Pathogenic Bacteroides fragilis strains can emerge from gut-resident commensals.

Bacteroides fragilis is a prominent member of the human gut microbiota, playing crucial roles in maintaining gut homeostasis and host health. Although it primarily functions as a beneficial commensal, B. fragilis can become pathogenic. To determine the genetic basis of its duality, we conducted a comparative genomic analysis of 813 B. fragilis strains, representing both commensal and pathogenic origins. Our findings reveal that pathogenic strains emerge across diverse phylogenetic lineages, due in part to rapid gene exchange and the adaptability of the accessory genome. We identified 16 phylogenetic groups, differentiated by genes associated with capsule composition, interspecies competition, and host interactions. A microbial genome-wide association study identified 44 genes linked to extra-intestinal survival and pathogenicity. These findings reveal how genomic diversity within commensal species can lead to the emergence of pathogenic traits, broadening our understanding of microbial evolution in the gut.

microbeMASST: a taxonomically informed mass spectrometry search tool for microbial metabolomics data.

microbeMASST, a taxonomically informed mass spectrometry (MS) search tool, tackles limited microbial metabolite annotation in untargeted metabolomics experiments. Leveraging a curated database of >60,000 microbial monocultures, users can search known and unknown MS/MS spectra and link them to their respective microbial producers via MS/MS fragmentation patterns. Identification of microbe-derived metabolites and relative producers without a priori knowledge will vastly enhance the understanding of microorganisms' role in ecology and human health.

A bacterial sialidase mediates early-life colonization by a pioneering gut commensal.

The early microbial colonization of the gastrointestinal tract can have long-term impacts on development and health. Keystone species, including Bacteroides spp., are prominent in early life and play crucial roles in maintaining the structure of the intestinal ecosystem. However, the process by which a resilient community is curated during early life remains inadequately understood. Here, we show that a single sialidase, NanH, in Bacteroides fragilis mediates stable occupancy of the intestinal mucosa in early life and regulates a commensal colonization program. This program is triggered by sialylated glycans, including those found in human milk oligosaccharides and intestinal mucus. NanH is required for vertical transmission from dams to pups and promotes B. fragilis dominance during early life. Furthermore, NanH facilitates commensal resilience and recovery after antibiotic treatment in a defined microbial community. Collectively, our study reveals a co-evolutionary mechanism between the host and microbiota mediated through host-derived glycans to promote stable colonization.

Commensal bacteria promote type I interferon signaling to maintain immune tolerance in mice.

Type I interferons (IFNs) exert a broad range of biological effects important in coordinating immune responses, which have classically been studied in the context of pathogen clearance. Yet, whether immunomodulatory bacteria operate through IFN pathways to support intestinal immune tolerance remains elusive. Here, we reveal that the commensal bacterium, Bacteroides fragilis, utilizes canonical antiviral pathways to modulate intestinal dendritic cells (DCs) and regulatory T cell (Treg) responses. Specifically, IFN signaling is required for commensal-induced tolerance as IFNAR1-deficient DCs display blunted IL-10 and IL-27 production in response to B. fragilis. We further establish that IFN-driven IL-27 in DCs is critical in shaping the ensuing Foxp3+ Treg via IL-27Rα signaling. Consistent with these findings, single-cell RNA sequencing of gut Tregs demonstrated that colonization with B. fragilis promotes a distinct IFN gene signature in Foxp3+ Tregs during intestinal inflammation. Altogether, our findings demonstrate a critical role of commensal-mediated immune tolerance via tonic type I IFN signaling.

Advanced practice nursing in Europe-Results from a pan-European survey of 35 countries.

AIM: To report the results of a mapping exercise by the European Federation of Nurses on current advanced practice nursing frameworks and developments across Europe. DESIGN: Online, cross-sectional, questionnaire study. METHODS: An online questionnaire was distributed among 35 national nurses' associations across Europe in March 2021. The questionnaire solicited input on 60 items concerning key features of advanced practice nursing, intending to map existing developments and better understand the current state of advanced practice nursing in Europe. Data analysis used descriptive statistics, including counts and percentages, tabulation; open-text responses were handled with thematic synthesis techniques. RESULTS: The definition, sense-making and operationalization of advanced practice nursing vary across Europe. Important variations were noted in the definition and requirements of advanced practice nursing, resulting in different views on the competencies and scope of practice associated with this role. Importantly, the level of education and training required to qualify and practice as an advanced practice nurse varies across European countries. Furthermore, only 11 countries reported the existence of a national legislation establishing minimum educational requirements. CONCLUSION: Significant variation exists in how countries define advanced practice nursing and how it is regulated at academic and practice levels. More research is needed to clarify whether this variation results from designing models of advanced practice nursing that work in different contexts; and what impact a standardized regulatory framework could have to grow the volume of advanced practice nurses across Europe. IMPACT: The current paper exposes the lack of clarity on the development and implementation of advanced practice nursing across Europe. We found significant variation in the definition, recognition, regulation and education of advanced practice nurses. Our data are essential to policymakers, professional associations and employers to ensure a coordinated and systematic effort in the consistency and ongoing development of advanced practice nurses across Europe. PATIENT OR PUBLIC CONTRIBUTION: No patient or public contribution applied; the participants were national nurses' associations.

A bacterial sialidase mediates early life colonization by a pioneering gut commensal.

The early microbial colonization of the gastrointestinal tract can lead to long-term impacts in development and overall human health. Keystone species, including Bacteroides spp ., play a crucial role in maintaining the structure, diversity, and function of the intestinal ecosystem. However, the process by which a defined and resilient community is curated and maintained during early life remains inadequately understood. Here, we show that a single sialidase, NanH, in Bacteroides fragilis mediates stable occupancy of the intestinal mucosa and regulates the commensal colonization program during the first weeks of life. This program is triggered by sialylated glycans, including those found in human milk oligosaccharides and intestinal mucus. After examining the dynamics between pioneer gut Bacteroides species in the murine gut, we discovered that NanH enables vertical transmission from dams to pups and promotes B. fragilis dominance during early life. Furthermore, we demonstrate that NanH facilitates commensal resilience and recovery after antibiotic treatment in a defined microbial community. Collectively, our study reveals a co-evolutionary mechanism between the host and the microbiota mediated through host-derived glycans to promote stable intestinal colonization.

A Taxonomically-informed Mass Spectrometry Search Tool for Microbial Metabolomics Data.

MicrobeMASST, a taxonomically-informed mass spectrometry (MS) search tool, tackles limited microbial metabolite annotation in untargeted metabolomics experiments. Leveraging a curated database of >60,000 microbial monocultures, users can search known and unknown MS/MS spectra and link them to their respective microbial producers via MS/MS fragmentation patterns. Identification of microbial-derived metabolites and relative producers, without a priori knowledge, will vastly enhance the understanding of microorganisms' role in ecology and human health.

Five-year quality of life in patients with high-risk localized prostate cancer treated with external beam radiotherapy alone versus external beam radiotherapy with high-dose-rate brachytherapy boost: a prospective multicenter study.

PURPOSE: Brachytherapy (BT) and external beam radiation therapy (EBRT) are effective treatments for high-risk prostate cancer (PCa). However, the impact of these treatments on health-related quality of life (HRQL) remains unclear. In this study, we compared EBRT alone with EBRT plus a boost with high-dose rate (HDR)-BT to determine the impact on HRQL in patients with high-risk PCa. MATERIAL AND METHODS: Prospective, multicenter study comparing patients with high-risk PCa treated with EBRT alone or EBRT + HDR-BT from 2004 to 2006. HRQL was assessed at baseline (pre-treatment) and periodically over the 5-year follow-up, using the SF-36 (v.2), EPIC, and FACT-G and FACT-P questionnaires. RESULTS: A total of 129 patients were included in the study, of these, 41 received EBRT alone and 88 EBRT + HDR-BT. All patients received hormonotherapy. Baseline clinical characteristics were similar, except for a slightly higher mean number of comorbidities in the EBRT group. During follow-up, the only significant between-group difference was a greater worsening on EPIC hormonal domain in the EBRT alone group (p = 0.028). There were no significant differences in time and interaction of treatment in SF-36, and FACT-G and FACT-P questionnaires or EPIC urinary incontinence, urinary irritative-obstructive, and bowel and sexual domains over the 5-year follow-up. Oncological outcomes were similar in both groups. CONCLUSIONS: After five years of follow-up, EBRT alone or combined with HDR-BT boost had a similar impact on HRQL in patients with high-risk localized PCa. However, patients in the EBRT alone group experienced greater worsening of hormonal domain according to EPIC questionnaire.

[Rapidly progressive dementia associated with leukoencephalopathy: A case report of lymphomatosis cerebri]. / Demencia rápidamente progresiva asociada a leucoencefalopatía: reporte de linfomatosis cerebri.

INTRODUCTION: Lymphomatosis cerebri is a rare form of primary central nervous system lymphoma characterized by an atypical clinical presentation and neuroimaging, with a poor short-term prognosis. CASE REPORT: A 51-year-old woman began with clinical manifestations characterized by rapidly progressing cognitive impairment associated with a behavioral disorder, myoclonus, and gait disturbance. The brain magnetic resonance image showed extensive signaling in the bilateral periventricular white matter. The 18F-FDG PET-CT showed severe dorsolateral neocortical hypometabolism in the absence of focal hypermetabolic lesion, a metabolic pattern indicative of cerebri lymphomatosis. A brain biopsy confirmed the diagnosis. The patient started chemotherapy achieving complete remission. Eighteen months after diagnosis, the patient had improved clinically and neuroimaging. CONCLUSION: This is the first report in Peru of an entity that should be considered in rapidly progressive dementia and leukoencephalopathy cases. Timely diagnosis and appropriate chemotherapy management can increase patient survival.

INTRODUCCIÓN: La linfomatosis cerebri es una forma infrecuente de linfoma primario del sistema nervioso central, caracterizado por una presentación clínica y de neuroimágenes atípicas con un mal pronóstico a corto plazo. REPORTE DE CASO: Mujer de 51 años que inició cuadro clínico caracterizado por deterioro cognitivo de rápido progreso asociado a trastorno conductual, mioclonías y alteración de la marcha. La resonancia cerebral presentó extensa hiperseñal en la sustancia blanca periventricular bilateral. La tomografía por emisión de positrones con fluoro dexosiglucosa evidenció severo hipometabolismo neocortical dorsolateral en ausencia de lesión hipermetabólica focal, con patrón metabólico sugestivo de linfomatosis cerebri. Se confirmó el diagnostico mediante biopsia cerebral. La paciente inició quimioterapia logrando remisión completa. A los 18 meses del diagnóstico la paciente presentó mejoría clínica y de neuroimágenes evidentes. CONCLUSIÓN: Es el primer reporte en Perú de una entidad que se debe de tener presente en casos de demencia rápidamente progresiva y leucoencefalopatía. El diagnóstico oportuno y manejo quimioterápico adecuado puede aumentar la sobrevida del paciente.

Physiological responses of Holstein calves to hot weather conditions.

The objectives of the study described were to (1) compare environmental temperature-humidity index (THI) with the THI measured within two different calf housing systems and (2) determine how THI affects Holstein heifer calf body temperatures, serum cortisol concentrations, and serum thyroxine concentrations. At 24 to 48 h of age, calves were assigned to one of two individual housing treatments: (1) stalls in a three-sided barn (n = 8) or 2) hutches placed outside (n = 8). Calves were observed until 42 days of age during the summer months. Ambient temperature and relative humidity within housing systems were recorded hourly. Calf body temperatures were measured hourly using devices attached to the underside of each calf's tail. Blood samples were collected at 7, 21, and 42 days of age via jugular venipuncture. Blood serum was analyzed for cortisol and thyroxine concentrations using enzyme-linked immunosorbent assays (ELISAs). Overall average THI was higher in hutches than in stalls (P < 0.0001). Calves housed in hutches had higher body temperatures (39 ± 0.18 °C vs 38 ± 0.15 °C, P = 0.005). No differences occurred in serum cortisol concentrations (P = 0.89) but at 21 days of age, calves housed in hutches had higher serum thyroxine concentrations (16.55 ± 0.51 µg/dl vs 13.91 ± 0.54 µg/dl, P = 0.0006) than calves housed in stalls. Although both housing systems in this study were located on the same dairy, calves housed in hutches were exposed to higher THI values, had higher body temperatures, and at 21 days of age had higher serum thyroxine concentrations than calves housed in stalls inside a three-sided barn.

Molecular Insights of CREB and MAP-K Phosphorylation by Modafinil in Wake-Related Brain Areas.

BACKGROUND: Modafinil (MOD) is a waking-promoting compound that is used for the treatment of sleep disorders such as sleepiness and narcolepsy. Despite its efficiency, there are missing pieces of evidence regarding the mechanism of action of MOD at molecular level. For example, current data have demonstrated that MOD induces alertness by activating several wake-related neurotransmitter receptors, including dopamine 1 (D1) receptor. Nevertheless, an intriguing point highlights that MOD might be activating intracellular elements bounded to D1 receptor, such as cAMP response element-binding (CREB) or mitogen-activated protein kinase (MAP-K) expression. OBJECTIVE: We tested whether administrations of MOD induce phosphorylation of either CREB or MAPK in wake-related brain areas, such as dorsomedial hypothalamic nucleus (DM) and tuberomammillary nucleus (TMN) in rats. METHODS: Rats that received a systemic injection of MOD (30 or 150 mg/Kg) were sacrificed and brains were processed for immunohistochemical analysis of phospho-CREB or phospho-MAP-K staining. RESULTS: MOD dose-dependently enhanced phospho-CREB and phospho-MAP-K immunoreactivity in DM and TMN. Moreover, the statistical analysis revealed that MOD increased the number of phospho- CREB and phospho-MAP-K immunoreactive neurons in these brain areas studied. CONCLUSION: These findings provide significative insights regarding the possible molecular mechanism of action of MOD engaging the activation of phospho-CREB and phospho-MAP-K in wake-linked brain areas. Indeed, further studies are required to fully understand the molecular mechanism of action of MOD.

Quality of life impact of treatments for localized prostate cancer: cohort study with a 5 year follow-up.

PURPOSE: To assess long-term quality of life (QoL) impact of treatments in localized prostate cancer patients treated with radical prostatectomy, external beam radiotherapy or brachytherapy. MATERIAL AND METHODS: Observational, prospective cohort study with pre-treatment QoL evaluation and follow-up until five years after treatment. 704 patients with low or intermediate risk localized prostate cancer were consecutively recruited in 2003-2005. QoL was measured by the EPIC questionnaire, with urinary irritative-obstructive, incontinence, bowel, sexual, and hormonal scores (ranging 0-100). RESULTS: Brachytherapy's QoL impact was restricted to the urinary domain, Generalized Estimating Equation models showed score changes at five years of -12.0 (95% CI=-15.0, -9.0) in incontinence and -5.3 (95% CI=-7.5, -3.1) in irritative-obstructive scales. Compared to brachytherapy, radical prostatectomy fared +3.3 (95% CI=+0.0, +6.5) points better in irritative-obstructive but -17.1 (95% CI=-22.7, -11.5) worse in incontinence. Sexual deterioration was observed in radical prostatectomy (-19.1; 95% CI=-25.1, -13.1) and external radiotherapy groups (-7.5; 95% CI=-12.5, -2.5). CONCLUSIONS: Brachytherapy is the treatment causing the least impact on QoL except for moderate urinary irritative-obstructive symptoms. Our study provides novel long-term valuable information for clinical decision making, supporting brachytherapy as a possible alternative to radical prostatectomy for patients seeking an attempted curative treatment, while limiting the risk for urinary incontinence and sexual impact on QoL.

Quality-of-life impact of primary treatments for localized prostate cancer in patients without hormonal treatment.

PURPOSE: Earlier studies evaluating the effect on quality of life (QoL) of localized prostate cancer interventions included patients receiving adjuvant hormone therapy, which could have affected their outcomes. Our objective was to compare the QoL impact of the three most common primary treatments on patients who were not receiving adjuvant hormonal treatment. PATIENTS AND METHODS: This was a prospective study of 435 patients treated with radical prostatectomy, external-beam radiotherapy, or brachytherapy. QoL was assessed before and after treatment with the Short Form-36 and the Expanded Prostate Cancer Index Composite. Differences between groups were tested by analysis of variance. Distribution of outcome at 3 years was examined by stratifying according to baseline status. Generalized estimating equation models were constructed to assess the effect of treatment over time. RESULTS: Compared with the brachytherapy group, the prostatectomy group showed greater deterioration on urinary incontinence and sexual scores but better urinary irritative-obstructive results (-18.22, -13.19, and +6.38, respectively, at 3 years; P < .001). In patients with urinary irritative-obstructive symptoms at baseline, improvement was observed in 64% of those treated with nerve-sparing radical prostatectomy. Higher bowel worsening (-2.87, P = .04) was observed in the external radiotherapy group, with 20% of patients reporting bowel symptoms. CONCLUSION: Radical prostatectomy caused urinary incontinence and sexual dysfunction but improved pre-existing urinary irritative-obstructive symptoms. External radiotherapy and brachytherapy caused urinary irritative-obstructive adverse effects and some sexual dysfunction. External radiotherapy also caused bowel adverse effects. Relevant differences between treatment groups persisted for up to 3 years of follow-up, although the difference in sexual adverse effects between brachytherapy and prostatectomy tended to decline over long-term follow-up. These results provide valuable information for clinical decision making.

Evaluación de la incidencia y los factores de riesgo para hemorragia intraventricular (HIV) en la cohorte de recién nacidos prematuros atendidos en la unidad neonatal del Hospital Universitario San Vicente de Paúl, de Medellín, en el período comprendido entre enero de 1999 y diciembre de 2004 / Incidence and risk factors of intraventricular hemorrhage in preterm newborns

La hemorragia intraventricular (HIV) es la principal complicación neurológica de los recién nacidos prematuros, cuyas frecuencia y gravedad aumentan con el menor peso al nacer y la menor edad gestacional. Se han encontrado otros factores asociados con el aumento o disminución de su frecuencia.Objetivo: determinar la incidencia de HIV en prematuros atendidos en el Hospital Universitario San Vicente de Paúl (HUSVP), de Medellín, Colombia, entre 1999 y 2004 y establecer su asociación con condiciones de la madre y del recién nacido.Metodología: estudio retrospectivo de los prematuros menores de 32 semanas y por debajo de 1.500 gramos, atendidos en el HUSVP entre 1999 y 2004. Se calculó una muestra de 330 historias clínicas, seleccionadas en forma aleatoria, con un nivel de confianza de 95 por ciento, error del 3 por ciento y poder del 80 por ciento,con base en una incidencia del 15 por ciento de HIV en la población general.Resultados: la incidencia encontrada de HIV fue 29,8 por ciento. Como factores protectores se encontraron los siguientes: parto por cesárea, parto en un centro de tercer nivel y maduración pulmonar. Como factores que aumentaron el riesgo de HIV se encontraron: parto vaginal, edad gestacional menor de 28 semanas, uso de surfactante, ventilación mecánica, cateterismo umbilical, acidosis e hipercapnia.Conclusiones: se debe insistir en la importancia de que haya programas adecuados de control prenatal para tratar de disminuir la frecuencia de parto prematuro, procurar la remisión oportuna de las gestantes de alto riesgo a centros de referencia, estimular el uso antenatal de esteroides y el control cuidadoso de los parámetros ventilatorios en los pacientes que requieran este soporte, buscando mantener un adecuado equilibrio ácido-base en los recién nacidos.

Glutamic acid decarboxylase isoforms are differentially distributed in the septal region of the rat.

The septal region of the brain consists of a heterogeneous population of GABAergic neurons that play an important role in the generation of hippocampal theta rhythms. While GABAergic neurons employ two isoforms of the enzyme glutamic acid decarboxylase (GAD) for the synthesis of GABA, distribution of GAD isoforms has not been investigated in the septum. Immunohistochemical techniques were used to investigate the expression of GAD enzymes in medial and lateral septum. GAD65 and GAD67 immunohistochemistry revealed dense fibers and punctuated immunoreactivity in septal regions. While few GAD65-positive neuronal somas were detected in medial septum, a significantly higher number of immunoreactive neurons were detected in lateral septum. GAD65- and GAD67-positive neurons in the lateral septum exhibit higher complexity of dendritic arborizations than in the medial septum where staining was mainly restricted to the soma. Presumptive axon terminals (puncta) showed abundant immunoreactivity predominantly for GAD65 isoforms in all septal regions. This suggests that septal GABAergic neurons differentially express GAD enzymes thereby potentially reflecting functional differences. Differences found between medial and lateral septal GABAergic neuronal populations are in agreement with the concept that medial and lateral septum are brain structures with highly different connectivity and function despite anatomical proximity.

Factor estimulante de colonias de granulocitos y monocitos (GM-CSF): propiedades generales y aplicaciones terapeuticas / Granulocyte-macrophage colony stimulating factors (GM-CSF)

El factor estimulante de colonias de granulocitos y monocitos (GM-CSF) pertenece a la familia de glicoproteínas que modulan la hematopoyesis y la capacidad funcional de los leucocitos maduros; sus acciones sobre las células fagocíticas incluyen incremento en la síntesis de citoquinas (IL-1, TNF alfa), de la capacidad fagocítica y destrucción de patógenos (aumentando la generación de radicales derivados del oxígeno y la citotoxicidad dependiente de anticuerpos); regula, además, el tráfico de los leucocitos. Estas acciones se pueden superponer con las de otros factores estimulantes. Desde su aislamiento mediante la tecnología del DNA recombinante, el GM-CSF humano se comercializó y ha despertado un gran interés por investigar su utilidad en el tratamiento de diferentes enfermedades. Por sus características, se está utilizando para la recuperación hematopoyética, tratamiento de enfermedades infecciosas, adyuvante de vacunas; además se ha planteado su aplicación local en la mucositis después de la quimio y radioterapia, y en las úlceras crónicas, entre otras, con un buen margen de seguridad y pocos efectos adversos severos conocidos hasta el momento

Infecciones nosocomiales frecuentes que se presentan en el recién nacido atendido en el Hospital Policlínico de Riobamba / Frequent nosocomiales infections that appear in new born taken care of in the Hospital Policlínico de Riobamba

Este trabajo se basará en una amplia revisión de bibliografía, datos de laboratorio, experiencias vividas tanto de nosotros como del personal auxiliar de enfermería, madres de los recién nacidos (RN); cuadros estadísticos, que se derivan de las encuestas que se aplicaron a tres grupos humanos: Persona Auxiliar de Enfermería, Madres de los Recién Nacidos y Personal Auxiliar de limpieza...