Genital ulcer disease (GUD), a common clinical presentation at health facilities in Uganda, is often caused by sexually transmitted infections (STIs) and increases the risk of HIV. Family planning (FP) methods are effective for preventing unintended pregnancies, while some methods, namely male and female condoms, also reduce the risk of STI transmission. However, little has been documented about FP use among individuals with GUD in Uganda. Patients with clinician-confirmed genital ulcers were enrolled for a GUD study at six sites across government clinics and community outreaches in Kampala, Wakiso, and Kalangala, Uganda, between July/2023 and June/2024. Demographic, behavioral, and family planning use data were collected in English and Luganda using prespecified questionnaires. Urine and genital swabs were collected for gonorrhea and chlamydia testing and blood for HIV and syphilis antibodies using rapid diagnostic tests (RDT). Pregnant women were excluded from the analysis. Associations with FP use were explored using rank sum tests, chi-square, and Fisher's exact tests as appropriate. Of 104 participants with confirmed genital ulceration, 75(72.1%) were women, 12(16.0%) of whom were pregnant. Overall, of 92 non-pregnant participants, 36(39.1%) had a reactive HIV RDT; 10(27.8%) were new diagnoses. Nine (9.8%) had positive tests for gonorrhea, chlamydia, or syphilis. No men reported condom use. Of the 63 non-pregnant female participants analyzed, 29(46.0%) reported current FP use. Subdermal implants were the most used method in 15/29(51.7%). Twenty-one (33.3%) reported ≥ 2 sexual partners in the past 3 months. FP use was significantly associated with younger age, being married, transactional sex, ≥ 2 sexual partners in the past 3 months, and being sexually active in the past month. More than one-sixth of women with GUD were pregnant. The uptake of FP among individuals with GUD was low, and HIV/STI prevalence was high. Effective FP has a key role in preventing unintended pregnancies and mother-to-child transmission of STIs. These findings highlight the need for educational and policy strategies to increase sensitization on sexual health, including increasing uptake of FP and encouraging male condom use in a population at high risk of STIs.
Fungicides remain the primary approach for preventing and controlling agricultural and forestry fungal diseases. However, the inevitable emergence of antifungal drug resistance in plant pathogenic fungi necessitates novel multi-target fungicides. A series of novel indole-3-pyrimidine hydrazones were designed and synthesized using pharmacophore fusion/fragment hybridization strategies, with ferimzone, PMDD-5Y, melatonin, and chloroinconazide as lead compounds. All synthesized compounds exhibited inhibitory effects against the tested seven agricultural and forestry pathogens. Notably, compound IPH-18 exhibits excellent broad-spectrum activity, with inhibition rates exceeding 90% against Cytospora chrysosperma, Magnaporthe oryzae, and Fusarium graminearum at 50 μg/mL (half-maximal effective concentration (EC50) = 6.98, 6.62, and 8.18 μg/mL, respectively), outperforming the positive control azoxystrobin. In vivo trials revealed that IPH-18 (20 and 50 μg/mL) effectively suppressed Sphaeropsis sapinea infection, demonstrating bioactivity comparable to the commercial fungicide carbendazim. Scanning electron microscopy (SEM) and transmission electron microscopy (TEM) confirmed that IPH-18 disrupts pathogenic fungi by damaging submicro- and ultra-structural components (cell wall and membrane). Quantitative structure-activity relationship (QSAR) modeling further revealed that introducing unsaturated substituents and electronegative atoms significantly enhanced antifungal potency. Molecular docking simulation results demonstrate that compound IPH-18 displays promising multi-target inhibitory activity. The calculated binding energies for glycogen synthase, enoyl-CoA hydratase, glutathione S-transferase, monopolar spindle kinase 1 (Mps-1), and laccase were -8.12, -8.56, -8.05, -7.80, and -7.92 kcal/mol, respectively. The QSAR analysis of 34 novel indole-3-pyrimidine hydrazones, combined with molecular docking simulations, established a crucial theoretical foundation for developing multi-target fungicides by enabling structural optimization and elucidating precise fungicidal mechanisms of action. © 2026 Society of Chemical Industry.
Cancer stem cells (CSCs) characterized by the capacity of self-renewal and drug resistance, are a major cause of tumour recurrence and metastasis. However, CSCs are mainly localized in the deep and hypoxic regions of the tumour microenvironment that hinder drug penetration. Furthermore, their overexpression of the CD24/Siglec10 immune checkpoint axis markedly suppresses immune clearance, severely limiting the efficacy of current therapeutic strategies. To address this challenge, this study developed an in situ engineered "cascade-amplified" drug-loaded vesicle delivery system, aiming to achieve deep drug delivery into CSC-enriched regions and enhance anti-tumour immune responses. Based on a biomimetic "core-shell" nanoplatform (siXkr8/Dox@PMLC), this system initiates a cascade within the TME where Doxorubicin (Dox) induces tumour cells to generate drug-loaded apoptotic bodies (ApoBDs). These ApoBDs serve as primary vesicles that, upon uptake by adjacent tumour cells, trigger secondary apoptosis, establishing a "cascade-amplified" cycle of enhanced drug delivery. Meanwhile, the silencing of the phospholipid scramblase Xkr8 via siRNA inhibits phosphatidylserine (PS) exposure on the surface of ApoBDs, thereby preventing their recognition and clearance by M2-type macrophages and facilitating immune phenotype remodelling. Furthermore, through targeted blockade of the CD24/Siglec-10 immune axis, the nanoplatform enhances macrophage-mediated phagocytosis of CSCs. In summary, this strategy achieves deep eradication of CSCs and synergistically enhances anti-tumour immunotherapy, demonstrating significant translational potential.
Methicillin-resistant Staphylococcus aureus (MRSA) has become one of the most prevalent drug-resistant pathogens in many countries, posing a serious threat to global healthcare. Consequently, there is an urgent need to develop novel antibacterial agents. This study aimed to evaluate the antibacterial and antibiofilm activities of SX-682-an orally bioavailable allosteric inhibitor of CXCR1/2-against S. aureus and to elucidate its underlying mechanisms. Our findings demonstrate that SX-682 exhibits potent antibacterial activity against S. aureus, with minimum inhibitory concentration (MIC) values ranging from 8 to 16 µg/mL. Time-kill curves revealed a concentration-dependent bactericidal effect. Sub-inhibitory concentrations of SX-682 significantly inhibited the formation of S. aureus biofilms and effectively eradicated preformed mature biofilms. SX-682 enhances the membrane permeability of S. aureus and causes depolarization of the membrane potential, thereby damaging the integrity of the bacteria. By suppressing hemolytic activity and staphyloxanthin biosynthesis, SX-682 reduced the virulence of S. aureus. Additionally, proteomic analysis revealed that SX-682 treatment induced dysregulated expression of proteins in S. aureus, including SasG, FnbA, SdrC, SdrD, SaeR, SaeS, and SarX, which are associated with bacterial biofilm formation, bacterial virulence, and amino acid metabolism. Notably, in a murine model of MRSA-infected skin wounds, SX-682 significantly accelerated wound healing. Collectively, these findings highlight the considerable antibacterial and antibiofilm efficacy of SX-682 against S. aureus, supporting its potential as a promising therapeutic candidate for preventing and treating S. aureus infections.
Neuroinflammation induces astrogliosis, a process marked by astrocyte hypertrophy, increased migration, and altered protein expression. While these changes involve both up- and downregulation of specific genes, the mechanisms governing protein turnover-particularly degradation-remain poorly understood. Here, we investigated how astrocyte endo-lysosomal function is altered during inflammation and explored the role of key regulators such as RAB7 in this response. We analyzed gene expression datasets from an optic nerve injury model to identify pathways associated with reactive gliosis. RAB7 expression and astrocyte reactivity markers, including β3 integrin and GFAP, were assessed in a postnatal rat model of brain injury to evaluate glial responses during early brain maturation. In vitro, TNF-treated astrocytes were used to evaluate changes in gene and protein expression, RAB GTPase activity, lysosomal function, migration, and reactivity markers. RAB7 was overexpressed in selected experiments to confirm its role. The effects of reactive astrocytes on neurite outgrowth were assessed using co-culture assays. In silico analysis revealed an alteration in the endo-lysosomal pathway under inflammatory conditions. Consistently, downregulation of active and total RAB7, along with GFAP and β3 integrin upregulation, were observed in TNF-treated astrocytes and in the in vivo injury model. Reduced RAB7 was associated with impaired lysosomal function, enhanced astrocyte migration, and reduced neurite outgrowth in neurons co-cultured with reactive astrocytes. Overexpression of RAB7 protected cells from the effects of inflammation, preventing TNF-induced impairment of lysosomal function, astrocyte migration, and neurite outgrowth. Our results suggest that inflammation downregulates RAB7, resulting in the appearance of various traits associated with astrocyte reactivity, such as elevated β3 Integrin and GFAP levels. Moreover, RAB7 overexpression prevents these changes. These findings identify RAB7 as a key regulator of astrogliosis and reveal a mechanistic link between RAB-dependent endo-lysosomal pathways and astrocyte reactivity under inflammatory conditions.
Transjugular intrahepatic portosystemic shunt (TIPS) and plug-assisted retrograde transvenous obliteration (PARTO) are the standard of care for managing portal hypertension-related complications. However, the role of peri-procedural antibiotics in preventing infections during these interventions remains unclear because of limited evidence, and this study aimed to address this gap. In this single-centre, double-blind, placebo-controlled, randomised trial, adult patients with portal hypertension were randomised to receive ceftriaxone (1 g twice daily until discharge) or placebo. The primary outcome was the incidence of clinically significant infection defined as fever and a quick Sequential Organ Failure Assessment (qSOFA) score ≥ 2, and secondary outcomes were hospital stay duration, in-hospital mortality and adverse events. Of the 70 patients, 35 received placebo and 35 received ceftriaxone (antibiotic). Twenty-one patients in the placebo arm and 22 in the antibiotic arm underwent PARTO, and the rest underwent TIPS or direct intrahepatic portocaval shunt. On Kaplan-Meier analysis, the risk of clinically significant infection (fever and qSOFA ≥ 2) was 17.1% in the placebo arm and 8.6% in the antibiotic arm (P = 0.31). Fever rates were similar (20% in the placebo arm compared with 22.9% in the antibiotic arm, P = 0.77). Hospital stay duration (4.4 ± 1.7 days in the placebo arm compared with 4.1 ± 2.2 days in the antibiotic arm, P = 0.47) and in-hospital mortality (one death per arm) were comparable. One patient in the placebo arm experienced an injection-site rash. No significant predictors of infection were identified due to the small sample size. Peri-procedural ceftriaxone did not significantly reduce infection rates in patients undergoing elective TIPS or PARTO.
To identify and report how gender justice is conceptualised and discussed in contemporary health literature in relation to the Triple Planetary Crisis of climate change, pollution and biodiversity loss, with a particular focus on the experiences of women and gender-diverse populations, and the representation of nurses and other healthcare professionals dominated by women. Scoping review. Searches were conducted across MEDLINE (Ovid), Scopus, CINHAL, Embase and ProQuest, focusing on studies published from January 1 2000-23 September 2024. The review was conducted in accordance with the JBI methodology for scoping reviews and reported against the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) guidelines. Data were extracted according to a pre-specified extraction framework, developed a priori, encompassing components of gender justice and intersectionality. A total of 39 studies were included: 17 (43.6%) qualitative, 17 (43.6%) quantitative and 5 (12.8%) mixed methods. The focus of the studies included gendered experiences of climate change (30.8%), decision-making and governance (20.5%), health and wellbeing (17.9%), women's economic participation (15.4%), cultural and spiritual connections to land (7.7%), and intersectionality and human rights (7.7%). Gender-diverse populations, nurses and other healthcare professions dominated by women were not represented in the literature. The literature reported that women experienced differentiated exposure to the Triple Planetary Crisis. The underrepresentation of gender diverse people and nurses in recent studies remains a significant barrier to advancing understanding of gender justice. Integrating gender justice into health systems is increasingly important to prevent women from being disproportionately impacted by the Triple Planetary Crisis. More attention to inclusion of frontline healthcare professionals, including nurses, in governance, policy discussions and leadership roles could strengthen the response to systemic environmental threats. No patient or public involvement.
The eggs of Samia cynthia ricini are a promising host for mass-rearing Trichogramma chilonis, but the effects of egg collection methods, fertilization status, and cold storage on rearing efficiency remain unclear. We evaluated the combined impacts of egg collection methods (spontaneous oviposition vs. manual dissection) and fertilization status on host egg yield and T. chilonis' rearing performance, and examined the cold storage effectiveness for unparasitized and parasitized S. c. ricini eggs. Fertilization status and collection method interacted significantly to affect the host egg yield and parasitoid progeny. Spontaneously laid unfertilized egg treatment had the highest total eggs per female, T. chilonis emergence rate, total progeny, and reproductive coefficient. Spontaneous oviposition outperformed manual dissection, increasing female ratio and emerged adults per egg. At 2 ± 1 °C, underwater storage of unparasitized eggs yielded significantly more parasitized eggs than conventional storage. Compared to fresh eggs, 10-day storage significantly increased total emerged T. chilonis adults and emerged adults per host egg. However, storage beyond 20 days significantly reduced reproductive performance. For parasitized eggs stored at 10 ± 1 °C for 7-21 days, T. chilonis emergence rate and progeny per host egg did not differ significantly from the non-stored control. However, storage for 21 days significantly inhibited progeny emergence. Spontaneously laid unfertilized eggs are the optimal host for rearing T. chilonis. Unparasitized eggs should not undergo underwater cold storage beyond 20 days. Parasitized eggs should not be cold-stored over 21 days. These findings offer valuable insights for optimizing T. chilonis mass production. © 2026 Society of Chemical Industry.
Isolated greater tuberosity (GT) fractures account for approximately 20% of proximal humeral fractures and are frequently associated with glenohumeral dislocation and rotator cuff injuries. Displacement exceeding 5 mm is recommended for surgery to prevent subacromial impingement and functional impairment. Current fixation methods, such as cannulated screws, suture anchors, and locking plates, each have limitations, including inadequate stability for comminuted fractures, risk of impingement, and suboptimal anatomical adaptation. This underscores the necessity of a hybrid technique that integrates the benefits of both soft tissue and rigid fixation. This retrospective study analyzed 12 patients with comminuted split-type or avulsion-type greater tuberosity fractures treated with a hybrid surgical technique from January 2023 to June 2025. A deltopectoral approach was utilized to achieve fracture reduction, which was temporarily stabilized via K-wires. Two anchors were placed at the greater tuberosity, and a double-row suture technique was employed, with the sutures secured through an external row anchor arranged in a parachute configuration. A low-profile anatomic locking plate was subsequently applied to provide buttress support, resulting in a composite construct referred to as a "suture plate." The outcomes measured included operative time, blood loss, Constant-Murley and ASES scores, VAS pain scores, and radiographic healing status. All patients were followed up for a mean duration of 11.3 ± 5.0 months. The mean operative time was 82.5 ± 15.8 min, and the mean blood loss volume was 170.8 ± 52.6 ml. All fractures achieved clinical union at a mean of 11.0 ± 1.5 weeks, with no instances of anchor pullout, suture cutout, or implant failure. The Constant-Murley scores improved from 30.5 ± 4.8 preoperatively to 90.3 ± 3.7, the ASES scores improved from 32.1 ± 5.8 to 89.4 ± 3.6, and the VAS scores decreased from 6.8 ± 2.1 to 1.0 ± 0.6. Excellent or good outcomes were observed in 91.7% (11/12) of the patients. The combination of the double-row parachute suture technique and a low-profile anatomic locking plate provides a hybrid fixation system that integrates flexible and rigid stabilization. This construct can provide reliable fixation, supporting early rehabilitation, and yielding satisfactory short-term functional outcomes for comminuted split-type or avulsion-type greater tuberosity fractures, representing a potentially feasible alternative to conventional methods, although further high-level studies are required to confirm its long-term efficacy and safety.
The Fatu Hiva monarch (Pomarea whitneyi) is a Critically Endangered (IUCN) passerine species restricted to a single island in French Polynesia, with fewer than 20 individuals remaining. In the Pacific region, avian malaria caused by Plasmodium relictum lineage GRW4 is a major conservation concern because it has been linked to severe population declines and extinctions in Hawai'i and poses a documented threat to endemic birds in New Zealand. On 17 June 2022, a recently fledged juvenile Fatu Hiva Monarch (Pomarea whitneyi) was found dead in its natural habitat on Fatu Hiva. A necropsy was performed on site in humid tropical conditions, with real-time online guidance from an expert based in Switzerland. Gross examination revealed severe emaciation, an empty gastrointestinal tract, diffuse pallor with scant intravascular blood and hepatosplenomegaly with dark discolouration. Despite advanced autolysis having occurred, cytologic tissue imprint and blood-smear assessment revealed high parasitaemia with intraerythrocytic developmental stages and abundant birefringent malarial pigment. Histopathology confirmed a hemozoin-producing haemosporidian infection due to the presence of widespread polarisation-positive and Prussian blue-negative intracytoplasmic pigment in erythrocytes and macrophages. Molecular testing was performed on dried blood pressed onto household filter paper, that had been stored and shipped at ambient temperature for several weeks. Nested cytochrome b polymerase chain reaction and sequencing confirmed a single infection with the GRW4 lineage of Plasmodium relictum. This first confirmed fatal case of avian malaria in this critically depleted island endemic species highlights the urgent need to integrate disease surveillance and vector management into conservation planning. The results suggest that acute severe P. relictum (GRW4) infection was the proximate cause of death, likely occurring against a background of prolonged negative energy balance and chronic stress exposure. Although the direction of causality cannot be fully determined post-mortem, aggressive malaria prevention measures remain justified to avoid further demographic decline in the critically low Fatu Hiva monarch population. To effectively reduce risk, vector control measures must be combined with measures to enhance host resilience and continuous surveillance to monitor transmission and guide adaptive management. Furthermore, this case study shows that a scientifically defensible, lineage-level diagnosis can be achieved using simple, low-cost samples and techniques adapted for remote tropical fieldwork, even when carcass quality is compromised by warm, humid conditions.
Cardiovascular disease (CVD) remains a leading cause of morbidity and mortality worldwide. Although traditional cardiovascular risk models primarily rely on biomedical factors, socioeconomic and occupational characteristics are increasingly recognized as important correlates of cardiovascular health. However, applying machine learning to population-based survey data raises methodological concerns, particularly reverse causation and post-diagnosis information leakage. We conducted a cross-sectional analysis using data from the 2023 Behavioral Risk Factor Surveillance System (BRFSS). The analytic objective was classification of prevalent myocardial infarction (MI) or coronary heart disease (CHD) rather than prospective risk prediction. Four supervised machine learning algorithms (logistic regression, decision tree, random forest, and gradient boosting) were evaluated. To address potential label leakage, we implemented two model variants: an inclusive model incorporating all available predictors (Model A) and a model excluding post-diagnosis proxy variables such as medication use, functional limitations, and disability indicators (Model B). Model performance was assessed using receiver operating characteristic area under the curve (ROC-AUC), precision-recall area under the curve (PR-AUC), precision, recall, and F1 score. Gradient boosting demonstrated the strongest discriminative performance among the evaluated models. In the inclusive setting, the model achieved a ROC-AUC of 0.867 and a PR-AUC of 0.389, with a best F1 score of 0.433. After removal of post-diagnosis variables, performance remained robust (ROC-AUC = 0.858; PR-AUC = 0.372; F1 = 0.418), suggesting that predictive capacity was not driven solely by downstream disease indicators. Feature importance analyses showed that socioeconomic and employment-related variables remained prominent predictors in Model B alongside established clinical risk factors. Machine learning models can effectively classify prevalent MI and CHD using large-scale survey data even after explicit mitigation of post-diagnosis information leakage. Socioeconomic and occupational characteristics appear to function primarily as contextual correlates rather than causal determinants of CVD. These findings highlight the value of interpretable machine learning approaches for the population-level classification of prevalent cardiovascular disease while underscoring the limitations inherent to cross-sectional data.
The sensitivity of bladder cancer detection using a single biomarker from single sample type is limited. This study aimed to investigate whether a combined approach utilizing multiple biomarkers from different clinical samples could improve detection sensitivity. A total of 85 patients with bladder cancer and 30 healthy individuals were enrolled in this study. Urine and blood samples were collected for the isolation of urine-derived epithelial cells (UDECs) and circulating tumor cells (CTCs). These cells were then analyzed via PD-L1 assay and fluorescence in situ hybridization (FISH) targeting chromosomes 7 and 8. In parallel, matched urine samples from patients underwent conventional urine exfoliation cytology testing (UEC). All data were analyzed in conjunction with pathological information using specialized statistical software. Analysis of CTCs demonstrated a significantly higher bladder cancer detection rate (78.6%) compared to UEC (36.7%). The combination of UDEC-FISH and CTC analysis utilizing urine and blood samples achieved a higher detection rate (94.1%) than the combination of UDEC-FISH with UEC performed on the same urine sample (79.8%). Furthermore, combined analysis of three markers of CTC, UEC, and UDEC-FISH (96.5%) or CTC, UEC, and UDEC-PD-L1 (90.6%) yielded significantly higher detection rates than any single biomarker analysis alone. Integrating multiple biomarkers from distinct sample types significantly enhances the detection sensitivity for bladder cancer.
Degradation dynamics is an essential aspect in the field of environmental science and is crucial in understanding the interaction between microbes and explosive compounds. Explosive compounds and their residues, such as nitramines, nitro-substituted aromatics, picric acid, TETRYL, and HEXYL), and aliphatic, RDX, etc.are highly persistent in the environment. These compounds are toxic to many life forms at high concentrations, specific microbial species have evolved resistance and degradation capabilities, though their growth can still be inhibited beyond certain thresholds, The results of microbial biodegradation can range from complete mineralization to only the biotransformation into less toxic or more resistant metabolites. Research using pure cultures of bacteria and fungi has provided insight into the degradation pathways of certain nitro-organic compounds, and some key enzymes (laccases and lignin peroxidases) have been identified and studied. This review mainly aims to provide an overview of the current state of research on the degradation dynamics of explosive compounds Recent advancements have pivoted toward 'Bio-omics' and synthetic biology tools, such as CRISPR/Cas systems, to engineer high-activity microbial strains.
Female genital mutilation is a major public health and human rights concern, with the highest burden reported in countries of the Horn of Africa. Despite long-standing legal bans and prevention efforts, the practice remains nearly universal in Somaliland, driven by deeply rooted social and cultural norms. Evidence on the prevalence, types, and population-level determinants of female genital mutilation in Somaliland remains limited. This study assessed the prevalence, types, and associated factors of female genital mutilation among women of reproductive age in Somaliland. This population-based study analyzed data from 5,143 women aged 15-49 years who participated in the 2020 Somaliland Demographic and Health Survey. A two-stage cluster sampling design was used, involving the selection of enumeration areas followed by households. Descriptive analyses were conducted to estimate prevalence and types of female genital mutilation. Binary logistic regression was used to identify factors associated with the pharaonic type of female genital mutilation in comparison with other types. The overall prevalence of female genital mutilation was 99.49% (95% confidence interval: 99.30-99.70). The most common form was type three (pharaonic), affecting 66.97% of women, followed by type one (sunni) at 22.01% and type two (intermediate) at 9.50%. Women from nomadic communities, those with no formal education, those in lower wealth households, women who had never used the internet, and those circumcised by traditional practitioners had significantly higher odds of experiencing the pharaonic form of female genital mutilation. Female genital mutilation remains nearly universal among women of reproductive age in Somaliland, with severe forms predominating. Social disadvantage, limited access to education and information, and reliance on traditional circumcisers are key population-level drivers of harmful practices. Interventions that expand educational and digital access and engage traditional practitioners may be critical to reducing the persistence and severity of female genital mutilation in Somaliland.
Primary insomnia is a highly prevalent sleep disorder that significantly affects quality of life. Acupoint injection (AJ), a traditional therapy that combines pharmacological and acupuncture effects, has been increasingly applied in clinical practice. However, evidence of its efficacy and economic value is lacking. This study determined the clinical effectiveness of AJ and established the relative ranks of AJ-related therapies for the treatment of primary insomnia. The clinical effectiveness and cost-effectiveness of AJ-related therapies for primary insomnia were evaluated through a systematic review and network meta-analysis (NMA) of randomized controlled trials (RCTs). We searched 11 electronic databases for relevant studies published up to June 10, 2025. The Pittsburgh Sleep Quality Index (PSQI) and effective rate were used as outcome measures. The quality of included studies was assessed using the Risk of Bias 2.0 tool. Pairwise meta-analysis and NMA were performed using RevMan 5.4 and R, respectively. The cost-effectiveness of the interventions was subsequently determined based on regional intervention costs. Twenty-four randomized controlled trials involving 1,851 participants were included in the meta-analysis. AJ combined with manual acupuncture (MA) significantly reduced PSQI scores based on the results of the pairwise meta-analysis and was among the most effective interventions based on the results of the network meta-analysis. The cost-effectiveness analysis revealed that AJ combined with MA was associated with better outcomes at modest additional costs, as indicated by the favorable incremental cost-effectiveness ratio (ICER) values for PSQI improvement and additional responders. This study is the first to comprehensively synthesize evidence on the clinical effectiveness and cost-effectiveness of acupoint injection for primary insomnia. AJ combined with MA significantly improves sleep quality and may be a cost-effective and safe adjunctive therapy within the context of traditional medicine practice. It may be a feasible treatment option for primary insomnia. However, this conclusion should be validated through future studies due to the limitations of the quality of the literature. Further high-quality RCTs with standardized economic evaluations are warranted to confirm these findings.
The increased intake of added sweeteners, such as high-fructose corn syrup, has been associated with a rise in metabolic dysfunctions in gut and brain. While different evidence showed that dietary fructose induces gut microbiota reshaping, the sugar impact on specific bacteria-derived metabolites remains an understudied topic. In this study, we identified secondary bile acids (sBAs) as molecules differentially represented in plasma of rats fed a fructose-rich diet compared to control animals, and hypothesized that these metabolites might be a target for probiotic-based strategies to counteract sugar-induced metabolic disorders. To this aim, we investigated whether probiotic spores of Shouchella clausii SF174 ameliorate fructose-induced cognitive and metabolic dysfunctions and prevent molecular alterations in hippocampus and frontal cortex. Wistar rats were fed a fructose-rich diet, alone or in combination with the daily administration of Shouchella clausii spores, for six weeks. At the end of treatment, behavioral, metabolomic and molecular analyses were performed. The probiotic spores exerted a protective effect on the memory function of fructose fed rats and prevented the decrease of markers of synaptic plasticity. This was associated with the maintenance of plasma and brain levels of the sBA deoxycholic acid and of its specific receptor Takeda G protein-coupled receptor 5. Further, spores beneficial modulation of fructose-induced peripheral and central inflammation was observed. Also, probiotic spores produced reshaping of the gut microbiota towards a composition exerting neuroprotective and anti-inflammatory effects. These results suggest that sBAs might act as a communication bridge along the microbiota gut-brain axis and suggest that their modulation, through probiotic administration, represents an effective strategy to counteract fructose-induced neuroinflammation and gut-brain dysfunction.
Migraine is a common and disabling neurological disorder in children, often requiring preventive treatment. This study aimed to compare the efficacy and tolerability of cinnarizine and topiramate in the prophylaxis of migraine in children and adolescents. In this randomized, double-blind, parallel-group clinical trial, 96 children aged 6-15 years with a diagnosis of migraine according to the International Classification of Headache Disorders (ICHD-3) [1], including both migraine with and without aura, without restriction to specific subtypes were enrolled. Participants were randomly assigned to receive either cinnarizine (25 mg once daily) or topiramate (25 mg once daily) for 12 weeks. Migraine attack frequency and severity were recorded using headache diaries at baseline, one month, and three months after treatment initiation. The primary outcome was the change in monthly migraine attack frequency. Secondary outcomes included changes in headache severity and the occurrence of adverse events. Between-group comparisons were performed using the Mann-Whitney U test, and within-group changes over time were analyzed using the Friedman test. Both cinnarizine and topiramate significantly reduced monthly migraine attack frequency and headache severity over the 12-week treatment period (P < 0.001 for within-group comparisons). At three months, the median number of migraine attacks decreased to two attacks per month in both groups, with no statistically significant difference observed between the two treatments (P = 0.81). Headache severity scores also improved significantly in both groups, and no between-group differences were observed at follow-up (P = 0.74). Both medications were generally well tolerated, with no statistically significant differences in the incidence of adverse events between groups. Appetite reduction was reported in 4.2% of the cinnarizine group versus 14.6% of the topiramate group. While a numerically lower incidence of appetite reduction was observed in the cinnarizine group (4.2% vs. 14.6%), this difference was not statistically significant (P = 0.159, Fisher's exact test; OR = 0.255, 95% CI: 0.05-1.27). Both cinnarizine and topiramate significantly reduced the frequency and severity of migraine attacks in children. No statistically significant difference in efficacy was detected between the two treatments. A numerically lower incidence of appetite reduction was observed with cinnarizine, although this difference was not statistically significant. Larger studies are needed to evaluate potential differences in tolerability. Iranian Registry of Clinical Trials (IRCT) IRCT20221108056444N1. Registered 12 February 2023 Retrospectively registered, https://www.en.irct.ir/trial/66774.
To determine whether anterior fibromuscular stroma (AFS) preservation within an anteroposterior (AP) HoLEP platform independently reduces ultra-early postoperative incontinence. We retrospectively analyzed consecutive HoLEP cases (April 2019-June 2025) performed by a single surgeon. Of 719 procedures, 272 consecutive cases using a standardized AP platform were included and classified into conventional AP-HoLEP (CON, n = 60), mucosal incision-first AP-HoLEP (MI, n = 180), and AFS-preserving AP-HoLEP (AFS, n = 32). The primary endpoint was Day-1 incontinence, defined as any objective leakage (> 0 mL) within 24 h after catheter removal on Postoperative Day 2. Multivariable logistic regression was used to identify independent predictors. Day-1 incontinence occurred in 55% (33/60) of CON, 58% (104/180) of MI, and 25% (8/32) of AFS cases (p = 0.003). In multivariable analysis, AFS preservation was independently associated with lower odds of Day-1 incontinence versus CON (odds ratio [OR], 0.30; 95% confidence interval [CI], 0.11-0.80; p = 0.016), whereas MI was not (OR, 1.14; 95% CI, 0.62-2.11; p = 0.680). Perioperative safety outcomes were comparable, with low rates of Clavien-Dindo ≥ III events. Within an AP-HoLEP platform, AFS preservation was associated with improved Day-1 continence without compromising safety, supporting ventral-support preservation as a key lever for ultra-early continence recovery.
Foot-and-mouth disease (FMD) is a highly contagious animal disease caused by foot-and-mouth disease virus (FMDV), primarily affecting cloven-hoofed animals such as swine, cattle, and sheep. As a core metabolic pathway for maintaining cellular homeostasis, lipid metabolism is frequently hijacked by viruses via metabolic reprogramming mechanisms to support their infection cycle. Studies have demonstrated that positive-sense single-stranded RNA viruses can reshape the host cell membrane system and modulate the lipid metabolic network, thereby constructing a favorable microenvironment for their invasion and replication. However, the molecular mechanisms by which FMDV-also a positive-sense single-stranded RNA virus-promotes viral replication through the regulation of lipid metabolism remain incompletely elucidated. In this study, we found that inhibiting the key enzymes involved in the lipid metabolic pathway could significantly suppress FMDV proliferation. Exogenous supplementation of the downstream products catalyzed by these key enzymes notably restored FMDV replication, indicating that FMDV replication is dependent on lipids. Furthermore, we observed a significant upregulation in the protein expression of carnitine palmitoyltransferase 1A (CPT1A) in host cells following FMDV infection. Inhibition of this enzyme led to a marked reduction in FMDV replication, suggesting that FMDV may enhance the fatty acid β-oxidation pathway to supply energy for its replication. In conclusion, this study comprehensively verified the critical role of lipid metabolism in FMDV replication through multidimensional assays involving the administration of inhibitors targeting key enzymes in the lipid metabolic pathway. These findings provide novel theoretical insights for the development of antiviral drugs and the prevention and control of FMD.
Digital phenotyping - the moment-by-moment quantification of individual-level human behavior using data from personal digital devices - offers a novel approach to continuous, passive monitoring of psychiatric patients. Changes in behavioral digital phenotypes may serve as early warning signs of relapse or clinical deterioration, creating an opportunity for timely preventive intervention. A systematic search of PubMed, PsycINFO, and IEEE Xplore was conducted for studies published up to January 2026. We included prospective and retrospective observational studies using passively collected smartphone or wearable data to predict relapse or clinical deterioration in individuals with diagnosed psychiatric disorders, with reported quantitative model performance metrics. Study quality was assessed using the modified Newcastle-Ottawa Scale [16] and the PROBAST [25, 26] tool. Data were synthesized narratively in accordance with the SWiM guideline. Fifty-two studies encompassing 4,814 participants met inclusion criteria. Disorders studied included schizophrenia spectrum disorders (35%), bipolar disorder (27%), and major depressive disorder (23%). Key predictive features included alterations in sleep patterns (83% of studies), physical activity (83%), GPS-derived mobility (75%), and social communication frequency (65%). Machine learning models reported AUC values ranging from 0.70 to 0.88 for predicting relapse one to four weeks in advance, although the majority of these estimates were derived from internal validation and are likely to overestimate real-world performance. Multi-modal data integration and individual-level modeling consistently outperformed single-modality and population-level approaches. High risk of bias was identified in 75% of studies, primarily attributable to inadequate analytic methodology and reliance on internal validation. Passive digital phenotyping demonstrates significant promise for predicting psychiatric relapse across diagnostic categories, with moderate-to-good predictive discrimination (AUC 0.70-0.88) achievable up to four weeks prior to confirmed relapse. However, substantial methodological limitations - including reliance on internal validation, heterogeneous outcome definitions, and limited demographic diversity - must be addressed. Standardized outcome definitions, prospective external validation in diverse cohorts, and closed-loop intervention trials are required before widespread clinical implementation can be responsibly pursued.