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Abstract Background Pituitary neuroendocrine tumors (PitNET) are among the most common intracranial tumors. Despite a frequent benign course, aggressive behavior can occur. Tumor behavior is known to be under the influence of the tumor microenvironment (TME). However, the relationship between TME cells and aggressive tumor behavior has not been adequately explored in PitNET. Methods We performed differential expression analysis as well as gene expression program identification based on single-cell RNA sequencing to comparatively characterize the transcriptome of seven gonadotroph and three lactotroph PitNET and correlate it with clinical features using bulk RNA-seq data from an independent cohort of 134 PitNET. Tumor immune infiltration was quantified via immunostaining on tissue sections of gonadotroph and lactotroph PitNET. Results In lactotroph PitNET, we detect a highly proliferative gene profile with significantly increased expression levels in aggressively growing tumors within bulk RNA-seq data of an independent cohort of 134 PitNET samples. We also report high intratumoral heterogeneity in gonadotroph PitNET (GoPN) and lactotroph PitNET (LaPN) and identify signatures of epithelial, endocrine, and immunological gene networks in both subtypes. A comparison of their TME composition shows enrichment of SPP1+ macrophages and CD4+ T cells in GoPN, as well as enrichment of CD4/CD8 double-negative T cells (DN) and natural killer cells (NK) in LaPN. Also notable is the presence of proliferative lymphocytes, the occurrence of which positively correlates with more aggressive tumor behavior in the bulk RNA-seq cohort. However, increased CD8+ T and NK cell abundances correlate significantly with reduced aggressiveness indicating potential anti-tumoral effects. Conclusions Our study expands the knowledge of the differences in cellular composition of gonadotroph and lactotroph PitNET subtypes. It lays the foundation for further studies on the influence of lymphoid cells on the variable aggressive behavior of PitNET. Regarding the treatment of drug-resistant lactotroph PitNET, proliferative lymphocytes, CD8+ T, and NK cells could represent potentially valuable targets for developing new cancer immunotherapies.

Abstract Peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS) is a heterogeneous group of malignancies with poor outcome. Here, we identify a subgroup, PTCL-NOS SMARCB1- , which is characterized by the lack of the SMARCB1 protein and occurs more frequently in young patients. Human and murine PTCL-NOS SMARCB1- show similar DNA methylation profiles, with hypermethylation of T-cell-related genes and hypomethylation of genes involved in myeloid development. Single-cell analyses of human and murine tumors revealed a rich and complex network of interactions between tumor cells and an immunosuppressive and exhausted tumor microenvironment (TME). In a drug screen, we identified histone deacetylase inhibitors (HDACi) as a class of drugs effective against PTCL-NOS Smarcb1- . In vivo treatment of mouse tumors with SAHA, a pan-HDACi, triggered remodeling of the TME, promoting replenishment of lymphoid compartments and reversal of the exhaustion phenotype. These results provide a rationale for further exploration of HDACi combination therapies targeting PTCL-NOS SMARCB1- within the TME.

Abstract Background The genetic progress of fertility and reproduction traits in dairy cattle has been constrained by the low heritability of these traits. Identifying candidate genes and variants associated with fertility and reproduction could enhance the accuracy of genetic selection and expedite breeding process of dairy cattle with low-heritability traits. While the bovine LAP3 and SIRT1 genes exhibit well-documented associations with milk production traits in dairy cattle, their effect on cow fertility have not yet been explored. Eleven single nucleotide polymorphisms (SNPs), comprising five in the promoter (rs717156555: C > G, rs720373055: T > C, rs516876447: A > G, rs461857269: C > T and rs720349928: G > A), two in 5’UTR (rs722359733: C > T and rs462932574: T > G), two in intron 12 (rs110932626: A > G and rs43702363: C > T), and one in 3’UTR of exon 13 (rs41255599: C > T) in LAP3 and one in SIRT1 (rs718329990:T > C) genes, have previously been reported to be associated with various traits of milk production and clinical mastitis in Sahiwal and Karan Fries dairy cattle. In this study, the analysis primarily aimed to assess the impact of SNPs within LAP3 and SIRT1 genes on fertility traits in Sahiwal and Karan Fries cattle. Association studies were conducted using mixed linear models, involving 125 Sahiwal and 138 Karan Fries animals in each breed. The analysis utilized a designated PCR-RFLP panel. Results In the promoter region of the LAP3 gene, all variants demonstrated significant (P T. However, specific variants with the LAP3 gene’s promoter region, namely rs722359733: C > T, rs110932626: A > G, rs43702363: C > T, and rs41255599: C > T, showed significant associations with CI and DO in Sahiwal and Karan Fries cows, respectively. The SNP rs718329990: T > C in the promoter region of SIRT1 gene exhibited a significant association with CI and DO in Sahiwal cattle. Haplotype-based association analysis revealed significant associations between haplotype combinations and AFC, CI and DO in the studied dairy cattle population. Animals with H2H3 and H2H4 haplotype combination exhibited higher AFC, CI and DO than other combinations. Conclusions These results affirm the involvement of the LAP3 and SIRT1 genes in female fertility traits, indicating that polymorphisms within these genes are linked to the studied traits. Overall, the significant SNPs and haplotypes identified in this study could have the potential to enhance herd profitability and ensure long-term sustainability on dairy farms by enabling the selection of animals with early age first calving and enhance reproductive performance in the dairy cattle breeding program.

Retinoblastoma is a pediatric intraocular cancer caused by biallelic inactivation of RB1 gene in retinal progenitor cells. Here, we report the generation of a patient-specific induced pluripotent stem cell (iPSC) line (LVPEIi002-A) from a patient diagnosed with retinoblastoma and showing familial inheritance of a nonsense mutation (c.1735C > T) within exon 18 of one of the two alleles. This RB1+/- iPSC line, LVPEIi002-A was generated by reprogramming the peri-orbital fat tissue derived mesenchymal cells and was stably expanded and characterized. It maintains the stemness, pluripotency, normal karyotype, and forms embryoid bodies comprising of all three lineage committed progenitor cells.

Abstract Pediatric high-grade gliomas of the subclass MYCN (HGG-MYCN) are highly aggressive tumors frequently carrying MYCN amplifications, TP53 mutations, or both alterations. Due to their rarity, such tumors have only recently been identified as a distinct entity, and biological as well as clinical characteristics have not been addressed specifically. To gain insights into tumorigenesis and molecular profiles of these tumors, and to ultimately suggest alternative treatment options, we generated a genetically engineered mouse model by breeding hGFAP-cre::Trp53 Fl/Fl ::lsl-MYCN mice. All mice developed aggressive forebrain tumors early in their lifetime that mimic human HGG-MYCN regarding histology, DNA methylation, and gene expression. Single-cell RNA sequencing revealed a high intratumoral heterogeneity with neuronal and oligodendroglial lineage signatures. High-throughput drug screening using both mouse and human tumor cells finally indicated high efficacy of Doxorubicin, Irinotecan, and Etoposide as possible therapy options that children with HGG-MYCN might benefit from.

Selecting female cows for productivity based on udder and teat traits is essential in field due to lack of available records. The objective of the present study was to reduce the dimensionality of the 17 udder and teat traits and to analyse their impact on milk productivity. The data on 256 cattle comprising 133 Sahiwal and 123 Karan Fries cows were used in this study over the years 2017-2019 from Livestock Research Centre (LRC) of ICAR-National Dairy Research Institute, Karnal. The 17 udder and teat traits were fore udder attachment (FUA), rear udder width (RUW), rear udder height (RUH), udder balance (UB), udder depth (UD), udder length (UL), udder width (UW), udder circumference (UC), central ligament/udder cleft (CL), teat circumference (TC), fore teat length (FTL), rear teat length (RTL), distance between fore and rear teat (DFR), distance between left and right teat (DLR), shortest distance from floor to fore teat (SDFT), shortest distance from floor to rear teat (SDRT) and teat diameter (TD). In the factor analysis, first five latent factors accounted for 62.22% of total variance in udder and teat measurements for Sahiwal cows and 65.67% in Karan Fries (KF) cows, respectively. In Sahiwal cows F1 represented better udder support and wideness (wide udders, udders were supported by strong suspensory ligament), whereas in KF cows, first factor reflected better udder dimension and distance between teats (longer length, width of udder and well placed teats). Factor analysis could reduce the multicollinearity of the data. It can be concluded that inclusion of udder and teat measurements in selection index can be a reliable criteria for selecting cows for higher milk yield.

Abstract Background Development of emotional distress (ED) among adolescents living with perinatally acquired HIV (ALPHIV) affects their adherence behaviour and social and psychological functioning. Data on stressors among ALPHIV demonstrates the gap on the predictors of ED experienced by ‘perinatally infected ALHIV’ in the Indian socio-cultural milieu. This study aimed to identify the predictors of ED and examine their mediating and moderating role in the development of ED among Indian ALPHIV. Methods Utilizing the sequential exploratory mixed-methods design, 43 qualitative interviews were conducted with ALPHIV, parents/guardians, and health care providers, followed by the cross-sectional survey among 100 ALPHIV (10–19 years). The distress subscale of the Weinberger Adjustment Inventory was used to measure ED. Qualitative data, analyzed using grounded theory were utilized to develop a survey tool. Bivariate and regression analyses were conducted to identify predictors of ED. Mediation and moderation models were tested to examine underlying mechanisms associated with ED. The study was approved by the institutional ethics committee. Results Strong parental control, compulsive asexuality, perceived negatively different from peers, and anger toward parents were the major themes emerging from the qualitative component which eventually led to survey tool domains viz., HIV awareness, parental control, hypervigilance, adolescent-parent relationship, adolescent-parent communication, body image and perceived negatively different from peers (PNDP). Quantitative analysis indicated high ED among ALPHIV and ED was significantly associated with PNDP, anger, body image, and hypervigilance. The relationship between PNDP and ED was significantly mediated by anger, and moderated by body image and hypervigilance. Conclusions The study stresses the need for early mental health interventions for Indian ALPHIV before an ALPHIV develops ED. Focused counseling on anger assessment, body image issues, and self-perception is critical for leading a 'normal' life by ALPHIV. Besides, skill building of primary caregivers is recommended to draw a line between protection and overprotection.

Aim. The current study was aimed to analyze the etiology and the clinical spectrum of acute symptomatic seizures (ASS) and the predictors of in- hospital mortality in the elderly population. Methods. We evaluated ninety-four elderly (≥60 years of age) hospitalized patients with ASS for clinical profile, etiologies and predictors of in-hospital mortality. Results. Mean age of onset of ASS was 67.63 ± 11.48 years. Main seizure type was focal seizure in 62 (59.7%) cases followed by tonic-clonic seizures in 30 (31.9%) cases. Most common etiologies in ASS were stroke in 61.7% followed by infective cause in 30.9% of cases. In-hospital mortality in the ASS in the elderly was 21 (22.3%) in our series and the stroke was the most common cause of mortality. Conclusion. Stroke was the most common etiology of ASS in the elderly and was also related with mortality. It is necessary for us to analysis the causes of ASS in the elderly, in order to reduce the in-hospital mortality.

Abstract Background Bovine mastitis continues to remain as the most challenging disease in dairy cattle, as a result improvement of selection methods has great economic relevance while a deeper understanding of the genetic mechanisms regulating milk production traits and mastitis is of general scientific interest. Objectives This study aimed to evaluate the association of SNPs of the LAP3 and SIRT1 genes with estimated breeding values (EBVs) of milk production traits and clinical mastitis in dairy cattle of Indian origin. Methods DNA samples from 263 animals (Sahiwal and Karan Fries cattle) were genotyped by PCR‐RFLP to assess their pattern of genetic variation. EBVs of milk production traits and phenotypic records of incidences of clinical mastitis were used for association analysis. Results A total of 9 SNPs were identified, including three (rs110932626: A>G, rs716493845: C>T and rs43702363: C>T) in intron 12, four (g.24904G>C, rs110839532: G>T, rs43702361: T>C and rs41255599: C>T) in exon 13 and within 3’UTR of LAP3 gene and two (rs110250233: G>A and rs42140046: C>G) in the promoter region of SIRT1 gene. Eight of these identified SNPs were chosen for subsequent genotyping and association analyses. Association analysis revealed that SNP rs41255599: C>T was significantly associated with lactation milk yield, 305‐day milk yield, 305‐day fat yield, 305‐day solid not fat yield, lactation length and incidence of clinical mastitis (p G and rs43702363: C>T showed significant association with 305‐day milk yield. Conclusion Overall, these findings provide evidence for association of the LAP3 gene with milk production traits and clinical mastitis in dairy cattle, indicating the potential role of LAP3 variants in these traits.

Background: Epilepsy is the second most common neurological disorder that affects 1 percent of global population. Since antiepileptics have narrow therapeutic index having multiple adverse drug reactions (ADRs) thus have significant safety concerns. The aim of this study was to observe adverse drug reactions due to antiepileptics in neurology department M.Y.H. Indore, India.Methods: An observational prospective study was done from November 2021 to January 2022. Patients having history of seizures attending neurology outpatient department at MYH Hospital, who were on antiepileptic drugs were recruited. Suspected adverse drug reaction forms were recorded and their causality assessment was done by Naranjo’s scale. Results: Data of total 70 patients were recorded. Males reporting ADRs due to antiepileptics were 67.1% and females 32.8%. Using Naranjo’s scale, we noted 93.3% ADRs as “probable” and 6.7% as “possible”. Common causes of prescribing antiepileptic drugs were known case of epilepsy (78.5%),old case of neurocysticercosis (11.4%),post traumatic(4.3%),gliosis (2.8%) and tuberculoma (2.8%) .Most ADRs were dermatological 76% (rashes),central nervous system (16%) (nocturnal enuresis, poor school performance, dizziness, headache, sleep disturbances, personality changes) ,Gastrointestinal (8%) (gastric irritation, nausea, vomiting and hepatotoxicity) .Most common drug for causing ADRs were sodium valproate(58.5%),carbamazepine(17.14%),phenytoin(14.2%),leviteracetam(7.1%),and lamotrigine(2.8%). Conclusion: Our study aimed us to know the incidence and patterns of adverse drug reactions due to antiepileptics in a tertiary care institute of central India. Despite of recent advances and novel therapies used for the treatment of epilepsy, conventional drugs like sodium valproate, phenytoin and carbamazepine still are the first choice for the management and treatment of seizures and their ADRs are very common.

Land degradation is one of the most important factors responsible for the alarming situation of food security, human health, and socioeconomic development in the country. Currently, 120.7 M ha of land in the country is affected by land degradation, out of which 85.7 M ha of land is affected by soil erosion caused by water and wind. Moreover, physical, chemical, and biological degradation are the major forms of land degradation in the country. Deforestation or tree cover loss (2.07 M ha) from 2001 to 2021, intensive rainfall (>7.5 mm ha−1), uncontrolled grazing (5.65 M ha), indiscriminate use of fertilizers (32 MT year−1), and shifting cultivation (7.6 M ha) are other major factors that further aggravate the process of land degradation. In order to alleviate the problem of land degradation, numerous agroforestry technologies have been developed after years of research in different agroclimatic zones of the country. The major agroforestry systems observed in the country are agri-horticulture, silvipasture, and agri-silviculture. This review indicates the potential of agroforestry in enhancing carbon sequestration (1.80 Mg C ha−1 year−1 in the Western Himalayan region to 3.50 Mg C ha−1 year−1 in the island regions) and reduced soil loss and runoff by 94% and 78%, respectively, in Northeast India. This can be concluded that the adoption of the agroforestry system is imperative for the rehabilitation of degraded lands and also found to have enough potential to address the issues of food, environmental, and livelihood security. This review’s findings will benefit researchers, land managers, and decision-makers in understanding the role of agroforestry in combating land degradation to enhance ecosystem service in India and planning suitable policies for eradicating the problem effectively.

The purpose of this study was to identify genetic variants in the promoter and 5'UTR regions of bovine leucine amino peptidase three (LAP3) gene and analysed their associations with estimated breeding values (EBVs) of milk production traits and clinical mastitis in Sahiwal and Karan Fries cattle. Eleven SNPs were identified within the region under study of the LAP3 gene, including seven promoter variants (rs717156555: C>G, rs720373055: T>C, rs715189731: A>G, rs516876447: A>G, rs461857269: C>T, rs136548163: C>T, and rs720349928: G>A) and four 5'UTR variants (rs717884982: C>T, rs722359733: C>T, rs481631804: C>T and rs462932574: T>G). Out of them, 10 SNPs variants were found in both Sahiwal and Karan Fries cattle, with one SNP variant (rs481631804: C>T) being unique to Karan Fries cattle. Seven of these identified SNPs were chosen for association analyses. Individual SNP based association analysis revealed that two SNPs (rs720373055: T>C and rs720349928: G>A) were significantly associated with EBVs of lactation milk yield (LMY), 305-day milk yield (305dMY), and one significant association of SNP rs722359733: C>T with lactation length (LL) was observed. Haplotype based association analysis indicated that diplotypes are significantly associated with EBVs of LMY, 305dMY, and LL, individuals with H1H3 (CTACGCT/GCGTACG) being linked to higher lactation performance than other diplotypes. Further logistic regression analysis revealed that, animals with diplotype H1H3 was less susceptible to the incidence of clinical mastitis than other cows, as the odds ratio for the non-incidence of clinical mastitis was found to be low. Altogether, variations in the LAP3 gene promoter could be used as a genetic marker, most notably diplotype H1H3, may greatly benefit the simultaneous improvement of mastitis resistance and milk yield traits in dairy cattle. Moreover, bioinformatics analysis predicted that the SNPs rs720373055: T>C, rs715189731:A>G and rs720349928: G>A is located in the core promoter region and in TFBs, play key role in regulation of studied phenotypes.

BackgroundDespite the Link Worker Scheme to address the HIV risk and vulnerabilities in rural areas, reaching out to unreached men having sex with men (MSM) remains a challenge in rural India. This study explored issues around health care access and programmatic gaps among MSM in rural settings of India.MethodsWe conducted eight Focused Group Discussions (FGDs), 20 Key Informant Interviews (KIIs), and 20 In-Depth Interviews (IDIs) in four rural sites in Maharashtra, Odisha, Madhya Pradesh, and Uttar Pradesh between November 2018 and September 2019. The data in the local language were audio-recorded, transcribed, and translated. Data were analyzed in NVivo version 11.0 software using the grounded theory approach.ResultsPrimary barriers to health care access were lack of knowledge, myths and misconceptions, not having faith in the quality of services, program invisibility in a rural setting, and anticipated stigma at government health facilities. Government-targeted intervention services did not seem to be optimally advertised in rural areas as MSM showed a lack of information about it. Those who knew reported not accessing the available government facilities due to lack of ambient services, fear of the stigma transforming into fear of breach of confidentiality. One MSM from Odisha expressed, "…they get fear to go to the hospital because they know that hospital will not maintain confidentiality because they are local people. If society will know about them, then family life will be disturbed" [OR-R-KI-04]. Participants expressed the desire for services similar to those provided by the Accredited Social Health Activists (ASHA), frontline health workers for MSM.ConclusionProgramme invisibility emerges as the most critical issue for rural and young MSM. Adolescent and panthis emerged as Hidden MSM and they need focused attention from the programme. The need for village-level workers such as ASHA specifically for the MSM population emerged. MSM-friendly health clinics would help to improve healthcare access in rural MSMs under Sexual and Reproductive Health Care.

Mastitis in cattle is a prevalent mammary gland disease that contributes significantly to the increase in veterinary expenditures in the dairy sector. KCNB1 (Potassium voltage-gated channel, subfamily B member 1) gene is involved in regulating apoptosis, cell proliferation and differentiation, udder epithelial tissue maintenance and repair, mammary gland development and recommended as a candidate gene for production related traits in cattle. The purpose of this research was to detect the genetic variants of KCNB1 gene in Sahiwal cattle and to analyze the association between polymorphisms with milk production traits, udder traits, and teat traits in Sahiwal cattle. A total of 87 cattle were genotyped by polymerase chain reaction-restriction fragment length polymorphism technique. Two single nucleotide polymorphisms within the non-coding sequence of KCNB1 gene were identified (g.78216220G>A and g.78216335A>G). Analysis of productivity traits within the genotyped animals revealed that the SNP1-Msp1 locus (g.78216220G>A) located at intron 1 was associated with milk production traits, but the SNP2-BspHI locus (g.78216335A>G) had no association with milk production. Significant associations were also observed between SNP1-Msp1 and SNP2-BspHI loci with both udder and teat traits. Our results demonstrate that polymorphisms in the cattle KCNB1 gene were associated with milk production, udder and teat traits and might be utilized as a genetic marker for marker-assisted selection in cattle breeding programs.

Heat shock proteins (HSPs) are known to modulate cellular response during summer stress in dairy cattle. Among different classes of HSPs, heat shock protein 20 (HSPB6) is a member of the small HSP family protein, the role of which has not been fully characterized in the context of heat stress in cattle. This study identified single nucleotide polymorphisms (SNPs) in the HSPB6 gene in Sahiwal cattle and their associations with heat tolerance traits (RR, RT and HTC). Three SNPs (SNP 1-3) were reported, which included two transitions, viz. SNP1-g.436G>A (Intron 1) and SNP2-g.2152A>G (3′-UTR) and one transversion, viz. SNP3-g.2417A>T (3′-UTR). The association analysis revealed that SNPs loci, viz. SNP1-g.436G>A and SNP2-g.2152A>G were significantly associated with heat tolerance traits. The GG genotype of SNP2-g.2152A>G was significantly associated with heat tolerance traits in Sahiwal cattle. The association analysis of four available haplotypes, viz. Hap1 (GGA), Hap2 (AAA), Hap3 (GAA), and Hap4 (AAT) of HSPB6 gene with heat tolerance traits did not differ significantly with any haplotype in Sahiwal cattle. This study provides the first association analyses between the SNPs of HSPB6 gene and heat tolerance traits in Sahiwal cattle, which could be used as effective SNP markers in genetic selection for heat tolerance in cattle breeding programs.

Abstract Background Empowering female sex workers (FSWs) through women controlled HIV prevention option has been in focus globally. FSWs are important target for oral pre exposure prophylaxis (PrEP). A multi-centric qualitative study was conducted to explore the FSWs’ willingness to use oral PrEP in India. Methods Seventy three interviews and 02 focus group discussions were conducted at 3 high HIV prevalent states in India during 2013–14. Study explored issues around willingness to use oral PrEP. The study was approved by the respective institutional ethics committee of the study sites. Thematic analysis using grounded theory approach was used to analyze the data in N-VIVO version 8.0. Results Thematic analysis showed events of forced condom-less sex. FSWs believed that oral PrEP could provide independence, financial gains, and privacy and therefore hoped to use it as an alternative to male condom. However, any impact on physical/ aesthetic attributes and reproductive system were not acceptable and could become a barrier. Provider initiated oral PrEP was not preferred. Providers voiced safety monitoring concerns. Adherence emerged as a challenge because of: (1) alcohol use; (2) taking PrEP tablet each day being boring; (3) Stigma because Oral PrEP is ARV based. Alcohol use and dread of repetitive dose brings forth the need for long acting oral PrEP. Conclusion Oral PrEP is acceptable among FSWs; it should be rolled out alongside strong messages on STI protection and PrEP as compliment to condoms. PrEP roll out requires educating communities about HIV treatment versus prevention. Long-acting oral PrEP could address both ‘boredom’ and alcoholism and sustain adherence.

Dengue fever is endemic in over 100 countries, with the majority of cases reported in the World Health Organisation (WHO) regions of the Americas, Southeast Asia and the Western Pacific. Dengue fever is endemic in almost every state in India, and it is the leading cause of hospitalisation. The presentation may vary from being asymptomatic to having mild syndrome. Among other neuro-ophthalmological manifestations, oculomotor neuropathy, optic neuropathy and unilateral abducens nerve palsy has been reported but to the best of authors' knowledge this is the first reported case of dengue virus related type three internuclear ophthalmoplegia. A 47-year-old male patient presented with complaints of fever on and off for the last three days along with speech defects. At admission his blood pressure was 120/86 mmHg, pulse rate was 96 per minute. Oxygen saturation (SpO2) was 94%. He was thoroughly investigated for various viral and bacterial infections, none of which was detected in Polymerase Chain Reaction (PCR) serum test. Hepatitis B virus surface antigen (HBsAg), antibody against Hepatitis C Virus (anti-HCV), antibody against Human Immunodeficiency Virus type 1/2 (anti-HIV 1/2) were all negative. Anti-dengue virus Immunoglobulin M (IgM) antibody was found to be positive. The patient complained of double vision and on examination diplopia in both lateral gaze with maximum separation of images in right gaze. Due to the wider range of possible presentations, it is imperative to consistently follow-up with all dengue patients to check for any neurological sequalae.

The continuous monitoring of arterial blood pressure (BP) is vital for assessing and treating cardiovascular instability in a sick infant. Currently, invasive catheters are inserted into an artery to monitor critically-ill infants. Catheterization requires skill, is time consuming, prone to complications, and often painful. Herein, we report on the feasibility and accuracy of a non-invasive, wearable device that is easy to place and operate and continuously monitors BP without the need for external calibration. The device uses capacitive sensors to acquire pulse waveform measurements from the wrist and/or foot of preterm and term infants. Systolic, diastolic, and mean arterial pressures are inferred from the recorded pulse waveform data using algorithms trained using artificial neural network (ANN) techniques. The sensor-derived, continuous, non-invasive BP data were compared with corresponding invasive arterial line (IAL) data from 81 infants with a wide variety of pathologies to conclude that inferred BP values meet FDA-level accuracy requirements for these critically ill, yet normotensive term and preterm infants.

Background: It is suggested that there is a positive association between vitamin D deficiency and benign paroxysmal positional vertigo (BPPV). We suggest, as a hypothesis, there is a positive association between vitamin D deficiency and BPPV. The current study aimed to investigate the association between vitamin D levels and BPPV. Methods: The present observational case-control study was planned and conducted on 100 participants (50 cases and 50 controls) in the Department of Neurology, Choithram Hospital & Research Center (CHRC), Indore, MP, India, from January 2018 to December 2018. All consecutive patients with diagnosis of idiopathic BPPV who were above the age of 18 years with a negative neurological status were included. Analyses were performed using SPSS software version 10. Results: BPPV was more common among those aged 50 to 70 years (64%). Out of 100 participants, 72 (72%) had vitamin D deficiency, in which 40 (80%) were cases and 32 (64%) were controls. 32 (64%) patients had posterior canal involved, out of them 20 (40%) were females and 12 (24%) were males, and in both groups posterior canal was more involved. Canal involvement according to gender was not statistically significant (P value=0.45). Mean vitamin D level for cases and controls was 34.9 and 46.5 nmol/L, respectively, and this difference was statically very significant with a p-value of 0.01 (P value < 0.05). Conclusion: According to the findings, there is a statistically significant association between vitamin D3 deficiency and Idiopathic BPPV. It can be noted that vitamin D3 deficiency may be a risk factor for the BPPV.

In the present study, the effect of genetic polymorphism of WD-repeat containing protein 41 (WDR41) and Ankyrin repeat domain containing protein 31 (ANKRD31) gene on 17 traits related to udder and teat type and mastitis in 123 Karan Fries cows was studied. Restriction Fragment Length Polymorphism (RFLP) was used to identify the SNP (410 bp and 475 bp) in PCR amplified product of intron 4 and exon 10 in WDR41 gene. Both of them were polymorphic with Guanine to Adenine transition, and three genotypes namely AA, AG and GG were observed. In ANKRD31 gene, RFLP was used to identify the SNP in 513 bp PCR amplified product of intron 24 and two SNPs were found. We report for the first time that intron 4 and exon 10 of WDR41 gene is significantly associated with udder depth (UD), udder balance (UB), central ligament (CL), teat circumference (TC), SFF and tear diameter (TD), rear udder width (RUW), and mastitis. SNP rs110012582 in intron 24 of ANKRD31 gene is associated significantly with UD, distance between left and right teat (DLR), SFF, and SNP rs473512406 with udder length (UL), udder width (UW), udder circumference (UC), fore teat length (FTL), rear teat length (RTL), distance between fore and rear teat (DFR), DLR and mastitis. This information can augment future studies to determine the role of WDR41 and ANKRD31 genes as a candidate gene marker with desired udder and teat conformation and mastitis. Thus, it is essential to work for better udder health and prevent the incidence of mastitis in the herd.

The premises for the potential success of molecular breeding is the ability to identify major genes associated with important dairy related traits. The present study was taken up with the objectives to identify single nucleotide polymorphism (SNP) of bovine MASP2 and SIRT1 genes and its effect on estimated breeding values (EBVs) and to estimate genetic parameters for lactation milk yield (LMY), 305-day milk yield (305dMY), 305-day fat yield (305dFY), 305-day solid not fat yield (305dSNFY) and lactation length (LL) in Sahiwal dairy cattle to devise a promising improvement strategy. Genetic parameters and breeding values of milk production traits were estimated from 935 Sahiwal cattle population (1979-2019) reared at National Dairy Research Institute at Karnal, India. A total of 7 SNPs, where one SNP (g.499C>T) in exon 2 and four SNPs (g.576G>A, g.609T>C, g.684G>T and g.845A>G) in exon 3 region of MASP2 gene and 2 SNPs (g.-306T>C and g.-274G>C) in the promoter region of SIRT1 gene were identified in Sahiwal cattle population. Five of these identified SNPs were chosen for further genotyping by PCR-RFLP and association analysis. Association analysis was performed using estimated breeding values (n = 150) to test the effect of SNPs on LMY, 305dMY, 305dFY, 305dSNFY and LL. Association analysis revealed that, three SNP markers (g.499C>T, g.609T>C and g.-306T>C) were significantly associated with all milk yield traits. The estimates for heritability using repeatability model for LMY, 305dMY, 305dFY, 305dSNFY and LL were low, however the corresponding estimates from first parity were 0.20±0.08, 0.17±0.08, 0.13±0.09, 0.13±0.09 and 0.24, respectively. The repeatability estimates were moderate to high indicating consistency of performance over the parities and hence reliability of first lactation traits. Genetic correlations among the traits of first parity were high (0.55 to 0.99). From the results we could conclude that optimum strategy to improve the Sahiwal cattle further would be selecting the animals based on their first lactation 305dMY. Option top include the significant SNP in selection criteria can be explored. Taken together, a 2-stage selection approach, select Sahiwal animals early for the SNP and then on the basis of first lactation 305dMY will help to save resources.

Murrah breed of buffalo is an excellent dairy germplasm known for its superior milk quality in terms of milk fat and solids-not-fat (SNF); however, it is often reported that Indian buffaloes had lower lactation and fertility potential compared to the non-native cattle of the country. Recent techniques, particularly the genome-wide association studies (GWAS), to identify genomic variations associated with lactation and fertility traits offer prospects for systematic improvement of buffalo. DNA samples were sequenced using the double-digestion restriction-associated DNA (RAD) tag genotyping-by-sequencing. The bioinformatics pipeline was standardized to call the variants, and single-nucleotide polymorphisms (SNPs) qualifying the stringent quality check measures were retained for GWAS. Over 38,000 SNPs were used to perform GWAS on the first two principal components of test-day records of milk yields, fat percentages, and SNF percentages, separately. GWAS was also performed on 305 days’ milk yield; lactation persistency was estimated through the rate of decline after attaining the peak yield method, along with three other standard methods; and breeding efficiency, post-partum breeding interval, and age at sexual maturity were considered fertility traits. Significant association of SNPs was observed for the first principal component, explaining the maximum proportion of variation in milk yield. Furthermore, some potential genomic regions were identified to have a potential role in regulating milk yield and fertility in Murrah. Identification of such genomic regions shall help in carrying out an early selection of high-yielding persistent Murrah buffaloes and, in the long run, would be helpful in shaping their future genetic improvement programs.

The main objective of this study was to determine the association of production traits with genetic variants in exon 5 and intron 3 of bovine growth hormone (bGH) gene in Sahiwal cattle. The analyses were based on the detection of single nucleotide polymorphisms (SNPs) in GH-AluI (exon 5) and GH-MspI (intron 3) using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay. The frequency of AluI (L/V) and MspI (T/C) alleles were 86.20/13.70 and 89.80/9.50, respectively. The distribution of the frequency of GH genotypes for LL, LV, and VV were 73.4, 25.5, and 1.0 and for TT, TC, and CC genotypes were 80.9, 17.7, and 13.0, respectively. Season of calving had none but period of calving had significant effect on the studied production traits. The phenotypic data was adjusted for non-genetic factors and regression analysis was done. There was detectable significant effect of the GH-AluI and GH-MspI on the analyzed production traits. The cows with LL genotype had significantly higher milk yield traits than the LV genotype. Similarly, the productive performance of the studied cows with TT genotype was also significantly higher than TC and CC genotypes. Results revealed that the Sahiwal cows with LL and TT genotypes of the bGH locus can be considered to be a favourable genotype for production traits, although these findings need to be confirmed by further research before SNPs can be used in a marker assisted selection program by the animal breeder.

The aim of this study was to determine the associations of persistency with genetic variants of bovine growth hormone (bGH) gene in Indian Sahiwal cows. The data pertaining to the monthly test day milk yield (MTDMY) and first lactation length (FLL) of 305 lactating Sahiwal cows over a period of 23 years (1993–2016) were subjected to analysis. Persistency of milk yield was estimated by using test day based ratio method and Wilmink b function. Mean LL was 220.06±8.15 days in all studied Sahiwal cows, however, 276.67±10.25 days in cows with ≥100 days of LL and having 500 kg MY. The peak of milk yields was achieved at third TD of the first lactation. Macrophage stimulating protein 1 (MspI) and Arthrobacter luteus1 (AluI) restriction endonucleases were used to digest the amplified regions in intron 3 and exon 5, respectively of bGHgene. The bGHMspI restriction fragment length polymorphism (RFLP) yielded TT, CT and CC genotypes, whereas bGH-AluIRFLP yielded CC, CG and GG genotypes. Significant association was found between first lactation persistency estimated using test day based ratio method and bGH-MspI polymorphism. No significant association was found between first lactation persistency and bGH-AluI polymorphism. In summary, results of present study revealed that the TT genotype of bGH–MspI gene in Sahiwal cows has better lactation persistency than other genotypes.

GH has important role in milk production and their polymorphisms may alter quality and quantity of gene's products and affects the phenotype. This study was designed to find the polymorphisms on GH-Msp1 loci and to find its association with milk production traits in Sahiwal cattle. Msp1 polymorphism of the bGH gene was identified in a population of Sahiwal cows. PCR-RFLP genotyping of 329 bp fragment of GH in exon 3 revealed three different allelic variants. The T allele was the major allele in Sahiwal cattle. The TT genotype Sahiwal cows yielded more FL305DMY, FLTMY and also had higher FLL than that of CT and CC genotypes cows. Results of the present findings reveal that TT allele of GH locus should be the favoured genotype in Sahiwal cattle breed and can be used in marker-assisted selection programmes.

Lactoferrin is one of the important candidate genes for mastitis resistance in dairy animals. The gene is located on Bos taurus autosome (BTA) 22 and consists of 17 exons spanning over 34.5 kb of genomic DNA. The present study was undertaken to identify allelic variant in exons 6 and 11 of lactoferrin gene and to analyze association with incidence of clinical mastitis in Murrah buffalo. The amplification of exons 6 and 11 of lactoferrin gene yielded 301 and 131 bp amplicon size. Comparison of nucleotide sequence of exonic region of lactoferrin gene with Bos taurus (NCBI accession number AC_000179.1) revealed 6 mutations; among them 3 were in coding DNA sequence and remaining 3 were in flanking intronic region. All these mutations were found in exon 6 and synonymous in nature without affecting the sequence of amino acid. PCR-restriction fragment length polymorphism (RFLP) analysis of 301 bp amplicon using FokI restriction enzyme exhibited polymorphic pattern with two genotypes (AA and AB) with respective frequency of 0.625 and 0.375. The frequencies of two alleles, A and B were estimated as 0.81 and 0.19 respectively. RE Hpy188I and HinfI used for digestion of exon 11 had exhibited monomorphic pattern. The chi-square (χ2) analysis revealed significant association between incidence of clinical mastitis and genetic variant of exon 6 and animals with AA genotype were found to be less susceptible to mastitis. The findings indicate potential scope for incorporation of lactoferrin gene in selection and breeding of Murrah buffaloes for improved genetic resistance to mastitis.

Aim: This study was conducted with the objective to identify single nucleotide polymorphism (SNP) in protein phosphatase 1 regulatory subunit 11 (PPP1R11) gene in Murrah bulls. Materials and Methods: Genomic DNA was isolated by phenol–chloroform extraction method from the frozen semen samples of 65 Murrah bulls maintained at Artificial Breeding Research Centre, ICAR-National Dairy Research Institute, Karnal. The quality and concentration of DNA was checked by spectrophotometer reading and agarose gel electrophoresis. The target region of PPP1R11 gene was amplified using four sets of primer designed based on Bos taurus reference sequence. The amplified products were sequenced and aligned using Clustal Omega for identification of SNPs. Animals were genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) using EcoNI restriction enzyme. Results: The sequences in the NCBI accession number NW_005785016.1 for Bubalus bubalis were compared and aligned with the edited sequences of Murrah bulls with Clustal Omega software. A total of 10 SNPs were found, out of which 1 at 5’UTR, 3 at intron 1, and 6 at intron 2 region. PCR-RFLP using restriction enzyme EcoNI revealed only AA genotype indicating monomorphism in PPP1R11 gene of all Murrah animals included in the study. Conclusion: A total of 10 SNPs were found. PCR-RFLP revealed only AA genotype indicating monomorphism in PPP1R11 gene of all Murrah animals included in the study, due to which association analysis with conception rate was not feasible.

Treatment transition for 'adolescents living with perinatally acquired HIV' (ALPH) from paediatric to adult care is not addressed adequately. This study explores the ALPH's health care needs and programmatic gaps in health systems for the care of ALPH in India. Forty-nine in-depth interviews were conducted with purposively selected primary and key stakeholders in India. Thematic analysis utilizing grounded theory was performed in QSR NUD*IST 6. Stakeholders explicitly recognized adolescent HIV to be a critical public health issue which requires a separate mandate in India. It was found that none of the health policies in India focus on adolescent age group; ALPH is therefore even more neglected population. No/partial HIV disclosure to ALPH is the first crisis for retention in care continuum and adherence to the treatment becomes sub-optimal. Unmet needs of transitioning from paediatric to adult care in existing settings was the major gap. Age-specific counselling guidelines and counselling skills among HCPs were found lacking where tailored counseling and capacity building of HCPs was an expectation. Need of holistic approach for adolescents led to consensus on establishing 'adolescent transition clinic' with a strict 'no' for 'standalone Adolescent HIV' clinics. School setting having peer-based counselling provision was recommended. Age disaggregated health data is required to inform the policymakers about adolescents' specific needs for developing interventions. Situational analysis to identify and shape health priorities of adolescents is recommended.

Jatropha curcas is a flowering, deciduous and poisonous plant. It is commonly found growing throughout the tropical & sub tropical regions of world particularly in India. Accidental poisoning due to its fruits & seeds has been reported in remote and tribal areas, invariably among children who often fail to recognize it. Sporadic cases often remain unreported, misdiagnosed or neglected; usually it is mass calamities which came to attention. Presented here is an unfortunate incident of mass poisoning, where some people (mostly children) consumed jatropha fruits & seeds mistaking them for edible sunflower seeds. Victims were hospitalized, promptly managed and recuperated successfully.

The study was planned with objective to screen single nucleotide polymorphisms (SNPs) in bovine HSPB1 gene and to find its effect on age at calving in Karan-Fries (Bos taurus × Bos indicus) and Sahiwal (Bos indicus) breeds of cattle. Genomic DNA was extracted from whole blood of 180 cows of both breeds. Based on publically available bovine HSPB1 gene sequence, one primer set was used for polymerase chain reaction amplification of the target region. Further DNA sequencing revealed a transition of thymine to cytosine at SNP rs208395876 in 5-UTR and a silent transversion of guanine to thymine at SNP rs723061520 in first coding sequence of bovine HSPB1 gene in both the studied breeds. Effect of individual SNP genotypes of bovine HSPB1 gene with age at calving (months) was analyzed separately in both breeds via regression using a repeated gene substitution MIXED model and least-squares means.The overall observed heterozygosity in both breeds and the F-Statistics values indicated that there was lesser genetic diversity in studied genomic region of bovine HSPB1 gene in Bos indicus compared to crossbred cattle. Association analysis revealed that SNP rs208395876 significantly delayed age at calving in Karan-Fries cows. In conclusion, the studied genomic region of bovine HSPB1 gene is polymorphic. In addition, these polymorphisms were informative with regard to age at calving of crossbred cows. Therefore, this gene is an important candidate for cow fertility.

Snakebite is an important medical problem in India. Among their various manifestations, cerebral complications are uncommonly found in literature. Moreover, Ischemic stroke following snake bite is quite rare. Here we report a case series of two such cases that developed neurological manifestations following Russell’s viper bite. On computerized tomography (CT) scan of brain; cerebral infarcts were revealed. Their likely mechanisms are discussed in present study which include disseminated intravascular coagulation, toxin induced vasculitis and endothelial damage.

Aim: The present study was undertaken to identify novel single nucleotide polymorphism (SNP) in Exon 3 of HSP90AA1 gene and to analyze their association with respiration rate (RR) and rectal temperature (RT) in Sahiwal cows. Materials and Methods: The present study was carried out in Sahiwal cows (n=100) with the objectives to identify novel SNP in exon 3 of HSP90AA1 gene and to explore the association with heat tolerance traits. CLUSTAL-W multiple sequence analysis was used to identify novel SNPs in exon 3 of HSP90AA1 gene in Sahiwal cows. Gene and genotype frequencies of different genotypes were estimated by standard procedure POPGENE version 1.32 (University of Alberta, Canada). The significant effect of SNP variants on physiological parameters, e.g. RR and RT were analyzed using the General Linear model procedure of SAS Version 9.2. Results: The polymerase chain reaction product with the amplicon size of 450 bp was successfully amplified, covering exon 3 region of HSP90AA1 gene in Sahiwal cows. On the basis of comparative sequence analysis of Sahiwal samples (n=100), transitional mutations were detected at locus A1209G as compared to Bos taurus (NCBI GenBank AC_000178.1). After chromatogram analysis, three genotypes AA, AG, and GG with respective frequencies of 0.23, 0.50, and 0.27 ascertained. RR and RT were recorded once during probable extreme hours in winter, spring, and summer seasons. It was revealed that significant difference (p

Acute toxicity is a frequent but avoidable cause of morbidity and mortality in children especially in developing countries, including India. Present study assesses their pattern with relation to different age groupings. This retrospective study was conducted among all hospitalised paediatric victims of acute accidental poisoning at the King George Medical University; Lucknow during 2010 -11. Their history, baseline characteristics, clinical course and outcome was studied. Most children were male of less than three years with 4% overall mortality. Kerosene oil was implicated in most cases. Childhood poisoning is commonest during 1-3 years with a male preponderance. Household poisons; especially kerosene oil was responsible for most cases which was consumed accidentally. Parents must be educated and warned to keep these toxic ingredients safely in suitable containers and out of reach of their beloved children. Keywords: Forensic Science, Paediatric, Acute Poisoning, Kerosene, Outcome.

Leptin is a 16 kD protein, synthesized by adipose tissue and is involved in regulation of feed intake, energy balance, fertility and immune functions. Present study was undertaken with the objectives of sequence characterization and studying the nucleotide variation in leptin gene in Murrah buffalo. The leptin gene consists of three exons and two introns which spans about 18.9kb, of which the first exon is not transcribed into protein. In buffaloes, the leptin gene is located on chromosome eight and maps to BBU 8q32. The leptin gene was amplified by PCR using oligonucleotide primers to obtain 289 bp fragment comprising of exon 2 and 405 bp fragment containing exon 3 of leptin gene. The amplicons were sequenced to identify variation at nucleotide level. Sequence comparison of buffalo with cattle reveals variation at five nucleotide sequences at positions 983, 1083, 1147, 1152, 1221 and all the SNPs are synonymous resulting no in change in amino acids. Three of these eight nucleotide variations have been reported for the first time in buffalo. The results indicate conservation of DNA sequence between cattle and buffalo. Nucleotide sequence variations observed at leptin gene between Bubalus bubalis and Bos taurus species revealed 97% nucleotide identity.

Present study was undertaken with the objective to identify the genetic variation in exon 2 and exon 3 of leptin gene and to determine the association of variants with milk production and fat% in Murrah buffaloes. Genomic DNA was isolated from 150 lactating Murrah buffaloes.The targeted segment was amplified by PCR using oligonucleotide primers and respective amplicons of 289 bp and 405 bp size comprising of exon 2 and exon 3 were obtained. PCR-RFLP was carried out using a battery of restriction endonucleases viz. AluI, AciI, MspI, PvuII, HindIII, HinfI, Eco32I,Eco147I and Kpn2I to explore genetic variation. Data were recorded pertaining to parity-wise milk production and fat%. Results indicated monomorphic patterns of both the exons of leptin gene in Murrah buffalo. Data on milk yield and fat percentage were recorded. However, association study was not possible due to monomorphic exhibition of the gene in all the animals included in the study.

A 37-year old man presented with 5 months history of left scrotal mass and had underwent left orchidectomy following a presumptive diagnosis of testicular tumour. Histopathological diagnosis of testicular tuberculosis was subsequently made, which revealed a case of isolated TB orchitis. It signifies that the careful evaluation of patients with testicular mass is extremely significant for diagnostic accuracy, optimal treatment and avoiding unnecessary surgery in case of testicular tuberculosis. Simultaneously it will also help in early detection of testicular malignancies and vital for the clinicians to avoid negligence charges.

Incidence of mastitis may be associated with single nucleotide polymorphism (SNP). Cows (350) belonging to Sahiwal and Karan Fries were screened. Polymorphism of bovine lactoferrin gene promoter was determined by using created restriction site polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Results indicated that lactorferrin gene promoter is polymorphic and showed varied levels of polymorphism among Sahiwal and Karan Fries cattle. Three genotypes were identified, viz. EE, EF and FF in Sahiwal cattle and EE genotype was absent in Karan Fries cattle. Association of SNP identified with incidence of mastitis using chi square test, revealed nonsignificant association with mastitis incidence.

Psychiatric disorders including anxiety, psychosis, and aggressive behaviors are frequently diagnosed in patients with epilepsy. In this communication, we report a patients with mesial temporal lobe sclerosis with interictal affective-somatoform (dysphoric) disorders who was never treated for psychiatric manifestations, and who deliberately took a massive dose of phenytoin and phenobarbitone with a motive of suicide, resulting in severe combined toxicity. Such unfortunate incidences may be prevented, and quality of life can be improved with early diagnosis, through the selection of the right antiepileptic drugs, reasonable psychiatric consultation, and appropriate biological and psychological treatments.