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Abstract Background Transcript variants and protein isoforms are central to unique tissue functions and maintenance of homeostasis, in addition to being associated with aberrant states such as cancer, where their crosstalk with the mutated tumor suppressor p53 may contribute to genomic instability and chromosomal rearrangements. We previously identified several novel splice variants in ovarian cancer RNA-sequencing datasets; herein, we aimed to elucidate the biological effects of the Integrin Subunit Beta 8 variant (termed pITGB8-205). Methods Resolution of the full-length sequence of pITGB8-205 through rapid amplification of cDNA ends (RACE-PCR). Cell cycle analysis and karyotype studies were performed to further explore genomic instability. RNA-seq and proteomics analyses were used to identify the differential expression of the genes. Results This full-length study revealed a unique 5’ sequence in pITGB8-205 that differed from the reported ITGB8-205 sequence, suggesting differential regulation of this novel transcript. Under a p53 mutant background, overexpression of pITGB8-205 triggered genetic instability reminiscent of oncogene-induced replicative stress with extensive abnormal mitoses and chromosomal and nuclear aberrations indicative of chromosomal instability, leading to near whole-genome duplication that imposes energy stress on cellular resources. Micronuclei and aneuploidy are striking features of pITGB8-205-overexpressing p53-mutant cells but are not enhanced in p53 wild-type (WT) cells. RNA-seq and proteomics analyses further suggested that p53 inactivation in ovarian cancer provides a permissive intracellular molecular niche for pITGB8-205 to mediate its effects on genomic instability. This observation is pivotal considering that most high-grade serous ovarian carcinoma (HGSC) tumors express mutant p53. The resulting aneuploid clones with enhanced self-renewal and survival capabilities disrupt clonal dominance under stress yet maintain a balance between replicative stress and prosurvival advantages. Conclusion pITGB8-205-overexpressing clones sustain ovarian tumor cell survival, achieve homeostasis and are formidable opponents of therapy.

Background This study assessed trends in healthcare utilisation in relation to the implementation of an economic policy in India wherein 500 and 1000 rupee notes were demonetised.Methods In this ambidirectional observational study of private not-for-profit hospitals, data on hospital outpatient and inpatient numbers, surgeries, emergency department (ED) visits, obstetric admissions and mortality were obtained for pre-demonetisation (September/October 2016), early (November/December 2016) and late demonetisation (January/February 2017), and post-demonetisation periods (March/April 2017) and compared with the control period (2015–2016) from 11 centres (three tertiary hospitals; eight secondary). A Bayesian regression analysis was performed to adjust for seasonal (winter) effect. Monthly financial data, including the proportion of cash versus non-cash transactions, were collected.Findings Overall, at the pooled all-hospital level, Bayesian analysis showed non-significant increase in outpatients (535.4, 95% CI −7097 to 8116) and decrease in deaths (–6.3 per 1000 inpatients, 95% CI −15.45 to 2.75) and a significant decrease in inpatients (−145.6, 95% CI −286.4 to −10.63) during demonetisation. Analysis at the level of secondary and tertiary hospitals showed a variable effect. For individual hospitals, after adjusting for the seasonal effect, some hospitals observed a significant reduction in outpatient (n=2) and inpatient (n=3) numbers, ED visits (n=4) and mortality (n=2) during demonetisation, while others reported significantly increased outpatient numbers (n=3) and ED visits (n=2). Deliveries remained unchanged during demonetisation in the hospitals that provided the service. There was no significant reduction in hospital incomes during demonetisation. In tertiary hospitals, there was a significant increase in non-cash component of transactions from 35% to 60% (p=0.02) that persisted beyond the demonetisation period.Conclusions The effect of demonetisation on healthcare utilisation was variable. Some hospitals witnessed a significant reduction in utilisation in some areas, while others reported increased utilisation. There was an increase in non-cash transactions that persisted beyond the period of demonetisation.

Purpose: We recently reported that curcumin attenuates ionizing radiation (IR)-induced survival signaling and proliferation in human neuroblastoma cells. Also, in the endothelial system, we have demonstrated that NFκB regulates IR-induced telomerase activity (TA). Accordingly, we investigated the effect of curcumin in inhibiting IR-induced NFκB-dependent hTERT transcription, TA, and cell survival in neuroblastoma cells.Methods and Materials: SK-N-MC or SH-SY5Y cells exposed to IR and treated with curcumin (10-100 nM) with or without IR were harvested after 1 h through 24 h. NFκB-dependent regulation was investigated either by luciferase reporter assays using pNFκB-, pGL3-354-, pGL3-347-, or pUSE-IκBα-Luc, p50/p65, or RelA siRNA-transfected cells. NFκB activity was analyzed using an electrophoretic mobility shift assay and hTERT expression using the quantitative polymerase chain reaction. TA was determined using the telomerase repeat amplification protocol assay and cell survival using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltertrazolium bromide and clonogenic assay.Results: Curcumin profoundly inhibited IR-induced NFκB. Consequently, curcumin significantly inhibited IR-induced TA and hTERT mRNA at all points investigated. Furthermore, IR-induced TA is regulated at the transcriptional level by triggering telomerase reverse transcriptase (TERT) promoter activation. Moreover, NFκB becomes functionally activated after IR and mediates TA upregulation by binding to the κB-binding region in the promoter region of the TERT gene. Consistently, elimination of the NFκB-recognition site on the telomerase promoter or inhibition of NFκB by the IκBα mutant compromises IR-induced telomerase promoter activation. Significantly, curcumin inhibited IR-induced TERT transcription. Consequently, curcumin inhibited hTERT mRNA and TA in NFκB overexpressed cells. Furthermore, curcumin enhanced the IR-induced inhibition of cell survival.Conclusions: These results strongly suggest that curcumin inhibits IR-induced TA in an NFκB dependent manner in human neuroblastoma cells. [ABSTRACT FROM AUTHOR]

Black raspberry extracts (RSE) have been shown to inhibit cancer cell growth and stimulate apoptosis. Also, studies have demonstrated that RSE inhibits transcriptional regulators including NFkB. Accordingly, we investigated the effect of RSE in inhibiting radiation (IR) induced NFkB mediated radioprotection in breast adenocarcinoma cells. MCF-7 cells were exposed to IR (2Gy), treated with RSE (0.5, 1.0, 2.0 µg/ml) or treated with RSE (1.0 µg/ml) followed by IR exposure, and harvested after 1, 3, 6, 24, 48, and 72 h. NFkB DNA-binding activity was measured by EMSA and phosphorylated IkB-alpha by immunoblotting. Expression of IAP1, IAP2, XIAP and survivin were measured by QPCR and immunoblotting. Cell survival was measured usingMTT assay and cell death using Caspase-3/7 activity. Effect of RSE on IR induced MnSOD, TNF-alpha, IL-1alpha and MnSOD activity was also determined. RSE inhibited NFkB activity in a dose-dependent manner. Also, RSE inhibited IR-induced sustained activation ofNFkB, andNFkB regulated IAP1, IAP2, XIAP, and survivin. In addition, RSE inhibited IR-induced TNF-alpha, IL-1alpha, and MnSOD levels and MnSOD activity. RSE suppressed cell survival and enhanced cell death. These results suggest that RSE may act as a potent radiosensitizer by overcoming the effects of NFkB mediated radioprotection in human breast cancer cells. [ABSTRACT FROM AUTHOR]

Background: Papillary thyroid microcarcinoma (PTMC) describes a focus of papillary thyroid cancer that is less than 1 cm in size. These tumors are frequently found on histopathological examination of thyroid specimens, operated upon for an indication other than suspected malignancy. Materials and Methods: From 2005 to 2012, 94 of 1300 thyroidectomy specimens in our institution were found to have PTMC. Of these, 77 were isolated PTMC while the others were associated with other differentiated cancers. We studied their clinicopathologic features, treatment and long-term outcome. Results: There were 18 men and 59 women (the male: female ratio was 1:3), their mean age was 44 ± 10.5 years (range: 18-72 years). Multinodular goiter was the most common indication for surgery. Malignancy was suspected in only 31.4% cases. The mean tumor size was 4.1 ± 2.3 mm. Nearly 17% cases had slightly larger tumors measuring >6 but

Background: Medullary thyroid carcinoma (MTC) is a tumor arising from the para follicular (C) cells of the thyroid gland and can occur either sporadically or as part of an inherited syndrome. A proportion of these cases carry an autosomal dominant mutation in the RET (REarranged during Transfection) proto-oncogene. Screening for these mutations in the affected patients and the carriers ′′at risk′′ which includes the first-degree relatives is of utmost importance for early detection and prompt treatment including prophylactic thyroidectomy in cases that harbor these mutations. Results: This report presents details of screening and subsequent follow-up of a large Indian family, where the index case was found to carry p.Cys634Ser mutation involving exon 11 of the RET gene. These data are of value considering the paucity of information within the region in context of screening large families affected by these mutations.

Background : Micro-RNAs (miRNAs) are expressed in a tissue-specific manner and are known to demonstrate differential expression even among the various subtypes of a given tumor. This differential expression has been harnessed successfully in the development of diagnostic assays for various malignant tumors. These assays have been found to be relevant and of value as additional diagnostic tools even among thyroid tumors, particularly with regard to thyroid carcinomas of follicular morphology. Materials and Methods : A limited set of miRNA have been assessed as part of this study in an effort to use minimal number of miRNA markers (miR-187, miR-221, miR-222, and miR-224) to differentiate the benign from the malignant thyroid tumors using miRNA derived from paraffin embedded material. Results : While miR-221 and miR-222 were found to provide good accuracy as individual markers (86% and 84%), a combination of the two provided slightly better accuracy (91%). Both miR-221 and 222 were able to significantly differentiate malignant tumors from the benign samples (P< 0.001) individually and as a combination of markers. However, inclusion of miR-187 and miR-224 in the panel did not provide any additional benefit. Conclusion : While a combination of miR-221 and 222 when used in a diagnostic panel could provide fairly good accuracy additional markers may need to be investigated to augment their diagnostic utility.

Various missense mutations in the VHL gene have been reported among patients with familial bilateral pheochromocytoma. However, the p.Arg82Leu mutation in the VHL gene described here among patients with familial bilateral pheochromocytoma, has never been reported previously in a germline configuration. Interestingly, long-term follow-up of these patients indicated that the mutation might have had little impact on the normal function of the VHL gene, since all of them have remained asymptomatic. We further attempted to correlate this information with the results obtained by in silico analysis of this mutation using SIFT, PhD-SNP SVM profile, MutPred, PolyPhen2, and SNPs&GO prediction tools. To gain, new mechanistic insight into the structural effect, we mapped the mutation on to 3D structure (PDB ID 1LM8). Further, we analyzed the structural level changes in time scale level with respect to native and mutant protein complexes by using 12 ns molecular dynamics simulation method. Though these methods predict the mutation to have a pathogenic potential, it remains to be seen if these patients will eventually develop symptomatic disease.

Introduction Adolescence is a critical period known for presenting specific challenges in disease treatment and health promotion. Studies have highlighted that increased nutritional awareness is associated with healthier eating habits, while regular physical activity aids in controlling and preventing non-communicable diseases. Equipping adolescents with health education in schools prepares them to adopt and maintain healthy lifestyles throughout their lives. To assess and compare the efficacy of health education packages targeting nutrition knowledge, practices, and physical activity levels, a cluster-randomized trial was conducted among school-going adolescents. Methodology Two distinct health education packages were developed for the two intervention groups. In group 1, a health talk supported by a flip chart was delivered, followed by pamphlet distribution. In contrast, in group 2, only information pamphlets were distributed. The study was conducted in government schools in Rishikesh, with four schools selected. Two schools were randomly allocated to each intervention arm. In each school, a questionnaire was administered to assess the students' nutrition knowledge, practices and physical activity levels. This was followed by the intervention, and the students were reassessed for the same parameters after two weeks. Result The pre-intervention and post-intervention comparisons within the same group- the mean scores for nutrition knowledge, food practice, sleep duration, and recreational screen time were comparable in the intervention group 1 (p>0.05). There was a decrease in the mean physical activity score and screen time for studies in intervention group 1, and these differences were statistically significant (p<0.05). The mean scores for nutrition knowledge, physical activity, sleep duration, and screen time for studies were comparable in the intervention group 2 (p>0.05). There was an increase in the mean food practice score and a decrease in recreational screen time in intervention group 2, and these differences were statistically significant (p<0.05). On comparing the groups with each other, it was found that Group 2 exhibited a significantly higher mean food practice score compared to group 1 post-intervention. While there was a statistically significant decrease in the mean physical activity score in intervention group 1, this group still had higher physical activity levels than group 2. Post-intervention, group 2 exhibited a higher screen time for studies compared to group 1. Both groups had comparable sleep durations at baseline and post-intervention, with intervention group 1's mean sleep duration falling within the recommended range set by the American Academy of Sleep Medicine. Regression analysis provided valuable insights into the relationship between baseline values of various variables and their post-intervention values, aiding in understanding the impact of the health education packages. Conclusion The findings emphasize the significance of incorporating nutrition and physical activity education into the curriculum of students., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Institutional Ethics Committee of All India Institute of Medical Science,s Rishikesh issued approval AIIMS/IEC/22/551; AIIMS/IEC/23/203. Data collected has been used only for research purposes and will remain protected from disclosure outside of the research setting or to unauthorized persons. Before beginning the study, permission was taken from the Institutional Ethics Committee of AIIMS Rishikesh, Block Education Officer, and school principals. Informed written consent and assent were obtained from the parents/ guardian and adolescents respectively. CTRI registration was done before beginning data collection. Permission to use the nutrition knowledge questionnaire was taken from the author. Questionnaires for food practice and physical activity were under open-access. Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Mallick et al.)

Background: Adolescents experience rapid physical, cognitive, and psychosocial growth in their transition from childhood to adulthood, affecting health outcomes and well-being. Health-related quality of life (HRQoL) is a useful indicator of health outcomes, assessed in the current study along with associated determinants., Methods: A cross-sectional study was conducted among 634 randomly selected adolescents from 13 randomly selected schools in Gharwal division, Uttarakhand, India, from August 2019 to September 2020. The students studying in the 8 th -11 th standard and those providing assent and consent from their parents were included in the study. They were screened using the short version of the Physical Activity Readiness Questionnaire. Along with physical activity and fitness assessment, the Global School-based Student Health Survey questionnaire was administered. The transformed HRQoL domain scores were calculated using the WHOQOL-BREF questionnaire. A univariate and multivariable linear regression model was applied to identify the determinants of HRQoL using SPSS version 23., Results: The study included 324 (51.1%) boys and 310 (48.9%) girls. The mean age of the students was 14.4±1.4 years. The highest mean score was 72.3±21.0 for the social relationship domain and the lowest was 55.6±15.0 for the physical domain. The age, parents using any form of tobacco, a history of ever-use of alcohol and physical fitness were significantly associated with HRQoL domain scores. The non-dominant back stretch test was also significantly associated (Beta coefficient; SE, P-value) with physical (-4.1; 1.4, 0.002), psychosocial (-3.9; 1.5, 0.010) and environmental (-3.5; 1.4, 0.014) domain scores., Conclusion: All domains of HRQoL need to be improved and should address the psychological, social, and mental well-being of adolescents. Physical activity and fitness of students emerged as a strong modifiable predictor affecting almost all the domains of HRQoL, warranting its promotion in schools and the promotion of healthy behavior among parents and adolescents., Competing Interests: None declared., (Copyright: © International Journal of Community Based Nursing and Midwifery.)