoV-2 co-infection should not be overlooked even when other viruses including influenza can explain the clinical symptoms, especially in high-risk patients.

Steroid 5α-reductase deficiency (5ARD) is a rare autosomal recessive disorder caused by mutation in the 5α-reductase type 2 gene (SRD5A2). 5ARD results in the impaired conversion of testosterone (T) to dihydrotestosterone (DHT) and is characterized by undervirilization in 46XY individuals. We report a case series of three siblings presenting with ambiguous genitalia and different phenotypes. They did not meet the widely accepted biochemical criteria for 5ARD. In view of strong clinical suspicion, genetic analysis was performed which revealed pathogenic mutation in SRD5A2. This report highlights the importance of definitive diagnosis with molecular methods as the treatment and prognosis differs greatly among the close differential diagnoses. Reliance on the biochemical criteria alone may lead to misdiagnosis.

Background: Polycystic Ovary Syndrome (PCOS) is the most common endocrine disorder in women of reproductive age, characterized by chronic anovulation, hyperandrogenism, with varying severity of reproductive and long-term metabolic consequences. Aim and Objectives: To study the effect of vitamin D supplementation on menstrual cycle dysfunction and metabolic parameters in PCOS women. Material and Methods: Seventy-five PCOS women who presented with oligomenorrhoea/ amenorrhea with varying severity of hypovitaminosis D were retrospectively analysed. Thirty eight women were compliant with vitamin D supplementation, whereas 37 were noncompliant. Baseline demographic, menstrual cycle dysfunction and metabolic parameters were compared with the data at 6 months follow up in both groups, and change in weight and vitamin D levels were compared in women with regularized vs non regularized menstruation. Results: Mean age was 23.87 ± 3.74 years, with mean BMI 28.9 ± 4.88kg/m2. Vitamin D deficiency and insufficiency was seen in 85.3% and 14.7% subjects. Baseline characteristics among vitamin D deficient Vs insufficient were not significantly different except for vitamin D levels. Significant decrease in BMI and waist circumference was observed among both compliant and non-compliant groups. Menstrual cycles were regularized in 39.4% of compliant group and 43.2% of non-compliant women. Conclusion: Vitamin D supplementation was not associated with menstrual regularization, and may play a role in synergy with weight loss in improving metabolic parameters. Our study reemphasizes the beneficial role of lifestyle modifications aiming at weight loss in PCOS women.

Introduction: Type 1 diabetes mellitus (T1DM) is a long-standing metabolic disease caused by autoimmune beta cell destruction leading to absence or lowered insulin production. T1DM is associated with various other autoimmune disorders, including autoimmune thyroid disease, Celiac disease, and Addison disease. Detection of these antibodies is crucial to prevent morbidity related to unrecognized disease. Indian data regarding prevalence of these antibodies in T1DM is lacking, particularly antibodies against 21 hydroxylase. Patients and Methods: Total 100 patients with T1DM were taken into the study, in all patients anti-transglutaminase (anti-tTG) IgA, anti-thyroid peroxidase (anti-TPO) were done, and 21 hydroxylase anti bodies were done in 86 cases. Descriptive statistics were reported using mean, SD, numbers, and percentages. Student's t-test was used to assess the differences between the groups. Results: Fifteen cases were found to be TPOAb positive (eight had hypothyroidism, two had sub-clinical hypothyroidism, and five cases had normal thyroid function). tTGAb were positive in four cases, three were positive for 21-Hyroxylase antibody, and all had normal cortisol levels. Conclusion: Organ-specific autoimmune antibodies were elevated in T1DM when compared to general population. Screening of all these antibodies in T1DM patient should become standard of care.

Many injection site cutaneous complications such as lipohypertrophy and atrophy are known to occur in type 1 diabetic individuals. Acanthosis nigricans (AN) with insulin injection is a rare complication described in few case reports. It is also described as a paraneoplastic manifestation of malignancies such as hepatocellular carcinoma (HCC). Here we describe a case of injection site acanthosis in a type 1 diabetic with underlying HCC. This case report highlights the importance of knowledge on proper injection technique to prevent such unfortunate complications. High degree of suspicion of underlying malignancies is warranted in atypical presentation of AN.

Adaptation to changing environmental conditions is a driver of plant diversification. Elevational gradients offer a unique opportunity for investigating adaptation to a range of climatic conditions. The use of specialized metabolites as volatile and phenolic compounds is a major adaptation in plants, affecting their reproductive success and survival by attracting pollinators and protecting themselves from herbivores and other stressors. The wormseed Artemisia brevifolia can be found across multiple elevations in the Western Himalayas, a region that is considered a biodiversity hotspot and is highly impacted by climate change. This study aims at understanding the volatile and phenolic compounds produced by A. brevifolia in the high elevation cold deserts of the Western Himalayas with the view to understanding the survival strategies employed by plants under harsh conditions. Across four sampling sites with different elevations, polydimethylsiloxane (PDMS) sampling and subsequent GCMS analyses showed that the total number of volatile compounds in the plant headspace increased with elevation and that this trend was largely driven by an increase in compounds with low volatility, which might improve the plant’s resilience to abiotic stress. HPLC analyses showed no effect of elevation on the total number of phenolic compounds detected in both young and mature leaves. However, the concentration of the majority of phenolic compounds decreased with elevation. As the production of phenolic defense compounds is a costly trait, plants at higher elevations might face a trade-off between energy expenditure and protecting themselves from herbivores. This study can therefore help us understand how plants adjust secondary metabolite production to cope with harsh environments and reveal the climate adaptability of such species in highly threatened regions of our planet such as the Himalayas.

Abstract Purpose Preclinical in vivo nuclear imaging of mice offers an enabling perspective to evaluate drug efficacy at optimal dose and schedule. In this study, we interrogated sufficient estrogen receptor occupancy and degradation for the selective estrogen receptor degrader (SERD) compound SAR439859 using molecular imaging and histological techniques. Material and methods [18F]FluoroEstradiol positron emission tomography (FES-PET), [18F]FluoroDeoxyGlucose (FDG) PET, and [18F]FluoroThymidine (FLT) PET were investigated as early pharmacodynamic, tumor metabolism, and tumor proliferation imaging biomarkers, respectively, in mice bearing subcutaneous MCF7-Y537S mutant ERα+ breast cancer model treated with the SERD agent SAR439859. ER expression and proliferation index Ki-67 were assessed by immunohistochemistry (IHC). The combination of palbociclib CDK 4/6 inhibitor with SAR439859 was tested for its potential synergistic effect on anti-tumor activity. Results After repeated SAR439859 oral administration over 4 days, FES tumoral uptake (SUVmean) decreases compared to baseline by 35, 57, and 55% for the 25 mg/kg qd, 12.5 mg/kg bid and 5 mg/kg bid treatment groups, respectively. FES tumor uptake following SAR439859 treatment at different doses correlates with immunohistochemical scoring for ERα expression. No significant difference in FDG uptake is observed after SAR439859 treatments over 3 days. FLT accumulation in tumor is significantly decreased when palbociclib is combined to SAR439859 (− 64%) but not different from the group dosed with palbociclib alone (− 46%). The impact on proliferation is corroborated by Ki-67 IHC data for both groups of treatment. Conclusions In our preclinical studies, dose-dependent inhibition of FES tumoral uptake confirmed target engagement of SAR439859 to ERα. FES-PET thus appears as a relevant imaging biomarker for measuring non-invasively the impact of SAR439859 on tumor estrogen receptor occupancy. This study further validates the use of FLT-PET to directly visualize the anti-proliferative tumor effect of the palbociclib CDK 4/6 inhibitor alone and in combination with SAR439859.

The severe acute respiratory syndrome virus (SARS-CoV-2), a novel coronavirus first discovered in Wuhan, China in December 2019 causes the Coronavirus Disease 19 (COVID-19), which presents with a wide range of clinical symptoms from mild or moderate to severe and critical illnesses. With the continuing transmission of the virus worldwide and the rapidly evolving situation globally, the World Health Organization (WHO) declared the COVID-19 outbreak a pandemic in March. Currently, there is no proven specific treatment for this potentially deadly disease beyond supportive care. However, a massive effort has been put globally into the investigation of medications and other interventional measures to fight COVID-19. Convalescent plasma therapy from recovered patients has recently drawn considerable interest. Several alternative medical treatments, although evidence of their efficacy still lacking, have also gained popularity, especially in countries with such traditions such as India and China. Rapid repurposing of drugs for COVID-19 has revealed a few promising candidate antiviral agents, but further research, especially high quality randomized controlled trials, will be needed to prove their efficacy and safety in the clinical use to treat COVID-19. Vaccine development has been the imperative task in the battle against SARS-CoV-2. While clinical trials have been launched for several candidate vaccines, research on COVID-19 vaccines is still at an early stage. So far, optimized supportive care remains the best practice against COVID-19.

Aim: To evaluate the range and scientific nature of oral presentations in the Scientific Program of IAPSCON from 2014-18 Methods: The oral presentations in Scientific Program of IAPSCON from 2014 – 18 were tabulated and categorised as per: type of presentation, Paediatric Surgery related clinical subject heading, nature of the content and scientific quality as per Oxford levels of clinical evidence. Results: Most oral presentations were in the form of Short papers. The most common clinical section and clinical condition presented were Urology and Hypospadias respectively. Clinical management followed by operative management represent the majority of the presentations when categorized by the type of content. Certain sections of clinical practice were not represented at all, notably anterior abdominal wall defects and gastro-oesophageal reflux. Most presentations (82.5%) are in Level 4 and 5 as per Oxford levels of clinical evidence, with Levels 1–3 accounting for 5% of presentations. Minimally Invasive Surgery (including robotic) accounted for 8.4% presentations. Conclusions: This qualitative evaluation shows the variety of oral presentations and areas of greater and lesser interest in the conference meetings. It shows that the scientific quality of the presentations can be improved and highlights certain areas of clinical and scientific research for future consideration.

Cancer: How a plant metabolite analog suppresses tumor growth A synthetic analog of a chemical found in fruit suppresses tumor growth by targeting an RNA-binding protein (hnRNPA2B1) and preventing the production of a pro-cancer regulatory factor. Nak-Kyun Soung from the Korea Research Institute of Bioscience and Biotechnology, Cheongju, South Korea, and coworkers built on their previous discovery that a compound derived from a medicinal plant metabolite can suppress the activity of hypoxia-inducible factor-1α (HIF-1α). This protein, which is involved in many aspects of cancer biology, is activated in the low-oxygen microenvironments found inside tumors. The researchers show that the compound binds to a protein that helps with the conversion of HIF-1α–encoding RNA transcripts into HIF-1α proteins. Liver cancer cells treated with the compound grew slowly and produced less HIF-1α under both normal and low-oxygen culture conditions, highlighting the potential of this anti-cancer strategy.

India is the seventh largest producer of coffee with 395,000 tons of coffee exports that earn 10 billion US dollars annually. Two varieties of coffee are grown in India, Coffea arabica (arabica) and Coffea canephora (robusta). Xylotrechus quadripes, commonly known as Coffee White Stem Borer (CWSB), is a major pest of arabica, causing yearly crop damage of 17–40 million dollars. Management strategies, over 100 years in development, have provided successful, yet inconsistent solutions due to differences in local climate, elevation, natural enemies, grower diligence, and other factors. In addition, increased pesticide use affects both pests as well as their natural enemies, which has severe negative impacts on the biodiverse regions where coffee is grown. As a result, our goal is to develop an ecology-based solution for long term management of CWSB that reduces the use of pesticides and focuses on the importance of natural enemies and native hosts. In situ behavioral experiments were performed to examine the preferences of CWSB for various local species under field conditions. We found that CWSB beetles were attracted to both healthy arabica and robusta plants, and host plant volatiles played a key role in host selection. In addition, the beetles were attracted to the leaves of these coffee plants and also two species of cut stems from common shade trees; Spathodea campanulata (nandi flame) and Grevillea robusta (silver oak). Beetles were not attracted toward cut stems of Tectona grandis (teak) or Coffea arabica. GC-EAD and EAG experiments were then performed to identify host plant volatiles for these species, and these compounds were tested in field conditions to assess their effectiveness against the known chemical attractant pheromone. We found that the CWSB was attracted to our identified host volatile blend as much as the pheromone lure, although trap catches in general were very low. Having an understanding of the behavioral ecology of this pest can form the basis for new methods that use natural attractant and repellent plants to control the pests, reduce the cost of plantation pest management, and avoid the extensive use of insecticides.

A simulation experiment was carried out using Agriculture Production Systems Simulator (APSIM) model to assess the impact of climate change (change in temperature and rainfall patterns) on productivity of maize in the state Madhya Pradesh. Thirty districts with 74 soil profiles from Madhya Pradesh state were considered for the study. However, we are presenting the average results over districts and soil profiles. A well-parameterised and validated APSIM model was used to simulate the effects of temperature and rainfall on maize grain and biomass yield. Increase in temperature having negative effects on both grain and biomass yield of maize. While increasing the temperature from base to 5 °C, the grain and biomass yield of maize decreased by 40% and 28%, respectively. Further, increasing the temperature by 1 °C could reduce the grain and biomass yield by 10% and 8 %, respectively. A small increase in maize yield was observed by 10% decrease of rainfall from the base. While rainfall increase by 10% or more and decrease by >20% would results in lower maize yield and biomass. The decrease in maize yield due to increase in temperature could be attributed to decrease in duration of the crop. One-degree increase in temperature may decrease the duration of crop by 4.3 days. This study also revealed that agronomic management practices such as delaying of sowing dates could reduce the impact of climate change on crop yield to a considerable extent. By adopting the sowing date between 7th and 14th July, it may be possible to reduce the impact of temperature change on maize grain and biomass yield in central Indian condition.

Purpose: The purpose of this study is to compare the effect of implant-abutment connections, abutment angulations, and screw lengths on screw loosening (SL) of preloaded abutment using three dimensional (3D) finite element analysis. Materials and Methods: 3D models of implants (conical connection with hex/trilobed connections), abutments (straight/angulated), abutment screws (short/long), and crown and bone were designed using software Parametric Technology Corporation Creo and assembled to form 8 simulations. After discretization, the contact stresses developed for 150 N vertical and 100 N oblique load applications were analyzed, using ABAQUS. By assessing damage initiation and shortest fatigue load on screw threads, the SL for 2.5, 5, and 10 lakh cyclic loads were estimated, using fe-safe program. The obtained values were compared for influence of connection design, abutment angulation, and screw length. Results: In straight abutment models, conical connection showed more damage (14.3%–72.3%) when compared to trilobe (10.1%–65.73%) at 2.5, 5, and 10 lakh cycles for both vertical and oblique loads, whereas in angulated abutments, trilobe (16.1%–76.9%) demonstrated more damage compared to conical (13.5%–70%). Irrespective of the connection type and abutment angulation, short screws showed more percentage of damage compared to long screws. Conclusions: The present study suggests selecting appropriate implant-abutment connection based on the abutment angulation, as well as preferring long screws with more number of threads for effective preload retention by the screws.

Epiretinal membrane over macula secondary to toxoplasmosis compromises vision. We describe the outcome of pars plana vitrectomy and epiretinal membrane removal after adequate treatment of acute infection. The average age of all four male patients was 36 years (range 20–60 years). Following surgery there was an average three or more lines visual acuity improvement, restoration of foveal contour with reduction in central macular thickness. One patient developed choroidal neovascular membrane postsurgery and was effectively treated with intravitreal bevacizumab. Surgery for ERM secondary to healed toxoplasmosis infection has good anatomical outcome and reasonable visual improvement, when the surgery is done in a quiet eye.

Aim: The present study was conducted to evaluate the physico-chemical and microbiological characteristics of chicken nuggets coated with sodium alginate (SA) coatings at refrigerated (4±1°C) and frozen (−18±1°C) storage condition at regular periodic intervals. Materials and Methods: Chicken meat nuggets were separated into three groups: Uncoated control (C), coated with alginate coating (T1), and coated with alginate coating incorporated with 1% green tea extract (GTE) (T2). The nuggets were analyzed at regular intervals of 5days for refrigerated storage and 15 days for frozen storage period in terms of pH, 2-thiobarbituric acid value (TBA), peroxide value (PV), total plate count (TPC), water loss, and sensory characteristics. Results: The results indicated that the nuggets coated with alginate-based coatings effectively reduced the spoilage as indicated by pH, TBA, and PVs. pH values of the formulations ranged from 6.15 to 6.34 at refrigerated storage temperature (4±1°C) and 6.49-6.71 at frozen storage temperature (−18±1°C). TBA value of the treatments ranged from 1.28 to 1.54 mg MDA/kg and 1.34 to 1.50 mg MDA/kg under refrigerated and frozen storage temperatures, respectively. Color, flavor, juiciness, tenderness, and overall acceptability of the nuggets differed significantly (p

This in vitro study evaluated the effectiveness of a novel dentifrice containing stabilized chlorine dioxide, sodium lauroyl sarcosinate (sarkosyl), and sodium fluoride in enhancing enamel fluoride uptake, remineralization, pellicle cleaning and inhibiting biofilm regrowth. Remineralization was measured by fluoride uptake and surface microhardness assessment tests. Artificial stains were removed and scored based on pellicle cleaning ratio. Biofilm regrowth was measured by counting colonies on the agar plates. All studies were conducted using bovine teeth specimens. The efficacy of Toothpaste C (CloSYS anticavity toothpaste) was compared with United States Pharmacopoeia Reference Dentifrice, Toothpaste B (discontinued CloSYS anticavity toothpaste formulation) and leading commercial toothpastes. The enamel fluoride uptake and remineralization by Toothpaste C was 96.1% to 303.3% and 38.0% to 102.4% higher than the tested toothpastes, respectively. The mean pellicle cleaning ratio of Toothpaste C was similar to American Dental Association Reference Material. Toothpaste C had a significant reduction in regrowth of the oral polymicrobial biofilm compared to the control. All tested toothpastes contained 0.24% sodium fluoride. Toothpaste C exhibited significantly superior performance towards fluoride uptake and remineralization compared to the tested toothpastes. Therefore, toothpaste ingredients other than sodium fluoride accounted for the enhanced fluoride uptake and remineralization.