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Globally, breast cancer is the most common cancer among women, with 2.3 million women newly diagnosed in 2020. In Africa, most women present with advanced disease necessitating nurse-led palliative care interventions. This study pilot tested a nurse-led palliative care programme for women receiving palliative chemotherapy for breast cancer at a teaching hospital in the Volta Region of Ghana. An intervention design and pre-test post-test approach was used. The primary outcome focused on unmet palliative care needs and secondary outcomes included pain, quality of life, and spiritual needs, measured by means of the Symptoms Distress Scale (SDC), Brief Pain Inventory (BPI), Spiritual Needs Questionnaire (SpNQ), and European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire - Breast Cancer Module 45 items (EORTC QLQ-BR45). Census sampling entered 31 women in the programme but only 24 completed it. Descriptive statistics were used to analyzed the data and the Wilcoxon signed-rank test, with significance set at p ≤ 0.05, compared the medians of the two samples. The study was registered with Pan African Clinical Trial Registry (PACTR202509735988120) on September 29th, 2025. Results showed positive outcomes post-intervention. Symptom distress decreased from x̄ 2.98 to x̄ 1.97, pain severity reduced from x̄ 9.34 to x̄ 2.75, and quality of life improved from x̄ 2.79 to x̄ 1.94. Spiritual needs increased from x̄ 1.04 to x̄ 3.00. The study provided evidence that a nurse-led palliative care programme, based on the care needs of women with advanced breast cancer receiving palliative chemotherapy in the Volta Region of Ghana, lessened symptom distress, pain and improved quality of life.
Low and high body mass index (BMI) are reported to be associated with frailty in older adults. Since the optimal BMI associated with a low risk of mortality varies with age, the association between BMI and frailty might also differ by age. This study examined the association between BMI and frailty in middle-aged and older adults in Japan. We conducted face-to-face and mail surveys in Settsu city and mail survey in Hannan city in Osaka, Japan. The association between BMI and frailty was analyzed among 8,815 participants using mail surveys. Frailty was evaluated using two tools, the Kihon Checklist (KCL) and the Frailty Screening Index (FSI). BMI (kg/m2) was categorized into the < 18.5, ≥ 18.5–<20.0, ≥ 20–<22.5, ≥ 22.5–<25.0, ≥ 25.0–<27.5, and ≥ 27.5 kg/m2 groups. We analyzed the association between BMI and frailty using multivariable logistic regression, with BMI ≥ 22.5–<25.0 kg/m2 as the reference to calculate the odds ratios (OR) and 95% confidence intervals (95%CI). Restricted cubic spline analyses were also performed, with knots placed at the 5th, 50th (as reference), and 95th percentiles of BMI. We performed all analyses separately for the < 65 and ≥ 65 years age groups. BMI < 18.5 (OR = 1.882, 95%CI: 1.263–2.805) was significantly associated with KCL-measured frailty in individuals aged < 65 years, and BMI < 18.5 (OR = 1.807, 95%CI: 1.291–2.531) and ≥ 27.5 (OR = 1.562, 95%CI: 1.156–2.111) were significantly associated with KCL-measured frailty in those aged ≥ 65 years. BMI ≥ 25.0–<27.5 (OR = 1.426, 95%CI: 1.055–1.927) and ≥ 27.5 (OR = 1.473, 95%CI: 1.093–1.985) were significantly associated with FSI-measured frailty in individuals aged < 65 years, and BMI ≥ 27.5 (OR = 1.988, 95%CI: 1.432–2.759) was significantly associated with frailty in those aged ≥ 65 years. The spline models showed U-shaped associations for KCL-measured frailty for both age groups, a positive linear association for FSI-measured frailty among those aged < 65 years, and an L-shaped association for FSI-measured frailty among those aged ≥ 65 years. The association between BMI and frailty differed by age. The collation of all the results of this study suggests that both low and high BMI are associated with frailty in middle-aged and older adults. Based on the results, it is speculated lifestyle habits that promote proximity to “normal weight” may help prevent frailty. UMIN000008105 (Registration date: May 29th 2019; Website: https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000042027). The online version contains supplementary material available at 10.1186/s12889-026-27331-2.
Syrian refugees across diverse host countries, including high-income European countries, face increased mental health needs. Digital interventions can scale support, but global scalability limits human guidance and contextual adaptations. We evaluated the effectiveness of a potentially scalable digital intervention (Step-by-Step; SbS) with minimal contact-on-demand (COD) in reducing psychological distress and functional impairment among Syrian refugees in Germany and Sweden. These trials were conducted in parallel with SbS studies in Egypt and Lebanon, using the same content to test broader contextual applicability without further adaptations. Separate two-arm pragmatic RCTs were conducted in Germany (N = 559) and Sweden (N = 184) with Syrians screening positive for elevated distress (K10 > 15) and impaired functioning (WHODAS 2.0 > 16). Participants were randomized to SbS (five sessions) + care-as-usual (CAU) or CAU-only. Primary outcomes were psychological distress (HSCL-25) and functioning (WHODAS 2.0) at 3-month follow-up. Secondary outcomes were PTSD symptoms (PCL-5 short) and self-defined problems (PSYCHLOPS). Intention-to-treat (ITT) analyses were run separately by trial. Exploratory per-protocol analyses combined datasets. ITT analyses showed no statistically significant time × condition effects for any primary or secondary outcome in both trials. Dropout was high (Germany: 86.3%; Sweden: 82.1%). In per-protocol analyses (participants completing ≥ 4 of 5 sessions), the SbS + CAU arm showed significantly lower standardized mean scores at 3 months for psychological distress (HSCL-25; Hedges' g = 0.31; p = .03) and PTSD symptoms (PCL-5 short; Hedges' g = 0.27; p < .05). COD use was low (Germany: 15.1%; Sweden: 8.4%), leaving the intervention effectively unguided for most participants. While limiting guidance and contextual tailoring can enhance scalability across borders, digital interventions may struggle with engagement, adherence, and contextual relevance. In high-income settings, an unguided approach for refugees may not work, showing that prioritizing scalability could potentially compromise clinical impact in this population. Some level of human guidance may be necessary to balance scalability and effectiveness, and it remains unclear how minimal that guidance can be without compromising outcomes. German Register for Clinical Studies (Germany: DRKS00022143-registered June 29th, 2020, and Sweden: DRKS00022144-registered July 1st, 2020).
Mycoplasma pneumoniae (MP) has re-emerged with a surging incidence in China following the lifting of COVID-19 non-pharmaceutical interventions, posing a critical challenge for clinical diagnosis and management of acute respiratory infections (ARI). We aimed to investigate the epidemiological characteristics of MP infection among all-age patients with ARI in China, as well as the temporal dynamics of serum MP-specific antibodies. This retrospective study was based on the data of patients detected by total MP antibodies (predominantly IgM) in Chinese PLA General Hospital, Beijing, China between December 2022 and January 2024. Blood samples were collected from patients who visited or were hospitalized due to ARI for the detection of MP antibody. Adjusted odds ratio (aOR) and its 95% confidence interval (CI) were calculated to evaluate the association between MP antibody and outcome using logistic regression models adjusted by age groups, sex and diagnosis. Totally 18,054 patients were included in this study with the MP antibody detection rate of 36.2% (95% CI 35.5%-36.9%). The detection rate of MP antibody was higher in female than that in male (40.5% vs. 32.4%, aOR = 1.493, 95% CI 1.402-1.590, P < 0.001) and it was lower in adults compared to children (26.8% vs. 46.7%, aOR = 0.403, 95% CI 0.378-0.429, P < 0.001). The detection rate of MP antibody was the highest in the group of 10 ~ 20 years (53.7%, 95% CI 52.0%-55.4%). In all patients, the detection rate of MP antibody peaked at the 3rd week with 94.4% (95% CI 91.9%-95.0%), and then went down gradually, falling to 89.5% (95% CI 83.8%-95.1%) at the 8th week. The MP antibody peaked at the 1st week after symptom onset, followed by a gradual decline, and was predicted to turn to negative at about the 29th week. In children aged < 18 years, the interval between symptom onset and the MP antibody turning negative was about 24 weeks while it was 59 weeks in adults aged 18 ~ 59 years and 18 weeks in those aged ≥ 60 years. The detection rate of MP antibody differed in the patients with different characteristics. MP antibody could persist for 29 weeks and age was a significant factor affecting the duration of MP antibody. The lack of population representativeness and other relevant variables may have some impact on the results, but these findings still provided new evidence for the understanding of the epidemiology and immunology MP.
Existing mobilisation literature has largely focused on groups and collective sensemaking processes as the primary drivers of collective action. However, online influencers have emerged as key leaders and mobilisers, which can shape collective action through one-to-many communication. Using self-categorisation theory, we examine indirect mobilisation and the legitimation of violence during the August 2024 UK riots through a case study of a far-right influencer's Telegram channel. The dataset consists of 230 posts and 156 pieces of multimedia content from the Tommy Robinson News Telegram channel from 29th July to 7th August 2024. We employed an abductive thematic analysis approach, revealing how throughout the progression of the riots, posts in the Telegram channel construct group identities, establish epistemic authority and leadership legitimacy, and legitimise violence. Our findings extend the social identity approach of mobilisation into the digital realm, revealing how broadcast-style, unidirectional affordances of Telegram channels can impact the dynamics of leadership, identity construction and mobilisation of (violent) collective action.
With microbes critical for ocean ecological and biogeochemical processes, we need to understand their abundance and diversity distributions. While traditional amplicon sequencing provides only relative abundance data, and the strongly preferred absolute abundances can be determined from samples spiked with internal standards, few oceanographic studies with absolute abundances exist. However, many have flow cytometry (FCM) data that should allow us to retrospectively "anchor" the relative abundances into absolute abundances. We tested this hypothesis with data from the 29th Atlantic Meridional Transect (AMT29) cruise where we had FCM of Synechococcus and Prochlorococcus, amplicons corrected with internal standards, and absolute cell count estimates from single copy recA and radA metagenomics. Anchoring the AMT29 amplicon data with Synechococcus FCM (used because phycoerythrin in Synechococcus is reliably detected by FCM in surface waters) yielded results strongly correlated with amplicon data corrected with internal standards (Pearson's r = 0.94, slope = 0.73), FCM (r = 0.80, slope = 0.43), and recA-based genome counts (Pearson's r = 0.94, slope = 0.62). Seeing this method worked reasonably well, we then generated estimates of absolute rRNA gene abundances from the Global rRNA Universal Metabarcoding of Plankton (GRUMP) transects that had FCM data (Pacific ~65 N to ~40S). These FCM-anchored gene copy estimates also showed strong correlations to FCM data (i.e. anchor with Synechococcus and predict Prochlorococcus), with r values ranging from 0.48-0.86. While the results are clearly only reasonable estimates, we believe the approach has the potential to significantly enhance the value of amplicon data which have accompanying FCM data.
Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are increasingly used for weight loss and may therefore have a role in preoperative optimisation for arthroplasty candidates. However, their effect on arthroplasty outcomes remains unclear. This systematic review aims to evaluate existing evidence on preoperative GLP-1 RA use and postoperative outcomes following joint arthroplasty, and to identify priorities for future research and perioperative optimisation. A systematic literature search of PubMed, Embase, ClinicalTrials.gov and the Cochrane Library was conducted for articles published from inception to 29th July 2025, using terms related to GLP-1 RAs and arthroplasty, in accordance with the PRISMA 2020 guidelines. Studies were included if they assessed postoperative outcomes in adult patients undergoing arthroplasty with documented preoperative GLP-1 RA use. Data were extracted on study design, participant characteristics, GLP-1 RA use, arthroplasty procedure, outcome measures, duration of follow-up, and key results. Fifteen retrospective studies met the inclusion criteria, comprising a total of 39,355 patients undergoing hip, knee or shoulder arthroplasty. Nine studies reported more favourable postoperative outcomes among GLP-1 RA users, three showed mixed results, two predominantly reported worse outcomes, and one found no significant difference. The most frequently reported favourable associations were lower periprosthetic joint infection and hospital readmission rates following hip and knee arthroplasty, particularly among individuals with diabetes or morbid obesity, although results were not uniform across studies. In contrast, evidence relating to shoulder arthroplasty outcomes was limited and showed greater variability. Preoperative GLP-1 RA use has been associated with lower rates of periprosthetic joint infection and readmission in several retrospective database studies, particularly in diabetic and morbidly obese arthroplasty populations; however, the overall certainty of evidence is low due to non-randomised designs, heterogeneity and risk of bias. These findings should be considered hypothesis-generating, and well-designed prospective studies and randomised controlled trials are required to establish the role of GLP-1 RAs in preoperative optimisation.
Climate change is increasing children’s exposure to heat and, consequently, their risk of dehydration during their primary school years. Yet hydration education is not consistently embedded in education policy or primary curricula. This systematic review, reported in accordance with PRISMA 2020, examined school-based educational practices designed to promote healthy hydration in Primary Education (6 to 12 years). A search was conducted in the Web of Science Core Collection on January 29th, 2025 for studies published between 2015 and 2024. Two reviewers independently screened records and assessed risk of bias using design-appropriate tools (RoB 2, ROBINS-I, and JBI checklists). Given the substantial heterogeneity in intervention components and outcome indicators, a narrative synthesis was performed. Twelve studies were included, spanning randomized and non-randomized interventions and observational and qualitative or documentary designs across diverse school contexts. Overall, multi-component approaches, particularly those combining improved access to drinking water with classroom-based educational activities and routine supports, were associated with increased water intake, and when measured, improved physiological hydration indicators. Evidence for broader outcomes, including cognitive or academic measures and sustainability-related awareness, was mixed and dependent on the outcome assessed. Risk of bias ranged from low to high; common limitations included reliance on self-reported intake, short intervention duration, limited control for confounding in non-randomized designs, and scarce medium- to long-term follow-up. Future research should prioritize standardized and validated hydration measures, clearer specification of educational strategies, including teacher roles and competencies, and longer follow-up to strengthen the evidence base under climate-related heat risks. The online version contains supplementary material available at 10.1186/s12887-026-06773-y.
Enclosure space constitutes the fundamental habitat for captive animals, directly influencing domestication success and production performance. Alpine musk deer (Moschus chrysogaster), an endangered ungulate present on the Tibet plateau and surrounding areas, has been commonly farmed in captivity as an essential strategy for the ex situ conservation and sustainable musk production. In captive musk deer farming, understanding spatial selection patterns within enclosures is critical for improving farming practices. To evaluate patterns of space use under captive conditions and the effect of enclosure designing, we studied 70 captive Alpine musk deer housed in 17 enclosures at the Zhuanglang Musk Deer Breeding Farm (Gansu, China) during the summer of 2022 (from July 1st to August 29th). Focal sampling and all-occurrence recording were adopted to collect the behavioral data of the musk deer, and the point occupancy rate was calculated to analyze the enclosure space utilization patterns. The results showed significant differences in activity site selection and shelter use time among captive musk deer (p < 0.05). The central enclosure site (G5), which contains the shelter, exhibited the highest utilization rate (21.21 ± 9.19%). Shelter use was significantly higher in adults (22.09 ± 7.80%) than in subadults (17.27 ± 3.98%) (p < 0.05), and significantly higher in males (29.55 ± 5.65%) than in females (20.86 ± 7.95%) (p < 0.05). However, at equal population density, the shelter use time between all-male and mixed-sex groups was not significant (p > 0.05). These results reveal that captive Alpine musk deer display distinct shelter use patterns, with shelters acting as key spatial resources. Therefore, this study provides practical implications for optimizing enclosure design (e.g., increasing shelter quantity and improving spatial distribution) to enhance the welfare and productivity of captive Alpine musk deer.
Objective: To explore the regulatory effect of the phosphatidylinositol 3-kinase (PI3K) /protein kinase B (AKT) /hypoxia-inducible factor 1α (HIF-1α) glycolysis signaling pathway on urinary metabolites during the progression of silicosis fibrosis and its related metabolic pathway mechanisms. Methods: From March to June 2023, 36 SPF-grade C57BL/6 mice were randomly divided into the control group, the silica (SiO(2)) model group, the PI3K inhibitor LY294002 early/late intervention group, and the HIF-1α inhibitor 2-methoxyestradiol (2-ME2) early/late intervention group, totaling 6 groups, with 6 mice in each group. The silicosis mice model was established by tracheal instillation 50 μl of 200 mg/ml SiO(2) suspension. Corresponding intervention agents were intraperitoneally injected on the 2nd day (early stage) and on the 29th day (late stage) after dust exposure, and the intervention was carried out continuously for 55 d and 28 d respectively. On the 56th day of the experiment, the mice were sacrificed and the lung tissues were subjected to pathological examination. Non-targeted metabolomics analysis of urine was conducted using ultra-performance liquid chromatography-tandem mass spectrometry. Principal component analysis (PCA) and orthogonal partial least squares-discriminant analysis (OPLS-DA) were used to screen out the differential metabolites, and metabolic pathway enrichment analysis was performed. Results: Mice in the SiO(2) model group exhibited dull fur coloration, reduced activity, diffuse pulmonary fibrosis, alveolar structural damage, and extensive inflammatory cell infiltration after dust exposure. All intervention groups showed significantly improved general condition compared to the SiO(2) model group, with markedly reduced pulmonary fibrosis severity. Early intervention groups demonstrated superior pathological improvement outcomes compared to the late intervention groups. Metabolomics analysis revealed that PCA and OPLS-DA of urine samples demonstrated significant differences in metabolic profiles between the control group and SiO(2) model group. A total of 13 differential metabolites were identified, involving two core metabolic pathways: sphingolipid metabolism and riboflavin metabolism. All intervention groups exhibited a trend of metabolic profiling regression toward the control group, with 5-10 differential metabolites screened out, capable of reversing 2-4 core abnormal metabolite levels. Post-intervention differential metabolites were primarily enriched in four metabolic pathways: sphingolipid metabolism, riboflavin metabolism, unsaturated fatty acid biosynthesis, and linoleic acid metabolism (P<0.05) . Conclusion: This study demonstrates that silicosis development is closely associated with dysregulation of sphingolipid and riboflavin metabolic pathways. Targeted interventions can mitigate pulmonary fibrosis damage by restoring core metabolite levels. The PI3K/Akt/HIF-1α signaling pathway may serve as a key mechanism regulating these metabolic abnormalities, providing an experimental foundation for early intervention and metabolic biomarker screening in pneumoconiosis. 目的: 探讨磷脂酰肌醇3-激酶/蛋白激酶B/缺氧诱导因子1α(PI3K/AKT/HIF-1α)糖酵解信号通路在矽肺纤维化进程中对尿液代谢物的调控作用及其相关代谢通路机制。 方法: 于2023年3至6月,将36只SPF级C57BL/6小鼠随机分为对照组、二氧化硅(SiO(2))模型组、PI3K抑制剂LY294002早期/晚期干预组、HIF-1α抑制剂2-甲氧基雌二醇(2-ME2)早期/晚期干预组,共6组,每组6只。采用气管灌注50 μl 200 mg/ml SiO(2)悬浊液建立矽肺小鼠模型,分别于染尘第1天(早期)、第29天(晚期)腹腔注射对应干预剂,分别连续干预55、28 d。实验第56天处死小鼠,行肺组织病理学观察,采用超高效液相色谱-串联质谱技术开展尿液非靶向代谢组学分析,通过主成分分析(PCQ)、正交偏最小二乘判别分析OPLS-DA筛选差异代谢物,并进行代谢通路富集分析。 结果: 染尘后SiO(2)模型组小鼠毛色暗淡、活动减少,肺组织呈现弥漫性纤维增生、肺泡结构破坏及广泛炎症细胞浸润;各干预组小鼠一般状态较SiO(2)模型组明显改善,肺纤维化程度明显减轻,早期干预组病理改善效果优于晚期干预组。代谢组学分析发现,尿液样本PCA与OPLS-DA显示,对照组与SiO(2)模型组代谢轮廓存在明显差异,共筛选出13个差异代谢物,涉及鞘脂类代谢、核黄素代谢2条核心通路;各干预组代谢谱均呈现向对照组回调趋势,分别筛选出5~10个差异代谢物,可逆转2~4种核心异常代谢物水平,干预后的差异代谢物主要富集于鞘脂类代谢、核黄素代谢、不饱和脂肪酸生物合成、亚油酸代谢4条通路(P<0.05)。 结论: 本研究显示矽肺发生与鞘脂、核黄素代谢通路紊乱密切相关,靶向干预可通过回调核心代谢物水平减轻肺纤维化损伤,PI3K/Akt/HIF-1α信号通路可能是调控上述代谢异常的关键机制,为尘肺病早期干预及代谢标志物筛选提供了实验基础。.
This study aimed to explore pharmacists' attitudes, beliefs, and perceptions regarding the supply of Mifepristone and Misoprostol (MS-2 Step), in order to identify potential barriers and enablers to providing this service. A cross-sectional study was conducted between 29th of August 2024 to the 10th of February 2025. Registered community pharmacists were recruited through convenience sampling via direct email to pharmacies and professional social media platforms to complete a 19-item online survey. Data were analysed in SPSS to using descriptive statistics, non-parametric tests, and logistic regression to examine factors associated with willingness to dispense MS-2 Step. Two hundred thirty-four registered community pharmacists were recruited from all states/territories in Australia with the majority working full-time (47.9%) and practicing for 1-5 years (30.8%). The main perceived benefit to the service was increased accessibility to medical abortion for women (69.5%), while a key barrier to the provision of the service was the lack of sufficient training/education for pharmacists (29.5%). Participants also expressed wanting to expand their scope of practice but being restricted by work constraints/pressures. Cultural and religious beliefs were also identified as a barrier to providing the service (26.1%). This study revealed that most pharmacists are willing to provide medical abortion to reduce burden on the healthcare system and increase accessibility. However, they are restricted by lack of training, and conscientious objection as well as religious or moral beliefs.
Anakinra is a recombinant human interleukin-1 receptor antagonist primarily administered by subcutaneous injection for the treatment of autoinflammatory conditions. Intravenous use of anakinra is only sparsely described in the literature. The aim of this study was to assess the safety of intravenous use of anakinra in a cohort of pediatric patients. This is a multicenter, retrospective cohort study. All patients who received intravenous anakinra from January 1st, 2017, to February 29th 2024 were enrolled. Collected data comprised: demographic characteristics, underlying clinical conditions, infusion-related data, anakinra-related adverse events and clinical response. The case series included 113 patients: 64 (56.6%) with underlying rheumatologic diseases, 27 (23.9%) with onco-hematologic diseases, 22 (19.5%) with severe systemic infections. Fifty-nine patients (52.2%) were admitted to intensive care units. The intravenous anakinra dose ranged from 2 to 20 mg/kg/day, and treatment duration ranged from 1 to 80 days. Adverse events were observed in 10 of 113 treated children (8.8%). The most common events were transient elevation of liver or pancreatic enzymes in seven patients (6.2%) and maculopapular rash in two patients (1.2%). One patient (0.9%) experienced an anaphylactoid reaction immediately after the infusion. Sixteen patients (14.2%) died. Among those who died, ten were receiving ongoing anakinra treatment, with a median treatment duration of 27 days (range 2–42), while six patients had discontinued the drug several days earlier. Intravenous administration of anakinra appears to be safe and not associated with severe adverse events. Reported side effects were transient, not life-threatening, and resolved either with specific treatment or after drug discontinuation. Intravenous anakinra may therefore be considered a safe therapeutic option for selected life-threatening acute clinical conditions.
Neonatal mortality remains a significant public health challenge in Ethiopia. Despite efforts to implement key evidence-based interventions, their coverage and utilization remain low. The Saving Little Lives (SLL) program aims to scale-up a Minimum Care Package (MCP) of synergistic, life-saving interventions for all liveborn neonates, with a focus on preterm and low birth weight (LBW) infants, across 290 hospitals in Ethiopia (206 primary, 69 general, and 15 referral hospitals), representing 82% of all hospitals in the country at the time of the study, and evaluate the impact on neonatal mortality. A non-randomized stepped-wedge trial will be conducted to evaluate the impact of implementing the SLL MCP interventions. Quantitative evaluation data will be collected from 36 primary hospitals, selected from 206 primary hospitals across four regions, receiving the interventions. An independent evaluation research assistant will be deployed in each of the hospitals to collect data using Open Data Kit (ODK) through interviewing mothers before discharge, on the 29th day of life if discharged, and reviewing medical records. A mixed-method, cross-sectional formative assessment will be conducted prior to implementation, employing quantitative facility assessment and qualitative interviews with mothers, healthcare providers, and facility managers. This will be followed by continuous program learning assessment once implementation begins. Descriptive data will be presented using numbers, percentages, tables, and graphs. Regression modeling and generalized estimating equations (GEEs) will be used to estimate the impact of the SLL MCP interventions. Qualitative data will be gathered through in-depth interviews, digitally recorded, transcribed, and thematically analyzed using ATLAS.ti Version 7.5 software to assess facility readiness, barriers, and enablers of implementing the SLL MCP interventions. Expected Outcome: We hypothesize that achieving 80% coverage of the SLL MCP interventions among eligible neonates will result in a 35% reduction in neonatal mortality at implementation facilities.
Di (2-ethylhexyl) phthalate (DEHP) is an environmental toxicant which is commonly used as plasticizer in various plastic products. While the nephrotoxic potential of DEHP has been reported, the exact molecular mechanism behind DEHP-induced nephrotoxicity is still unexplored. This study aims to elucidate the specific role of ER stress in DEHP-induced nephrotoxicity and evaluate the targeted therapeutic potential of 4-Phenylbutyric acid (4-PBA), a chemical chaperone known to alleviate ER stress, against this toxicity. 24 Wistar albino rats were randomly divided into 4 groups (n = 6 each). In control group, corn oil was administered orally (p.o.) for 28 days. DEHP toxic group received DEHP (500 mg/kg, p.o., mixed in corn oil) for 28 days. In 4-PBA treatment groups, DEHP was administered for 28 days and afterwards 4-PBA co-treatment (500 mg/kg and 1000 mg/kg, p.o.) for last 14 days (day 15 to day 28) was given. On 29th day, rats were euthanized and blood as well as kidney samples were collected. Mechanistically, DEHP exposure resulted in severe renal dysfunction, evidenced by elevates levels of creatinine, urea, and BUN. At the molecular level, DEHP triggered significant oxido-nitrosative stress and upregulated the protein expression of key ER stress markers GRP78, CHOP, and Caspase 12, correlating with distorted renal histology. Notably, 4-PBA treatment significantly attenuated these biochemical and histological aberrations and downregulated protein expression of GRP78, CHOP, and Caspase 12. Our findings provide novel evidence that ER stress plays a crucial role in the development of DEHP-induced nephrotoxicity and 4-PBA has an ameliorative effect against it.
To identify factors associated with hepatitis A infection in Curitiba, Paraná, Brazil. This is a case-control study with individuals aged ≥16 years, living in Curitiba, Paraná, selected from the municipal laboratory base. We defined as cases individuals with reactive serology for hepatitis A and as controls those with non-reactive serology, from November 1st, 2023 to May 29th, 2024. Data were collected using a self-administered questionnaire. Bivariate analysis was performed followed by hierarchical logistic regression to estimate odds ratio (OR) and respective 95% confidence intervals (95%CI). A total of 242 individuals participated (121 cases and 121 controls). The cases had a higher proportion of males (64.5% vs. 52.5%), Whites (78.5% vs. 63.8%), and men who have sex with men (MSM) (25.6% vs. 12.4%) when compared to controls. In the adjusted multivariate model, hepatitis A infection maintained a significant association with raw fish consumption (aOR 2.54; 95%CI 1.39; 4,64; p-value 0.002) and with MSM (aOR 2.38; 95%CI 1.10; 4,85; p-value 0.027). Not eating out had a protective effect (aOR 0.22; 95%CI 0.08; 0,62; p-value 0.004). In the context of the investigated outbreak, hepatitis A infection was associated with the consumption of raw fish and identification as MSM, while not eating out was a protective factor. These findings indicate the relevance of prevention measures related to both food security and specific population groups, especially in scenarios of urban outbreaks. Identificar los factores asociados a la infección por hepatitis A en Curitiba, Paraná (Brasil). Se trata de un estudio de caso-control con individuos ≥16 años de edad, residentes en Curitiba, Paraná, seleccionados de la base del laboratorio municipal. Definimos como casos a individuos con serología reactiva para hepatitis A y como controles aquellos con serología no reactiva, en el periodo del 1/11/2023 al 29/5/2024. Los datos se recopilaron mediante un cuestionario autoadministrado. Se realizó un análisis bivariado, seguido de una regresión logística jerárquica, para estimar odds ratios (OR) y los respectivos intervalos de confianza del 95% (IC 95%). Participaron 242 individuos (121 casos y 121 controles). Los casos mostraron una mayor proporción de individuos del sexo masculino (64,5% versus 52,5%), blancos (78,5% vs. 63,8%) y de hombres que tienen sexo con hombres (HSH) (25,6% vs. 12,4%) en comparación con los controles. En el modelo multivariado ajustado, la infección por hepatitis A mantuvo una significativa asociación con el consumo de pescado crudo (ORa 2,54; IC 95% 1,39; 4,64; p-valor 0,002) y con ser HSH (ORa 2,38; IC 95% 1,10; 4,85; p-valor 0,027). No comer fuera de casa tuvo un efecto protector (ORa 0,22; IC 95% 0,08; 0,62; p-valor 0,004). En el contexto del brote investigado, la infección por hepatitis A se asoció con el consumo de pescado crudo y con la identificación como HSH, mientras que no comer fuera de casa demostró ser un factor protector. Estos hallazgos indican la relevancia de las medidas de prevención relacionadas tanto con la seguridad alimentaria como con grupos poblacionales específicos, especialmente en escenarios de brotes urbanos.
D-galactose-induced aging is an invincible phenomenon causing neurological disorders like depression, memory impairment etc., In the experiment, 30 male rats were allocated on an arbitrary basis into five groups (n = 6): (i) Water + Water; (ii) Water + D-galactose; (iii) D-galactose + Gallic acid; (iv) D-galactose + ZnO NPs, and (v) D-galactose + ZnO-gallic acid NPs. Each group received its respective treatment intraperitoneally, once daily for 28 days, according to body weight. After the treatment period, on the 29th and 30th days, behavioural tests Forced Swimming test and Morris Water Maze tests were performed for the assessment of depression and memory function, respectively. After that, decapitation was performed on the 31st day, and the rat brains were extracted and stored for biochemical, neurochemical, and histopathological analysis. Results showed that D-galactose-induced depression-like effects and impaired memory. D-galactose induced an increase in oxidative stress and inflammatory markers while decreasing antioxidant enzymes. The activity of AChE also increased by D-galactose administration. Histopathological assessment revealed deteriorative alterations in the brain. All of these behavioral, biochemical, neurochemical, and histopathological alterations caused by D-galactose were regulated by ZnO-gallic acidNPs. It is concluded that ZnO-gallic acidNPs, a nanocomposite, could be a better remedy for aging-related depression and cognitive impairment.
The current study aims to explore the role of endoplasmic reticulum stress (ER stress) in acrylamide (ACR)-induced nephrotoxicity. In addition, the role of ER stress is pharmacologically validated by a chemical chaperone, 4-phenylbutyric acid (4-PBA). In the present study, 24 male Albino Wistar rats (n = 6) were randomly divided into four groups. The control group received normal saline orally (p.o.) for 4 weeks. The acrylamide toxic group received ACR (10 mg/kg, p.o. in normal saline) for 4 weeks. The 4-PBA treatment groups received ACR for 28 days and 4-PBA (500 mg/kg and 1000 mg/kg, p.o. in saline) for the last 14 days. On the 29th day, rats were euthanized, and blood as well as kidney samples were collected. Renal function parameters along with oxido-nitrosative stress biomarkers in kidney were analyzed. Western blotting was used to quantify the protein expression of key ER stress indicators, and finally, histopathological examination was conducted. Findings from the study indicated that ACR markedly increased the levels of kidney function markers, renal oxido-nitrosative stress, upregulated protein expression of ER stress-related proteins and disrupted normal morphology as compared to the control group. However, 4-PBA treatment reduced oxido-nitrosative stress, improved renal functioning, downregulated ER stress-related proteins and recovered the distorted morphology of the rat's kidney. These findings suggest the significant role of ER stress in the progression of ACR-induced nephrotoxicity as well as the ameliorative effect of 4-PBA against ACR-induced nephrotoxicity. Moreover, our findings provide the first evidence that activation of the ER stress pathway plays a critical role in acrylamide-induced nephrotoxicity.
Dengue incidence has increased sharply worldwide, placing nearly half of the global population at risk. In response, various innovative technologies and interventions, including biocontrol strategies that deploy Wolbachia-infected mosquitoes, are being explored. These can be used to either replace the existing mosquito population with one that is less likely to transmit infection or to suppress the existing mosquito population. We conducted a scoping review of economic evaluations of Wolbachia-based interventions for dengue control, aimed at summarising assumptions and results of existing studies. A scoping review of the published literature was conducted on the 29th of April 2024 using the MEDLINE (via OVID), Embase Classic+Embase (via OVID), Global Health - OVID, PubMed, and Econ Lit electronic databases. No date or language restrictions were applied to the searches. We identified nine studies that reported the results of economic evaluations of Wolbachia-based interventions for dengue control. The majority (eight out of nine studies) investigated Wolbachia replacement-based programmes. Overall, the results were supportive for the use of replacement-based programmes in large urban settings, with the intervention likely to generate cost savings from a societal perspective. The available economic evaluations consistently suggest that Wolbachia-based replacement interventions can be cost-effective for dengue control when targeted to densely populated urban areas, and several studies indicate that they can generate substantial long‑term cost savings from a societal perspective. Further research is needed to understand how heterogeneity in epidemiological effectiveness influences long-term projected cost‑effectiveness and to investigate the combination of Wolbachia-based interventions with other dengue control/prevention measures (such as vaccination). To support more robust and comparable analyses, we provide recommendations for future studies in this area, emphasising the importance of reporting results disaggregated by cost and outcome components, and making important underlying assumptions related to the intervention more explicit.
This study aims to quantify the concentration and characterize the morphology of microplastics (MPs) and microbial contaminants in sediment and dust samples from areas affected by the "DANA", an Isolated High-Level Depression or cold drop. The floods caused by the DANA on October 29th, 2024, resulted in significant damage across several regions in eastern Spain, transporting sediments and (emerging)-contaminants to urban, agricultural, and aquatic ecosystems. Samples were collected from the main affected municipalities. MPs were identified using Raman spectroscopy, while microbial contaminants were analyzed through ISO-standard culture methods, plaque assays for coliphages, and RT-qPCR for enteric viruses. The results of this study showed that dust samples contained twice the concentration of MPs per gram compared to sediment samples, primarily composed of polyethylene (PE), polypropylene (PP), polystyrene (PS), polyvinyl chloride (PVC), rubber (SBR) and polyethylene terephthalate (PET). Morphological analysis revealed a prevalence of fragments over fibres and films, with smaller particle sizes in the dust samples, increasing their potential for dispersion and inhalation. The presence of microbial contaminants in dust was low. In contrast, the sediments were identified as key reservoirs of pathogenic microorganisms, including Salmonella spp., Escherichia coli, and human enteric viruses, which may lead to prolonged environmental persistence and increased risks to ecosystems and human health. These results confirm that flood events can redistribute MPs and pathogens differently across sludge and dust, representing a critical pathway for human exposure. These findings underline the urgent need for control and mitigation strategies to limit the environmental dispersal of these contaminants. Given their potential impacts on ecosystems, soil quality, and human health, further research is required to evaluate the long-term consequences of microplastics and associated pollutants in the affected regions.