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Objective: We aimed to determine the prevalence of self-reported swallowing difficulty (dysphagia) among older Colombians and to explore the factors associated with this condition. Methods: This study presents a secondary analysis of the SABE-Colombia survey, a cross-sectional study of community-dwelling older adults. The dependent variable was self-reported swallowing difficulty, assessed through the question: “How often do you have difficulty or discomfort swallowing?” Descriptive and bivariate analyses of the sample were performed, followed by multivariate analysis, adjusting for confounding variables. Results: The final sample included 19 004 older Colombians, whose mean age was 69 years (56% women). The overall prevalence of swallowing difficulty was 12.2%. In the multivariate analysis, significant associations were observed between swallowing difficulty and several factors, including male sex (OR 1.14, 95%CI 1.03 – 1.26), age > 80 years (OR 1.26, 95%CI 1.08 – 1.47), dependence in activities of daily living (OR 1.62, 95%CI 1.23 – 2.13), cognitive impairment (OR 1.49, 95%CI 1.30 – 1.70), depressive symptoms (OR 1.38, 95%CI 1.15 – 1.65), sarcopenia (OR 1.32, 95%CI 1.02 – 1.69), malnutrition (OR 1.35, 95%CI 1.23 – 1.49), and osteoarticular disease (OR 1.18, 95%CI 1.07 – 1.38). Conclusion: There was a high prevalence of swallowing difficulty among older community-dwelling Colombians. Our results showed a strong correlation between swallowing difficulty and risk factors such as cognitive impairment, depressive symptoms, osteoarticular disease, and dependence in activities of daily living, but not with malnutrition or sarcopenia.

This study aimed at estimating the macro- and micronutrient concentrations in leaves of Valencia oranges (Citrus sinensis [L.] Osbeck) through multiple regression analysis using multispectral images and vegetation indices (VIs) selected through the stepwise regression method. The data were collected in a commercial orchard of Valencia oranges in El Barretal, Tamaulipas, Mexico. The leaf samples were analysed in a laboratory to determine the concentrations of N, P, K, Ca, Mg, Cu, Fe, Mn, and Zn using traditional chemical methods; the relative chlorophyll values were obtained using a chlorophyll metre (SPAD502 Plus). Multi-spectral images of the tree canopy were acquired using a UAV equipped with a multispectral camera with five wavelengths (blue, green, red, red edge, and near-infrared); based on these data, 85 VIs were calculated. To select the predictor variables that were most relevant for the model, 90 candidate variables were divided into three groups with 30 VIs grouped by nutrients based on the highest and lowest absolute values found in the correlation matrix. Heteroscedasticity and autocorrelation were also assessed through the Breusch-Pagan and Durbin-Watson tests, respectively. The selected variables were used in multiple regression analysis. The resulting models were validated by mean absolute error (MAE), root-mean-square error (RMSE), mean absolute percentage error (MAPE), and coefficient of determination (${R^2}$ R 2 ). The prediction models showed satisfactory results, with values ${R^2}$ R 2 between 0.79 and 0.95 and relatively low (<10) MAE and RMSE for all nutrients, except Fe ($ \lt 30$ < 30) in all phenological stages; MAPE values were lower than 0.5% for all nutrients. This study showed that multispectral imaging combined with multiple regression analysis effectively predicts nutrient levels in the leaves of Valencia oranges in various phenological stages. This study presents a new perspective on agricultural systems, offering an effective alternative to assess the nutritional conditions of crops. [ABSTRACT FROM AUTHOR]

In view of both the latest LHCb measurement of R K ∗ and the new 2.7σ deviation reported by Belle II on B + → K + ν ν ¯ decays, we present a fit to the B meson anomalies for various one and two dimensional hypothesis including complex Wilson coefficients. We show in a model-independent way that the generic non-universal U(1)′ extensions of the SM, without flavour violation, fail to simultaneously fit those observables and corroborate that they can modify BR B + → K + ν ν ¯ up to only a 10%. In view of this deficit, we propose a new way in which those models can accommodate the data at tree level by introducing lepton flavour violating couplings and non-diagonal elements of the charged lepton mixing matrix, with implications in future charged lepton flavour violation searches. [ABSTRACT FROM AUTHOR]

OBJECTIVE: The aim of this study was to perform a systematic review of the usefulness of suPAR as a prognostic marker in non-critical COVID-19 patients. MATERIALS AND METHODS: We carried out a literature search in MEDLINE, Embase, and Web of Science using the following keywords: ("soluble urokinase receptor" OR "urokinase plasminogen activator receptor" OR "suPAR" OR "soluble uPAR" OR "soluble uPA receptor") AND ("COVID-19" OR "SARS-CoV-2"). We included observational studies (descriptive or analytic) that measured plasma suPAR on COVID-19 patients 18 years old or older, with non-critical disease at the beginning of the study. RESULTS: After screening and eligibility assessment, a total of 16 articles were included in the review. Most studies that measured mean differences found that suPAR levels were higher in patients with worse outcomes. The studies that measured diagnostic accuracy concluded that suPAR was highly sensitive and moderately specific to predicting bad outcomes. Studies that performed a survival analysis found that patients with high suPAR levels were more at risk of bad outcomes. Most of the studies included in this review were performed before extensive vaccination and omicron wave. CONCLUSIONS: COVID-19 patients with moderate initial disease and elevated suPAR levels are more at risk of poor outcomes. Larger prospective clinical trials are needed to confirm the results obtained in this review. [ABSTRACT FROM AUTHOR]

Treatment of pyoderma gangrenosum (PG) is challenging due to the absence of standardized guidelines and the lack of evidence-based, effective treatment options. Here, we performed a systematic review to summarize the use of biologics and their efficacy in the treatment of PG. We searched PubMed/MEDLINE, EMBASE, and Cochrane electronic databases from their inception to September 22nd, 2022, and included 82 peer-reviewed studies with a total of 108 patients. Infliximab, adalimumab, and etanercept were the most utilized biologic therapies in the treatment of PG in 64.8% (70/108), 16.7% (18/108), and 11.1% (12/108) of the cases, respectively. With respect to treatment response, 88.9% (96/108) of the patients achieved complete resolution of PG with biologic therapies. The average number of days to improvement and resolution of PG treated after starting biologic therapies was 30 and 161, respectively. PG recurred in 15.5% (11/71) of those reported the outcome. Our study suggests that biologic therapies may be an attractive therapeutic option for PG with an excellent efficacy., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Within patients with sepsis, there exists significant heterogeneity, and while all patients should receive conventional therapy, there are subgroups of patients who may benefit from specific therapies, often referred to as rescue therapies. Therefore, the identification of these specific patient subgroups is crucial and lays the groundwork for the application of precision medicine based on the development of targeted interventions. Over the years, efforts have been made to categorize sepsis into different subtypes based on clinical characteristics, biomarkers, or underlying mechanisms. For example, sepsis can be stratified into different phenotypes based on the predominant dysregulated host response. These phenotypes can range from hyperinflammatory states to immunosuppressive states and even mixed phenotypes. Each phenotype may require different therapeutic approaches to improve patient outcomes. Rescue strategies for septic shock may encompass various interventions, such as immunomodulatory therapies, extracorporeal support (e.g., ECMO), or therapies targeted at specific molecular or cellular pathways involved in the pathophysiology of sepsis. In recent years, there has been growing interest in precision medicine approaches to sepsis and phenotype identification. Precision medicine aims to tailor treatments to each individual patient based on their unique characteristics and disease mechanisms., 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 Chiscano-Camón, Ruiz-Sanmartin, Bajaña, Bastidas, Lopez-Martinez, Franco-Jarava, Gonzalez, Larrosa, Riera, Nuvials-Casals, Ruiz-Rodríguez and Ferrer.)

Introduction: The detection of pancreatic autoantibodies in first-degree relatives of patients with type 1 diabetes (T1D) is considered a risk factor for disease. Novel available immunotherapies to delay T1D progression highlight the importance of identifying individuals at risk who might benefit from emerging treatments. The objective was to assess the autoimmunity in first-degree relatives of patients with T1D, estimate the time from autoimmunity detection to the onset of clinical diabetes, and identify the associated risk factors., Methods: Retrospective multicenter study of 3,015 first-degree relatives of patients with T1D recruited between 1992 and 2018. Pancreatic autoantibodies (IAA, GADA, IA2A, and ZnT8A) were determined by radioimmunoassay, starting the analyses at diagnosis of the proband. All those with positive autoimmunity and normal fasting blood glucose without clinical symptoms of diabetes were followed up in the study. The progression rate to T1D was assessed according to sex, relationship with the proband, age at autoimmunity detection, type/number of autoantibodies, and HLA-DRB1 genotype. Cox proportional-hazard models and Kaplan-Meier survival plots were used for statistical analyses., Results: Among the relatives, 21 progenitors [43.7 years (IQR: 38.1-47.7)] and 27 siblings [7.6 years (IQR: 5.8-16.1)] had positive autoantibodies. Of these, 54.2% (95% CI: 39.2%-68.6%) developed T1D (age at autoimmunity detection 11 months to 39 years) in a median of 5 years (IQR: 3.6-8.7; ranged from 0.9 to 22.6 years). Risk factors associated with faster progression to T1D were multiple autoimmunity and <20 years at autoimmunity detection. Younger relatives (<20 years) with multiple autoantibodies had a 5-year cumulative risk of developing diabetes of 52.9% (95% CI: 22.1%-71.6%) and a 20-year risk of 91.2% (95% CI: 50.5%-98.4%). The 20-year risk decreased to 59.9% (95% CI: 21.9%-79.5%) if only one risk factor was met and to 35.7% (95% CI: 0.0%-66.2%) if the relative was older than 20 years with one autoantibody., Conclusions: In first-degree relatives with autoimmunity, the time to progression to T1D is faster in children and adolescents with multiple autoantibodies. Young adults are also at risk, which supports their consideration in screening strategies for people at risk of developing T1D., 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 Urrutia, Martinez, Calvo, Marcelo, Saso-Jimenez, Martinez de Lapiscina, Bilbao, Castano, Rica and The Collaborative Working Group.)

The role of commensal anaerobic bacteria in chronic respiratory infections is unclear, yet they can exist in abundances comparable to canonical pathogens in vivo . Their contributions to the metabolic landscape of the host environment may influence pathogen behavior by competing for nutrients and creating inhospitable conditions via toxic metabolites. Here, we reveal a mechanism by which the anaerobe-derived short chain fatty acids (SCFAs) propionate and butyrate negatively affect Staphylococcus aureus physiology by disrupting branched chain fatty acid (BCFA) metabolism. In turn, BCFA impairment results in impaired growth, diminished expression of the agr quorum sensing system, as well as increased sensitivity to membrane-targeting antimicrobials. Altered BCFA metabolism also reduces S. aureus fitness in competition with Pseudomonas aeruginosa , suggesting that airway microbiome composition and the metabolites they produce and exchange directly impact pathogen succession over time. The pleiotropic effects of these SCFAs on S. aureus fitness and their ubiquity as metabolites in animals also suggests that they may be effective as sensitizers to traditional antimicrobial agents when used in combination.

Previous studies have found inconsistent associations between heavy metals and metalloids (cadmium, lead, mercury, and arsenic), and reproductive outcomes. The biofluid concentrations of ten non-essential trace elements (Hg, Pb, As, Ba, Sr, Rb, Cs, Sn, Ni, and Co) were evaluated in 51 Spanish women undergoing ICSI, PGT-A, and SET/FET. Nine out of ten non-essential elements were detectable in follicular fluid, whole blood, and urine collected the day of vaginal oocyte retrieval (VOR) and the day of embryo transfer and then analyzed by ICP-MS or Tricell DMA-80 for mercury. Elevated mercury and strontium concentrations in follicular fluid were associated with poor ovarian response and preimplantation outcomes. Worst preimplantation outcomes were also identified in women with elevated whole-blood strontium or mercury, urinary arsenic, barium, and tin the day of VOR. High concentrations of urinary rubidium on VOR day were linked with enhanced fertilization and blastocyst development. Excessive titanium in whole blood was associated with lower odds of implantation, clinical pregnancy, and achieving a live birth in a given IVF cycle. Excessive urinary arsenic on the day of embryo transfer was associated with lower odds of live birth. Although these preliminary results need to be confirmed in larger populations, distinguishing organic and inorganic element forms, our findings show that some non-essential elements have a detrimental impact on human IVF outcomes.

Desmosomes are intercellular adhesion complexes providing mechanical coupling and tissue integrity. Previously, a correlation of desmosomal molecule expression with invasion and metastasis formation in several tumor entities was described together with a relevance for circulating tumor cell cluster formation. Here, we investigated the contribution of the desmosomal core adhesion molecule desmoglein-2 (DSG2) to the initial steps of liver metastasis formation by pancreatic cancer cells using a novel ex vivo liver perfusion mouse model. We applied the pancreatic ductal adenocarcinoma cell line AsPC-1 with and without a knockout (KO) of DSG2 and generated mouse lines with a hepatocyte-specific KO of the known interacting partners of DSG2 (DSG2 and desmocollin-2). Liver perfusion with DSG2 KO AsPC-1 cells led to smaller circulating cell clusters and a reduced number of cells adhering to murine livers compared to control cells. While this was independent of the expression levels of desmosomal adhesion molecules in hepatocytes, we show that increased cluster size of cancer cells, which correlates with stronger cell-cell adhesion and expression of desmosomal molecules, is a major factor contributing to the early phase of metastatic spreading. In conclusion, impaired desmosomal adhesion results in reduced circulating cell cluster size, which is relevant for seeding and attachment of metastatic cells to the liver., (© 2024. The Author(s).)

The attachment of porous media to a blunt trailing edge (TE) can significantly suppress vortex shedding processes and the related tonal noise, yet the near-wall and internal flow fields of porous media are difficult to analyze experimentally and rely on numerical simulations to elucidate the internal flow features. A structured porous trailing edge (SPTE) has been recently designed that follows a methodology of a structured porous coated cylinder. The SPTE acoustic response was compared against randomized porous media with 10 and 30 pores/in. in an anechoic wind tunnel over a range of flow velocities. Acoustic beamforming revealed that the dominant acoustic sources were at the end of the solid plate, even when a porous TE was attached. A region of integration was used to extract acoustic spectra without additional noise sources, revealing that the SPTE possesses superior noise reduction capability. Dipolar directivity patterns were observed at the vortex shedding frequency for each TE, and the coherence between microphones revealed the complex acoustic propagation of the high-frequency content. A wavelet analysis revealed how the SPTE breaks periodic vortex shedding cycles into smaller cycles over a wider frequency range, leading to an overall noise reduction relative to the other TEs., (© 2024 Acoustical Society of America.)

Experimental access to cell types within the mammalian spinal cord is severely limited by the availability of genetic tools. To enable access to lower motor neurons (LMNs) and LMN subtypes, which function to integrate information from the brain and control movement through direct innervation of effector muscles, we generated single cell multiome datasets from mouse and macaque spinal cords and discovered putative enhancers for each neuronal population. We cloned these enhancers into adeno-associated viral vectors (AAVs) driving a reporter fluorophore and functionally screened them in mouse. The most promising candidate enhancers were then extensively characterized using imaging and molecular techniques and further tested in rat and macaque to show conservation of LMN labeling. Additionally, we combined enhancer elements into a single vector to achieve simultaneous labeling of upper motor neurons (UMNs) and LMNs. This unprecedented LMN toolkit will enable future investigations of cell type function across species and potential therapeutic interventions for human neurodegenerative diseases., Competing Interests: Declaration of interests T.L.D., B.P.L, B.T., E.S.L, H.Z, J.T.T., N.J., Y.G., Z.Y., are inventors on one or more U.S. provisional patent applications related to this work. All authors declare no other competing interests.

Introduction: Prior to the introduction of novel food ingredients into the food supply, safety risk assessments are required, and numerous prediction models have been developed and validated to evaluate safety., Methods: The allergenic risk potential of Helaina recombinant human lactoferrin (rhLF, Effera™), produced in Komagataella phaffii ( K. phaffii ) was assessed by literature search, bioinformatics sequence comparisons to known allergens, glycan allergenicity assessment, and a simulated pepsin digestion model., Results: The literature search identified no allergenic risk for Helaina rhLF, K. phaffii , or its glycans. Bioinformatics search strategies showed no significant risk for cross-reactivity or allergenicity between rhLF or the 36 residual host proteins and known human allergens. Helaina rhLF was also rapidly digested in simulated gastric fluid and its digestibility profile was comparable to human milk lactoferrin (hmLF), further demonstrating a low allergenic risk and similarity to the hmLF protein., Conclusion: Collectively, these results demonstrate a low allergenic risk potential of Helaina rhLF and do not indicate the need for further clinical testing or serum IgE binding to evaluate Helaina rhLF for risk of food allergy prior to introduction into the food supply., Competing Interests: Authors YA, RR, SV, XL, BB, KN, RP, AC, and C-AM are all employees of Helaina, Inc. RG is an employee of RE Goodman Consulting. Corresponding author C-AM is a review editor for Frontiers in Immunology. The remaining 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 Anaya, Rosario Martinez, Goodman, Johnson, Vajpeyi, Lu, Peterson, Weyers, Breen, Newsham, Scottoline, Clark and Malinczak.)

Background: Pompe Disease (PD) is a metabolic myopathy caused by variants in the GAA gene, resulting in deficient enzymatic activity. We aimed to characterize the clinical features and related genetic variants in a series of Mexican patients., Methods: We performed a retrospective study of clinical records of patients diagnosed with LOPD, IOPD or pseudodeficiency., Results: Twenty-nine patients were included in the study, comprising these three forms. Overall, age of symptom onset was 0.1 to 43 years old. The most frequent variant identified was c.-32-13T>G, which was detected in 14 alleles. Among the 23 different variants identified in the GAA gene, 14 were classified as pathogenic, 5 were likely pathogenic, and 1 was a variant of uncertain significance. Two variants were inherited in cis arrangement and 2 were pseudodeficiency-related benign alleles. We identified two novel variants (c.1615 G>A and c.1076-20&#95;1076-4delAAGTCGGCGTTGGCCTG)., Conclusion: To the best of our knowledge, this series represent the largest phenotypic and genotypic characterization of patients with PD in Mexico. Patients within our series exhibited a combination of LOPD and IOPD associated variants, which may be related to genetic diversity within Mexican population. Further population-wide studies are required to better characterize the incidence of this disease in Mexican population., (© 2024 The Author(s). Molecular Genetics & Genomic Medicine published by Wiley Periodicals LLC.)

Background: Paracoccidioidomycosis (PCM) may involve the hepatic pedicle and peripancreatic lymph nodes, cause damage to the bile duct and manifest, exceptionally, in combination with extrahepatic cholestasis (EHC), making investigation and treatment challenging., Aim: To investigate the management of patients with visceral PCM admitted with EHC., Methods: All patients diagnosed with PCM treated in a public, tertiary teaching hospital between 1982 and 2020 were retrospectively evaluated. Those also identified with EHC were allocated to two groups according to the treatment approach for the purpose of comparing clinical, laboratory, and imaging findings, resources used for etiological diagnosis, treatment results, and prognosis. Statistical analyses were performed using the linear mixed-effects model (random and fixed effects), which was adjusted using the PROC MIXED procedure of the SAS ® 9.0 software, and Fisher's exact test., Results: Of 1645 patients diagnosed with PCM, 40 (2.4%) had EHC. Of these, 20 (50.0%) lived in the rural area and 29 (72.5%) were men, with a mean age of 27.1 years (3-65 years). Jaundice as first symptom and weight loss of at least 10 kg were observed in 16 patients (40.0%), and a mass in the head of the pancreas was observed in 8 (20.0%). The etiological diagnosis was made by tissue collection during surgery in 4 cases (10.0%) and by endoscopic methods in 3 cases (7.5%). Twenty-seven patients (67.5%) received drug treatment alone (Group 1), whereas 13 (32.5%) underwent endoscopic and/or surgical procedures in combination with drug treatment (Group 2). EHC was significantly reduced in both groups (40.7% in Group 1, with a mean time of 3 months; and 38.4% in Group 2, with a mean time of 7.5 months), with no statistically significant difference between them. EHC recurrence rates, associated mainly with treatment nonadherence, were similar in both groups: 37% in Group 1 and 15.4% in Group 2. The mortality rate was 18.5% in Group 1 and 23% in Group 2, with survival estimates of 71.3% and 72.5%, respectively, with no statistically significant difference., Conclusion: Although PCM-related EHC is rare, it needs to be included in the differential diagnosis of malignancies, as timely treatment can prevent hepatic and extrahepatic sequelae., Competing Interests: Conflict-of-interest statement: The authors report no conflicts of interest., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)