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Clonal hematopoiesis (CH) is defined by the expansion of a lineage of genetically identical cells in blood. Genetic lesions that confer a fitness advantage, such as point mutations or mosaic chromosomal alterations (mCAs) in genes associated with hematologic malignancy, are frequent mediators of CH. However, recent analyses of both single cell-derived colonies of hematopoietic cells and population sequencing cohorts have revealed CH frequently occurs in the absence of known driver genetic lesions. To characterize CH without known driver genetic lesions, we used 51,399 deeply sequenced whole genomes from the NHLBI TOPMed sequencing initiative to perform simultaneous germline and somatic mutation analyses among individuals without leukemogenic point mutations (LPM), which we term CH-LPMneg. We quantified CH by estimating the total mutation burden. Because estimating somatic mutation burden without a paired-tissue sample is challenging, we developed a novel statistical method, the Genomic and Epigenomic informed Mutation (GEM) rate, that uses external genomic and epigenomic data sources to distinguish artifactual signals from true somatic mutations. We performed a genome-wide association study of GEM to discover the germline determinants of CH-LPMneg. After fine-mapping and variant-to-gene analyses, we identified seven genes associated with CH-LPMneg ( TCL1A, TERT, SMC4, NRIP1, PRDM16 , MSRA , SCARB1 ), and one locus associated with a sex-associated mutation pathway ( SRGAP2C) . We performed a secondary analysis excluding individuals with mCAs, finding that the genetic architecture was largely unaffected by their inclusion. Functional analyses of SMC4 and NRIP1 implicated altered HSC self-renewal and proliferation as the primary mediator of mutation burden in blood. We then performed comprehensive multi-tissue transcriptomic analyses, finding that the expression levels of 404 genes are associated with GEM. Finally, we performed phenotypic association meta-analyses across four cohorts, finding that GEM is associated with increased white blood cell count and increased risk for incident peripheral artery disease, but is not significantly associated with incident stroke or coronary disease events. Overall, we develop GEM for quantifying mutation burden from WGS without a paired-tissue sample and use GEM to discover the genetic, genomic, and phenotypic correlates of CH-LPMneg.
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Background: Sleep problems occur in many university students which affects their mental health and daily functioning. Cognitive behavioural therapy for insomnia (CBT-I) has been proven effective in adults but research in university students, who struggle to maintain a 24-hour rhythm, is still limited. We hypothesize that a guided digital CBT-I intervention, enriched with components on the biological clock ('i-Sleep & BioClock') will be effective in reducing insomnia severity and improving mental health outcomes for students with sleep problems. Objectives: We aim to evaluate the effectiveness of a guided online sleep and biological clock self-help intervention in improving sleep, depression symptoms, anxiety symptoms, functioning, academic performance, and quality of life in university students at 6 weeks and 18 weeks. Methods: This is a two-arm parallel-group superiority randomized controlled trial, comparing a 5-week guided online 'i-Sleep & BioClock' intervention to online psychoeducation (PE). We aim to include 192 university students (Bachelor, Master, and PhD) with at least subthreshold insomnia (Insomnia Severity Index ≥10), aged ≥16, who can speak Dutch or English. We are excluding students with current risk for suicide or night shifts. The primary outcome is insomnia severity. Secondary outcomes include sleep estimates (sleep and light exposure diary), depression, anxiety, functioning, quality of life, and academic performance. The effectiveness of the intervention compared to online PE will be evaluated using linear mixed models. Discussion: The current study tests the effectiveness of an online self-help intervention for university students who suffer from sleep problems. This trial builds upon an open feasibility study and will provide evidence of an online guided self-help program for students. The findings of this study will determine the potential wider dissemination of the intervention to address the high need for available and accessible help for students experiencing insomnia. Trial registration: ClinicalTrials.Gov (NCT06023693), registered on August 3rd, 2023.
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Substance use, including cigarettes and cannabis, is associated with poorer sustained attention in late adolescence and early adulthood. Previous studies were predominantly cross-sectional or under-powered and could not indicate if impairment in sustained attention was a predictor of substance use or a marker of the inclination to engage in such behavior. This study explored the relationship between sustained attention and substance use across a longitudinal span from ages 14 to 23 in over 1000 participants. Behaviors and brain connectivity associated with diminished sustained attention at age 14 predicted subsequent increases in cannabis and cigarette smoking, establishing sustained attention as a robust biomarker for vulnerability to substance use. Individual differences in network strength relevant to sustained attention were preserved across developmental stages and sustained attention networks generalized to participants in an external dataset. In summary, brain networks of sustained attention are robust, consistent, and able to predict aspects of later substance use.
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Atenção , Encéfalo , Transtornos Relacionados ao Uso de Substâncias , Humanos , Adolescente , Masculino , Adulto Jovem , Feminino , Atenção/fisiologia , Transtornos Relacionados ao Uso de Substâncias/fisiopatologia , Encéfalo/fisiologia , Estudos Longitudinais , Adulto , Imageamento por Ressonância Magnética , Fumar Cigarros/efeitos adversosRESUMO
OBJECTIVES: Dose exposure is considered relevant for drug-associated falls in older adults, pointing to an importance of drug metabolism. Aim was to analyze individual factors altering drug metabolism such as enzyme saturation by drug exposure and pharmacogenetics in the context of drug-associated falls. DESIGN: Prospective population-based study (ActiFE-Ulm study). SETTING AND PARTICIPANTS: Community-dwelling older adults. METHODS: Focus was laid on the metabolism by polymorphic cytochrome P450 (CYP) enzymes CYP2C19, 2C9, and 2D6. Relevant variants of pharmacogenes were analyzed. Logistic binary regression analysis was used to calculate odds ratios (ORs) and 95% CIs for falls observed prospectively over a 1-year period with drug metabolism characteristics. RESULTS: In total, 1377 participants were included in the analysis. Although the phenotype predicted by the genotype was not, the use of drugs metabolized by CYP2C19 was associated with falls. Drugs not known as fall risk-increasing drugs (FRIDs; ie, non-FRIDs), but metabolized by CYP2C19, showed an OR of 1.46 (1.11-1.93) in adjusted analysis. Significant effect modification was observed for a reduced CYP2C19 activity phenotype with non-FRIDs metabolized by CYP2C19. CONCLUSIONS AND IMPLICATIONS: This study suggests an association between the occurrence of falls in older adults and the metabolic capacity of CYP2C19. Thus, an important step toward prevention of falls might be to personalize dosage and treatment length of the main drug classes known to be CYP2C19 substrates, such as many antidepressants, opioids, and sedatives, but also proton pump inhibitors in particular in poor and intermediate metabolizers.
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Peripheral neuropathies of the foot and ankle can be challenging to diagnose clinically due to concomitant traumatic and nontraumatic or degenerative orthopedic conditions. Although clinical history, physical examination, and electrodiagnostic testing comprised of nerve conduction velocities and electromyography are used primarily for the identification and classification of peripheral nerve disorders, MR neurography (MRN) can be used to visualize the peripheral nerves as well as the skeletal muscles of the foot and ankle for primary neurogenic pathology and skeletal muscle denervation effect. Proper knowledge of the anatomy and pathophysiology of peripheral nerves is important for an MRN interpretation.
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Tornozelo , Pé , Imageamento por Ressonância Magnética , Doenças do Sistema Nervoso Periférico , Humanos , Imageamento por Ressonância Magnética/métodos , Doenças do Sistema Nervoso Periférico/diagnóstico por imagem , Doenças do Sistema Nervoso Periférico/diagnóstico , Pé/diagnóstico por imagem , Pé/inervação , Tornozelo/diagnóstico por imagem , Tornozelo/inervação , Nervos Periféricos/diagnóstico por imagemRESUMO
BACKGROUND: Microglial activation is one hallmark of Alzheimer disease (AD) neuropathology but the impact of the regional interplay of microglia cells in the brain is poorly understood. We hypothesized that microglial activation is regionally synchronized in the healthy brain but experiences regional desynchronization with ongoing neurodegenerative disease. We addressed the existence of a microglia connectome and investigated microglial desynchronization as an AD biomarker. METHODS: To validate the concept, we performed microglia depletion in mice to test whether interregional correlation coefficients (ICCs) of 18 kDa translocator protein (TSPO)-PET change when microglia are cleared. Next, we evaluated the influence of dysfunctional microglia and AD pathophysiology on TSPO-PET ICCs in the mouse brain, followed by translation to a human AD-continuum dataset. We correlated a personalized microglia desynchronization index with cognitive performance. Finally, we performed single-cell radiotracing (scRadiotracing) in mice to ensure the microglial source of the measured desynchronization. RESULTS: Microglia-depleted mice showed a strong ICC reduction in all brain compartments, indicating microglia-specific desynchronization. AD mouse models demonstrated significant reductions of microglial synchronicity, associated with increasing variability of cellular radiotracer uptake in pathologically altered brain regions. Humans within the AD-continuum indicated a stage-depended reduction of microglia synchronicity associated with cognitive decline. scRadiotracing in mice showed that the increased TSPO signal was attributed to microglia. CONCLUSION: Using TSPO-PET imaging of mice with depleted microglia and scRadiotracing in an amyloid model, we provide first evidence that a microglia connectome can be assessed in the mouse brain. Microglia synchronicity is closely associated with cognitive decline in AD and could serve as an independent personalized biomarker for disease progression.
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Doença de Alzheimer , Encéfalo , Disfunção Cognitiva , Microglia , Animais , Microglia/metabolismo , Doença de Alzheimer/metabolismo , Doença de Alzheimer/patologia , Camundongos , Disfunção Cognitiva/metabolismo , Humanos , Encéfalo/metabolismo , Encéfalo/patologia , Modelos Animais de Doenças , Tomografia por Emissão de Pósitrons , Receptores de GABA/metabolismo , Masculino , Camundongos Transgênicos , Conectoma/métodos , FemininoRESUMO
Dimethyl disulfide (DMDS), one of the smallest organic molecules with an S-S bond, serves as a model system for understanding photofragmentation in polypeptides and proteins. Prior studies of DMDS photodissociation excited at â¼266 nm and â¼248 nm have elucidated the mechanisms of S-S and C-S bond cleavage, which involve the lowest excited electronic states S1 and S2. Far less is known about the dissociation mechanisms and electronic structure of relevant excited states of DMDS excited at â¼200 nm. Herein we present calculations of the electronic structure and properties of electronic states S1-S6 accessed when DMDS is excited at â¼200 nm. Our analysis includes a comparison of theoretical and experimental UV spectra, as well as theoretically predicted one-dimensional cuts through the singlet and triplet potential energy surfaces along the S-S and C-S bond dissociation coordinates. Finally, we present calculations of spin-orbit coupling constants at the Franck-Condon geometry to assess the likelihood of ultrafast intersystem crossing. We show that choosing an accurate yet computationally efficient electronic structure method for calculating the S0-S6 potential energy surfaces along relevant dissociation coordinates is challenging due to excited states with doubly excited character and/or mixed Rydberg-valence character. Our findings demonstrate that the extended multi-state complete active space second-order perturbation theory (XMS-CASPT2) balances this computational efficiency and accuracy, as it captures both the Rydberg character of states in the Franck-Condon region and multiconfigurational character toward the bond-dissociation limits. We compare the performance of XMS-CASPT2 to a new variant of equation of motion coupled cluster theory with single, double, and perturbative triple corrections, EOM-CCSD(T)(a)*, finding that EOM-CCSD(T)(a)* significantly improves the treatment of doubly excited states compared to EOM-CCSD, but struggles to quantitatively capture asymptotic energies along bond dissociation coordinates for these states.
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OBJECTIVE: The aim of the study was to evaluate time to closure, bursting pressures and luminal diameters of a single and double-layer end-to-end anastomoses in normal equine descending colon. STUDY DESIGN: Experimental study. SAMPLE POPULATION: Eight adult horses. METHODS: Four segments of descending colon from each horse were randomly assigned to a control (n = 8, CON), one-layer (n = 12, group 1; continuous Lembert pattern), or two-layer group (n = 12, group 2; simple continuous oversewn with Cushing pattern). Anastomoses were performed, and time to closure and luminal diameter were measured. Bursting pressures were determined, and location of failure was recorded. Mixed analysis of variance (ANOVA) was employed. RESULTS: Mean time to completion was decreased (p = .003) in group 1 (18.6 min ± 22.8 s) compared with group 2 (21.35 min ± 22.8 s). Luminal diameter was reduced (p < .0001) in group 2 (47 ± 2.46 mm) compared to group 1 (65 ± 2.77 mm). Location of failure was remote to the anastomosis in all but one segment; therefore, differences in anastomotic bursting pressures could not be determined. CONCLUSION: Two-layer closures resulted in significant luminal reduction and took longer to complete than one-layer anastomoses. CLINICAL SIGNIFICANCE: Use of one-layer closures may be advantageous primarily with respect to luminal diameter.
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Recent advances in imaging suggested that spatial organization of hematopoietic cells in their bone marrow microenvironment (niche) regulates cell expansion, governing progression, and leukemic transformation of hematological clonal disorders. However, our ability to interrogate the niche in pre-malignant conditions has been limited, as standard murine models of these diseases rely largely on transplantation of the mutant clones into conditioned mice where the marrow microenvironment is compromised. Here, we leveraged live-animal microscopy and ultralow dose whole body or focal irradiation to capture single cells and early expansion of benign/pre-malignant clones in the functionally preserved microenvironment. 0.5 Gy whole body irradiation (WBI) allowed steady engraftment of cells beyond 30 weeks compared to non-conditioned controls. In-vivo tracking and functional analyses of the microenvironment showed no change in vessel integrity, cell viability, and HSC-supportive functions of the stromal cells, suggesting minimal inflammation after the radiation insult. The approach enabled in vivo imaging of Tet2+/- and its healthy counterpart, showing preferential localization within a shared microenvironment while forming discrete micro-niches. Notably, stationary association with the niche only occurred in a subset of cells and would not be identified without live imaging. This strategy may be broadly applied to study clonal disorders in a spatial context.
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Hematopoiese Clonal , Nicho de Células-Tronco , Animais , Camundongos , Nicho de Células-Tronco/efeitos da radiação , Células-Tronco Hematopoéticas/efeitos da radiação , Células-Tronco Hematopoéticas/metabolismo , Irradiação Corporal Total , Camundongos Endogâmicos C57BL , Rastreamento de Células/métodos , Microscopia Intravital/métodosRESUMO
The modern global food system is highly unsustainable, shaped by industrialisation and corporate consolidation, with negative repercussions on the environment and biodiversity as well as human health. This paper looks at the burgeoning economy in neglected and underutilised species (NUS) in the Western Cape, South Africa, as a potential innovation that could make the local food system more socially and ecologically resilient. Although, at present, NUS are only marginally included in the local food system and policy discussions, NUS increasingly appear in the high-end food industry, driven by international gastronomic trends. These species hold potential as climate resilient, nutritionally dense, and socially and culturally significant foods in the region, but they also carry ecological and social risks. We critically examine the fledgling NUS economy in the Cape Town area to unpack the motivations and challenges associated with the potentially transformative inclusion of these foods into the local food system. We demonstrate that the main risks associated with NUS are negative ecological repercussions, privatisation of the NUS economy, and the reproduction and further entrenchment of unequal power and race dynamics in the region. To mitigate these risks and actualise the related benefits associated with NUS, engagement with the ecological, social, and political context of NUS needs to be significantly deepened. This is particularly true for those working in the high-end food industry, who appear to be driving the NUS economy, and will require education around sustainability and Traditional Ecological Knowledge (TEK), as well as a foregrounding awareness of power dynamics.
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BACKGROUND: Mobile Integrated Health-Community Paramedicine (MIH-CP) is a novel approach that may reduce the rural-urban disparity in vaccination uptake in the United States. MIH-CP providers, as physician extenders, offer clinical follow-up and wrap-around services in homes and communities, uniquely positioning them as trusted messengers and vaccine providers. This study explores stakeholder perspectives on feasibility and acceptability of community paramedicine vaccination programs. METHODS: We conducted semi-structured qualitative interviews with leaders of paramedicine agencies with MIH-CP, without MIH-CP, and state/regional leaders in Indiana. Interviews were audio recorded, transcribed verbatim, and analyzed using content analysis. RESULTS: We interviewed 24 individuals who represented EMS organizations with MIH-CP programs (MIH-CP; n = 10), EMS organizations without MIH-CP programs (non-MIH-CP; n = 9), and state/regional administrators (SRA; n = 5). Overall, the sample included professionals with an average of 19.6 years in the field (range: 1-42 years). Approximately 75% (n = 14) were male, and all identified as non-Hispanic white. MIH-CPs reported they initiated a vaccine program to reach underserved areas, operating as a health department extension. Some MIH-CPs integrated existing services, such as food banks, with vaccine clinics, while other MIH-CPs focused on providing vaccinations as standalone initiatives. Key barriers to vaccination program initiation included funding and vaccinations being a low priority for MIH-CP programs. However, participants reported support for vaccine programs, particularly as they provided an opportunity to alleviate health disparities and improve community health. MIH-CPs reported low vaccine hesitancy in the community when community paramedics administered vaccines. Non-CP agencies expressed interest in launching vaccine programs if there is clear guidance, sustainable funding, and adequate personnel. CONCLUSIONS: Our study provides important context on the feasibility and acceptability of implementing an MIH-CP program. Findings offer valuable insights into reducing health disparities seen in vaccine uptake through community paramedics, a novel and innovative approach to reduce health disparities in rural communities.
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Estudos de Viabilidade , Pesquisa Qualitativa , Humanos , Masculino , Feminino , Entrevistas como Assunto , Indiana , Adulto , Vacinação/estatística & dados numéricos , Vacinação/psicologia , Programas de Imunização/organização & administração , Serviços de Saúde Comunitária/organização & administração , Pessoa de Meia-Idade , Aceitação pelo Paciente de Cuidados de Saúde/estatística & dados numéricos , Aceitação pelo Paciente de Cuidados de Saúde/psicologia , ParamedicinaRESUMO
While multiple factors impact disease, artificial intelligence (AI) studies in medicine often use small, non-diverse patient cohorts due to data sharing and privacy issues. Federated learning (FL) has emerged as a solution, enabling training across hospitals without direct data sharing. Here, we present FL-PedBrain, an FL platform for pediatric posterior fossa brain tumors, and evaluate its performance on a diverse, realistic, multi-center cohort. Pediatric brain tumors were targeted due to the scarcity of such datasets, even in tertiary care hospitals. Our platform orchestrates federated training for joint tumor classification and segmentation across 19 international sites. FL-PedBrain exhibits less than a 1.5% decrease in classification and a 3% reduction in segmentation performance compared to centralized data training. FL boosts segmentation performance by 20 to 30% on three external, out-of-network sites. Finally, we explore the sources of data heterogeneity and examine FL robustness in real-world scenarios with data imbalances.
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Inteligência Artificial , Neoplasias Encefálicas , Humanos , Criança , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/patologia , Adolescente , Feminino , Masculino , Pré-Escolar , Disseminação de Informação/métodosRESUMO
Genetic studies have identified numerous regions associated with plasma fibrinogen levels in Europeans, yet missing heritability and limited inclusion of non-Europeans necessitates further studies with improved power and sensitivity. Compared with array-based genotyping, whole genome sequencing (WGS) data provides better coverage of the genome and better representation of non-European variants. To better understand the genetic landscape regulating plasma fibrinogen levels, we meta-analyzed WGS data from the NHLBI's Trans-Omics for Precision Medicine (TOPMed) program (n=32,572), with array-based genotype data from the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium (n=131,340) imputed to the TOPMed or Haplotype Reference Consortium panel. We identified 18 loci that have not been identified in prior genetic studies of fibrinogen. Of these, four are driven by common variants of small effect with reported MAF at least 10 percentage points higher in African populations. Three signals (SERPINA1, ZFP36L2, and TLR10) contain predicted deleterious missense variants. Two loci, SOCS3 and HPN, each harbor two conditionally distinct, non-coding variants. The gene region encoding the fibrinogen protein chain subunits (FGG;FGB;FGA), contains 7 distinct signals, including one novel signal driven by rs28577061, a variant common in African ancestry populations but extremely rare in Europeans (MAFAFR=0.180; MAFEUR=0.008). Through phenome-wide association studies in the VA Million Veteran Program, we found associations between fibrinogen polygenic risk scores and thrombotic and inflammatory disease phenotypes, including an association with gout. Our findings demonstrate the utility of WGS to augment genetic discovery in diverse populations and offer new insights for putative mechanisms of fibrinogen regulation.
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Evidence indicating that exercise benefits mental health symptoms across a range of mental health diagnoses spans decades of scientific literature; however, fewer studies have examined the impact of exercise on posttraumatic stress disorder (PTSD). Exercise is an accessible, cost-effective, and scalable treatment option that has the potential to improve both physiological and psychological symptoms among individuals with PTSD. The purpose of this chapter is to review empirical literature on the role of exercise in the treatment of PTSD. Researchers have demonstrated that exercise improves PTSD symptoms as both a stand-alone treatment and as an adjunct to cognitive behavioral and trauma-focused therapies. Additional research is needed to clarify mechanisms that account for the impacts of exercise on PTSD and to identify which components of exercise (e.g., type of exercise, dose, intensity, frequency) are the most beneficial.
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OBJECTIVE: The Nine Item ARFID Scale (NIAS) is a widely used measure assessing symptoms of avoidant/restrictive food intake disorder (ARFID). Previous studies suggest that individuals with eating disorders driven by shape/weight concerns also have elevated scores on the NIAS. To further describe NIAS scores among individuals with diverse current and previous eating disorders, we characterized NIAS scores in a large sample of individuals with eating disorders and evaluated overlap in symptoms measured by the NIAS and the Eating Disorder Examination-Questionnaire (EDE-Q) version 6.0. METHOD: Our sample comprised 9148 participants from the Eating Disorders Genetics Initiative Sweden (EDGI-SE), who completed surveys including NIAS and EDE-Q. NIAS scores were calculated and compared by eating disorder diagnostic group using descriptive statistics and linear models. RESULTS: Participants with current anorexia nervosa demonstrated the highest mean NIAS scores and had the greatest proportion (57.0%) of individuals scoring above a clinical cutoff on at least one of the NIAS subscales. Individuals with bulimia nervosa, binge-eating disorder, and other specified feeding or eating disorder also demonstrated elevated NIAS scores compared to individuals with no lifetime history of an eating disorder (ps < 0.05). All subscales of the NIAS showed small to moderate correlations with all subscales of the EDE-Q (rs = 0.26-0.40). DISCUSSION: Our results substantiate that individuals with eating disorders other than ARFID demonstrate elevated scores on the NIAS, suggesting that this tool is inadequate on its own for differentiating ARFID from shape/weight-motivated eating disorders. Further research is needed to inform clinical interventions addressing the co-occurrence of ARFID-related drivers and shape/weight-related motivation for dietary restriction.
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The use of glucagon-like peptide-1 receptor agonists (GLP-1RA) has experienced rapid growth amidst the obesity epidemic in the United States. While originally developed for glucose control in Type 2 Diabetes Mellitus, the scope of these agents now extends to encompass weight loss and cardiovascular risk reduction. GLP-1RAs have the potential to induce significant weight loss, in combination with lifestyle modifications, among adults who are overweight or obese. Furthermore, these agents demonstrate efficacy in ameliorating hyperglycemia, enhancing insulin sensitivity, regulating blood pressure, improving cardiometabolic parameters, mitigating kidney dysfunction, and potentially reducing the risk of several obesity-related cancers. Drug-related toxicity is primarily gastrointestinal and active management can prevent drug discontinuation. Obesity is associated both with an increased incidence of malignancy but also with decreased survival. More research is needed to evaluate the potential use of GLP-1RA to modify the endocrine function of adipocytes, regulate the chronic inflammatory state associated with obesity, and prospective applications in oncology. These agents can impact patients with gynecologic malignancies both through their direct mechanism of action as well as potential drug toxicity.
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Varicocele is a prevalent condition in the infertile male population. However, to date, which patients may benefit most from varicocele repair is still a matter of debate. The purpose of this study was to evaluate whether certain preintervention sperm parameters are predictive of successful varicocele repair, defined as an improvement in total motile sperm count (TMSC). We performed a retrospective study on 111 patients with varicocele who had undergone varicocele repair, collected from the Department of Endocrinology, Metabolic Diseases and Nutrition, University of Catania (Catania, Italy), and the Unit of Urology at the Selcuk University School of Medicine (Konya, Türkiye). The predictive analysis was conducted through the use of the Brain Project, an innovative tool that allows a complete and totally unbiased search of mathematical expressions that relate the object of study to the various parameters available. Varicocele repair was considered successful when TMSC increased by at least 50% of the preintervention value. For patients with preintervention TMSC below 5 × 106, improvement was considered clinically relevant when the increase exceeded 50% and the absolute TMSC value was >5 × 106. From the preintervention TMSC alone, we found a model that predicts patients who appear to benefit little from varicocele repair with a sensitivity of 50.0% and a specificity of 81.8%. Varicocele grade and serum follicle-stimulating hormone (FSH) levels did not play a predictive role, but it should be noted that all patients enrolled in this study were selected with intermediate- or high-grade varicocele and normal FSH levels. In conclusion, preintervention TMSC is predictive of the success of varicocele repair in terms of TMSC improvement in patients with intermediate- or high-grade varicoceles and normal FSH levels.
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A series of Au(I) complexes containing unsymmetrical N-heterocyclic carbene (imidazolylidene and benzimidazolylidene) functionalized with a xyloside group and an alkyl moiety (methyl and mesityl) was prepared using efficient procedures from D-xylose. Their characterization was carried out in solution by multinuclear NMR, HR-MS spectrometry and cyclic voltammetry, as well as in the solid state by means of single crystal X-ray diffraction analysis for two of them. Evaluation of their ability to inhibit bacterial growth showed a preference for a Gram-positive strain, Staphylococcus aureus, over a Gram-negative strain, Pseudomonas aeruginosa.