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Abstract Background Fish with vertebral monstrosities are very rare in the wild, as those individuals in the natural populations tend to perform poorly to survive in any ecosystem. Species of the fish genus Hypselobarbus as reported (Bleeker in De visschen van den Indischen Archipel, Lange, 1860) are freshwater endemic barbs of Western Ghats and peninsular India. Four species of the genus, namely Hypselobarbus dobsoni (Krishna carp), H. jerdoni (Jerdon’s Carp), H. lithopidos (Canara barb) and H. thomassi (Red Canarese barb), were collected from three different river systems of the Western Ghats biodiversity hotspot of India. Some individuals were found to be different from normal specimens, with extremely large body depth compared to normal specimens. The study was initiated with the aim of bringing an understanding on monstrosities of these four species along with identifying the normal and abnormal individuals in an integrated approach; employing traditional morphometry, X-ray imaging and barcoding mtDNA COI X-ray imaging could elucidate the vertebral monstrosities, which are discussed in detail. The mtDNA COI gene sequences generated were used to draw conclusions on identity of both normal and deformed individuals. Results The phenotypic deformities have led to deepening of the body with a more robust and reduced length which is evident from the morphometric comparison of normal specimens with deformed ones. The radiographic images revealed reduced intra-vertebral space in comparison with the normal vertebrae, deformed vertebrae were between 25 and 32, showing significantly altered intra-vertebral space. Slight genetic divergence of 1.1% between normal and deformed specimens in mitochondrial DNA COI gene of H. lithopidos and H. thomassi and no divergence in H. dobsoni and H. jerdoni were also observed. Conclusion The specimens were collected from areas with high anthropogenic stresses, abate water quality, and habitat, which could be possible reasons of appearance of individuals with deformed vertebrae. Several environmental and genetic factors might have influenced the development of these robust short-bodied phenotypes in these rivers and possess slight genetic divergence from normal specimens. However, these deformities may also be the result of the stress during embryonic and early life stages in the wild.

Aim: This study was designed to enumerate regulatory T‑cells (Tregs) and estimate transforming growth factor‑β1 (TGF‑β1) levels in type 1 diabetic (T1D) patients with respect to disease duration and associated autoimmune diseases. Methods: One hundred and fifty patients and twenty healthy controls were recruited in the study. The patients were subcategorized into eight categories on the basis of disease duration (new onset [NO] and long standing [LS]) and associated diseases, i.e., celiac disease (CD) and autoimmune thyroid disease (AiTD). Treg cells were assessed as CD4+ CD25hi+, FOXP3+ cells and serum TGF‑β1 levels were assessed by ELISA. Results: The frequency of Tregs and levels of TGF‑β1 were significantly increased in the patients compared to the healthy controls. Among the different categories of the patients, no significant differences were seen for TGF- β1 levels, but for Tregs in patients with T1D and AiTD (P = 0.035). A significant correlation was also found between percentage count of Tregs and TGF‑β1 levels in NO cases in all disease subcategories, but not in LS patients. Conclusion: Thus, there was an increased percentage of Tregs and serum levels of TGF‑β1 in T1D patients, irrespective of the disease duration and associated autoimmune diseases. The significant correlation in these two parameters at the onset of the disease, but not in LS disease, indicates that the immunological milieu in LS autoimmune diseases is more complicated with disease‑associated conditions such as prolonged hyperglycemia, insulin therapy, and/or continued gluten in diet. Treatment and modulation of these long‑term complications for improving immunological parameters require further research. [ABSTRACT FROM AUTHOR]

Zygomycosis is a frequently fatal infection in the immunocompromised and diabetic host. A 12 year old girl with type 1 diabetes presented in diabetic ketoacidosis and consolidation of right lung along with thymic abscess causing persistent respiratory symptoms. A diagnosis of mucormycosis was made on smear examination of the thymic aspirate. Intravenous amphotericin along with surgical excision of the abscess resulted in clinical cure. Thymic involvement as seen in this case is an extremely rare occurrence in a diabetic patient which has not been reported in literature so far . [ABSTRACT FROM AUTHOR]

The article explains that infantile cortical hyperostosis or Caffey's disease classically presents in infants less than 5 months of age, though has also been reported to occur in utero. Mandibular involvement is seen in 75-80%. Radiological findings are diagnostic; however, other conditions with similar clinicoradiological features such as scurvy, osteomyleitis, syphilitic osteochondritis, hypervitaminosis A, metastatic neuroblastoma, and battered baby syndrome need to be excluded. Treatment is palliative with NSAIDs, and sometimes steroids.

Background. While exogenous obesity is consistently associated with early sexual maturation in girls, the reports in boys show conflicting results with some showing a positive association and others a negative or no association at all. Aim. To assess the pattern of sexual maturation in boys with exogenous obesity. Design: Mixed longitudinal study. Subjects and methods. In the present study, 102 boys between 8 yrs (+3 months) and 16 yrs (+3 months) of age with exogenous obesity who belonged to mixed socioeconomic strata were assessed at 6 monthly intervals for development of genitalia, pubic, facial and axillary hair as per the criteria laid down by Tanner 1962 in addition to their general anthropometric assessments. The data obtained was compared with previously published normative auxological and sexual maturity related data. Results. The attainment of G2 and G3 stage of genitalia development was earlier as compared with their Indian and western peers while G3 and G4 stages were found to be relatively delayed. None of the obese boys could attain G5 stage by the age of 16yrs. The appearance of facial (11.68±1.73yr), pubic (11.7±1.79yr) and axillary hair (12.41±1.69yr) occurred earlier than their Indian and western counterparts. Conclusion. The onset of sexual maturation amongst obese boys in this study as compared to their normal counterparts was earlier even though the progression of maturation was found to be relatively delayed. [ABSTRACT FROM AUTHOR]

Objective: To assess the parental stress, coping mechanism and quality of life of caregivers of children with Differences of Sex Development (DSD)., Methods: Mothers of children (6 months - 12 years) with DSD were enrolled after excluding mothers of children with syndromic diagnosis, developmental delay, cognitive impairments, chronic diseases, or if the duration of DSD diagnosis was less than six months, and mothers with psychiatric illnesses (n = 35). Mothers of age and gender-matched children with congenital hypothyroidism served as controls (n = 35). Psychological assessments were performed using structured questionnaires: the Parent Stress Scale, PRIME MD PHQ-9 Scale, and Ways of Coping Questionnaire., Results: Mothers of children with DSD exhibited significantly higher mean (SD) stress levels [24.34 (4.25) vs 19.57 (1.89); P < 0.001]. Prevalence of depression prevalence was higher in mothers in the DSD group than in the hypothyroidism group (71% vs 42.9%, P < 0.001). Mothers of children with DSD also had poorer quality of life, and both high negative coping behavior and low positive coping behavior (P < 0.001) compared to controls, and stigma related to social exclusion was more pronounced., Conclusion: Beyond medical interventions, addressing family members' psychological well-being is essential in effectively managing DSD in the Indian context.

Background: Evidence is mounting that the biopsychosocial paradigm is more accurate and useful than the biomedical paradigm of care. Habits of thought can hinder the implementation of this knowledge into daily care strategies. To understand and lessen these potential barriers, we asked: 1) What is the relative implicit and explicit attitudes of musculoskeletal surgeons towards the biomedical or biopsychosocial paradigms of medicine? 2) What surgeon factors are associated with these attitudes?, Methods: An online survey-based experiment was distributed to members of the Science of Variation Group (SOVG) with a total of 163 respondents. Implicit bias towards the biomedical or biopsychosocial paradigms was measured using an Implicit Association Test (IAT) designed by our team using open-source software; explicit preferences were measured using ordinal scales., Results: On average, surgeons demonstrated a moderate implicit bias towards the biomedical paradigm (d-score: -0.21; Interquartile range [IQR]: -0.56 to 0.19) and a moderate explicit preference towards the biopsychosocial paradigm (mean: 14; standard deviation: 14). A greater implicit bias towards the biomedical paradigm was associated with male surgeons (d-score: -0.30; IQR: -0.57 to 0.14; P = 0.005). A greater explicit preference towards the biomedical paradigm was independently associated with a European practice location (Regression coefficient: -9.1; 95% CI: -14 to -4.4; P <0.001) and trauma subspecialty (RC: -6.2; 95% CI: -11 to -1.0; P <0.001)., Conclusions: The observation that surgeons have an implicit bias favoring the biomedical paradigm might inform strategies for implementation of care strategies based on evidence favoring the biopsychosocial paradigm., Competing Interests: NO authors have competing interests pertinent to this study., (Copyright: © 2024 Ramtin et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Objective: In the hypothalamic-pituitary-gonadotrophin axis, estrogen plays a key role in the regulation of bone maturation and growth plate closure. This study was designed to explore the link between single nucleotide polymorphisms (SNPs) in the estrogen receptor 1 ( ESR1 ) gene with idiopathic short stature (ISS) susceptibility in a North Indian population., Methods: Four SNPs of ESR1 (rs543650, rs6557177, rs2234693 and rs9340799) were genotyped by Sanger sequencing in ISS patients and controls. Linkage disequilibrium (LD) and haplotyping were done by SNPStat and SHEsisPlus software. The extent of LD was determined by calculating D’ and R 2 values in SNP paired combinations., Results: Fifty-two ISS patients were compared with 68 controls. A significant positive association was found between rs6557177 and rs543650 genotype and ISS susceptibility. The frequencies of the rs6557177 CC genotype [p=0.030; odds ratio (OR)=0.13; 95% confidence interval (CI): 0.01-1.10] and rs543650 genotype TT (p=0.043; OR=0.29; 95% CI: 0.09-0.92) were increased in the ISS group compared with controls. However, no significant correlation was observed between clinical parameters of patients and these SNPs. rs543650 showed strong LD with rs2234693 and rs9340799, similarly rs2234693 and rs9340799., Conclusion: Our study showed that the CC genotype at rs6557177 and TT genotype at rs543650 of ESR1 constituted a risk factor for developing ISS in North Indian children. These findings may lead to a better understanding of the SNPs associated with ISS susceptibility., Competing Interests: Conflict of interest: None declared., (©Copyright 2024 by Turkish Society for Pediatric Endocrinology and Diabetes / The Journal of Clinical Research in Pediatric Endocrinology published by Galenos Publishing House.)

Objective: To evaluate the role of basal and follicle-stimulating hormone (FSH)-stimulated inhibin B in differentiating premature thelarche from gonadotropin-dependent precocious puberty (GDPP)., Methods: This was a prospective interventional study. Basal and FSH-stimulated inhibin B levels were estimated in girls presenting with thelarche < 8 years age (n = 10), healthy girls with normal pubertal development (pubertal control) (n = 8) and healthy prepubertal girls (prepubertal control) (n = 7). Girls with early puberty were classified as premature thelarche or GDPP based on GnRH agonist stimulation test., Results: Median (IQR) basal inhibin B levels (pg/mL) in premature thelarche was 5.42 (2.91, 30.58) and FSH-stimulated inhibin B was 236.72 (111.53, 4431.73) (P = 0.043). Median (IQR) basal inhibin B in GDPP was 64.11 (24.96, 792.45) pg/mL and FSH-stimulated inhibin B was 833.66 (500.11-1266.18) pg/mL (P = 0.043). Basal inhibin B was discriminatory between GDPP and premature thelarche (P = 0.032). Median (IQR) basal inhibin B in prepubertal and pubertal controls was 20.36 (9.61, 29.12) and 75.48 (58.55, 165.55) pg/mL, respectively., Conclusion: Basal inhibin B is useful in differentiation of premature thelarche from GDPP while the role of FSH-stimulated inhibin B needs to be further explored in large sample size.

Satellite-based precipitation estimates are a critical source of information for understanding and predicting hydrological processes at regional or global scales. Given the potential variability in the accuracy and reliability of these estimates, comprehensive performance assessments are essential before their application in specific hydrological contexts. In this study, six satellite-based precipitation products (SPPs), namely, CHIRPS, CMORPH, GSMaP, IMERG, MSWEP, and PERSIANN, were evaluated for their utility in hydrological modeling, specifically in simulating streamflow using the Variable Infiltration Capacity (VIC) model. The performance of the VIC model under varying flow conditions and timescales was assessed using statistical indicators, viz., R 2 , KGE, PBias, RMSE, and RSR. The findings of the study demonstrate the effectiveness of VIC model in simulating hydrological components and its applicability in evaluating the accuracy and reliability of SPPs. The SPPs were shown to be valuable for streamflow simulation at monthly and daily timescales, as confirmed by various performance measures. Moreover, the performance of SPPs for simulating extreme flow events (streamflow above 75%, 90%, and 95%) using the VIC model was assessed and a significant decrease in the performance was observed for high-flow events. Comparative analysis revealed the superiority of IMERG and CMORPH for streamflow simulation at daily timescale and high-flow conditions. In contrast, the performances of CHIRPS and PERSIANN were found to be poor. This study highlights the importance of thoroughly assessing the SPPs in modeling diverse flow conditions., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Mycobacterium avium subspecies paratuberculosis (MAP) infection leads to chronic, persistent granulomatous enteritis, causing prolonged diarrhoea and emaciation. The disease is managed using medications such as antibiotics, live vaccines, mycobacteriophage therapies and other treatments; however, a notable proportion of affected animals do not show improvement with this approach. We hypothesise that immunoinhibitory receptors TIM-3 (T cell immunoglobulin mucin protein-3) and PD-1 (Programmed death receptor 1) may be upregulated on Peripheral blood mononuclear cells (PBMCs) of MAP-seropositive bovines, potentially contributing to immune exhaustion. Samples (blood and faeces) were collected from 32 diarrhoeic bovines suspected of MAP infection; eight apparently healthy buffaloes from the dairy farm at Hisar, Haryana and from 14 cows (suffering from chronic diarrhoea, weakness and emaciation) housed in stray cattle shed. MAP infection was estimated using indigenous ELISA (i-ELISA), faecal IS 900 PCR, culture and acid-fast staining. TIM-3 and PD-1 gene expression on PBMCs were determined using qRT-PCR. TIM3 expression was relatively higher (~400-fold, 330-fold, 112-fold, 65-fold and 16-fold) in 5 chronically diarrhoeic PBMCs samples (MAP-seropositive), and higher PD-1 expression (around ~7-fold, 1.75-fold, 2.5-fold, 7.6-fold) was recorded in 4 diarrhoeic MAP-seropositive animals, compared to apparently healthy and other MAP-seronegative diarrhoeic animals. High co-expression of TIM-3 and PD-1 levels was also recorded in chronically diarrhoeic, emaciated stray cattle. Understanding immune responses in field conditions might aid in the therapeutic management of paratuberculosis.

Objective: Short stature homeobox ( SHOX ) haploinsufficiency underlies idiopathic short stature (ISS) and Leri-Weill dyschondrosteosis. The worldwide prevalence of SHOX variations in ISS varies from 2.5% to 15.0%. The aim of this study was to assess the implication of SHOX variation in ISS in North Indians and compare this with other cases of SHOX variations from Asian population., Methods: SHOX gene analysis was carried out by multiplex ligation-dependent probe amplification followed by Sanger sequencing in 54 patients with variable phenotypes. Comparison with other reports in a meta-analysis comprising the current study and 11 previous studies (n=979) was performed., Results: SHOX analysis resulted in 12.9% positivity (7.4% deletions and 5.5% duplications). SHOX association was seen significantly related to gender, with predominance in females (p=0.047). Short arms and forearms were the only significantly associated trait seen in 51.9% of children. The overall prevalence of SHOX variation was 15.2% in Asians with ISS. No significant difference was found in geographical region-specific analysis., Conclusion: This study summarises findings from the last decade and provides an updated picture of the prevalence of SHOX variations in Asians, emphasizing their potential as therapeutic targets in ISS patients. Further high quality, large investigations including functional validation is warranted to validate this association., Competing Interests: Conflict of interest: None declared., (©Copyright 2024 by Turkish Society for Pediatric Endocrinology and Diabetes / The Journal of Clinical Research in Pediatric Endocrinology published by Galenos Publishing House.)

This study investigates the fish assemblage in a temporarily-closed sandbar estuary along India's west coast, across different zones and seasons. Moderate species diversity (54 species), low species abundance, varying fish diversity from lower to upper estuarine gradient (higher counts in lower zones, and decreasing from middle to upper zones), and higher prevalence of marine migrants (estuarine use) and piscivorous species (feeding mode) were the significant characteristics of the estuary. Distinct spatial, seasonal, and estuarine mouth state-based variations were recorded in the estuary, based on diversity indices and count of taxa. Peak diversity and abundance were noted during the pre-monsoon, and during the open mouth state of the estuary. The entire estuarine gradient is anthropogenically impacted by a multitude of stressors, except at the estuarine mouth region, which is favored by marine connectivity. The fish assemblage structure in Poonthura estuary (PE) has thus far remained unaffected by anthropogenic disturbances. Nevertheless, growth and nursery function of the estuary have been significantly compromised. The predominance of juvenile fish in the ecosystem, and prevailing anthropogenic stressors from point and non-point sources underscore the necessity for long-term maintenance of the population of coastal species, as well as a need for developing and implementing urgent management strategies for this fragile ecosystem., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Fish of the genus Hypselobarbus (Bleeker 1860) are widely dispersed in the rivers of the Western Ghats in India and endemic to southern Indian peninsular freshwaters. These are small- to medium-sized fishes of the family Cyprinidae. Although fish with deformed bodies or body parts are rare in natural waters, this article deals with four abnormal specimens of Hypselobarbus curmuca (Hamilton 1807) collected from the rivers Tunga, Bhadra, and Kali during 2022. The abnormalities observed in four different individuals are pughead deformity, pelvic fin deformity, pectoral fin deformity, and enlarged scales. The morphological comparison of normal individuals of Hypselobarbus curmuca (Hamilton 1807) with abnormal specimens revealed variation. Using the MT-COI gene, species identity was confirmed and the mean genetic divergence between the normal and abnormal specimens was estimated to be less than 1%.

Introduction: To study the clinical profile and molecular diagnosis of children with severe early-onset non-syndromic monogenic obesity., Methods: The clinical and molecular data (performed using whole exome sequencing) of 7 children with early-onset (< 5 years) non-syndromic monogenic obesity were extracted from the Obesity Clinic files and analysed retrospectively., Results: The median (IQR) age at presentation was 18 (10.5-27) months. Of the 7 patients, 5 were boys, 3 had a history of parental consanguinity, and 4 had a family history of severe early-onset obesity. All patients exhibited hyperphagia and showed signs of insulin resistance. Dyslipidaemia and fatty liver were observed in 4. The variants identified in 6 patients included 2 in leptin receptor, and one each in melanocortin 4 receptor, pro-opiomelanocortin, leptin, and neurotrophic tyrosine kinase receptor type 2 genes. Notably, 4 of these variants were novel., Conclusions: This case series provides valuable insights into the spectrum of genetic mutations associated with non-syndromic monogenic obesity in North Indian children. The findings underscore the significance of next-generation sequencing in identifying the aetiology of severe early-onset obesity.

Purpose: Intermittent or concurrent use of Complementary and Alternative medicines (CAM) with insulin may have adverse effects in children with Type 1 Diabetes (T1DM). This study explores the practices of CAM use in children with T1DM., Methods: An exploratory study was conducted among parents of children with T1DM attending a tertiary-level diabetes clinic. Data were collected using a structured pre-tested questionnaire., Results: Two-hundred parents were invited; 183 (91.5%) completed the study. The mean age of the children was lower among CAM users than others (7.9 ± 4.3 vs 9.3 ± 4.3 years, p 0.032). The two groups were similar in gender, family income, parental education, and age at diagnosis. Sixty-seven (36.6%) had used CAM. The parents' reasoning for CAM use was to cure diabetes (62.7%), to improve glycemic control (28.3%), or considering it harmless (17.9%). The most commonly used CAMs were Ayurveda (32.8%) and homeopathic preparations (31.3%). The time interval between diagnosis and CAM use ranged from 1 day to 4 years. The duration of CAM use varied widely; 50.7% used CAM for < 1 month. Only 10 CAM users had HbA1C estimated during CAM use; their mean HbA1C was 12.4 ± 3.6%. Twenty-seven CAM users (40.2%) reported poorer glycemic control; 26.8% had no effect, and the rest had undefined effects due to too short duration of use., Conclusion: CAM, mostly herbal, is frequently used among children with T1DM in North India and has detrimental effects on glycemic control. This information should be used during diabetes education to avoid medical emergencies related to sub-optimal insulin dosing., Supplementary Information: The online version contains supplementary material available at 10.1007/s13340-023-00663-9., Competing Interests: Conflict of interestNo conflict of interest for any of the authors., (© The Japan Diabetes Society 2023. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Background: Patient use of verbal and nonverbal communication to signal what is most important to them can be considered empathetic opportunities. Orthopaedic surgeons may have mixed feelings toward empathetic opportunities, on one hand wanting the patient to know that they care, and on the other hand fearing offense, prolonged visit duration, or discussions for which they feel ill prepared. Evidence that action about empathetic opportunities does not harm the patient's experience or appreciably prolong the visit could increase the use of these communication tactics with potential for improved experience and outcomes of care., Questions/purposes: Using transcripts from musculoskeletal specialty care visits in prior studies, we asked: (1) Are there factors, including clinician attentiveness to empathetic opportunities, associated with patient perception of clinician empathy? (2) Are there factors associated with the number of patient-initiated empathetic opportunities? (3) Are there factors associated with clinician acknowledgment of empathetic opportunities? (4) Are there factors associated with the frequency with which clinicians elicited empathetic opportunities?, Methods: This study was a retrospective, secondary analysis of transcripts from prior studies of audio and video recordings of patient visits with musculoskeletal specialists. Three trained observers identified empathetic opportunities in 80% (209 of 261) of transcripts of adult patient musculoskeletal specialty care visits, with any uncertainties or disagreements resolved by discussion and a final decision by the senior author. Patient statements considered consistent with empathetic opportunities included relation of emotion, expression of worries or concerns, description of loss of valued activities or loss of important roles or identities, relation of a troubling psychologic or social event, and elaboration on daily life. Clinician-initiated empathetic opportunities were considered clinician inquiries about these factors. Clinician acknowledgment of empathetic opportunities included encouragement, affirmation or reassurance, or supportive statements. Participants completed post-visit surveys of perceived clinician empathy, symptoms of depression, and health anxiety. Factors associated with perceived clinician empathy, number of empathetic opportunities, clinician responses to these opportunities, and the frequency with which clinicians elicited empathetic opportunities were sought in bivariate and multivariable analyses., Results: After controlling for potentially confounding variables such as working status and pain self-efficacy scores in the multivariable analysis, no factors were associated with patient perception of clinician empathy, including attentiveness to empathetic opportunities. Patient-initiated empathetic opportunities were modestly associated with longer visit duration (correlation coefficient 0.037 [95% confidence interval 0.023 to 0.050]; p < 0.001). Clinician acknowledgment of empathetic opportunities was modestly associated with longer visit duration (correlation coefficient 0.06 [95% CI 0.03 to 0.09]; p < 0.001). Clinician-initiated empathetic opportunities were modestly associated with younger patient age (correlation coefficient -0.025 [95% CI -0.037 to -0.014]; p < 0.001) and strongly associated with one specific interviewing clinician as well as other clinicians (correlation coefficient -1.3 [95% CI -2.2 to -0.42]; p = 0.004 and -0.53 [95% CI -0.95 to -0.12]; p = 0.01)., Conclusion: Musculoskeletal specialists can respond to empathic opportunities without harming efficiency, throughput, or patient experience., Clinical Relevance: Given the evidence that patients prioritize feeling heard and understood, and evidence that a trusting patient-clinician relationship is protective and healthful, the results of this study can motivate specialists to train and practice effective communication tactics., Competing Interests: Each author certifies that there are no funding or commercial associations (consultancies, stock ownership, equity interest, patent/licensing arrangements, etc.) that might pose a conflict of interest in connection with the submitted article related to the author or any immediate family members. All ICMJE Conflict of Interest Forms for authors and Clinical Orthopaedics and Related Research® editors and board members are on file with the publication and can be viewed on request., (Copyright © 2023 by the Association of Bone and Joint Surgeons.)

White dwarfs, the extremely dense remnants left behind by most stars after their death, are characterized by a mass comparable to that of the Sun compressed into the size of an Earth-like planet. In the resulting strong gravity, heavy elements sink towards the centre and the upper layer of the atmosphere contains only the lightest element present, usually hydrogen or helium 1,2 . Several mechanisms compete with gravitational settling to change a white dwarf's surface composition as it cools 3 , and the fraction of white dwarfs with helium atmospheres is known to increase by a factor of about 2.5 below a temperature of about 30,000 kelvin 4-8 ; therefore, some white dwarfs that appear to have hydrogen-dominated atmospheres above 30,000 kelvin are bound to transition to be helium-dominated as they cool below it. Here we report observations of ZTF J203349.8+322901.1, a transitioning white dwarf with two faces: one side of its atmosphere is dominated by hydrogen and the other one by helium. This peculiar nature is probably caused by the presence of a small magnetic field, which creates an inhomogeneity in temperature, pressure or mixing strength over the surface 9-11 . ZTF J203349.8+322901.1 might be the most extreme member of a class of magnetic, transitioning white dwarfs-together with GD 323 (ref. 12 ), a white dwarf that shows similar but much more subtle variations. This class of white dwarfs could help shed light on the physical mechanisms behind the spectral evolution of white dwarfs., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)

Clustered regularly interspaced short palindromic repeats (CRISPR) is a third-generation genome editing method that has revolutionized the world with its high throughput results. It has been used in the treatment of various biological diseases and infections. Various bacteria and other prokaryotes such as archaea also have CRISPR/Cas9 systems to guard themselves against bacteriophage. Reportedly, CRISPR/Cas9-based strategy may inhibit the growth and development of triple-negative breast cancer (TNBC) via targeting the potentially altered resistance genes, transcription, and epigenetic regulation. These therapeutic activities could help with the complex issues such as drug resistance which is observed even in TNBC. Currently, various methods have been utilized for the delivery of CRISPR/Cas9 into the targeted cell such as physical (microinjection, electroporation, and hydrodynamic mode), viral (adeno-associated virus and lentivirus), and non-viral (liposomes and lipid nano-particles). Although different models have been developed to investigate the molecular causes of TNBC, but the lack of sensitive and targeted delivery methods for in-vivo genome editing tools limits their clinical application. Therefore, based on the available evidences, this review comprehensively highlighted the advancement, challenges limitations, and prospects of CRISPR/Cas9 for the treatment of TNBC. We also underscored how integrating artificial intelligence and machine learning could improve CRISPR/Cas9 strategies in TNBC therapy., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Tiwari, Ko, Dubey, Chouhan, Tsai, Singh, Chaubey, Dayal, Chiang and Kumar.)

Background: Celiac disease (CD) is frequently associated with type I diabetes mellitus (T1D), where its diagnosis may be a challenging task. This study aims to test the usefulness of the double staining immunofluorescence (dsIF) technique for the detection of intestinal anti-tissue transglutaminase specific IgA antibody (tTG-IgA) deposits in CD and T1D children with coexisting CD., Methods: A total of 46 patients (30 cases of CD and 16 cases of T1D with CD) and 16 non-diabetic, non-celiac children were recruited. Endoscopic biopsies were taken and analyzed by light microscopy, quantitative histology (QH), and a dsIF technique., Results: Histologically, villous atrophy was most severe in CD, followed by T1D with CD, while all control biopsies except 1 were normal. QH showed a statistically significant difference in villous height (Vh), crypt depth (CrD), and Vh:CrD ratio between diabetic and non-diabetic patients with CD. dsIF technique could detect tTG-IgA deposits in 85.7% of cases of CD alone and 93.8% of biopsies from diabetic children. Surprisingly, deposits were more extensive in biopsies with minimal villous shortening. Also, all 5 biopsies from T1D patients with normal histology were dsIF positive., Conclusion: In-situ analysis of tTG-IgA immune deposits facilitates the detection of positive serology early-onset CD. Quantitative analysis may be used as an ancillary tool to increase the reliability of histological findings in these patients., Competing Interests: Declaration of competing interest None of the authors has any conflict of interest to disclose., (Copyright © 2023 Taiwan Pediatric Association. Published by Elsevier B.V. All rights reserved.)

Background: Acromioclavicular joint (AC) arthritis (A) is a common incidental finding on shoulder imaging. An improved knowledge of the age- and sex-specific prevalence (or base rate) of incidental ACA can inform diagnosis and treatment strategies for shoulder pain., Hypothesis: There is no relationship between age or gender and the presence or severity of MRI findings consistent with osteoarthritis of the acromioclavicular joint., Methods: We rated ACA on 475 MRIs from a database of patients who had MRIs for non-AC indications. The cohort consisted of 51% men, 49% women and had an average age of 55. Bivariate analyses were used for analysis of age and sex-specific prevalence., Results: The prevalence of findings consistent with ACA on MRI for non-AC indications was 83%. The prevalence increased from 75% between ages 40 and 50 to 100% after age 70. Logistic regression demonstrated an association between age and ACA (Odds Ratio 2.89; 95% confidence interval [CI]=2.30 to 3.63; p=0.001). No difference was seen by sex (Chi-Square, 0.16; p=0.67). There was a positive correlation between age and ACA severity (Spearman's rho=0.43; p=0.000010)., Discussion: The observation that MRI evidence of ACA is the norm (75%) after age 40 and is universal with human aging (100% after age 70), makes it very difficult to discern ACA as a cause of shoulder symptoms. Given the near universal prevalence of radiological ACA, imaging cannot be used as a reference standard for diagnosis of symptomatic ACA based on symptoms and signs., Level of Evidence: Not applicable., (Copyright © 2022 Elsevier Masson SAS. All rights reserved.)

Background: Unhelpful thoughts and feelings of distress regarding symptoms account for a large proportion of variation in a patient's symptom intensity and magnitude of capability. Clinicians vary in their awareness of this association, their ability to identify unhelpful thoughts or feelings of distress regarding symptoms, and the skills to help address them. These nontechnical skills are important because they can improve treatment outcomes, increase patient agency, and foster self-efficacy without diminishing patient experience., Questions/purposes: In this survey-based study, we asked: (1) Are there any factors, including exposure of surgeons to information about language reflecting unhelpful thoughts about symptoms, associated with the total number of identified instances of language rated as reflecting unhelpful thoughts or feelings of distress regarding symptoms in transcripts of patient encounters? (2) Are there any factors, including exposure of surgeons to information about language reflecting unhelpful thoughts about symptoms, associated with the interobserver reliability of a surgeon's identification of language rated as reflecting unhelpful thoughts or feelings of distress regarding symptoms in transcripts of patient encounters?, Methods: Surgeons from an international collaborative consisting of mostly academic surgeons (Science of Variation Group) were invited to participate in a survey-based experiment. Among approximately 200 surgeons who participate in at least one experiment per year, 127 surgeons reviewed portions of transcripts of actual new musculoskeletal specialty encounters with English-speaking patients (who reported pain and paresthesia as primary symptoms) and were asked to identify language believed to reflect unhelpful thoughts or feelings of distress regarding symptoms. The included transcripts were selected based on the rated presence of language reflecting unhelpful thinking as assessed by four independent researchers and confirmed by the senior author. We did not study accuracy because there is no reference standard for language reflecting unhelpful thoughts or feelings of distress regarding symptoms. Observers were randomized 1:1 to receive supportive information or not regarding definitions and examples of unhelpful thoughts or feelings of distress regarding symptoms (referred to herein as "priming") once at the beginning of the survey, and were not aware that this randomization was occurring. By priming, we mean the paragraph was intended to increase awareness of and attunement to these aspects of human illness behavior immediately before participation in the experiment. Most of the participants practiced in the United States (primed: 48% [29 of 60] versus not primed: 46% [31 of 67]) or Europe (33% [20 of 60] versus 36% [24 of 67]) and specialized in hand and wrist surgery (40% [24 of 60] versus 37% [25 of 67]) or fracture surgery (35% [21 of 60] versus 28% [19 of 67]). A multivariable negative binomial regression model was constructed to seek factors associated with the total number of identified instances of language believed to reflect unhelpful thoughts or feelings of distress regarding symptoms. To determine the interobserver agreement, Fleiss kappa was calculated with bootstrapped 95% confidence intervals (resamples = 1000) and standard errors., Results: After controlling for potential confounding factors such as location of practice, years of experience, and subspecialty, we found surgeons who were primed with supportive information and surgeons who had 11 to 20 years of experience (compared with 0 to 5 years) identified slightly more instances of language believed to reflect unhelpful thoughts or feelings of distress regarding symptoms (regression coefficient 0.15 [95% CI 0.020 to 0.28]; p = 0.02 and regression coefficient 0.19 [95% CI 0.017 to 0.37]; p = 0.03). Fracture surgeons identified slightly fewer instances than hand and wrist surgeons did (regression coefficient -0.19 [95% CI -0.35 to -0.017]; p = 0.03). There was limited agreement among surgeons in their ratings of language as indicating unhelpful thoughts or feelings of distress regarding symptoms, and priming surgeons with supportive information had no influence on reliability (kappa primed: 0.25 versus not primed: 0.22; categorically fair agreement)., Conclusion: The observation that surgeons with brief exposure to supportive information about language associated with unhelpful thoughts and feelings of distress regarding symptoms identified slightly more instances of such language demonstrates the potential of training and practice to increase attunement to these important aspects of musculoskeletal health. The finding that supportive information did not improve reliability underlines the complexity, relative subjectivity, and imprecision of these mental health concepts., Level of Evidence: Level I, therapeutic study., Competing Interests: Each author certifies that there are no funding or commercial associations (consultancies, stock ownership, equity interest, patent/licensing arrangements, etc.) that might pose a conflict of interest in connection with the submitted article related to the author or any immediate family members. All ICMJE Conflict of Interest Forms for authors and Clinical Orthopaedics and Related Research® editors and board members are on file with the publication and can be viewed on request., (Copyright © 2022 by the Association of Bone and Joint Surgeons.)

The lumpy skin disease virus (LSDV) infects cattle and buffalo and causes lumpy skin disease (LSD). It affects the lymph nodes of the sick animals, causing them to enlarge and appear as lumps (cutaneous nodules) that are 2-5 cm in diameter on their heads, necks, limbs, udders, genitalia, and perinea. A high temperature, a sharp drop in milk supply, discharge from the eyes and nose, salivation, a loss of appetite, depression, damaged hides, and emaciation are further warning signs and symptoms. As per the Food and Agriculture Organization (FAO), the incubation period, or the time between an infection and symptoms, is approximately 28 days. Infected animals can transfer the virus by direct contact with the vectors, direct virus secretion from mouth or nose, shared feeding and watering troughs, and even artificial insemination. The World Organization for Animal Health (WOAH) and the FAO both warn that the spread of illnesses could lead to serious economic losses. This illness reduces cow's milk production because oral ulcers make the animal weak and lead them to lose their appetite. There are many diagnostics available for LSDV. However, very few tests yield accurate findings. The best methods for preventing and controlling the lumpy skin condition include vaccination and movement restrictions. As a specific cure is not available, the only available treatment for this illness is supportive care for cattle. Recently, India has developed a homologous, live-attenuated vaccine, Lumpi-ProVacInd, which is specifically intended to protect animals against the LSD virus. This study's primary goal is to accumulate data on symptoms, the most accurate method of diagnosis, treatments, and controls to stop infections from spreading as well as to explore future possibilities for the management of LSDV.

Objective: To investigate the effects of combination therapy with cholecalciferol and lansoprazole on residual β-cell function and glycemic control in children with new-onset type 1 diabetes., Methods: Children aged 6-12 years with type 1 diabetes were allocated to receive cholecalciferol and lansoprazole (Group 1) or no treatment (Group 2). Children were maintained on their respective insulin regimens and kept records of blood sugar and insulin doses taken. Children were followed at three-month intervals for six months. Changes in mean fasting C-peptide and HbA1c levels, daily insulin doses, fasting blood glucose and mean blood glucose levels from baseline to end of the study were analyzed., Results: Twenty-eight children (14 per group) met the eligibility criteria. Fasting C-peptide levels decreased significantly from baseline to study end in both groups (mean decrease -0.19±0.09ng/mL and -0.28±0.08ng/mL, p=0.04 and p=0.001; Group 1 and Group 2 respectively). However, fasting C-peptide level drop was significantly smaller in Group 1 compared to Group 2 (30.6% and 47.5% respectively; p=0.001). Likewise, daily insulin doses decreased significantly in both groups (-0.59±0.14units/kg and -0.37±0.24units/kg respectively; p=0.001). All patients recruited completed the study. No adverse events were reported., Conclusion: Combined therapy with cholecalciferol and lansoprazole for six months was associated with smaller decline in residual β-cell function and lower insulin requirements in children with new-onset type 1 diabetes. Preliminary findings of this small-scale study need to be confirmed by larger studies., Registry of Clinical Trials: (www.ctri.nic.in) under number REF/2021/03/041415 N.

In this study, the long-term trends in climatological parameters, viz., maximum temperature (T MAX ) and minimum temperature (T MIN ), are determined over 68 years (i.e., June 1951 to May 2019) using the gridded observation datasets (1° × 1° spatial resolution) of India Meteorological Department over the Narmada river basin, India. Multiple non-parametric techniques, viz., modified Mann-Kendall (MMK), Sen's slope (SS), and Spearman's rho (SR) tests, are used to determine monthly, seasonal, and annual trends over individual grids. The trends are also analyzed for the climatic variables spatially averaged over the entire basin to draw general conclusions on historical climate change. The results reveal a significant spatiotemporal variation in trends of T MAX and T MIN over the basin. In general, both the parameters are found to be increasing. Furthermore, the hottest months (April and May) have become hotter, and the coldest month (January) has become colder, implying a higher probability of increasing temperature extremes. Furthermore, the entire duration of 68 years is divided into two epochs of 34 years, i.e., 1951-1984 and 1985-2018, and the trend analysis of T MAX and T MIN is also carried out epoch-wise to better understand/assess the signals of climate change in recent years. In general, a relatively higher warming trend was observed in the latter epoch. As a majority of the basin area is dominated by agricultural lands, the implications of the temperature trends and their impacts on agriculture are succinctly discussed. The information reported in this study will be helpful for proper planning and management of water resources over the basin under the changing climatic conditions., (© 2022. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Drought is considered among the most perilous events with catastrophic consequences, particularly from the agro-economic point of view. These consequences are expected to exacerbate under the increasing meteorological aberrations due to changing climate, which necessitates investigating drought variabilities. This study presents a thorough spatiotemporal assessment of drought trends and variabilities over the agriculture-dominated Marathwada Region, Maharashtra, India. The precipitation data is extracted from the India Meteorological Department (IMD) gridded product, whereas actual evapotranspiration (ET) and Evaporative Stress Index (ESI) are obtained from Global Land Evaporation Amsterdam Model (GLEAM) datasets. Standardized Precipitation Index (SPI) is used to characterize drought occurrences at multiple time frames, whereas non-parametric tests, i.e., modified Mann-Kendall (MMK) and Sen's slope (SS) tests, are employed to detect trends. The results reveal the region to be prone to droughts, and SPI at a longer time frame (i.e., 12-monthly moving frame) can capture drought occurrences better than the shorter time frames, which can be attributed to the lesser randomness in the time series in the longer frame. A mix of positive/negative trends of SPI series are found for the monsoonal months; however, they are relatively more concentrated towards negative Z MMK . Hence, the Marathwada Region can be inferred to have exhibited a relatively increased tendency towards drought occurrences. The seasonal differences in mean values and trends of rainfall, ET, and ESI are discussed in detail. Since the Marathwada Region has a monsoon-dominated climate with high agricultural importance, the information reported in this study will help in devising water management strategies to minimize the repercussions of droughts., (© 2022. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Purpose: We aimed to provide a scientometric assessment of global research in stem cell therapy (SCT) for type 1 diabetes (T1D) during 1999-2020., Methods: The published data on SCT in T1D were retrieved from Elsevier's Scopus database and analyzed using select bibliometric tools. We used VOSviewer software and the Biblioshiny app to construct and visualize bibliometric networks., Results: The global yield totaled 1806 publications in the 22-year study period, registering a 17.7% annual growth peaking at 196.9% in the last 11 years. The average citations per publication (CPP) decreased from 62.0 during 1999-2009 to 24.3 during 2010-2020. The funded publications were 727 (40.2%). Randomized controlled trials (RCTs) were only 2.4% (45). Amongst 70 participating countries, the USA led with a 38.6% share. Of the 388 global organizations, Harvard Medical School, USA, San Raffaele Scientific Institute, Italy, and the University of Florida, USA were the topmost contributors. Florina, Couri, and Trucco were the top productive authors, whereas Melton, Abdi, and Simoes were the most impactful. Only 129 (3.1%) publications were highly-cited; their total and average CPP were 31,228 and 214.0 (range 101-1841), respectively., Conclusions: The quantity of research in SCT for T1D has increased during the last two decades while the quality has dipped. The research landscape is dominated by high-income North-American and Western-European countries. There is a need for conducting large-scale RCTs and promoting research collaborations between high- and low-income countries for long-term sustainability and global impact., Competing Interests: Competing interestsNone., (© The Author(s), under exclusive licence to Tehran University of Medical Sciences 2022, Springer Nature or its licensor holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Introduction: Type 1 diabetes (T1D) incurs substantial out-of-pocket expenses (OOPE) on insulin and diabetes-related supplies. The information on OOPE is scarce from low- and middle-income countries. We aimed to estimate annual OOPE for children with T1D attending our diabetes clinic located in North India., Methods: An online survey was conducted among parents of 380 children with T1D (mean age: 10.3 ± 4.6 years). Modified BG Prasad scale was used to estimate the socioeconomic status (SES)., Results: The mean duration of T1D was 3.6 ± 2.6 years; 54.9% of children were boys. The median HbA1c (IQR) was 7.9% (5-15%). 51.9% belonged to lower or lower-middle SES. Mean annual spending on glucose monitoring, insulin administration, and laboratory investigations were Indian Rupee (INR) 21,576, INR 28,965, and INR 5069, respectively (total INR 55,185, IQR: 26,575-105,027). The cost of a single visit to the doctor was approximately INR 2889. Thirty children required hospitalization during the last year, which costs INR 27,495 on average. 30.3% had more than 50% of their total family income spent on diabetes care, with a significant negative correlation with their SES ( r  =  - 0.738, p  = 0.00). Only 11.6% were receiving financial support from any agency. 36.6% of families had to borrow money; the OOPE exceeded income from all sources in 8.2% of families., Conclusions: There is a high financial burden of T1D care for North Indian children, almost on the verge of losing sustainability. Further studies are warranted to furnish larger OOPE data to guide policy decisions aimed at reducing direct costs to patients., Competing Interests: Conflict of interestNone., (© The Japan Diabetes Society 2022.)

Background: Children with type 1 diabetes (T1D) take multiple subcutaneous injections of insulin daily to survive. It is controversial whether the insulin needles can be reused safely or not. This study assesses the effect of the reuse versus single-use of insulin needle on glycaemic control and injection-related complications., Methods: Nearly 121 children (<15 years) with T1D were prospectively observed for existing practice of needle reuse for first 3 months and then were asked to practice single-use for the next 3 months., Results: It was found that 78% participants were reusing needles more than three times. After 3 months of needle reuse, 91.3% patients had lipodystrophy. Frequency of reuse positively correlated with local redness, bleeding and leakage of insulin. The patients achieving HbA1c ≤7.5% was significantly low among those reusing needles more than four times. After 3 months of single-use, no significant difference was found in mean HbA1c. However, hyperglycaemic episodes, lipodystrophy and local complications reduced significantly. There was a significant reduction in mean HbA1c among those using needles more than six times earlier., Conclusion: Reuse of insulin needles up to six times does not affect the glycaemic control significantly. To achieve target HbA1c (<7.5%) the needle reuse should be restricted to three times only, which can also reduce injection-related local complications., Competing Interests: There are no conflicts of interest., (Copyright: © 2022 Indian Journal of Endocrinology and Metabolism.)

Introduction and Importance: Inflammatory myofibroblastic tumour (IMT) is a rare tumour with malignant potential and has been described in many major organs with the most frequent site being the lungs. However, bladder is an extremely rare location. IMT presents a unique diagnostic challenge because of the characteristics it shares with malignant neoplasms., Case Presentation: Here we report the case of a 47-yearold male who presented with storage lower urinary tract symptoms associated with non-specific lower abdominal pain for one month duration. Contrast-enhanced computed tomography of abdomen and pelvis revealed a 6 cm tumour at the dome and left side anterior wall of the bladder. He underwent laparotomy and partial cystectomy. Histopathology results were consistent with an IMT., Clinical Discussion: Even though bladder IMT is indolent in course, typical IMTs can be locally aggressive. Due to the lack of specificity in clinical symptoms, it is not easy to arrive at a precise diagnosis before surgery. Hence, the final diagnosis depends on histomorphological features and the immune histochemical profile., Conclusion: It can be challenging to distinguish IMT from malignant neoplasms both clinically and histologically. As such, local surgical resection with close follow-up remains the mainstay of treatment for urinary tract IMT., (Copyright © 2022. Published by Elsevier Ltd.)

Identifying the potential for SARS-CoV-2 reinfection is crucial for understanding possible long-term epidemic dynamics. We analysed longitudinal PCR and serological testing data from a prospective cohort of 4,411 United States employees in 4 states between April 2020 and February 2021. We conducted a multivariable logistic regression investigating the association between baseline serological status and subsequent PCR test result in order to calculate an odds ratio for reinfection. We estimated an odds ratio for reinfection ranging from 0.14 (95% CI: 0.019 to 0.63) to 0.28 (95% CI: 0.05 to 1.1), implying that the presence of SARS-CoV-2 antibodies at baseline is associated with around 72% to 86% reduced odds of a subsequent PCR positive test based on our point estimates. This suggests that primary infection with SARS-CoV-2 provides protection against reinfection in the majority of individuals, at least over a 6-month time period. We also highlight 2 major sources of bias and uncertainty to be considered when estimating the relative risk of reinfection, confounders and the choice of baseline time point, and show how to account for both in reinfection analysis., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: GA is a founder of Seromyx Systems Inc., a company developing platform technology that describes the antibody immune response. GA’s interests were reviewed and are managed by Massachusetts General Hospital in accordance with their conflict-of-interest policies. MJG, SB, DD, YH, JR, EP, BM, ASM, and ERM are employees of Space Exploration Technologies Corp. All other authors have declared that no conflict of interest exists.

SARS-CoV-2 mRNA vaccines confer robust protection against COVID-19, but the emergence of variants has generated concerns regarding the protective efficacy of the currently approved vaccines, which lose neutralizing potency against some variants. Emerging data suggest that antibody functions beyond neutralization may contribute to protection from the disease, but little is known about SARS-CoV-2 antibody effector functions. Here, we profiled the binding and functional capacity of convalescent antibodies and Moderna mRNA-1273 COVID-19 vaccine-induced antibodies across SARS-CoV-2 variants of concern (VOCs). Although the neutralizing responses to VOCs decreased in both groups, the Fc-mediated responses were distinct. In convalescent individuals, although antibodies exhibited robust binding to VOCs, they showed compromised interactions with Fc-receptors. Conversely, vaccine-induced antibodies also bound robustly to VOCs but continued to interact with Fc-receptors and mediate antibody effector functions. These data point to a resilience in the mRNA-vaccine-induced humoral immune response that may continue to offer protection from SARS-CoV-2 VOCs independent of neutralization., Competing Interests: Declaration of interests G.A. is the founder of Seromyx Systems Inc. A.C. is an employee of Moderna Inc. D.D., P.M., A.S.M., and E.R.M. are employees of Space Exploration Technologies Corp. All other authors have declared no competing interests., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Haemonchus contortus is a major constraint in the development of small ruminant subsector due to significant production losses incurred by it. The present study explores the antiparasitic potential of three anthelmintic plants ( Butea monosperma, Vitex negundo and Catharanthus roseus (L.) G.Don ) against H . contortus taking albendazole as the standard. In silico molecular docking and pharmacokinetic prediction studies were conducted with known bioactive molecules of these plants (palasonin, vinblastine, vincristine, betulinic acid and ursolic acid) against Glutamate Dehydrogenase (GDH) and tubulin molecules of the parasite. Methanolic extracts of these herbs were fractionated (hexane, ethyl acetate, chloroform and methanol) and used in in vitro larvicidal studies. Based on the in vitro data, two herbal prototypes were developed and clinically tested. All the 5 ligand molecules showed better binding affnity for GDH and tubulin protein as compared with albendazole and shared similar binding site in the core of the GDH hexamer with slight variations. Albendazole approximately stacked against GLY190A residue, showing hydrophobic interactions with PRO157A and a Pi-cation electrostatic interaction with ARG390 along with four hydrogen bonds. Vincristine formed 2 pi-anionic electrostatic bonds with ASP158 of B and C subunits alongwith hydrogen bonding and hydrophobic interaction and an additional pi-anion electrostatic interaction at ASP158A for vinblastine. Albendazole bound to α-tubulin next to colchicine site whereas vinblastine is bound at the nearby laulimalide/peloruside site of the dimer. Betulinic acid showed lateral interaction between the H2-H3 loop of one alpha subunit and H10 of the adjacent alpha subunit of two tubulin dimers. Ursolic acid and palasonin bound at the intradimer N site of microtubulin involving the H1-H7 and H1-H2 zone, respectively. The in vitro studies demonstrated good dose dependent anthelmintic potential. Both the prototypes were quite efficacious in clearing the infection, keeping it to a minimal for more than 5 months, probably, through direct anthelmintic effect through GDH, tubulin depolymerization and uncoupling as well as indirectly through immunomodulation along with antioxidant and anti-inflammatory properties., Competing Interests: The authors declare no conflict of interest., (© 2022 The Author(s).)

Introduction: Optimal glycaemic control is essential for the prevention of future micro- and macrovascular complications in type 1 diabetes (T1D). The type of insulin, the type of insulin delivery device, the caregiver's knowledge, the patient's age, duration of diabetes, and self-monitoring of blood glucose affect glycaemic control in type 1 diabetes. In the present study, we analysed glycaemic control and factors affecting it at a tertiary care centre in northern India., Material and Methods: A retrospective review of records of patients registered between 2015 and 2018 was done. The data on demographic and disease-related factors were collected from the records. The different groups were compared with the t-test, one-way ANOVA, or Kruskal-Wallis test., Results: The mean age at the time of evaluation was 10.43 ±4.04 years (2-21 years), and the mean disease duration was 46.61 ±28.49 months (16-141 months). Most of the patients were prepubertal and using a basal-bolus regimen. The mean glycated haemoglobin (HbA1c ) was 7.96 ±1.46%, but only 24% had HbA1c below the International Society of Paediatric and Adolescent Diabetes (ISPAD) recommended desirable level of below 7%. Forty-six patients suffered one or more micro-macrovascular complications, and dyslipidaemia was the most common complication. Children with a longer duration of disease (8.39 ±1.42% vs. 7.59 ±1.65%), an episode of DKA (diabetes ketoacidosis) within a year of evaluation (9.19 ±2.54% vs. 7.93 ±1.39%), lower maternal (8.22 ±1.37% vs. 7.56 ±1.45%) and paternal education (8.26 ±1.67% vs. 7.78 ±1.30%), and hyperthyroid state (9.43 ±2.28% vs. 7.91 ±1.45%) had higher HbA1c., Conclusions: Better diabetes education focusing on parents with lower education strata and children with longer disease duration and poor compliance can help improve glycaemic control in developing countries like India.

Background: Acute kidney injury (AKI) due to Diabetic Ketoacidosis (DKA) is rather common. Novel biomarkers to diagnose AKI are being increasingly used in different settings. The use of urinary Neutrophil Gelatinase-Associated Lipocalin (uNGAL) in predicting persistent AKI in pediatric DKA cases is still not thoroughly investigated., Methods: This was a secondary analysis of Saline versus Plasma-Lyte in Ketoacidosis (SPinK) trial data; 66 children (> 1 month-12 years) with DKA, defined by the International Society for Pediatric and Adolescent Diabetes (ISPAD), were analyzed. Children with cerebral edema, chronic kidney disease and those who received pre-referral fluids and/or insulin were excluded. uNGAL and urine NGAL-creatinine ratio (uNCR) at 0 and 24 h were measured in all. Persistent AKI was defined as a composite outcome of continuance of AKI defined by the Kidney Disease Improving Global Outcomes (KDIGO) stage 2 or 3 beyond 48 h from AKI onset, progression of AKI from either KDIGO stage 0 or 1 to a worse stage, need of renal replacement therapy or death., Main Outcomes: Thirty-five (53%) children had AKI at admission; 32 (91.4%) resolved within 48 h. uNGAL was significantly higher in the AKI group at admission [79.8 ± 27.2 vs 54.6 ± 22.0, p = 0.0002] and at 24 h [61.4 ± 28.3 vs 20.2 ± 14.5, p = 0.0003]. Similar trend was observed with uNCR at admission [6.7 ± 3.7 vs 4.1 ± 2.6, p = 0.002] and at 24 h [6.3 ± 2.5 vs 1.2 ± 1.0, p = 0.01]. Furthermore, uNGAL at admission showed a moderate positive linear correlation with serum creatinine. Additionally, elevated uNGAL at 0 and 24 h correlated with corresponding KDIGO stages. Admission uNGAL >88 ng/ml and uNCR of >11.3 ng/mg had a sensitivity of 66% and 67%, specificity of 76% and 95%, and Area under the receiver operating characteristic curve (AUC) of 0.78 and 0.89 respectively for predicting persistent AKI at 48 h., Conclusions: Majority of AKI resolved with fluid therapy. While uNGAL and uNCR both correlated with serum creatinine and AKI stages, serial uNCR was a better predictor of persistent AKI than uNGAL alone. However, feasibility of routine uNGAL measurement to predict persistent AKI in DKA needs further elucidation., Trial Registration: This was a secondary analysis of the data of SPinK trial [CTRI/2018/05/014042 ( ctri.nic.in )]., (© 2021. The Author(s).)