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Toxin-antitoxin (TA) systems are widespread in bacteria and implicated in genome stability, virulence, phage defense, and persistence. TA systems have diverse activities and cellular targets, but their physiological roles and regulatory mechanisms are often unclear. Here, we show that the NatR-NatT TA system, which is part of the core genome of the human pathogen Pseudomonas aeruginosa, generates drug-tolerant persisters by specifically depleting nicotinamide dinucleotides. While actively growing P. aeruginosa cells compensate for NatT-mediated NAD + deficiency by inducing the NAD + salvage pathway, NAD depletion generates drug-tolerant persisters under nutrient-limited conditions. Our structural and biochemical analyses propose a model for NatT toxin activation and autoregulation and indicate that NatT activity is subject to powerful metabolic feedback control by the NAD + precursor nicotinamide. Based on the identification of natT gain-of-function alleles in patient isolates and on the observation that NatT increases P. aeruginosa virulence, we postulate that NatT modulates pathogen fitness during infections. These findings pave the way for detailed investigations into how a toxin-antitoxin system can promote pathogen persistence by disrupting essential metabolic pathways., (© 2024. The Author(s).)

Thirty to seventy percent of proteins in any given genome have no assigned function and have been labeled as the protein "unknome". This large knowledge gap prevents the biological community from fully leveraging the plethora of genomic data that is now available. Machine-learning approaches are showing some promise in propagating functional knowledge from experimentally characterized proteins to the correct set of isofunctional orthologs. However, they largely fail to predict enzymatic functions unseen in the training set, as shown by dissecting the predictions made for over 450 enzymes of unknown function from the model bacteria Escherichia coli uxgsing the DeepECTransformer platform. Lessons from these failures can help the community develop machine-learning methods that assist domain experts in making testable functional predictions for more members of the uncharacterized proteome., Article Summary: Many proteins in any genome, ranging from 30 to 70%, lack an assigned function. This knowledge gap limits the full use of the vast available genomic data. Machine learning has shown promise in transferring functional knowledge from proteins of known functions to similar ones, but largely fails to predict novel functions not seen in its training data. Understanding these failures can guide the development of better machine-learning methods to help experts make accurate functional predictions for uncharacterized proteins.

Purpose: Tinnitus, the perception of sound without any external sound source, is a prevalent hearing health concern. Mounting evidence suggests that a confluence of genetic, environmental, and lifestyle factors can influence the pathogenesis of tinnitus. We hypothesized that alteration in DNA methylation, an epigenetic modification that occurs at cytosines of cytosine-phosphate-guanine (CpG) dinucleotide sites, where a methyl group from S-adenyl methionine gets transferred to the fifth carbon of the cytosine, could contribute to tinnitus. DNA methylation patterns are tissue-specific, but the tissues involved in tinnitus are not easily accessible in humans. This pilot study used saliva as a surrogate tissue to identify differentially methylated CpG regions (DMRs) associated with tinnitus. The study was conducted on healthy young adults reporting bilateral continuous chronic tinnitus to limit the influence of age-related confounding factors and health-related comorbidities., Methods: The present study evaluated the genome-wide methylation levels from saliva-derived DNA samples from 24 healthy young adults with bilateral continuous chronic tinnitus (> 1 year) and 24 age, sex, and ethnicity-matched controls with no tinnitus. Genome-wide DNA methylation was evaluated for > 850,000 CpG sites using the Infinium Human Methylation EPIC BeadChip. The association analysis used the Bumphunter algorithm on 23 cases and 20 controls meeting the quality control standards. The methylation level was expressed as the area under the curve of CpG sites within DMRs.The FDR-adjusted p-value threshold of 0.05 was used to identify statistically significant DMRs associated with tinnitus., Results: We obtained 25 differentially methylated regions (DMRs) associated with tinnitus. Genes within or in the proximity of the hypermethylated DMRs related to tinnitus included LCLAT1, RUNX1, RUFY1, NUDT12, TTC23, SLC43A2, C4orf27 (STPG2), and EFCAB4B. Genes within or in the proximity of hypomethylated DMRs associated with tinnitus included HLA-DPB2, PM20D1, TMEM18, SNTG2, MUC4, MIR886, MIR596, TXNRD1, EID3, SDHAP3, HLA-DPB2, LASS3 (CERS3), C10orf11 (LRMDA), HLA-DQB1, NADK, SZRD1, MFAP2, NUP210L, TPM3, INTS9, and SLC2A14. The burden of genetic variation could explain the differences in the methylation levels for DMRs involving HLA-DPB2, HLA-DQB1, and MUC4, indicating the need for replication in large independent cohorts., Conclusion: Consistent with the literature on comorbidities associated with tinnitus, we identified genes within or close to DMRs involved in auditory functions, chemical dependency, cardiovascular diseases, psychiatric conditions, immune disorders, and metabolic syndromes. These results indicate that epigenetic mechanisms could influence tinnitus, and saliva can be a good surrogate for identifying the epigenetic underpinnings of tinnitus in humans. Further research with a larger sample size is needed to identify epigenetic biomarkers and investigate their influence on the phenotypic expression of tinnitus., (© 2024. The Author(s) under exclusive licence to Association for Research in Otolaryngology.)

Background: Burnout, anxiety, and depression continue to affect physicians, postgraduate medical trainees, and medical students globally and in Canada particularly after the COVID-19 pandemic., Objective: The primary goal of this project is to design, implement, monitor, and evaluate a daily supportive SMS text messaging program (Wellness4MDs, Global Psychological e-Health Foundation). The program aims to reduce the prevalence and severity of burnout, anxiety, and depression symptoms among physicians, postgraduate medical trainees, and medical students in Canada., Methods: This longitudinal study represents a multistakeholder, mixed methods, multiyear implementation science project. Project evaluation will be conducted through a quantitative prospective longitudinal approach using a paired sample comparison, a naturalistic cross-sectional controlled design, and satisfaction surveys. Prevalence estimates for psychological problems would be based on baseline data from self-completed validated rating scales. Additional data will be collected at designated time points for paired comparison. Outcome measures will be assessed using standardized rating scales, including the Maslach Burnout Inventory for burnout symptoms, the 9-item Patient Health Questionnaire for depression symptoms, the 7-item Generalized Anxiety Disorder scale for anxiety symptoms, and the World Health Organization-Five Well-Being Index., Results: The project launched in the last quarter of 2023, and program evaluation results will become available within 36 months. The Wellness4MDs program is expected to reduce the prevalence and severity of psychological problems among physicians in Canada and achieve high subscriber satisfaction., Conclusions: The results from the Wellness4MDs project evaluation will provide key information regarding the effectiveness of daily supportive SMS text messages and links to mental health resources on these mental health parameters in Canadian physicians, postgraduate trainees, and medical students. Information will be useful for informing policy and decision-making concerning psychological interventions for physicians in Canada., International Registered Report Identifier (irrid): PRR1-10.2196/44368., (©Reham Shalaby, Belinda Agyapong, Raquel Dias, Gloria Obuobi-Donkor, Medard K Adu, Sharron Spicer, Natalie L Yanchar, Vincent I O Agyapong. Originally published in JMIR Research Protocols (https://www.researchprotocols.org), 16.09.2024.)

Integrated production systems have been proposed as alternative to sustainable land use. However, information regarding bacterial community structure and diversity in soils of integrated Crop-Livestock-Forest systems remains unknown. We hypothesize that these integrated production systems, with their ecological intensification, can modulate the soil bacterial communities. However, Yet, it remains unclear whether the modulation of bacterial biodiversity is solely attributable to the complexity of root exudates or if seasonal climatic events also play a contributory role. The objective of this study is to evaluate the impact of monoculture and integrated production systems on bacterial soil communities in the Amazon Biome, Brazil. Three monoculture systems, each with a single crop over time and space (Eucalyptus (E), Crop Soybean (C), Pasture (P)), and three integrated systems with multiple crops over time and space (ECI, PI, ECPI) were evaluated, along with a Native forest serving as a reference area. Soil samples were collected at a depth of 0-10 cm during both the wet and dry seasons. Bacterial composition was determined using Illumina high-throughput sequencing of the 16 S rRNA gene. The sequencing results revealed the highest abundance classified under the phyla Firmicutes, Actinobacteria, and Proteobacteria. The Firmicutes correlated with the Crop in the rainy period and in the dry only ECPI and Forest. For five classes corresponding to the three phyla, the Crop stood out with the greatest fluctuations in their relative abundance compared to other production systems. In cluster analysis by genus during the rainy season, only Forest and ECPI showed no similarity with the other production systems. However, in the dry season, both were grouped with Forest and EPI. Therefore, the bacterial community in integrated systems proved to be sensitive to management practices, even with only two years of use. ECPI demonstrated the greatest similarity in bacterial structure to the Native forest, despite just two years of experimental deployment. Crop exhibited fluctuations in relative abundance in both seasons, indicating an unsustainable production system with changes in soil microbial composition. These findings support our hypothesis that integrated production systems and their ecological intensification, as exemplified by ECPI, can indeed modulate soil bacterial communities., (© 2024. The Author(s) under exclusive licence to Sociedade Brasileira de Microbiologia.)

Background: Large vessel occlusion acute ischemic stroke prognosis improved following the 2015 endovascular therapy (EVT) trials. Blood-based biomarkers may improve outcome prediction. We aimed to assess plasma brain-derived tau (BD-Tau) performance in predicting post-EVT large vessel occlusion acute ischemic stroke outcomes., Methods: We included 2 temporally independent prospective cohorts of anterior circulation in patients with large vessel occlusion acute ischemic stroke who successfully recanalized post-EVT. We measured plasma BD-Tau, GFAP (glial-fibrillary-acidic-protein), NfL (neurofilament-light-chain), and total-Tau upon admission, immediately, 24 hours, and 72 hours post-EVT. Twenty-four-hour neuroimaging and 90-day functional outcomes were independently assessed using the Alberta Stroke Program Early Computed Tomography Score (good outcome: >7 or unchanged) and the modified Rankin Scale (favorable outcome <3 or unchanged), respectively. Based on the first cohort (derivation), we built a multivariable logistic regression model to predict a 90-day functional outcome. Model results were evaluated using the second cohort (evaluation)., Results: In the derivation cohort (n=78, mean age=72.9 years, 50% women), 62% of patients had a good 24-hour neuroimaging outcome, and 45% had a favorable 90-day functional outcome. GFAP admission-to-EVT rate-of-change was the best predictor for early neuroimaging outcome but not for 90-day functional outcome. At admission, BD-Tau levels presented the highest discriminative performance for 90-day functional outcomes (area under the curve, 0.76 [95% CI, 0.65-0.87]; P <0.001). The model incorporating age, admission BD-Tau, and 24-hour Alberta Stroke Program Early Computed Tomography Score achieved excellent discrimination of 90-day functional outcome (area under the curve, 0.89 [95% CI, 0.82-0.97]; P <0.001). The score's predictive performance was maintained in the evaluation cohort (n=66; area under the curve, 0.82 [95% CI, 0.71-0.92]; P <0.001)., Conclusions: Admission plasma BD-Tau accurately predicted 90-day functional outcomes in patients with large vessel occlusion acute ischemic stroke after successful EVT. The proposed model may predict functional outcomes using objective measures, minimizing human-related biases and serving as a simplified prognostic tool for AIS., Competing Interests: Dr Maia reports compensation from Alnylam Pharmaceuticals and Bristol-Myers Squibb Company for consultant services. Dr Blennow reports compensation from Eli LIlly, EISAI INC, and F. Hoffmann-La Roche for consultant services. Dr Karikari reports grants from Vetenskapsrådet; a patent issued for Use of a ps396 assay to diagnose tauopathies https://patents.google.com/patent/WO2020193500A1/en; and grants from National Institutes of Health. Dr Zetterberg has served at scientific advisory boards and/or as a consultant for Abbvie, Acumen, Alector, Alzinova, ALZPath, Annexon, Apellis, Artery Therapeutics, AZTherapies, CogRx, Denali, Eisai, Nervgen, Novo Nordisk, Optoceutics, Passage Bio, Pinteon Therapeutics, Prothena, Red Abbey Labs, reMYND, Roche, Samumed, Siemens Healthineers, Triplet Therapeutics, and Wave, and given lectures in symposia sponsored by Cellectricon, Fujirebio, Alzecure, Biogen, and Roche, and is a co-founder of Brain Biomarker Solutions in Gothenburg AB, which is a part of the GU Ventures Incubator Program (outside submitted work). N.L. Knuth reports a patent on the use of BD-Tau.

Phenothiazines inhibit antioxidant enzymes in trypanosomatids. However, potential interferences with host cell antioxidant defenses are central concerns in using these drugs to treat Trypanosoma cruzi-induced infectious myocarditis. Thus, the interaction of thioridazine (TDZ) with T. cruzi and cardiomyocytes antioxidant enzymes, and its impact on cardiomyocytes and cardiac infection was investigated in vitro and in vivo. Cardiomyocytes and trypomastigotes in culture, and mice treated with TDZ and benznidazole (Bz, reference antiparasitic drug) were submitted to microstructural, biochemical and molecular analyses. TDZ was more cytotoxic and less selective against T. cruzi than Bz in vitro. TDZ-pretreated cardiomyocytes developed increased infection rate, reactive oxygen species (ROS) production, lipid and protein oxidation; similar catalase (CAT) and superoxide dismutase (SOD) activity, and reduced glutathione's (peroxidase - GPx, S-transferase - GST, and reductase - GR) activity than infected untreated cells. TDZ attenuated trypanothione reductase activity in T. cruzi, and protein antioxidant capacity in cardiomyocytes, making these cells more susceptible to H 2 O 2 -based oxidative challenge. In vivo, TDZ potentiated heart parasitism, total ROS production, myocarditis, lipid and protein oxidation; as well as reduced GPx, GR, and GST activities compared to untreated mice. Benznidazole decreased heart parasitism, total ROS production, heart inflammation, lipid and protein oxidation in T. cruzi-infected mice. Our findings indicate that TDZ simultaneously interact with enzymatic antioxidant targets in cardiomyocytes and T. cruzi, potentiating the infection by inducing antioxidant fragility and increasing cardiomyocytes and heart susceptibility to parasitism, inflammation and oxidative damage., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Women remain underrepresented in leadership roles, faculty roles, and among residents in orthopaedic surgery. It has been suggested that having women in leadership positions in orthopaedic surgery may help to increase the gender diversity of residency programs. However, to our knowledge, no study has explored the relationship, if any, between the gender of the residency program director and the percentage of women in the residency program., Questions/purposes: (1) Is the program director's gender associated with differences in the percentage of women orthopaedic surgery residents? (2) Do women and men differ in the time to appointment of program director?, Methods: A list of 207 orthopaedic surgery residencies was obtained from the Accreditation Council for Graduate Medical Education (ACGME) website for the academic year 2021 to 2022. The study excluded 6% (13) of programs; 4% (8) were those without ACGME accreditation and those with initial accreditation, and 2% (5) did not have updated 2021 to 2022 resident lists. Descriptive information on 194 programs was obtained from publicly accessible resources from July 2021 through July 2022. The institution's website and the American Medical Association's (AMA) Fellowship and Residency Electronic Interactive Database (FREIDA) was used to collect residency program characteristics and resident demographics [ 2 ]. Doximity, Healthgrades, and LinkedIn were used to further collect current orthopaedic surgery residency program director demographics, including gender, age, and education/training history. To determine gender, photographs and pronouns (she/her/hers or he/him/hers) used in their biographies were used first. To confirm this, secondary sources were used including their NPI profile, which lists gender; Doximity; and their LinkedIn profile. Scopus was used to analyze research output by the program directors-using the Hirsch index (h-index) as the primary bibliometric metric. A total of 194 program directors were identified, of whom of 12% (23) were women and 88% (171) were men. Of the 4421 total residents among these programs, 20% (887) were women and 80% (3534) were men. A univariate analysis comparing program directors was conducted, with continuous variables analyzed using an independent-sample t-test and categorical variables analyzed using a Pearson chi-square test. With the numbers available, a post hoc statistical power calculation indicated that we could detect an 32% difference in the percentage of women in a program as significant with 80% power at the p < 0.05 level, whereas we might have been underpowered to discern smaller differences than that., Results: With the numbers available, we found no difference in the percentage of women in residency programs run by women program directors than in programs in which the program director was a man (22% [125 of 558] versus 20% [762 of 3863], mean difference 2% [95% CI -1.24% to 7.58%]; p = 0.08). Comparing women to men program directors, women had fewer years between residency completion and appointment to the position of program director (8 ± 2 years versus 12 ± 7 years, mean difference 4 years [95% CI 2.01 to 7.93 years]; p = 0.02) and had a lower mean h-index (7 ± 4 versus 11 ± 11, mean difference 4 [95% CI 1.70 to 6.56]; p = 0.03) and number of publications (24 ± 23 versus 41 ± 62, mean difference 17 [95% CI 3.98 to 31.05]; p = 0.01), although they did not differ in terms of their advanced degrees, duration of training, or likelihood of having taken a fellowship., Conclusion: Orthopaedic residency programs that were run by women did not contain a higher percentage of women residents, suggesting that the gender of the individual in that role may not be as important as has been speculated by others. Future studies should investigate the intersectionality of gender, race, and ethnicity of residents, program directors, and current faculty., Clinical Relevance: The fact that women were placed in program director roles earlier in career may also carry special jeopardy for them. Those roles are difficult and can impair a faculty member's ability to conduct individual research, which often is key to further academic promotions. Given that and the fact that the gender of the program director was not associated with differences in gender composition of residency programs, we believe that increasing mentorship and access to pipeline programs will help promote diversity in residency programs., Competing Interests: Each author certifies that there are no funding or commercial associations (consultancies, stock ownership, equity interest, patent/licensing arrangements, etc.) that might pose a conflict of interest in connection with the submitted article related to the author or any immediate family members. All ICMJE Conflict of Interest Forms for authors and Clinical Orthopaedics and Related Research ® editors and board members are on file with the publication and can be viewed on request., (Copyright © 2024 by the Association of Bone and Joint Surgeons.)

Purpose: Age-related hearing loss is the most common form of permanent hearing loss that is associated with various health traits, including Alzheimer's disease, cognitive decline, and depression. The present study aims to identify genetic comorbidities of age-related hearing loss. Past genome-wide association studies identified multiple genomic loci involved in common adult-onset health traits. Polygenic risk scores (PRS) could summarize the polygenic inheritance and quantify the genetic susceptibility of complex traits independent of trait expression. The present study conducted a PRS-based association analysis of age-related hearing difficulty in the UK Biobank sample (N = 425,240), followed by a replication analysis using hearing thresholds (HTs) and distortion-product otoacoustic emissions (DPOAEs) in 242 young adults with self-reported normal hearing. We hypothesized that young adults with genetic comorbidities associated with age-related hearing difficulty would exhibit subclinical decline in HTs and DPOAEs in both ears., Methods: A total of 111,243 participants reported age-related hearing difficulty in the UK Biobank sample (> 40 years). The PRS models were derived from the polygenic risk score catalog to obtain 2627 PRS predictors across the health spectrum. HTs (0.25-16 kHz) and DPOAEs (1-16 kHz, L1/L2 = 65/55 dB SPL, F2/F1 = 1.22) were measured on 242 young adults. Saliva-derived DNA samples were subjected to low-pass whole genome sequencing, followed by genome-wide imputation and PRS calculation. The logistic regression analyses were performed to identify PRS predictors of age-related hearing difficulty in the UK Biobank cohort. The linear mixed model analyses were performed to identify PRS predictors of HTs and DPOAEs., Results: The PRS-based association analysis identified 977 PRS predictors across the health spectrum associated with age-related hearing difficulty. Hearing difficulty and hearing aid use PRS predictors revealed the strongest association with the age-related hearing difficulty phenotype. Youth with a higher genetic predisposition to hearing difficulty revealed a subclinical elevation in HTs and a decline in DPOAEs in both ears. PRS predictors associated with age-related hearing difficulty were enriched for mental health, lifestyle, metabolic, sleep, reproductive, digestive, respiratory, hematopoietic, and immune traits. Fifty PRS predictors belonging to various trait categories were replicated for HTs and DPOAEs in both ears., Conclusion: The study identified genetic comorbidities associated with age-related hearing loss across the health spectrum. Youth with a high genetic predisposition to age-related hearing difficulty and other related complex traits could exhibit sub-clinical decline in HTs and DPOAEs decades before clinically meaningful age-related hearing loss is observed. We posit that effective communication of genetic risk, promoting a healthy lifestyle, and reducing exposure to environmental risk factors at younger ages could help prevent or delay the onset of age-related hearing difficulty at older ages., (© 2024. The Author(s) under exclusive licence to Association for Research in Otolaryngology.)

With the purpose of establishing a consensus around clinical orientations for professionals involved in managing patients with sleep breathing disorders (SBD), an interdisciplinary group of scientific societies involved in this field discussed and reviewed all the published international guidelines from the American Dental Association, American Academy of Sleep Medicine, American Academy of Dental Sleep Medicine and the European counterparts. Treatment of SBD is multidisciplinary and should be made in concert with the patient, the sleep physician, and the qualified dentist to solve the individual, social, and economic burden of the disease,. This consensus document represents the current thinking of a team of Portuguese experts on managing patients with SBD based on the available evidence., Competing Interests: Conflicts of interest Susana Sousa has no interests to declare. Sílvia Correia has no interests to declare. André Mariz de Almeida has no interests to declare. Gabriela Videira has no interests to declare. Ricardo Dias has no interests to declare. Susana Falardo Ramos receives speaker's fees as international speaker at the Orthoapnea Academy. Júlio Fonseca has no interests to declare., (Copyright © 2024 Sociedade Portuguesa de Pneumologia. Published by Elsevier España, S.L.U. All rights reserved.)

The family Sarcophagidae is very diverse in Brazil. Due to their living habits, they are the subject of many medical, veterinary, sanitary, and entomological studies. However, Sarcophagidae species are still poorly studied in forensic entomology, although they are frequently reported in carcasses and even human corpses. Thus, this study aims to identify and compare the developmental stages and intrapuparial morphological characteristics of Peckia (Euboettcheria) collusor to serve as an auxiliary tool in forensic entomology. The pupae collected after zero hour at 27 °C and 32 °C were sacrificed every three hours until the first 24 h and then every six hours until the emergence of the first adults, using 30 pupae each time, totaling 1560 for 27 °C and 1290 for 32 °C. The intrapuparial development time of this fly species under laboratory-controlled conditions was 288 h at 27 °C and 228 h at 32 °C. The 2820 pupae were analyzed according to temperature and classified into eight possible stages. This contributed to the selection of 16 key morphological characteristics to identify the age of the pupae. The identified intrapupal morphological characteristics have great potential to help researchers, experts, technical assistants, and forensic entomologists estimate the minimum post-mortem interval (minPMI) of cadavers., (© 2024. The Author(s).)

Objective: The Ecological Momentary Assessment (EMA) concept was the basis for developing a smartphone application for the real-time report of awake bruxism (AB) activities. The aim of this study was to assess the effects of the EMA with a randomised controlled trial designed to compare the frequency of AB reported in two separate single observation points between a group of students monitored over time with an EMA smartphone application and a non-EMA monitored group., Methods: Sixty-four (N = 64) dental students (22.3 YO [±2.6]; 52F; 12 M) answered the Oral Behaviour Checklist (OBC-1) and were randomised into an EMA-group (EG) and control group (CG). EG were monitored with a smartphone application for AB report during seven consecutive days and completed three EMA monitoring periods (EMA-1, 2 and 3) at one-month intervals. After the third period (EMA-3), both EG and CG answered again the OBC (OBC-2). Descriptive statistics were performed to characterise the sample. Pearson's chi-squared test, Fixer Exact test and post hoc Z test with Bonferroni correction were performed. The study hypothesis was that EMA could influence the AB reported by the participants because it implies an increase in the awareness, self-recognition, and self-control of bruxism behaviours. The level of significance was set at p < .05., Result: The percentage of participants who changed the report of the activity of clenching their teeth while awake between OBC-1 and OBC-2 was significantly higher among participants in EG, when compared to CG (p = .027). For all other behaviours reported the within- and between-group differences from OBC-1 to OBC-2 were not significant. Clenching and bracing were the most frequently reported, whilst grinding was the less frequent behaviour., Conclusion: A smartphone-based EMA approach demonstrated be useful to monitor AB over time, increasing individual's awareness, particularly to bracing and clenching behaviours., (© 2024 The Authors. Journal of Oral Rehabilitation published by John Wiley & Sons Ltd.)

Background: Robotic-assisted radical cystectomy (RARC) with intracorporeal urinary diversion (ICUD) is associated with significant morbidity and mortality. We present an alternative technique that preserves the complete mesenteric vascularization during the isolation of the intestinal segment used in ICUD, including distal vessels. This approach aims to minimize the risk of ischemia in both the ileal anastomosis and the isolated loop at the diversion site., Methods: This cohort study included 31 patients, both male and female, who underwent RARC with ICUD from February 2018 to November 2023, performed by a single surgeon. Intraoperative and postoperative complications data were retrieved for analysis, employing our proposed mesentery-sparing technique in all cases. The primary endpoint was the incidence of intraoperative and postoperative complications directly attributable to the mesentery-sparing approach in ICUD. Secondary endpoints included other postoperative variables not directly related to mesentery preservation, such as the incidence of postoperative ileus requiring parenteral nutrition and the duration of hospitalization., Results: None of the patients experienced intraoperative or postoperative complications directly related to mesentery-sparing, such as intestinal fistulae or internal hernias. The median duration of hospitalization was 6 days, and postoperative ileus necessitating total parenteral nutrition occurred in 19% of the patients. Minor complications (Clavien-Dindo grades I-II) accounted for 27.6% of the cases and major complications (grades III-V) accounted for 20.6%., Conclusion: The mesentery-sparing technique outlined herein offers an alternative method for preserving the vascularization of intestinal segments and reducing the risk of intestinal complications in ICUD during RARC., Competing Interests: None declared., (Copyright® by the International Brazilian Journal of Urology.)

Background: A RCT of a novel intervention to detect antidepressant medication response (the PReDicT Test) took place in five European countries, accompanied by a nested study of its acceptability and implementation presented here. The RCT results indicated no effect of the intervention on depression at 8 weeks (primary outcome), although effects on anxiety at 8 weeks and functioning at 24 weeks were found., Methods: The nested study used mixed methods. The aim was to explore patient experiences of the Test including acceptability and implementation, to inform its use within care. A bespoke survey was completed by trial participants in five countries (n = 778) at week 8. Semi-structured interviews were carried out in two countries soon after week 8 (UK n = 22, Germany n = 20). Quantitative data was analysed descriptively; for qualitative data, thematic analysis was carried out using a framework approach. Results of the two datasets were interrogated together., Outcomes: Survey results showed the intervention was well received, with a majority of participants indicating they would use it again, and it gave them helpful extra information; a small minority indicated the Test made them feel worse. Qualitative data showed the Test had unexpected properties, including: instigating a process of reflection, giving participants feedback on progress and new understanding about their illness, and making participants feel supported and more engaged in treatment., Interpretation: The qualitative and quantitative results are generally consistent. The Test's unexpected properties may explain why the RCT showed little effect, as properties were experienced across both trial arms. Beyond the RCT, the qualitative data sheds light on measurement reactivity, i.e., how measurements of depression can impact patients., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Fungal infections represent a serious health problem worldwide. The study evaluated the antifungal activity of 4-chlorobenzyl p-coumarate, an unprecedented semi-synthetic molecule. Docking molecular and assay experiments were conducted to determine the Minimum Inhibitory Concentration (MIC) and Minimum Fungicidal Concentration (MFC), mode of action, effect on growth, fungal death kinetics, drug association, effects on biofilm, micromorphology, and against human keratinocytes. The investigation included 16 strains of Candida spp, including C. albicans, C. krusei, C. glabrata, C. tropicalis, C. dubliniensis, C. lusitaniae, C. utilis, C. rugosa, C. guilhermondi, and C. parapsilosis. Docking analysis predicted affinity between the molecule and all tested targets. MIC and MFC values ranged from 3.9 μg/mL (13.54 μM) to 62.5 μg/mL (217.01 μM), indicating a probable effect on the plasma membrane. The molecule inhibited growth from the first hour of testing. Association with nystatin proved to be indifferent. All concentrations of the molecule reduced fungal biofilm. The compound altered fungal micromorphology. The tested compound exhibited an IC50 of 7.90±0.40 μg/mL (27.45±1.42 μM) for keratinocytes. 4-chlorobenzyl p-coumarate showed strong fungicidal effects, likely through its action on the plasma membrane and alteration of fungal micromorphology, and mildly cytotoxic to human keratinocytes., (© 2024 Wiley-VHCA AG, Zurich, Switzerland.)

This article explores the impact of thermally treated asbestos-cement waste (ACW T ) on metakaolin-based geopolymers, using liquid sodium silicate (LSS) and liquid potassium silicate (LKS) as alkali activators. Through statistical mixture design, various formulations were tested for rheological parameters, mineralogical composition, efflorescence mass, electrical conductivity, compressive strength, and CO 2 emissions. Formulations with sodium silicate exhibited higher yield stress compared to those with potassium silicate, while flash setting occurred in LKS-activated mixtures with high ACW T content. Alkali activator content significantly affected mechanical strength and leachate electrical conductivity. CO 2 emissions were higher for LKS-activated formulations but lower for those with more ACW T . Finally, by incorporating ACW T , it was possible to optimize the formulations, resulting in high compressive strength, reduced free ions, and reduced negative environmental impact., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: An active search for tuberculosis cases through mass screening is widely described as a tool to improve case detection in hyperendemic settings. However, its effectiveness in high-risk populations, such as incarcerated people, is debated., Methods: Between 2017 and 2021, 3 rounds of mass screening were carried out in 3 Brazilian prisons. Social and health questionnaires, chest X-rays, and Xpert MTB/RIF were performed., Results: More than 80% of the prison population was screened. Overall, 684 cases of pulmonary tuberculosis were diagnosed. Prevalence across screening rounds was not statistically different. Among incarcerated persons with symptoms, the overall prevalence of tuberculosis per 100 000 persons was 8497 (95% confidence interval [CI], 7346-9811), 11 115 (95% CI, 9471-13 082), and 7957 (95% CI, 6380-9882) in screening rounds 1, 2, and 3, respectively. Similar to our overall results, there were no statistical differences between screening rounds and within individual prisons. We found no statistical differences in Computer-Aided Detection for TB version 5 scores across screening rounds among people with tuberculosis-the median scores in rounds 1, 2, and 3 were 82 (interquartile range [IQR], 63-97), 77 (IQR, 60-94), and 81 (IQR, 67-92), respectively., Conclusions: In this environment with hyperendemic rates of tuberculosis, 3 rounds of mass screening did not reduce the overall tuberculosis burden. In prisons, where a substantial number of tuberculosis cases is undiagnosed annually, a range of complementary interventions and more frequent tuberculosis cases screening may be required., Competing Interests: Potential conflicts of interest . The authors: No reported conflicts of interest. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Products derived from medicinal plants with antimicrobial activity are considered a promising alternative in the treatment of fungal infections. In this perspective, this study proposed to evaluate the antifungal activity of the dichloromethane fraction of Annona crassiflora Mart. against C. albicans strains. Tests were carried out to determine Minimum Inhibitory Concentration (MIC), Minimum Fungicide Concentration (MFC), microbial growth kinetics, fungal cell wall and membrane mechanisms of action, antifungal biofilm activity, and cytotoxic effects on human erythrocytes. The extract presented MIC and MFC values that ranged from 256 µg/mL to 1,024 µg/mL, with fungicidal activity in the microbial growth kinetics assay. The mechanism of action did not occur through damage to the cell wall or via binding to ergosterol in the membrane, though the fraction presents activity against biofilm and is not cytotoxic in human erythrocytes. The dichloromethane fraction of Annona crassiflora Mart. presented antifungal activity and reduced biofilm growth, without toxicity against human erythrocytes; however, further studies are needed to define its mechanism of action.

Speech-in-noise (SIN) perception is a primary complaint of individuals with audiometric hearing loss. SIN performance varies drastically, even among individuals with normal hearing. The present genome-wide association study (GWAS) investigated the genetic basis of SIN deficits in individuals with self-reported normal hearing in quiet situations. GWAS was performed on 279,911 individuals from the UB Biobank cohort, with 58,847 reporting SIN deficits despite reporting normal hearing in quiet. GWAS identified 996 single nucleotide polymorphisms (SNPs), achieving significance (p < 5*10 -8 ) across four genomic loci. 720 SNPs across 21 loci achieved suggestive significance (p < 10 -6 ). GWAS signals were enriched in brain tissues, such as the anterior cingulate cortex, dorsolateral prefrontal cortex, entorhinal cortex, frontal cortex, hippocampus, and inferior temporal cortex. Cochlear cell types revealed no significant association with SIN deficits. SIN deficits were associated with various health traits, including neuropsychiatric, sensory, cognitive, metabolic, cardiovascular, and inflammatory conditions. A replication analysis was conducted on 242 healthy young adults. Self-reported speech perception, hearing thresholds (0.25-16 kHz), and distortion product otoacoustic emissions (1-16 kHz) were utilized for the replication analysis. 73 SNPs were replicated with a self-reported speech perception measure. 211 SNPs were replicated with at least one and 66 with at least two audiological measures. 12 SNPs near or within MAPT, GRM3, and HLA-DQA1 were replicated for all audiological measures. The present study highlighted a polygenic architecture underlying SIN deficits in individuals with self-reported normal hearing., (© 2024. The Author(s).)

Data from the UK suggests 13-55 % of depression patients experience some level of treatment resistance. However, little is known about how physicians manage inadequate response to antidepressants in primary care. This study aimed to explore the incidence of inadequate response to antidepressants in UK primary care. One-hundred-eighty-four medication-free patients with low mood initiated antidepressant treatment and monitored severity of depression symptoms, using the QIDS-SR16, for 48 weeks. Medication changes, visits to healthcare providers, and health-related quality of life were also recorded. Patients were classified into one of four response types based on their QIDS scores at three study timepoints: persistent inadequate responders (<50 % reduction in baseline QIDS at all timepoints), successful responders (≥50 % reduction in baseline QIDS at all timepoints), slow responders (≥50 % reduction in QIDS at week 48, despite earlier inadequate responses), and relapse (initial ≥50 % reduction in baseline QIDS, but inadequate response by week 48). Forty-eight weeks after initiating treatment 47 % of patients continued to experience symptoms of depression (QIDS >5), and 20 % of patients had a persistent inadequate response. Regardless of treatment response, 96 % (n = 176) of patients did not visit their primary care physician over the 40-week follow-up period. These results suggest that despite receiving treatment, a considerable proportion of patients with low mood remain unwell and fail to recover. Monitoring depression symptoms remotely can enable physicians to identify inadequate responders, allowing patients to be reassessed or referred to secondary services, likely improving patients' quality of life and reducing the socioeconomic impacts of chronic mental illness., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: GRD and JK own shares in the study sponsor (P1vital Products Ltd) which also owns the PReDicT predictive algorithm. ACB, RD, and JK are employees of P1vital Products Ltd. GRD owns shares in P1vital Ltd. ABA and GRD are employees of P1vital Ltd. HGR reports speakers’ bureau honoraria from Janssen, Lundbeck, and received research grants from ZonMW, HersenStichting, EU Horizon 2020, the Dutch Ministry of Health, and an unrestricted Educational grant from Janssen. AR has received honoraria for lectures and/or advisory boards from Janssen, Boehringer Ingelheim, COMPASS, SAGE/Biogen, LivaNova, Medice, Shire/Takeda and cyclerion. Also, he has received research grants from Medice and Janssen. GMG is Chief Medical Officer at Compass pathways, holds shares and options in Compass pathways and has served as consultant, advisor or CME speaker in the last 3 years for Beckley Psytech, Boehringer Ingelheim, Clerkenwell Health, Compass pathways, Evapharma, Janssen, Lundbeck, Medscape, Novartis, Ocean Neuroscience, P1Vital Ltd., Sage, Servier and Takeda. MB has acted as a consultant for Janssen Research, P1vital Ltd, Boehringer and CHDR, and was previously a paid employee of P1vital Ltd. RM has received payment from Novartis plc but have no other conflicts of interest to report. All other authors declare that they have no conflicts of interest. JS has received research grants from the ECNP, EU Horizon 2020, EU Horizon Europe, FWF, NIHR, WWTF, and academic advisor honoraria from the European Brain Council, (Copyright © 2024 Elsevier B.V. and ECNP. All rights reserved.)

Geopropolis resins are produced by stingless bees (Meliponinae), developed from the collection of resinous materials, waxes and exudates, from the flora of the region where stingless bees are present, in addition to the addition of clay or earth in its composition. Several biological activities are attributed to Ethanol Extracts of Geopropolis (EEGP). The bioactive properties are associated with the complex chemical composition that the samples have. This work aims to evaluate the biological activities of the EEGP, in order to contribute with a natural therapeutic alternative, to face infections, mainly those caused by resistant strains of Staphylococcus aureus. The EEGP MIC tests showed antibacterial activity against two strains of S. aureus, both at concentrations of 550 μg/mL. The MBC performed with the inhibition values showed that the EEGP has bacteriostatic activity in both strains. Biofilm inhibition rates exhibited an average value greater than 65 % at the highest concentration. The EEGP antioxidant potential test showed good antioxidant activity (IC50) of 11.05±1.55 μg/mL. In the cytotoxicity test against HaCat cells, after 24 hours, EEGP induced cell viability at the three tested concentrations (550 μg/mL: 81.68±3.79 %; 1100 μg/mL: 67.10±3.76 %; 2200 μg/mL: 67.40±1.86 %). In view of the above, the safe use of EEGP from the brazilian northeast could be proven by the cytotoxicity test, and its use as an antioxidant and antibacterial agent has proven to be effective, as an alternative in combating oxidative stress and microorganisms such as S. aureus, which, through the spread and ongoing evolution of drug resistance, generates an active search for effective solutions., (© 2024 Wiley-VHCA AG, Zurich, Switzerland.)

Among all living beings, mosquitoes account for the highest number of human fatalities. Our study aimed to determine mosquito egg abundance fluctuation from 2015 to 2020, in order to observe which years had the highest mosquito vector densities and whether they coincided with yellow fever virus outbreaks in both human and nonhuman primates. The study area included Atlantic Forest fragments in the state of Rio de Janeiro. Studies from the Diptera Laboratory at FIOCRUZ were selected and compared along a timeline period of the field collections. The highest peak in egg abundance from the analyzed studies was observed from 2016 to 2017 and from 2015 to 2016. The lowest egg abundance was during the collection periods from 2018 to 2019 and 2019 to 2020. The species with the highest abundance throughout all the periods of the studies analyzed was Haemagogus leucocelaenus, representing 87% of all epidemiological species identified. The species with the lowest abundance was Hg. Janthinomys, representing only 1%. Monitoring the population of mosquitoes is imperative for disease surveillance, as the rise in specimens of various vector species directly impacts the occurrence of yellow fever cases in both nonhuman primates and human populations., (Copyright © 2024 by The American Mosquito Control Association, Inc.)

Diverse larval habitats significantly influence female mosquito oviposition. Utilizing traps that simulate these habitats is helpful in the study of the bioecology and characteristics of pathogen-transmitting species during oviposition. This study evaluated the feasibility of different traps in natural environments by comparing sampling methods and detecting the oviposition of epidemiologically important mosquitoes, with emphasis on Haemagogus species, in a fragment of the Atlantic Forest in Silva Jardim, Rio de Janeiro State, Brazil. Monthly collections were conducted from March 2021 to October 2023 using four types of traps: plastic containers, tires, bamboo, and sapucaia. Immatures were collected from these traps using a pipette, placed in plastic bags, and transported to the laboratory. Tire was the most efficient trap, showing the highest mosquito abundance (n = 1239) and number of species (S = 11). Conversely, the plastic container trap exhibited the lowest diversity (H = 0.43), with only two species and a low mosquito abundance (n = 26). The bamboo trap captured six species and recorded the second-highest diversity index (H = 1.04), while the sapucaia trap captured five species and had the third-highest diversity index (H = 0.91). Of the total immatures collected, 1817 reached adulthood, comprising 13 species, two of which are vectors of the sylvatic yellow fever virus: Haemagogus leucocelaenus and Haemagogus janthinomys . In conclusion, detecting key vectors of the sylvatic yellow fever virus in Brazil highlights the need for ongoing entomological and epidemiological surveillance in the study area and its vicinity. These efforts are crucial for monitoring vector presence and activity, identifying potential transmission hotspots, and devising effective control and prevention strategies.

Parasiticide fungi are considered an accurate, sustainable, and safe solution for the biocontrol of animal gastrointestinal (GI) parasites. This research provides an initial characterization of the virulence of the native parasiticide fungus Mucor circinelloides (FMV-FR1) and an assessment of its impact on birds' gut microbes. The genome of this fungus was sequenced to identify the genes coding for virulence factors. Also, this fungus was checked for the phenotypic expression of proteinase, lecithinase, DNase, gelatinase, hemolysin, and biofilm production. Finally, an in vivo trial was developed based on feeding M. circinelloides spores to laying hens and peacocks three times a week. Bird feces were collected for 3 months, with total genomic DNA being extracted and subjected to long-read 16S and 25S-28S sequencing. Genes coding for an iron permease (FTR1), iron receptors (FOB1 and FOB2), ADP-ribosylation factors (ARFs) (ARF2 and ARF6), and a GTPase (CDC42) were identified in this M. circinelloides genome. Also, this fungus was positive only for lecithinase activity. The field trial revealed a fecal microbiome dominated by Firmicutes and Proteobacteria in laying hens, and Firmicutes and Bacteroidetes in peacocks, whereas the fecal mycobiome of both bird species was mainly composed of Ascomycetes and Basidiomycetes fungi. Bacterial and fungal alpha-diversities did not differ between sampling time points after M. circinelloides administrations ( P = 0.62 and P = 0.15, respectively). Although findings from this research suggest the lack of virulence of this M. circinelloides parasiticide isolate, more complementary in vitro and in vivo research is needed to conclude about the safety of its administration to birds, aiming at controlling their GI parasites.IMPORTANCEA previous study revealed that the native Mucor circinelloides isolate (FMV-FR1) can develop parasiticide activity toward coccidia oocysts, one of the most pathogenic GI parasites in birds. However, ensuring its safety for birds is of utmost importance, namely by studying its virulence profile and potential effect on commensal gut microbes. This initial study revealed that although this M. circinelloides isolate had genes coding for four types of virulence factors-iron permease, iron receptors, ADP-ribosylation factors, and GTPase-and only expressed phenotypically the enzyme lecithinase, the administration of its spores to laying hens and peacocks did not interfere with the abundances and diversities of their gut commensal bacteria and fungi. Although overall results suggest the lack of virulence of this M. circinelloides isolate, more complementary research is needed to conclude about the safety of its administration to birds in the scope of parasite biocontrol programs., Competing Interests: The authors declare no conflict of interest.

A large public nursing data set was used to determine whether orientation and/or preceptor programs impact job satisfaction among registered nurses in Maine and Massachusetts. There was no association between orientation and preceptor programs and satisfaction, nor evidence that new nurse status modified the relationship. There is a need for evaluation of orientation and preceptor programs' structure and effectiveness, and innovation is needed in promoting job satisfaction, thereby increasing nurse retention., (Copyright © 2024 The Authors. Published by Wolters Kluwer Health, Inc.)

The kinetics, thermodynamics, and degradation of malvidin mono- and diglucosides were studied following a holistic approach by extending to the basic medium. In acidic conditions, the reversible kinetics of the flavylium cation toward the equilibrium is controlled by the hydration and cis - trans isomerization steps, while in the basic medium, the OH - nucleophilic addition to the anionic quinoidal bases is the slowest step. There is a pH range (transition pHs), between the acidic and basic paradigms, that includes physiological pH (7.4), where degradation reactions occur faster, preventing the system from reaching the equilibrium. The transition pH of the diglucoside is narrower, and in contrast with the monoglucoside, there is no evidence for the formation of colored oligomers among the degradation products. Noteworthy, OH - addition in position 4 to form B4 2- , a kinetic product that decreases the overall equilibration rate, was observed only for the diglucoside.

Objective: To assess and compare the validity of 2D modified Easy Box and measurement of the Beta angle on standard conventional orthopantomogram (OPG) versus 3D cone-beam computed tomography (CBCT) OPG-constructed view., Design: A retrospective agreement study., Methods: The aim of this study was to construct an Easy Box on a standard conventional OPG and to validate this novel method by comparing it with the Easy Box method on 3D CBCT. After approval from the Ethics Committee, OPG and CBCT radiographs were obtained for the study from departmental records and five private practices in the same location (Indore, India). The radiographs were selected based on record availability and with written consent from the participants before the commencement of the study. The records were analysed to enable a comparison and to assess the accuracy of Easy Box construction on both 3D CBCT and standard conventional OPG radiographs. The location of the impacted canine within the Easy Box boundaries and the measurement of the Beta angle were determined on both views., Results: A perfect agreement was obtained for the comparison of 3D Easy Box CBCT analysis with 2D modified Easy Box on OPG for impacted maxillary canines (Kappa = 1.0). A Bland-Altman (LoA) analysis showed no proportional bias in the comparison of the Beta angle on 3D and 2D OPG radiographs., Conclusion: Beta angle and 2D modified Easy Box on a conventional OPG yield similar results when compared to Easy Box on 3D CBCT OPG-constructed view. The standard OPG was valuable and cost-effective, particularly in the early stages of diagnosis and treatment planning, either as a substitute or when CBCT was unavailable., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background and Objectives: With continued advances in treatment options, patients with endoprosthetic reconstruction are living longer and consequently relying upon their devices for a longer duration. Major causes of endoprosthesis failure include aseptic loosening and mechanical failure. In the setting of tumor resection, loss of bone stock and use of radiation therapy increase the risk for these complications. As such, considerations of remaining native bone and stem length and diameter may be increasingly important. We asked the following questions: (1) What was the overall rate of endoprosthesis failure at a minimum of 5-year follow-up? (2) Does resection length increase implant failure rates? (3) Does implant size and its ratio to cortical width of bone alter implant failure rates?, Methods: We retrospectively analyzed patient outcomes at a single institution between the years of 1999-2022 who underwent cemented endoprosthetic reconstruction at the hip or knee and identified 150 patients. Of these 150, 55 had a follow-up of greater than 5 years and were used for analysis. Radiographs of these patients at time of surgery were assessed and measured for resection length, bone diameter, stem diameter, and remaining bone length. Resection percentage, and stem to bone diameter ratios were then calculated and their relationship to endoprosthesis failure were analyzed., Results: Patients in this cohort had a mean age of 55.8, and mean follow-up of 59.96 months. There were 78 distal femoral replacements (52%), 16 proximal femoral replacements (10.7%), and 56 proximal tibial replacements (37.3%). There were five patients who experienced aseptic loosening and six patients who experienced mechanical failure. Patients with implant failure had a smaller mean stem to bone diameter (36% vs. 44%; p = 0.002). A stem to bone diameter of 40% appeared to be a breaking point between success and failure in this series, with 90% of patients with implant failure having a stem: bone ratio less than 40%. Stem to bone ratio less than 40% increased risk for failure versus stems that were at least 40% the diameter of bone (6/19 [31.6%] vs. 0/36 [0%]; odds ratio 0.68; p < 0.001). Resection length did not appear to have an impact on the rates of aseptic loosening and mechanical failure in this series., Conclusions: Data from this series suggests a benefit to using stems with a larger diameter when implanting cemented endoprostheses at the hip or knee. Stems which were less than 40% the diameter of bone were substantially more likely to undergo implant failure., (© 2024 Wiley Periodicals LLC.)

Policing is a highly demanding and stressful profession. Virtual reality (VR) has emerged as a promising tool for enhancing stress management programs, including for police officers. The use of VR in combination with biosensors enables measurement of psychophysiological responses such as peripheral temperature (PT) and skin conductance level (SCL). This study investigated the psychophysiological responses of police officers exposed to a VR scenario simulating a car accident. The study included a total of 63 police officers from the Public Security Police. Participants were divided into three groups based on their police divisions: the Investigation Brigade of Traffic Accidents, the Traffic Surveillance Squad (TSS), and a control group from the Lisbon Metropolitan Command. The results indicated that the VR environment effectively induced psychophysiological arousal, particularly in less experienced officers (TSS), that is, there were significant group differences in mean SCL and PT, showing this group with higher SCL and lower PT during the VR exposure. These results support the potential of VR as a stress inoculation strategy for training police officers and highlight the complex nature of stress responses that are influenced by individual factors and psychopathology.

Although tropical forests are home to most of the global diversity, they suffer from the most significant knowledge gaps concerning their fauna. Despite its high biodiversity, Brazil is facing an alarming destruction of habitats, with species becoming extinct before they can be discovered or described via science. Therefore, there is an urgent need to expand wildlife inventories, including entomofauna surveys. The present study aimed to analyze the bionomic aspects and the influence of abiotic factors on mosquito fauna whose immature phases develop in two bamboo species, Guadua tagoara and Bambusa vulgaris , in Tijuca National Park, Rio de Janeiro, Brazil. Immatures were collected in 10 artificially drilled bamboo plants, in five stalk internodes per plant, at two sampling points, from March 2022 to March 2023, during 23 collections. A total of 1845 immatures were obtained, 72.14% at sampling point 1 and 27.86% at sampling point 2. Of this, 1162 individuals reached adulthood, belonging to the following species: Culex iridescens , Culex neglectus , Haemagogus leucocelaenus , Orthopodomyia albicosta , Sabethes identicus , Sabethes melanonymphe , Sabethes purpureus , Toxorhynchites bambusicola , Toxorhynchites sp., Trichoprosopon compressum , Trichoprosopon pallidiventer , Wyeomyia arthrostigma , Wyeomyia codiocampa , Wyeomyia lutzi , Wyeomyia oblita , Wyeomyia personata , Wyeomyia serrata , and Wyeomyia sp. The Tijuca National Park is a tourist spot and receives a large number of visitors. Thus, humans can become an accessible food source for mosquitoes in this area, making the species survey critical since important arbovirus vectors have been recorded in Rio de Janeiro.

Statement of the Problem: Periodontitis is an inflammatory disease that causes bone loss. Some patients do not respond well to the classic treatment and need therapies that minimize bone loss, the main sequel of the disease. Chenopodium ambrosioides L. has stood out due to its anti-inflammatory and anti-oxidative activities. However, no study has yet investigated its effect on periodontitis., Purpose: This study aimed to evaluate the bone protective effect of Chenopodium ambrosioides L. (CAL) extract on ligature-induced periodontitis model in rats., Materials and Method: For this, a pre-clinical assay was performed, using male Wistar rats divided into 3 groups: Naive (N) (n=6), not submitted to any procedure; Saline (SAL) (n=6), submitted to ligature-induced periodontitis and receiving 2 ml/kg of 0.9% saline solution; and CAL extract, which was subdivided into 3 subgroups (n=6/subgroup) receiving the CAL at 3 (CAL3), 10 (CAL10) or 30 mg/kg (CAL30). All agents were given, by oral gavage, 30 min before periodontitis induction and daily until euthanasia (11 th day). By then, maxillae were removed for macroscopic, histological, and histometric analyses. Kidneys, liver, and stomach were collected to evaluate the safety of CAL extract. High-performance liquid chromatography (HPLC) assay was used to investigate the flavonoid content in the extract., Results: Chenopodium ambrosioides L. extract at 30mg/kg showed a reduction by 58% in bone loss marked by an increase (+35%) in the number of osteoblasts and a reduction (-51%) on the number of osteoclasts ( p < 0.05). No significant alteration in the liver, kidney, or stomach was seen. Rutin was the main flavonoid found., Conclusion: In summary, it was observed that Chenopodium ambrosioides L. extract has shown important anti-inflammatory and bone anabolic and anti-resorptive properties without causing toxicity in the main organs. Rutin, as the main flavonoid of the extract, seems to be responsible for the beneficial effect of this agent., Competing Interests: Authors declare that there are no conflicts of interest in this study., (Copyright: © Journal of Dentistry.)

Space travel has transformed in the past several years. Given the burgeoning market for space tourism, in-flight medical emergencies are likely to be expected. Ultrasound is one of the few diagnostic and therapeutic modalities available for astronauts in space. However, while point-of-care ultrasound (POCUS) is available, there is no current standard of training for astronaut preparation. We suggest an organized and structured methodology by which astronauts should best prepare for space with the medical equipment available on board. As technology continues to evolve, the assistance of other artificial intelligence and augmented reality systems are likely to facilitate training and dynamic real-time needs during space emergencies. Summary: As space tourism continues to evolve, an organized methodology for POCUS use is advised to best prepare astronauts for space., Competing Interests: Conflicts of Interest: By the WestJEM article submission agreement, all authors are required to disclose all affiliations, funding sources and financial or management relationships that could be perceived as potential sources of bias. Drs. Emily Frisch, Andrew Goldsmith, and Nicole Duggan all have received consulting or advising fees from Centaur Labs. Dr. Chanel Fischetti was formerly employed by Centaur Labs and owns equity in the company. She also is a consultant for Philips Ultrasound and LevelEx. Select authors (Drs. Dias, Savage, Loesche and Mormann) have received funding from, are currently employed by, or receive related funding/grant support from NASA or SpaceX.

Food allergies are becoming ever more prevalent around the world. This pathology is characterized by the breakdown of oral tolerance to ingested food allergens, resulting in allergic reactions in subsequent exposures. Due to the possible severity of the symptoms associated with this pathology, new approaches to prevent it and reduce associated symptoms are of utmost importance. In this framework, dietary phenolic compounds appear as a tool with a not fully explored potential. Some phenolic compounds have been pointed to with the ability to modulate food allergies and possibly reduce their symptoms. These compounds can modulate food allergies through many different mechanisms, such as altering the bioaccessibility and bioavailability of potentially immunogenic peptides, by modulating the human immune system and by modulating the composition of the human microbiome that resides in the oral cavity and the gastrointestinal tract. This review deepens the state-of-the-art of the modulation of these mechanisms by phenolic compounds. While this review shows clear evidence that dietary supplementation with foods rich in phenolic compounds might constitute a new approach to the management of food allergies, it also highlights the need for further research to delve into the mechanisms of action of these compounds and decipher systematic structure/activity relationships.

Since the Orthoflavivirus zikaense (ZIKV) has been considered a risk for Zika congenital syndrome development, developing a safe and effective vaccine has become a high priority. Numerous research groups have developed strategies to prevent ZIKV infection and have identified the domain III of the ZIKV envelope protein (zEDIII) as a promising target. Subunit antigens are often poorly immunogenic, necessitating the use of adjuvants and/or delivery systems to induce optimal immune responses. The subject of nanotechnology has substantial expansion in recent years in terms of research and applications. Nanoparticles could be used as drug delivery systems and to increase the immunogenicity and stability of a given antigen. This work aims to characterize and validate the potential of a vaccine formulation composed of domain zEDIII and bovine serum albumin nanoparticles containing polyinosinic-polycytidylic acid (NPPI). NPPI were uptake in vitro by immature bone marrow dendritic cells and histological analysis of the skin of mice treated with NPPI showed an increase in cellularity. Immunization assay showed that mice immunized with zEDIII in the presence of NPPI produced neutralizing antibodies. Through the passive transfer of sera from immunized mice to ZIKV-infected neonatal mice, it was demonstrated that these antibodies provide protection, mitigating weight loss, clinical or neurological signs induced by infection, and significantly increased survival rates. Protection was further substantiated by the reduction in the number of viable infectious ZIKV, as well as a decrease in inflammatory cytokines and tissue alterations in the brains of infected mice. Taken together, data presented in this study shows that NPPI + zEDIII is a promising vaccine candidate for ZIKV., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Pigmented wheat varieties (Triticum aestivum spp.) are getting increasingly popular in modern nutrition and thoroughly researched for their functional and nutraceutical value. The colour of these wheat grains is caused by the expression of natural pigments, including carotenoids and anthocyanins, that can be restricted to either the endosperm, pericarp and/or aleurone layers. While contrasts in phytochemical synthesis give rise to variations among purple, blue, dark and yellow grain's antioxidant and radical scavenging capacities, little is known about their influence on gluten proteins expression, digestibility and immunogenic potential in a Celiac Disease (CD) framework. Herein, it has been found that the expression profile and immunogenic properties of gliadin proteins in pigmented wheat grains might be affected by anthocyanins and carotenoids upregulation, and that the spectra of peptide released upon simulated gastrointestinal digestion is also significantly different. Interestingly, anthocyanin accumulation, as opposed to carotenoids, correlated with a lower immunogenicity and toxicity of gliadins at both protein and peptide levels. Altogether, this study provides first-level evidence on the impact modern breeding practices, seeking higher expression levels of health promoting phytochemicals at the grain level, may have on wheat crops functionality and CD tolerability., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

There is a relationship between acute bouts of aerobic exercise and cognition in adults, yet the exact nature of this relationship remains unclear. The current pilot study aims to investigate how different modes of cycling (active-assisted cycling vs recumbent cycling) at different moderate-to-vigorous physical activity (MVPA) intensity levels (prescribed 65-70% Heart Rate Max and self-selected 12-13 Rate of Perceived Exertion) modulate neurocognitive, and behavioral markers of cognition in healthy older adults. A sample of 10 adults (aged 50-74years) participated in baseline (no exercise), active-assisted, and recumbent cycling interventions at different intensity levels. The P3 event-related potential (ERP), a neural index of executive functions, was recorded at baseline and following each exercise condition during an auditory odd-ball paradigm. Results revealed that greater amplitudes within the P3 ERP component were associated with post-exercise recumbent bike cycling compared to baseline and active-assisted cycling. Further, post-exercise behavioral cognitive measures (i.e., button press accuracy) were significantly greater than baseline for both active-assisted and recumbent bikes at both intensity levels. These findings suggest that exercise modulated both neurocognitive and behavioral measures of executive functions in older healthy adults, and that exercise modalities and intensity levels differentially modulate neurocognitive measures., (Copyright © 2024 Elsevier B.V. All rights are reserved, including those for text and data mining, AI training, and similar technologies.)

Competing Interests: There are no conflicts of interest.

Competing Interests: There are no conflicts of interest.

Competing Interests: There are no conflicts of interest.

Background: Maine (ME) and Massachusetts (MA) nursing programs aim to develop collaborative training programs, but need to identify which nurses have interest in such programs., Purpose: We sought to determine sociodemographics of nurses seeking advanced nursing degrees nationally, and in ME and MA using the 2018 publicly available, National Sample Survey of Registered Nurses (NSSRN)., Methods: Weighted multivariable logistic regression for advanced degree-seeking, adjusted for sociodemographics., Results: Of the n = 47,274 nurses (weighted n [Wn] = 3,608,633), 90.7 % were female, 74.1 % were white, and 15.8 % sought an advanced nursing degree on average 12.7 (SD 0.2) years after their first. Females vs. males had lower odds (OR 0.63, 95%CI [0.44-0.90]) and Black vs. White race had higher odds (OR 1.30, 95%CI [1.05-1.60]) of seeking doctorates. In Maine (Wn = 20,389), age 24-29 had higher odds (OR 2.98 (95%CI [1.06-3.74]), but in Massachusetts (Wn = 101,984), age 30+ had lower odds (OR 0.32, 95%CI [0.13-0.78]) of degree-seeking vs. <24 years. Initial nursing degrees earned between 1980 and 1989 had higher odds (OR 1.99, 95%CI [1.06-3.74]) in Maine, but between 2010 and 2014 had lower odds (OR 0.32, 95%CI [0.14-0.72]) in Massachusetts of degree-seeking, vs. before 1980., Conclusions: Targets for advanced nursing training programs may vary by state and sociodemographic profile., Competing Interests: Declaration of competing interest The authors declare no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

This study investigates the antifungal and cytotoxic properties of 7-(pentyloxy)-2H-chromen-2-one. Through molecular docking and dynamics simulations, we explored the compound's interactions with fungal cell protein targets. Notably, it exhibited strong affinities for 1,3β-glucan synthase, squalene epoxidase, δ-14-sterol reductase, 14-α-demethylase, and thymidylate synthase, with binding energies ranging from -100.39 to -73.15 kcal/mol. Molecular dynamics simulations confirmed its stable binding at active targets. The MIC and MFC values ranged from 67.16 μM (15.6 μg/mL) to 537.28 μM (125.0 μg/mL). The compound displayed promising antifungal effects, inhibiting fungal growth for at least 24 hours. Fungal plasma membrane function alteration likely contributed to these antifungal mechanisms. Additionally, the combination of the compound with nystatin, fluconazole, and caspofungin showed indifferent effects on antifungal activity. Cytotoxicity assessment in human keratinocyte cells (HaCaT) revealed an IC50 of 100 μM, which was approximately 1.5 times higher than the MIC for C. krusei. Thus, the compound exhibited strongly in silico and in vitro antifungal activity with low cytotoxicity in HaCaT cells. These findings support its potential as a candidate for further development as an antifungal compound., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 British Mycological Society. Published by Elsevier Ltd. All rights reserved.)

Evidence suggests that nursing students in a prelicensure nursing program lack the required preparation to care for patients at the end of life (EOL), causing feelings of inadequacy and stress. New graduate nurses (years 0-5) struggle to address the needs of this patient population, leading to considering career changes. Nursing simulation has been shown to enhance competency and is gaining increasing favor in prelicensure nursing education. Little research has been conducted on the application of simulation using standardized patients in EOL patient scenarios. This study used live standardized patients who simulated a home health patient encounter with the nursing student acting as a home health hospice nurse. Watson's theory of caring and interpretive phenomenological analysis guided the qualitative research method and analysis. Five students chose to participate in this simulation and completed 6 reflective questions. After simulation, they felt more comfortable having difficult discussions about EOL care, treatment options, and patient fears. Participants noted the importance of communication in a team setting, which included the caregiver as an integral member. The use of standardized patient-simulated experiences increases realism and provides students the opportunity to bridge the gap between didactic education and clinical practice. This will enhance their readiness and confidence in providing EOL care., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2023 by The Hospice and Palliative Nurses Association. All rights reserved.)

Introduction: Language barriers can pose a significant hurdle to successfully educating children and young people with type 1 diabetes (CYPD) and their families, potentially influencing their glycaemic control., Methods: Retrospective case-control study assessing HbA1c values at 0, 3, 6, 9, 12 and 18 months post-diagnosis in 41 CYPD requiring interpreter support (INT) and 100 age-, sex- and mode-of-therapy-matched CYPD not requiring interpreter support (CTR) in our multi-diverse tertiary diabetes centre. Data were captured between 2009-2016. English indices of deprivation for each cohort are reported based on the UK 2015 census data., Results: The main languages spoken were Somali (27%), Urdu (19.5%), Romanian (17%) and Arabic (12%), but also Polish, Hindi, Tigrinya, Portuguese, Bengali and sign language. Overall deprivation was worse in the INT group according to the Index of Multiple Deprivation (IMD [median]: INT 1.642; CTR 3.741; p=0.001). The median HbA1c was higher at diagnosis in the CTR group (9.95% [85.2 mmol/mol] versus 9.0% [74.9 mmol/mol], p=0.046) but was higher in the INT group subsequently: the median HbA1c at 18 months post diagnosis was 8.3% (67.2 mmol/mol; INT) versus 7.9% (62.8 mmol/mol; CTR) (p=0.014). There was no hospitalisation secondary to diabetes-related complications in either cohorts., Summary and Conclusions: Glycaemic control is worse in CYPD with language barriers. These subset of patients also come from the most deprived areas which adds to the disadvantage. Health care providers should offer tailored support for CYP/families with language barriers, including provision of diabetes-specific training for interpreters, and explore additional factors contributing to poor glycaemic control. The findings of this study suggest that poor health outcomes in CYPD with language barriers is multifactorial and warrants a multi-dimensional management approach., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Idkowiak, Uday, Elhag, Barrett, Dias, Kershaw, Mohamed, Saraff and Krone.)

It has been increasingly demonstrated over the past few years that some proteolytically resistant gluten peptides may directly affect intestinal cell structure and functions by modulating pro-inflammatory gene expression and oxidative stress. The relationship between oxidative cell damage and Celiac Disease (CD) is supported by several studies on human intestinal epithelial cell lines, such as the Caco-2 cell model, already shown to be particularly sensitive to the pro-oxidative and pro-apoptotic properties of gluten protein digests. Through providing valuable evidence concerning some of the pathophysiological mechanisms that may be at play in gluten-related disorders, most of these in vitro studies have been employing simplified digestion schemes and intestinal cell systems that do not fully resemble mature enterocytes in terms of their characteristic tight junctions, microvilli and membrane transporters. Herein the peptide profile and pro-oxidative effect of two different gastrointestinal gliadin digestions was thoroughly characterized and comprehensively compared: one following the complete INFOGEST workflow and a second one by-passing gastric processing, to assess the dependence of gliadin-triggered downstream cell effects on pepsin activity. In both matrices, gluten-derived immunogenic peptide sequences were identified by non-targeted LC-MS/MS. Altogether, this study provides first-hand data concerning the still unexplored peptide composition, gastric-dependence and immunogenicity of physiologically representative gliadin protein digests as well as foundational clues stressing the need for more complex and integrated in vitro cell systems when modelling and exploiting gluten-induced perturbations in the nucleophilic tone and inflammatory status of intestinal epithelial cells., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Purpose: Speech-in-noise (SIN) traits exhibit high inter-subject variability, even for healthy young adults reporting normal hearing. Emerging evidence suggests that genetic variability could influence inter-subject variability in SIN traits. Genome-wide association studies (GWAS) have uncovered the polygenic architecture of various adult-onset complex human conditions. Polygenic risk scores (PRS) summarize complex genetic susceptibility to quantify the degree of genetic risk for health conditions. The present study conducted PRS-based association analyses to identify PRS risk factors for SIN and hearing threshold measures in 255 healthy young adults (18-40 years) with self-reported normal hearing., Methods: Self-reported SIN perception abilities were assessed by the Speech, Spatial, and Qualities of Hearing Scale (SSQ12). QuickSIN and audiometry (0.25-16 kHz) were performed on 218 participants. Saliva-derived DNA was used for low-pass whole genome sequencing, and 2620 PRS variables for various traits were calculated using the models derived from the polygenic risk score (PGS) catalog. The regression analysis was conducted to identify predictors for SSQ12, QuickSIN, and better ear puretone averages at conventional (PTA 0.5-2 ), high (PTA 4-8 ), and extended-high (PTA 12.5-16 ) frequency ranges., Results: Participants with a higher genetic predisposition to HDL cholesterol reported better SSQ12. Participants with high PRS to dementia revealed significantly elevated PTA 4-8 , and those with high PRS to atrial fibrillation and flutter revealed significantly elevated PTA 12.5-16 ., Conclusion: These results indicate that healthy individuals with polygenic risk of certain health conditions could exhibit a subclinical decline in hearing health measures at young ages, decades before clinically meaningful SIN deficits and hearing loss could be observed. PRS could be used to identify high-risk individuals to prevent hearing health conditions by promoting a healthy lifestyle., (© 2023. The Author(s) under exclusive licence to Association for Research in Otolaryngology.)

Over the last decades, significant strides were made in understanding the biochemical factors influencing the nutritional content and flavor profile of fruits and vegetables. Product differentiation in the produce aisle is the natural consequence of increasing consumer power in the food industry. Cotton-candy grapes, specialty tomatoes, and pineapple-flavored white strawberries provide a few examples. Given the increased demand for flavorful varieties, and pressing need to reduce micronutrient malnutrition, we expect breeding to increase its prioritization toward these traits. Reaching this goal will, in part, necessitate knowledge of the genetic architecture controlling these traits, as well as the development of breeding methods that maximize their genetic gain. Can artificial intelligence (AI) help predict flavor preferences, and can such insights be leveraged by breeding programs? In this Perspective, we outline both the opportunities and challenges for the development of more flavorful and nutritious crops, and how AI can support these breeding initiatives., Competing Interests: Declaration of Competing Interest The authors declare no competing interests., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Faecal Microbiota Transplantation (FMT) is a promising strategy for modulating the gut microbiome. We aimed to assess the effect of the oral administration of capsules containing lyophilised faeces on dogs with diarrhoea for 2 months as well as evaluate their long-term influence on animals' faecal consistency and intestinal microbiome. This pilot study included five dogs: two used as controls and three with diarrhoea. Animals were evaluated for four months by performing a monthly faecal samples collection and physical examination, which included faecal consistency determination using the Bristol scale. The total number of viable bacteria present in the capsules was quantified and their bacterial composition was determined by 16S rRNA gene sequencing, which was also applied to the faecal samples. During the assay, no side effects were reported. Animals' faecal consistency improved and, after ending capsules administration, Bristol scale values remained stable in two of the three animals. The animals' microbiome gradually changed toward a composition associated with a balanced microbiota. After FMT, a slight shift was observed in its composition, but the capsules' influence remained evident during the 4-month period. Capsules administration seems to have a positive effect on the microbiota modulation; however, studies with more animals should be performed to confirm our observations.

Acacia longifolia is one of the most aggressive invaders worldwide whose invasion is potentiated after a fire, a common perturbation in Mediterranean climates. As a legume, this species establishes symbioses with nitrogen-fixing bacteria inside root nodules; however, the overall microbial diversity is still unclear. In this study, we addressed root nodules' structure and biodiversity through histology and Next-Generation Sequencing, targeting 16S and 25S-28S rDNA genes for bacteria and fungi, respectively. We wanted to evaluate the effect of fire in root nodules from 1-year-old saplings, by comparing unburnt and burnt sites. We found that although having the same general structure, after a fire event, nodules had a higher number of infected cells and greater starch accumulation. Starch accumulated in uninfected cells can be a possible carbon source for the microbiota. Regarding diversity, Bradyrhizobium was dominant in both sites (ca. 77%), suggesting it is the preferential partner, followed by Tardiphaga (ca. 9%), a non-rhizobial Alphaproteobacteria, and Synechococcus , a cyanobacteria (ca. 5%). However, at the burnt site, additional N-fixing bacteria were included in the top 10 genera, highlighting the importance of this process. Major differences were found in the mycobiome, which was diverse in both sites and included genera mostly described as plant endophytes. Coniochaeta was dominant in nodules from the burnt site (69%), suggesting its role as a facilitator of symbiotic associations. We highlight the presence of a large bacterial and fungal community in nodules, suggesting nodulation is not restricted to nitrogen fixation. Thus, this microbiome can be involved in facilitating A. longifolia invasive success.