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Rectal and vaginal temperatures are utilised in both in vivo and in vitro models to study the effects of heat stress on oocyte competence and embryo viability in cattle. However, uterine temperature increases by only 0.5 °C in heat-stressed cows, significantly lower than simulated increases in in vitro models. Temperature variations within oviducts and ovarian follicles during heat stress are poorly understood or unavailable, and evidence is lacking that oocytes and pre-implantation embryos experience mild (40 °C) or severe (41 °C) heat stress inside the ovarian follicle and the oviduct and uterus, respectively. Gathering detailed temperature data from the reproductive tract and follicles is crucial to accurately assess oocyte competence and embryo viability under realistic heat stress conditions. Potential harm from heat stress on oocytes and embryos may result from reduced nutrient availability (e.g., diminished blood flow to the reproductive tract) or other unidentified mechanisms affecting tissue function rather than direct thermal effects. Refining in vivo stress models in cattle is essential to accurately identify animals truly experiencing heat stress, rather than assuming heat stress exposure as done in most studies. This will improve model reliability and aid in the selection of heat-tolerant animals.

Invasive fungal disease causes high morbidity and mortality among immunocompromised patients. Resistance to conventional antifungal drugs and the toxicity associated with high doses highlight the need for effective antifungal therapies. In this study, the antifungal potential of the ethanolic extract of Anacardium occidentale (Cashew Leaf) leaves were evaluated against Candida albicans and C. auris. The antifungal activity was tested by the broth microdilution method and growth kinetic test. To further explore its antifungal action mode, spectrofluorophotometry, confocal microscopy and scanning and transmission electron microscopy were performed. Additionally, heterozygous knockout strains associated with resistance to oxidative stress were included in the study. We found that A. occidentale could inhibit the proliferation and growth of C. albicans at concentrations of 62.5 and 125 μg/mL. The doubling time was also drastically affected, going from 2.8 h to 22.5 h, which was also observed in C. auris. The extract induced the accumulation of intracellular reactive oxygen species (ROS), resulting in endoplasmic reticulum stress and mitochondrial dysfunction, while it did not show cytotoxicity or hemolytic activity at the concentrations evaluated. Our work preliminarily elucidated the potential mechanisms of A. occidentale against C. albicans on a cellular level, and might provide a promising option for the design of a new treatment for invasive candidiasis.

Since the 1960s, various surgical procedures have been developed to treat the temporomandibular joint (TMJ) disease, including stock or customized prostheses for severe TMJ diseases. Understanding the appropriate indications and timing for joint replacement is crucial for evaluating the prognosis of the treatment. This study sought to identify the indications for joint replacement surgery in three countries in Latin America and to determine characteristics associated with its surgical planning. The study was conducted by interviewing surgeons who performed surgery on patients using customized TMJ prostheses between 2022 and 2024 and who had surgical planning under the same protocol. Only preoperative information related to the indication and complementary procedures related to the customized prosthesis was used, comprising 133 subjects, 41 male subjects (30.82%) and 92 female subjects (69.17%), with significant differences. Degenerative TMJ disease presented the highest indication for replacement with 47 (35.33%) cases, followed by malformations with 26 (19.54%), ankylosis with 22 (16.54%), TMJ deformity by trauma sequelae with 20 (15.03%) and replacement by another joint prosthesis 18 (13.53%). We found a significant correlation between indications and the use of orthognathic surgery in some diseases (P<0.001). In 72.34% of subjects with degenerative disease, orthognathic surgery with bilateral prosthesis was indicated. In subjects with facial malformation, orthognathic surgery with unilateral prosthesis was indicated in 76.92%. We can conclude that female subjects are more common than male subjects in the treatment with TMJ replacement. TMJ prostheses presented the highest indication in degenerative TMJ disease, and they were significantly related to orthognathic surgery., Competing Interests: The authors report no conflicts of interest., (Copyright © 2024 by Mutaz B. Habal, MD.)

Bone nonunion following a fracture represents a significant global healthcare challenge, with an overall incidence ranging between 2 and 10% of all fractures. The management of nonunion is not only financially prohibitive but often necessitates invasive surgical interventions. This comprehensive manuscript aims to provide an extensive review of the published literature involving growth factors, stem cells, and novel delivery mechanisms for the treatment of fracture nonunion. Key growth factors involved in bone healing have been extensively studied, including bone morphogenic protein (BMP), vascular endothelial growth factor (VEGF), and platelet-derived growth factor. This review includes both preclinical and clinical studies that evaluated the role of growth factors in acute and chronic nonunion. Overall, these studies revealed promising bridging and fracture union rates but also elucidated complications such as heterotopic ossification and inferior mechanical properties associated with chronic nonunion. Stem cells, particularly mesenchymal stem cells (MSCs), are an extensively studied topic in the treatment of nonunion. A literature search identified articles that demonstrated improved healing responses, osteogenic capacity, and vascularization of fractures due to the presence of MSCs. Furthermore, this review addresses novel mechanisms and materials being researched to deliver these growth factors and stem cells to nonunion sites, including natural/synthetic polymers and bioceramics. The specific mechanisms explored in this review include BMP-induced osteoblast differentiation, VEGF-mediated angiogenesis, and the role of MSCs in multilineage differentiation and paracrine signaling. While these therapeutic modalities exhibit substantial preclinical promise in treating fracture nonunion, there remains a need for further research, particularly in chronic nonunion and large animal models. This paper seeks to identify such translational hurdles which must be addressed in order to progress the aforementioned treatments from the lab to the clinical setting.

Autism is a common neurodevelopmental disorder that despite its complex etiology, is marked by deficits in prediction that manifest in a variety of domains including social interactions, communication, and movement. The tendency of individuals with autism to focus on predictable schedules and interests that contain patterns and rules highlights the likely involvement of the cerebellum in this disorder. One candidate-autism gene is contact in associated protein 2 ( CNTNAP2 ), and variants in this gene are associated with sensory deficits and anatomical differences. It is unknown, however, whether this gene directly impacts the brain's ability to make and evaluate predictions about future events. The current study was designed to answer this question by training a genetic knockout rat on a rapid speech sound discrimination task. Rats with Cntnap2 knockout (KO) and their littermate wildtype controls (WT) were trained on a validated rapid speech sound discrimination task that contained unpredictable and predictable targets. We found that although both genotype groups learned the task in both unpredictable and predictable conditions, the KO rats responded more often to distractors during training as well as to the target sound during the predictable testing conditions compared to the WT group. There were only minor effects of sex on performance and only in the unpredictable condition. The current results provide preliminary evidence that removal of this candidate-autism gene may interfere with the learning of unpredictable scenarios and enhance reliance on predictability. Future research is needed to probe the neural anatomy and function that drives this effect., Competing Interests: This work was partially funded by 1R15HD103479-01A1 to TMC. The authors have no other competing financial interests.

Motile cilia are unique organelles with the ability to autonomously move. Force generated by beating cilia propels cells and moves fluids. The ciliary skeleton is made of peripheral doublet microtubules and a central pair (CP) with a distinct structure at the tip. In this study, we present a high-resolution structure of the CP in the ciliary tip of the ciliate Tetrahymena thermophila and identify several tip proteins that bind and form unique patterns on both microtubules of the tip CP. Two of those proteins that contain tubulin polymerization-promoting protein (TPPP)-like domains, TLP1 and TLP2, bind to high curvature regions of the microtubule. TLP2, which contains two TPPP-like domains, is an unusually long protein that wraps laterally around half a microtubule and forms the bridge between the two microtubules. Moreover, we found that the conserved protein SPEF1 binds to both microtubule seams. In vitro , human SPEF1 not only binds to the microtubule seam but also crosslinks two parallel microtubules. Single-molecule microtubule dynamics assays indicate that SPEF1 stabilizes microtubules in vitro . Together, these data show that the proteins in the tip CP maintain stable microtubule structure and probably play important roles in maintaining the integrity of the axoneme.

This video-article describes a laparoscopic cervico-isthmic cerclage technique for managing cervical insufficiency in both pregnant and non-pregnant patients, utilizing a port-site closure device for precise suture placement. Two cases-one non-pregnant and one at 12 weeks gestation-underwent the procedure, with details on trocar placement, dissection, and suture passage documented. Both surgeries were completed successfully, with minimal blood loss and no complications. The use of the port-site closure device allowed for precise suture placement near the uterine vessels, contributing to favorable postoperative outcomes. This laparoscopic approach offers a minimally invasive alternative to the open technique in specialized centers., 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.)

Lathyrus odoratus L., commonly known as sweet pea, is a plant with a distinctive aroma that can develop in various habitats. An analysis of the aromatic profile of the species was conducted using the HS-SPME (solid-phase microextraction headspace) technique. This study aimed to explore the composition of and variation in the floral scent emissions of L. odorathus . The floral scents from fresh flowers were collected over different months and analyzed using gas chromatography coupled with mass spectrometry on apolar and polar stationary phase columns. In the apolar column, the majority compounds included linalool (19.27-5.79%), α-trans-bergamotene (29.4-14.21%), and phenyl ethyl alcohol (30.01-1.56%), while on the polar column, the predominant compounds included myrcene (13.25%), (E,E)-α-farnesene (26.33-8.16%), α-trans-bergamotene (42.09-24.82%), and others. This investigation was complemented by enantioselective analysis using a chiral phase based in cyclodextrins, which revealed the presence of (1 R )-(+)-α-pinene, ( S )-(-)-limonene, ( R )-(+)-germacrene D, and (R)-(E)-nerolidol as enantiomerically pure components and linalool as a racemic mixture. Notably, the principal component analysis (PCA) and heatmap revealed variations among the chemical compounds collected at different harvest times. This demonstrates that temporal factors indeed impact chemical compound production. Furthermore, research on the aromatic properties of flowers provides a theoretical basis for studying and improving the components of their scent.

Eating less meat is associated with a healthier body and planet. Yet, we remain reluctant to switch to a plant-based diet, largely due to the sensory experience of plant-based meat. Food scientists characterize meat using a double compression test, which only probes one-dimensional behavior. Here we use tension, compression, and shear tests-combined with constitutive neural networks-to automatically discover the behavior of eight plant-based and animal meats across the entire three-dimensional spectrum. We find that plant-based sausage and hotdog, with stiffnesses of 95.9 ± 14.1 kPa and 38.7 ± 3.0 kPa, successfully mimic their animal counterparts, with 63.5 ± 45.7 kPa and 44.3 ± 13.2 kPa, while tofurky is twice as stiff, and tofu is twice as soft. Strikingly, a complementary food tasting survey produces in nearly identical stiffness rankings for all eight products (ρ = 0.833, p = 0.015). Probing the fully three-dimensional signature of meats is critical to understand subtle differences in texture that may result in a different perception of taste. Our data and code are freely available at https://github.com/LivingMatterLab/CANN., Competing Interests: Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Background: Anatomical reduction of posterior malleolar fracture is a key goal in achieving good functional outcomes in patients with ankle fractures. Although there are many approaches for managing this type of fracture, no studies have shown reduction quality of posterior malleolar fracture in postoperative CT scan using the modified posteromedial ankle approach., Methods: A retrospective case series of 66 patients of 2 health centers with type 2, 3, and 4 posterior malleolar fractures according to Bartonicek classification treated using the modified posteromedial ankle approach was performed. The postoperative CT scan was used to assess syndesmotic reduction and articular step-off and residual gap in posterior malleolus reduction., Results: Reduction of posterior malleolus fracture was determined to be <2 mm in 62 patients and >2 mm in 4 cases. Syndesmotic reduction quality was considered to be anatomical in 61 patients. Four patients showed mild anterior fibular translation in the axial plane and were not reoperated. One syndesmotic malreduction was considered poor., Conclusion: In this study, we found that 92% (61 of 66) of patients with posterior malleolar fracture were reduced with <2 mm step-off using this modified posteromedial ankle approach and fracture fixation strategy., Level of Evidence: Level IV, case series., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article. Disclosure forms for all authors are available online., (© The Author(s) 2024.)

Niemann-Pick disease Type C (NPC) is caused by mutations in the cholesterol transport protein NPC1 leading to the endolysosomal accumulation of the lipid and to psychiatric alterations. Using an NPC mouse model (Npc1 nmf164 ) we show aberrant mGluR 5 lysosomal accumulation and reduction at plasma membrane in NPC1 deficient neurons. This phenotype was induced in wild-type (wt) neurons by genetic and pharmacological NPC1 silencing. Extraction of cholesterol normalized mGluR 5 distribution in NPC1-deficient neurons. Intracellular accumulation of mGluR 5 was functionally active leading to enhanced mGluR-dependent long-term depression (mGluR-LTD) in Npc1 nmf164 hippocampal slices. mGluR-LTD was lower or higher in Npc1 nmf164 slices compared with wt when stimulated with non-membrane-permeable or membrane-permeable mGluR 5 agonists, respectively. Oral treatment with the mGluR 5 antagonist 2-chloro-4-((2,5-dimethyl-1-(4-(trifluoromethoxy)phenyl)-1H-imidazol-4-yl)ethynyl)pyridine (CTEP) reduced mGluR-LTD and ameliorated psychiatric anomalies in the Npc1 nmf164 mice. Increased neuronal mGluR 5 levels were found in an NPC patient. These results implicate mGluR 5 alterations in NPC psychiatric condition and provide a new therapeutic strategy that might help patients suffering from this devastating disease., (© 2024. The Author(s).)

This study examines the intermolecular interactions between small molecules and solvents, with a particular focus on pyruvic acid (PA). PA plays a significant role in biochemistry, astrochemistry, and atmospheric chemistry, particularly in aerosol particle formation. Previous studies on PA have been expanded upon by exploring its hydration and complexation with 2,2,2-trifluoroethanol (TFE). The clusters were generated using a supersonic expansion and characterized by broadband Fourier transform microwave spectroscopy. The structures of the clusters were identified by comparing the experimental results with high-level quantum-chemical computations. Among the possible isomers for the hydrated complex, the Tc-(H2O)2 kinetic complex, where PA exhibits an internal hydrogen bond, was favored over the Tt-(H2O)2 form, predicted to be the most stable conformer. Transitions from both the A and E internal rotation substates were observed exclusively in the dihydrate. The complex with TFE did not exhibit splitting due to the internal rotation of the methyl top. This is attributed to the presence of electronegative fluorine groups in TFE, stabilizing the complex through additional CH⋯F interactions, thereby hindering the internal rotation motion of the methyl top., (© 2024 Author(s). Published under an exclusive license by AIP Publishing.)

Rapid microbiological diagnosis of the antibiotic susceptibility of Gram-negative bacilli is a priority in clinical microbiology, especially in cases of bacteremia. The rapid advancement of antimicrobial resistance proposes a challenge for empirical antibiotic therapy and shows the need for fast antibiotic susceptibility diagnostics to guide treatments. The QuickMIC System (Gradientech AB, Uppsala, Sweden) is a recently developed rapid diagnostic tool for antibiotic susceptibility testing. Our study evaluates a rapid phenotypic system (QuickMIC) that provides information on the susceptibility of 12 antibiotics against Escherichia coli , Klebsiella spp ., Pseudomonas aeruginosa , Acinetobacter baumannii , Enterobacter cloacae , Proteus spp ., Citrobacter spp., and Serratia marcescens . A total of 816 antibiotic/microorganism combinations were tested, resulting in eight discrepancies. The concordance between the antibiotics offered by QuickMIC and reference methods (MicroScan WalkAway plus system, Beckman Coulter; Etest (BioMerieux microdilution system (Bruker); Real-time PCR (GeneXpert, Cepheid); and immunochromatography (Biotech) was 99.02%. Time elapsed to obtain a valid minimal inhibitory concentration (MIC) was between 2 and 4 h. The QuickMIC system allows for the early adjustment of antibiotic treatment in these infections. Given the existing limitations of currently available rapid methods, its clinical utility is particularly relevant in the management of P. aeruginosa infections and AmpC-producing Enterobacterales. The use of rapid methods can help diversify antibiotic use and reduce carbapenem consumption., Importance: The rapid diagnosis of antibiotic sensitivity in Gram-negative bacilli is of paramount importance in clinical microbiology, particularly in cases of bacteremia. The escalating challenge of antimicrobial resistance underscores the need for expeditious antibiotic susceptibility diagnostics to guide empirical antibiotic therapy effectively. In light of this, we present our study that evaluates the QuickMIC System, a recently developed rapid diagnostic antibiogram. QuickMIC System, offers a novel approach to phenotypic testing, providing information on the activity of 12 antibiotics against key pathogens, including Escherichia coli , Klebsiella spp ., Pseudomonas aeruginosa , Acinetobacter baumannii , Enterobacter cloacae , Proteus spp ., Citrobacter spp ., and Serratia marcescens . Our investigation involved testing a total of 816 antibiotic/microorganism combinations. The study demonstrated an impressive 99.02% concordance between the QuickMIC System and the reference methods, with only eight discrepancies observed. The time to actionable minimum inhibitory concentration (MIC) ranged between 2 and 4 h, highlighting the system's efficiency in providing rapid results., Competing Interests: The authors declare no conflict of interest.

Purpose: Significant methodological shortcomings limit the validity of prior research on pregnancy decision-making and the effects of 'unintended' pregnancies on people's health and well-being. The Attitudes and Decisions After Pregnancy Testing (ADAPT) study investigates the consequences for individuals unable to attain their pregnancy and childbearing preferences using an innovative nested prospective cohort design and novel conceptualisation and measurement of pregnancy preferences., Participants: This paper describes the characteristics of the ADAPT Study Cohort, comprised of 2015 individuals aged 15-34 years, assigned female at birth, recruited between 2019 and 2022 from 23 health facilities in the southwestern USA., Findings to Date: The cohort was on average 25 years old. About 59% identified as Hispanic/Latine, 21% as white, and 8% as black, 13% multiracial or another race. Over half (56%) were nulliparous. About 32% lived in a household with income <100% of the federal poverty level. A significant minority (37%) reported a history of a depressive, anxiety or other mental health disorder diagnosis, and 30% reported currently experiencing moderate or severe depressive symptoms. Over one-quarter (27%) had ever experienced physical intimate partner violence, and almost half (49%) had ever experienced emotional abuse. About half (49%) had been diagnosed with a chronic health condition, and 37% rated their physical health as fair or poor. The 335 (17%) participants who experienced incident pregnancy over 1 year were similar to selected non-pregnant matched comparison participants in terms of age, racial and ethnic identity, and parity but were more likely to live with a main partner than comparison participants., Future Plans: We will continue to follow participants who experienced incident pregnancy and non-pregnant comparison participants until 2026. Analyses will examine pregnancy decision-making and investigate differences in health and well-being by prepregnancy pregnancy desires and feelings after the discovery of pregnancy, offering new insights into the consequences of not attaining one's reproductive preferences., Trial Registration Number: NCT03888404., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Aedes mosquito-borne viruses (ABVs) place a substantial strain on public health resources in the Americas. Vector control of Aedes mosquitoes is an important public health strategy to decrease or prevent spread of ABVs. The ongoing Targeted Indoor Residual Spraying (TIRS) trial is an NIH-sponsored clinical trial to study the efficacy of a novel, proactive vector control technique to prevent dengue virus (DENV), Zika virus (ZIKV), and chikungunya virus (CHIKV) infections in the endemic city of Merida, Yucatan, Mexico. The primary outcome of the trial is laboratory-confirmed ABV infections in neighborhood clusters. Despite the difficulties caused by the COVID-19 pandemic, by early 2021 the TIRS trial completed enrollment of 4,792 children aged 2-15 years in 50 neighborhood clusters which were allocated to control or intervention arms via a covariate-constrained randomization algorithm. Here, we describe the makeup and ABV seroprevalence of participants and mosquito population characteristics in both arms before TIRS administration. Baseline surveys showed similar distribution of age, sex, and socio-economic factors between the arms. Serum samples from 1,399 children were tested by commercially available ELISAs for presence of anti-ABV antibodies. We found that 45.1% of children were seropositive for one or more flaviviruses and 24.0% were seropositive for CHIKV. Of the flavivirus-positive participants, most were positive for ZIKV-neutralizing antibodies by focus reduction neutralization testing which indicated a higher proportion of participants with previous ZIKV than DENV infections within the cohort. Both study arms had statistically similar seroprevalence for all viruses tested, similar socio-demographic compositions, similar levels of Ae. aegypti infestation, and similar observed mosquito susceptibility to insecticides. These findings describe a population with a high rate of previous exposure to ZIKV and lower titers of neutralizing antibodies against DENV serotypes, suggesting susceptibility to future outbreaks of flaviviruses is possible, but proactive vector control may mitigate these risks., Competing Interests: The authors have declared that no competing interests exist., (Copyright: This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.)

Melothria pendula L., a wild relative of cucurbit crops, is also used for food and as a medicinal plant in Mexico. The objective of this study was to ecogeographically characterize the known populations of M. pendula in Mexico, determining its adaptive range and possible sites for in situ and ex situ conservation. To achieve this goal, we compiled a dataset of 1270 occurrences of M. pendula from herbarium and botanical databases and individual observations. Adaptive scenarios were generated through the development of an ecogeographic land characterization (ELC) map, preceded by the identification of abiotic variables influencing the species' distribution. Eleven bioclimatic, edaphic, and geophysical variables were found to be important for the species' distribution. The ELC map obtained contained 21 ecogeographic categories, with 14 exhibiting the presence of M. pendula. By analyzing ecogeographic representativeness, 111 sites of high interest were selected for the efficient collection of M. pendula in Mexico. Eight high-priority hotspots for future in situ conservation of M. pendula were also identified based on their high ecogeographic diversity, with only three of these hotspots located within protected natural areas. In this study, ecogeographic approaches show their potential utility in conservation prioritization when genetic data are scarce, a very common condition in crop wild relatives.

The "One Health" approach provides a comprehensive framework for understanding antimicrobial resistance. This perspective is of particular importance in the study of Pseudomonas aeruginosa , as it is not only a pathogen that affects humans but also persists in environmental reservoirs. To assess evolutionary selection for niche-specific traits, a genomic comparison of 749 P. aeruginosa strains from three environments (clinical, aquatic, and soil) was performed. The results showed that the environment does indeed exert selective pressure on specific traits. The high percentage of persistent genome, the lack of correlation between phylogeny and origin of the isolate, and the high intrinsic resistance indicate that the species has a high potential for pathogenicity and resistance, regardless of the reservoir. The flexible genome showed an enrichment of metal resistance genes, which could act as a co-selection of antibiotic resistance genes. In the plasmids, resistance genes were found in multigenic clusters, with the presence of a mobile integron being prominent. This integron was identified in several pathogenic strains belonging to distantly related taxa with a worldwide distribution, showing the risk of rapid evolution of resistance. These results provide a more complete understanding of the evolution of P. aeruginosa , which could help develop new prevention strategies.

The ability to predict and respond to upcoming stimuli is a critical skill for all animals, including humans. Prediction operates largely below conscious awareness to allow an individual to recall previously encountered stimuli and prepare an appropriate response, especially in language. The ability to predict upcoming words within typical speech patterns aids fluent comprehension, as conversational speech occurs quickly. Individuals with certain neurodevelopmental disorders such as autism and dyslexia have deficits in their ability to generate and use predictions. Rodent models are often used to investigate specific aspects of these disorders, but there is no existing behavioral paradigm that can assess prediction capabilities with complex stimuli like speech sounds. Thus, the present study modified an existing rapid speech sound discrimination paradigm to assess whether rats can form predictions of upcoming speech sound stimuli and utilize them to improve task performance. We replicated prior work showing that rats can discriminate between speech sounds presented at rapid rates. We also saw that rats responded exclusively to the target at slow speeds but began responding to the predictive cue in anticipation of the target as the speed increased, suggesting that they learned the predictive value of the cue and adjusted their behavior accordingly. This prediction task will be useful in assessing prediction deficits in rat models of various neurodevelopmental disorders through the manipulation of both genetic and environmental factors., Competing Interests: Declaration of Competing Interest None., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Periodontitis is a bacteria-induced chronic inflammatory disease characterized by degradation of the supporting tissue and bone in the oral cavity. Treatment modalities seek to facilitate periodontal rehabilitation while simultaneously preventing further gingival tissue recession and potentially bone atrophy. The aim of this study was to compare two differently sourced membranes, a resorbable piscine collagen membrane and a porcine-derived collagen membrane, in the repair of soft tissue defects utilizing a preclinical canine model. This in vivo component consisted of 10 beagles which were subjected to bilateral maxillary canine mucogingival flap defects, as well as bilateral soft tissue defects (or pouches) with no periodontal ligament damage in the mandibular canines. Defects received either a piscine-derived dermal membrane, (Kerecis® Oral, Ísafjörður, Iceland) or porcine-derived dermal membrane (Geistlich Mucograft®, Wolhusen, Switzerland) in a randomized fashion (to avoid site bias) and were allowed to heal for 30, 60, or 90 days. Statistical evaluation of tissue thickness was performed using general linear mixed model analysis of variance and least significant difference (LSD) post hoc analyses with fixed factors of time and membrane. Semi-quantitative analysis employed for inflammation assessment was evaluated using a chi-squared test along with a heteroscedastic t-test and values were reported as mean and corresponding 95% confidence intervals. In both the mucogingival flap defects and soft tissue gingival pouches, no appreciable qualitative differences were observed in tissue healing between the membranes. Furthermore, no statistical differences were observed in the thickness measurements between piscine- and porcine-derived membranes in the mucogingival flap defects (1.05 mm [±0.17] and 1.29 mm [±0.17], respectively [p = .06]) or soft tissue pouches (1.36 mm [±0.14] and 1.47 mm [±0.14], respectively [p = .27]), collapsed over time. Independent of membrane source (i.e., piscine or porcine), similar inflammatory responses were observed in both the maxilla and mandible at the three time points (p = .88 and p = .79, respectively). Histologic and histomorphometric evaluation results indicated that both membranes yielded equivalent tissue responses, remodeling dynamics and healing patterns for the mucogingival flap as well as the soft tissue gingival pouch defect models., (© 2024 Wiley Periodicals LLC.)

A series of ruthenium complexes of formulae [RuCl(triazenide)( p -cymene)] have been synthesized using as ligand a triazenide monofunctionalized with an N-heterocyclic moiety. Nuclear magnetic resonance, high resolution mass spectrometry and X-ray diffraction were used to characterize the triazenide ligands and their complexes. In addition, these ruthenium complexes catalyzed the reduction of nitrobenzene to aniline in the presence of sodium borohydride and ethanol as solvent at room temperature. Notably, complex 5 was especially active in the reduction of nitroarenes substituted at the aromatic ring with electron-withdrawing or electron-donating fuctional groups affording the desired arylamines in good to excellent yields (80-100%). The role of the N-heterocyclic moiety on catalysis was explored., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Carbapenem-resistant Pseudomonas aeruginosa infections represent a critical public health concern, highlighting the need for the development of effective antibiotics. Cefiderocol demonstrated potent in vitro activity against Pseudomonas aeruginosa , particularly in strains that are resistant to other drugs. However, concerns regarding the emergence of drug-resistant strains persist. This study, conducted with 109 carbapenem-resistant Pseudomonas aeruginosa strains from the Spanish Hospital (Dr. Balmis, Alicante). The study evaluated susceptibility to cefiderocol in comparison to alternative antibiotics and including their susceptibility to bacterial inoculum, while assessing various testing methods. Our findings revealed high susceptibility to cefiderocol against carbapenem-resistant strains, with only 2 of 109 strains exhibiting resistance. Comparative analysis demonstrated superiority of cefiderocol towards alternative antibiotics. Both the E-test and disk-diffusion methods showed 100% concordance with the microdilution method in classifying strains as susceptible or resistant. However, 4.6% (5/109) of disc zone diameters fell within the technical uncertainty zone, so the E-test technique was found to be more useful in routine clinical practice. Additionally, escalating bacterial inoculum correlated with decreases in vitro activity, so this parameter should be adjusted very carefully in in vivo studies. This study underscores cefiderocol's potential as a therapeutic option for carbapenem-resistant Pseudomonas aeruginosa infections. However, the emergence of drug-resistant strains emphasizes the critical need for a wise use of antibiotics and a continuous monitoring of resistance to antibiotics. Based on our in vitro data, further investigation concerning the impact of bacterial inoculum on drug efficacy is warranted in order to detect resistance mechanisms and optimize treatment strategies, thereby mitigating the risk of resistance.

Background: Establishing adequate reference intervals (RIs) for vitamins A and E is essential for diagnosing and preventing deficiencies. Due to the current boom in data mining and its easy applicability, more laboratories are establishing RIs using indirect methods. Our study aims to obtain RIs using four indirect data-mining procedures (Bhattacharya, Hoffmann, Kosmic, and RefineR) for vitamins A and E., Material and Methods: 8943 individuals were collected to establish the RIs. After using different data cleaning steps and checking whether these data should be divided according to age and gender based on multiple linear regression and variance component analyses, indirect RIs were calculated using specific Excel spreadsheets or R-packages software., Results: A total of 2004 records were eligible. For vitamin A, the RIs obtained were (1.11 - 2.68) µmol/L, (1.13 - 2.70) µmol/L, (1.13 - 2.71) µmol/L, and (1.17 - 2.66) µmol/L using the Bhattacharya, Hoffmann, Kosmic and RefineR approaches, respectively. For vitamin E, these intervals were (17.3 - 49.9) µmol/L (Bhattacharya), (17.3 - 48.9) µmol/L (Hoffmann), (19.6 - 50.3) µmol/L (Kosmic), and (19.4 - 50.9) µmol/L (RefineR). In all cases, the RIs were comparable., Conclusions: Suitable RIs for vitamins A and E were calculated using four indirect methods that are suitable and adapted to our population's demographic characteristics., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Introduction: Pneumatosis intestinalis is a radiological finding characterized by the presence of gas in the bowel wall that is associated with multiple entities. Our aim is to know its incidence in lung transplant patients, its physiopathology and its clinical relevance., Methods: A search of patients with pneumatosis intestinalis was performed in the database of the Lung Transplant Unit of our hospital. The presence of pneumatosis after transplantation was confirmed in all of them and relevant demographic, clinical and imaging variables were collected to evaluate its association and clinical expression, as well as the therapeutic approach after the findings., Results: The incidence of pneumatosis intestinalis after lung transplantation in our center was 3.1% (17/546), developing between 9 and 1270 days after transplantation (mean, 198 days; median 68 days). Most of the patients were asymptomatic or with mild symptoms, without any major analytical alterations, and with a cystic and expansive radiological appearance. Pneumoperitoneum was associated in 70% of the patients (12/17). Conservative treatment was chosen in all cases. The mean time to resolution was 389 days., Conclusion: Pneumatosis intestinalis in lung transplant patients is a rare complication of uncertain origin, which can appear for a very long period of time after transplantation. It has little clinical relevance and can be managed without other diagnostic or therapeutic interventions., (Copyright © 2023 SERAM. Published by Elsevier España, S.L.U. All rights reserved.)

Facial contouring relates to hard and soft structures that make up the face. Skeletal class II and III subjects present bone structure and position changes, significantly impacting the soft tissues. This study aims to analyze the morphology of the mandible at mandibular ramus and angle level in subjects with skeletal facial deformity class II and III who are candidates for orthognathic surgery and to define implications in facial contour. A cross-sectional study used cone beam computed tomography to compare the mandibular contour (mandibular angle and ramus region) in orthognathic surgery candidates. One hundred sixty orthognathic surgery candidates were analyzed, ranging in age from 18 to 58 years (31.29 ± 11.97). Regarding the skeletal class, 95 (59.37%) were skeletal class II, and 65 (40.62%) were skeletal class III. Class II subjects had a larger antegonial notch than class III subjects. Concerning the mandibular contour, class II subjects presented less vertical distance than class III subjects, but both presented similar gonial angles. Concerning the ideas to assess the need for mandibular contouring surgery, the 2 proposals to determine the need for mandibular contouring surgery in class II and III subjects present a similar distribution. The mandibular notch is an objective element and is commonly present in subjects with a class II facial pattern; this element can be used in contour analysis to define expected facial characteristics, including the patient's facial sex, in the decision of surgical techniques for lower facial contour augmentation or reduction., Competing Interests: The authors report no conflicts of interest., (Copyright © 2024 by Mutaz B. Habal, MD.)

Background: Velopharyngeal insufficiency (VPI) is a condition characterized by incomplete separation of the oral and nasal cavities during speech production, thereby leading to speech abnormalities and audible nasal emissions. Subsequently, this adversely impacts communication and potentially interpersonal social interactions. Autologous fat grafting (AFG) to the velopharynx, a minimally invasive technique, aims to improve oronasal separation by providing bulk and advancing the posterior pharyngeal wall toward the soft palate. Despite its potential, the relative novelty of AFG in treating VPI has resulted in reporting of inconsistent indications, varied surgical techniques, and mixed outcomes across existing literature., Methods: This systemic review examined the evidence of AFG for VPI treatment over the past decade (2013-2023). A thorough search across five electronic databases yielded 233 studies, with 20 meeting the inclusion criteria (e.g., utilized fat injection as their selected VPI treatment, conducted study in human subjects, did not perform additional surgical procedure at time of fat injection). Selected studies encompassed patient and surgical intervention characteristics, perceptual speech assessment (PSA) scores, gap sizes, nasalance measurements, and complications., Results: The majority of patients had a prior cleft palate diagnosis (78.2%), in which nasoendoscopy was the prevalent method for visualizing the velopharyngeal port defect. Fat harvesting predominantly occurred from the abdomen (64.3%), with an average injection volume of 6.3 mL across studies. PSA and subjective gap size scores were consistently higher preoperatively than postoperatively. PSA score analysis from seven studies revealed significant and sustained improvements postoperatively. Gap size score analysis from four studies demonstrated similar preoperative and postoperative differences. Complications were reported in 17 studies, yielding a 2.7% summative complication rate among 594 cases., Conclusions: Autologous fat grafting has emerged as a minimally invasive, safe, and effective treatment for mild to moderate VPI. However, challenges remain because of variability in patient selection criteria, diagnostic modalities, and outcome measurements. This review underscores the need for randomized control trials to directly compare AFG with standard-of-care surgical interventions, providing more conclusive evidence of its clinical efficacy., Competing Interests: Conflicts of interest and sources of funding: none declared., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: The primary aim of this study was to identify and stratify candidate metrics used by anesthesiology residency program directors (PDs) to develop their residency rank lists through the National Resident Matching Program., Methods: Sixteen PDs comprised the participants, selected for diversity in geography and program size. We used a 3-round iterative survey to identify and stratify candidate metrics. In the first round, participants listed metrics they planned to use to evaluate candidates. In the second round, metrics from the first round were ranked by importance, and criteria were solicited to define an exceptional, strong, average, marginal, and uncompetitive candidate for each metric. In the third round, aggregated results were presented and participants refined their rankings., Results: Of the 16 PDs selected, 15 participated in the first and second survey rounds, and 10 in the third. Eighteen candidate metrics were indicated by 8 or more PDs for residency selection. All 10 PDs from the final round identified passing Step 1 of the United States Medical Licensing Exam (USMLE) and the absence of "red flags" like a failed rotation as key selection metrics, both averaging an importance score of 4.9 out of 5. Other metrics identified by all PDs included clerkship evaluation comments, USMLE Step 2 scores, class rank, letters of recommendation, personal statement, and program and geographical signals., Conclusions: The study reveals key metrics anesthesiology residency PDs use for candidate ranking, which may offer candidates insights into their competitiveness for anesthesiology residency., (© 2024 Society for Education in Anesthesia.)

Bone regeneration remains a significant clinical challenge, often necessitating surgical approaches when healing bone defects and fracture nonunions. Within this context, the modulation of adenosine signaling pathways has emerged as a promising therapeutic option, encouraging osteoblast activation and tempering osteoclast differentiation. A literature review of the PubMed database with relevant keywords was conducted. The search criteria involved in vitro or in vivo models, with clear methodological descriptions. Only studies that included the use of indirect adenosine agonists, looking at the effects of bone regeneration, were considered relevant according to the eligibility criteria. A total of 29 articles were identified which met the inclusion and exclusion criteria, and they were reviewed to highlight the preclinical translation of adenosine agonists. While preclinical studies demonstrate the therapeutic potential of adenosine signaling in bone regeneration, its clinical application remains unrealized, underscoring the need for further clinical trials. To date, only large, preclinical animal models using indirect adenosine agonists have been successful in stimulating bone regeneration. The adenosine receptors (A 1 , A 2A , A 2B , and A 3 ) stimulate various pathways, inducing different cellular responses. Specifically, indirect adenosine agonists act to increase the extracellular concentration of adenosine, subsequently agonizing the respective adenosine receptors. The agonism of each receptor is dependent on its expression on the cell surface, the extracellular concentration of adenosine, and its affinity for adenosine. This comprehensive review analyzed the multitude of indirect agonists currently being studied preclinically for bone regeneration, discussing the mechanisms of each agonist, their cellular responses in vitro, and their effects on bone formation in vivo.

Vitamin B 6 is a critical molecule for metabolism, development, and stress sensitivity in plants. It is a cofactor for numerous biochemical reactions, can serve as an antioxidant, and has the potential to increase tolerance against both biotic and abiotic stressors. Due to the importance of vitamin B 6 , its biosynthesis is likely tightly regulated. Plants can synthesize vitamin B 6 de novo via the concerted activity of Pyridoxine Biosynthesis Protein 1 (PDX1) and PDX2. Previously, PDX proteins have been identified as targets for ubiquitination, indicating they could be marked for degradation by two highly conserved pathways: the Ubiquitin Proteasome Pathway (UPP) and the autophagy pathway. Initial experiments show that PDXs are in fact degraded, but surprisingly, in a ubiquitin-independent manner. Inhibitor studies pointed toward cathepsin B, a conserved lysosomal cysteine protease, which is implicated in both programed cell death and autophagy in humans and plants. In plants, cathepsin Bs are poorly described, and no confirmed substrates have been identified. Here, we present PDX proteins from Arabidopsis thaliana as interactors and substrates of a plant Cathepsin B. These findings not only describe a novel cathepsin B substrate in plants, but also provide new insights into how plants regulate de novo biosynthesis of vitamin B 6 ., (© 2024 Federation of European Biochemical Societies.)

Although structural information on sugars is wide, experimental studies on the oxidation products of sugars in the gas phase, free from solvent interactions, have been rarely reported. We present an experimental work on the changes in the structure and interactions of two products of glucose oxidation (D-glucono-1,5-lactone (GlcL) and D-glucurono-6,3-lactone (GlcurL)) with respect to their precursor. Features such as intramolecular interactions, ring puckering and tautomerism were observed.

[Cu(NN 1 ) 2 ]ClO 4 is a copper (I) complex, where NN 1 is an imine ligand 6-((quinolin-2-ylmethylene) amino)-2H-chromen-2-one obtained by derivatization of natural compound coumarin, developed for the treatment of infectious diseases that affect salmonids. In previous research, we showed that the Cu(I) coordination complex possesses antibacterial activity against Flavobacterium psychrophilum , providing protection against this pathogen in rainbow trout during challenge assays (with an RPS of 50%). In the present study, the effects of administering [Cu(NN 1 ) 2 ]ClO 4 to Oncorhynchus mykiss over a 60-days period were evaluated with regard to systemic immune response and its potential to alter intestinal microbiota composition. In O. mykiss , an immunostimulatory effect was evident at days 30 and 45 after administration, resulting in an increment of transcript levels of IFN-γ, IL-12, TNF-α, lysozyme and perforin. To determine whether these immunomodulatory effects correlated with changes in the intestinal microbiota, we analyzed the metagenome diversity by V4 16S rRNA sequencing. In O. mykiss , both [Cu(NN 1 ) 2 ]ClO 4 and commercial antibiotic florfenicol had comparable effects at the phylum level, resulting in a predominance of proteobacteria and firmicutes. Nonetheless, at the genus level, florfenicol and [Cu(NN 1 ) 2 ]ClO 4 complex exhibited distinct effects on the intestinal microbiota of O. mykiss . In conclusion, our findings demonstrate that [Cu(NN 1 ) 2 ]ClO 4 is capable of stimulating the immune system at a systemic level, while inducing alterations in the composition of the intestinal microbiota in O. mykiss ., 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 © 2024 Parra, Aldabaldetrecu, Arce, Soto-Aguilera, Vargas, Guerrero, Tello and Modak.)

Introduction: Alzheimer's disease (AD) and behavioral variant frontotemporal dementia (bvFTD) lack mechanistic biophysical modeling in diverse, underrepresented populations. Electroencephalography (EEG) is a high temporal resolution, cost-effective technique for studying dementia globally, but lacks mechanistic models and produces non-replicable results., Methods: We developed a generative whole-brain model that combines EEG source-level metaconnectivity, anatomical priors, and a perturbational approach. This model was applied to Global South participants (AD, bvFTD, and healthy controls)., Results: Metaconnectivity outperformed pairwise connectivity and revealed more viscous dynamics in patients, with altered metaconnectivity patterns associated with multimodal disease presentation. The biophysical model showed that connectome disintegration and hypoexcitability triggered altered metaconnectivity dynamics and identified critical regions for brain stimulation. We replicated the main results in a second subset of participants for validation with unharmonized, heterogeneous recording settings., Discussion: The results provide a novel agenda for developing mechanistic model-inspired characterization and therapies in clinical, translational, and computational neuroscience settings., (© 2024 The Authors. Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)

The energy state of endosteal implants is dependent on the material, manufacturing technique, cleaning procedure, sterilization method, and surgical manipulation. An implant surface carrying a positive charge renders hydrophilic properties, thereby facilitating the absorption of vital plasma proteins crucial for osteogenic interactions. Techniques to control the surface charge involve processes like oxidation, chemical and topographical adjustments as well as the application of nonthermal plasma (NTP) treatment. NTP at atmospheric pressure and at room temperature can induce chemical and/or physical reactions that enhance wettability through surface energy changes. NTP has thus been used to modify the oxide layer of endosteal implants that interface with adjacent tissue cells and proteins. Results have indicated that if applied prior to implantation, NTP strengthens the interaction with surrounding hard tissue structures during the critical phases of early healing, thereby promoting rapid bone formation. Also, during this time period, NTP has been found to result in enhanced biomechanical fixation. As such, the application of NTP may serve as a practical and reliable method to improve healing outcomes. This review aims to provide an in-depth exploration of the parameters to be considered in the application of NTP on endosteal implants. In addition, the short- and long-term effects of NTP on osseointegration are addressed, as well as recent advances in the utilization of NTP in the treatment of periodontal disease.

Piscirickettsia salmonis is the pathogen that most affects the salmon industry in Chile. Large quantities of antibiotics have been used to control it. In search of alternatives, we have developed [Cu(NN 1 ) 2 ]ClO 4 where NN 1 = 6-((quinolin-2-ylmethylene)amino)-2H-chromen-2-one. The antibacterial capacity of [Cu(NN 1 ) 2 ]ClO 4 was determined. Subsequently, the effect of the administration of [Cu(NN 1 ) 2 ]ClO 4 on the growth of S. salar , modulation of the immune system and the intestinal microbiota was studied. Finally, the ability to protect against a challenge with P. salmonis was evaluated. The results obtained showed that the compound has an MIC between 15 and 33.9 μg/mL in four isolates. On the other hand, the compound did not affect the growth of the fish; however, an increase in the transcript levels of IFN-γ, IL-12, IL-1β, CD4, lysozyme and perforin was observed in fish treated with 40 μg/g of fish. Furthermore, modulation of the intestinal microbiota was observed, increasing the genera of beneficial bacteria such as Lactobacillus and Bacillus as well as potential pathogens such as Vibrio and Piscirickettsia . Finally, the treatment increased survival in fish challenged with P. salmonis by more than 60%. These results demonstrate that the compound is capable of protecting fish against P. salmonis , probably by modulating the immune system and the composition of the intestinal microbiota.

Aquaculture is a growing industry worldwide, but it faces challenges related to animal health. These challenges include infections by parasites, bacteria, and viral pathogens. These harmful pathogens have devastating effects on the industry, despite efforts to control them through vaccination and antimicrobial treatments. Unfortunately, these measures have proven insufficient to address the sanitary problems, resulting in greater environmental impact due to the excessive use of antimicrobials. In recent years, probiotics have emerged as a promising solution to enhance the performance of the immune system against parasitic, bacterial, and viral pathogens in various species, including mammals, birds, and fish. Some probiotics have been genetically engineered to express and deliver immunomodulatory molecules. These promote selective therapeutic effects and specific immunization against specific pathogens. This review aims to summarize recent research on the use of probiotics in fish aquaculture, with a particular emphasis on genetically modified probiotics. In particular, we focus on the advantages of using these microorganisms and highlight the main barriers hindering their widespread application in the aquaculture industry.

Since the Zika virus (ZIKV) pandemic in 2015-2017, there has been a near absence of reported cases in the Americas outside of Brazil. However, the conditions for Aedes-borne transmission persist in Latin America, and the threat of ZIKV transmission is increasing as population immunity wanes. Mexico has reported only 70 cases of laboratory-confirmed ZIKV infection since 2020, with no cases recorded in the Yucatán peninsula. Here, we provide evidence of active ZIKV transmission, despite the absence of official case reports, in the city of Mérida, Mexico, the capital of the state of Yucatán. Capitalizing on an existing cohort, we detected cases in participants with symptoms consistent with flavivirus infection from 2021 to 2022. Serum samples from suspected cases were tested for ZIKV RNA by polymerase chain reaction or ZIKV-reactive IgM by ELISA. To provide more specific evidence of exposure, focus reduction neutralization tests were performed on ELISA-positive samples. Overall, we observed 25 suspected ZIKV infections for an estimated incidence of 2.8 symptomatic cases per 1,000 persons per year. Our findings emphasize the continuing threat of ZIKV transmission in the setting of decreased surveillance and reporting.

Background: The birthplace has a crucial role in shaping the childbirth experience and mothers' satisfaction levels. This study aimed to identify the experiences and perceptions that may have an impact in the long-term on mothers' birthing experience, considering hospital design features in the birthing environment until discharge., Methods: Inductive thematic analysis of twenty-five hospital labor testimonies employing a phenomenological research approach and utilizing a biographical method. Participants were women with a professional background in architecture, landscape architecture, engineering, or interior design., Results: The results are organized into four themes and seven subthemes. The first theme is "First sight and long term impression" which is subdivided into the subthemes "Depersonalized itinerary in entrances and corridors" and "Instinctive search for connection with nature". The second theme deals with "Accompaniment and tucking in during the birthing process", subdivided into "Hotel-like: space for movement and personalized adaptation" and "Helplessness, cold and uncertainty: spaces to be against one's will". The third theme is "Damage in collateral rooms", which includes "The integration of toilets in the birthing process", "Operating rooms unchangeable in the face of cesarean delivery" and "Neonatal units that do not integrate families". Finally, the fourth theme includes "Improvement proposals for new designs"., Conclusions: This study contributes to the existing literature by deepening the understanding of the design features identified in hospitals in recent studies. Further research incorporating the experiences of women in the birthing process is needed to facilitate evidence-based design policies.

Background: The cerebroplacental ratio is associated with perinatal mortality and morbidity, but it is unknown whether routine measurement improves pregnancy outcomes. We aimed to evaluate whether the addition of cerebroplacental ratio measurement to the standard ultrasound growth assessment near term reduces perinatal mortality and severe neonatal morbidity, compared with growth assessment alone., Methods: RATIO37 was a randomised, open-label, multicentre, pragmatic trial, conducted in low-risk pregnant women, recruited from nine hospitals over six countries. The eligibility criteria were designed to be broad; participants were required to be 18 years or older, with an ultrasound-dated confirmed singleton pregnancy in the first trimester, an alive fetus with no congenital malformations at the routine second-trimester ultrasound, an absence of adverse medical or obstetric history, and the capacity to give informed consent. Women were randomly assigned in a 1:1 ratio (block size 100) using a web-based system to either the concealed group or revealed group. In the revealed group, the cerebroplacental ratio value was known by clinicians, and if below the fifth centile, a planned delivery after 37 weeks was recommended. In the concealed group, women and clinicians were blinded to the cerebroplacental ratio value. All participants underwent ultrasound at 36 + 0 to 37 + 6 weeks of gestation with growth assessment and Doppler evaluation. In both groups, planned delivery was recommended when the estimated fetal weight was below the tenth centile. The primary outcome was perinatal mortality from 24 weeks' gestation to infant discharge. The study is registered at ClinicalTrials.gov (NCT02907242) and is now closed., Findings: Between July 29, 2016, and Aug 3, 2021, we enrolled 11 214 women, of whom 9492 (84·6%) completed the trial and were eligible for analysis (4774 in the concealed group and 4718 in the revealed group). Perinatal mortality occurred in 13 (0·3%) of 4774 pregnancies in the concealed group and 13 (0·3%) of 4718 in the revealed group (OR 1·45 [95% CI 0·76-2·76]; p=0·262). Overall, severe neonatal morbidity occurred in 35 (0·73%) newborns in the concealed group and 18 (0·38%) in the revealed group (OR 0·58 [95% CI 0·40-0·83]; p=0·003). Severe neurological morbidity occurred in 13 (0·27%) newborns in the concealed group and nine (0·19%) in the revealed group (OR 0·56 [95% CI 0·25-1·24]; p=0·153). Severe non-neurological morbidity occurred in 23 (0·48%) newborns in the concealed group and nine (0·19%) in the revealed group (0·58 [95% CI 0·39-0·87]; p=0·009). Maternal adverse events were not collected., Interpretation: Planned delivery at term based on ultrasound fetal growth assessment and cerebroplacental ratio at term was not followed by a reduction of perinatal mortality although significantly reduced severe neonatal morbidity compared with fetal growth assessment alone., Funding: La Caixa foundation, Cerebra Foundation for the Brain Injured Child, Agència per la Gestió d'Ajuts Universitaris i de Recerca, and Instituto de Salud Carlos III., Competing Interests: Declaration of interests EG declares payment to their institution in support of the present study from La Caixa Foundation (LCF/PR/ GN18/10310003); Cerebra Foundation for the Brain Injured Child (Carmarthen, Wales, UK); AGAUR (grant 2017 SGR number 1531); and Instituto de Salud Carlos III (PI15/00903). EG declares payment to their institution outside the present study from Roche Diagnostic International; and book royalties from Comumna Edicions and Editorial Médica Panamericana. FF declares payment to their institution outside the present study from Roche Diagnostic International; book royalties from Editorial Médica Panamericana; and consulting fees and payments for lectures from Roche Diagnostic International, outside the present study., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: Digital cognitive assessment is becoming increasingly widespread in ageing research and care, especially since the COVID-19 pandemic. Remote online collection provides opportunities for ageing and dementia professionals to collect larger datasets, increase the diversity of research participants and patients and offer cost-effective screening and monitoring methods for clinical practice and trials. However, the reliability of self-administered at-home tests compared to their lab-based counterparts often goes unexamined, compromising the validity of adopting such measures., Objective: Our aim is to validate a self-administered web-based version of the visual short-term memory binding task (VSTMBT), a potential digital biomarker sensitive to Alzheimer's disease processes, suitable for use on personal devices., Methods: A final cross-sectional sample of 37 older-adult (51-77 years) participants without dementia completed our novel self-administered version of the VSTMBT, both at home on a personal device and in the lab, under researcher-controlled conditions., Results: ANOVA and Bayesian t -test found no significant differences between the task when it was remotely self-administered by participants at home compared to when it was taken under controlled lab conditions., Conclusions: These results indicate the VSTMBT can provide reliable data when self-administered at-home using an online version of the task and on a personal device. This finding has important implications for remote screening and monitoring practices of older adults, as well as supporting clinical practices serving diverse patient communities. Future work will assess remote administration in older adults with cognitive impairment and diverse socio-economic and ethno-cultural backgrounds as well as a bench-to-bedside application., Competing Interests: The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2024.)

Menopause causes a reduction in estradiol (E2) and may be associated with neuromuscular degeneration. Compared to pre-menopausal (PRE-M) women, this study sought to determine dietary protein intake and whether lower levels of circulating E2 in post-menopausal women (POST-M) were occurring alongside increased levels of biomarkers of axonal and neuromuscular junction degeneration (NMJ), inflammation, muscle protein degradation, and reduced indices of muscle quality and performance. Employing a cross-sectional design, PRE-M ( n = 6) and POST-M ( n = 6) dietary analysis data were collected and participants then donated a blood and urine sample followed by assessments for body composition, motor unit activation, and muscle performance. Independent group t -tests were performed to determine differences between groups ( p ≤ 0.05). In POST-M women, E2, motor unit activity, muscle quality, and muscle performance were significantly less than those for PRE-M women; however, the levels of c -terminal fragment of agrin, tumor necrosis factor-α, and urinary titin were significantly greater ( p < 0.05). POST-M women were also shown to be ingesting fewer total calories and less protein than PRE-M ( p < 0.05). Reduced E2 and dietary protein intake in POST-M women occurs in conjunction with increased levels of biomarkers of NMJ degradation, inflammation, and muscle proteolysis, which may be associated with reduced motor unit activation and muscle quality.

The 2-week, virtual Future of the Search for Life science and engineering workshop brought together more than 100 scientists, engineers, and technologists in March and April 2022 to provide their expert opinion on the interconnections between life-detection science and technology. Participants identified the advances in measurement and sampling technologies they believed to be necessary to perform in situ searches for life elsewhere in our Solar System, 20 years or more in the future. Among suggested measurements for these searches, those pertaining to three potential indicators of life termed "dynamic disequilibrium," "catalysis," and "informational polymers" were identified as particularly promising avenues for further exploration. For these three indicators, small breakout groups of participants identified measurement needs and knowledge gaps, along with corresponding constraints on sample handling (acquisition and processing) approaches for a variety of environments on Enceladus, Europa, Mars, and Titan. Despite the diversity of these environments, sample processing approaches all tend to be more complex than those that have been implemented on missions or envisioned for mission concepts to date. The approaches considered by workshop breakout groups progress from nondestructive to destructive measurement techniques, and most involve the need for fluid (especially liquid) sample processing. Sample processing needs were identified as technology gaps. These gaps include technology and associated sampling strategies that allow the preservation of the thermal, mechanical, and chemical integrity of the samples upon acquisition; and to optimize the sample information obtained by operating suites of instruments on common samples. Crucially, the interplay between science-driven life-detection strategies and their technological implementation highlights the need for an unprecedented level of payload integration and extensive collaboration between scientists and engineers, starting from concept formulation through mission deployment of life-detection instruments and sample processing systems.