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Background: We performed a multicentre randomised controlled trial to evaluate the effect on participation in organised screening programmes of a self-sampling device mailed home or picked up at a pharmacy compared with the standard recall letter. Methods: Women aged 30–64 non-responding to screening invitation were eligible. Response rate to first invitation ranged from 30% to 60% between centres. The control was the standard reminder letter to undergo the test used by the programme (Pap test in three centres and HPV DNA test in three other centres). Home mailing of the self-sampler was preceded by a letter with a leaflet about HPV. The analysis was intention-to-treat. Results: In all, 14 041 women were randomised and recruited: 5012 in the control arm, 4516 to receive the self-sampler at home, and 4513 to pick up the self-sampler at a pharmacy. Participation was 11.9% in the control, 21.6% (relative participation: 1.75; 95% CI 1.60–1.93) in home, and 12.0% (relative participation: 0.96; 95% CI 0.86–1.07) in the pharmacy arms, respectively. The heterogeneity between centres was high (excess heterogeneity of that expected due to chance, i.e., I 2 , 94.9% and 94.1% for home and pharmacy arm, respectively). The estimated impact on the overall coverage was +4.3% for home mail self-sampling compared with +2.2% for standard reminder. Conclusions: Home mailing of self-sampler proved to be an effective way to increase participation in screening programmes, even in those with HPV as primary testing. Picking up at pharmacies showed effects varying from centre to centre.

BackgroundPleural infection is common, and has a >30% major morbidity and mortality—particularly when infection is caused by Gram-negative, Staphylococcus aureus or mixed aerobic pathogens. Standard pleural fluid culture is negative in ∼40% of cases. Culturing pleural fluid in blood culture bottles may increase microbial yield, and is cheap and easy to perform.ObjectivesTo determine whether inoculating pleural fluid into blood culture bottles increases the culture positivity of pleural infection over standard laboratory culture, and to assess the optimum volume of inoculum to introduce.Methods62 patients with pleural infection were enrolled. Pairs of aerobic and anaerobic blood culture bottles were inoculated at the bedside with 2, 5 or 10 ml of pleural fluid, and two pleural fluid specimens were sent for standard culture. Pleural fluid from nine control patients was cultured to test for ‘false-positive’ results.ResultsThe addition of blood culture bottle culture to standard culture increased the proportion of patients with identifiable pathogens by 20.8% (20/53 (37.7%) to 31/53 (58.5%) (difference 20.8%, 95% CI difference 8.9% to 20.8%, p<0.001)). The second standard culture did not similarly improve the culture positivity (19/49 (38.8%) to 22/49 (44.9%) (difference 6.1%, 95% CI difference −2.5% to 6.1%, p=0.08)). The culture inoculum volume did not influence bacterial isolation frequency. The control fluids were culture negative.ConclusionsBlood culture bottle culture of infected pleural fluid increases microbial yield when used in addition to standard culture. This technique should be part of routine care.

Human papillomavirus (HPV) testing of self-collected vaginal samples has potential to improve coverage of cervical screening programmes, but current guidelines mostly require those HPV positive on a self-sample to attend for routine screening. A pragmatic modified stepped-wedge implementation feasibility trial was conducted at primary care practices in England. Individuals aged 25 to 64 years who were at least 6 months overdue for cervical screening could provide a self-collected sample. The primary outcomes included the monthly proportion of non-attenders screened, changes in coverage, and uptake within 90 days. Self-samples from 7,739 individuals were analysed using Roche Cobas 4800. Individuals with a positive self-sample were encouraged to attend clinical screening. In this post hoc study of the trial, we related the HPV type (HPV16, HPV18, or other high-risk type) and cycle threshold (Ct) value on the self-sample to the results of clinician-collected sample and cervical intraepithelial neoplasia grade 2 or worse (CIN2+). We wished to triage HPV-positive individuals to immediate colposcopy, clinician sampling, or 12-month recall depending on risk. A total of 1,001 women tested positive through self-samples, and 855 women who had both an HPV-positive self-sample and a subsequent clinician-sample were included in this study. Of these, 71 (8.3%) had CIN2+. Self-sample Ct values were highly predictive of HPV in the clinician sample. Combining HPV type and Ct value allowed stratification into 3 risk groups; 44/855 (5%) were high-risk of whom 43% (19/44, 95% confidence interval [29.7%, 57.8%]) had CIN2+. The majority (52.9%, 452/855) were low-risk, of whom 4% (18/452, 95% CI [2.5%, 6.2%]) had CIN2+. The main limitation of our study was the colposcopy assessment was restricted to individuals who had abnormal cytology after positive results of both self-sample and clinician-collected sample. HPV type and Ct value on HPV-positive self-samples may be used for triage. The difference in the risk of CIN2+ in these groups appears sufficient to justify differential clinical management. A prospective study employing such triage to evaluate laboratory workflow, acceptability, and follow-up procedure and to optimise clinical performance seems warranted. ISRCTN12759467.

The use of acid to obscure human remains is a tactic frequently associated with criminal activity, yet research on its effects on human dentition remains inconsistent. Dental tissues, among the body's most durable components, play a vital role in forensic identification. However, existing studies on acid dissolution of dentition often lack standardized methods, resulting in findings that are difficult to reproduce or generalize. This study addresses these gaps by examining the effects of hydrochloric acid (HCl) on permanent maxillary molars under controlled conditions, using a replicable methodology that incorporates experimental controls and evaluates the impact of handling techniques such as removal, rinsing, and drying. Five permanent maxillary molar samples were submerged in HCl (37 %) under varied handling conditions. Findings reveal that undisturbed samples dissolved more slowly than those subjected to periodic removal and rinsing, which accelerated dissolution rates by over 100 %. This highlights the significant influence of handling techniques on experimental outcomes. The study also identifies inconsistent reporting and the absence of standardized protocols in prior research as critical barriers to reproducibility. By providing a clear and replicable framework, this study advances understanding of the dissolution process and emphasizes the importance of methodological rigor in forensic science. These findings have broader implications for improving the reliability of forensic evidence and ensuring its applicability in criminal investigations. Addressing these issues is essential for enhancing public trust in forensic methods and strengthening their role in the justice system. •Clear, replicable research is critical to maintaining credibility in forensic applications.•Variability in dentition studies reveals critical gaps in forensic science's methodological rigor.•Introducing controls in forensic research can significantly improve the accuracy of findings.•It found that handling methods, like periodic rinsing, accelerate tooth dissolution compared to undisturbed conditions.•This study explores how hydrochloric acid affects human molars using a controlled, replicable approach.

ObjectivesTo establish temporal links between vaginal microbiota (VMB) data and incident clinical events, frequent longitudinal vaginal sampling is required. Self-collection of swabs at the participant’s home may be useful to avoid overburdening research clinics and participants. One-off vaginal self-sampling for STI or cervical cancer screening programmes has been shown to be feasible and acceptable to women in multiple studies, including in sub-Saharan Africa, but the feasibility and acceptability of frequent longitudinal vaginal sampling in the context of VMB sequencing studies is unknown.MethodsTwelve participants of a randomised clinical trial in Kigali, Rwanda, self-collected vaginal swabs three times a week for a month. We studied feasibility by comparing DNA concentrations, proportions of samples with >1000 16S rRNA amplicon sequencing reads and VMB composition outcomes of self-collected swabs with clinician-collected swabs. We evaluated the acceptability of self-collection using structured face-to-face interviews and a focus group discussion.ResultsThe participants collected vaginal swabs at 131 different time points. One woman stopped self-sampling after one try due to a social harm. All self-sampled swabs generated >1000 rRNA amplicon sequencing reads, and the DNA concentration of self-sampled swabs and clinician-sampled swabs did not differ significantly (Kruskal-Wallis p=0.484). Self-sampled and clinician-sampled swabs generated similar VMB composition data. Participants reported feeling very comfortable during self-sampling (11/12; 91.7%) and that self-sampling had become easier over time (12/12; 100%). They mentioned reduced travel time and travel costs as advantages of self-sampling at home.ConclusionsFrequent longitudinal vaginal sampling at home is feasible and acceptable to participants, even in the context of a low-resource setting, as long as adequate counselling is provided.Trial registration number NCT02459665.

Risk of anal cancer is high in certain populations and screening involves collection of anal swabs for HPV DNA and/or cytology testing. However, barriers exist, such as the need for an intimate examination, and stigma around HIV status, sexual orientation, and sexual practices. Self-collected anal swabs (SCA) are a proposed alternative to clinician-collected swabs (CCA) to overcome these barriers. Participants were order-randomised to undergo SCA or CCA first, with a second swab taken immediately afterwards. Sample adequacy was assessed for HPV DNA and cytology testing. CCA was used as the gold standard to calculate sensitivity and specificity of SCA for cytology and HPV results. Acceptability of swab collection was assessed following the procedure. There was no significant difference in sample validity for HPV DNA testing between SCA and CCA (p = 0.564). Concordance was >90% for detection of any HR-HPV and HPV16. There was no significant difference in cellular adequacy for cytological testing between SCA and CCA, (p = 0.162). Concordance for cytologic prediction was 88.2% for any cytologic abnormality. Almost half (48.5%) of participants expressed no preference for SCA versus CCA; 15.2% preferred SCA and 35.4% CCA. SCA may be an acceptable and feasible alternative to CCA for detecting HPV and cytological abnormalities in a clinic population.

PurposeTo investigate the differences concerning post-thawing/warming follicle survival, DNA damage and apoptosis in human ovarian tissues cryopreserved by slow freezing, open, or closed vitrification methods.MethodsA total of 50 pieces of 5 × 5 × 1 mm ovarian cortical pieces were harvested (5 donor ovaries; mean age 31 ± 6.62 years). From each donor, one cortical piece was used as baseline; the remaining were randomly assigned to slow freezing (SF), vitrification using open device (VF-open), or closed device (VF-closed) groups. After 8–10 weeks of cryostorage, tissues were evaluated 4 h after thawing/warming. Histological analysis was evaluated for follicle survival (primordial and primary follicle densities) by H&E staining. The percentages of primordial and primary follicles with DNA double-strand breaks (γH2AX) and apoptotic cell death pathway activation (AC3) were immunohistochemically assessed. Data were analysed using one-way ANOVA and LSD post hoc comparison.ResultsCompared to the baseline, primordial follicle (pdf) densities significantly declined in all cryopreserved groups (SF, VF-open, and VF-closed, P < 0.05). However, the total and non-apoptotic pdf densities were similar among SF, VF-open, and VF-closed. SF and VF with either open or closed devices did not increase the percentages of primordial or primary follicles with DNA double-strand breaks (DSBs) or apoptosis compared to the baseline or among the freezing methods in the present study.ConclusionBased on the intact primordial follicle survival, DNA damage, and apoptosis rates after thawing/warming, SF vs VF with either open or newly developed closed devices appear to be comparable.

Background The World Health Organization’s 90-70-90 goal aims to eliminate cervical cancer (CC) as a public health issue, with a target of up to 70% of women screened by 2030. However, many countries, including Cameroon, are far from achieving this goal. Home-based human papillomavirus (HPV) self-sampling is a promising approach to improve participation rates. The main objective of this study was to explore the acceptability and feasibility of home-based HPV self-sampling in the West region of Cameroon. Methods A quantitative, descriptive, cross-sectional study conducted between January 11 and February 05, 2024, was embedded in a cluster-randomised controlled trial comparing home- vs. hospital-based CC screening. Women eligible for CC screening, male partners or close relatives, community leaders, and healthcare professionals (HCPs) living in Dschang health district responded to a structured questionnaire. Simple and multivariate analyses were performed to assess the association between acceptability of home-based HPV self-sampling, CC screening practices, and sociodemographic factors such as education, professional status, residence, and income. Preferences for implementation (e.g., seasonal timing) were also explored. Results A total of 556 participants (300 women, 70 male partners, 153 HCPs, and 33 community leaders) were recruited. Overall, 77.5% of participants expressed favourable attitudes toward home-based HPV self-sampling, with acceptability rates of 73.7% for women, 65.7% for men, 90% for community leaders, and 87.6% for HCPs. Previous CC screening was reported by 33% of women, and was significantly associated with being over 40 years old (aOR = 2.1, p  = 0.007), with a monthly income of > 50,000 XAF (aOR = 2.2, p  = 0.049), and having good knowledge of CC (aOR = 2.6, p  = 0.001). Morning screening implementation was preferred by most participants, with 60% favouring year-round screening. More than 70% preferred face-to-face communication of HPV test results from SMS or phone calls, at hospitals for women (63%), men (50%), and HCPs (65.4%); while community leaders preferred home disclosure. Conclusion Home-based HPV self-sampling was highly accepted across all study groups and was unaffected by sociodemographic factors. Previous screening practices were associated with age, income, and knowledge. Home-based HPV self-sampling screening can address access disparities to CC screening. Community involvement in planning and implementing these programs is essential to ensure their success. Trial registration Ethical Cantonal Board of Geneva, Switzerland (CCER, N°202100085), (ClinicalTrials.govID NCT06166420 / 20231204) and the National Ethics Committee for Human Health Research in Cameroon (N°2023/09/1579/CE/CNERSH/SP).

Although multiple studies have offered self-collection for human papillomavirus (HPV)-based cervical screening in community settings, there are no randomised controlled trials (RCTs) that have compared implementation outcomes of programme approaches for self-collection. This trial will compare two such approaches in low-resource settings in the states of Tamil Nadu and Mizoram, India. A cluster RCT will be conducted over a year, offering self-collection to 3000 women aged 30-49 from 28 clusters (average size 101) in selected districts. Clusters in tribal, rural and urban low-income settings will be randomised to two arms. The intervention arm, co-designed with multiple stakeholders, will involve campaigns to offer self-collection in the community. The comparison arm will be offered self-collection at the nearest health facilities.HPV-based cervical screening will be performed at central laboratories using clinically validated screening assays that can identify the highest risk carcinogenic HPV types (Group 1a-c - HPV16/18/31/33/45/52/58, ±35). Ablative treatment will be based on positivity with this extended genotyping triage, while those with any of the lower carcinogenic HPV types (Group 1d - 39, 51, 56, 59, ±35, Groups 2a/b - 66, 68) will undergo further assessment with visual inspection with acetic acid. Outcomes will be evaluated quantitatively and qualitatively using RE-AIM and the Theoretical Framework of Acceptability. The primary outcome will be percentage of women well-managed (screened and appropriately treated) in both arms, with secondary outcomes including proportion screened, proportion treated, acceptability (willingness to screen, rescreen, and/or recommend to others) to women, community and healthcare providers, adoption (by providers), implementation fidelity, costs, sustainability assessment and systematically identified implementation barriers and facilitators. The reach, effectiveness and acceptability of community-based self-collection and the use of extended genotyping for triage in resource-constrained, hard-to-reach populations will be assessed, with lessons that can inform future statewide and national programmes. Ethics approval has been obtained from the Institutional Review Board (IRB) and Ethics Committee of the Christian Medical College Vellore, Tamil Nadu, India (IRB Min. No 14314; INTERVEN), the Alfred Hospital Ethics Committee (HREC Ref 80134, Local Reference: project 601/21), Melbourne, Australia, the IARC Ethics Committee (IEC 21-32), Lyon, France, the Salem Polyclinic Institutional Ethics Committee (SPCIEC/2022/June/01/02), Tamil Nadu, India and the Institutional Ethics Committee, Civil Hospital, Aizawl, Mizoram, India (No.B.12018/1/13-CHA(A)/IEC/115). The study is also approved by the State Scientific Advisory Committee, Directorate of Public Health and Preventive Medicine, Chennai, Tamil Nadu (R. No. 011575/HEB/A2/2023). The Alfred Hospital Approval, as an authorised Australian ethics committee for national mutual recognition, is recognised and registered with the University of Melbourne Human Research Ethics Committee (2024-25255-57650-1). Written informed consent will be obtained from participants. The results of the trial will be disseminated through a peer-reviewed medical journal, and also through workshops, reports and conferences. The trial has been registered with the Clinical Trials Registry - India: CTRI/2022/04/042327.

PurposeTo compare the effect of two different sperm preparation techniques, including swim-up and gradient methods on sperm deoxyribonucleic acid (DNA) fragmentation status of semen samples from unexplained and mild male factor subfertile patients undergoing intrauterine insemination (IUI).DesignA prospective randomized study was conducted in 65 subfertile patients, including 34 unexplained and 31 male factor infertility to compare basal and post-procedure DNA fragmentation rates in swim-up and gradient techniques. Sperm DNA fragmentation rates were evaluated by a sperm chromatin dispersion (SCD) test in two portions of each sample of semen that was prepared with either swim-up or gradient techniques. Sperm motility and morphology were also assessed based on WHO 2010 criteria.ResultsSwim-up but not gradient method yielded a statistically significant reduction in the DNA fragmented sperm rate after preparation as compared to basal rates, in the semen samples of both unexplained (41.85 ± 22.04 vs. 28.58 ± 21.93, p < 0.001 for swim-up; and 41.85 ± 22.04 vs. 38.79 ± 22.30, p = 0.160 for gradient) and mild male factor (46.61 ± 19.38 vs. 30.32 ± 18.20, p < 0.001 for swim-up and 46.61 ± 19.38 vs. 44.03 ± 20.87, p = 0.470 for gradient) subgroups.ConclusionsSwim-up method significantly reduces sperm DNA fragmentation rates and may have some prognostic value on intrauterine insemination in patients with decreased sperm DNA integrity.