Exploring the influence of weather variability and climate change on health outcomes in people living with dementia: A scoping review protocol.

Environmental factors resulting from climate change and air pollution are risk factors for many chronic conditions including dementia. Although research has shown the impacts of air pollution in terms of cognitive status, less is known about the association between climate change and specific health-related outcomes of older people living with dementia. In response, we outline a scoping review protocol to systematically review the published literature regarding the evidence of climate change, including temperature and weather variability, on health-related quality of life, morbidity, mobility, falls, the utilization of health resources, and mortality among older adults living with dementia. This scoping review will be guided by the framework proposed by Arksey and O'Malley. Electronic search (Medline, Embase, PsycINFO, CINAHL, Scopus, Web of Science) using relevant subject headings and synonyms for two concepts (older people with dementia, weather/ climate change). No publication date or other restrictions will be applied to the search strategy. No language restriction will be applied in order to understand the impact of non-English studies in the literature. Eligible studies must include older adults (65+years) with dementia living in the community and investigate the impacts of climate change and/or weather on their health-related quality of life, morbidity, mobility, falls, use of health resources and mortality. Two independent reviewers will screen abstracts and select those for a full-text review, perform these reviews, select articles for retention, and extract data from them in a standardized manner. This data will then be synthesized and interpreted. OSF registration: DOI: 10.17605/OSF.IO/YRFM8.

Long-term Environmental Enrichment Normalizes Schizophrenia-like Abnormalities and Promotes Hippocampal Slc6a4 Promoter Demethylation in Mice Submitted to a Two-hit Model.

Here, we explored the impact of prolonged environmental enrichment (EE) on behavioral, neurochemical, and epigenetic changes in the serotonin transporter gene in mice subjected to a two-hit schizophrenia model. The methodology involved administering the viral mimetic PolyI:C to neonatal Swiss mice as a first hit during postnatal days (PND) 5-7, or a sterile saline solution as a control. At PND21, mice were randomly assigned either to standard environment (SE) or EE housing conditions. Between PND35-44, the PolyI:C-treated group was submitted to various unpredictable stressors, constituting the second hit. Behavioral assessments were conducted on PND70, immediately after the final EE exposure. Following the completion of behavioral assessments, we evaluated the expression of proteins in the hippocampus that are indicative of microglial activation, such as Iba-1, as well as related to neurogenesis, including doublecortin (Dcx). We also performed methylation analysis on the serotonin transporter gene (Slc6a4) to investigate alterations in serotonin signaling. The findings revealed that EE for 50 days mitigated sensorimotor gating deficits and working memory impairments in two-hit mice and enhanced their locomotor and exploratory behaviors. EE also normalized the overexpression of hippocampal Iba-1 and increased the expression of hippocampal Dcx. Additionally, we observed hippocampal demethylation of the Slc6a4 gene in the EE-exposed two-hit group, indicating epigenetic reprogramming. These results contribute to the growing body of evidence supporting the protective effects of long-term EE in counteracting behavioral disruptions caused by the two-hit schizophrenia model, pointing to enhanced neurogenesis, diminished microglial activation, and epigenetic modifications of serotonergic pathways as underlying mechanisms.

Impact of the COVID-19 pandemic on food insecurity in Brazil: Construction of a hypothetical-deductive theoretical model / Impacto da pandemia de COVID-19 na insegurança alimentar no Brasil: Construção de um modelo teórico hipotético-dedutivo

The article addresses Brazil's return to the Hunger Map in 2022 during the COVID-19 pandemic. After public policies in 2014-2015, food insecurity worsened from 2016 onwards, intensifying during the pandemic. Social inequality, unemployment, informality and family changes contributed to the worsening. The research used hypothetical-deductive models, based on two national surveys and regional studies. The process involved formulating hypotheses, reviewing the literature, deducing predictions and identifying variables. Two general hypotheses were formulated, relating the pandemic to worsening inequalities and introducing new sociodemographic variables. Contextual variables and impact mechanisms of the pandemic were identified. Contextual and individual consequences include food insecurity, health impacts and widening inequalities. The intersection between food insecurity and social inequalities highlights the need for comprehensive public policies. The rise in food insecurity during the pandemic has had significant implications and will require a long-term, sustainable approach. The proposed theoretical model, represented by a DAG, points out paths and causal relationships between events, highlighting the complexity of the scenario. The study concludes that, in addition to trends prior to the pandemic, the health emergency introduced crucial variables for understanding food insecurity in Brazil. The hypothetical-deductive theoretical model offers a more accurate understanding of the causes and effects of the pandemic.

O artigo aborda o retorno do Brasil ao Mapa da Fome em 2022 durante a pandemia de COVID-19. Após políticas públicas em 2014-2015, a insegurança alimentar piorou a partir de 2016, intensificando-se na pandemia. A desigualdade social, desemprego, informalidade e mudanças familiares contribuíram para o agravamento. A pesquisa utilizou modelos hipotético-dedutivos, baseados em dois inquéritos nacionais e estudos regionais. O processo envolveu formulação de hipóteses, revisão da literatura, dedução de previsões e identificação de variáveis. Duas hipóteses gerais foram formuladas, relacionando a pandemia agravando desigualdades e introduzindo novas variáveis sociodemográficas. Foram identificadas variáveis contextuais e mecanismos de impacto da pandemia. As consequências contextuais e individuais incluem insegurança alimentar, impacto na saúde e ampliação das desigualdades. A interseção entre insegurança alimentar e desigualdades sociais destaca a necessidade de políticas públicas abrangentes. O aumento da insegurança alimentar durante a pandemia teve implicações significativas e exigirá abordagem sustentável a longo prazo. O modelo teórico proposto, representado por um DAG, aponta caminhos e relações causais entre eventos, destacando a complexidade do cenário. O estudo conclui que, além das tendências anteriores à pandemia, a emergência sanitária introduziu variáveis cruciais para o entendimento da insegurança alimentar no Brasil. O modelo teórico hipotético-dedutivo oferece uma compreensão mais precisa das causas e efeitos da pandemia.

Dynamics of transcription is affected by oxygen tension and developmental speed during in vitro production of bovine embryos.

This study examines the impact of oxygen tension and embryo kinetics on gene transcription dynamics in pathways crucial for embryonic preimplantation development, including lipid metabolism, carbohydrate transport and metabolism, mitochondrial function, stress response, apoptosis and transcription regulation. Bovine embryos were generated in vitro and allocated into two groups based on oxygen tension (20% or 5%) at 18 h post insemination (hpi). At 40 hpi, embryos were categorized into Fast (≥4 cells) or Slow (2 cells) groups, resulting in four experimental groups: FCL20, FCL5, SCL20 and SCL5. Embryo collection also occurred at 72 hpi (16-cell stage; groups FMO20, FMO5, SMO20 and SMO5) and at 168 hpi (expanded blastocyst (BL) stage; groups FBL20, FBL5, SBL20 and SBL5). Pools of three embryos per group were analysed in four replicates using inventoried TaqMan assays specific for Bos taurus, targeting 93 genes. Gene expression patterns were analysed using the K-means algorithm, revealing three main clusters: genes with low relative abundance at the cleavage (CL) and 16-cell morula (MO) stages but increased at the BL stage (cluster 1); genes with higher abundances at CL but decreasing at MO and BL (cluster 2); and genes with low levels at CL, higher levels at MO and decreased levels at BL (cluster 3). Within each cluster, genes related to epigenetic mechanisms, cell differentiation events and glucose metabolism were particularly influenced by differences in developmental kinetics and oxygen tension. Fast-developing embryos, particularly those cultured under low oxygen tension, exhibited transcript dynamics more closely resembling that reported in vivo-produced embryos.

The Role of Biomarkers in Diagnosis of Sepsis and Acute Kidney Injury.

Sepsis and acute kidney injury (AKI) are two major public health concerns that contribute significantly to illness and death worldwide. Early diagnosis and prompt treatment are essential for achieving the best possible outcomes. To date, there are no specific clinical, imaging, or biochemical indicators available to diagnose sepsis, and diagnosis of AKI based on the KDIGO criterion has limitations. To improve the diagnostic process for sepsis and AKI, it is essential to continually evolve our understanding of these conditions. Delays in diagnosis and appropriate treatment can have serious consequences. Sepsis and AKI often occur together, and patients with kidney dysfunction are more prone to developing sepsis. Therefore, identifying potential biomarkers for both conditions is crucial. In this review, we talk about the main biomarkers that evolve the diagnostic of sepsis and AKI, namely neutrophil gelatinase-associated lipocalin (NGAL), proenkephalin (PENK), and cell-free DNA.

Maternal and neonatal effects of epidural levobupivacaine combined with fentanyl or sufentanil for elective cesarean-section in brachycephalic breeds.

The aim of this study was to compare the safety and clinical efficacy of epidural levobupivacaine combined with fentanyl or sufentanil for bitches undergoing elective cesarean-section and the impact of these anesthetic protocols on neonatal viability. The anesthetic protocol consisted of intramuscular morphine (0.2 mg/kg), followed by an intravenous bolus of propofol, in a dose sufficient to allowed the puncture of the lumbosacral space. The dogs were randomly allocated to receive 0.5 % levobupivacaine plus fentanyl (2.5 µg/kg; LF: n = 9) or sufentanil (1 µg/kg; LS; n = 11). Maternal cardiorespiratory parameters were monitored at specific time points during surgery. Intraoperative propofol supplementation was based on the presence of head and/or thoracic limb movements. Neonatal reflex responses and the Apgar score (range 0-10 points) were assessed at 5 and 60 minutes after birth. Puppy mortality rate was recorded until 24 hours after birth. Data were analyzed using two-way ANOVA, Tukey's test, Wilcoxon signed rank test, and Fisher's exact test (P < 0.05). Intraoperatively, maternal cardiorespiratory variables and propofol requirements were similar between groups, with no detection of anesthetic complications. The puppy reflex responses did not differ between groups at any time point. The medians (range) of Apgar scores were lower (P = 0.016) in the LF [5 (1-9)] at 5 minutes in comparison with LS [6 (2-9)], while no intergroup differences were recorded at 60 minutes [LF = 8 (2-10); LS = 9 (6-10]. The total mortality rate was 4.1 %. In the LS group, no puppies died, while in the LF 8 % of the puppies died in the first 24 hours after birth (P = 0.11). Epidural levobupivacaine combined with fentanyl or sufentanil provided minimal maternal and neonatal adverse effects, but neither protocol enabled the performance of a C-section in 100 % of the French and English bulldogs, without propofol supplementation.

Shoulder specific exercise therapy is effective in reducing chronic shoulder pain: A network meta-analysis.

BACKGROUND: Exercise therapy (ET) is frequently an early treatment of choice when managing shoulder pain, yet evidence on its efficacy to expedite recovery is inconsistent. Moreover, the value of adding adjunct therapies (i.e. injections, manual therapy, electrotherapy) to ET is currently unclear. This study combined both direct and indirect evidence across studies on the effectiveness of ET with/without adjunct therapies compared to usual medical care for adults with chronic shoulder pain. METHODS AND FINDINGS: Using a network meta-analysis, randomized control trials comparing ET along with adjunct therapies were identified in MEDLINE, Embase, CINAHL, Sportdiscus, CENTRAL, Conference Proceedings Citation Index-Science, clinicaltrials.gov, and association websites. Outcomes included pain, range of motion (ROM), and health-related quality of life (HRQL) measures in adult patients with chronic shoulder pain. Data analysis used a Frequentist hierarchical model. CINeMA tool assessed the confidence in the results and Cochrane Risk of Bias tool assessed quality of studies. 54 studies primarily from Europe (40.38%) included 3,893 participants who were followed up to 52 weeks. Shoulder-specific ET (Mean difference (MD) = -2.1; 95% confidence interval (CI) = -3.5 to -0.7) or in combination with electro-physical agents (MD = -2.5; 95% CI = -4.2 to -0.7), injections (MD = -2.4; 95% CI = -3.9 to-1.04) or manual therapy (MD = -2.3; 95% CI = -3.7 to -0.8) decreased pain compared to usual medical care. Trends with ROM and HRQL scores were seen; however, only Manual Therapy (MD = -12.7 and 95% CI = -24.4 to -1.0) achieved meaningfully important changes. Sensitivity analysis excluding studies with high risk of bias showed similar results, with exception of injections that did not reach significance (MD = -1.3; 95% CI = -4.3 to 1.7). CONCLUSION(S): Shoulder-specific ET provided pain relief up to 52 weeks. Adjunct therapies to shoulder-specific ET added little value in reducing pain. The quality of evidence varied between moderate and very low.

Impact of Extraction Methods and Transportation Conditions on Lipid Profiles of Bovine Oocytes.

Lipids play numerous pivotal physiological roles in mammalian reproduction, being indispensable for oocyte competence acquisition and post-fertilization embryonic development. Profiling lipids in minute samples, such as oocytes, presents challenges but has been accomplished through mass spectrometry technologies like Multiple Reaction Monitoring (MRM) profiling. With the dual objectives of simplifying workflow and examining the influence of preanalytical conditions, we assessed whether transportation at room temperature affects the lipid profile of bovine oocytes. To this end, samples were prepared using either monophasic (methanol only) or biphasic liquid extraction protocols (Bligh & Dyer method) and transported either on dry ice or at room temperature inside sealed-vacuum packages to prevent lipid oxidation. Subsequently, employing a comprehensive method, we screened a list of 316 MRMs from 10 different lipid subclasses in oocyte lipid extracts. Principal Component Analysis (PCA) revealed similar lipid profiles concerning temperature during transportation, whereas clear differentiation among samples was observed based on the lipid extraction method. Univariate analysis indicated that the one-phase methanol extraction resulted in higher relative abundances of phospholipids, except for phosphatidylserines. Conversely, the Bligh & Dyer extraction favored the detection of neutral intracellular lipids (triacylglycerols, free fatty acids, cholesteryl esters, and acyl-carnitines). Consequently, lipid recovery was directly correlated with the polarity of lipid class and the extraction method. Regarding transportation temperature, phosphatidylethanolamine, triacylglycerol, and free fatty acids exhibited lower abundances when samples were transported at room temperature. Based on multivariate and univariate analyses, we conclude that if samples undergo the same lipid extraction protocol and are transported in the same batch at room temperature inside vacuum-sealed bags, it is feasible to analyze lipid extracts of bovine oocytes and still obtain informative lipid profiling results.

Plant-based compositions for the treatment of local and topical bacterial infections: a patent review.

Aim: To examine recent patents related to plants with antimicrobial effects. Methods: Our investigation was carried out using the Espacenet database, searching patents related to International Patent Classification (IPC) codes A61P31/04, and A61K36/00 between 2008 and 2023. Results: The study began with 360 patents, of which 15 were found to be duplicates; 144 were not related to the research topic and six were not available. Then, 48 patents were related to other administration routes. The final selection was 47 patents related to local administration compositions. The potential for these herbal compositions to be marketed as over-the-counter medicines was evident. Conclusion: Developing new plant-origin anti-infective agents could provide promising solutions for combating resistant infections and offer accessible treatment options.

[Box: see text].

Association between environmental factors during the COVID-19 pandemic and functioning of infants with biological risk in the first year of life: Cross-sectional exploratory study.

BACKGROUND: Child development can be influenced by family and environmental factors, which changed during the COVID-19 pandemic. Thus, it is important to explore how these factors are associated with the functioning of infants with biological risk in the first year of life. OBJECTIVE: This study aimed to investigate associations between family factors, home opportunities, caregiver perception of environmental support and barriers at home and environmental factors during the COVID-19 pandemic and gross motor skills and home participation in infants with biological risk in the first year of life. METHODS: Fifty-six infants aged two to 12 months (M = 5.80 months; ±2.44) and their mothers performed remote assessments of gross motor skills using the Alberta Infant Motor Scale (AIMS); participation and environment (phone call) by the Young Children's Participation and Environment Measure (YC-PEM); family factors (income, age and maternal education), home opportunities - The Affordances in the Home Environment for Motor Development - Infant Scale (AHEMD-IS) and environmental factors during the COVID-19 pandemic (social distancing, emotional and financial factors and physiotherapy) (online forms). Regression models were constructed, considering gross motor skills and home participation as outcome variables, with a 5 % significance level. RESULTS: We found that older maternal age (p = 0.001), more home opportunities (p = 0.043), and less rigorous social distancing (as opposed to total social distancing [p = 0.045]) were significantly associated with better gross motor skills; and higher maternal education (p = 0.050) was associated with more involvement in home activities. CONCLUSION: Family factors, home opportunities and social distancing were differently associated with the gross motor skills and home participation of infants with biological risk in the first year of life.

Blood epigenome-wide association studies of suicide attempt in adults with bipolar disorder.

Suicide attempt (SA) risk is elevated in individuals with bipolar disorder (BD), and DNA methylation patterns may serve as possible biomarkers of SA. We conducted epigenome-wide association studies (EWAS) of blood DNA methylation associated with BD and SA. DNA methylation was measured at >700,000 positions in a discovery cohort of n = 84 adults with BD with a history of SA (BD/SA), n = 79 adults with BD without history of SA (BD/non-SA), and n = 76 non-psychiatric controls (CON). EWAS revealed six differentially methylated positions (DMPs) and seven differentially methylated regions (DMRs) between BD/SA and BD/non-SA, with multiple immune-related genes implicated. There were no epigenome-wide significant differences when BD/SA and BD/non-SA were each compared to CON, and patterns suggested that epigenetics differentiating BD/SA from BD/non-SA do not differentiate BD/non-SA from CON. Weighted gene co-methylation network analysis and trait enrichment analysis of the BD/SA vs. BD/non-SA contrast further corroborated immune system involvement, while gene ontology analysis implicated calcium signalling. In an independent replication cohort of n = 48 BD/SA and n = 47 BD/non-SA, fold changes at the discovery cohort's significant sites showed moderate correlation across cohorts and agreement on direction. In both cohorts, classification accuracy for SA history among individuals with BD was highest when methylation at the significant CpG sites as well as information from clinical interviews were combined, with an AUC of 88.8% (CI = 83.8-93.8%) and 82.1% (CI = 73.6-90.5%) for the combined epigenetic-clinical classifier in the discovery and replication cohorts, respectively. Our results provide novel insight to the role of immune system functioning in SA and BD and also suggest that integrating information from multiple levels of analysis holds promise to improve risk assessment for SA in adults with BD.

The central role of pyruvate metabolism on the epigenetic maturation and transcriptional profile of bovine oocytes.

In brief: Pyruvate metabolism is one of the main metabolic pathways during oocyte maturation. This study demonstrates that pyruvate metabolism also regulates the epigenetic and molecular maturation in bovine oocytes. Abstract: Pyruvate, the final product of glycolysis, undergoes conversion into acetyl-CoA within the mitochondria of oocytes, serving as a primary fuel source for the tricarboxylic acid (TCA) cycle. The citrate generated in the TCA cycle can be transported to the cytoplasm and converted back into acetyl-CoA. This acetyl-CoA can either fuel lipid synthesis or act as a substrate for histone acetylation. This study aimed to investigate how pyruvate metabolism influences lysine 9 histone 3 acetylation (H3K9ac) dynamics and RNA transcription in bovine oocytes during in vitro maturation (IVM). Bovine cumulus-oocyte complexes were cultured in vitro for 24 h, considering three experimental groups: Control (IVM medium only), DCA (IVM supplemented with sodium dichloroacetate, a stimulant of pyruvate oxidation into acetyl-CoA), or IA (IVM supplemented with sodium iodoacetate, a glycolysis inhibitor). The results revealed significant alterations in oocyte metabolism in both treatments, promoting the utilization of lipids as an energy source. These changes during IVM affected the dynamics of H3K9ac, subsequently influencing the oocyte's transcriptional activity. In the DCA and IA groups, a total of 148 and 356 differentially expressed genes were identified, respectively, compared to the control group. These findings suggest that modifications in pyruvate metabolism trigger the activation of metabolic pathways, particularly lipid metabolism, changing acetyl-CoA availability and H3K9ac levels, ultimately impacting the mRNA content of in vitro matured bovine oocytes.

Metabolic stressful environment drives epigenetic modifications in oviduct epithelial cells.

The oviduct provides a suitable microenvironment from the gametes' final maturation until initial embryo development. Dynamic functional changes are observed in the oviduct cells, mainly controlled by steroid hormones and well-orchestrated during the estrous cycle. However, based on the roles played by the oviduct, additional layers of complexity might be present in its regulatory process. There is a cellular process that includes metabolic adaptation that can guide molecular modifications. This process is known as metaboloepigenetics. Therefore, we aimed to better understand how this crosstalk occurs in oviductal epithelial cells (OEC). Due to limited in situ access to the oviduct, we used the primary in vitro cell culture as a culture model and glucose as a metabolic disturbed factor. For that, cells derived from the oviductal epithelial layer were collected from cows at either follicular or luteal stages (n = 4 animals per group). They were cultured on a monolayer culture system under normoglycemic (2.7 mM glucose) or hyperglycemic conditions (27 mM glucose). On day five of culture, attached cells were submitted to analysis of mitochondrial metabolism (mitochondrial membrane potential - MMP) and epigenetics markers (5- methylcytosine - 5 mC and histone 3 lysine 9 acetylation - H3K9ac). Moreover, the culture media were submitted to the metabolites analysis profile by Raman spectrometry. Data were analyzed considering the effect of glucose level (normoglycemic vs. hyperglycemic), stages when OEC were harvested (follicular vs. luteal), and their interaction (glucose level * cycle stage) by two-way ANOVA. As a result, the high glucose level decreased the H3K9ac and MMP levels but did not affect the 5 mC. Regardless of the metabolic profile of the culture media, the glucose level was the only factor that changed the Raman shifts abundance. Although this present study evaluated oviductal epithelial cells after being submitted to an in vitro monolayer culture system, which is known to lead to cell dedifferentiation, yet, these results provide evidence of a relationship between epigenetic reprogramming and energy metabolism under these cell culture conditions. In conclusion, the levels of metabolites in culture media may be crucial for cellular function and differentiation, meaning that it should be considered in studies culturing oviductal cells.

Simple and selective screening method for the synthetic cathinone MDPT in forensic samples using carbon nanofiber screen-printed electrodes.

3',4'-Methylenedioxy-N-tert-butylcathinone (MDPT), also known as tBuONE or D-Tertylone, is a synthetic cathinone (SC) frequently abused for recreational purposes due to its potent stimulant effects and similarity to illegal substances like methamphetamine and ecstasy. The structural diversity and rapid introduction of new SC analogs to the market poses significant challenges for law enforcement and analytical methods for preliminary screening of illicit drugs. In this work, we present, for the first time, the electrochemical detection of MDPT using screen-printed electrodes modified with carbon nanofibers (SPE-CNF). MDPT exhibited three electrochemical processes (two oxidations and one reduction) on SPE-CNF. The proposed method for MDPT detection was optimized in 0.2 mol L-1 Britton-Robinson buffer solution at pH 10.0 using differential pulse voltammetry (DPV). The SPE-CNF showed a high stability for electrochemical responses of all redox processes of MDPT using the same or different electrodes, with relative standard deviations less than 4.7% and 1.5% (N = 3) for peak currents and peak potentials, respectively. Moreover, the proposed method provided a wide linear range for MDPT determination (0.90-112 µmol L-1) with low LOD (0.26 µmol L-1). Interference studies for two common adulterants, caffeine and paracetamol, and ten other illicit drugs, including amphetamine-like compounds and different SCs, showed that the proposed sensor is highly selective for the preliminarily identification of MDPT in seized forensic samples. Therefore, SPE-CNF with DPV can be successfully applied as a fast and simple screening method for MDPT identification in forensic analysis, addressing the significant challenges posed by the structural diversity of SCs.

Assessment of River-Aquifer Interaction and Nitrogen Contamination in an Agricultural Zone Located in the Guarani Aquifer System Outcrop Area.

The excessive use of nitrogen fertilizers is responsible for an increase in nitrate concentrations in water bodies, which in the future could led to an irreversible contamination compromising the water resource quality. In this way, understand the water movement within a watershed and evaluate the impacts related to agricultural practices is relevant for water management, especially in an environmental fragile region, such as the outcrop area of the Guarani Aquifer. Water samples from a small watershed located at the Guarani Aquifer region in São Paulo state, representing surface water and groundwater discharge in riverbeds from two creeks, as well as groundwater (springs and wells) were collected for isotopic ratios (δ18O e δ2H) and nitrate determination. The results indicated that the river flow is mostly supplied by groundwater discharge, and despite the observed concentrations of nitrate in groundwater reaching the creeks, the current scenario indicate contamination in the surface water, above the regulatory levels. Therefore, the expansion in sugarcane production increases the possibility that the released nitrate reaches high levels in the future in this watershed.

Mitochondrial health index correlates with plasma circulating cell-free mitochondrial DNA in bipolar disorder.

Although mitochondrial dysfunction is known to play an essential role in the pathophysiology of bipolar disorder (BD), there is a glaring gap in our understanding of how mitochondrial dysfunction can modulate clinical phenotypes. An emerging paradigm suggests mitochondria play an important non-energetic role in adaptation to stress, impacting cellular resilience and acting as a source of systemic allostatic load. Known as mitochondrial allostatic load, this (phenomenon) occurs when mitochondria are unable to recalibrate and maintain cell homeostasis. This study aimed to evaluate the composite mitochondrial health index (MHI) in BD subjects and non-psychiatry controls. We will also explore whether lower MIH will be related to higher cell-free mtDNA (ccf-mtDNA) levels and poor clinical outcomes. In this study, 14 BD-I patients and 16 age- and sex-matched non-psychiatry controls were enrolled. Peripheral blood mononuclear cells (PBMCs) were used to measure the enzymatic activities of citrate synthase and complexes I, II, and IV and mtDNA copy number. Ccf-mtDNA was evaluated by qPCR in plasma. Mitochondrial quality control (MQC) proteins were evaluated by western blotting. After adjusting for confounding variables, such as age, sex, body mass index (BMI), and smoking status, patients with BD presented lower MHI compared to non-psychiatry controls, as well as higher ccf-mtDNA levels that negatively correlated with MHI. Because the MQC network is essential to maintain mitochondrial health, MHI and ccf-mtDNA were also examined in relation to several MQC-related proteins, such as Fis-1, Opa-1, and LC3. Our results showed that MHI correlated negatively with Fis-1 and positively with Opa-1 and LC3. Accordingly, ccf-mtDNA had a positive correlation with Fis-1 and a negative correlation with Opa-1 and LC3. Furthermore, we found a noteworthy inverse correlation between illness severity and MHI, with lower MHI and higher ccf-mtDNA levels in subjects with a longer illness duration, worse functional status, and higher depressive symptoms. Our findings indicate that mitochondrial allostatic load contributes to BD, suggesting mitochondria represent a potential biological intersection point that could contribute to impaired cellular resilience and increased vulnerability to stress and mood episodes. Ultimately, by linking mitochondrial dysfunction to disease progression and poor outcomes, we might be able to build a predictive marker that explains how mitochondrial function and its regulation contribute to BD development and that may eventually serve as a treatment guide for both old and new therapeutic targets.

Multimaterial fiber as a physical simulator of a capillary instability.

Capillary breakup of cores is an exclusive approach to fabricating fiber-integrated optoelectronics and photonics. A physical understanding of this fluid-dynamic process is necessary for yielding the desired solid-state fiber-embedded multimaterial architectures by design rather than by exploratory search. We discover that the nonlinearly complex and, at times, even chaotic capillary breakup of multimaterial fiber cores becomes predictable when the fiber is exposed to the spatiotemporal temperature profile, imposing a viscosity modulation comparable to the breakup wavelength. The profile acts as a notch filter, allowing only a single wavelength out of the continuous spectrum to develop predictably, following Euler-Lagrange dynamics. We argue that this understanding not only enables designing the outcomes of the breakup necessary for turning it into a technology for materializing fiber-embedded functional systems but also positions a multimaterial fiber as a universal physical simulator of capillary instability in viscous threads.

Sonication as a tool for disrupting biofilms and recovering microorganisms in bladder catheters / Sonicação como uma ferramenta para romper biofilmes e recuperar microrganismos em cateteres vesicais

Abstract Introduction: Urinary catheter-related infection is commonly associated with bacterial biofilm. The impact of anaerobes is unknown, but their detection in the biofilm on this device has not been previously reported. This study aimed to evaluate the capability to recovery strict, facultative, and aerobic microorganisms in patients using bladder catheters from ICUs using conventional culture, sonication, urinary analysis, and mass spectrometry. Methods: Parallel, sonicated bladder catheters from 29 critically ill patients were compared with their routine urine culture. Identification was performed using matrix-assisted laser desorption/ionization with time-of-flight mass spectrometry. Results: The positivity rate in urine (n = 2, 3.4%) was lower than that in sonicated catheters (n = 7, 13.8%). Conclusion: Bladder catheter sonication showed more positive culture results than urine samples for anaerobic and aerobic microorganisms. The role of anaerobes in urinary tract infection and catheter biofilm is discussed.

Resumo Introdução: A infecção relacionada ao cateter urinário é comumente associada ao biofilme bacteriano. O impacto dos anaeróbios é desconhecido, mas sua detecção no biofilme deste dispositivo não foi relatada anteriormente. Este estudo teve como objetivo avaliar a capacidade de recuperar microrganismos estritos, facultativos e aeróbios em pacientes que utilizam cateteres vesicais de UTIs utilizando cultura convencional, sonicação, análise urinária e espectrometria de massa. Métodos: Paralelamente, foram comparados cateteres vesicais sonicados de 29 pacientes gravemente enfermos com sua urocultura de rotina. A identificação foi realizada utilizando dessorção/ionização a laser assistida por matriz com espectrometria de massa por tempo de voo. Resultados: A taxa de positividade na urina (n = 2; 3,4%) foi inferior à dos cateteres sonicados (n = 7; 13,8%). Conclusão: A sonicação do cateter vesical apresentou resultados de cultura mais positivos do que as amostras de urina para microrganismos anaeróbios e aeróbios. É discutido o papel dos anaeróbios na infecção do trato urinário e no biofilme do cateter.

Physiology of Stretch-Mediated Hypertrophy and Strength Increases: A Narrative Review.

Increasing muscle strength and cross-sectional area is of crucial importance to improve or maintain physical function in musculoskeletal rehabilitation and sports performance. Decreases in muscular performance are experienced in phases of reduced physical activity or immobilization. These decrements highlight the need for alternative, easily accessible training regimens for a sedentary population to improve rehabilitation and injury prevention routines. Commonly, muscle hypertrophy and strength increases are associated with resistance training, typically performed in a training facility. Mechanical tension, which is usually induced with resistance machines and devices, is known to be an important factor that stimulates the underlying signaling pathways to enhance protein synthesis. Findings from animal studies suggest an alternative means to induce mechanical tension to enhance protein synthesis, and therefore muscle hypertrophy by inducing high-volume stretching. Thus, this narrative review discusses mechanical tension-induced physiological adaptations and their impact on muscle hypertrophy and strength gains. Furthermore, research addressing stretch-induced hypertrophy is critically analyzed. Derived from animal research, the stretching literature exploring the impact of static stretching on morphological and functional adaptations was reviewed and critically discussed. No studies have investigated the underlying physiological mechanisms in humans yet, and thus the underlying mechanisms remain speculative and must be discussed in the light of animal research. However, studies that reported functional and morphological increases in humans commonly used stretching durations of > 30 min per session of the plantar flexors, indicating the importance of high stretching volume, if the aim is to increase muscle mass and maximum strength. Therefore, the practical applicability seems limited to settings without access to resistance training (e.g., in an immobilized state at the start of rehabilitation), as resistance training seems to be more time efficient. Nevertheless, further research is needed to generate evidence in different human populations (athletes, sedentary individuals, and rehabilitation patients) and to quantify stretching intensity.

Blood epigenome-wide association studies of suicide attempt in adults with bipolar disorder.

Suicide attempt (SA) risk is elevated in individuals with bipolar disorder (BD), and DNA methylation patterns may serve as possible biomarkers of SA. We conducted epigenome-wide association studies (EWAS) of blood DNA methylation associated with BD and SA. DNA methylation was measured at > 700,000 positions in a discovery cohort of n = 84 adults with BD with a history of SA (BD/SA), n = 79 adults with BD without history of SA (BD/non-SA), and n = 76 non-psychiatric controls (CON). EWAS revealed six differentially methylated positions (DMPs) and seven differentially methylated regions (DMRs) between BD/SA and BD/non-SA, with multiple immune-related genes implicated. There were no epigenome-wide significant differences when BD/SA and BD/non-SA were each compared to CON, and patterns suggested that epigenetics differentiating BD/SA from BD/non-SA do not differentiate BD/non-SA from CON. Weighted gene co-methylation network analysis and trait enrichment analysis of the BD/SA vs. BD/non-SA contrast further corroborated immune system involvement, while gene ontology analysis implicated calcium signalling. In an independent replication cohort of n = 48 BD/SA and n = 47 BD/non-SA, fold-changes at the discovery cohort's significant sites showed moderate correlation across cohorts and agreement on direction. In both cohorts, classification accuracy for SA history among individuals with BD was highest when methylation at the significant CpG sites as well as information from clinical interviews were combined, with an AUC of 88.8% (CI = 83.8-93.8%) and 82.1% (CI = 73.6-90.5%) for the combined epigenetic-clinical predictor in the discovery and replication cohorts, respectively. Our results provide novel insight to the role of immune system functioning in SA and BD and also suggest that integrating information from multiple levels of analysis holds promise to improve risk assessment for SA in adults with BD.