In this review, we delineate the unique set of characteristics associated with cryosphere environments (namely, ice and permafrost) which present both challenges and opportunities for studying ancient environmental microbiomes (AEMs). In a field currently reliant on several assumptions, we discuss the theoretical and empirical feasibility of recovering microbial nucleic acids (NAs) from ice and permafrost with varying degrees of antiquity. We also summarize contamination control best practices and highlight considerations for the latest approaches, including shotgun metagenomics, and downstream bioinformatic authentication approaches. We review the adoption of existing software and provide an overview of more recently published programs, with reference to their suitability for AEM studies. Finally, we summarize outstanding challenges and likely future directions for AEM research.

Science, Volume 386, Issue 6721, Page 494-495, November 2024.

Physician Magda Robalo has dedicated her career to supporting health equity in Africa. At the age of 16 years, she moved from her home in Guinea-Bissau to Portugal, later studying medicine at the Universidade do Porto and then public health and tropical medicine at the Universidade Nova. After graduating, Robalo\'s plan was to specialise in neurosurgery, until her final residency took her to the Egas Moniz Hospital in Lisbon, which, she says, “from colonial times, was dedicated to infectious tropical diseases.

by Alexis M. Hill, Tanvi A. Ingle, Claus O. Wilke Bacteriophage ϕX174 has been widely used as a model organism to study fundamental processes in molecular biology. However, several aspects of ϕX174 gene regulation are not fully resolved. Here we construct a computational model for ϕX174 and use the model to study gene regulation during the phage infection cycle. We estimate the relative strengths of transcription regulatory elements (promoters and terminators) by fitting the model to transcriptomics data. We show that the specific arrangement of a promoter followed immediately by a terminator, which occurs naturally in the ϕX174 genome, poses a parameter identifiability problem for the model, since the activity of one element can be partially compensated for by the other. We also simulate ϕX174 gene expression with two additional, putative transcription regulatory elements that have been proposed in prior studies. We find that the activities of these putative elements are estimated to be weak, and that variation in ϕX174 transcript abundances can be adequately explained without them. Overall, our work demonstrates that ϕX174 gene regulation is well described by the canonical set of promoters and terminators widely used in the literature.

by Ananya Datta, Xin Yi Li, Manshul Nagpaul Purpose Osteopontin (OPN) is a glycosylated, secreted phosphoprotein known to be elevated in both human and mouse retinas during various stages of diabetic retinopathy. However, its specific roles in modulating ocular surface dynamics and immune responses in diabetes remain unexplored. This study aims to investigate the role of OPN in the development of ocular surface disease (OSD) in type 2 diabetic (T2D) mice. Methods Three- to four-week-old C57BL/6 wild-type (WT) and OPN-knockout (OPN-/-) mice were fed a high-fat diet (HFD) and were rendered diabetic by streptozotocin (STZ; 40 mg/kg body weight) in citrate buffer (vehicle); non-diabetic controls were injected with vehicle alone. Diabetes was confirmed if blood glucose levels were >200 mg/dL, measured 1–2 weeks post-STZ injection. Control, age- and sex-matched db/db diabetic mice fed a standard chow diet were also included in this study. Ocular surface inflammation was assessed using ELISA to quantify inflammatory cytokine proteins and wheat germ agglutinin (WGA) staining was utilized to highlight corneal surface irregularities. Clinical signs were evaluated by corneal fluorescein staining, tear production measurements, and tear sodium (Na+) concentration assessments. These evaluations were conducted 4, 6, 8 and 16-weeks post-diabetes onset in WT and OPN-/- mice and were compared to those obtained in non-diabetic controls. Statistical analysis was performed using a two-way ANOVA, with significance set at P < 0.05. Results Both WT and OPN-/- mice developed T2D within 4 and 8 weeks, respectively, following HFD + STZ treatment. Corneal OPN levels in WT diabetic mice increased ~2-fold at 2 weeks and ~4-fold at 16 weeks compared to non-diabetic controls, with similar elevations observed in their tear fluid. Diabetic db/db mice also exhibited elevated OPN levels in the blood and ocular surface, which persisted as diabetes progressed. Enhanced fluorescein staining, indicating corneal irregularities, appeared in WT mice at 8 weeks and in OPN-/- mice at 10 weeks post-T2D induction. Additionally, WGA staining showed a significant reduction in fluorescence intensity in WT mice treated with HFD and STZ, confirming corneal surface irregularities that were delayed in OPN-/- mice. Elevated tear sodium concentration was observed in both WT and OPN-/- diabetic mice without affecting tear production rates. Notably, OPN levels increased early, at week 2, following HFD and STZ treatment, preceding changes in interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), and matrix metalloproteinase-9 (MMP-9). Upregulation of IL-6 became apparent at 6 weeks in WT mice and was delayed until 10 weeks in OPN-/- mice post-T2D induction. Conclusions Elevated OPN levels were detected early post-T2D induction in diabetic WT and db/db mice corneas without initial subclinical changes. This early increase in OPN precedes other proinflammatory cytokines associated with eventual ocular surface inflammation as diabetes progresses. Persistence of OPN also correlated with clinical signs such as increased corneal surface irregularities and elevated tear Na+ concentration. Future research will explore OPN’s role as a biomarker in ocular surface disease (OSD), including dry eye disease (DED), and investigate its impact on inflammatory processes and other mechanistic pathways in diabetic ocular complications. …

by Sarah M. Khatibzadeh, Linda A. Dahlgren, Clayton C. Caswell, William A. Ducker, Stephen R. Werre, Sophie H. Bogers Biofilms reduce antibiotic efficacy and lead to complications and mortality in human and equine patients with orthopedic infections. Equine bone marrow-derived mesenchymal stromal cells (MSC) kill planktonic bacteria and prevent biofilm formation, but their ability to disrupt established orthopedic biofilms is unknown. Our objective was to evaluate the ability of MSC to reduce established S. aureus or E. coli biofilms in vitro. We hypothesized that MSC would reduce biofilm matrix and colony-forming units (CFU) compared to no treatment and that MSC combined with the antibiotic, amikacin sulfate, would reduce these components more than MSC or amikacin alone. MSC were isolated from 5 adult Thoroughbred horses in antibiotic-free medium. 24-hour S. aureus or E. coli biofilms were co-cultured in triplicate for 24 or 48 hours in a transwell plate system: untreated (negative) control, 30 μg/mL amikacin, 1 x 106 passage 3 MSC, and MSC with 30 μg/mL amikacin. Treated biofilms were photographed and biofilm area quantified digitally. Biomass was quantified via crystal violet staining, and CFU quantified following enzymatic digestion. Data were analyzed using mixed model ANOVA with Tukey post-hoc comparisons (p < 0.05). MSC significantly reduced S. aureus biofilms at both timepoints and E. coli biofilm area at 48 hours compared to untreated controls. MSC with amikacin significantly reduced S. aureus biofilms versus amikacin and E. coli biofilms versus MSC at 48 hours. MSC significantly reduced S. aureus biomass at both timepoints and reduced S. aureus CFU at 48 hours versus untreated controls. MSC with amikacin significantly reduced S. aureus biomass versus amikacin at 24 hours and S. aureus and E. coli CFU versus MSC at both timepoints. MSC primarily disrupted the biofilm matrix but performed differently on S. aureus versus E. coli. Evaluation of biofilm-MSC interactions, MSC dose, and treatment time are warranted prior to testing in vivo.

by Ngoc Nha Thao Nguyen, Thi Trang Dai Nguyen, Duc Linh Vo, Dang Tuyet Minh Than, Gia Phuoc Tien, Duy Toan Pham Current treatments for severe acne include combinations of synthetic anti-inflammatory and antibacterial drugs, which possess numerous side effects. Therefore, this study developed microemulsion-based hydrogel containing lemongrass leaf essential oil (Cymbopogon citratus (DC.) Stapf) and mango seed kernel extract (Mangifera indica Linn) as a potential natural therapy for inflammatory acne. To this end, the microemulsions were first prepared using pseudo-ternary phase diagrams with soybean oil and coconut oil, cremophor RH40, and PEG 400. The optimal formula could load 1% lemongrass oil and 10% mango extract, possessed a spherical droplet size of ~18.98 nm, a zeta potential of -5.56 mV, and a thermodynamic stability. Secondly, the microemulsion-based hydrogel was developed by simple mixing the optimal microemulsion in carbopol-940 hydrogel (3.5% w/w). The product showed a viscosity of ~3728 cPs, a pH of 5.4-6.2, a spreadability of ~24 cm, an in-vitro Franz-cell cumulative release rate of ~80% for polyphenol content and ~60% for citral within 12 h, and a good physicochemical stability of > 3 months. Thirdly, the skin compatibility/irritability of the microemulsion-based hydrogel was determined by the HET-CAM assay, which showed non-irritation level. Finally, the anti-inflammatory activities of the hydrogel, using heat-induced BSA denaturation assay and LPS-stimulated RAW 264.7 NO inhibition assay, was 4-times higher than that of the reference drug Klenzit-C® (adapalene and clindamycin gel). Moreover, the hydrogel possessed strong anti-biofilm activity in Cutibacterium acnes, comparable with Klenzit-C®. Conclusively, the microemulsion-based hydrogel containing lemongrass oil and mango seed extract demonstrated much potentials to be a promising natural drug for acne treatment.

by Sindhu Bhaarrati Naidu, Anita Saigal, Amar Jitu Shah, Chibueze Ogbonnaya, Shiuli Bhattacharyya, Karthig Thillaivasan, Songyuan Xiao, Camila Nagoda Niklewicz, George Seligmann, Heba Majed Bintalib, John Robert Hurst, Marc Caeroos Isaac Lipman, Swapna Mandal Introduction Ethnicity can influence susceptibility to SARS-CoV-2 infection, hospitalisation and death. Its association with ongoing symptomatic COVID-19 is unclear. We assessed if, among a population followed up after discharge from hospital with COVID-19, adults from Asian, black, mixed and other backgrounds are at increased risk of physical and mental health symptoms. Methods Adults discharged after hospitalisation with COVID-19 between 03/03/2020 and 27/11/2021 were routinely offered follow-up six to 12 weeks post-discharge and reviewed for ongoing symptomatic COVID-19, as defined by persisting physical symptoms (respiratory symptoms, fatigue, impaired sleep and number of other symptoms), mental health symptoms and inability to return to work if employed. Descriptive statistics and multiple regression analyses were used to compare differences in characteristics, follow-up outcomes and blood tests between ethnic groups. To account for possible selection bias, analyses were adjusted for propensity scores. Results 986 adults completed follow-up: 202 (20.5%) Asian, 105 (10.6%) black, 18 (1.8%) mixed, 468 (47.5%) white and 111 (11.3%) from other backgrounds. Differences between groups included white adults being older than those from Asian/‘other’ backgrounds and black adults being more likely from deprived areas than those from Asian/white/‘other’ backgrounds. After adjusting for these differences, at follow-up, black adults had fewer respiratory (adjusted odds ratio 0.49 (0.25–0.96)) and other symptoms (adjusted count ratio 0.68 (0.34–0.99)) compared to white adults. There were otherwise no significant differences between ethnic groups in terms of physical health, mental health or ability to return to work if employed. These findings were not altered after adjustment for propensity scores. Conclusions In our population, despite having more co-morbidities associated with worse outcomes, adults from Asian, black, mixed and other ethnic backgrounds are not more likely to develop ongoing symptomatic COVID-19. However, it is important that healthcare services remain vigilant in ensuring the provision of timely patient-centred care. …

by Srisan Phupaboon, Maharach Matra, Ronnachai Prommachart, Pajaree Totakul, Metha Wanapat The objective was to assess the supplementation with microencapsulation of hemp leaf extract (mHLE) utilized as a rumen enhancer on in vitro rumen fermentation and to enhance the bioavailability of active compounds for antimicrobial action, particularly in protozoa and methanogen populations. The feed treatments were totally randomized in the experimental design, with different levels of mHLE diet supplemented at 0, 4, 6 and 8% of total DM substrate and added to an R:C ratio of 60:40. During fermentation, gas kinetics production, nutrient degradability, ammonia nitrogen concentration, volatile fatty acid (VFA) profiles, methane production, and the microbial population were measured. The supplemented treatment at 6% of total DM substrate affected reductions in gas kinetics, cumulative gas production, and volatile fatty acid profiles, especially the acetate and acetate to propionate ratio. Whereas propionate proportion and total volatile fatty acid concentration were enhanced depending on the increase of nutrients in vitro dry matter degradability (IVDMD) after 12 h of post-fermentation at a R:C ratio of 60:40 (P < 0.05). Consequently, mHLE addition resulted in optimal ruminal pH and increased nutrient degradability, followed by ammonia nitrogen concentrations (P < 0.05), which were enhanced by dominant cellulolytic bacteria, particularly Ruminococcus albus and Ruminococcus flavefaciens, which showed the highest growth rates in the rumen ecology. Therefore, mHLE, a rich phytonutrient feed additive, affected the methanogen population, reduced the calculated methane production and can be a potential supplement in the ruminant diet.

by Osama A. Mohammed, Mahmoud E. Youssef, Rabab S. Hamad, Mustafa Ahmed Abdel-Reheim, Lobna A. Saleh, Mohannad Mohammad S. Alamri, Muffarah Hamid Alharthi, Jaber Alfaifi, Masoud I. E. Adam, Ali M. S. Eleragi, Ahmed Senbel, Alshaimaa A. Farrag, Assad Ali Rezigalla, Hend S. El-wakeel, Mohammed A. Attia, Hussein M. El-Husseiny, Tohada M. AL-Noshokaty, Ahmed S. Doghish, Ahmed Gaafar Ahmed Gaafar, Sameh Saber The development of new drugs for the inhibition of hepatocellular carcinoma (HCC) development and progression is a critical and urgent need. The median survival rate for HCC patients remains disappointingly low. Vinpocetine is a safe nootropic agent that is often used to enhance cognitive function. The impact of vinpocetine on HCC development and progression has not been fully explored. Our main objective was to investigate the possible inhibitory role of vinpocetine in rats exposed to diethylnitrosamine. We observed that vinpocetine increased the survival rate of these rats and improved the ultrastructure of their livers. Additionally, vinpocetine reduced the liver weight index, mitigated liver oxidative stress, and improved liver function. In both in vitro and in vivo settings, vinpocetine demonstrated antiproliferative and apoptotic properties. It downregulated the expression of CCND1 and Ki-67 while exhibiting anti-BCL-2 effects and enhancing the levels of Bax and cleaved caspase-3. Vinpocetine also successfully deactivated NF-κB, STAT3, and HIF-1α, along with their associated transcription proteins, thereby exerting anti-inflammatory and anti-angiogenic role. Furthermore, vinpocetine showed promise in reducing the levels of ICAM-1 and TGF-β1 indicating its potential role in tissue remodeling. These findings strongly suggest that vinpocetine holds promise as a hepatoprotective agent by targeting a range of oncogenic proteins simultaneously. However, further approaches are needed to validate and establish causal links between our observed effects allowing for a more in-depth exploration of the mechanisms underlying vinpocetine’s effects and identifying pivotal determinants of outcomes.

New England Journal of Medicine, Volume 391, Issue 17, Page 1663-1663, October 31, 2024.

New England Journal of Medicine, Volume 391, Issue 17, Page 1658-1660, October 31, 2024.

New England Journal of Medicine, Volume 391, Issue 17, Page 1662-1663, October 31, 2024.

New England Journal of Medicine, Volume 391, Issue 17, Page 1632-1632, October 31, 2024.

New England Journal of Medicine, Volume 391, Issue 17, Page 1648-1650, October 31, 2024.

New England Journal of Medicine, Ahead of Print.

Infection and Immunity, Ahead of Print.

Abstract Background Since 2015, malaria vector control on Bioko Island has relied heavily upon long-lasting insecticidal nets (LLIN) to complement other interventions. Despite significant resources utilised, however, achieving and maintaining high coverage has been elusive. Here, core LLIN indicators were used to assess and redefine distribution strategies. Methods LLIN indicators were estimated for Bioko Island between 2015 and 2022 using a 1x1 km grid of areas. The way these indicators interacted was used to critically assess coverage targets. Particular attention was paid to spatial heterogeneity and to differences between urban Malabo, the capital, and the rural periphery. Results LLIN coverage according to all indicators varied substantially across areas, decreased significantly soon after mass distribution campaigns (MDC) and, with few exceptions, remained consistently below the recommended target. Use was strongly correlated with population access, particularly in Malabo. After a change in strategy in Malabo from MDC to fixed distribution points, use-to-access showed significant improvement, indicating those who obtained their nets from these sources were more likely to keep them and use them. Moreover, their use rates were significantly higher than those of whom sourced their nets elsewhere. Conclusions Striking a better balance between LLIN distribution efficiency and coverage represents a major challenge as LLIN retention and use rates remain low despite high access resulting from MDC. The cost-benefit of fixed distribution points in Malabo revealed significant advantages, offering a viable alternative for ensuring access to LLINs to those who use them. …

Antimicrobial Agents and Chemotherapy, Ahead of Print.

Abstract Background/Objective Information about occurrence and affected groups of symptoms/diagnoses indicative of an HIV infection (so-called HIV indicator conditions; HIV-ICs) is lacking. We analyse HIV-IC incidence, transmission risks and immune status among people living with HIV (PLWH) antiretroviral therapy (ART) naive. Methods Diagnoses reported for ART-naive PLWH from two multicentre observational, prospective cohort studies between 1999–2023 were analysed. Incidence rates per 1,000 person-years (PYs) were calculated for the overall study period and time periods defined by ART treatment recommendations. For further description, CD4 counts around HIV-IC diagnosis (+ -30 days) and HIV-transmission routes were collected. Results In total 15,940 diagnoses of 18,534 PLWH in Germany were included. Of those 81% were male (median age: 36 years) and 56% reported being men, who have sex with men as the likely HIV-transmission route. Incidence rates varied between the different HIV-ICs. Syphilis had the highest incidence rate (34 per 1,000 PYs; 95% confidence interval [CI] 29–40) for sexually transmitted infections (STIs), hepatitis B was highest for viral hepatitis diagnoses (18 per 1,000 PYs; 95% CI 17–20); according to CDC-classification herpes zoster for HIV-associated diagnoses (22 per 1,000; 95% CI 20–24) and candidiasis for AIDS-defining diagnoses (30 per 1,000 PYs; 95% CI 29–32). Most PLWH with HIV-ICs (hepatitis, HIV-associated diagnoses and AIDS-defining conditions) had CD4 cell counts 

Abstract Purpose C-reactive protein (CRP) is a common proxy of inflammation, but accurate characterizations of its dynamics during acute infections are scant. The goal of this study was to examine C-reactive protein (CRP) trajectories in hospitalized patients with viral infections, confirmed bacteremia (stratified by Gram-negative or Gram-positive bacteria), and non-bacteremic infections/inflammations, considering antibiotic treatment. Methods Electronic medical records from Tel Aviv Sourasky Medical Center (July 2007-May 2023) were analyzed. Patients with blood cultures or positive viral tests were included. CRP levels were modeled using generalized additive mixed-effects models (GAMMs) and observed up to 150 h after initial infection diagnosis. Patients with initial CRP levels > 31.9 were excluded, to remove individuals already in a highly active inflammatory process. The shapes of the CRP curves were characterized and peak CRP as well as area under the CRP curve were the primary variables of interest. Results Viral infections had the lowest and flattest CRP curves. Non-bacteremic infections showed intermediate levels, while bacteremia (especially Gram-negative under antibiotic treatment) had the highest CRP peaks. For instance, peak CRP ranged from 15.4 mg/L in viral infections without antibiotics to 140.9 mg/L in Gram-negative bacteremia with antibiotics. Conclusions CRP trajectories significantly differ based on infection type and antibiotic treatment. Frequent CRP measurement could be a valuable diagnostic and risk stratification tool in hospitalized patients. …

ObjectivesThe use of awake extracorporeal membrane oxygenation (ECMO, without intubation or sedation under ECMO support in patients with cardiogenic shock is growing rapidly because emerging clinical investigations indicates it may reduce morbidity associated with sedation and intubation. We systematically reviewed the efficacy of awake ECMO and provided evidence for clinical practitioners and researchers. DesignSystematic review and trial sequential meta-analysis based on observational studies. Data sourcesData was retrieved from seven databases (PubMed, Web of Science, Embase, China National Knowledge Infrastructure, Wanfang, Chinese Biomedical Literature Database and Cochrane Library) up to 1 March 2024. Eligibility criteriaWe included observational studies that compared the differences in clinical outcomes between awake ECMO and non-awake ECMO in patients with cardiogenic shock. Data extraction and synthesisTwo reviewers rigorously conducted literature retrieval, screening and data extraction. The RevMan software was used for data synthesis. ResultsFive retrospective observational studies involving 1044 patients with cardiogenic shock were included. Compared with non-awake ECMO, awake ECMO was associated with a lower mortality rate of patients with cardiogenic shock (OR=0.28; 95% CI, (0.15, 0.49); p

BackgroundIn South Africa, women disproportionately bear the burden of intimate partner violence (IPV), HIV or AIDS, and poor mental health. ObjectiveThis study investigated parenting practices among women affected by IPV, HIV and poor mental health syndemics. Study settingThe study was conducted in two sites, a peri-urban area and a rural area in Mpumalanga, South Africa. Study designA qualitative research design using a narrative approach with in-depth interviews supported by arts-based methods was used. Data were analysed thematically using MAXQDA (2022). Participants20 women aged 20–60 who screened positive for HIV, IPV and/or poor mental health in a larger three-generational cohort study were selected. ResultsLiving with the syndemics exacerbated socioeconomic challenges that often translated into an inability to meet basic child needs. Socioeconomic challenges also led to more harsh parenting practices among women living with IPV-Mental Health and HIV-Mental Health syndemics. Due to lack of trust from family members, women living with the HIV-Mental Health-IPV syndemic were often separated from their children. These women exhibited less harsh parenting practices than the women in the other syndemic groups when they did see their children. A history of childhood trauma, leading to overprotective parenting, was common across the groups except for the IPV-Mental Health group. Women in the IPV-Mental Health group often had strained relations with their children’s fathers, affecting their engagement and connection with their children. ConclusionThe study underlines challenges experienced by women with IPV-Mental Health, HIV-Mental Health and HIV-Mental Health-IPV syndemics. The overlap of these epidemics strains women’s relationships and affects women’s parenting practices detrimentally resulting in an inadequate provision for children’s needs. …

IntroductionLinezolid is a broadly used antibiotic to treat complicated infections caused by gram-positive bacteria. Therapeutic drug monitoring of linezolid concentrations is recommended to maximise its efficacy and safety, mainly haematological toxicity. Different pharmacokinetic/pharmacodynamic targets have been proposed to improve linezolid exposure: the ratio of the area under the concentration–time curve during a 24-hour period to minimum inhibitory concentration (MIC) between 80 and 120; percentage of time that the drug concentration remains above the MIC during a dosing interval greater than 85% and the trough concentration between 2 and 7 mg/L. This clinical trial aims to evaluate the safety, efficacy and the clinical and economic utility of personalised dosing of linezolid using Bayesian forecasting methods to attain pharmacokinetic/pharmacodynamic targets, known as model-informed precision dosing. Methods and analysisThis is a pragmatic, multicentre, randomised, parallel, controlled, phase IV and low intervention trial. Participants will be randomly assigned 1:1 to each group (n=346 per group). Control group will receive the standard dose of linezolid. Intervention group will receive personalised dosage of linezolid based on pharmacokinetic–pharmacodynamic adjustments. The primary outcome will be the incidence of thrombocytopenia in both groups. Ethics and disseminationThis protocol was approved by the Ethical Committee of the Investigation with Medicines of Galicia (code 2022/140) and authorised by the Spanish Agency for Medicines and Medical Devices. The trial is implemented in accordance with the Declaration of Helsinki and the international ethical and scientific quality standard, the Good Clinical Practice. The results will be published in peer-reviewed journals. Trial registration numberEudraCT registration code: 2022-000144-30. …

ObjectivesInternational guidelines recommend cervical screening cessation at age 50 following two consecutive negative screens. However, many women aged 50 and older in low-income and middle-income countries (LMICs) have not had prior opportunity to screen. We examine the prevalence of cervical dysplasia and cervical cancer stage in Botswana women aged 50+ compared with 30–49, stratified by HIV status. DesignSecondary analysis of data from two prospective cohort studies. SettingThe screening cohort was recruited at health facilities in South East District. The cancer cohort was recruited from the primary public tertiary referral hospital and a private hospital in Gaborone, Botswana. ParticipantsThe screening cohort included 2570 women aged 30 and older recruited from February 2021 to August 2022. Screening eligibility included anyone with a cervix and without a prior history of cervical cancer. The cancer cohort included 1520 patients diagnosed with cervical cancer who sought care at the facilities where recruitment took place from January 2015 to December 2022. Primary and secondary outcome measuresThe prevalence of cervical intraepithelial neoplasia (CIN)2+ and cancer stage at diagnosis was compared across age groups, stratified by HIV status. Prevalence ratios were calculated for the association between age and CIN2+/CIN3+via log-binomial regression. ResultsThe prevalence of CIN2+ was similar between 30–49 years old and 50+, both among women with HIV (WWH, 15.9% and 19.3%, respectively) and without HIV (13.3% and 10.4%, respectively). Similar findings were found when CIN3+ was used as the outcome. There were no statistically significant differences in prevalence ratios (PRs) across age groups for CIN2+ (adjusted PR (aPR) WWH 1.1 (95% CI 0.80 to 1.6); aPR HIV– 0.78 (95% CI 0.45 to 1.4) nor CIN3+ (aPR WWH 1.1 (95% CI 0.70 to 1.6); aPR HIV– 0.81 (95% CI 0.40 to 1.7)). Nearly half of cervical cancer diagnoses were made in women 50+; three-quarters of cases in women without HIV were diagnosed at 50+ years. ConclusionsOur findings demonstrate the prevalence of high-grade cervical dysplasia and cervical cancer remains high beyond age 50 in both women with and without HIV in an LMIC context with high HIV prevalence. Screening women 50+ will allow treatment for cervical dysplasia and may provide early diagnosis of curable cervical cancer. These findings support the rapid introduction of high-performance cervical screening to increase access for women 50+. Trial registration number NCT04242823. …

ObjectivesThis study aimed to investigate the knowledge, attitude and practice (KAP) towards chemotherapy-related neutropenia and febrile neutropenia (FN) among breast cancer patients. The major hypothesis was that demographic characteristics influence patients’ KAP regarding chemotherapy-related neutropenia and FN. DesignA multi-centre cross-sectional study. SettingConducted in four secondary care hospitals between April and June 2023. ParticipantsThe study enrolled 246 breast cancer patients undergoing chemotherapy. Participants were aged 18 years or older, currently on chemotherapy and willing to complete the questionnaire. Exclusion criteria included significant cognitive impairments. Primary and secondary outcome measuresPrimary outcome measures were KAP scores regarding chemotherapy-related neutropenia and FN. Secondary outcomes included factors associated with adequate knowledge and positive attitudes. ResultsA total of 246 patients completed the questionnaire. The mean knowledge score was 12.46±6.21 (range: 0–26), and the mean attitude score was 30.00±2.58 (range: 7–35). Less than half of the patients (45.95%) knew whether their chemotherapy protocol was high risk for FN, while 79.67% were aware of the need for prophylactic administration of leukocyte-raising agents. Multivariate logistic regression analysis revealed that having a junior college education or higher was significantly associated with knowledge scores (OR=4.69, 95% CI 2.23 to 9.89, p

ObjectiveTo evaluate the prevalence, resistance and risk factors of community-onset urinary tract infections (COUTIs) caused by extended-spectrum β-lactamase-producing Escherichia coli (ESBL-EC) for providing a basis for the selection of clinical therapeutic agents. DesignA retrospective case–control study. SettingThe Affiliated Dazu Hospital of Chongqing Medical University (also known as The People’s Hospital of Dazu Chongqing), a 1000-bed tertiary hospital in China. Data and participantsThis study encompassed adult patients diagnosed with community-acquired urinary tract infections (UTIs) caused by E. coli between May 2017 and December 2022 with exclusion criteria including incomplete clinical data, disagreement to participate in the study, hospitalisation duration exceeding 48 hours prior to confirmation of diagnosis and prior history of urinary tract infection caused by E. coli. Outcome measuresThe risk factors for COUTIs caused by ESBL-EC were evaluated using a case–control design, defining patients who were diagnosed with UTIs and had an ESBL-positive urine culture as the case group and patients who were diagnosed with UTIs and had an ESBL-negative urine culture as the control group. Perform drug susceptibility testing and resistance analysis on isolated ESBL-EC. ResultsIn total, 394 cases of COUTIs caused by E. coli were included; 192 cases were ESBL-positive with a detection rate of 48.7% (192/394). Parenchymal tumour, history of urolithiasis stone fragmentation, history of urological surgery, hospitalisation within 6 months, indwelling catheter outside the hospital and antibiotic use (mainly third-generation cephalosporins) were the factors significantly associated with COUTIs caused by ESBL-EC (p

ObjectiveTo assess the knowledge and acceptability of the human papillomavirus (HPV) vaccine and the associated factors among adolescent girls in public primary schools in Dessie Town, South Wollo, Northeast Ethiopia in 2020. Design, participants and methodsThis was an institutional cross-sectional study conducted from 1 November to 30 November 2020 among 844 adolescent girls. A systematic random sampling method was used to select participants, who completed a pretested, self-administered questionnaire. Data were entered into EpiData V.4.6 and exported to SPSS V.25 for analysis. A binary logistic regression model identified the contributing factors to HPV vaccine knowledge and acceptance. Adjusted OR (AOR) and 95% CI computed at p