Medicinal Orchids of Mexico: A Review.

Some species of the Orchidaceae family are used in Mexican traditional medicine. However, there are no current and critical compilations of the medicinal uses and pharmacological effects of the members of the Orchidaceae family. This review provides a current, critical, and comprehensive analysis of the traditional medicinal uses, pharmacological reports, and active compounds isolated from Mexican orchids. A total of 62 Mexican orchids with medicinal potential have been recorded, of which 14 have scientific evidence. The remaining 48 plant species have ethnomedicinal information but have not been validated with scientific studies. These orchids are distributed in 14 states of the Mexican Republic, mainly in the southern region of Mexico. The most common pharmacological activities reported are anti-inflammatory, vasorelaxant, antinociceptive, antioxidant, spasmolytic, antihypertensive, and hallucinogenic activities. It is necessary to increase the number of pharmacological, phytochemical, and toxicological studies with medicinal orchids from Mexico because there are scientific studies on only 22.5% of these species. In further studies, it will be possible to evaluate the pharmacological effects of Mexican orchids in clinical trials. In addition, the mechanisms of action by which plant extracts and their active compounds exert medicinal effects remain to be studied. Plant extracts from orchids and their active compounds show promising antinociceptive and spasmolytic effects, respectively.

The real-world observational prospective study of health outcomes with dulaglutide and liraglutide in type 2 diabetes patients (TROPHIES): resource use and costs of treatment in clinical practice in France, Germany, and Italy.

AIMS: To describe healthcare resource utilization (HCRU) and associated costs after initiation of injectable glucagon-like peptide-1 receptor agonist (GLP-1 RA) therapy by adult patients with type 2 diabetes (T2D) in the prospective, observational, 24-month TROPHIES study in France, Germany, and Italy. MATERIALS AND METHODS: HCRU data for cost calculations were collected by treating physicians during patient interviews at baseline and follow-up visits approximately 6, 12, 18, and 24 months after GLP-1 RA initiation with once-weekly dulaglutide or once-daily liraglutide. Costs were evaluated from the national healthcare system (third-party payer) perspective and updated to 2018 prices. RESULTS: In total, 2,005 patients were eligible for the HCRU analysis (1,014 dulaglutide; 991 liraglutide). Baseline patient characteristics were generally similar between treatment groups and countries. The largest proportions of patients using ≥2 oral glucose-lowering medications (GLMs) at baseline (42.9-43.4%) and month 24 (44.0-45.1%) and using another injectable GLM at month 24 (15.3-23.2%) were in France. Mean numbers of primary and secondary healthcare contacts during each assessment period were highest in France (range = 4.0-10.7) and Germany (range = 2.9-5.7), respectively. The greatest proportions (≥60%) of mean annualized costs per patient comprised medication costs. Mean annualized HCRU costs per patient varied by treatment cohort and country: the highest levels were in the liraglutide cohort in France (€909) and the dulaglutide cohort in Germany (€883). LIMITATIONS: Limitations included exclusion of patients using insulin at GLP-1 RA initiation and collection of HCRU data by physician, not via patient-completed diaries. CONCLUSIONS: Real-world HCRU and costs associated with the treatment of adults with T2D with two GLP-1 RAs in TROPHIES emphasize the need to avoid generalization with respect to HCRU and costs associated with a particular therapy when estimating the impact of a new treatment in a country-specific setting.

Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have become frequent treatments of hyperglycemia in type-2 diabetes (T2D). Not all types of clinical study provide information about the cost of these treatments or the effects they might have on use of other medicines and equipment to control T2D or the need for visits to a doctor or nurse and different types of treatment in hospital. This study collected this information during the regular care of adults in France, Germany, or Italy who were prescribed either dulaglutide or liraglutide (both types of GLP-1 RAs) by their family doctor or a specialist in T2D. There were differences in costs and the need for other medicines and medical services between people using either dulaglutide or liraglutide and for people who were using the same GLP-1 RA in each of the three countries. The information from this study could be used to more accurately understand the overall costs and medical care needed when patients use dulaglutide or liraglutide in France, Germany, or Italy.

Differential impacts of furfural and acetic acid on the bioenergetics and fermentation performance of Scheffersomyces stipitis.

Lignocellulosic material is a leading carbon source for economically viable biotechnological processes; however, compounds such furfural and acetic acid exhibit toxicity to yeasts. Nonetheless, research about the molecular mechanism of furfural and acetic acid toxicity is still scarce in yeasts like Scheffersomyces stipitis. Thus, this study aims to elucidate the impact of furfural and acetic acid on S. stipitis regarding bioenergetic and fermentation parameters. Here, we provide evidence that furfural and acetic acid induce a delay in cell growth and extend the lag phase. The mitochondrial membrane potential decreased in all treatments with no significant differences between inhibitors or concentrations. Interestingly, reactive oxygen species increased when the inhibitor concentrations were from 0.1 to 0.3 % (v/v). The glycolytic flux was not significantly (p > 0.05) altered by acetic acid, but furfural caused different effects. Ethanol production decreased significantly (4.32 g·L-1 in furfural and 5.06 g·L-1 in acetic acid) compared to the control (26.3 g·L-1). In contrast, biomass levels were not significantly different in most treatments compared to the control. This study enhances our understanding of the effects of furfural and acetic acid at the mitochondrial level in a pentose-fermenting yeast like S. stipitis.

Abnormal open states patterns in the ATXN2 DNA sequence depends on the CAG repeats length.

Hereditary ataxias are one of the «anticipation diseases¼ types. Spinocerebral ataxia type 2 occurs when the number of CAG repeats in the coding region of the ATXN2 gene exceeds 34 or more. In healthy people, the CAG repeat region in the ATXN2 gene usually consists of 22-23 CAG trinucleotides. Mutations that increase the length of CAG repeats can cause severe neurodegenerative and neuromuscular disorders known as trinucleotide repeat expansion diseases. The mechanisms causing such diseases are associated with non-canonical configurations that can be formed in the CAG repeat region during replication, transcription or repair. This makes it relevant to study the zones of open states that arise in the region of CAG repeats under torque. The purpose of this work is to study, using mathematical modeling, zones of open states in the region of CAG repeats of the ATXN2 gene, caused by torque. It has been established that the torque effect on the 1st exon of the ATXN2 gene, in addition to the formation of open states in the promoter region, can lead to the formation of additional various sizes open states zones in the CAG repeats region. Moreover, the frequency of additional large zones genesis increases with increasing number of CAG repeats. The inverse of this frequency correlates with the dependence of the disease onset average age on the CAG repeats length. The obtained results will allow us to get closer to understanding the genetic mechanisms that cause trinucleotide repeat diseases.

Morphofunctional Assessment beyond Malnutrition: Fat Mass Assessment in Adult Patients with Phenylketonuria-Systematic Review.

Morphofunctional assessment was developed to evaluate disease-related malnutrition. However, it can also be used to assess cardiometabolic risk, as excess adiposity increases this risk. Phenylketonuria (PKU) is the most prevalent inherited metabolic disease among adults, and obesity in PKU has recently gained interest, although fat mass correlates better with cardiometabolic risk than body mass index. In this systematic review, the objective was to assess whether adult patients with PKU have higher fat mass than healthy controls. Studies of adult PKU patients undergoing dietary treatment in a metabolic clinic reporting fat mass were included. The PubMed and EMBASE databases were searched. Relevance of articles, data collection, and risk of bias were evaluated by two independent reviewers. Ten articles were evaluated, six with a control group, including 310 subjects with PKU, 62 with mild hyperphenylalaninemia, and 157 controls. One study reported a significant and four a tendency towards an increased fat mass in all patients or only females with PKU. Limitations included not having a healthy control group, not reporting sex-specific results and using different techniques to assess fat mass. Evaluation of fat mass should be included in the morphofunctional assessment of cardiometabolic risk in adult patients with PKU.

Psychosocial risk and protective factors for youth problem behavior are associated with food addiction in the Generation Z.

Objective: Food Addiction (FA) and other well-known risk behavior as substance misuse tend to co-occur and may share similar risk and protective factors. The aim of this study was to assess the association between the diagnosis/severity of FA and psychosocial domains typically related to risk behavior syndrome in a large, nationally representative community sample of Generation Z underage Italian students. Method: The sample consisted of 8,755 students (3,623 from middle schools, 5,132 from high schools). A short version of the Yale Food Addiction Scale 2.0 was administered to evaluate FA. Risk and protective factors related to demographic, personality, behavior, and family variables were examined. Stepwise multivariate logistic and linear regressions were conducted. Results: The prevalence of FA was 30.8%. Female gender, social anxiety and depression symptoms, social withdrawal risk, Internet gaming disorder, social media addiction, current substance use, social challenge engagement and experienced doxing boosted the chance of FA diagnosis, whereas eating fruit and vegetables, playing competitive sports and an average sleep duration of 7-8 h per night reduced these odds. FA severity was significantly and positively associated with trait impulsiveness, social anxiety and depressive symptoms, risk of social withdrawal, recent substance use, social media, and gaming addiction, doxing suffered and risky social challenges participation. Negative associations between the severity of FA and fruit and vegetable diet habits were found. Conclusion: Our findings confirm that FA is widespread among Italian adolescents. The associations between the diagnosis and severity of FA and psychosocial risk factors for health, including, addictive and deviant behaviors related to digital misuse, suggest its belonging to the risk behavior constellation. Health promotion schemes based on a multicomponent strategy of intervention should consider the inclusion of FA and its psychosocial correlates.

Bacterioplankton taxa compete for iron along the early spring-summer transition in the Arctic Ocean.

Microbial assemblages under the sea ice of the Dease Strait, Canadian Arctic, were sequenced for metagenomes of a small size fraction (0.2-3 µm). The community from early March was typical for this season, with Alpha- and Gammaproteobacteria as the dominant taxa, followed by Thaumarchaeota and Bacteroidetes. Toward summer, Bacteroidetes, and particularly the genus Polaribacter, became increasingly dominant, followed by the Gammaproteobacteria. Analysis of genes responsible for microbial acquisition of iron showed an abundance of ABC transporters for divalent cations and ferrous iron. The most abundant transporters, however, were the outer membrane TonB-dependent transporters of iron-siderophore complexes. The abundance of iron acquisition genes suggested this element was essential for the microbial assemblage. Interestingly, Gammaproteobacteria were responsible for most of the siderophore synthesis genes. On the contrary, Bacteroidetes did not synthesize siderophores but accounted for most of the transporters, suggesting a role as cheaters in the competition for siderophores as public goods. This cheating ability of the Bacteroidetes may have contributed to their dominance in the summer.

GNN Codon Adjacency Tunes Protein Translation.

The central dogma treats the ribosome as a molecular machine that reads one mRNA codon at a time as it adds each amino acid to its growing peptide chain. However, this and previous studies suggest that ribosomes actually perceive pairs of adjacent codons as they take three-nucleotide steps along the mRNA. We examined GNN codons, which we find are surprisingly overrepresented in eukaryote protein-coding open reading frames (ORFs), especially immediately after NNU codons. Ribosome profiling experiments in yeast revealed that ribosomes with NNU at their aminoacyl (A) site have particularly elevated densities when NNU is immediately followed (3') by a GNN codon, indicating slower mRNA threading of the NNU codon from the ribosome's A to peptidyl (P) sites. Moreover, if the assessment was limited to ribosomes that have only recently arrived at the next codon, by examining 21-nucleotide ribosome footprints (21-nt RFPs), elevated densities were observed for multiple codon classes when followed by GNN. This striking translation slowdown at adjacent 5'-NNN GNN codon pairs is likely mediated, in part, by the ribosome's CAR surface, which acts as an extension of the A-site tRNA anticodon during ribosome translocation and interacts through hydrogen bonding and pi stacking with the GNN codon. The functional consequences of 5'-NNN GNN codon adjacency are expected to influence the evolution of protein coding sequences.

First Bioprospecting Study of Skin Host-Defense Peptides in Odontophrynus americanus.

The adaptation of amphibians to diverse environments is closely related to the characteristics of their skin. The complex glandular system of frog skin plays a pivotal role in enabling these animals to thrive in both aquatic and terrestrial habitats and consists of crucial functions such as respiration and water balance as well as serving as a defensive barrier due to the secretion of bioactive compounds. We herein report the first investigation on the skin secretion of Odontophrynus americanus, as a potential source of bioactive peptides and also as an indicator of its evolutionary adaptations to changing environments. Americanin-1 was isolated and identified as a neutral peptide exhibiting moderate antibacterial activity against E. coli. Its amphipathic sequence including 19 amino acids and showing a propensity for α-helix structure is discussed. Comparisons of the histomorphology of the skin of O. americanus with other previously documented species within the same genus revealed distinctive features in the Patagonian specimen, differing from conspecifics from other Argentine provinces. The presence of the Eberth-Katschenko layer, a prevalence of iridophores, and the existence of glycoconjugates in its serous glands suggest that the integument is adapted to retain skin moisture. This adaptation is consistent with the prevailing aridity of its native habitat.

Paraneoplastic leukocytosis secondary to carcinosarcoma: a report of two cases and literature review.

BACKGROUND: Neutrophilia is an increase in the number of neutrophils over 7.5×103/µL. An increase in leukocytes over 50×103/µL is called a leukemoid reaction; and when it is associated with a solid tumor, it is considered a paraneoplastic syndrome called paraneoplastic leukemoid reaction (PLR). It is a very rare clinical condition and it is very unusual for it to be associated with carcinosarcoma. We present two cases of a leukemoid reaction observed in the Medical Oncology Department of the University Hospital of Salamanca between May and September 2023. The main objectives of our article are to describe the unusual appearance of paraneoplastic leukocytosis at the diagnosis of carcinosarcoma carcinosarcoma, explain in a detailed way its diagnostic procedure and to show the poor prognosis to which it is associated. CASE DESCRIPTION: In our presentation, we describe two similar cases: first of all, a 60-year-old woman without relevant medical history. She was referred by her primary physician to the Department of Internal Medicine in August 2023 with asthenia, lumbar pain, and weight loss of 12 kg of 3 months of evolution. The physical examination revealed a palpable hypogastric mass. An abdominal, pelvic, and thoracic computed tomography (CT) scan revealed a heterogenous solid mass with necrotic areas originating in the uterus. The anatomopathological diagnosis was carcinosarcoma. The patient showed a progressive worsening in her renal function associated with hyperviscosity secondary to hyperleukocytosis caused by 170×103/µL neutrophils. In the second case we describe the diagnosis of a PLR secondary to a kidney carcinosarcoma. When the patient started chemotherapy, he presented 55.08×103/µL leukocytes, 53.16×103/µL neutrophils. Eight days after receiving chemotherapy, the patient was admitted as an emergency with oligoanuria and decreased consciousness. He presented creatinine 6.25 mg/dL, phosphate 12.4 mg/dL, leukocytes 1.05×103/µL, and neutrophils 0.71×103/µL. The clinical diagnosis was acute exacerbation of multifactorial mixed (renal and prerenal) chronic kidney disease associated with tumor lysis syndrome and grade 3 neutropenia. The patient presented a poor evolution, dying after 2 months. CONCLUSIONS: PLR is a severe paraneoplastic syndrome associated with different types of solid tumors. Its appearance at the time of diagnosis of a tumor implies a poor vital prognosis.

Knowledge and practices regarding prostate cancer screening in Spanish men: The importance of personal and clinical characteristics (PROSHADE study).

INTRODUCTION: Patients' decisions on prostate cancer (PCa) opportunistic screening may vary. This study aimed to assess how demographic and health-related characteristics may influence knowledge and decisions regarding PCa screening. METHODS: A cross-sectional survey was conducted among men aged over 40, randomly sampled from the Spanish population, 2022. The survey underwent development and content validation using a modified Delphi method and was administered via telephone. Binomial logistic regression was used to explore the relationship between respondents' characteristics and participants' knowledge and practices concerning PCa and the PSA test. RESULTS: Out of 1,334 men, 1,067 (80%) respondents were interviewed with a mean age of 58.6 years (sd 11.9). Most had secondary or university studies (787, 73.8%) and 61 (5.7%) self-reported their health status as bad or very bad. Most of the respondents (1,018, 95.4%) had knowledge regarding PCa with nearly 70% expressed significant concern about its potential development (720, 70.8%), particularly among those under 64 years (p = 0.001). Out of 847 respondents, 573 (67.7%) reported that they have knowledge regarding the PSA test: 374 (65.4%) reported receiving information from a clinicians, 324 (86.6%) information about the benefits of the test and 189 (49,5%) about its risks, with differences based on educational background. In a multivariable analysis (adjusted for age, educational level and previous prostate problems), respondents with higher levels of education were more likely to have higher knowledge regarding the PSA test (OR 1.75, 95%CI 1.24-2.50, p<0.001). CONCLUSIONS: Although most of the patients reported to have knowledge regarding PCa, half of the interviewed men reported knowledge about PSA test. Differences in knowledge prostate cancer screening and undesirable consequences highlight the need to develop and provide tailored information for patients.

Short- and mid-term morbidity and primary-care burden due to infant respiratory syncytial virus infection: A Spanish 6-year population-based longitudinal study.

BACKGROUND: The morbidity burden of respiratory syncytial virus (RSV) in infants extends beyond hospitalization. Defining the RSV burden before implementing prophylaxis programs is essential for evaluating any potential impact on short- to mid-term morbidity and the utilization of primary healthcare (PHC) and emergency services (ES). We established this reference data using a population-based cohort approach. METHODS: Infants hospitalized for RSV from January 2016 to March 2023 were matched with non-hospitalized ones based on birthdate and sex. We defined the exposure as severe RSV hospitalization. The main study outcomes were as follows: (1) PHC and ES visits for RSV, categorized using the International Classification of Primary Care codes, (2) prescriptions for respiratory airway obstructive disease, and (3) antibacterial prescriptions. Participants were followed up from 30 days before hospitalization for severe RSV until the outcome occurrence or end of the study. Adjusted incidence rate ratios (IRRs) of the outcomes along with their 95% confidence intervals (CI) were estimated using Poisson regression models. Stratified analyses by type of PHC visit (nurse, pediatrician, or pharmacy) and follow-up period were undertaken. We defined mid-term outcomes as those taking place up to 24 months of follow-up period. RESULTS: The study included 6626 children (3313 RSV-hospitalized; 3313 non-hospitalized) with a median follow-up of 53.7 months (IQR = 27.9, 69.4). After a 3-month follow-up, severe RSV was associated with a considerable increase in PHC visits for wheezing/asthma (IRR = 4.31, 95% CI: 3.84-4.84), lower respiratory infections (IRR = 4.91, 95% CI: 4.34-5.58), and bronchiolitis (IRR = 4.68, 95% CI: 2.93-7.65). Severe RSV was also associated with more PHC visits for the pediatrician (IRR = 2.00, 95% CI: 1.96-2.05), nurse (IRR = 1.89, 95% CI: 1.75-1.92), hospital emergency (IRR = 2.39, 95% CI: 2.17-2.63), primary healthcare emergency (IRR: 1.54, 95% CI: 1.31-1.82), as well as with important increase in prescriptions for obstructive airway diseases (IRR = 5.98, 95% CI: 5.43-6.60) and antibacterials (IRR = 4.02, 95% CI: 3.38-4.81). All findings remained substantial until 2 years of post-infection. CONCLUSIONS: Severe RSV infection in infants significantly increases short- to mid-term respiratory morbidity leading to an escalation in healthcare utilization (PHC/ES attendance) and medication prescriptions for up to 2 years afterward. Our approach could be useful in assessing the impact and cost-effectiveness of RSV prevention programs.

Different Diagnostic Criteria for Determining the Prevalence of Sarcopenia in Older Adults: A Systematic Review.

Background: Sarcopenia is defined as a loss of muscle mass, strength, and physical function associated with aging. It is due to a combination of genetic, environmental, and physiological factors. It is also associated with an increased risk of health problems. Since there are many different researchers in the field, with their own algorithms and cut-off points, there is no single criterion for diagnosis. This review aims to compare the prevalence of sarcopenia according to these different diagnostic criteria in older adult populations by age group and sex. Methods: Different databases were searched: Web of Science, Pubmed, Dialnet, Scopus, and Cochrane. The keywords used were "sarcopenia", "diagnosis", "prevalence", "assessment", "aged", "aging" and "older". Studies conducted in a population aged ≥65 assessing the prevalence of sarcopenia were selected. Results: Nineteen articles met the inclusion criteria, with a total of 33,515 subjects, 38.08% female and 61.42% male, at a mean age of 74.52. The diagnostic algorithms used were 52.63% AWGS2, 21.05% EWGSOP2, 10.53% AWGS1 and EWGS1, and 5.26% FNIH. Prevalence ranged from 1.7% to 37.47%, but was higher in males and increased with age. Conclusions: The prevalence of sarcopenia varies depending on the diagnostic algorithm used, but it increases with age and is higher in men. The EWGSOP2 and AWGS2 are the most used diagnostic criteria and measure the same variables but have different cut-off points. Of these two diagnostic algorithms, the one with the highest prevalence of sarcopenia and severe sarcopenia is the AWGS2. These differences may be due to the use of different tools and cut-off points. Therefore, a universal diagnostic criterion should be developed to allow early diagnosis of sarcopenia.

Incidence of metabolic bone disease in neonates under 32 gestational weeks at the Hospital Universitario de Santander in Colombia. / Incidencia de enfermedad metabólica ósea en neonatos con menos de 32 semanas de gestación en el Hospital Universitario de Santander en Colombia

INTRODUCTION: Metabolic bone disease of premature infants is a rare complication characterized by a lower mineral content in bone tissue. OBJECTIVE: To establish the incidence of metabolic bone disease in premature infants and to determine associated risk factors. MATERIALS AND METHOD: We conducted a descriptive prospective cohort study for one year in all newborns under 32 gestational weeks, or 1,500 g, at the Hospital Universitario de Santander to determine the incidence of metabolic bone disease. We collected demographic data and prenatal histories of the selected patients, and later, we measured serum alkaline phosphatase and serum phosphorus at the third week of birth, having as reference values for diagnosis less than 5.6 mg/dl for the first one and more than 500 UI/L for the second one. We applied statistical tools for data analysis, such as average proportions, dispersion, distribution and association measures, and binomial regression. RESULTS: From a total of 58 patients, 7 had a diagnosis of metabolic bone disease, with an incidence of 12%. The weight was reported as an independent variable for the development of the disease, being significant in children under 1,160 g, as well as prolonged parenteral nutrition for more than 24 days. When performing the multivariate analysis, low weight and short time of parenteral nutrition appeared as risk factors; in the same way, maternal age below 22 years is associated with a higher relative risk, even more than a newborn weight inferior to 1,160 g. CONCLUSION: Establishing an early intervention in patients with metabolic bone disease enhancing risk factors, such as low weight and prolonged parenteral nutrition, is critical to prevent severe complications.

Introducción. La enfermedad metabólica ósea de neonatos prematuros es una complicación poco común que se caracteriza por una disminución del contenido mineral en el hueso. Objetivo. Establecer la incidencia de la enfermedad metabólica ósea en neonatos prematuros y los factores de riesgo asociados. Materiales y métodos. Durante un año, se realizó un estudio prospectivo de cohorte, descriptivo, con todos los neonatos nacidos con menos de 32 semanas de gestación o un peso menor de 1.500 g en el Hospital Universitario de Santander. Se recolectaron datos demográficos y antecedentes prenatales de los pacientes seleccionados. A la tercera semana de nacimiento, se midieron la fosfatasa alcalina y el fósforo sérico, tomando como valores de referencia diagnóstica aquellos inferiores a 5,6 mg/dl para el primero y aquellos mayores de 500 UI/L para la segunda. Para el análisis de la información, se emplearon herramientas estadísticas, como proporciones de promedios, medidas de dispersión, distribución y asociación, y regresión binomial. Resultados. De un total de 58 pacientes, 7 tuvieron diagnóstico de enfermedad metabólica ósea, con una incidencia del 12 %. De las variables estudiadas, el peso se reportó como una variable independiente para el desarrollo de la enfermedad, significativa en aquellos neonatos con peso menor de 1.160 g, al igual que la nutrición parenteral prolongada por más de 24 días. Al hacer el análisis multivariado, La edad materna menor de 22 años representó un riesgo relativo mayor, en comparación con un peso inferior a 1.160 g. Conclusión. Se estableció la importancia de una intervención temprana en pacientes con factores de riesgo para enfermedad metabólica ósea, como bajo peso (menor de 1.160 g) y nutrición parenteral prolongada (mayor de 24 días), con el fin de prevenir complicaciones graves.

Macro- and Micro-Structural Alterations in the Midbrain in Early Psychosis.

Introduction: Early psychosis (EP) is a critical period in the course of psychotic disorders during which the brain is thought to undergo rapid and significant functional and structural changes 1 . Growing evidence suggests that the advent of psychotic disorders is early alterations in the brain's functional connectivity and structure, leading to aberrant neural network organization. The Human Connectome Project (HCP) is a global effort to map the human brain's connectivity in healthy and disease populations; within HCP, there is a specific dataset that focuses on the EP subjects (i.e., those within five years of the initial psychotic episode) (HCP-EP), which is the focus of our study. Given the critically important role of the midbrain function and structure in psychotic disorders (cite), and EP in particular (cite), we specifically focused on the midbrain macro- and micro-structural alterations and their association with clinical outcomes in HCP-EP. Methods: We examined macro- and micro-structural brain alterations in the HCP-EP sample (n=179: EP, n=123, Controls, n=56) as well as their associations with behavioral measures (i.e., symptoms severity) using a stepwise approach, incorporating a multimodal MRI analysis procedure. First, Deformation Based Morphometry (DBM) was carried out on the whole brain 3 Tesla T1w images to examine gross brain anatomy (i.e., seed-based and voxel-based volumes). Second, we extracted Fractional Anisotropy (FA), Axial Diffusivity (AD), and Mean Diffusivity (MD) indices from the Diffusion Tensor Imaging (DTI) data; a midbrain mask was created based on FreeSurfer v.6.0 atlas. Third, we employed Tract-Based Spatial Statistics (TBSS) to determine microstructural alterations in white matter tracts within the midbrain and broader regions. Finally, we conducted correlation analyses to examine associations between the DBM-, DTI- and TBSS-based outcomes and the Positive and Negative Syndrome Scale (PANSS) scores. Results: DBM analysis showed alterations in the hippocampus, midbrain, and caudate/putamen. A DTI voxel-based analysis shows midbrain reductions in FA and AD and increases in MD; meanwhile, the hippocampus shows an increase in FA and a decrease in AD and MD. Several key brain regions also show alterations in DTI indices (e.g., insula, caudate, prefrontal cortex). A seed-based analysis centered around a midbrain region of interest obtained from freesurfer segmentation confirms the voxel-based analysis of DTI indices. TBSS successfully captured structural differences within the midbrain and complementary alterations in other main white matter tracts, such as the corticospinal tract and cingulum, suggesting early altered brain connectivity in EP. Correlations between these quantities in the EP group and behavioral scores (i.e., PANSS and CAINS tests) were explored. It was found that midbrain volume noticeably correlates with the Cognitive score of PA and all DTI metrics. FA correlates with the several dimensions of the PANSS, while AD and MD do not show many associations with PANSS or CAINS. Conclusions: Our findings contribute to understanding the midbrain-focused circuitry involvement in EP and complimentary alteration in EP. Our work provides a path for future investigations to inform specific brain-based biomarkers of EP and their relationships to clinical manifestations of the psychosis course.

A Novel Decision Tree Model for Predicting the Cancer-Specific Survival of Patients with Bladder Cancer Treated with Radical Cystectomy.

Background/Objectives: The aim was to develop a decision tree and a new prognostic tool to predict cancer-specific survival in patients with urothelial bladder cancer treated with radical cystectomy. Methods: A total of 11,834 patients with bladder cancer treated with radical cystectomy between 2004 and 2019 from the SEER database were randomly split into the derivation (n = 7889) and validation cohorts (n = 3945). Survival curves were estimated using conditional decision tree analysis. We used Multiple Imputation by Chained Equations for the treatment of missing values and the pec package to compare the predictive performance. We extracted data from our model following CHARMS and assessed the risk of bias and applicability with PROBAST. Results: A total of 4824 (41%) patients died during the follow-up period due to bladder cancer. A decision tree was made and 12 groups were obtained. Patients with a higher AJCC stage and older age have a worse prognosis. The risk groups were summarized into high, intermediate and low risk. The integrated Brier scores between 0 and 191 months for the bootstrap estimates of the prediction error are the lowest for our conditional survival tree (0.189). The model showed a low risk of bias and low concern about applicability. The results must be externally validated. Conclusions: Decision tree analysis is a useful tool with significant discrimination. With this tool, we were able to stratify patients into 12 subgroups and 3 risk groups with a low risk of bias and low concern about applicability.

SARS-CoV-2 Omicron BA.1 Variant Infection of Human Colon Epithelial Cells.

The Omicron variant of SARS-CoV-2, characterized by multiple subvariants including BA.1, XBB.1.5, EG.5, and JN.1, became the predominant strain in early 2022. Studies indicate that Omicron replicates less efficiently in lung tissue compared to the ancestral strain. However, the infectivity of Omicron in the gastrointestinal tract is not fully defined, despite the fact that 70% of COVID-19 patients experience digestive disease symptoms. Here, using primary human colonoids, we found that, regardless of individual variability, Omicron infects colon cells similarly or less effectively than the ancestral strain or the Delta variant. The variant induced limited type III interferon expression and showed no significant impact on epithelial integrity. Further experiments revealed inefficient cell-to-cell spread and spike protein cleavage in the Omicron spike protein, possibly contributing to its lower infectious particle levels. The findings highlight the variant-specific replication differences in human colonoids, providing insights into the enteric tropism of Omicron and its relevance to long COVID symptoms.

Value per Statistical Life at the Sub-National Level as a Tool for Assessing Public Health and Environmental Problems.

This article aims to estimate the Value per Statistical Life (VSL) and Value per Statistical Life Year (VSLY) at the sub-national level, which can be used to calculate the economic impact of health and environmental problems. We estimate the value of life for Mexico and its 32 states, grouped into 5 regions for 2021. We used the OECD's guidelines on "Mortality Risk Valuation in Environment, Health and Transport Policies," which applies the measure of Willingness to Pay (WTP) and Cost-Benefit Analysis (CBA). Mexico's overall VSL of $2 000 000 USD in 2021 showcases the value placed on human life. The variation in VSL across the 32 states, with Chiapas having the lowest VSL of $400 000 USD and Mexico City boasting the highest VSL of $3 300 000 USD highlights the different levels of regional development and people's willingness to pay to reduce the risk of mortality. Our estimates of VSL and VSLY have the potential to contribute to the evaluation of public policies in the fields of health and the environment. Monetizing human life through these estimates can offer valuable insights to policymakers at both the national and sub-national levels. By quantifying the economic value placed on human life, this paper helps decision-makers prioritize investments, assess the cost-effectiveness of interventions, and allocate resources to maximize societal well-being.

Prognostic value of bioelectrical impedance analysis in head and neck cancer patients undergoing radiotherapy: a VALOR® study.

Introduction: Bioelectrical impedance analysis (BIA) serves as a method to estimate body composition. Parameters such as phase angle (PA), standardized phase angle (SPA), body mass cell (BCM), BCM index (BCMI), and fat-free mass (FFM) might significantly impact the prognosis of head and neck cancer (HNC) patients. The present study aimed to investigate whether bioelectrical parameters can be used to predict survival in the HNC population and establish the optimal cutoff points for predictive accuracy. Methods: A multicenter observational study was performed across 12 tertiary hospitals in Andalusia (a region from the south of Spain). A total of 494 patients diagnosed with HNC between 2020 and 2022 at different stages were included in this study, with a minimum follow-up period of 12 months. The BIA assessment was carried out during the first 2 weeks of radical radiotherapy treatment with chemotherapy or other systemic treatments. A multivariate logistic regression analysis of overall survival, complications, hospital admission, and palliative care and its relationship with BIA nutritional assessment was performed. Results: Significant prognostic factors identified in the multivariable analysis encompassed phase angle (PA), standardized phase angle (SPA), body cell mass (BCM), and BCM index (BCMI). Lower PA and BCM values were significantly associated with adverse clinical outcomes. A BCM threshold above 17 kg/m2 was the most significant predictor for predicting survival within the overall HNC population. The PA values of <5.1° in male and <4.8° in female patients showed the best predictive potential for mortality. Increased PA (as a continuous variable) demonstrated a significantly reduced risk for mortality (OR, 0.64; 95% CI, 0.43-0.94; p < 0.05) and a decreased likelihood of hospital admission (OR, 0.75; 95% CI, 0.52-1.07; p < 0.05). Higher BCM correlated with a lower risk of mortality (OR, 0.88; 95% CI, 0.80-0.96; p < 0.01) and a diminished probability of hospital admission (OR, 0.91; 95% CI, 0.83-0.99; p < 0.05). Conclusion: BIA is a crucial tool in the nutritional assessment of HNC patients. BCM and PA are the main bioelectrical parameters used to predict clinical outcomes in this population. Future studies are needed to validate BIA variables in a large cohort to ensure whether early intensification of nutritional treatment would improve survival.