Understanding how symptom domains relate to one another (e.g., whether generalized anxiety is more similar to depression than to panic) is central to psychiatric classification. We demonstrate a procedure for quantifying relative proximity, defined as whether one symptom domain is statistically closer to another compared to other domains. As a motivating application, we examine the structure of internalizing symptoms characterized by fear, distress, avoidance, and heightened arousal. Using a network approach, we analyzed data from six questionnaires assessing depression, generalized anxiety disorder (GAD), social anxiety disorder, panic disorder, posttraumatic stress disorder (PTSD), and obsessive-compulsive disorder (OCD) symptoms. In a community sample of young adults (n = 2051; ages 17-23), we estimated a symptom-level Gaussian graphical model, used community detection to characterize the network's modular structure, and derived shortest path length to quantify the relative proximity of predefined symptom domains. We then used permutation testing to determine whether distress-related symptom domains (depression, GAD, and PTSD) showed greater empirical proximity to one another compared to fear-related domains (social anxiety, panic, and OCD). Results indicated reciprocal proximity between the depressive and GAD symptom domains compared to other internalizing domains. PTSD showed its greatest relative proximity to depression and GAD. Panic, social anxiety, and OCD did not form a cohesive fear community and showed variable relative proximity to both distress- and fear-related domains. Overall, these findings lend support for a distress-based internalizing dimension encompassing depression, GAD, and possibly PTSD, while providing limited evidence for a fear-based dimension including social anxiety, panic, and OCD.
Familial hypercholesterolaemia (FH) is a common but underdiagnosed genetic condition that leads to high low-density lipoprotein cholesterol and premature cardiovascular disease. Cascade genetic testing remains underutilised as a screening approach. Implementation strategies can increase the diffusion of innovations such as genetic medicine into non-genetic specialty settings more rapidly through dissemination networks. This study aimed to evaluate the success of a multifaceted implementation strategy to increase cascade testing for relatives of a person diagnosed with FH using a primary-tertiary shared care model. A multisite effectiveness-implementation hybrid type III pre-post study was conducted between 2022 and 2024 to compare the implementation of a new shared care model for FH cascade testing in NSW, Australia. During the control period, cascade testing of relatives was offered to FH index cases by a genetic counsellor at the lipid clinic. In the implementation strategy period, FH index cases were offered a cascade testing expression of interest form to provide to their relatives. Relatives were contacted by a genetic counsellor and provided with a pre- and post-cascade testing package, which was also provided to their general practitioner. A total of n = 25 index and n = 6 cascade cases were included in the control period and n = 81 index and n = 56 cascade cases in the implementation period. The number of cascade genetic tests per index case increased significantly from 0.24 in the control period to 0.52 in the implementation strategy period (incident rate ratio = 4.62; 95% CI: 0.39, 8.84; p = 0.032). Among relatives tested, there was no difference in the proportion with a confirmed FH gene change per index case (IRR = 2.15; 95% CI: 0.65, 7.01; p = 0.207). There was no difference in the proportion of index cases with at least one cascade test (OR = 1.49; 95% CI: 0.53, 4.19; p = 0.442). Implementation of our model increased FH cascade testing compared to previous standard care. These findings suggest a greater role for cascade testing in primary care settings. This opens new opportunities for integrating genetic screening into routine general practice, particularly for autosomal dominant conditions such as FH.
U.S. military veterans face an elevated suicide risk compared to the general population. Both the use and misuse of tranquilizers (i.e. several classes of medications that treat anxiety and muscle spasms via central nervous system action, including benzodiazepines) have been associated with suicidal thoughts and behaviors among veterans. However, it remains unclear whether risk varies across different patterns of tranquilizer use. Participants included 12,584 U.S. military veterans (13.0% female; 78.1% non-Hispanic White; 49.3% age 65 and older), from the 2015-2019 National Survey on Drug Use and Health (NSDUH). Tranquilizer use without misuse was associated with greater odds of suicidal ideation and planning, relative to nonuse (p's < 0.01). Tranquilizer misuse was associated with greater odds of suicide ideation, planning, and attempts compared to nonuse (p's < 0.01). Relative to use without misuse, tranquilizer misuse was associated with greater odds of suicide ideation, planning, and attempts (p's < 0.01). These results support a graded association between tranquilizer use/misuse and suicidal thoughts and behaviors, suggesting that risk for suicide-related outcomes may increase from no use, to use without misuse, to misuse. Future research should explore the clinical utility of addressing tranquilizer use/misuse as part of targeted suicide prevention strategies among veterans.
Unraveling the potential horizontal transfer of resistance genes/virulence genes (RGs/VGs) in gut microbiota from patients with Crohn disease (CD) is an interesting but poorly characterized issue. Quantitative assessment was performed to estimate the relative abundance and diversity of RGs/VGs/mobile genetic elements (MGEs). Differential analysis was applied to identify the CD-specific enriched genetic subtypes. A species-RGs/VGs/MGEs association network was constructed to explore possible co-occurrence patterns of these genetic elements across potential microbial hosts. Integrated with topological metrics and Zi-Pi computational modeling, co-occurrence network analysis was conducted to characterize potential associations among RGs, VGs, and MGEs. Comparative metagenomic analyses indicated that the microbiome in group CD exhibited significantly higher relative abundance of RGs compared to that in healthy controls (HC; P = .040), with 131 specific RG/VG subtypes (eg, acrA/T6SS) exhibiting marked enrichment (P < .05). The co-occurrence network revealed intensified interconnectivity between RGs/VGs and MGEs in group CD, in which MGEs accounted for 71% of network nodes (vs 60.80% in HC), and 99.14% of the edges were positively correlated (vs 93.60% in HC). Network topology and Zi-Pi analysis further suggested reduced modularity (0.709 vs 0.979 in HC) and enhanced intergene connectivity (average degree: 12.288 vs 2.156; average weighted degree: 23.359 vs 3.688 in HC). There were no network hubs (0 vs 5 in HC) but abundant modular hubs (60 vs 25 in HC), peripheral nodes (2317 vs 1549 in HC), and connectors (61 vs 36 in HC), which may reflect conditions favorable for enhanced gene transfer potential. Cross-species transfer events were predicted across clinical-environmental-commensal boundaries, exemplified by tet(M) dissemination between Clostridioides difficile and Bacteroides sp., probably implying progressive erosion of ecological barriers. Collectively, we inferred that the gut microbiome of CD patients might represent a high-risk reservoir for the horizontal transfer of pathogenic determinants, which may pose a potential threat for public health and biosecurity. This study indicated that gut microbiota in patients with Crohn disease carried more genes involved in resistance and virulence traits, compared to that in healthy controls. These genes were closely linked to mobile genetic elements, which might create a high-risk environment for their spread across species and would pose a broader public health concern.
Lonicera caerulea is a commercial fruit crop. A polysaccharide (LCP) was extracted from its fruits and characterized as a pyranose polysaccharide with a molecular weight of 4.096 × 105 Da. Monosaccharide composition analysis revealed that LCP was a heteropolysaccharide composed of glucose, mannose, xylose, glucuronic acid, galacturonic acid, rhamnose, and galactose. In a mouse model of acute alcoholic liver injury, oral administration of LCP for 14 days was associated with dose-dependent improvements in serum transaminases, lipid accumulation, oxidative stress markers, and pro-inflammatory cytokines. Histopathological examination confirmed that LCP attenuated alcohol-induced hepatic steatosis and inflammatory infiltration. To explore potential mechanisms, 16S rRNA and ITS-1 sequencing of cecal contents were performed. LCP treatment was associated with increased relative abundance of the bacterial phylum Bacteroidetes and the fungal genus Kazachstania, and decreased relative abundance of the bacterial genus Dubosiella and the fungal genus Mortierella. Correlation analyses revealed that the bacterial and fungal taxa enriched by LCP were negatively correlated with liver injury markers. These findings suggest that LCP may alleviate alcoholic liver disease in association with modulation of the gut bacteriome and mycobiome, providing experimental evidence for the involvement of cross-kingdom microbial interactions in this process.
Sensory symptoms have been increasingly recognized as core characteristics of tic disorders (TD). This study aimed to systematically investigate the core features of sensory processing abnormalities in Chinese children with tic disorders, analyze their association with tic severity, and explore potential subtypes based on sensory profiles. This cross-sectional study recruited 151 children diagnosed with TD (encompassing Tourette syndrome, chronic motor tic disorders, and provisional tic disorders) along with 100 age-matched healthy controls (HC). Sensory processing characteristics were assessed using the Short Sensory Profile, and tic severity was evaluated with the Yale Global Tic Severity Scale. Principal component analysis (PCA) and latent profile analysis (LPA) were employed to explore sensory subtypes. Correlation analyses and regression models were used to examine sensory-symptom relationships. Children with TD showed significantly lower total SSP scores than HCs (P < 0.001), with deficits primarily in "under-responsive/sensation seeking", "auditory filtering" and "low energy/weakness". PCA extracted two core dimensions: "sensory dysfunction" and "sensory hypersensitivity". A significant positive graded relationship was found between the degree of sensory abnormality and tic severity (P for trend = 0.025). The "under-responsive/ sensation seeking" dimension was an independent predictor of tic severity (β = -0.164, P = 0.044). LPA identified two subtypes: a "relatively typical sensory processing" subtype (88.7%) and a "sensory over-responsivity" subtype (11.3%). However, no significant difference in tic severity was found between these subtypes. Sensory processing abnormalities, particularly generalized sensory modulation dysfunction, are prevalent across TD subtypes and are closely associated with tic severity. Sensory under-responsivity represents a core risk dimension, while the unique "sensory over-responsivity" subtype may be relatively independent of tic severity. This study provides important evidence for sensory-based subtyping of TD and for developing individualized interventions targeting sensory symptoms.
Future work self-salience is critical for vocational college students in China to navigate the school-to-work transition effectively. However, there is limited research on the distinct profiles of career resources that shape these students'agency in envisioning and pursuing their professional identities. This study aimed to identify latent profiles of vocational college students based on their configuration of career resources (i.e., psychological, identity, and social resources) and to examine differences in future work self-efficacy and the mediating role of personal growth initiative across the identified profiles. The present study involved 1,093 first- and second-year vocational college students in China. Latent Profile Analysis (LPA) was conducted in Mplus to classify career resource profiles. The BCH method was applied to examine differences in future work self-salience across identified subgroups. Finally, relative mediation effect analysis was performed to assess the mediating role of personal growth initiative. The LPA results indicated that vocational college students can be classified into four distinct subgroups based on career resources: the deficient group, the relatively high external employability group, the sufficient group, and the balanced group. The sufficient group demonstrated the highest levels of personal growth, initiative, and future work self-salience. Moreover, personal growth initiative mediates the relationship between different subgroups and future work self-salience. These findings highlight the active role individuals play in translating resources into a clearer future work self. Despite limitations, this study contributed to the literature by offering implications for supporting the developmental transition of vocational students entering the workforce.
To our knowledge, no previous systematic review and meta-analysis of doping prevalence in sport from indirect estimation models (IEM) exists. To conduct a systematic review and meta-analysis of empirical IEM-based studies of admitted doping prevalence in sport. We conducted electronic database and ad hoc searches up to March 2025, and estimated lifetime and past year prevalence rates through a cross-classified model including prevalence (lifetime vs. past year), sample (competitive vs. recreational) and sports (multi-sport vs. single-sport) types. Forty-six records (K) were included in the review (k [subset records included in the meta-analysis] = 30, n [independent studies from the records] = 34). The World Anti-Doping Agency's definition of doping use was applied for data collection in most studies (k = 18), and doping prevalence was mostly assessed as past year/season (k = 20). Studies included in the meta-analysis were mostly conducted in Europe (k = 22) and applied the Unrelated Question (k = 8) and Forced Response with Cheater Detection (k = 6) models. Study participants were mostly multi-sport (k = 20) and competed at diverse levels, and most data (k = 28) was collected outside sport events. The corpus included articles that re-analysed existing data (k = 4). Lifetime prevalence was highest for multi-sport competitive athletes (22.6%) and lowest for single-sport competitive athletes (12.7%), whereas past year prevalence was highest for single-sport recreational sportspersons (15.5%) and lowest for multi-sport recreational sportspersons (8.7%). Under IEM, about one of five multi-sport competitive athletes admitted to ever doping whereas about one of six of single-sport recreational sportspersons admitted to doping in the past year. Furthermore, multi-sport (vs. single-sport) competitive athletes show relatively higher doping prevalences, whereas single-sport (vs. multi-sport) recreational sportspersons report relatively higher doping prevalences. Secondary (re-)analysis presents a novel methodological challenge for meta-analyses. Registration PROSPERO: CRD42022373691.
The gut microbiota regulates skeletal muscle physiology, with an increasingly recognised role in Duchenne muscular dystrophy (DMD), the most severe X-linked myopathy. Unlike previous studies, we focussed on the genus Bacteroides and its metabolites, assessing their abundance in DMD mice and patients to clarify their potential contribution to the disease. The relative abundance of Bacteroides species was analysed in fecal samples from dystrophic mdx mice and DMD patients, compared with age-matched healthy controls, using PCR-based tecniques. Synthetic and analitical chemistry approaches followed by cell-based assays, in silico and bioinformatic analyses, were employed to identify an unknown mechanism of action of the Bacteroides-derived metabolites. DMD patients and mdx mice exhibited a significant reduction in commensal Bacteroides species, including Bacteroides vulgatus, known producers of SCFAs and commendamide, an endocannabinoid-like molecule with largely uncharacterized biological functions. In skeletal muscles of mdx mice, we observed biochemical features consistent with increased susceptibility to ferroptosis. In murine C2C12 cells and primary human myotubes exposed to the ferroptosis inducer erastin, commendamide conferred significant protective effects, which were further enhanced in the presence of SCFAs. Additionally, we discovered that commendamide acts as an endogenous activator of PPARα and PPARγ, with PPARα preferentially promoting the transcription of the antioxidant genes Gpx4 and Nrf2. These findings provide new insights into the gut-muscle axis in DMD, suggesting that the depletion of Bacteroides vulgatus and its metabolites may contribute to skeletal muscle degeneration. In vitro evidence demonstrates that commendamide, through PPARα signaling; and SCFAs, enhances antioxidant mechanisms. Overall, these results support further investigation of microbiota-derived metabolites as postbiotic candidates for DMD therapy.
Although changes in the lung microbiome have been observed in many respiratory diseases, the lung microbiome of patients with tuberculosis (TB) remains largely undefined. The aim of this study was to determine and compare the composition of upper and lower respiratory microbial communities, changes in host gene expression, and functional pathway activation in patients with TB and community-acquired pneumonia using a Metatranscriptomic approach. From November 2020 to November 2021, 42 bronchoalveolar lavage fluid samples, 10 oropharyngeal swabs, and 10 nasopharyngeal swabs were collected from patients hospitalized with TB or community-acquired pneumonia for RNA-sequencing, within 72 h of admission. Data from 28 healthy controls were downloaded from the National Center for Biotechnology Information database. The most common microorganisms in the samples from patients with TB were Prevotella, Escherichia, Mycobacterium, and Verrucoccus. Notable differences in microorganism diversity were observed between the TB and community-acquired pneumonia groups as well as between the upper and lower respiratory tracts compared to that in healthy controls. Altered microbial interactions were also observed. Rothia and Mycobacterium were identified as marker microorganisms in the TB group, which exhibited increased expression of SNAP25, MGAM2, CNTN4, MMP12, and GPR174, in parallel to IL36A, RHCG, and CYP2B6 downregulation relative to the community-acquired pneumonia group. The pathways enriched for differential genes were similar among all patient groups, particularly involving neuroactive ligand receptor interaction and Ca2+ signaling. Patients with TB differed from those with community-acquired pneumonia, particularly with regard to the cytokine-cytokine receptor interaction pathway. The most commonly detected antibiotic resistance genes conferred resistance against β-lactams and macrolides. Antibiotic resistance genes were more abundant in oropharyngeal than in nasopharyngeal samples. The composition of microbial communities and host expression landscapes differs between TB and community-acquired pneumonia as well as between different respiratory tract sites. These changes in lung microbiota may impact lung disease development and prognosis.
To review extant literature for the use of digital technology to deliver cognitive training perioperatively to prevent or mitigate postoperative delirium (POD). Increasing rates of surgical care place pressures on healthcare systems. POD is a prevalent complication in older adults, worsening patient outcomes and up to 40% may be preventable. Since preoperative cognitive dysfunction is a primary risk factor, understanding the impact of technology-assisted cognitive enhancement on POD may improve patient experience and alleviate costs. Five databases were searched, and articles were reviewed by two investigators. Clinical trials that used digital technology perioperatively to prevent POD in older adults and written in English or French were included in the study. Relevant information was extracted. Out of the 630 articles identified, six (n = 6) were included. Surgical type, targeted cognitive domains and intervention dosing varied, exclusion criteria were restrictive and effectiveness was both positive and null. Relatively few relevant studies were identified indicating the literature is in its infancy. While two of the studies showed positive outcome trends, further research is needed to address adherence, modifiability of cognitive training programs, intervention dosage and less restrictive sampling.
Schizophrenia spectrum disorders (SSD) commonly involve deficits in social cognition and facial processing. The N170 and N250 event-related potentials (ERP), indexing perceptual and recognition stages of face processing respectively, have shown alterations in schizophrenia. Given diagnostic advances, an updated analysis is necessary to examine these ERP across SSD, including high-risk individuals and those exhibiting schizotypal traits. To update previous meta-analysis findings by evaluating the effects of SSD on N170 and N250 amplitude and latency. Studies comparing N170 and N250 amplitude and latency between individuals with SSD and healthy controls were identified through a literature search, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses recommendations. Results showed a small reduction in N170 amplitudes in SSD (n = 50), statistically significant in SSD but not in schizotypy or high-risk individuals. A small but significant difference was also found for N170 latency, whereas no significant effects were observed for N250 amplitude or latency. Findings indicate reduced N170 amplitudes and subtle latency alterations in SSD, reflecting early-stage visual perceptual deficits, with no consistent differences observed for N250 amplitude or latency, suggesting relative preservation of later face processing stages. The main limitation of this work is the high heterogeneity across studies analysed.
Dose intensity is critical in diffuse large B-cell lymphoma (DLBCL) but can be limited by toxicity risk. The influence of treatment intensity, illness burden, and socioeconomic status (SES) on survival in DLBCL has not been evaluated on a patient-level analysis. We performed a retrospective study of 344 patients with DLBCL from an urban academic cancer center; 55% received lower intensity treatment (average relative dose intensity [ARDI] of cyclophosphamide and doxorubicin <0.9). ARDI, performance status (PS), Charlson comorbidity index (CCI), and double expressor lymphoma (DEL) were associated with progression-free (PFS) and overall survival (OS). Lower ARDI was linked to worse illness burden, treatment intolerance, and higher-risk disease features. Lower ARDI was associated with worse PFS (HR 2.59, p < 0.001) and OS (HR 4.26, p < 0.001) as well as DLBCL progression (sHR 1.86 p = 0.004) and non-relapse mortality (NRM) (sHR 5.45 p = 0.001) in competing risks analysis. Comprehensive multidisciplinary care is needed to reduce the risks associated with undertreatment in DLBCL.
Organic photocatalysts have attracted extensive attention, while multiple interrelated factors influence photocatalytic activity, making it challenging to identify the dominant structural features that govern performance. Here, we report two pyrene-based hydrogen-bonded organic framework polymorphs, H4PTBA-AA and H4PTBA-ABC, which exhibit nearly identical light absorption, hydrophilicity, and dispersed particle sizes, but they show markedly different excited-state behaviors. Spectroscopic studies reveal that H4PTBA-AA shows smaller exciton binding energy and preferentially forms a charge-transfer (CT)-like state, whereas H4PTBA-ABC is more prone to evolve into an excimer-like state. As a result, the photocatalytic H2 evolution rate of H4PTBA-AA is approximately six times higher than that of H4PTBA-ABC. For the first time, through a relatively well-controlled comparison, this study shows that molecular packing plays an important role in exciton dissociation in HOF frameworks and provides useful insights for the rational design of efficient photocatalytic organic frameworks.
Oncolytic viruses are promising cancer biotherapies but often show limited durability as single agents due to tumor-intrinsic resistance mechanisms. Because therapeutic efficacy is shaped by dynamic virus-tumor-stromal interactions, pharmacologic strategies that reprogram this interface may enhance virotherapy responses. Here, we investigate whether targeting tumor stress and survival pathways with triptolide and its prodrug Minnelide can enhance the oncolytic efficacy of measles virus in colorectal cancer. The in vitro effects of CD46 targeted (MV-GFP) and dual targeted (MV-CD46-muPA) oncolytic MV, alone and with Triptolide were assessed in human CRC cell lines. Mechanistic studies included gene expression analysis, functional proteomics, and western blotting. In vivo efficacy of MV-CD46-muPA combined with Minnelide was evaluated in HT29 and HCT116 xenografts. Biological effects were further characterized using transcriptomic profiling (RNA-seq), targeted gene expression (NanoString), and histological analysis. Triptolide enhanced MV mediated oncolysis in vitro, particularly in BRAF V600E mutant CRC cell lines, and modulated key cancer pathways including AKT, apoptosis and metabolism. In vivo, Minnelide significantly improved the efficacy of systemically administered MV-CD46-muPA in human CRC xenografts, with greater effects in BRAF mutant (HT29) models. The combination modulated cell cycle, metabolism, and survival associated genes, promoted apoptosis, and improved intratumoral viral distribution. These molecular effects resulted in reduced tumor cell proliferation (Ki67), decreased angiogenesis (CD31), and increased apoptosis (TUNEL) relative to single agents. Triptolide and Minnelide significantly enhance the oncolytic efficacy of measles virus in colorectal cancer, particularly in BRAF-mutant tumors in vivo, through reprogramming of virus-tumor-stromal interactions. This reprogramming arises from coordinated modulation of survival, metabolic, and stromal signaling pathways and is accompanied by improved intratumoral viral distribution. These findings position virus-tumor-stromal crosstalk as a central mechanistic axis of virotherapy response and provide a strong rationale for the translational and clinical development of rational virus-drug combination strategies in colorectal cancer and other malignancies.
Existence of linguistic, gender and ethno-racial differences in patients with sepsis remains relatively unknown, especially in the public health domain. Retrospective analysis of data reported by a hospital in South Brooklyn to a New York State sepsis registry was undertaken over a 24-month period. Inclusion criteria were age over 18, available linguistic, gender and ethno-racial data, and registration in the New York State sepsis registry. Patients with missing data fields were excluded from the study. Primary outcome was the correlation of gender, race, ethnic & language-based differences with overall sepsis-based mortality. Secondary outcomes were the correlation of the same demographic variables with rates of mechanical ventilation, vasopressor use, intensive care unit (ICU) admission rates & overall incidence of sepsis and septic shock. Results: 677 patients were included in the final analysis in this single center retrospective observational cohort study and multiple statistically significant primary and secondary outcomes were found. Non-English-speaking patients had a higher incidence rate of sepsis-based mortality when compared to their English-speaking cohorts. The incidence rate difference is -0.36 (95% CI -0.49 to -0.22), with a P-value < 0.0001. A higher rate of vasopressor use was noted among non-English speaking patients when compared to their English speaking counterparts. The difference in incidence rates was -0.35, (95% CI -0.46 to -0.25) with a P-value of < 0.0001. Non-English-speaking patients had a higher incidence of receiving mechanical ventilation when compared to English-speaking cohorts. The incidence rate difference is -0.35 (95% CI -0.48 to -0.22), with a P-value < 0.0001. Non-English-speaking patients had a higher ICU admission rate with an incidence rate difference of -0.30, at a P value < 0.0001. Non-English-speaking patients had a higher sepsis incidence rate (0.70, 95% CI 0.63 to 0.78) compared to English-speaking patients (0.30, 95% CI 0.25 to 0.36), with a P-value of < 0.0001. Non-English-speaking patients experienced a higher incidence of septic shock (0.70, 95% CI 0.63 to 0.78) compared to English-speaking patients (0.30, 95% CI 0.25 to 0.36), with a P-value of < 0.0001. Caucasians showed statistically significant and higher rates across all primary and secondary outcomes albeit with greater statistical fragility. No significant differences were noted with regards to the impact of gender on all outcomes. Conclusion: Significant and multiple linguistic and ethno-racial differences were noted in this single center study with regards to sepsis-based morbidity and mortality outcomes. These differences need to be validated in larger, multi-center trials and could inform future efforts focused on identifying higher risk subsets in patients presenting with sepsis and septic shock in a public health setting.
Secondary Restless Legs Syndrome (RLS) has repeatedly been associated with psychopharmacotherapy, especially antidepressants (ADs) and antipsychotics (APs). However, existing evidence is conflicting in terms of the magnitude of the association as well as the significance of substance classes or individual compounds. The objective of the present study was to evaluate secondary RLS linked to psychotropic medication in real-world, inpatient clinical routine treatment settings. For this purpose, a large dataset from a multinational pharmacovigilance program in German-speaking countries (AMSP) from January 2001 to December 2016 was retrospectively analyzed. In a total of 340 099 monitored inpatients, 67 cases of newly diagnosed and severe RLS related to psychotropic drug treatment were recorded equivalent to a relative frequency of 0.02%. Over 80% of the cases were attributable to two compounds: the AD mirtazapine and the AP quetiapine. Mirtazapine was found in 39 patients, while quetiapine was found in 16 patients with secondary RLS. For both substances drug dosages were generally low at onset of secondary RLS. Most cases exhibited an onset within 1 or 2 days after dosage start or change. Histamine neurotransmission may represent a crucial common denominator in terms of secondary RLS in association with psychopharmacotherapeutics, as both substances exhibit antihistamingeric effects at lower dosages.
The deformation and rupture of a lipid vesicle due to the forced normal approach of an inclusion are essential for optimizing the design of magnetic giant unilamellar vesicles (GUV) [Malik et al., Nanoscale 17, 13720 (2025)NANOHL2040-336410.1039/D5NR00942A], with implications for active colloid-membrane interactions and cellular-scale chemical delivery. Here, we investigate vesicles propelled by a force-driven rigid inclusion and reveal a robust elastohydrodynamic mechanism: the inclusion outpaces the vesicle, sustaining a thinning film that drains symmetrically and self-similarly, largely independent of the initial shape. For soft membranes and small inclusions, the coupling drives a monotonic tension increase that can exceed the lysis tension. Evaluating the maximal tension over a delivery distance, we map an operating window in a vesicle reduced area and size relative to the inclusion.
Soil-transmitted helminth (STH) infections, caused by Ascaris lumbricoides, Trichuris trichiura, and hookworms, are widely distributed in tropical regions and significantly contribute to morbidity and mortality. These parasites share similar life cycles, and treatment is primarily based on benzimidazoles. This study aims to describe the clinical and epidemiological characteristics of STH cases among migrants and travelers who attended the Vall d'Hebron-Drassanes International Health Unit between 2014 and 2024, the treatments administered, and their efficacy. This retrospective descriptive study reviewed STH cases associated with migration or travel during the period 2014-2024. Diagnosis was established either through identification of eggs or larvae in stool samples or through the detection of adult Ascaris lumbricoides worms in digestive samples, always associated with a migratory process or international travel. Clinical and epidemiological data were collected and analyzed using SPSS. A total of 361 STH cases were identified, with a mean age of 32 years. Of these, 77% were migrants, 15.7% were travelers visiting friends and relatives (VFR), and 7.2% were travelers. Hookworm infection was diagnosed in 126 cases, Trichuris trichiura in 113 cases, Ascaris lumbricoides in 87 cases, and 35 patients presented with multiple STH infections. Forty-six (12.7%) were symptomatic, predominantly with gastrointestinal symptoms, and 38% presented with eosinophilia. Ninety-five percent of patients received benzimidazole-based treatment, and therapeutic failure was observed in 7.8% of cases. Cure rates were highest for A. lumbricoides (nearly 100%) and remained above 90% for T. trichiura, whereas hookworm infections showed lower rates, ranging from 83% with albendazole to 92% with mebendazole. Multiple STH infections showed, proportionally, higher rates of therapeutic failure. Most STH cases were diagnosed in asymptomatic migrants and VFRs, highlighting the importance of screening for imported diseases in migrant populations. The observed increase in therapeutic failure with commonly used regimens highlights the need to standardize treatment protocols and consider the incorporation of new drugs and combination therapies.
Preoperative intravenous iron has become increasingly popular as a strategy to optimize hemoglobin before major surgery. However, its potential benefit in non-anaemic patients undergoing cardiac surgery remains unclear. To address this uncertainty, we conducted a systematic review and meta-analysis to investigate whether preoperative IV iron reduces red blood cell transfusion requirements and improves hematologic and clinical outcomes in adults with normal baseline hemoglobin undergoing cardiac surgery. We conducted a systematic review and meta-analysis following PRISMA 2020 guidelines. We searched PubMed, Embase, Scopus, Web of Science, and the Cochrane Library until October 2025 for randomized controlled trials. Eligible studies compared preoperative IV iron to a control (placebo, saline, or standard care) in non-anaemic (per WHO definition) adult patients (≥ 18 years) undergoing cardiac surgery. The primary outcomes were the incidence of postoperative RBC transfusion and the number of units transfused. Secondary outcomes included postoperative hemoglobin level, Postoperative iron indices, length of ICU stay, length of hospital stay (LOS), overall postoperative infection, All-cause mortality, and adverse events possibly related to IV iron (hypersensitivity, anaphylaxis). We used the Cochrane ROB 2 tool for bias assessment and for evidence certainty. Pooled Risk ratios, odds ratios, mean difference, and standardized mean difference with 95% confidence intervals were calculated using random-effects models, with the fixed-effects model applied when heterogeneity was absent or low (I² < 10%). From 529 initial records, 3 RCTs met the inclusion criteria, encompassing 338 patients. The overall risk of bias was low to moderate. Preoperative IV iron significantly reduced the incidence of postoperative RBC transfusion compared to the control group (Risk Ratio [RR] = 0.62; 95% CI 0.43-0.88; p = 0.008; I² = 0%), representing a 38% relative risk reduction. Furthermore, IV iron significantly decreased the mean number of RBC units transfused (Mean Difference [MD] = - 1.08 units; 95% CI - 1.61 to - 0.54; I² = 0%). While no significant difference was observed in hemoglobin levels at 48 h or one week postoperatively, the IV iron group showed significantly higher hemoglobin at 4-6 weeks (MD = 0.84 g/dL; 95% CI 0.41-1.26; p = 0.0001). IV iron also significantly increased postoperative serum ferritin and transferrin saturation. There were no statistically significant differences in overall postoperative infection rates (RR = 1.16; 95% CI 0.64-2.08) or all-cause mortality (Risk Difference = - 0.00; 95% CI - 0.03 to 0.03). The GRADE certainty of evidence for the primary outcome was moderate. In non-anaemic adult patients undergoing cardiac surgery, preoperative IV iron administration significantly reduces the incidence of postoperative RBC transfusion and the total volume of blood transfused. This intervention also improves hemoglobin levels during the 4-6 week recovery period without an increased risk of infection or mortality. The moderate-certainty evidence suggests this is a beneficial strategy, though further adequately powered RCTs are warranted to strengthen these findings. CRD420251161421.