Water availability and extreme events under climate change scenarios in an experimental watershed of the Brazilian Atlantic Forest.

Climate change has diversified negative implications on environmental sustainability and water availability. Assessing the impacts of climate change is crucial to enhance resilience and future preparedness particularly at a watershed scale. Therefore, the goal of this study is to evaluate the impact of climate change on the water balance components and extreme events in Piabanha watershed in the Brazilian Atlantic Forest. In this study, extreme climate change scenarios were developed using a wide array of global climate models acquired from the Intergovernmental Panel on Climate Change (IPCC) Sixth Assessment Reports (AR6). Two extreme climate change scenarios, DryHot and WetCool, were integrated into the Soil and Water Assessment Tools (SWAT) hydrological model to evaluate their impacts on the hydrological dynamics in the watershed. The baseline SWAT model was first developed and evaluated using different model performance evaluation metrics such as coefficient of determination (R2), Nash-Sutcliffe (NSC), and Kling-Gupta efficiency coefficient (KGE). The model results illustrated an excellent model performance with metric values reaching 0.89 and 0.64 for monthly and daily time steps respectively in the calibration (2008 to 2017) and validation (2018 to 2023) periods. The findings of future climate change impacts assessment underscored an increase in temperature and shifts in precipitation patterns. In terms of streamflow, high-flow events may experience a 47.3 % increase, while low-flows could see an 76.6 % reduction. In the DryHot scenario, annual precipitation declines from 1657 to 1420 mm, with evapotranspiration reaching 54 % of precipitation, marking a 9 % rise compared to the baseline. Such changes could induce water stress in plants and lead to modifications on structural attributes of the ecosystem recognized as the Atlantic rainforest. This study established boundaries concerning the effects of climate change and highlighted the need for proactive adaptation strategies and mitigation measures to minimize the potential adverse impacts in the study watershed.

Burnout, Engagement, and Resilience During the COVID-19 Lockdown: Keys to a Model for Teachers' Self-Efficacy.

BACKGROUND: Social isolation measures by the COVID-19 pandemic have impacted teaching work. In an "Emergency Remote Teaching" (ERT) context, it is relevant to investigate the factors that affect teachers' self-efficacy. METHODS: A total of 289 teachers from schools in southern Spain have participated in this study. They have been asked about their levels of burnout, engagement, and resilience. Comparisons were made by groups in accordance with sex, type of center they belonged to, school social context, and educational level in which the teacher taught. Using a Structural Equations Model, the multivariate relationships between the variables related to burnout, engagement, and resilience were described. RESULTS: During the ERT, teachers' self-efficacy was influenced by the 3 factors: burnout-exhaustion and cynicism-engagement, and resilience. During the ERT, the teachers in semi-private and private centers showed greater self-efficacy. In turn, the teachers in childhood and primary education showed a significantly higher level of work engagement than the teachers in compulsory and post-compulsory secondary education. CONCLUSIONS: The results in relation to ERT are discussed in the context of the exceptionality and universal globality of the pandemic phenomenon and the complex self-perception of the social value of the teaching function.

Perturbations in mitochondrial metabolism associated with defective cardiolipin biosynthesis: An in-organello real-time NMR study.

Mitochondria are central to cellular metabolism; hence, their dysfunction contributes to a wide array of human diseases including cancer, cardiopathy, neurodegeneration, and heritable pathologies such as Barth syndrome. Cardiolipin, the signature phospholipid of the mitochondrion promotes proper cristae morphology, bioenergetic functions, and directly affects metabolic reactions carried out in mitochondrial membranes. To match tissue-specific metabolic demands, cardiolipin typically undergoes an acyl tail remodeling process with the final step carried out by the phospholipid-lysophospholipid transacylase tafazzin. Mutations in the tafazzin gene are the primary cause of Barth syndrome. Here, we investigated how defects in cardiolipin biosynthesis and remodeling impact metabolic flux through the tricarboxylic acid cycle and associated pathways in yeast. Nuclear magnetic resonance was used to monitor in real-time the metabolic fate of 13 C 3 -pyruvate in isolated mitochondria from three isogenic yeast strains. We compared mitochondria from a wild-type strain to mitochondria from a Δ taz1 strain that lacks tafazzin and contains lower amounts of unremodeled cardiolipin, and mitochondria from a Δ crd1 strain that lacks cardiolipin synthase and cannot synthesize cardiolipin. We found that the 13 C-label from the pyruvate substrate was distributed through about twelve metabolites. Several of the identified metabolites were specific to yeast pathways, including branched chain amino acids and fusel alcohol synthesis. Most metabolites showed similar kinetics amongst the different strains but mevalonate and α-ketoglutarate, as well as the NAD+/NADH couple measured in separate nuclear magnetic resonance experiments, showed pronounced differences. Taken together, the results show that cardiolipin remodeling influences pyruvate metabolism, tricarboxylic acid cycle flux, and the levels of mitochondrial nucleotides.

Fazirsiran for Adults with Alpha-1 Antitrypsin Deficiency Liver Disease: A Phase 2 Placebo Controlled Trial (SEQUOIA).

BACKGROUND & AIMS: Homozygous ZZ alpha-1 antitrypsin (AAT) deficiency produces mutant AAT (Z-AAT) proteins in hepatocytes, leading to progressive liver fibrosis. We evaluated the safety and efficacy of an investigational RNA interference therapeutic, fazirsiran, that degrades Z-AAT mRNA, reducing deleterious protein synthesis. METHODS: This ongoing, phase 2 study randomized 40 patients to subcutaneous placebo or fazirsiran 25/100/200 mg. The primary endpoint was percentage change in serum Z-AAT concentration from baseline to Week 16. Patients with fibrosis on baseline liver biopsy received treatment on Day 1, Week 4, and then every 12 weeks, and had a second liver biopsy at or after Weeks 48, 72, or 96. Patients without fibrosis received two doses on Day 1 and Week 4. RESULTS: At Week 16, least-squares mean percent declines in serum Z-AAT concentration were -61%, -83% and -94% with fazirsiran 25/100/200 mg, respectively, versus placebo (all P< .0001). Efficacy was sustained through Week 52. At post-dose liver biopsy, fazirsiran reduced median liver Z-AAT concentration by 93% compared with an increase of 26% with placebo. All fazirsiran-treated patients had histological reduction from baseline in hepatic globule burden. Portal inflammation improved in 5/12 and 0/8 patients with baseline score >0 in the fazirsiran and placebo groups, respectively. Histological METAVIR score improved by >1 point in 7/14 and 3/8 patients with fibrosis >F0 at baseline in the fazirsiran and placebo groups, respectively. No adverse events led to discontinuation and pulmonary function tests remained stable. CONCLUSIONS: Fazirsiran reduced serum and liver concentrations of Z-AAT in a dose dependent manner and reduced hepatic globule burden (NCT03945292).

Does curcumin improve liver enzymes levels in nonalcoholic fatty liver disease? A systematic review, meta-analysis, and meta-regression.

The aim of this meta-analysis is to investigate the sources of heterogeneity in randomized clinical trials examining the effects of curcumin supplementation on liver aminotransferases in subjects with nonalcoholic fatty liver disease (NAFLD). We conducted a systematic search of the PubMed, SCOPUS, and Web of Science databases for randomized clinical trials and identified 15 studies (n = 835 subjects). We used random-effects models with DerSimonian-Laird methods to analyze the serum levels of alanine aminotransferase and aspartate aminotransferase enzymes. Our results indicate that curcumin did not affect serum alanine aminotransferase, but it did reduce aspartate aminotransferase levels. Notably, both outcomes showed high heterogeneity (p < 0.01). Subgroup analysis revealed that adding piperine to curcumin did not benefit aminotransferase levels in NAFLD patients. Additionally, we found a negative correlation between the duration of the intervention and the relative (mg/kg/day) curcumin dose with the reduction in liver aminotransferases. In summary, the sources of heterogeneity identified in our study are likely attributed to the duration of the intervention and the relative dose of curcumin. Consequently, longer trials utilizing high doses of curcumin could diminish the positive impact of curcumin in reducing serum levels of aminotransferases in patients with NAFLD.

Anti-inflammatory and anti-hyperalgesic effects induced by an aqueous aged black garlic extract in rodent models of ulcerative colitis and colitis-associated visceral pain.

Inflammatory bowel disease (IBD) is a morbid condition characterized by relapsing-remitting inflammation of the colon, accompanied by persistent gut dysmotility and abdominal pain. Different reports demonstrated biological activities of aged black garlic (ABG), including anti-inflammatory and antioxidant effects. We aimed to investigate beneficial effects exerted by ABGE on colon inflammation by using ex vivo and in vivo experimental models. We investigated the anti-inflammatory effects of an ABG water extract (ABGE) on rat colon specimens exposed to E. coli lipopolysaccharide (LPS), a known ex vivo experimental model of ulcerative colitis. We determined gene expression of various biomarkers involved in inflammation, including interleukin (IL)-1ß, IL-6, nuclear factor-kB (NF-kB), tumor necrosis factor (TNF)-α. Moreover, we studied the acute effects of ABGE on visceral pain associated with colitis induced by 2,4-di-nitrobenzene sulfonic acid (DNBS) injection in rats. ABGE suppressed LPS-induced gene expression of IL-1ß, IL-6, NF-kB, and TNF-α. In addition, the acute administration of ABGE (0.03-1 g kg-1) dose-dependently relieved post-inflammatory visceral pain, with the higher dose (1 g kg-1) able to significantly reduce both the behavioral nociceptive response and the entity of abdominal contraction (assessed by electromyography) in response to colorectal distension after the acute administration in DNBS-treated rats. Present findings showed that ABGE could represent a potential strategy for treatment of colitis-associated inflammatory process and visceral pain. The beneficial effects induced by the extract could be related to the pattern of polyphenolic composition, with particular regard to gallic acid and catechin.

Race analysis in swimming: understanding the evolution of publications, citations and networks through a bibliometric review.

The aim of this study was to conduct a scoping and bibliometric review of swimming articles related to race analysis. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were used to identify relevant studies. Articles on race analysis in swimming published between 1984 and December 31, 2023 were retrieved from the Web of Science database. 366 records were screened and a total of 74 articles were retained for analysis. Until 2012, there were some time intervals with no or few publications. From 2012, there was a clear upward trend in publications and citations. This theme was led by the United States of America, Australia, and Spain. Australia and Spain maintain their status as the countries with the most publications. The analysis of author collaborations revealed two clusters with Spanish authors, and the remaining clusters are composed of Portuguese, Swiss, and Australian authors. With this bibliometric review, it has been possible to understand the evolution of the articles published on race analysis in swimming, the countries and the authors that have contributed most to this topic over the years. The prediction model shows that the number of articles and citations on this topic will continue to increase over the next 10 years (until 2034).

The potential role of liquid-liquid phase separation in the cellular fate of the compartments for unconventional protein secretion.

Eukaryotic cells have developed intricate mechanisms for biomolecule transport, particularly in stressful conditions. This interdisciplinary study delves into unconventional protein secretion (UPS) pathways activated during starvation, facilitating the export of proteins bypassing most of the components of the classical secretory machinery. Specifically, we focus on the underexplored mechanisms of the GRASP's role in UPS, particularly in biogenesis and cargo recruitment for the vesicular-like compartment for UPS. Our results show that liquid-liquid phase separation (LLPS) plays a key role in the coacervation of Grh1, the GRASP yeast homologue, under starvation-like conditions. This association seems a precursor to the Compartment for Unconventional Protein Secretion (CUPS) biogenesis. Grh1's self-association is regulated by electrostatic, hydrophobic, and hydrogen-bonding interactions. Importantly, our study demonstrates that phase-separated states of Grh1 can recruit UPS cargo under starvation-like situations. Additionally, we explore how the coacervate liquid-to-solid transition could impact cells' ability to return to normal post-stress states. Our findings offer insights into intracellular protein dynamics and cell adaptive responses to stress.

Large Language Models for Intraoperative Decision Support in Plastic Surgery: A Comparison between ChatGPT-4 and Gemini.

Background and Objectives: Large language models (LLMs) are emerging as valuable tools in plastic surgery, potentially reducing surgeons' cognitive loads and improving patients' outcomes. This study aimed to assess and compare the current state of the two most common and readily available LLMs, Open AI's ChatGPT-4 and Google's Gemini Pro (1.0 Pro), in providing intraoperative decision support in plastic and reconstructive surgery procedures. Materials and Methods: We presented each LLM with 32 independent intraoperative scenarios spanning 5 procedures. We utilized a 5-point and a 3-point Likert scale for medical accuracy and relevance, respectively. We determined the readability of the responses using the Flesch-Kincaid Grade Level (FKGL) and Flesch Reading Ease (FRE) score. Additionally, we measured the models' response time. We compared the performance using the Mann-Whitney U test and Student's t-test. Results: ChatGPT-4 significantly outperformed Gemini in providing accurate (3.59 ± 0.84 vs. 3.13 ± 0.83, p-value = 0.022) and relevant (2.28 ± 0.77 vs. 1.88 ± 0.83, p-value = 0.032) responses. Alternatively, Gemini provided more concise and readable responses, with an average FKGL (12.80 ± 1.56) significantly lower than ChatGPT-4's (15.00 ± 1.89) (p < 0.0001). However, there was no difference in the FRE scores (p = 0.174). Moreover, Gemini's average response time was significantly faster (8.15 ± 1.42 s) than ChatGPT'-4's (13.70 ± 2.87 s) (p < 0.0001). Conclusions: Although ChatGPT-4 provided more accurate and relevant responses, both models demonstrated potential as intraoperative tools. Nevertheless, their performance inconsistency across the different procedures underscores the need for further training and optimization to ensure their reliability as intraoperative decision-support tools.

Fast, Efficient Tailoring Growth of Nanocrystalline Diamond Films by Fine-Tuning of Gas-Phase Composition Using Microwave Plasma Chemical Vapor Deposition.

Nanocrystalline diamond (NCD) films are attractive for many applications due to their smooth surfaces while holding the properties of diamond. However, their growth rate is generally low using common Ar/CH4 with or without H2 chemistry and strongly dependent on the overall growth conditions using microwave plasma chemical vapor deposition (MPCVD). In this work, incorporating a small amount of N2 and O2 additives into CH4/H2 chemistry offered a much higher growth rate of NCD films, which is promising for some applications. Several novel series of experiments were designed and conducted to tailor the growth features of NCD films by fine-tuning of the gas-phase compositions with different amounts of nitrogen and oxygen addition into CH4/H2 gas mixtures. The influence of growth parameters, such as the absolute amount and their relative ratios of O2 and N2 additives; substrate temperature, which was adjusted by two ways and inferred by simulation; and microwave power on NCD formation, was investigated. Short and long deposition runs were carried out to study surface structural evolution with time under identical growth conditions. The morphology, crystalline and optical quality, orientation, and texture of the NCD samples were characterized and analyzed. A variety of NCD films of high average growth rates ranging from 2.1 µm/h up to 6.7 µm/h were successfully achieved by slightly adjusting the O2/CH4 amounts from 6.25% to 18.75%, while that of N2 was kept constant. The results clearly show that the beneficial use of fine-tuning of gas-phase compositions offers a simple and effective way to tailor the growth characteristics and physical properties of NCD films for optimizing the growth conditions to envisage some specific applications.

Molecular Characterization of the Chicken Parvovirus Based on VP1 Gene Circulating in Brazilian Chicken Flocks.

Parvovirus infection affects several animal species, especially young animals. In birds, parvovirus infection has been described in Muscovy ducks, turkeys, and chickens, all of which had enteric diseases characterized by diarrhea. Chicken parvovirus (ChPV) has been detected in poultry around the world in animals affected by enteric problems, showing dwarfism, cloacal pasting, and diarrhea. In Brazil, ChPV was detected in chickens affected by diarrhea fifteen years ago. However, the genetic characteristics of ChPV circulating in chicken flocks were not determined. Therefore, the aim of the present investigation was to determine the genetic characteristics of the VP1 gene from ChPV detected in chickens affected by enteric diseases in Brazil. For this purpose, a molecular approach was used. Specific primers were designed to flank the complete VP1 gene of ChPV and amplify it using PCR. The amplified products from samples of chickens with enteric diseases were sequenced, and 22 complete CDs of the VP1 gene were obtained. These samples, compared to the ABU-P1 sequence, showed 17 sequences with high nucleotide (NT) similarity of 92.7-97.4% and amino acid (AA) similarity of 94.8-99.5% associated with Runting and Stunting syndrome (RSS); there were also five samples associated with hens with diarrhea with unusual jejunal dilatation (JD) that had less similarity than the RSS sequences (NT of 86.5% and AA of 93-93.1%). The phylogenetic analysis determined four groups. Group I had sequences from Korea. The second group included sequences from Korea, China, and Brazil (not included in this work). The third group had studied RSS sequences grouped with the ABU-P1 strain and sequences from China and the United States. Finally, the sequences from JD were clustered in a separate group with a bootstrap of 100%, a group that was denoted as group IV, and included sequences from China. RDP4 and SimPlot analysis showed one point of recombination with the sequences of group III ChPV in the JD sequences. Herein, we show that circulating strains of ChPV exhibit genetic differences in the VP1 gene in Brazilian chicken flocks. Nevertheless, more studies are needed to determine the probability of a new genetic group of ChPV based on the analysis of the complete genome.

Exploring liquid-liquid phase separation in the organisation of Golgi matrix proteins.

The Golgi apparatus is a critical organelle in protein sorting and lipid metabolism. Characterized by its stacked, flattened cisternal structure, the Golgi exhibits distinct polarity with its cis- and trans-faces orchestrating various protein maturation and transport processes. At the heart of its structural integrity and organisation are the Golgi Matrix Proteins (GMPs), predominantly comprising Golgins and GRASPs. These proteins contribute to this organelle's unique stacked and polarized structure and ensure the precise localization of Golgi-resident enzymes, which is crucial for accurate protein processing. Despite over a century of research since its discovery, the Golgi architecture's intricate mechanisms still need to be fully understood. Here, we discuss that GMPs across different Eukaryotic lineages present a significant tendency to form biomolecular condensates. Moreover, we validated experimentally that members of the GRASP family also exhibit a strong tendency. Our findings offer a new perspective on the possible roles of protein disorder and condensation of GMPs in the Golgi organisation.

Implications of seasonal and daily variation on methane and ammonia emissions from naturally ventilated dairy cattle barns in a Mediterranean climate: A two-year study.

Seasonal and daily variations of gaseous emissions from naturally ventilated dairy cattle barns are important figures for the establishment of effective and specific mitigation plans. The present study aimed to measure methane (CH4) and ammonia (NH3) emissions in three naturally ventilated dairy cattle barns covering the four seasons for two consecutive years. In each barn, air samples from five indoor locations were drawn by a multipoint sampler to a photoacoustic infrared multigas monitor, along with temperature and relative humidity. Milk production data were also recorded. Results showed seasonal differences for CH4 and NH3 emissions in the three barns with no clear trends within years. Globally, diel CH4 emissions increased in the daytime with high intra-hour variability. The average hourly CH4 emissions (g h-1 livestock unit-1 (LU)) varied from 8.1 to 11.2 and 6.2 to 20.3 in the dairy barn 1, from 10.1 to 31.4 and 10.9 to 22.8 in the dairy barn 2, and from 1.5 to 8.2 and 13.1 to 22.1 in the dairy barn 3, respectively, in years 1 and 2. Diel NH3 emissions highly varied within hours and increased in the daytime. The average hourly NH3 emissions (g h-1 LU-1) varied from 0.78 to 1.56 and 0.50 to 1.38 in the dairy barn 1, from 1.04 to 3.40 and 0.93 to 1.98 in the dairy barn 2, and from 0.66 to 1.32 and 1.67 to 1.73 in the dairy barn 3, respectively, in years 1 and 2. Moreover, the emission factors of CH4 and NH3 were 309.5 and 30.6 (g day-1 LU-1), respectively, for naturally ventilated dairy cattle barns. Overall, this study provided a detailed characterization of seasonal and daily gaseous emissions variations highlighting the need for future longitudinal emission studies and identifying an opportunity to better adequate the existing mitigation strategies according to season and daytime.

Cannabinoid Analgesia in Postoperative Pain Management: From Molecular Mechanisms to Clinical Reality.

Postoperative pain (POP) is a challenging clinical phenomenon that affects the majority of surgical patients and demands effective management to mitigate adverse outcomes such as persistent pain. The primary goal of POP management is to alleviate suffering and facilitate a seamless return to normal function for the patient. Despite compelling evidence of its drawbacks, opioid analgesia remains the basis of POP treatment. Novel therapeutic approaches rely on multimodal analgesia, integrating different pharmacological strategies to optimize efficacy while minimizing adverse effects. The recognition of the imperative role of the endocannabinoid system in pain regulation has prompted the investigation of cannabinoid compounds as a new therapeutic avenue. Cannabinoids may serve as adjuvants, enhancing the analgesic effects of other drugs and potentially replacing or at least reducing the dependence on other long-term analgesics in pain management. This narrative review succinctly summarizes pertinent information on the molecular mechanisms, clinical therapeutic benefits, and considerations associated with the plausible use of various cannabinoid compounds in treating POP. According to the available evidence, cannabinoid compounds modulate specific molecular mechanisms intimately involved in POP. However, only two of the eleven clinical trials that evaluated the efficacy of different cannabinoid interventions showed positive results.

Improving the Detection of Potential Cases of Familial Hypercholesterolemia: Could Machine Learning Be Part of the Solution?

BACKGROUND: Familial hypercholesterolemia (FH), while highly prevalent, is a significantly underdiagnosed monogenic disorder. Improved detection could reduce the large number of cardiovascular events attributable to poor case finding. We aimed to assess whether machine learning algorithms outperform clinical diagnostic criteria (signs, history, and biomarkers) and the recommended screening criteria in the United Kingdom in identifying individuals with FH-causing variants, presenting a scalable screening criteria for general populations. METHODS AND RESULTS: Analysis included UK Biobank participants with whole exome sequencing, classifying them as having FH when (likely) pathogenic variants were detected in their LDLR, APOB, or PCSK9 genes. Data were stratified into 3 data sets for (1) feature importance analysis; (2) deriving state-of-the-art statistical and machine learning models; (3) evaluating models' predictive performance against clinical diagnostic and screening criteria: Dutch Lipid Clinic Network, Simon Broome, Make Early Diagnosis to Prevent Early Death, and Familial Case Ascertainment Tool. One thousand and three of 454 710 participants were classified as having FH. A Stacking Ensemble model yielded the best predictive performance (sensitivity, 74.93%; precision, 0.61%; accuracy, 72.80%, area under the receiver operating characteristic curve, 79.12%) and outperformed clinical diagnostic criteria and the recommended screening criteria in identifying FH variant carriers within the validation data set (figures for Familial Case Ascertainment Tool, the best baseline model, were 69.55%, 0.44%, 65.43%, and 71.12%, respectively). Our model decreased the number needed to screen compared with the Familial Case Ascertainment Tool (164 versus 227). CONCLUSIONS: Our machine learning-derived model provides a higher pretest probability of identifying individuals with a molecular diagnosis of FH compared with current approaches. This provides a promising, cost-effective scalable tool for implementation into electronic health records to prioritize potential FH cases for genetic confirmation.

Dietary supplementation with plant extracts for amelioration of persistent myofascial discomfort in the cervical and back regions: a randomized double-blind controlled study.

Background: Back pain is a common health problem that affects both workers and older people, reducing their quality of life. The primary objective was to assess the effect of dietary supplementation with plant extracts of rosemary, ashwagandha, and sesame consumed for 12 weeks on the intensity of back pain. Methods: A single-center randomized double-blind study with three parallel arms depending on the product consumed. The duration of treatment was 12 weeks. The investigational product, Berelief®, contained a blend of three polyphenolic standardized extracts: rosemary (Rosmarinus officinalis L.), ashwagandha (Withania somnifera L.), and sesame (Sesamum indicum L.) seed. Two doses were tested: low dose (400 mg) and high dose (800 mg). There were 42 subjects in the placebo group, 39 in the low dose and 42 in the high dose groups. Study variables included back pain intensity [VAS score, Patient-Reported Outcomes Measurement Information System (PROMIS-29), and Cornell Musculoskeletal Discomfort Questionnaire; functionality Roland-Morris Disability (RMD) questionnaire]; quality of life (QoL) [36-item Short Form Survey (SF-36), the Beck Depression Inventory-II (BDI-II), the State-Trait Anxiety Inventory (STAI), and the Perceived Stress Scale (PSS)]; sleep quality [accelerometer and Pittsburgh Sleep Quality Index (PSQI)]. Results: The improvement in back pain recorded by the visual analogue scale (VAS) at the study visits after the beginning of treatment, as well as on a weekly basis recorded in the diary card was significantly higher in the intervention group than in the placebo group (p < 0.044 dose-low; p < 0.005 dose-high). Significant differences in pain intensity of the PROMIS-29 (p = 0.002) and upper back pain in the Cornell questionnaire (p = 0.011) in favour of the investigational product were found. Furthermore, benefits in improving health-related quality of life, mood and sleep quality were also detected. Conclusion: Dietary supplementation for 12 weeks of a blend of polyphenolic standardized extracts of rosemary, ashwagandha, and sesame was effective in reducing the intensity of pain in subjects with chronic myofascial cervical and back pain.

Artificial Intelligence in Postoperative Care: Assessing Large Language Models for Patient Recommendations in Plastic Surgery.

Since their release, the medical community has been actively exploring large language models' (LLMs) capabilities, which show promise in providing accurate medical knowledge. One potential application is as a patient resource. This study analyzes and compares the ability of the currently available LLMs, ChatGPT-3.5, GPT-4, and Gemini, to provide postoperative care recommendations to plastic surgery patients. We presented each model with 32 questions addressing common patient concerns after surgical cosmetic procedures and evaluated the medical accuracy, readability, understandability, and actionability of the models' responses. The three LLMs provided equally accurate information, with GPT-3.5 averaging the highest on the Likert scale (LS) (4.18 ± 0.93) (p = 0.849), while Gemini provided significantly more readable (p = 0.001) and understandable responses (p = 0.014; p = 0.001). There was no difference in the actionability of the models' responses (p = 0.830). Although LLMs have shown their potential as adjunctive tools in postoperative patient care, further refinement and research are imperative to enable their evolution into comprehensive standalone resources.

FMR1 allelic complexity in premutation carriers provides no evidence for a correlation with age at amenorrhea.

BACKGROUND: Premutations in the Fragile X Messenger Ribonucleoprotein 1 (FMR1) gene, defined as between 55 and 200 CGGs, have been implicated in fragile X-associated primary ovarian insufficiency (FXPOI). Only 20% of female premutation carriers develop early ovulatory dysfunction, the reason for this incomplete penetrance is unknown. This study validated the mathematical model in premutation alleles, after assigning each allele a score representing allelic complexity. Subsequently, allelic scores were used to investigate the impact of allele complexity on age at amenorrhea for 58 premutation cases (116 alleles) previously published. METHODS: The allelic score was determined using a formula previously described by our group. The impact of each allelic score on age at amenorrhea was analyzed using Pearson's test and a contour plot generated to visualize the effect. RESULTS: Correlation of allelic score revealed two distinct complexity behaviors in premutation alleles. No significant correlation was observed between the allelic score of premutation alleles and age at amenorrhea. The same lack of significant correlation was observed regarding normal-sized alleles, despite a nearly significant trend. CONCLUSIONS: Our results suggest that the use of allelic scores combination have the potential to explain female infertility, namely the development of FXPOI, or ovarian dysfunction, despite the lack of correlation with age at amenorrhea. Such a finding is of great clinical significance for early identification of females at risk of ovulatory dysfunction, enhancement of fertility preservation techniques, and increasing the probability for a successful pregnancy in females with premutations. Additional investigation is necessary to validate this hypothesis.

Assessment of the shaping ability of R-Motion 30 .04 and 25 .06 in mesial canals of mandibular molars based on automated computational measurement.

INTRODUCTION: The aim of this study was to evaluate changes in geometry following root canal preparation using R-Motion instruments with different apical sizes and tapers. METHODS: 54 mesial canals of mandibular molars with single curvature of angles ranging between 20° and 30° were stratified into 3 groups according to their internal anatomy (R-Motion 25/.06, 30/.04, Reciproc Blue) (n=18 per group). Micro-computed tomography was used to standardize the samples before instrumentation and, after instrumentation, to assess canal transportation, changes in canal volume and centering ability. Canals were irrigated with 17% EDTA and sodium hypochlorite, and the final rinse included subsonic agitation of these solutions. Measurements were analyzed automatically using the Dragonfly software (Come, Montreal, Canada) and were confirmed by a technician and an endodontist, based on a previously validated methodology. The results were analyzed using the Kruskal-Wallis's and Mann-Whitney´s tests. The level of statistical significance was set at 5%. RESULTS: Significant differences were found in the coronal third for canal transportation, with Reciproc Blue R25 having greater values compared with both R-Motion instruments (p<0.05) and greater changes in volume when compared with R-Motion 30/.04 (p<0.05). CONCLUSIONS: R-Motion of apical size and taper 25/.06 and 30/.04 were associated with similar changes in geometry following root canal preparation in curved mesial canals of mandibular molars, whereas Reciproc Blue was associated with greater canal transportation in the coronal root third.

Association of Complement Factors With Disability Progression in Primary Progressive Multiple Sclerosis.

BACKGROUND AND OBJECTIVES: The complement system is known to play a role in multiple sclerosis (MS) pathogenesis. However, its contribution to disease progression remains elusive. The study investigated the role of the complement system in disability progression of patients with primary progressive MS (PPMS). METHODS: Sixty-eight patients with PPMS from 12 European MS centers were included in the study. Serum and CSF levels of a panel of complement components (CCs) were measured by multiplex enzyme-linked immunosorbent assay at a baseline time point (i.e., sampling). Mean (SD) follow-up time from baseline was 9.6 (4.8) years. Only one patient (1.5%) was treated during follow-up. Univariable and multivariable logistic regressions adjusted for age, sex, and albumin quotient were performed to assess the association between baseline CC levels and disability progression in short term (2 years), medium term (6 years), and long term (at the time of the last follow-up). RESULTS: In short term, CC played little or no role in disability progression. In medium term, an elevated serum C3a/C3 ratio was associated with a higher risk of disability progression (adjusted OR 2.30; 95% CI 1.17-6.03; p = 0.040). By contrast, increased CSF C1q levels were associated with a trend toward reduced risk of disability progression (adjusted OR 0.43; 95% CI 0.17-0.98; p = 0.054). Similarly, in long term, an elevated serum C3a/C3 ratio was associated with higher risk of disability progression (adjusted OR 1.81; 95% CI 1.09-3.40; p = 0.037), and increased CSF C1q levels predicted lower disability progression (adjusted OR 0.41; 95% CI 0.17-0.86; p = 0.025). DISCUSSION: Proteins involved in the activation of early complement cascades play a role in disability progression as risk (elevated serum C3a/C3 ratio) or protective (elevated CSF C1q) factors after 6 or more years of follow-up in patients with PPMS. The protective effects associated with C1q levels in CSF may be related to its neuroprotective and anti-inflammatory properties.