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Genetic polymorphisms in the C19orf66 gene influenced HIV-1 infection in a Yunnan population

PeerJ. 2023 Sep 7;11:e16005. doi: 10.7717/peerj.16005. eCollection 2023.

ABSTRACT

BACKGROUND: Due to the deficiencies of vaccines and effective medicine, the human immunodeficiency virus (HIV) infection mechanism should be studied. The C19orf66 gene, one of the interferon-stimulated genes (ISGs), expresses broad-spectra anti-viral activity, including inhibiting HIV replication.

METHODS: In this study, we collect 421 HIV-1 infected patients and 448 controls to genotype three SNPs in the C19orf66 gene. Then, the association between SNPs and biochemical indices/ HIV-1 subtypes are analyzed.

RESULTS: Genotypes CC and CT of rs12611087 show statistically lower and higher frequencies in HIV-1 infected patients than in controls, respectively. Alleles C and T of rs12611087 play protective and risk roles in Yunnan HIV population, respectively. Biochemical indices analysis shows that HIV-1 infected persons carried genotype TT of rs77076061 express significantly lower CD3+/CD45+ ratio level and higher IBIL level. The epidemic subtypes of HIV-1 patients in this study are CRF 07_BC and CRF 08_BC. Moreover, subtype CRF 08_BC tends to infect persons with genotype CC of rs12611087.

CONCLUSION: The genetic polymorphisms of the C19orf66 gene are firstly studied and reported to associate with HIV-1 infection and biochemical indices of patients in Yunnan. Furthermore, subtype CRF 08_BC infection could be influenced by genotypes of SNP in the C19orf66 gene.

PMID:37701839 | PMC:PMC10493081 | DOI:10.7717/peerj.16005

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Effects of transcranial pulse stimulation on autism spectrum disorder: a double-blind, randomized, sham-controlled trial

Brain Commun. 2023 Aug 18;5(5):fcad226. doi: 10.1093/braincomms/fcad226. eCollection 2023.

ABSTRACT

Transcranial pulse stimulation has been proven effective to improve cognition, memory and depressive symptoms of Alzheimer’s disease, but supporting evidence on other neurological diseases or neuropsychiatric disorders remains limited. This study aimed to investigate the effects of transcranial pulse stimulation on the right temporoparietal junction, which is a key node for social cognition for autism spectrum disorder, and to examine the association between transcranial pulse stimulation and executive and social functions. This double-blinded, randomized, sham-controlled trial included 32 participants (27 males), aged 12-17 years with autism spectrum disorder. All eligible participants were randomized into either the verum or sham transcranial pulse stimulation group, on a 1:1 ratio, based on the Childhood Autism Rating Scale screening score. Sixteen participants received six verum transcranial pulse stimulation sessions (energy level: 0.2-0.25 mJ/mm2; pulse frequency: 2.5-4.0 Hz, 800 pulse/session) in 2 weeks on alternate days. The remaining 16 participants received sham transcranial pulse stimulation. The primary outcome measure included Childhood Autism Rating Scale score changes, evaluated by parents, from baseline to 3-month follow-ups. Secondary outcomes included a self-reported questionnaire responded to by parents and cognitive tests responded to by participants. A licensed mental health professional evaluated clinical global impression severity, improvement, efficacy and total score. Results revealed significant interactions in Childhood Autism Rating Scale and other secondary outcomes. Significant group and time effects were found in most secondary outcomes. Additionally, significant differences were found between the transcranial pulse stimulation and sham transcranial pulse stimulation groups in Childhood Autism Rating Scale and clinical global impression improvement and total score immediately after 2 weeks of transcranial pulse stimulation intervention (all P < 0.05), and effects were sustainable at 1- and 3-month follow-up, compared with baseline. The effect size of Childhood Autism Rating Scale (d = 0.83-0.95) and clinical global impression improvement (d = 4.12-4.37) were large to medium immediately after intervention and sustained at 1-month post-stimulation; however, the effects were reduced to small at 3-month post-stimulation (d = 2.31). These findings indicated that transcranial pulse stimulation over right temporoparietal junction was effective to reduce the core symptoms of autism spectrum disorder, as evidenced by a 24% reduction in the total Childhood Autism Rating Scale score in the verum transcranial pulse stimulation group. Additionally, the clinical global impression total score was reduced by 53.7% in the verum transcranial pulse stimulation group at a 3-month follow-up, compared with the baseline. Participants in the verum transcranial pulse stimulation group had shown substantial improvement at 1- and 3-month follow-ups, compared with baseline, although some of the neuropsychological test results were deemed statistically insignificant. Future replication of this study should include a larger sample derived from multi-nations to determine transcranial pulse stimulation as an alternative top-on treatment option in neuropsychiatry.

PMID:37701816 | PMC:PMC10493640 | DOI:10.1093/braincomms/fcad226

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Relationship Between Ergonomic Awareness and Work-related Musculoskeletal Disorders Among Staff Nurses in Oman: An Observational Study

Oman Med J. 2023 Jul 31;38(4):e531. doi: 10.5001/omj.2023.93. eCollection 2023 Jul.

ABSTRACT

OBJECTIVES: To detect the level of ergonomic awareness related to work-related musculoskeletal disorders among 200 staff nurses in a tertiary hospital. The additional objective was to study the relationship of such awareness with the prevalence of these disorders.

METHODS: A group of 25-45-year-old staff nurses and a body mass index of ≤ 30 kg/m2, with at least one year working experience were randomly selected from different wards of the Royal Hospital, Muscat. The study excluded nurses who were on leave and those who had sustained traffic accidents or sports injuries in the preceding year. Cornell Musculoskeletal Discomfort Questionnaire (CMDQ) was used to measure the work-related musculoskeletal disorders experienced by the nurses. A second questionnaire was administered to measure their ergonomic awareness. The data was statistically analyzed. Correlations were established by Spearman’s rank correlation coefficient (ρ).

RESULTS: The participants were 200 staff nurses (male = 30 male, female = 170). Analysis of the ergonomics awareness construct indicated ‘agreement’ as an overall response with a mean of 3.2±0.6, indicating fair ergonomic awareness. For CMDQ, 50.3% reported discomfort in the low back region, 15.0% in the neck, and 6.9% in the right lower leg. The left wrist, left forearm, and right upper arm had the least reported discomfort (< 1.0%). The correlation between ergonomic awareness and working ability was weakly positive, yet statistically significant (ρ = 0.210; p = 0.003). Correlations were not statistically significant between ergonomic awareness and discomfort (ρ = -0.031; p = 0.664) and between ergonomic awareness and total frequency (ρ = 0.109; p = 0.123).

CONCLUSIONS: There is a strong need to develop practical ergonomic awareness among nursing staff for a sustainable and safe work environment.

PMID:37701791 | PMC:PMC10493555 | DOI:10.5001/omj.2023.93

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The influence of direct anterior approach and postero-lateral approach on wound complications after total hip arthroplasty: A meta-analysis

Int Wound J. 2023 Sep 12. doi: 10.1111/iwj.14395. Online ahead of print.

ABSTRACT

To date, we have reviewed the synthesis literature critically through four databases: PubMed, Embase, Cochrane Library and Web of Science. Eight relevant studies were examined after compliance with the criteria for inclusion and exclusion, as well as documentation quality evaluation. This report covered all randomised, controlled studies of total hip arthroplasty (THA) comparing the direct anterior approach (DAA) with the postero-lateral approach (PLA). The main result was surgical site infection rate. The secondary results were duration of the operation, length of the incision and VAS score after surgery. The results of the meta-analyses of wound infections in the present trial did not show any statistically significant difference in DAA versus PLA (between DAA and PLA) (OR = 1.42, 95%CI: 0.5 to 4.04, p = 0.51). Compared with PLA, DAA had shorter surgical incision (WMD = -3.2, 95%CI: -4.00 to -2.41; p < 0.001) and longer operative times(WMD = 14. 67, 95%CI: 9.24 to 20.09; p < 0.001). Postoperative VAS scores were markedly lower in DAA compared with PLA within 6 weeks of surgery (p < 0.05), with low heterogeneities(I2 = 0). We found that DAA did not differ significantly from PLA in terms of the risk of wound infection for THA and that the surgical incisions was shorter and less postoperative pain after surgery, even though DAA surgery takes longer.

PMID:37699722 | DOI:10.1111/iwj.14395

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Client-reported quality of facility-managed medication abortion compared with pharmacy-sourced self-managed abortion in Bangladesh

BMJ Sex Reprod Health. 2023 Sep 12:bmjsrh-2023-201931. doi: 10.1136/bmjsrh-2023-201931. Online ahead of print.

ABSTRACT

OBJECTIVE: We used the newly developed Abortion Care Quality Tool (ACQTool) to compare client-reported quality of medication abortion care by source (facility-managed vs pharmacy-sourced self-managed abortion (SMA)) in Bangladesh.

METHODS: We leveraged exit and 30-day follow-up surveys collected to develop and validate the ACQTool collected at nongovernmental organisation (NGO)-supported or -operated facilities in the public and private sector and pharmacies from three districts in Bangladesh. We used bivariate statistics to compare 18 client-reported quality indicators grouped in six domains and eight abortion outcomes, by source (facility vs pharmacy). We used multivariable logistic regression to identify factors associated with selected quality indicators and outcomes (abortion affordability, information provision, and knowing what to do for an adverse event), controlling for client sociodemographic characteristics.

RESULTS: Of 550 abortion clients, 146 (26.5%) received a facility-managed medication abortion and 404 (73.5%) had a pharmacy-sourced SMA. Clients reported higher quality in facilities for five indicators, and higher in pharmacies for two indicators; the remaining 11 indicators were not different by source. Compared with facility-based clients, pharmacy clients had higher odds of reporting that the cost of abortion was affordable (adjusted odds ratio (aOR) 3.55; 95% CI 2.27 to 5.58) but lower odds of reporting high information provision (aOR 0.14; 95% CI 0.09 to 0.23). Seven of eight abortion outcomes showed no differences; pharmacy clients had lower odds of knowing what to do if an adverse event occurred (aOR 0.45; 95% CI 0.23 to 0.82).

CONCLUSIONS: In Bangladesh, there is no difference in client-reported quality of medication abortion care between health facilities and pharmacies for the majority of quality and outcome indicators. However, information provision and preparedness were higher quality at facilities, while pharmacies were more affordable.

PMID:37699668 | DOI:10.1136/bmjsrh-2023-201931

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Social determinants of ethnic disparities in SARS-CoV-2 infection: UK Biobank SARS-CoV-2 Serology Study

J Epidemiol Community Health. 2023 Sep 12:jech-2023-220353. doi: 10.1136/jech-2023-220353. Online ahead of print.

ABSTRACT

BACKGROUND: The social determinants of ethnic disparities in risk of SARS-CoV-2 infection during the first wave of the pandemic in the UK remain unclear.

METHODS: In May 2020, a total of 20 195 adults were recruited from the general population into the UK Biobank SARS-CoV-2 Serology Study. Between mid-May and mid-November 2020, participants provided monthly blood samples. At the end of the study, participants completed a questionnaire on social factors during different periods of the pandemic. Logistic regression yielded ORs for the association between ethnicity and SARS-CoV-2 immunoglobulin G antibodies (indicating prior infection) using blood samples collected in July 2020, immediately after the first wave.

RESULTS: After exclusions, 14 571 participants (mean age 56; 58% women) returned a blood sample in July, of whom 997 (7%) had SARS-CoV-2 antibodies. Seropositivity was strongly related to ethnicity: compared with those of White ethnicity, ORs (adjusted for age and sex) for Black, South Asian, Chinese, Mixed and Other ethnic groups were 2.66 (95% CI 1.94-3.60), 1.66 (1.15-2.34), 0.99 (0.42-1.99), 1.42 (1.03-1.91) and 1.79 (1.27-2.47), respectively. Additional adjustment for social factors reduced the overall likelihood ratio statistics for ethnicity by two-thirds (67%; mostly from occupational factors and UK region of residence); more precise measurement of social factors may have further reduced the association.

CONCLUSIONS: This study identifies social factors that are likely to account for much of the ethnic disparities in SARS-CoV-2 infection during the first wave in the UK, and highlights the particular relevance of occupation and residential region in the pathway between ethnicity and SARS-CoV-2 infection.

PMID:37699665 | DOI:10.1136/jech-2023-220353

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Chromatin loop dynamics during cellular differentiation are associated with changes to both anchor and internal regulatory features

Genome Res. 2023 Sep 12. doi: 10.1101/gr.277397.122. Online ahead of print.

ABSTRACT

Three-dimensional (3D) chromatin structure has been shown to play a role in regulating gene transcription during biological transitions. Although our understanding of loop formation and maintenance is rapidly improving, much less is known about the mechanisms driving changes in looping and the impact of differential looping on gene transcription. One limitation has been a lack of well-powered differential looping data sets. To address this, we conducted a deeply sequenced Hi-C time course of megakaryocyte development comprising four biological replicates and 6 billion reads per time point. Statistical analysis revealed 1503 differential loops. Gained loop anchors were enriched for AP-1 occupancy and were characterized by large increases in histone H3K27ac (over 11-fold) but relatively small increases in CTCF and RAD21 binding (1.26- and 1.23-fold, respectively). Linear modeling revealed that changes in histone H3K27ac, chromatin accessibility, and JUN binding were better correlated with changes in looping than RAD21 and almost as well correlated as CTCF. Changes to epigenetic features between-rather than at-boundaries were highly predictive of changes in looping. Together these data suggest that although CTCF and RAD21 may be the core machinery dictating where loops form, other features (both at the anchors and within the loop boundaries) may play a larger role than previously anticipated in determining the relative loop strength across cell types and conditions.

PMID:37699658 | DOI:10.1101/gr.277397.122

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Anti-GM-CSF otilimab versus tofacitinib or placebo in patients with active rheumatoid arthritis and an inadequate response to conventional or biologic DMARDs: two phase 3 randomised trials (contRAst 1 and contRAst 2)

Ann Rheum Dis. 2023 Sep 12:ard-2023-224482. doi: 10.1136/ard-2023-224482. Online ahead of print.

ABSTRACT

OBJECTIVES: To investigate the efficacy and safety of otilimab, an antigranulocyte-macrophage colony-stimulating factor antibody, in patients with active rheumatoid arthritis.

METHODS: Two phase 3, double-blind randomised controlled trials including patients with inadequate responses to methotrexate (contRAst 1) or conventional synthetic/biologic disease-modifying antirheumatic drugs (cs/bDMARDs; contRAst 2). Patients received background csDMARDs. Through a testing hierarchy, subcutaneous otilimab (90/150 mg once weekly) was compared with placebo for week 12 endpoints (after which, patients receiving placebo switched to active interventions) or oral tofacitinib (5 mg two times per day) for week 24 endpoints.

PRIMARY ENDPOINT: proportion of patients achieving an American College of Rheumatology response ≥20% (ACR20) at week 12.

RESULTS: The intention-to-treat populations comprised 1537 (contRAst 1) and 1625 (contRAst 2) patients.

PRIMARY ENDPOINT: proportions of ACR20 responders were statistically significantly greater with otilimab 90 mg and 150 mg vs placebo in contRAst 1 (54.7% (p=0.0023) and 50.9% (p=0.0362) vs 41.7%) and contRAst 2 (54.9% (p<0.0001) and 54.5% (p<0.0001) vs 32.5%). Secondary endpoints: in both trials, compared with placebo, otilimab increased the proportion of Clinical Disease Activity Index (CDAI) low disease activity (LDA) responders (not significant for otilimab 150 mg in contRAst 1), and reduced Health Assessment Questionnaire-Disability Index (HAQ-DI) scores. Benefits with tofacitinib were consistently greater than with otilimab across multiple endpoints. Safety outcomes were similar across treatment groups.

CONCLUSIONS: Although otilimab demonstrated superiority to placebo in ACR20, CDAI LDA and HAQ-DI, improved symptoms, and had an acceptable safety profile, it was inferior to tofacitinib.

TRIAL REGISTRATION NUMBERS: NCT03980483, NCT03970837.

PMID:37699654 | DOI:10.1136/ard-2023-224482

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Screening for renal cell carcinoma in renal transplant recipients: a single-centre retrospective study

BMJ Open. 2023 Sep 12;13(9):e071658. doi: 10.1136/bmjopen-2023-071658.

ABSTRACT

OBJECTIVES: The primary objective of our study was to evaluate the effectiveness of renal cell carcinoma (RCC) screening in renal transplant (RT) recipients.

DESIGN: Single-centre retrospective study.

SETTING AND PARTICIPANTS: 1998 RT recipients who underwent RT at Memorial Hermann Hospital (MHH) Texas Medical Center (TMC) between 1 January 1999 and 31 December 2019 were included and we identified 16 patients (0.8%) with RCC. An additional four patients with RCC who underwent RT elsewhere but received follow-up at MHH TMC were also included. Subject races included white (20%), black (50%), Hispanic (20%) and Asian (10%).

OUTCOME MEASURES: The RCC stage at diagnosis and outcomes were compared between patients who were screening versus those who were not.

RESULTS: We identified a total of 20 patients with post-RT RCC, 75% of whom were men. The median age at diagnosis was 56 years. RCC histologies included clear cell (75%), papillary (20%) and chromophobe (5%). Patients with post-RT RCC who had screening (n=12) underwent ultrasound or CT annually or every 2 years, whereas eight patients had no screening. All 12 patients who had screening had early-stage disease at diagnosis (stage I (n=11) or stage II (n=1)) and were cured by nephrectomy (n=10) or cryotherapy (n=2). In patients who had no screening, three (37.5%) had stage IV RCC at diagnosis and all of whom died of metastatic disease. There was a statistically significant difference in RCC-specific survival in patients who were screened (p=0.01) compared with those who were not screened.

CONCLUSION: All RT recipients who had RCC diagnosed based on screening had early-stage disease and there were no RCC-related deaths. Screening is an effective intervention in RT recipients to reduce RCC-related mortality.

PMID:37699639 | DOI:10.1136/bmjopen-2023-071658

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Career intentions of medical students in the UK: a national, cross-sectional study (AIMS study)

BMJ Open. 2023 Sep 12;13(9):e075598. doi: 10.1136/bmjopen-2023-075598.

ABSTRACT

OBJECTIVE: To determine current UK medical students’ career intentions after graduation and on completing the Foundation Programme (FP), and to ascertain the motivations behind these intentions.

DESIGN: Cross-sectional, mixed-methods survey of UK medical students, using a non-random sampling method.

SETTING: All 44 UK medical schools recognised by the General Medical Council.

PARTICIPANTS: All UK medical students were eligible to participate. The study sample consisted of 10 486 participants, approximately 25.50% of the medical student population.

OUTCOME MEASURES: Career intentions of medical students postgraduation and post-FP, motivations behind these career intentions, characterising the medical student population and correlating demographic factors and propensity to leave the National Health Service (NHS).

RESULTS: The majority of participating students (8806/10 486, 83.98%) planned to complete both years of the FP after graduation, with under half of these students (4294/8806, 48.76%) intending to pursue specialty training thereafter. A subanalysis of career intentions after the FP by year of study revealed a significant decrease in students’ intentions to enter specialty training as they advanced through medical school. Approximately a third of surveyed students (3392/10 486, 32.35%) intended to emigrate to practise medicine, with 42.57% (n=1444) of those students not planning to return. In total, 2.89% of students intended to leave medicine altogether (n=303). Remuneration, work-life balance and working conditions were identified as important factors in decision-making regarding emigration and leaving the profession. Subgroup analyses based on gender, type of schooling, fee type and educational background were performed. Only 17.26% of surveyed students were satisfied or very satisfied with the overall prospect of working in the NHS.

CONCLUSIONS: The Ascertaining the career Intentions of UK Medical Students study highlights UK students’ views and career intentions, revealing a concerning proportion of those surveyed considering alternative careers or emigration. Addressing factors such as remuneration, work-life balance and working conditions may increase retention of doctors and improve workforce planning efforts.

PMID:37699638 | DOI:10.1136/bmjopen-2023-075598