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Purpose: To investigate the psychosocial and behavioral impact of oligodontia across three presentation types and determine if presentation type can infer impact. Materials and Methods: Thirty patients who had been diagnosed and treated for oligodontia between 2006 and 2021 were identified from hospital records. Patients received two questionnaires: (1) a modified version of a condition-specific questionnaire--the Cleft Research Questionnaire (CRQ), used to investigate demographic, life, and treatment details and impacts--and (2) the Oral Health Impact Profile (OHIP-14), used to investigate the oral health-related quality of life. Patients were assigned to three presentations (Types 1 to 3) of oligodontia, identified according to the edentulous space present and complexity of prosthodontic treatment required. The hypothesis that there is a relationship between oligodontia type and study variables was tested. Results: Twenty-two questionnaires were completed and returned. There were 13 men and 9 women. The age range was from 16 to 32 years. In total, 18 patients had nonsyndromic oligodontia and 4 had oligodontia associated with anhidrotic ectodermal dysplasia (AED). The main areas of impact were patient-reported: life less satisfying (64.5%, n = 14; pretreatment), making friends (45%, n = 10), school participation (45%, n = 10), and public speaking (45%, n = 10). No relationship was discovered between the degree of physical effect of the presentation type and study variables, including the degree of psychosocial impact or life satisfaction. Conclusions: Oligodontia can have a negative functional and social impact on a patient prior to prosthodontic treatment. Prosthodontic treatment improved the life satisfaction for most patients. Psychosocial outcomes could not be inferred by the presentation type of oligodontia. [ABSTRACT FROM AUTHOR]

All 32 Brazilian species of Parodia Speg (Cactaceae) occurring in Rio Grande do Sul State are considered threatened, according to the IUCN criteria. Until 2021, Parodia rechensis (CR) was known by only two small populations. However, a new population with over 400 individuals was discovered in 2021, prompting the study of its reproductive biology as a way to promote its conservation. Anthesis, breeding system, and natural pollination were studied in the field. The breeding system was studied by applying controlled pollination treatments to plants excluded from pollinators (bagged). Germination features were studied at the Seed Bank of the Porto Alegre Botanical Garden under controlled temperatures (20, 25, and 30 °C). The anthesis is diurnal and lasts for up to four days. The flowers offer pollen as the sole resource to the pollinators. The study species is unable to set fruit and seed without the agency of pollinators and has self-incompatible (unable to set fruit and seeds when pollinated with pollen of the same individual) characteristics that can considerably restrict its reproduction. Native bees of Halictidae and Apidae (Hymenoptera) are the main pollinators, with a smaller contribution of Melyridae (Coleoptera) and Syrphidae (Diptera). Natural fruit set is moderate (≤64%, per individual), but the species presents vegetative growth, producing several branches from the mother plant. Seeds showed the optimum germination rate at 20 °C and an inhibition of 75% in germinability at 30 °C. Our findings suggest the need to manage the species' habitat to guarantee the permanency of the plants and healthy populations of pollinators as well. Our findings raise concerns about the germination and establishment of new individuals in the context of rising temperatures caused by climate change. Suggestions for the possible management of the extant populations are made. [ABSTRACT FROM AUTHOR]

Reproductive isolation is one of the mechanisms of speciation. The two currently accepted subspecies of Parodia haselbergii (P. haselbergii subsp. haselbergii and P. haselbergii subsp. graessneri) were studied regarding flower traits, phenology, breeding systems and pollination. In addition, a principal component analysis with 18 floral characters and germination tests under controlled conditions were performed for both taxa. Pollination was studied in the field, in two localities of Southern Brazil. Pollinators were recorded through photos and film. Breeding system experiments were performed by applying controlled pollinations to plants excluded from pollinators. Both taxa mostly differ in asynchronous flowering periods, floral traits (including floral part measurements and nectar concentration) and pollinators. The flowers of both subspecies are functionally protogynous and perform remarkably long lifespans (≥ 15 days), both traits being novelties for Cactaceae. Whereas the reddish flowers of P. haselbergii subsp. haselbergii (nectar concentration: ca. 18%) are pollinated by hummingbirds of Thalurania glaucopis, the greenish flowers of P. haselbergii subsp. graessneri (nectar concentration: ca. 29%) are pollinated by Augochlora bees (Halictidae). Both subspecies are self-compatible, yet pollinator-dependent. The principal component analysis evidenced that both subspecies are separated, regarding flower traits. The seeds of both subspecies performed differently in the germination tests, but the best results were recovered at 20 °C and germination considerably decreased around 30 °C. In conclusion, all these results support that both taxa are in reproductive isolation, and can be treated as different species. [ABSTRACT FROM AUTHOR]

Antibiotic misuse in Romania has exacerbated the issue of antibiotic resistance, as patients often use antibiotics without proper medical consultation. This study aimed to assess the resistance of prevalent bacteria to different antibiotics. In this observational study conducted over six months, we analyzed 31 pediatric patients aged from 12 days to 13 years using the disk diffusion method. We identified 31 bacterial isolates, including 8 Gram-negative and 8 Gram-positive strains, with the most common being Pseudomonas aeruginosa, Escherichia coli, Streptococcus pneumoniae, methicillin-resistant Staphylococcus aureus, Streptococcus species, and Elizabethkingia meningoseptica. Our findings revealed that the most effective antibiotics were linezolid, ertapenem, and teicoplanin. In contrast, nearly all tested bacteria exhibited resistance to penicillin, followed by oxacillin and ampicillin. Resistance to cephalosporins varied with generation, showing higher resistance to lower-generation cephalosporins. The study highlights significant antibiotic resistance among common bacterial pathogens in Romanian pediatric patients, emphasizing the urgent need for controlled antibiotic use and alternative treatment strategies to combat this growing issue. Effective antibiotics such as linezolid and ertapenem offer potential solutions, whereas reliance on penicillin and lower-generation cephalosporins is increasingly futile. [ABSTRACT FROM AUTHOR]

Traditional theories of the nuclear magnetic resonance (NMR) autocorrelation function for intra-molecular dipole pairs assume a single-exponential decay, yet the calculated autocorrelation of realistic systems displays a rich, multi-exponential behavior, resulting in anomalous NMR relaxation dispersion (i.e., frequency dependence). We develop an approach to model and interpret the multi-exponential intra-molecular autocorrelation using simple, physical models within a rigorous statistical mechanical development that encompasses both rotational diffusion and translational diffusion in the same framework. We recast the problem of evaluating the autocorrelation in terms of averaging over a diffusion propagator whose evolution is described by a Fokker–Planck equation. The time-independent part admits an eigenfunction expansion, allowing us to write the propagator as a sum over modes. Each mode has a spatial part that depends on the specified eigenfunction and a temporal part that depends on the corresponding eigenvalue (i.e., correlation time) with a simple, exponential decay. The spatial part is a probability distribution of the dipole pair, analogous to the stationary states of a quantum harmonic oscillator. Drawing inspiration from the idea of inherent structures in liquids, we interpret each of the spatial contributions as a specific molecular mode. These modes can be used to model and predict the NMR dipole–dipole relaxation dispersion of fluids by incorporating phenomena on the molecular level. We validate our statistical mechanical description of the distribution in molecular modes with molecular dynamics simulations interpreted without any relaxation models or adjustable parameters: the most important poles in the Padé–Laplace transform of the simulated autocorrelation agree with the eigenvalues predicted by the theory. [ABSTRACT FROM AUTHOR]

To maximize the capabilities of minimally invasive implantable bioelectronic devices, we must deliver large amounts of power to small implants; however, as devices are made smaller, it becomes more difficult to transfer large amounts of power without a wired connection. Indeed, recent work has explored creative wireless power transfer (WPT) approaches to maximize power density [the amount of power transferred divided by receiver footprint area (length × width)]. Here, we analyzed a model for WPT using magnetoelectric (ME) materials that convert an alternating magnetic field into an alternating voltage. With this model, we identify the parameters that impact WPT efficiency and optimize the power density. We find that improvements in adhesion between the laminated ME layers, clamping, and selection of material thicknesses lead to a power density of 3.1 mW/mm2, which is over four times larger than previously reported for mm-sized wireless bioelectronic implants at a depth of 1 cm or more in tissue. This improved power density allows us to deliver 31 and 56 mW to 10 and 27-mm2 ME receivers, respectively. This total power delivery is over five times larger than similarly sized bioelectronic devices powered by radiofrequency electromagnetic waves, inductive coupling, ultrasound, light, capacitive coupling, or previously reported magnetoelectrics. This increased power density opens the door to more power-intensive bioelectronic applications that have previously been inaccessible using mm-sized battery-free devices. [ABSTRACT FROM AUTHOR]

Word embeddings are a fundamental tool in natural language processing. Currently, word embedding methods are evaluated on the basis of empirical performance on benchmark data sets, and there is a lack of rigorous understanding of their theoretical properties. This paper studies word embeddings from a statistical theoretical perspective, which is essential for formal inference and uncertainty quantification. We propose a copula-based statistical model for text data and show that under this model, the now-classical Word2Vec method can be interpreted as a statistical estimation method for estimating the theoretical pointwise mutual information (PMI). We further illustrate the utility of this statistical model by using it to develop a missing value-based estimator as a statistically tractable and interpretable alternative to the Word2Vec approach. The estimation error of this estimator is comparable to Word2Vec and improves upon the truncation-based method proposed by Levy and Goldberg (Adv. Neural Inf. Process. Syst., 27, 2177–2185 2014). The resulting estimator also is comparable to Word2Vec in a benchmark sentiment analysis task on the IMDb Movie Reviews data set and a part-of-speech tagging task on the OntoNotes data set. [ABSTRACT FROM AUTHOR]

Background: Alzheimer's disease (AD) is the most common neurodegenerative disorder in patient demographics over 65 years old causing debilitating cognitive impairment. Most commonly, AD is diagnosed clinically as "probable AD", and definitive diagnosis is confirmed through postmortem brain autopsies to detect extracellular amyloid-β (Aβ) plaques and intraneuronal hyperphosphorylated tau tangles. The exact mechanism causing AD is still unknown, but treatments for AD have been actively investigated. Currently, immunotherapies have shown substantial promise in reducing the pathologic and clinical signs of AD. Objective: This review aims to evaluate passive immunotherapies deemed to have promise for further development and use in the treatment of AD. Methods: Immunotherapies were selected via a narrative review of medications that have potential clinical effectiveness with a status of FDA accepted, FDA fast-track, FDA status pending, or emerging therapies poised to pursue FDA approval. Results: This review has yielded two anti-Aβ monoclonal antibodies (mAb) that are currently fully FDA approved, one mAb granted FDA fast-track status, two therapies on hold, three discontinued medications, and three promising emerging therapies. Conclusions: We conclude that, in the near future, passive immunotherapies will be the preferred and evidence-based method of treatment for AD with the presence of brain Aβ deposits for both symptom management and potential slowing of disease progression. Specifically, lecanemab and donanemab will require further clinical studies to optimize patient selection based on safety profiles. Despite some key limitations, these two drugs are paving the way for disease-modifying treatments in patients displaying early signs of amyloid pathology. [ABSTRACT FROM AUTHOR]

Summary: Cis‐regulatory elements (CREs) are integral to the spatiotemporal and quantitative expression dynamics of target genes, thus directly influencing phenotypic variation and evolution. However, many of these CREs become highly susceptible to transcriptional silencing when in a transgenic state, particularly when organised as tandem repeats. We investigated the mechanism of this phenomenon and found that three of the six selected flower‐specific CREs were prone to transcriptional silencing when in a transgenic context. We determined that this silencing was caused by the ectopic expression of non‐coding RNAs (ncRNAs), which were processed into 24‐nt small interfering RNAs (siRNAs) that drove RNA‐directed DNA methylation (RdDM). Detailed analyses revealed that aberrant ncRNA transcription within the AGAMOUS enhancer (AGe) in a transgenic context was significantly enhanced by an adjacent CaMV35S enhancer (35Se). This particular enhancer is known to mis‐activate the regulatory activities of various CREs, including the AGe. Furthermore, an insertion of 35Se approximately 3.5 kb upstream of the AGe in its genomic locus also resulted in the ectopic induction of ncRNA/siRNA production and de novo methylation specifically in the AGe, but not other regions, as well as the production of mutant flowers. This confirmed that interactions between the 35Se and AGe can induce RdDM activity in both genomic and transgenic states. These findings highlight a novel epigenetic role for CRE–CRE interactions in plants, shedding light on the underlying forces driving hypermethylation in transgenes, duplicate genes/enhancers, and repetitive transposons, in which interactions between CREs are inevitable. [ABSTRACT FROM AUTHOR]

Complex motor stereotypies are rhythmic, repetitive, fixed, and non-goal directed movements (e.g., bilateral flapping/waving movements of the hands/arms). Movements typically begin in early childhood and can occur in otherwise normally developing ("primary") or autistic ("secondary") children. Stereotypies persist, occur multiple times a day, have prolonged durations, can be socially stigmatizing, and may lead to bullying and isolation. Prior behavioral treatment studies have focused on older children (ages 6–12) and report modest reductions in stereotypy (i.e., between 14% and 33%). The current study involves the functional assessment and treatment of five children with Primary Complex Motor Stereotypy using a modified awareness training procedure, differential reinforcement of other behavior, and schedule thinning in a nonconcurrent multiple baseline design. Results suggest a 99% reduction of motor stereotypy from baseline across all participants. [ABSTRACT FROM AUTHOR]

Background: Post‐infectious disorders of gut‐brain interaction (PI‐DGBI) have significant impact on children and adolescents. The effect of COVID‐19 on PI‐DGBI‐associated symptoms in this population, however, is unknown. Methods: We performed electronic medical record searches to identify patients 8–17 years old with a SARS‐CoV2 PCR test at Lurie Children's Hospital between November 2020 and March 2021 (cohort 1) and April–October 2021 (cohort 2). Questionnaires were administered to assess symptoms prior to and 3 months following the test. This included the Pediatric Eosinophilic Esophagitis Symptom Score (PEESS), questionnaire of pediatric gastrointestinal symptoms—Rome IV, Nausea Profile (NP), dyspepsia symptom survey (DSS), nausea severity profile (NSP), and Pediatric Quality of Life Inventory (PedsQL). We grouped patients based on the presence of symptoms prior to COVID‐19 test or the test result. Results: One hundred and ninety‐six parent(s) or guardian(s) in cohort 1 and 274 in cohort 2 completed surveys and self‐reported their child's COVID‐19 result. Cohort 1 had increased PEESS and DSS scores, lower PedsQL scores, and increased frequency of abdominal pain disorders among patients with symptoms prior to COVID‐19 testing. Both cohorts had increased NP and NSP scores among patients with symptoms prior to COVID‐19 testing that was highest among patients with a positive COVID‐19 test. Abdominal pain and diarrhea prior to COVID‐19 testing predicted higher NP scores. Conclusions: Among symptomatic COVID‐19 tested children, we found increased severity of nausea‐associated somatic, emotional, and gastrointestinal symptoms in the 3 months following the test that was most increased among patients with a positive COVID‐19 test. [ABSTRACT FROM AUTHOR]

Artificial Intelligence (AI) is transforming systematic reviews (SRs) in health research by automating processes such as study screening, data extraction, and quality assessment. This perspective highlights recent advancements in AI tools that enhance efficiency and accuracy in SRs. It discusses the benefits, challenges, and future directions of AI integration, emphasising the need for human oversight to ensure the reliability of AI outputs in evidence synthesis and decision-making in healthcare. [ABSTRACT FROM AUTHOR]

Giardia duodenalis, an important zoonotic protozoan parasite, adheres to host intestinal epithelial cells (IECs) via the ventral disc and causes giardiasis characterized mainly by diarrhea. To date, it remains elusive how excretory-secretory products (ESPs) of Giardia enter IECs and how the cells respond to the entry. Herein, we initially demonstrated that ESPs evoked IEC endocytosis in vitro. We indicated that ESPs contributed vitally in triggering intrinsic apoptosis, pro-inflammatory responses, tight junction (TJ) protein expressional changes, and autophagy in IECs. Endocytosis was further proven to be implicated in those ESPs-triggered IEC responses. Ten predicted virulent excretory-secretory proteins of G. duodenalis were investigated for their capability to activate clathrin/caveolin-mediated endocytosis (CME/CavME) in IECs. Pyridoxamine 5'-phosphate oxidase (PNPO) was confirmed to be an important contributor. PNPO was subsequently verified as a vital promoter in the induction of giardiasis-related IEC apoptosis, inflammation, and TJ protein downregulation. Most importantly, this process seemed to be involved majorly in PNPO-evoked CME pathway, rather than CavME. Collectively, this study identified Giardia ESPs, notably PNPO, as potentially important pathogenic factors during noninvasive infection. It was also noteworthy that ESPs-evoked endocytosis might play a role in triggering giardiasis-inducing cellular regulation. These findings would deepen our understanding about the role of ESPs, notably PNPO, in the pathogenesis of giardiasis and the potential attributed endocytosis mechanism. [ABSTRACT FROM AUTHOR]

Harmful algal blooms (HABs) degrade water quality through the production of potent toxins that pose critical management challenges, especially in waterscarce regions. This study examined how dissolved oxygen (DO) conditions at the sediment–water interface in reservoirs in Southern California, United States, affect internal nutrient loading, which can promote HABs through the release of nutrients and metals from sediment to overlaying water. Replicate 2-liter laboratory chamber experiments with minimally disturbed sediment and bottom water from shallow, hypereutrophic Lake Henshaw and moderately deep, meso-eutrophic Lake Wohlford were conducted at ~25°C for ~30  days under oxic (~ 8 mg/L DO), hypoxic (< 2  mg/L DO), and anoxic (0  mg/L DO) conditions. Anoxic conditions in Lake Henshaw chambers resulted in elevated fluxes of ammonia (366 mg-N/m² ·d) and soluble reactive phosphorus (122 mg-P/m² ·d) from sediment, while hypoxic conditions promoted the flux of manganese (14.9 mg/m² ·d), iron (3.3 mg/m² ·d), and some SRP (44 mg-P/m² ·d). In Lake Wohlford, anoxic conditions resulted in sediment release of ammonia (82 mg-N/m² ·d), soluble reactive phosphorus (67  mg-P/m² ·d), manganese (24  mg/m² ·d) and iron (1.9  mg/m² ·d). Under oxic and hypoxic conditions, Lake Henshaw sediments exhibited some release of ammonia and soluble reactive phosphorus, while Lake Wohlford sediments exhibited negligible release. After adjusting for temperature, Lake Wohlford anoxic fluxes of ammonia and soluble reactive phosphorus appear consistent with other eutrophic systems (4–60  mg-N/m² ⋅d and 10–53  mg-P/m² ⋅d), while Lake Henshaw anoxic fluxes appear rather extreme. Results from Lake Henshaw suggest that different nitrogen to phosphorus ratios were released from sediment to overlaying water under hypoxia (very low ratio plus iron) versus anoxia (low ratio with high nutrient levels). This in turn could affect phytoplankton community composition and toxin production. Results are being used to help inform management strategies, such as dissolved oxygen or sediment amendments, to control internal nutrient loading and reduce HAB toxin production. [ABSTRACT FROM AUTHOR]

Objective: To obtain physicians' "real-world" perspectives on early experiences with triamcinolone acetonide suprachoroidal injection (SCS-TA) for treatment of patients with uveitic macular edema (UME). Results: Twelve retina/uveitis specialists in the United States were surveyed about SCS-TA injection procedure and patient outcomes. Survey participants administered ≥ 291 SCS-TA injections to 243 patients with UME with various disease characteristics (etiologies, chronicity, and anatomical subtypes). Commonly reported reasons for SCS-TA adoption included potential for lowering the risk of steroid-associated intraocular pressure elevations versus intravitreal injections or implants (100%), potential for longer duration of action versus intravitreal steroid injections or implants (92%), and desire to use a new delivery modality (83%). Nearly all participants (92%) found injection procedure relatively easy post-training, with most (75%) procedurally comfortable after completing 2–5 injections. 58% of participants indicated that their patients gained 2–3 lines of vision by first follow-up visit, and 92% reported having patients who experienced 100–150 μm or greater reduction in central subfield thickness. Overall, 92% of participants were satisfied with SCS-TA treatment outcomes. Findings from this survey of early adopters of SCS-TA indicate that the suprachoroidal injection technique was easy to learn and resulted in favorable patient outcomes consistent with clinical trial data. [ABSTRACT FROM AUTHOR]

Background: Pelvic organ prolapse (POP) increases in incidence and severity with aging. At least 1 in 4 women seek pelvic floor care and many more suffer with concurrent symptoms of bowel, bladder and sexual dysfunction, which can have a large impact on quality of life. It is estimated that 1 in 5 women will undergo surgery for POP. POP is difficult to cure with existing surgeries and therefore treatment failure and reoperations are common. Surgical innovation in this area is urgently needed and we have developed a novel technique of bilateral sacrospinous vaginal vault fixation with synthetic mesh arms (BSSVF-M). Based on preliminary studies it may be more successful, durable and cost-effective than standard sacrospinous ligament suspension with sutures (SSLS). Preliminary development and exploration studies showed safety and efficacy of BSSVF-M. Following an established framework for research in surgical innovations, we now wish to conduct a randomized comparative effectiveness trial for assessment of this novel technique. Methods: This is a multi-center randomized controlled trial in Canada comparing the surgical techniques of BSSVF-M vs. SSLS to address apical prolapse. In total, 358 women with symptomatic POP at five centers will be randomized with 80% power to detect a 15% difference in primary composite outcome and accounting for a 15% loss to follow-up over 2 years. The primary objective is to investigate BSSVF-M vs. SSLS using an established composite of 3 objective signs and 1 subjective symptom of POP measured 2 years postoperatively. Secondary objectives: 1) To determine changes in condition-specific pelvic symptoms, quality of life, pain and condition-specific body image post BSSVF-M vs. SSLS using validated questionnaires; 2) To determine changes in sexuality post BSSVF-M vs. SSLS; 3) To determine global impression of improvement, adverse events (validated classification scheme), reoperations and health utility post BSSVF-M vs. SSLS; 4) To determine the cost-effectiveness of BSSVF-M vs SSLS. Study Registration at clinicaltrials.gov (NCT02965313). Discussion: There is a need for innovation to improve the surgical approach to vaginal apical suspension. Despite controversies with mesh, it has been shown to be safe when used appropriately and to have higher durability when compared with sutures. As well, the importance of restoring anatomy and tension-free surgical approach in pelvic reconstructive surgery has led to better long-term outcomes and fewer side effects. These principles have been applied when developing the novel BSSVF-M technique. Anticipated challenges of this trial include recruitment, compliance problems and loss to follow up However, the robust methodology will provide evidence on the best surgical approach to correct POP, a common condition among aging women. [ABSTRACT FROM AUTHOR]

Obesity is a major public health crisis in the United States (US) affecting 42% of the population, exacerbating a spectrum of other diseases and contributing significantly to morbidity and mortality overall. Recent advances in pharmaceutical interventions, particularly glucagon-like peptide-1 (GLP-1) receptor agonists (e.g., semaglutide, liraglutide) and dual gastric inhibitory polypeptide and GLP-1 receptor agonists (e.g., tirzepatide), have shown remarkable efficacy in weight-loss. However, limited access to these medications due to high costs and insurance coverage issues restricts their utility in mitigating the obesity epidemic. We quantify the annual mortality burden directly attributable to limited access to these medications in the US. By integrating hazard ratios of mortality across body mass index categories with current obesity prevalence data, combined with healthcare access, willingness to take the medication, and observed adherence to and efficacy of the medications, we estimate the impact of making these medications accessible to all those eligible. Specifically, we project that with expanded access, over 42,000 deaths could be averted annually, including more than 11,000 deaths among people with type 2 diabetes. These findings underscore the urgent need to address barriers to access and highlight the transformative public health impact that could be achieved by expanding access to these novel treatments. [ABSTRACT FROM AUTHOR]

Background: PLA2G6-associated neurodegeneration (PLAN) comprises three diseases with overlapping features: infantile neuroaxonal dystrophy (INAD), atypical neuroaxonal dystrophy (atypical NAD), and PLA2G6-related dystonia-parkinsonism. INAD is an early onset disease characterized by progressive loss of vision, muscular control, and mental skills. The prevalence of PLA2G6-associated diseases has not been previously calculated. Methods: To provide the most accurate prevalence estimate, we utilized two independent approaches: database-based approach which included collecting variants from ClinVar, Human Gene Mutation Database (HGMD) and high confidence predicted loss-of-function (pLoF) from gnomAD (Rare Genomes Project Genetic Prevalence Estimator; GeniE), and literature-based approach which gathered variants through Mastermind Genomic Search Engine (Genomenon, Inc). Genetic prevalence of PLAN was calculated based on allele frequencies from gnomAD, assuming Hardy–Weinberg equilibrium. Results: In the PLA2G6 gene, our analysis found 122 pathogenic, 82 VUS, and 15 variants with conflicting interpretations (pathogenic vs VUS) between two approaches. Allele frequency was available for 58 pathogenic, 42 VUS, and 15 conflicting variants in gnomAD database. If pathogenic and/or conflicting variants are included, the overall genetic prevalence was estimated to be between 1 in 987,267 to 1 in 1,570,079 pregnancies, with the highest genetic prevalence in African/African-American (1 in 421,960 to 1 in 365,197) and East-Asian (1 in 683,978 to 1 in 190,771) populations. Conclusion: Our estimates highlight the significant underdiagnosis of PLA2G6-associated neurodegeneration and underscores the need for increased awareness and diagnostic efforts. Furthermore, our study revealed a higher carrier frequency of PLA2G6 variants in African and Asian populations, stressing the importance of expanded genetic sequencing in non-European populations to ensure accurate and comprehensive diagnosis. Future research should focus on confirming our findings and implementing expanded sequencing strategies to facilitate maximal and accurate diagnosis, particularly in non-European populations. [ABSTRACT FROM AUTHOR]

Background: Monocytes comprise subsets of classical, intermediate and non-classical monocytes with distinct anti- or pro-tumor effects in breast cancer (BC). They are modulated by estrogen, and can contribute to BC control by endocrine therapy in preclinical models. Methods: To elucidate whether changes in monocyte subsets are associated with treatment and response, we investigated peripheral blood samples of 73 postmenopausal women with estrogen receptor (ER) positive BC, who received aromatase inhibitor therapy with or without the mucin-1 vaccine tecemotide in the ABCSG34 trial. Blood was retrieved at baseline, midterm and end of therapy, and was analyzed for the distribution and ER expression of monocyte subsets by flow cytometry. Results: When 40 healthy, age-matched women were compared with BC patients before treatment start, ER levels of monocytes did not differ, yet patients presented with a higher frequency of classical and fewer non-classical monocytes. Endocrine therapy triggered a significant increase in ER levels in all monocyte subsets, without affecting subset distribution. Vaccination had no overall impact on subset frequency and ER expression. Yet, a shift from intermediate to classical monocytes during therapy correlated with changes in plasma cytokines and chemokines and was significantly associated with low residual cancer burden in vaccinated patients. Without tecemotide, baseline ER levels in classical monocytes were significantly higher in women with good response to endocrine therapy. Conclusions: This study identified classical monocytes to be associated with ER positive BC and with patient response to neoadjuvant endocrine treatment and cancer vaccination. [ABSTRACT FROM AUTHOR]

Background: Bidirectional crosstalk between HER2 and estrogen receptor (ER) pathways may influence outcomes and the efficacy of endocrine therapy (ET). Low HER2 expression levels (HER2-low) have emerged as a predictive biomarker in patients with breast cancer (BC). Methods: PALLAS is an open, international, phase 3 study evaluating the addition of palbociclib for 2 years to adjuvant ET in patients with stage II-III ER-positive/HER2-negative BC. To assess the impact of HER2 expression on patient outcomes in the phase III PALLAS trial, we analyzed (1) the association between rate of HER2-low with demographic and clinicopathological parameters, (2) the prognostic value of HER2-low status on invasive disease-free survival (iDFS), distant relapse-free survival (DRFS), and overall survival (OS) and (3) HER2 expression's value as a predictive biomarker of response to palbociclib. HER2-low was defined as HER2 immunohistochemistry (IHC) 1 + or IHC 2 + with negative in situ hybridization (ISH). All pathologic evaluation was performed locally. Prognostic and predictive power of HER2 were assessed with Cox models. Results: From the original PALLAS intention-to-treat population (N = 5753), 5304 patients (92.2%) were included in this analysis. Among these, 2254 patients (42.5%) were classified as having HER2 IHC 0 (HER2-0), and 3050 (57.5%) as having HER2-low disease (1838 with IHC 1 + and 1212 with IHC 2 +). Median follow-up was 59.8 months. HER2-low prevalence varied significantly across 21 participating countries (range 16.7% to 75.6%; p < 0.001) and was more frequent in patients enrolled in North America (63.1%) than in Europe (53.4%) or other regions (53.4%) (p < 0.001). HER2 status was not significantly associated with iDFS in a multivariable Cox model (hazard ratio 0.93, 95% confidence interval 0.81 – 1.06). No significant interaction was observed between treatment arm and HER2 status for iDFS (p = 0.43). Similar results were obtained for DRFS and OS. Conclusions: In this large, prospective, global patient cohort, no differences were observed in clinical parameters, prognosis, or differential benefit from palbociclib between HER2-0 and HER2-low tumors. Significant geographic variability was observed in the prevalence of HER2-low status, suggesting a high degree of variation in pathologic assessment of HER2 expression without impact on outcomes. [ABSTRACT FROM AUTHOR]

cis,cis-Muconic acid (MA) is a bio-based chemical that can be converted to direct replacement chemicals or performance-advantaged bioproducts. We recently engineered the bacterium Pseudomonas putida KT2440 for the co-utilization of glucose and xylose to produce MA. This study evaluates the effect of additional genetic modifications, media composition, and bioprocess strategy on MA titer, productivity, and yield in bioreactor cultivations. We achieve a MA titer of 47.2 g L−1, a productivity of 0.49 g L−1 h−1, and a yield of 0.50 C-mol C-mol−1 from glucose and xylose supplemented with 5% (v/v) corn steep liquor with a P. putida strain harboring the deletion of gacS. Additionally, we demonstrate efficient MA production from corn stover-derived sugars and scalability to 150 L bioreactors. Techno-economic analysis and life cycle assessment predict that adipic acid, derived from catalytic hydrogenation of MA, can achieve a selling price as low as $2.60 per kg, approaching cost parity and reducing greenhouse gas emissions by up to 80% relative to fossil carbon-based adipic acid. [ABSTRACT FROM AUTHOR]

Aim: Following the Hamas terror attack on Israeli towns on October 2023, 250 individuals were taken into captivity. On November–December 2023, during the cease‐fire deal, 26 women and children were released. This study is the first to describe the physical and behavioural findings in children and their mothers in the immediate phase of returning home from captivity. Methods: This is a retrospective study describing the clinical characteristics of the returnees after 49–53 days in captivity. Patients were admitted to a designated unit in the Schnieder Children's Medical Center of Israel on November–December 2023. The hospitalisation duration was 1–9 days. All patients were evaluated according to a detailed protocol and were treated respectively. Results: Patient population included 19 children (ranged 2–18 years old) and 7 women (ranged 34–78 years old). The most common clinical findings upon return included significant weight loss, psychological trauma, complications of poor hygiene and complications of recent shrapnel injuries. Microbiology tests were positive for multiple gastrointestinal pathogens. Serologic screening tests were positive for various infectious diseases. Conclusion: Clinical findings in this time period were diverse and required the attention of a multidisciplinary team. Long term clinical and psychological effects are yet to be known. [ABSTRACT FROM AUTHOR]

A strong connection between schools and families is vital for student success and well-being. Previous studies on school–family relationships found that open communication between parties may aid in supporting students' needs and ability to attend school. In this paper, authors analyze how leveraging relationships to gain an increased understanding of a family's attendance barriers is more beneficial than relationships built on accountability. From interviews with 38 caregivers, 29 students, and 40 staff members in an urban school district with high rates of chronic absenteeism, authors found that efforts to build relationships with families focused on accountability and caregiver education about their children's attendance and the importance of attending school. Families sometimes perceived these efforts as superficial and ineffective. Authors discuss how school districts and key school personnel, such as social workers, can intentionally use the power of relationships to identify student and family needs and connect them with resources. [ABSTRACT FROM AUTHOR]

Background: Finding the best energy and protein dose and timing for critically ill patients remains challenging. Distinct populations may react differently to protein load. This study aimed to characterize and predict outcomes of critically ill patients who received moderate energy and high or low protein doses during their stay in the intensive care unit (ICU). Methods: The cohort included 646 adult patients (70% men and 30% women) hospitalized in Beilinson Hospital ICU (Petah Tikva, Israel) for over 5 days between 2011 and 2018. Patients received 10–20 kcal/kg/day and were classified into two groups: low (LP) and high (HP) protein support (≤1 g/kg/day vs. >1 g/kg/day), the LP group comprising 531 patients (82%) and the HP group 115 patients (18%). Multiple logistic regression was used to describe associations between patients' characteristics and 90-day survival in the LP and HP groups. Results: Among LP, increased age, APACHE II, and receiving supplemental parenteral nutrition (SPN) were associated with decreased survival (OR = 0.986, 95% CI [0.973, 0.999]; OR = 0.915, 95% CI [0.886, 0.944], OR = 0.579, 95% CI [0.366, 0.917]). Trauma admission was associated with increased survival (OR = 1.826, 95% CI [1.001, 3.329]). Among HP, increased age was associated with decreased survival (OR = 0.956, 95% CI [0.924, 0.998]). Higher BMI was associated with improved survival (OR = 1.137, 95% CI [1.028, 1.258]). Likewise, in the HP group, the BMI of elderly survivors was higher compared to non-survivors (27.1 ± 6.2 vs. 24.7 ± 4.8, t (113) = 2.3, p < 0.05). Conclusions: Our results show that in patients with moderate energy support and low protein administration, survivors were younger, with a lower APACHE II score, mainly suffering from trauma and without renal failure. In the patients receiving high protein support, younger patients with a high BMI not suffering from sepsis were more likely to survive. We suggest confirming these findings with prospective RCTs. [ABSTRACT FROM AUTHOR]

Zebrafish (Danio rerio) is an important animal model for a wide range of neurodegenerative diseases. However, obtaining the cellular resolution that is essential for studying the zebrafish brain remains challenging as it requires high spatial resolution and signal-to-noise ratios (SNR). In the current study, we present the first MRI results of the zebrafish brain at the state-of-the-art magnetic field strength of 28.2 T. The performance of MRI at 28.2 T was compared to 17.6 T. A 20% improvement in SNR was observed at 28.2 T as compared to 17.6 T. Excellent contrast, resolution, and SNR allowed the identification of several brain structures. The normative T1 and T2 relaxation values were established over different zebrafish brain structures at 28.2 T. To zoom into the white matter structures, we applied diffusion tensor imaging (DTI) and obtained axial, radial, and mean diffusivity, as well as fractional anisotropy, at a very high spatial resolution. Visualisation of white matter structures was achieved by short-track track-density imaging by applying the constrained spherical deconvolution method (stTDI CSD). For the first time, an algorithm for stTDI with multi-shell multi-tissue (msmt) CSD was tested on zebrafish brain data. A significant reduction in false-positive tracks from grey matter signals was observed compared to stTDI with single-shell single-tissue (ssst) CSD. This allowed the non-invasive identification of white matter structures at high resolution and contrast. Our results show that ultra-high field DTI and tractography provide reproducible and quantitative maps of fibre organisation from tiny zebrafish brains, which can be implemented in the future for a mechanistic understanding of disease-related microstructural changes in zebrafish models of various brain diseases. [ABSTRACT FROM AUTHOR]

In recent decades, inland water remote sensing has seen growing interest and very strong development. This includes improved spatial resolution, increased revisiting times, advanced multispectral sensors and recently even hyperspectral sensors. However, inland waters are more challenging than oceanic waters due to their higher complexity of optically active constituents and stronger adjacency effects due to their small size and nearby vegetation and built structures. Thus, bio-optical modeling of inland waters requires higher ground-truthing efforts. Large-scale ground-based sensor networks that are robust, self-sufficient, non-maintenance-intensive and low-cost could assist this otherwise labor-intensive task. Furthermore, most existing sensor systems are rather expensive, precluding their employability. Recently, low-cost mini-spectrometers have become widely available, which could potentially solve this issue. In this study, we analyze the characteristics of such a mini-spectrometer, the Hamamatsu C12880MA, and test it regarding its application in measuring water-leaving radiance near the surface. Overall, the measurements performed in the laboratory and in the field show that the system is very suitable for the targeted application. [ABSTRACT FROM AUTHOR]

Toll‐like receptor 2 (TLR2) belongs to the TLR protein family that plays an important role in the immune and inflammation response system. While TLR2 is predominantly expressed in immune cells, its expression has also been detected in the brain, specifically in microglia and astrocytes. Recent studies indicate that genomic deletion of TLR2 can result in impaired neurobehavioural function. It is currently not clear if the genomic deletion of TLR2 leads to any alterations in the microstructural features of the brain. In the current study, we noninvasively assess microstructural changes in the brain of TLR2‐deficient (tlr2−/−) zebrafish using state‐of‐the art magnetic resonance imaging (MRI) methods at ultrahigh magnetic field strength (17.6 T). A significant increase in cortical thickness and an overall trend towards increased brain volumes were observed in young tlr2−/− zebrafish. An elevated T2 relaxation time and significantly reduced apparent diffusion coefficient (ADC) unveil brain‐wide microstructural alterations, potentially indicative of cytotoxic oedema and astrogliosis in the tlr2−/− zebrafish. Multicomponent analysis of the ADC diffusivity signal by the phasor approach shows an increase in the slow ADC component associated with restricted diffusion. Diffusion tensor imaging and diffusion kurtosis imaging analysis revealed diminished diffusivity and enhanced kurtosis in various white matter tracks in tlr2−/− compared with control zebrafish, identifying the microstructural underpinnings associated with compromised white matter integrity and axonal degeneration. Taken together, our findings demonstrate that the genomic deletion of TLR2 results in severe alterations to the microstructural features of the zebrafish brain. This study also highlights the potential of ultrahigh field diffusion MRI techniques in discerning exceptionally fine microstructural details within the small zebrafish brain, offering potential for investigating microstructural changes in zebrafish models of various brain diseases. [ABSTRACT FROM AUTHOR]

Communal coping theorists have advanced our understanding of stress management in relationships. We add to that work by exploring the content of messages that people exchange when they talk about how they coped with stress. We collected data from 39 online forums and analyzed 446 posts in which people described how they coped with sexual health stress. Results indicated the presence of five types of coping (individual coping, parallelism, communal coping, refused communal coping, reluctant communal coping), distinguished by posters' descriptions of emotions, communication, and relationships in each category. Our findings indicate the need to consider valence in the study of communal coping. [ABSTRACT FROM AUTHOR]

Copyright of Spektrum der Augenheilkunde is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

This article proposes a new mode of sensory literary history, illustrated through an attentive reading of the sonic world the chronicler Gilles li Muisis creates in his account of the plague in Tournai in 1349. It shows that the blind chronicler presents sound as operating according to a plague-like logic of contagion, as he records songs, sermons, bells, and popular speech from within the walls of his quiet Benedictine monastery. A fuller consideration of this writer's sonic environs, as well as the sound dynamics of his own compositional process, sheds new light on the auditory implications of his alternate choices of prose and verse, Latin and vernacular; and beyond the conclusions it draws about this one relatively little-known writer, it shows how more concentrated efforts at listening for medieval sonic cues can reveal significant sensory echoes in our own time. [ABSTRACT FROM AUTHOR]

For a subset of individuals known as sign‐trackers, discrete Pavlovian cues associated with rewarding stimuli can acquire incentive properties and exert control over behaviour. Because responsiveness to cues is a feature of various neuropsychiatric conditions, rodent models of sign‐tracking may prove useful for exploring the neurobiology of individual variation in psychiatric vulnerabilities. Converging evidence points towards the involvement of dopaminergic neurotransmission in the nucleus accumbens core (NAc) in the development of sign‐tracking, yet whether this phenotype is associated with specific accumbal postsynaptic properties is unknown. Here, we examined dendritic spine structural organisation, as well as presynaptic and postsynaptic markers of activity, in the NAc core of male and female rats following a Pavlovian‐conditioned approach procedure. In contrast to our prediction that cue re‐exposure would increase spine density, experiencing the discrete lever‐cue without reward delivery resulted in lower spine density than control rats for which the lever was unpaired with reward during training; this effect was tempered in the most robust sign‐trackers. Interestingly, this same behavioural test (lever presentation without reward) resulted in increased levels of a marker of presynaptic activity (synaptophysin), and this effect was greatest in female rats. Whilst some behavioural differences were observed in females during initial Pavlovian training, final conditioning scores did not differ from males and were unaffected by the oestrous cycle. This work provides novel insights into how conditioning impacts the neuronal plasticity of the NAc core, whilst highlighting the importance of studying the behaviour and neurobiology of both male and female rats. [ABSTRACT FROM AUTHOR]

Background: Secondary prevention interventions to reduce post-stroke cognitive impairment (PSCI) can be aided by the early identification of high-risk individuals who would benefit from risk factor modification. Aims: To develop and evaluate a predictive model to identify patients at increased risk of PSCI over 5 years using data easily accessible from electronic health records. Methods: Cohort study that included primary care patients from two academic medical centers. Patients were aged 45 years or older, without prior stroke or prevalent cognitive impairment, with primary care visits and an incident ischemic stroke between 2003 and 2016 (development/internal validation cohort) or 2010 and 2022 (external validation cohort). Predictors of PSCI were ascertained from the electronic health record. The outcome was incident dementia/cognitive impairment within 5 years and beginning 3 months following stroke, ascertained using International Classification of Diseases, Ninth/Tenth Revision (ICD-9/10) codes. For model variable selection, we considered potential predictors of PSCI and constructed 400 bootstrap samples with two-thirds of the model derivation sample. We ran 10-fold cross-validated Cox proportional hazards models using a least absolute shrinkage and selection operator (LASSO) penalty. Variables selected in >25% of samples were included. Results: The analysis included 332 incident diagnoses of PSCI in the development cohort (n = 3741), and 161 and 128 incident diagnoses in the internal (n = 1925) and external (n = 2237) validation cohorts, respectively. The C-statistic for predicting PSCI was 0.731 (95% confidence interval (CI): 0.694–0.768) in the internal validation cohort, and 0.724 (95% CI: 0.681–0.766) in the external validation cohort. A risk score based on the beta coefficients of predictors from the development cohort stratified patients into low (0–7 points), intermediate (8–11 points), and high (12–23 points) risk groups. The hazard ratios (HRs) for incident PSCI were significantly different by risk categories in internal (high, HR: 6.2, 95% CI: 4.1–9.3; Intermediate, HR: 2.7, 95% CI: 1.8–4.1) and external (high, HR: 6.1, 95% CI: 3.9–9.6; Intermediate, HR: 2.8, 95% CI: 1.9–4.3) validation cohorts. Conclusion: Five-year risk of PSCI can be accurately predicted using routinely collected data. Model output can be used to risk stratify and identify individuals at increased risk for PSCI for preventive efforts. Data access statement: Mass General Brigham data contain protected health information and cannot be shared publicly. The data processing scripts used to perform analyses will be made available to interested researchers upon reasonable request to the corresponding author. [ABSTRACT FROM AUTHOR]

Opioid-related deaths continue to rise and a sizable proportion of people who present the greatest risk for fatal overdose are admitted to local detention centers. Despite the evidence demonstrating the effectiveness of medication to address the symptoms of opioid use disorder and the recent legal decisions (Department of Justice, 2022) mandating access, this treatment is only available in about 25% of jails in the US and most of them are located in urban or semi-urban areas. The current study was designed to better understand the steps that need to be taken to implement these programs in rural detention centers. Semi-structured interviews were conducted with 19 sheriffs and jail administrators across a nine-county region in southern Appalachia to identify the best pathway toward the delivery of medication for opioid use in the detention centers. Administrators' views of these programs fell on a continuum from being completely opposed to highly receptive. Qualitative analysis of the barriers to implementation also varied according to these positions. Effective approaches to facilitating the adoption of medication programs in rural jails must address administrators' views, but they must also take into account the unique characteristics of the detention center and the community in which they are located. [ABSTRACT FROM AUTHOR]

Background Methotrexate (MTX) is administered for the treatment of central nervous system (CNS) hematologic cancers, prophylaxis of CNS dissemination of certain hematological cancers, and in solid tumor leptomeningeal disease. MTX treatment can be limited by CNS toxicity. Dextromethorphan is used to treat MTX neurotoxicity, with most data derived from pediatric case series. In this report, we profile 4 adult patients who developed intrathecal (IT) MTX neurotoxicity to better characterize their response to dextromethorphan treatment. Methods A case series of 4 patients who developed neurologic symptoms attributed to IT MTX neurotoxicity subsequently treated with dextromethorphan was devised. Demographic data, clinical characteristics, electroencephalography results, magnetic resonance imaging, cerebrospinal fluid (CSF) characteristics, and dextromethorphan treatment outcomes were described. Results Of the 4 patients developing MTX neurotoxicity, neurologic symptoms developed over a timeframe of 2 to 14 days from the precedent MTX exposure. Radiologic phenotypes included subcortical white matter diffusion-restricting lesions, bi-hemispheric subcortical white matter T2-FLAIR hyperintensities, as well as other findings described in the report. Time elapsed from initiation of dextromethorphan to neurologic symptom resolution ranged from 1 to 2 days. Conclusions The profiles of 4 adult patients developing suspected IT MTX neurotoxicity syndromes with subsequent response to Dextromethorphan add further data to guide the management of such patients. [ABSTRACT FROM AUTHOR]

Copyright of Die Unfallchirurgie is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Objectives. To compare the incidence, case-hospitalization rates, and vaccination rates of COVID-19 between people experiencing sheltered homelessness (PESH) and the broader community in Chicago, Illinois, and describe the impact of a whole community approach to disease mitigation during the public health emergency. Methods. Incidence of COVID-19 among PESH was compared with community-wide incidence using case-based surveillance data from March 1, 2020, to May 11, 2023. Seven-day rolling means of COVID-19 incidence were assessed for the overall study period and for each of 6 distinct waves of COVID-19 transmission. Results. A total of 774 009 cases of COVID-19 were detected: 2579 among PESH and 771 430 in the broader community. Incidence and hospitalization rates per 100 000 in PESH were more than 5 times higher (99.84 vs 13.94 and 16.88 vs 2.14) than the community at large in wave 1 (March 1, 2020–October 3, 2020). This difference decreased through wave 3 (March 7, 2021–June 26, 2021), with PESH having a lower incidence rate per 100 000 than the wider community (8.02 vs 13.03). Incidence and hospitalization of PESH rose again to rates higher than the broader community in waves 4 through 6 but never returned to wave 1 levels. Throughout the study period, COVID-19 incidence among PESH was 2.88 times higher than that of the community (70.90 vs 24.65), and hospitalization was 4.56 times higher among PESH (7.51 vs 1.65). Conclusions. Our findings suggest that whole-community approaches can minimize disparities in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission between vulnerable populations and the broader community, and reinforce the benefits of a shared approach that include multiple partners when addressing public health emergencies in special populations. (Am J Public Health. 2024;114(S7):S590–S598. https://doi.org/10.2105/AJPH.2024.307801) [ABSTRACT FROM AUTHOR]

Socioeconomic differences among low-income and racially minoritized students may be consequential for understanding the dynamics of school choice—especially in high-poverty and racially segregated urban contexts that are often targeted by school choice policies. Yet school choice research largely focuses on differences between groups and relies on measures that broadly categorize students as low-income or not. Drawing on parent interviews in Detroit, this study describes socioeconomic differences among low-income and racially minoritized families and examines how those differences relate to their engagement in the school choice process. While families faced a similar landscape of choice, relied on similar types of resources, and did not have drastically different preferences, relative socioeconomic disadvantages translated to more constrained access and engagement in school choice. [ABSTRACT FROM AUTHOR]

To foster bottom-up innovations, health care organizations are leveraging interdisciplinary frontline innovation teams. These teams include workers across hierarchical levels and professional backgrounds, pooling diverse knowledge sources to develop innovations that improve patient and worker experiences and care quality, equity, and costs. Yet, these frontline innovation teams experience barriers, such as time constraints, being new to innovation, and team-based role hierarchies. We investigated the practices that such teams in federally qualified health centers (FQHCs) used to overcome these barriers. Our 20-month study of two FQHC innovation teams provides one of the first accounts of how practices that sustained worker engagement in innovation and supported their ideas to implementation evolve over time. We also show the varied quantity of engagement practices used at different stages of the innovation process. At a time when FQHCs face pressure to innovate amid staff shortages, our study provides recommendations to support their work. [ABSTRACT FROM AUTHOR]

Background Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) down-regulates angiotensin-converting enzyme 2, potentially increasing angiotensin II. We hypothesized that losartan compared to usual care decreases mortality and is safe in patients hospitalized with coronavirus disease 2019 (COVID-19). We aimed to evaluate the effect of losartan versus usual care on 28-day mortality in patients hospitalized for acute COVID-19. Methods Eligibility criteria included adults admitted for acute COVID-19. Exclusion criteria were hypotension, hyperkalemia, acute kidney injury, and use of angiotensin receptor blockers (ARBs) or angiotensin-converting enzyme inhibitors within 7 days. Participants were randomized to losartan 25–100 mg/day orally for the hospital duration or 3 months or the control arm (usual care) in 29 hospitals in Canada and France. The primary outcome was 28-day mortality. Secondary outcomes were hospital mortality, organ support, and serious adverse events (SAEs). Results The trial was stopped early because of a serious safety concern with losartan. In 341 patients, any SAE and hypotension were significantly higher in the losartan versus usual care groups (any SAE: 39.8% vs 27.2%, respectively, P =.01; hypotension: 30.4% vs 15.3%, respectively, P <.001) in both ward and intensive care patients. The 28-day mortality did not differ between losartan (6.5%) versus usual care (5.9%) (odds ratio, 1.11 [95% confidence interval,.47–2.64]; P =.81), nor did organ dysfunction or secondary outcomes. Conclusions Caution is needed in deciding which patients to start or continue using ARBs in patients hospitalized with pneumonia to mitigate risk of hypotension, acute kidney injury, and other side effects. ARBs should not be added to care of patients hospitalized for acute COVID-19. Clinical Trials Registration NCT04606563. [ABSTRACT FROM AUTHOR]

Enterotoxigenic Escherichia coli (ETEC) cause hundreds of millions of diarrheal illnesses annually ranging from mildly symptomatic cases to severe, life-threatening cholera-like diarrhea. Although ETEC are associated with long-term sequelae including malnutrition, the acute diarrheal illness is largely self-limited. Recent studies indicate that in addition to causing diarrhea, the ETEC heat-labile toxin (LT) modulates the expression of many genes in intestinal epithelia, including carcinoembryonic cell adhesion molecules (CEACAMs) which ETEC exploit as receptors, enabling toxin delivery. Here, however, we demonstrate that LT also enhances the expression of CEACAMs on extracellular vesicles (EV) shed by intestinal epithelia and that CEACAM-laden EV increase in abundance during human infections, mitigate pathogen-host interactions, scavenge free ETEC toxins, and accelerate ETEC clearance from the gastrointestinal tract. Collectively, these findings indicate that CEACAMs play a multifaceted role in ETEC pathogen-host interactions, transiently favoring the pathogen, but ultimately contributing to innate responses that extinguish these common infections. [ABSTRACT FROM AUTHOR]

This national cohort survey of older adults assesses which health-related concerns they consider to be most salient in the 2024 election. [ABSTRACT FROM AUTHOR]