Although specific risk factors for brain alterations in bipolar disorders (BD) are currently unknown, obesity impacts the brain and is highly prevalent in BD. Gray matter correlates of obesity in BD have been well documented, but we know much less about brain white matter abnormalities in people who have both obesity and BD. We obtained body mass index (BMI) and diffusion tensor imaging derived fractional anisotropy (FA) from 22 white matter tracts in 899 individuals with BD, and 1287 control individuals from 20 cohorts in the ENIGMA-BD working group. In a mega-analysis, we investigated the associations between BMI, diagnosis or medication and FA. Lower FA was associated with both BD and BMI in six white matter tracts, including the corpus callosum and thalamic radiation. Higher BMI or BD were uniquely associated with lower FA in three and six white matter tracts, respectively. People not receiving lithium treatment had a greater negative association between FA and BMI than people treated with lithium in the posterior thalamic radiation and sagittal stratum. In three tracts BMI accounted for 10.5 to 17% of the negative association between the number of medication classes other than lithium and FA. Both overweight/obesity and BD demonstrated lower FA in some of the same regions. People prescribed lithium had a weaker association between BMI and FA than people not on lithium. In contrast, greater weight contributed to the negative associations between medications and FA. Obesity may add to brain alterations in BD and may play a role in effects of medications on the brain.
- MeSH
- Anisotropy MeSH
- White Matter * pathology diagnostic imaging metabolism MeSH
- Bipolar Disorder * pathology metabolism MeSH
- Adult MeSH
- Body Mass Index MeSH
- Middle Aged MeSH
- Humans MeSH
- Brain pathology MeSH
- Obesity * pathology metabolism complications MeSH
- Gray Matter MeSH
- Diffusion Tensor Imaging methods MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
INTRODUCTION: Despite national guidelines and use of intrapartum antibiotic prophylaxis (IAP), Streptococcus agalactiae (group B streptococci (GBS)) is still a leading cause of morbidity and mortality in newborns in Europe and the United States. The European DEVANI (Design of a Vaccine Against Neonatal Infections) program assessed the neonatal GBS infection burden in Europe, the clinical characteristics of colonized women and microbiological data of GBS strains in colonized women and their infants with early-onset disease (EOD). METHODS: Overall, 1083 pregnant women with a GBS-positive culture result from eight European countries were included in the study. Clinical obstetrical information was collected by a standardized questionnaire. GBS strains were characterized by serological and molecular methods. RESULTS: Among GBS carriers included in this study after testing positive for GBS by vaginal or recto-vaginal sampling, 13.4% had at least one additional obstetrical risk factor for EOD. The five most common capsular types (i.e., Ia, Ib, II, III and V) comprised ~ 93% of GBS carried. Of the colonized women, 77.8% received any IAP, and in 49.5% the IAP was considered appropriate. In our cohort, nine neonates presented with GBS early-onset disease (EOD) with significant regional heterogeneity. CONCLUSIONS: Screening methods and IAP rates need to be harmonized across Europe in order to reduce the rates of EOD. The epidemiological data from eight different European countries provides important information for the development of a successful GBS vaccine.
- MeSH
- Antibiotic Prophylaxis MeSH
- Adult MeSH
- Pregnancy Complications, Infectious * epidemiology microbiology MeSH
- Humans MeSH
- Young Adult MeSH
- Infant, Newborn MeSH
- Carrier State epidemiology microbiology MeSH
- Streptococcus agalactiae * isolation & purification classification MeSH
- Streptococcal Infections * epidemiology microbiology prevention & control MeSH
- Pregnancy MeSH
- Vagina microbiology MeSH
- Infectious Disease Transmission, Vertical statistics & numerical data prevention & control MeSH
- Check Tag
- Adult MeSH
- Humans MeSH
- Young Adult MeSH
- Infant, Newborn MeSH
- Pregnancy MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Multicenter Study MeSH
- Geographicals
- Europe MeSH
INTRODUCTION: Amyloid precursor protein (APP) undergoes striking changes following traumatic brain injury (TBI). Considering its role in the control of gene expression, we investigated whether APP regulates transcription and translation following TBI. METHODS: We assessed brain morphology (n = 4-9 mice/group), transcriptome (n = 3 mice/group), proteome (n = 3 mice/group), and behavior (n = 17-27 mice/group) of wild-type (WT) and APP knock-out (KO) mice either untreated or 10-weeks following TBI. RESULTS: After TBI, WT mice displayed transcriptional programs consistent with late stages of brain repair, hub genes were predicted to impact translation and brain proteome showed subtle changes. APP KO mice largely replicated this transcriptional repertoire, but showed no transcriptional nor translational response to TBI. DISCUSSION: The similarities between WT mice following TBI and APP KO mice suggest that developmental APP deficiency induces a condition reminiscent of late stages of brain repair, hampering the control of gene expression in response to injury. HIGHLIGHTS: 10-weeks after TBI, brains exhibit transcriptional profiles consistent with late stage of brain repair. Developmental APP deficiency maintains brains perpetually in an immature state akin to late stages of brain repair. APP responds to TBI by changes in gene expression at a transcriptional and translational level. APP deficiency precludes molecular brain changes in response to TBI.
- MeSH
- Amyloid beta-Protein Precursor * genetics MeSH
- Disease Models, Animal MeSH
- Brain * metabolism pathology MeSH
- Mice, Inbred C57BL MeSH
- Mice, Knockout MeSH
- Mice MeSH
- Brain Injuries * metabolism genetics pathology MeSH
- Proteome * metabolism MeSH
- Proteomics MeSH
- Transcriptome * MeSH
- Brain Injuries, Traumatic * metabolism genetics pathology MeSH
- Animals MeSH
- Check Tag
- Male MeSH
- Mice MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
Growing evidence suggests that specific volatile organic compound (VOC) profiles may reflect key pathophysiological processes in Parkinson's disease (PD), including alterations in the microbiome, metabolism, and oxidative stress. Identifying reliable VOC biomarkers could enable non-invasive tests for early diagnosis, disease monitoring, and therapy evaluation. This review examines VOC analysis in biological matrices such as breath, skin, and stool, outlining current research and future applications in PD. We evaluate analytical techniques based on sensitivity, specificity, and clinical applicability. Additionally, we classify VOCs identified in previous studies alongside their proposed biological origins. Special attention is given to short-chain fatty acids, produced by the gut microbiome, a novel target in PD research. Our findings highlight the need for larger cohort studies and standardized protocols to advance VOC-based diagnostics in PD. Understanding the interplay between VOCs and PD may facilitate biomarker discovery, enhancing non-invasive diagnostic strategies and personalized disease management.
- Publication type
- Journal Article MeSH
I po maximální standardní léčbě, která zahrnuje maximální chirurgickou resekci, adjuvantní radioterapii a souběžnou a následně adjuvantní chemoterapii alkylační látkou temozolomidem (TMZ), což je režim ověřený klinickými studiemi fáze III, zůstává celkové přežití u glioblastomu (GB), nejčastějšího a nejmalignějšího podtypu gliomu vysokého stupně, omezené. Pětileté přežití je nižší než 10 %, přičemž obvyklou příčinou úmrtí je lokální recidiva. Nejčastěji navrhovanými alternativami čistě paliativní léčby jsou reoperace, opětovné podání alkylačních látek včetně TMZ nebo léčba relapsu lomustinem a opakované ozařování. Opakované ozařování se jeví být možností pro GB v pečlivě vybraných případech a volba ozařovací metody mezi standardní frakcionací, stereotaktickou hypofrakcionovanou radioterapií a stereotaktickou radiochirurgií musí zohledňovat technické a s pacientem související faktory a průběh relapsu. Použití alkylačních látek TMZ a lomustinu v kombinaci s opakovaným ozařováním se zdá být strategií s přínosem zejména po výběru terapie na základě metylačního stavu promotoru O6-metylguanin-DNA-metyltransferázy. Budoucími směry výzkumu jsou neoadjuvantní imunoterapie a identifikace molekulárních biomarkerů, přesnější vymezení cílového objemu na základě pozitronové emisní tomografie/výpočetní tomografie s aminokyselinami, ale také použití inhibitorů glykolýzy ve spojení s látkami proti cévnímu endoteliálnímu růstovému faktoru. Omezení kumulativních ekvivalentních dávek po 2 Gy (EQD2) na mozkovou tkáň parenchym do výše 100 Gy v případě ultrahypofrakcionovaných režimů a do výše < 120 Gy EQD2 v případě jiných frakcionačních schémat by mohlo omezit riziko mozkové radionekrózy pod 10 %.
Even after administration of a maximal standard treatment, including gross surgical resection, adjuvant radiotherapy plus concurrent and subsequently adjuvant chemotherapy with an alkylating agent, temozolomide (TMZ), a regimen validated by phase III clinical trials, the overall survival in glioblastoma (GB), which is the most frequent and malignant subtype of high-grade glioma, remains limited. With a 5-year survival rate below 10%, local recurrence is the usual cause of death. Re-operation, re-challenge with alkylating agents including TMZ or treatment of relapse with lomustine, and re-irradiation are the most frequently proposed alternatives to purely palliative treatment. Re-irradiation seems to be an option for GB in carefully selected cases, and the choice of irradiation method between standard fractionation, stereotactic hypo-fractionated radiotherapy, and stereotactic radiosurgery must take into account technical and patient-related factors and relapse pattern. The use of alkylating agents TMZ and lomustine, in combination with re-irradiation, seems to be a strategy with benefits especially after a selection of therapy based on the methylation status of the O6-methylguanine-DNA-methyltransferase promoter. Neo-adjuvant immunotherapy and identification of molecular biomarkers, more precise delineation of the target volume, based on amino-acid positron emission tomography/CT (PET-CT), but also the use of glycolytic inhibitors in association with anti-vascular endothelial growth factor agents are future research directions. Limiting the cumulative equivalent dose in 2 Gy (EQD2) received by the brain tissue to 100 Gy in the case of ultra-hypo-fractionated regimens and to < 120 Gy EQD2 in the case of other fractionation schemes could limit the risk of cerebral radio-necrosis below 10%.
- Keywords
- radionekróza,
- MeSH
- Glioblastoma * radiotherapy MeSH
- Humans MeSH
- Retreatment MeSH
- Radiosurgery methods MeSH
- Radiotherapy methods MeSH
- Check Tag
- Humans MeSH
- Publication type
- Review MeSH
In this manuscript, we highlight the evolutionary origins of mitochondria from bacterial endosymbionts and explore their contributions to health, energy metabolism, and neural-immune communication. Mitochondrial adaptability and the roles played by these organelles in promoting oxygen-dependent ATP production provide critical regulation of cognition, motivation, and inflammation. Hypoxia has been identified as an important initiator of inflammation, neurodegeneration, and mitochondrial dysfunction, emphasizing the overall importance of oxygen homeostasis to health and well-being. The Behavior, Exercise, Relaxation, and Nutrition framework highlights these observations as tools that can be used to optimize mitochondrial efficiency. Interestingly, mitochondrial dysfunction may also be linked to psychiatric disorders (e.g., schizophrenia), a hypothesis that focuses on energy dynamics, a proposal that may extend our understanding of these disorders beyond traditional neurotransmitter-focused concepts. Collectively, these perspectives underscore the critical contributions of mitochondria to health and disease and offer a novel framework that may help to explain the connections featured in mind-body medicine.
- MeSH
- Biological Evolution MeSH
- Pain * metabolism physiopathology MeSH
- Exercise * physiology MeSH
- Energy Metabolism * MeSH
- Cognition * physiology MeSH
- Humans MeSH
- Mitochondria metabolism MeSH
- Motivation * MeSH
- Pleasure * physiology MeSH
- Animals MeSH
- Check Tag
- Humans MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Review MeSH
IMPORTANCE: The successful implementation of artificial intelligence (AI) in health care depends on its acceptance by key stakeholders, particularly patients, who are the primary beneficiaries of AI-driven outcomes. OBJECTIVES: To survey hospital patients to investigate their trust, concerns, and preferences toward the use of AI in health care and diagnostics and to assess the sociodemographic factors associated with patient attitudes. DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study developed and implemented an anonymous quantitative survey between February 1 and November 1, 2023, using a nonprobability sample at 74 hospitals in 43 countries. Participants included hospital patients 18 years of age or older who agreed with voluntary participation in the survey presented in 1 of 26 languages. EXPOSURE: Information sheets and paper surveys handed out by hospital staff and posted in conspicuous hospital locations. MAIN OUTCOMES AND MEASURES: The primary outcome was participant responses to a 26-item instrument containing a general data section (8 items) and 3 dimensions (trust in AI, AI and diagnosis, preferences and concerns toward AI) with 6 items each. Subgroup analyses used cumulative link mixed and binary mixed-effects models. RESULTS: In total, 13 806 patients participated, including 8951 (64.8%) in the Global North and 4855 (35.2%) in the Global South. Their median (IQR) age was 48 (34-62) years, and 6973 (50.5%) were male. The survey results indicated a predominantly favorable general view of AI in health care, with 57.6% of respondents (7775 of 13 502) expressing a positive attitude. However, attitudes exhibited notable variation based on demographic characteristics, health status, and technological literacy. Female respondents (3511 of 6318 [55.6%]) exhibited fewer positive attitudes toward AI use in medicine than male respondents (4057 of 6864 [59.1%]), and participants with poorer health status exhibited fewer positive attitudes toward AI use in medicine (eg, 58 of 199 [29.2%] with rather negative views) than patients with very good health (eg, 134 of 2538 [5.3%] with rather negative views). Conversely, higher levels of AI knowledge and frequent use of technology devices were associated with more positive attitudes. Notably, fewer than half of the participants expressed positive attitudes regarding all items pertaining to trust in AI. The lowest level of trust was observed for the accuracy of AI in providing information regarding treatment responses (5637 of 13 480 respondents [41.8%] trusted AI). Patients preferred explainable AI (8816 of 12 563 [70.2%]) and physician-led decision-making (9222 of 12 652 [72.9%]), even if it meant slightly compromised accuracy. CONCLUSIONS AND RELEVANCE: In this cross-sectional study of patient attitudes toward AI use in health care across 6 continents, findings indicated that tailored AI implementation strategies should take patient demographics, health status, and preferences for explainable AI and physician oversight into account.
- MeSH
- Adult MeSH
- Trust MeSH
- Internationality MeSH
- Middle Aged MeSH
- Humans MeSH
- Hospitals MeSH
- Delivery of Health Care * MeSH
- Cross-Sectional Studies MeSH
- Surveys and Questionnaires MeSH
- Aged MeSH
- Artificial Intelligence * MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
INTRODUCTION: Anti-amyloid antibodies for the treatment of Alzheimer ́s disease (AD) are currently being evaluated for approval and reimbursement in Europe. An approval brings opportunities, but also challenges to health care systems across Europe. The objective of this position paper is to provide guidance from experts in the field in terms of navigating implementation. METHODS: Members of the European Alzheimer's Disease Consortium and a representative of Alzheimer Europe convened to formulate recommendations covering key areas related to the possible implementation of anti-amyloid antibodies in AD through online discussions and 2 rounds of online voting with an 80% threshold for a position to be accepted. RESULTS: In total, 24 recommendations were developed covering the research landscape and priorities within research in AD following a possible approval, potential impact on health care systems and diagnostic pathways, and communication to patients about anti-amyloid antibodies. Anti-amyloid antibodies are regarded as a substantial innovation with an important clinical impact. In addition, however, new compounds with other mechanisms of action and/or route of administration are also needed. Approval of new treatments will require changes to existing patient pathways and real-world data needs to be generated. CONCLUSION: Comprehensive guidance is provided on the potential implementation of anti-amyloid antibody therapies in Europe following possible approval. Emphasis is placed on the necessity of regularly updating recommendations as new evidence emerges in the coming years.
- MeSH
- Alzheimer Disease * drug therapy therapy MeSH
- Amyloid beta-Peptides * immunology MeSH
- Humans MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Review MeSH
- Geographicals
- Europe MeSH
Well-defined gold nanoparticles (AuNPs) are accessible via simple synthetic methods, and their surface chemistry stands as a key factor in determining applications in the biomedical field. While macromolecules featuring amino groups are already known to successfully mediate the formation of stable gold colloids in one-pot, two-reactant, no workup reactions in aqueous media, we herein report the discovery that, under mild reaction temperatures, polymers of outstanding biomedical interest not only can play the simultaneous role of reducing and capping agent but also lead to particulate systems with unique features. From a library of samples that included branched polyethylenimine (BPEI), poly-(l-lysine) (PLL), bovine serum albumin (BSA), poly-(2-methyl-2-oxazoline) (PMeOx), poly-(N-(2-hydroxypropyl) methacrylamide) (PHPMA), and amine-functionalized poly-(N-(2-hydroxypropyl)-methacrylamide-co-N-(3-aminopropyl)-methacrylamide) P-(HPMA-co-APMA), we found that PHPMA end-functionalized with nitrile motifs generate spherical and stable AuNPs@PHPMA of very small size (diameter of ∼2.4 nm), as underlined by imaging experiments. Cell viability experiments indicated exceptionally good biocompatibility up to very high numerical particle concentrations as compared to the other systems. The reduced size imparted to the AuNPs@PHPMA outstanding catalytic properties (no induction time and high reaction rate constant for the hydrogenation of p-nitrophenol) and antimicrobial activity (total antibacterial activity against Escherichia coli and dose-dependent antibacterial activity against Staphylococcus aureus). The introduction of primary amine groups (13.4 mol %) of higher nucleophilicity known to work better for AuNP synthesis makes these unique features disappear, as evidenced for P-(HPMA-co-APMA). The other systems yielded 6-28 nm particles whose properties reflected both the size of the metallic core and chemical nature and conformation of the capping agent. These findings point to novel applications of PHPMA polymers worthy of further development, especially in light of their excellent water solubility and biocompatibility.
- Publication type
- Journal Article MeSH
