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PubMed2026

Estimated prevalence and distribution of causes of immune-mediated hypertrophic pachymeningitis in São Paulo, Brazil.

BACKGROUND: The prevalence of hypertrophic pachymeningitis (HP) remains poorly defined worldwide. In Japan, the estimated prevalence is 0.949 cases per 100,000 inhabitants, with most cases related to ANCA-associated vasculitis or IgG4-related disease. In contrast, epidemiological data from other regions, including Latin America, are scarce. METHODS: This study was conducted at a tertiary referral center in the city of São Paulo, Brazil. The prevalence of HP was estimated by comparison with the known prevalence of multiple sclerosis (MS), based on the number of patients with each condition followed at our institution. The etiological distribution of HP was also analyzed. In addition, HP prevalence was compared with that of tuberculous meningoencephalitis, a compulsory notifiable disease and a well-established cause of chronic meningitis in Brazil, using data from the national surveillance system (SINAN). RESULTS: We identified 55 patients with HP: 36 (65%) idiopathic, 10 (18%) IgG4-related disease, 4 (7%) ANCA-associated pachymeningitis, 4 (7%) probable or definite neurosarcoidosis, and 1 (2%) secondary to rheumatoid arthritis. Among 968 registered MS patients and assuming an MS prevalence of 15 per 100,000 inhabitants in São Paulo, the estimated HP prevalence was 0.85 per 100,000 inhabitants. This estimate was comparable to the prevalence of tuberculous meningoencephalitis in the same region. CONCLUSION: The estimated prevalence of HP in São Paulo (0.85 per 100,000) is consistent with reports from other regions and is comparable to that of tuberculous meningeal disease, although with a distinct etiological profile. IgG4-related disease was the most frequent systemic association, differing from previous reports. ANCA-associated HP appears to be less frequent than in other geographic regions, possibly reflecting differences in disease phenotype. Key Points • The estimated prevalence of HP in São Paulo was 0.85 per 100,000 inhabitants. • IgG4-related disease was the most common systemic disease identified among patients with HP. • ANCA-associated HP was less common than reported in Asian and European cohorts. • The prevalence of HP was comparable to that of tuberculous meningoencephalitis in São Paulo.

Humans↗

PubMed2026

A Systematic Review of Lived Experiences of Receiving a Diagnosis of ADHD in Adulthood.

OBJECTIVE: With rising numbers of adults seeking and receiving ADHD diagnoses, understanding their first-hand experiences of the diagnostic process is key for sensitive support and service design. This systematic review collates, evaluates and synthesises the existing evidence-base on lived experiences of adult ADHD diagnosis. METHOD: Keyword searches of six databases generated 10,357 citations, which were subjected to a systematic screening process that identified 21 relevant studies. Findings were analysed using thematic synthesis. RESULTS: Analysis generated three overarching themes, elaborating how diagnostic experiences are shaped by adults' Relationship with Self, Relationship with Others, and Relationship with Systems. Personally, diagnosis was widely experienced as a pivotal identity event, triggering biographical reflection that could foster greater self-compassion, but also grief, anger and identity confusion. Socially, diagnosis facilitated interpersonal understanding and communication, but also exposed adults to stigma and introduced dilemmas about diagnostic disclosure. Systemically, adults experienced the diagnostic process as beset by barriers and delays, and reported highly variable access to post-diagnosis supports or treatment. CONCLUSION: Results suggest receiving an ADHD diagnosis in adulthood is a complex relational process that can be both validating and destabilising, with variation in experiences resulting from individual biographies, interpersonal resources, stigma climates, and service structures.

Humans↗

PubMed2026

L-glutamine supplementation improves porcine sperm quality and early embryo development during in vitro fertilization.

L-glutamine (Gln), as a key additive in porcine sperm capacitation medium and in vitro fertilization (IVF) systems, has been shown to significantly improve sperm motility and survival rates. However, its precise roles during porcine IVF and subsequent early embryonic development remain elusive. This study utilized an IVF model in pigs to investigate the effects of glutamine on sperm quality and embryonic development. We found that Gln supplementation during sperm treatment significantly improved sperm quality, as evidenced by reduced reactive oxygen species (ROS) production and early apoptosis, while enhancing calcium ion levels and endoplasmic reticulum activity. Supplementing glutamine during embryo culture reduced polyspermy rates, promoted zygotic genome activation (ZGA) and accumulation of 5-ethynyluridine (EU) and histone modifications (H3K4me3 and H3K27ac) at the two-cell and four-cell stages, increased blastocyst formation rates and total cell numbers, while simultaneously reducing DNA damage and early apoptosis during the blastocyst stage. In summary, these findings demonstrate that Gln enhances porcine IVF outcomes by improving sperm quality, reducing polyspermy, and facilitating early embryonic development, thereby providing a basis for optimizing culture systems.

Animals↗

PubMed2026

Targeted Nanoparticle Delivery CRISPR/Cas9: overcoming biological barriers, enhancing stability, and improving therapeutic precision.

Clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) has emerged as a promising gene-editing platform for genetic disorders; however, its in vivo application remains limited by low delivery efficiency and biological barriers. Many CRISPR payloads fail to reach target sites due to extracellular degradation, immune clearance, and intracellular trafficking limitations. This review examines the interplay between biological barriers and nanoparticle engineering strategies for CRISPR/Cas9 delivery. A barrier-oriented engineering approach is proposed as a central framework, encompassing ligand-based surface modification for enhanced targeting and uptake, improved circulation stability via PEGylation and biomimetic coatings, and optimized payload release through endosomal escape strategies. Stimulus-responsive nanoparticle systems further enable spatiotemporal control over payload release. Nuclear targeting strategies, including optimization of nuclear localization signals (NLS) and exploitation of endogenous trafficking pathways, are highlighted as key factors for improving genome-level editing efficiency. Despite these advances, major challenges-including limited intracellular delivery efficiency, insufficient targeting precision, and safety concerns-continue to hinder clinical translation. Future directions highlight artificial intelligence-driven nanoparticle design, personalized delivery systems, and next-generation CRISPR platforms. Overall, an integrated, barrier-oriented engineering strategy is essential for advancing CRISPR/Cas9 delivery toward clinical applications, ultimately advancing global good health and well-being.

CRISPR/Cas9↗

PubMed2026

Improved quality of life and prolonged survival with add-on homeopathic treatment in patients with non-small cell lung cancer: a prospective, randomized, placebo-controlled, double-blind, three-arm, multicenter study.

BACKGROUND: Alongside conventional anticancer treatment, add-on homeopathy might help to alleviate adverse effects of conventional therapy. AIM: The aim of this study was to replicate previous studies on the effect of adjunctive homeopathy on quality of life (QoL) and survival in non-small cell lung cancer (NSCLC) patients. METHOD: In this prospective, randomized, placebo-controlled, double-blind, three-arm multicenter phase III study with quadruple-checked data analysis, we investigated the potential effects of an add-on homeopathic treatment compared to placebo in patients with stage IV NSCLC in terms of QoL. Ninety-eight received either individualized homeopathic medicinal products (HMPs; n = 51) or placebo (n = 47) in a double-blinded fashion. Fifty-two control patients without homeopathic treatment were only observed in terms of their survival rate. The ingredients of the various HMPs were mainly prepared of plant, mineral, or animal origin. The data entry and statistical analysis were subject to an exceptional quadruple-checked data analysis process. The analysis presented in this article was inspired by our earlier report of this trial published in The Oncologist in 2020, which was retracted by that journal in November 2025 after two corrections; a majority of the co-authors disagreed with this decision. The present article is based on the same trial dataset but was deliberately designed to highlight the unique research methodology: design and preparation by a lead statistician, data entry, data clearing and independent statistical evaluation were performed in four mutually independent steps, reporting follows the CONSORT statement, and the interpretation of the findings has been reframed conservatively. RESULTS: Global health status (QoL) was higher in the homeopathy group than in the placebo group after 9 weeks and after 18 weeks (p < 0.001). With the exception of cognitive functioning at 9 weeks and of pain, diarrhea and financial difficulties at 9 weeks, all functional and symptom scales of the EORTC QLQ-C30 favored the homeopathy group (p < 0.001 for the multivariate comparisons), with between-group differences exceeding the threshold of 10 points that is generally regarded as clinically meaningful. Median survival time over the 730-day observation period was 435 days in the homeopathy group, 257 days in the placebo group (p = 0.010), and 228 days in the non-randomized control group (p < 0.001); the corresponding 2-year survival rates were 45.1%, 23.4%, and 13.5% (homeopathy vs. placebo p = 0.020; homeopathy vs. control p < 0.001). The difference between the placebo group and the non-randomized control group was not statistically significant (p = 0.154). CONCLUSION: In this trial, add-on homeopathy was associated with better quality of life across most functional and symptom domains, with clinically meaningful effect sizes congruently to a previous open study. Survival time was significantly longer in the homeopathy group compared to both the placebo and control groups. Independent replication, ideally within contemporary immuno-oncological treatment regimens is required. TRIALS REGISTRATION: ClinicalTrials.gov; No.: NCT01509612; January 7, 2012.

Humans↗

PubMed2026

Recent advances in electrode materials for electrochemical detection of zearalenone.

Zearalenone (ZEN) is an estrogenic mycotoxin commonly found in cereals, animal feed, and processed foods, making it an important concern for food safety and public health. Conventional chromatographic and immunological methods can detect ZEN; however, they often require expensive instruments, lengthy sample preparation, and skilled personnel, which restrict their use for rapid and on-site testing. Electrochemical sensors have attracted enormous interest of the scientific community because of their high sensitivity, rapid response, low cost, miniaturization potential, and compatibility with portable systems. The analytical performance of the electrochemical sensors is strongly influenced by electrode materials, morphology, conductivity, porosity, surface functionality, and the efficiency of bioreceptor immobilization. Despite several reviews on mycotoxin detection, a systematic assessment connecting electrode-material design, modification strategies, sensing mechanisms, and electroanalytical performance specifically for ZEN sensing remain limited. This review critically evaluates recent advances in metal oxides, carbon-based materials, metal-organic- and covalent organic frameworks, MXenes, polymers, and hybrid composites for electrochemical ZEN detection. Particular attention has been given to their roles in electron transfer, analyte enrichment, selectivity, and real-sample analysis. The review also compares the major limitations of current sensing systems, including complex fabrication, matrix interference, insufficient long-term stability, poor inter-electrode reproducibility, and limited scalability. Finally, future directions for developing robust, cost-effective, portable, and commercially viable ZEN sensors are discussed.

Journal Article↗

PubMed2026

Exploring the mechanism of aroma production in fermented cherry juice by L. brevis LD1.0600 using flavomics and whole genome analysis.

This study focused on L.brevis LD1.0600 with excellent fermentation traits: it analyzed genome-wide key regulatory genes for micro-metabolites, combined with fermented cherry juice flavor metabolomics data, and used machine learning to explore correlations between gene regulation, metabolite production, and flavor formation. The SVM model screened and verified fermented cherry juice VOCs; through OAV and flavor wheel analysis, LD1.0600 emerged as the top-performing strain, with a sweet, fruity dominant aroma. Key aroma-active components (OAV > 100) included 2-methoxy-4-vinylphenol, benzaldehyde, 2-methyl-butanoic acid and hexanoic acid, and 2-methoxy-4-vinylphenol and hexanoic acid elevated by LD1.0600-regulated genes (Chrom1-001884, Chrom1-000925, fabF and Chrom1-000199). At the same time, through research, a "strain screening-SVM screening of DVCs-OAV screening of key aroma components-whole genome sequencing of flavor regulatory genes" system was established. This system can not only be applied to the screen fermentation strains, but also can be extended to the application of other fermentation products.

Fermentation↗

PubMed2026

Socket motility assessment of anophthalmic sockets: a systematic review.

PURPOSE: Systematically review and categorize the methods used to assess socket and prosthetic motility in anophthalmic patients following enucleation or evisceration. METHODS: A systematic review was conducted in accordance with PRISMA guidelines. PubMed, Embase, Web of Science, and Scopus were searched from inception through September 2024. Studies reporting qualitative or quantitative assessments of motility in anophthalmic sockets or ocular prostheses were included. Motility assessment methods were categorized as qualitative (descriptive or graded clinical evaluation) or quantitative (numerical measurements in millimeters, degrees, or objective tracking systems). RESULTS: Thirty-five studies encompassing 1,819 patients met inclusion criteria. Nineteen studies used qualitative assessment methods, including subjective observation, graded scales based on cardinal gaze positions, or comparison with the contralateral eye. Sixteen studies employed quantitative techniques, such as the Kestenbaum limbus test, Lister perimeter measurements, conjunctival or limbal markings, photographic image analysis, infrared eye-tracking systems, and magnetic search-coil technology. Considerable heterogeneity was observed in measurement techniques, reporting standards, timing of assessment, and distinction between socket and prosthetic motility. CONCLUSIONS: Substantial variability exists in the methods used to assess motility in anophthalmic sockets, limiting comparability across studies. Establishing standardized, feasible, and reproducible assessment approaches may improve outcome reporting and facilitate meaningful comparisons in future oculoplastic research.

Humans↗

PubMed2026

Divergent evolutionary strategies in spider venoms: A comparative proteomic profiling of four sympatric species from Yunnan.

Spider venoms comprise complex cocktails of bioactive molecules evolved for predation and defense, representing a valuable resource for biological research and pharmaceutical discovery. In this study, we performed a systematic analysis of venom gland extracts from four common spider species indigenous to Yunnan, China: Agelena limbata, Hippasa lycosina, Lycosa grahami, and Sinopoda pengi. Using an integrated transcriptomic and proteomic targeted profiling approach, we successfully annotated 141 distinct toxins. Comparative analysis revealed significant interspecific heterogeneity, suggesting distinct evolutionary trajectories and "weapon system economics." Both A. limbata and L. grahami exhibited a "peptide-dominant" profile anchored by neurotoxic peptides and isomerases, optimized for rapid chemical paralysis. In contrast, S. pengi displayed a distinct "protein-dominant" signature enriched with high-molecular-weight enzymes and CAP superfamily proteins, likely functioning to facilitate tissue degradation and toxin diffusion. Occupying an intermediate position, H. lycosina demonstrated a hybrid composition. These findings suggest that although these species share the same geographical range, their venom systems have undergone divergent evolutionary adaptations driven by specific ecological niches and hunting strategies. This study represents the first systematic proteomic characterization of these venom components, providing a valuable reservoir of molecular candidates while highlighting the bioinformatic nuances of analyzing whole-gland homogenates.

Animals↗

PubMed2026

Implicit and explicit statistical learning in reading: Evidence from a randomized controlled-learning study and computational modeling.

A key challenge in reading acquisition is understanding how learners extract the complex probabilistic mappings between print, meaning, and sound. Statistical learning (SL) theory offers a mechanistic account of how such mappings are acquired, whether implicitly through exposure or explicitly through instruction. We conducted a randomized controlled-learning study in Chinese, a writing system characterized by multiple sub-lexical regularities linking orthography, semantics, and phonology. Ninety-five 2nd-3rd graders with or at risk for dyslexia were randomly assigned to one of three groups: an implicit-SL training group exposed to repeated lexical and sublexical orthography-semantics-phonology associations, an explicit-SL training group receiving the same input plus explicit instruction on the sublexical print-sound mapping, and a no-SL control group. Both SL groups outperformed controls on the characters they were trained on, as well as on untrained characters that required generalization. However, only the explicit group demonstrated abstraction of print-sound mapping to novel items. Neural network simulations further revealed distinct mechanisms supporting implicit and explicit SL, consistent with a dual-system account of reading acquisition. Together, these findings (1) clarify how implicit and explicit learning distinctly support the discovery of statistical structure in written language and (2) underscore the implicit-explicit dual learning mechanism underlying reading acquisition.

Humans↗

PubMed2026

The Thyroid-Brain Network: Exploring Inflammation, Immune Mechanisms and Common Triggers in Thyroid-Related Neurological Dysfunction.

Autoimmune thyroid diseases (AITD), including Hashimoto's thyroiditis and Graves' disease, represent the most prevalent endocrine disorders worldwide, affecting hundreds of millions with profound but often under recognized neurological consequences. There are emerging lines of evidence establishing inflammation and immunity as the critical missing link connecting peripheral thyroid dysfunction to central nervous system manifestations. Thyroid hormones function as essential neuromodulators governing neurodevelopment, synaptic plasticity, and cognitive processing through integrated genomic and non-genomic mechanisms, with region-specific cerebral metabolic disturbances correlating with distinct neuropsychiatric symptoms. The immunological perspective reveals that AITD propagates neuroinflammation through convergent pathways: molecular mimicry enabling cross-reactivity between thyroid and neural antigens, cytokine-mediated disruption of neurotransmitter metabolism, HMGB1-driven glial activation, and blood-brain barrier compromise facilitating immune cell infiltration. The thyroid-gut-microbiota axis emerges as a critical mediator wherein dysbiosis perpetuates both thyroid autoimmunity and neuroinflammation through impaired serotonin precursor availability and increased intestinal permeability. Mitochondrial dysfunction represents an energetic common denominator, as thyroid hormone dysregulation directly impairs oxidative phosphorylation, producing region-specific cerebral metabolic disturbances. Simultaneous compromise of monoamine systems, cholinergic signaling abnormalities, and glutamate excitotoxicity creates a particularly toxic neurochemical state in untreated thyroid dysfunction. Common triggers such as psychological stress, gut dysbiosis, and mitochondrial impairment may activate interconnected pathways that simultaneously compromise thyroid and brain function, revealing that these disorders share fundamental mechanistic origins. These insights have been discussed in the current review to enhance the understanding of thyroid-brain function, the core mechanisms and consequences of functional deficits.

Journal Article↗

PubMed2026

Using Organoids to Unlock the Potential of Human Torpor for Spaceflight.

PURPOSE OF REVIEW: This paper reviews the current understanding of the potential for humans to enter a state of torpor/hibernation, and discusses the possibility of inducing torpor in astronauts for long-duration space travel, including some of the physiological, technological, and ethical considerations associated with its implementation. By exploring means to induce torpor in various human organoid systems, we hope such research can provides insights to comprehensive solutions to overcome some of the major hurdles that limit the potential for human to enter a state of torpor during long-duration deep-space missions, and contribute to the ongoing efforts to make such missions more feasible and safer for astronauts. RECENT FINDINGS: On future deep space missions such as NASA's planned missions to the Moon, Mars, and near-Earth asteroids, astronauts will be continuously exposed to environments that are radically different from those on Earth, each presenting multiple logistical and physiological challenges. Beyond the well-documented physiological effects of microgravity, space travelers will encounter a complex radiation environment that may contribute to significant short- and long-term adverse effects on human physiology and increase the risk of cancer and other diseases. Besides these physical challenges, life support systems must also be designed to mitigate psychological impacts of long-term isolation and confinement - all of which collectively pose formidable engineering problems. Hibernation/torpor is a state of prolonged inactivity and metabolic depression used by a wide variety of mammals to survive periods of cold temperatures and food scarcity, including some primates and perhaps even an extinct early line of hominins that lived nearly half a million years ago. Since modern humans share common ancestry with these hominins and hibernating primates, it is likely the human genome encodes the necessary genetic information to hibernate, or at least enter the similar, more transient state of torpor. The reduced body activity, lowered metabolism, and decreased energy requirements that characterize torpor suggest that developing means of inducing such a state in astronauts could address these challenges, including providing a degree of radioprotection. SUMMARY: This review explores the potential application of human torpor as a countermeasure to address the many challenges posed by long-duration spaceflight beyond low-Earth orbit (LEO), discusses various natural hibernating model systems for studying means of inducing a torpor-like state in humans, and highlights the vast potential of using human organoids to test and validate mechanisms that govern induction and maintenance of torpor to identify the means to one day safely induce this state in astronauts to provide additional protection from the myriad stressors of spaceflight.

Astronaut Health↗

PubMed2026

Are there any common effects in preclinical models of micro- and nanoplastic (MNP) exposure? A systematic review.

Micro- and nanoplastics (MNPs) are emerging contaminants detected in food sources and the marine food chain, raising concerns about human health. Although no causal relationship has been established between MNP exposure and specific diseases, growing evidence suggests adverse developmental, behavioral, cognitive and biochemical effects. This systematic review synthesized evidence from common preclinical neurotoxicology models, including C. elegans, D. rerio, D. melanogaster, in vitro systems and rodents, to identify convergent developmental, behavioral and biochemical outcomes. The protocol was preregistered in OSF, followed PRISMA-P guidelines, applied PICOS criteria, and assessed methodological quality using the European Commission's ToxRTool. Overall, 185 studies were included. Consistent findings showed impaired survival and disrupted development across all models. Behavioral alterations affecting anxiety, memory, learning, sociability and locomotor activity were also consistently reported. In addition, numerous studies identified disruptions in the serotonergic (5-HT) system, including changes in neurotransmitter levels, transporters and metabolic enzymes. Despite methodological heterogeneity, these findings indicate that MNP exposure produces reproducible neurodevelopmental and neurochemical alterations across experimental models. Future studies should improve methodological harmonization, strengthen cross-model comparability and identify robust biomarkers and key mechanisms underlying MNP-induced neurotoxicity, facilitating translation to human health risk assessment frameworks.

Animals↗

PubMed2026

Prostate morcellation devices: a systematic review and meta-analysis of clinical outcomes and efficiency.

OBJECTIVE: To systematically evaluate the efficiency and safety of different prostate morcellators used during prostate enucleation for benign prostatic hyperplasia (BPH). METHODS: A systematic review was performed according to the Preferred Reporting Items for Systematic Review and Meta-analyses guidelines. PubMed/Medline, Scopus, and Web of Science were searched for studies published between October 2012 and May 2025. Studies reporting clinical outcomes of morcellators used during prostate enucleation were included. Primary outcome was morcellation efficiency (g/min). Secondary outcomes included intraoperative complications, device malfunction, and cost when available. Risk of bias (RoB) was assessed using the Risk Of Bias In Non-randomised Studies of Interventions (ROBINS-I), RoB 2 tool, and European Association of Urology case-series criteria. Random-effects meta-analyses and multilevel meta-regression adjusted for prostate volume were conducted. RESULTS: A total of 22 studies comprising 5980 patients were included, most undergoing holmium laser enucleation of the prostate. The most frequently evaluated devices were the Piranha™ (Richard Wolf GmbH, Knittlingen, Germany) and Lumenis VersaCut™ (Lumenis Ltd., Yokneam, Israel; 12 and 13 studies, respectively), followed by DrillCut™ (Karl Storz SE & Co. KG, Tuttlingen, Germany), MultiCut™ (Asclepion Laser Technologies GmbH, Jena, Germany), and Cyber Blade™ (Quanta System SpA, Milan, Italy) systems. Unadjusted weighted mean morcellation efficiency was 7.80 g/min (95% confidence interval [CI] 6.26-9.34 g/min) for Piranha, 4.70 g/min (95% CI 3.61-5.79 g/min) for VersaCut, 5.90 g/min (95% CI 3.16-8.64 g/min) for DrillCut, and 9.59 g/min (95% CI 4.78-14.39 g/min) for MultiCut. In volume-adjusted meta-regression using Piranha as reference, VersaCut remained significantly less efficient (-2.75 g/min; 95% CI -4.58 to -0.92 g/min; P = 0.003), with an even greater difference in prostates >70 mL (-4.34 g/min). Bladder mucosal injury was the most frequently reported complication; however, relatively rare across all devices. Meta-analysis demonstrated a significantly higher risk with VersaCut compared to Piranha (risk ratio 3.22, 95% CI 1.81-5.71), with low heterogeneity. CONCLUSION: This systematic review provides a contemporary clinical benchmark of the efficiency and safety of currently available prostate morcellators. Oscillating blade systems, particularly the Piranha morcellator, demonstrated higher morcellation efficiency and a more favourable safety profile than reciprocating blade devices, with the largest performance differences observed in patients with larger prostates.

Humans↗

PubMed2026

Civil liability in oral & maxillofacial surgery: Α systematic review.

Maxillofacial surgery is a surgical specialty with anatomical, functional, and aesthetic requirements, which makes it a field at increased risk of medical negligence and subsequent legal claims. The review was conducted in accordance with the PRISMA guidelines and used international medical and legal databases. Studies that analyzed court decisions, insurance claims, or recorded compensation data related to maxillofacial surgery were included. The extracted data included, among others, the year and country of publication, the causes of action, and the amounts of financial compensation. Most lawsuits originate from countries with developed medical liability systems, primarily the United States and the United Kingdom, and there has been an increasing trend in publications over the last two decades. The most common causes of lawsuits involve nerve injuries, delayed or incorrect diagnoses, technical errors during surgery, and inadequate informed consent. The amounts of compensation vary widely, from lower five-digit amounts in milder cases to particularly high amounts in cases of permanent functional or aesthetic damage, placing a significant overall financial burden on health systems. Medical negligence in maxillofacial surgery constitutes an important forensic and socioeconomic issue. Understanding the causes of lawsuits and their financial consequences can help improve clinical practice, inform patients, and prevent legal disputes.

Humans↗

PubMed2026

Fluoride as a Modifier of Metallome Homeostasis: A Systematic Review of Animal Studies.

Fluoride is widely used for caries prevention due to its effects on mineralized tissues, yet its potential role as a modifier of systemic metal homeostasis remains insufficiently explored. This systematic review synthesizes preclinical evidence on the association between fluoride exposure and changes in metal and semi-metal concentrations across biological matrices. A comprehensive search strategy was conducted across major databases without language or date restrictions, following SyRF, CAMARADES and PRISMA 2020 guidelines. Thirty-one animal studies were included, encompassing multiple species, exposure conditions and analytical approaches. Despite substantial methodological heterogeneity, consistent patterns emerged. Fluoride exposure was associated with element-specific redistribution of the metallome rather than uniform change. Essential elements were predominantly depleted, most consistently zinc, copper and manganese, whereas the toxic metals lead and cadmium tended to be retained. This contrast between homeostatically regulated essential elements that are lost and non-regulated toxic metals that accumulate supports the hypothesis that fluoride differentially modifies the distribution and retention of co-existing elements. The novelty of this review lies in integrating metallomic outcomes across experimental models, highlighting fluoride as a potential systemic modulator rather than a tissue-specific agent. Although variability in study design and risk of bias limits causal inference, the consistent directionality of findings across models reinforces their biological plausibility and translational relevance.

Animals↗

PubMed2026

Increasing gut short-chain fatty acids protects intestinal barrier function but does not spare muscle glycogen or impact aerobic performance.

Animal studies suggest gut microbiota-derived short-chain fatty acids (SCFA) provide an intestinal barrier-protecting, glycogen-sparing energy source that increases aerobic endurance performance, but confirmation in humans is needed. This study aimed to determine whether increasing colonic SCFA availability impacts intestinal barrier function, substrate metabolism, muscle glycogen and aerobic performance in healthy adults. Using a randomized, double-blind, crossover design 12 active men (age 18-30 years;40.0 ± 7.1 mL/kg/min) performed prescribed exercise and consumed a provided diet supplemented with acetylated and butyrylated high-amylose maize starch engineered to deliver SCFA to the colon (HAMS-A/B) or low-amylose maize starch (LAMS) for 7 days, separated by a 2 week washout. Indirect calorimetry, stable isotopes and blood, muscle and urine biomarkers were measured on intervention day 8 while participants completed 90 min of steady-state cycle ergometry (ExSS; 60 ± 5%) followed by a 5 km treadmill time trial. HAMS-A/B, relative to LAMS, increased faecal and serum SCFA. Multiple markers of intestinal barrier damage and permeability were lower, and the respiratory exchange ratio during ExSS was higher (0.02 [95% confidence interval (CI): 0.01, 0.03], Ptreatment < 0.001) following HAMS-A/B versus LAMS. However no between-treatment difference in glucose turnover, muscle glycogen depletion (14 µmol/kg/g dry wt. [95% CI: -116, 143], Pinteractio n = 0.613) or TT performance (5 s [95%CI: -44, 54], Ptreatment = 0.816) was observed. Increasing colonic and circulating SCFA modestly altered substrate oxidation and preserved intestinal barrier function during endurance exercise. However effects were not sufficient to spare muscle glycogen or increase aerobic endurance performance, leaving the practical relevance unclear and underscoring challenges inherent in translating promising preclinical findings to humans. KEY POINTS: Animal studies suggest gut microbiota-derived short-chain fatty acids (SCFA) provide an intestinal barrier-protecting, glycogen-sparing energy source that increases aerobic endurance performance, but confirmation in humans is lacking. A gut microbiota-targeted dietary supplementation strategy was used to deliver SCFA to the colon and successfully increased colonic and systemic SCFA concentrations in healthy, physically active adults before and during an endurance exercise bout and aerobic performance test. Increasing colonic and systemic SCFA availability preserved intestinal barrier function but did not impact glucose turnover, alter protein expression in muscle or spare muscle glycogen during endurance exercise. Increasing colonic and systemic SCFA availability did not impact aerobic endurance performance.

Humans↗

PubMed2026

Driven toward care, avoiding the end: A systematic review and meta-analysis of the relationship between death anxiety and healthcare utilisation.

Both overuse and underuse of the healthcare system have been recognised as significant problems. Relatedly, growing research has recognised the key role of death anxiety in driving various health-relevant behaviours. However, the relationship between death anxiety and healthcare utilisation has not yet been systematically explored. The current systematic review and meta-analysis addressed this gap. In total, 987 papers were screened for inclusion, of which 63 were included in the final review (Ntotal = 21,271). This included 33 quantitative studies, 27 qualitative studies and 3 mixed-methods designs. In total, 17 studies contained sufficient data to be meta-analysed. Overall, the included studies highlighted a significant relationship between death anxiety and healthcare utilisation; in particular, positive associations with desire for life-prolonging treatments and contact with hospitals and medical professionals. By contrast, a negative association was found with other aspects of healthcare utilisation, including hospice use and end-of-life communication. The sample type emerged as a significant moderator, suggesting that the relationship between death anxiety and healthcare usage was strongest in non-medical samples. The current findings suggest that death anxiety plays a key role in utilisation of the healthcare system. The fear of death may need to be targeted in psychological interventions, in order to ensure maximal effectiveness of health services, and improve outcomes for healthcare users.

Humans↗