Category: Nevin Manimala

J Anim Breed Genet. 2023 Jun 22. doi: 10.1111/jbg.12813. Online ahead of print.

ABSTRACT

Non-additive genetic effects are well known to play an important role in the phenotypic expression of complex traits, such as fertility and reproduction. In this study, a genome scan was performed using 41,640 single nucleotide polymorphism (SNP) markers to identify genomic regions associated with epistatic (additive-by-additive) effects in fertility and reproduction traits in Holstein cattle. Nine fertility and reproduction traits were analysed on 5825 and 6090 Holstein heifers and cows with phenotypes and genotypes, respectively. The Marginal Epistasis Test (MAPIT) was used to identify SNPs with significant marginal epistatic effects at a chromosome-wise 5% and 10% false discovery rate (FDR) level. The -log₁₀ (p) values were adjusted by the genomic inflation factor (λ) to correct for the potential bias on the p-values and minimize the possible effects of population stratification. After adjustments, MAPIT enabled the identification of genomic regions with significant marginal epistatic effects for heifers on BTA5 for age at first insemination, BTA3 and BTA24 for non-return rate (NRR); BTA16 and BTA28 for gestation length (GL); BTA1, BTA4 and BTA17 for stillbirth (SB). For the cow traits, MAPIT enabled the identification of regions on BTA11 for GL, BTA11 and BTA16 for SB and BTA19 for calf size (CZ). An additional approach for mapping epistasis in a genome-wide association study was also proposed, in which the genome scan was performed using estimates of epistatic values as the input pseudo-phenotypes, computed using single-trait animal models. Significant SNPs were identified at the chromosome-wise 5% and 10% FDR levels for all traits. For the heifer traits, significant regions were found on BTA7 for AFS; BTA12 for NRR; BTA14 and BTA19 for GL; BTA19 for calving ease (CE); BTA5, BTA24, BTA25 and in the X chromosome for SB; BTA23 and in the X chromosome for CZ and in the X chromosome for the number of services (NS). For the cow traits, significant regions were found on BTA29 and in the X chromosome for NRR, BTA11, BTA16 and in the X chromosome for SB, BTA2 for GL, BTA28 for CZ, BTA19 for calving to first insemination, and in the X chromosome for NS and first insemination to conception. The results suggest that the epistatic genetic effects are likely due to many loci with a small effect rather than few loci with a large effect and/or a single SNP marker alone do not capture the epistatic effects well. The genomic architecture of fertility and reproduction traits is complex, and these results should be validated in independent dairy cattle populations and using alternative statistical models.

PMID:37350080 | DOI:10.1111/jbg.12813

Trials. 2023 Jun 22;24(1):426. doi: 10.1186/s13063-023-07348-3.

ABSTRACT

BACKGROUND: Many randomized trials that aim to assess new or commonly used medical or surgical interventions have been so small that the validity of conclusions becomes questionable.

METHODS: We illustrate the small trial problem using the power calculation of five Cochrane-reviewed studies that compared vertebroplasty versus placebo interventions. We discuss some of the reasons why the statistical admonition not to dichotomize continuous variables may not apply to the calculation of the number of patients required for trials to be meaningful.

RESULTS: Placebo-controlled vertebroplasty trials planned to recruit between 23 and 71 patients per group. Four of five studies used the standardized mean difference of a continuous pain variable (centimeters on the visual analog scale (VAS)) to plan implausibly small trials. What is needed is not a mean effect at the population level but a measure of efficacy at the patient level. Clinical practice concerns the care of individual patients that vary in many more respects than the variation around the mean of a single selected variable. The inference from trial to practice concerns the frequency of success of the experimental intervention performed one patient at a time. A comparison of the proportions of patients reaching a certain threshold is a more meaningful method that appropriately requires larger trials.

CONCLUSION: Most placebo-controlled vertebroplasty trials used comparisons of means of a continuous variable and were consequently very small. Randomized trials should instead be large enough to account for the diversity of future patients and practices. They should offer an evaluation of a clinically meaningful number of interventions performed in various contexts. Implications of this principle are not specific to placebo-controlled surgical trials. Trials designed to inform practice require a per-patient comparison of outcomes and the size of the trial should be planned accordingly.

PMID:37349843 | DOI:10.1186/s13063-023-07348-3

AIDS Res Ther. 2023 Jun 22;20(1):39. doi: 10.1186/s12981-023-00529-9.

ABSTRACT

BACKGROUND: In 2016 the WHO declared HIV self-testing and self-sampling an effective and safe test option that can reduce testing barriers. HIV self-tests and self-sampling kits (HIVST/HIVSS) are available for purchase at Dutch community pharmacies since 2019. We investigated the availability and accessibility of HIVST/HIVSS in community pharmacies, and factors associated with test availability.

METHODS: An online survey among all Dutch community pharmacies (n = 1,987) was conducted between April and June 2021. Availability of HIVST/HIVSS and experiences of pharmacists with the test offer were analyzed with descriptive statistics. The association of pharmacy and pharmacists’ characteristics with HIVST/HIVSS availability was explored by logistic regression analysis.

RESULTS: In total, 465 pharmacists completed the questionnaire. Of the responding pharmacists, 6.2% (n = 29) offered HIVST/HIVSS. The majority (82.8%) sold between 0 and 20 tests per year. In total, pharmacies sold an estimated 370 HIVST/HIVSS per year. Pharmacies having HIVST/HIVSS available were less often located in moderately-urbanized to rural neighborhoods (OR 0.35, 95%CI 0.16-0.77 versus highly-urbanized), and were less often located in moderate-to-low SES neighborhoods (OR 0.40, 95%CI 0.18-0.88 versus high-SES). Reasons for not offering HIVST/HIVSS by pharmacists were no or little demand (69.3%), and not being familiar with these tests (17.4%). 52% of the pharmacists provided information about testing to test buyers. Reported options to improve the test offer were giving advice about (performing) the test to test buyers (72.4%), placing tests visible on the counter (51.7%), and advertisement (37.9%).

CONCLUSION: HIVST/HIVSS have a limited practical availability in Dutch community pharmacies since their introduction in 2019, especially in lower-urbanized and lower-SES areas. Further research is needed to explore how to expand access to HIVST/HIVSS through community pharmacies in the Netherlands, and how to tailor it to the needs of pharmacy clients.

PMID:37349835 | DOI:10.1186/s12981-023-00529-9

BMC Chem. 2023 Jun 22;17(1):64. doi: 10.1186/s13065-023-00964-9.

ABSTRACT

In addition to its pure form, three accurate, rapid, and simple methods have been established for determining perindopril (PRD) in its tablet form. At pH 9.0 using a borate buffer, developing the three designated methods was successful according to the reaction between PRD and 4-chloro-7-nitrobenzo-2-oxa-1,3-diazole (NBD-Cl) and the formation of a chromogen (with a yellow color) measurable at 460 nm using the spectrophotometric method (Method I). In addition, the produced chromogen was assessed using the spectrofluorimetric method (Method II) at 535 nm following excitation at 461 nm. Afterward, the same reaction product was separated and determined using the HPLC method with fluorescence detection (Method III). A Promosil C₁₈ stainless steel column (Q7 5 mm particle size, 250-4.6 mm) has proven suitable for separation. The mobile phase adjustment was made at pH 3.0, with a 1.0 mL min ^-1 flow rate; its composition was methanol-sodium dihydrogen phosphate, 0.02 M (60: 40, v/v). Through concentration ranges of 5.0-60.0, 0.5-6.0, and 1.0-10.0 μg mL^-1, the calibration curves were rectilinear for Methods I, II, and III, respectively, with limits of quantification (LOQ) of 1.08, 0.16 and 0.19 μg mL^-1 as well as limits of detection (LOD) of 0.36, 0.05 and 0.06 μg mL^-1. The developed methods were implemented to estimate PRD in tablets, and a comparison between the obtained outcomes utilizing the developed methods as well as obtained from the official method revealed that they were comparable. The official BP method was based on dissolving PRD in anhydrous acetic acid and titrating with 0.1 M perchloric acid, then the potentiometric determination of the end-point. The designated methods were also implemented in content uniformity testing with satisfying results. The reaction pathway proposal was speculated, and according to ICH Guidelines, the statistical evaluation of the data was performed. The three proposed methods were confirmed to be green, eco-friendly and safe to environment using Green Analytical procedure index (GAPI) method.

PMID:37349827 | DOI:10.1186/s13065-023-00964-9

Malar J. 2023 Jun 22;22(1):192. doi: 10.1186/s12936-023-04623-1.

ABSTRACT

BACKGROUND: A better understanding of vector distribution and malaria transmission dynamics at a local scale is essential for implementing and evaluating effectiveness of vector control strategies. Through the data gathered in the framework of a cluster randomized controlled trial (CRT) evaluating the In2Care (Wageningen, Netherlands) Eave Tubes strategy, the distribution of the Anopheles vector, their biting behaviour and malaria transmission dynamics were investigated in Gbêkê region, central Côte d’Ivoire.

METHODS: From May 2017 to April 2019, adult mosquitoes were collected monthly using human landing catches (HLC) in twenty villages in Gbêkê region. Mosquito species wereidentified morphologically. Monthly entomological inoculation rates (EIR) were estimated by combining the HLC data with mosquito sporozoite infection rates measured in a subset of Anopheles vectors using PCR. Finally, biting rate and EIR fluctuations were fit to local rainfall data to investigate the seasonal determinants of mosquito abundance and malaria transmission in this region.

RESULTS: Overall, Anopheles gambiae, Anopheles funestus, and Anopheles nili were the three vector complexes found infected in the Gbêkê region, but there was a variation in Anopheles vector composition between villages. Anopheles gambiae was the predominant malaria vector responsible for 84.8% of Plasmodium parasite transmission in the area. An unprotected individual living in Gbêkê region received an average of 260 [222-298], 43.5 [35.8-51.29] and 3.02 [1.96-4] infected bites per year from An. gambiae, An. funestus and An. nili, respectively. Vector abundance and malaria transmission dynamics varied significantly between seasons and the highest biting rate and EIRs occurred in the months of heavy rainfall. However, mosquitoes infected with malaria parasites remained present in the dry season, despite the low density of mosquito populations.

CONCLUSION: These results demonstrate that the intensity of malaria transmission is extremely high in Gbêkê region, especially during the rainy season. The study highlights the risk factors of transmission that could negatively impact current interventions that target indoor control, as well as the urgent need for additional vector control tools to target the population of malaria vectors in Gbêkê region and reduce the burden of the disease.

PMID:37349819 | DOI:10.1186/s12936-023-04623-1

Int Breastfeed J. 2023 Jun 22;18(1):33. doi: 10.1186/s13006-023-00570-4.

ABSTRACT

BACKGROUND: Early initiation of breastfeeding within the first hour of life prevents neonatal and infant mortality. Sustainable Development Goals (SDGs) Target 3.2 aims to reduce neonatal mortality and under 5 mortality globally. The decline in the early initiation of breastfeeding in The Gambia coincides with deviations from the SDGs, due to poor indicators of child survival. Our work studied the determinants of early initiation of breastfeeding in The Gambia.

METHODS: We used the 2019-2020 Gambia Demographic Health Survey (GDHS) conducted across all regions of the country. Since our population of interest was children born two years preceding the study, we only included children less than 24 months of age, living with an eligible respondent. Thus, a weighted sample of 5691 mother-child pairs was applied in the analysis. We reported summary statistics of individuals’ sociodemographic, obstetrics and antenatal, household, and community-level factors. A logistic regression model was used to determine associations between early initiation of breastfeeding and covariates.

RESULTS: The prevalence of early initiation of breastfeeding was 64.3% (n = 3659). Mothers who had secondary education or higher educational level had higher odds of early initiation of breastfeeding (AOR 1.22; 95% CI 1.07, 1.40). Regions with rural population notably Lower and Central and Upper River Region had lower odds of early initiation of breastfeeding [Mansakonko (AOR 0.37; 95% CI 0.26, 0.15), Kerewan (AOR 0.26; 95% CI 0.19, 0.36), Kuntaur (AOR 0.39; 95% CI 0.28, 0.54), Janjanbureh (AOR 0.48; 95% CI 0.35, 0.66) and Basse (AOR 0.64; 95%CI 0.49, 0.85)]. Also, women in the high quintile of the wealth index were more likely to initiate breastfeeding early (AOR 1.29; 95% CI 1.06, 1.57). Four or more antenatal care visits did not increase early initiation of breastfeeding.

CONCLUSIONS: The results of the analyses demand affirmative action to improve maternal education, reduce poverty and inequality and empower rural communities in The Gambia. The IYCF component in antenatal care needs to be strengthened. Programs and policies on IYCF must resonate to address determinants of timely breastfeeding initiation to chart progress towards the SDG.

PMID:37349805 | DOI:10.1186/s13006-023-00570-4

BMC Health Serv Res. 2023 Jun 22;23(1):677. doi: 10.1186/s12913-023-09616-z.

ABSTRACT

BACKGROUND: Adolescents have special sexual and reproductive health (ASRH) needs and are susceptible to poor health outcomes. The global burden of ill sexual health includes a significant proportion of Adolescents. The existing ASRH services in Ethiopia and particularly in the Afar region are currently not well suited to meet the needs of pastoralist adolescents. This study assesses the level of ASRH service utilization among pastoralists in Afar regional state, Ethiopia.

METHOD: A community based cross-sectional study was conducted from January to March 2021 in four randomly chosen pastoralist villages or kebeles of Afar, Ethiopia. A multistage cluster sampling procedure was used to select 766 volunteer adolescents aged 10-19. SRH services uptake was measured asking whether they had used any SRH service components during the last year. Data was collected through face-to-face interviews with a structured questionnaire; data entry was done with Epi info 3.5.1. Logistic regression analyses was used to assess associations with SRH service uptake. SPSS version 23 statistical software package was used for advanced logistic regression analyses to assess the associations between dependent and predictor variables.

RESULTS: The study revealed that two-thirds or 513 (67%) of the respondents are aware of ASRH services. However, only one-fourth (24.5%) of the enrolled adolescents used at least one ASRH service in the past twelve months. ASRH services utilization was significantly associated with gender (being female [AOR = 1.87 (CI 1.29-2.70)], being in school [AOR = 2.38(CI: 1.05-5.41), better family income [AOR = 10.92 (CI; 7.10-16.80)], prior discussions of ASRH issues [AOR = 4.53(CI: 2.52, 8.16)], prior sexual exposure [AOR = 4.75(CI: 1.35-16.70)], and being aware of ASRH services [AOR = 1.96 (CI: 1.02-3.822)]. Being pastoralist, religious and cultural restrictions, fear of it becoming known by parents, services not being available, income, and lack of knowledge were found to deter ASRH service uptake.

CONCLUSION: Addressing ASRH needs of pastoralist adolescents is more urgent than ever, sexual health problems are increasing where these groups face broad hurdles to SRH service uptake. Although Ethiopian national policy has created an enabling environment for ASRH, multiple implementation issues require special attention to such neglected groups. “Gender-culture-context-appropriate” interventions are favorable to identify and meet the diverse needs of Afar pastoralist adolescents. Afar regional education bureau and concerned stakeholders need to improve adolescent education to overcome social barriers (e.g. humiliation, disgrace, and deterring gender norms) against ASRH services through community outreach programs. In addition, economic empowerment, peer education, adolescent counseling, and parent-youth communication will help address sensitive ASRH issues.

PMID:37349790 | DOI:10.1186/s12913-023-09616-z

BMC Musculoskelet Disord. 2023 Jun 22;24(1):509. doi: 10.1186/s12891-023-06618-0.

ABSTRACT

BACKGROUND: A mechanism-based approach to the evaluation and management of pain has been suggested across disciplines in contemporary research. However, the translation of pain mechanism assessment strategies in research to clinical practice is unclear. This study sought to explore perceptions and use of clinical pain mechanism assessment by physical therapists managing musculoskeletal pain.

METHODS: This was an electronic cross-sectional survey. After initial development, refinement, and piloting for comprehensiveness, comprehensibility and relevance, the survey was disseminated to members of the Academy of Orthopaedic Physical Therapy via email listserv. Data was maintained anonymously using the online database REDCap. Descriptive statistics and Spearman’s correlations for non-parametric data were analyzed for frequencies and associations across variables.

RESULTS: In total, 148 respondents completed all aspects of the survey. Respondent age ranged from 26 to 73 years, with a mean (SD) of 43.9 (12.0). Most respondents (70.8%) reported performing clinical pain mechanism assessments at least ‘sometimes’. A majority (80.4%) believed clinical pain mechanism assessments are useful in guiding management strategies while 79.8% reported specifically choosing interventions to alter aberrant pain mechanisms. The most commonly used pain severity, physical examination testing and questionnaires were the numeric pain rating scale, pressure pain thresholds and pain diagrams, respectively. However, the vast majority of instruments to clinically assess pain mechanisms were performed by a small proportion of respondents (< 30%). There were no significant correlations between age, years of experience, highest earned degree, completion of advanced training or specialist certification and testing frequency.

CONCLUSION: The evaluation of pain mechanisms involved in the pain experience is becoming common in research. The clinical application of pain mechanism assessment is unclear. Based on the results of this survey, physical therapists in the orthopedic setting believe pain mechanism assessment is useful, but data suggests it is infrequently performed. Additional research to uncover clinician motivation related to pain mechanism assessment is warranted.

PMID:37349782 | DOI:10.1186/s12891-023-06618-0

Alzheimers Res Ther. 2023 Jun 22;15(1):116. doi: 10.1186/s13195-023-01263-0.

NO ABSTRACT

PMID:37349779 | DOI:10.1186/s13195-023-01263-0

BMC Chem. 2023 Jun 22;17(1):63. doi: 10.1186/s13065-023-00970-x.

ABSTRACT

The application of QSAR analysis dates back a half-century ago and is currently continuously employed in any rational drug design. The multi-dimensional QSAR modeling can be a promising tool for researchers to develop reliable predictive QSAR models for designing novel compounds. In the present work, we studied inhibitors of human aldose reductase (AR) to generate multi-dimensional QSAR models using 3D- and 6D-QSAR methods. For this purpose, Pentacle and Quasar’s programs were used to produce the QSAR models using corresponding dissociation constant (K_d) values. By inspecting the performance metrics of the generated models, we achieved similar results with comparable internal validation statistics. However, considering the externally validated values, 6D-QSAR models provide significantly better prediction of endpoint values. The obtained results suggest that the higher the dimension of the QSAR model, the higher the performance of the generated model. However, more studies are required to verify these outcomes.

PMID:37349775 | DOI:10.1186/s13065-023-00970-x