Opposing diet, microbiome, and metabolite mechanisms regulate inflammatory bowel disease in a genetically susceptible host.

Inflammatory bowel diseases (IBDs) are chronic conditions characterized by periods of spontaneous intestinal inflammation and are increasing in industrialized populations. Combined with host genetics, diet and gut bacteria are thought to contribute prominently to IBDs, but mechanisms are still emerging. In mice lacking the IBD-associated cytokine, interleukin-10, we show that a fiber-deprived gut microbiota promotes the deterioration of colonic mucus, leading to lethal colitis. Inflammation starts with the expansion of natural killer cells and altered immunoglobulin-A coating of some bacteria. Lethal colitis is then driven by Th1 immune responses to increased activities of mucin-degrading bacteria that cause inflammation first in regions with thinner mucus. A fiber-free exclusive enteral nutrition diet also induces mucus erosion but inhibits inflammation by simultaneously increasing an anti-inflammatory bacterial metabolite, isobutyrate. Our findings underscore the importance of focusing on microbial functions-not taxa-contributing to IBDs and that some diet-mediated functions can oppose those that promote disease.

Pseudo-Normalization of the T-wave During Stress and Its Relationship With Myocardial Ischemia: Evaluation by Myocardial Perfusion Single Photon Emission Computed Tomography (SPECT).

Background The T-wave alterations are suggestive of ischemia, among them there is the pseudo-normalization (positivization of the T-wave, previously negative, during stress exercise). Myocardial single photon emission computed tomography (SPECT) at rest and stress is usually performed with Technetium 99 (Tc-99), which has high sensitivity and specificity for the detection of ischemic heart disease. In this study, we decided to investigate the patients who pseudo-normalized the T-wave in the stress test to correlate with the existence of ischemia diagnosed by myocardial perfusion study, specifically myocardial SPECT in perfusion and rest with Tc-99. Methodology T - wave pseudo-normalization patients who underwent a myocardial perfusion SPECT between January 2018 and June 2019 were included in this retrospective study. We analyzed 81 patients: 50 patients with pseudo-normalization of T-waves and 31 patients, as a control group, without pseudo-normalization. A descriptive analysis of the quantitative variables was performed using Student's t-test or Mann-Whitney U test, and for the qualitative variables, the χ2 test or Fisher's exact test was performed. Results The degree of ischemia according to the presence or absence of pseudo-normalization of the T-wave. The pseudo-normalization of the T-wave in the group without ischemia (48.4% vs. 36%), for the mild degree the proportions were the same (38.7% vs. 38%), the moderate degree it was slightly higher in the pseudo-normalization of the T-wave (9.7% vs. 18%) and severe (3.2% vs. 6%). Conclusions In this study, the relationship between pseudo-normalization of the T waveform and ischemia, predominantly moderate to severe, was demonstrated. However, it was not statistically significant due to the size of the sample studied.

Concerted action of extracellular and cytoplasmic esterase and urethane-cleaving activities during Impranil biodegradation by Alicycliphilus denitrificans BQ1.

The concerted action of commercial esterases, proteases and amidases has been demonstrated to be relevant in polyurethane (PU) degradation by in vitro experiments. However, the spatial and temporal dynamics of these activities during PU biodegradation by PU-degrading bacteria have not been addressed. Here, we examined the capability of Alicycliphilus denitrificans BQ1 to biodegrade the polyester (PS)-PU Impranil, analyzed the temporal and spatial coordination between the extracellular and cytoplasmic esterase and urethane-cleaving activities, and their independent and combined effects on Impranil biodegradation. A. denitrificans BQ1 grew in Impranil, and its clearing was correlated with the cleavage of ester and urethane groups since early times, with decrements of some Impranil compounds and the appearance of biodegradation products. While extracellular esterase was active at early times with its maximum at 18 h, urethanase appeared at this time and increased up to the end of the analysis (48 h), with the cytoplasmic activities behaving similarly but with lower levels than the extracellular ones. Both enzymatic activities exhibited distinct substrate specificity depending on their cellular localization and cultivation times, suggesting they cleave differentially located groups. As the urethane cleavage occurred since early times, when no urethane-cleaving activity was detected, different proteins should be acting at early and late times. In vitro experiments with independent or combined cellular protein fractions supported the previous deduction and confirmed the concerted action of extracellular and cytoplasmic esterase and urethane-cleaving activities. A two-stage process for Impranil degradation by A. denitrificans BQ1 is proposed.

Beta adrenergic receptor antagonist can modify Pseudomonas aeruginosa biofilm formation in vitro: Implications for chronic wounds.

Non-healing wounds are a major medical challenge, affecting over 6.5 million people in the US alone, with associated healthcare costs of about $16 billion annually. They can result in prolonged hospitalizations, work loss, disability, poor quality of life, and in diabetic patients with foot ulcers, amputation of the affected limb in 25% of patients. Though chronic ulcers may arise from different underlying diseases, the unifying feature is chronic infection, driving persistent inflammation that prolongs the healing process. One of the most frequently cultured or genetically identified pathogens in skin wounds is Pseudomonas aeruginosa. This species avidly forms biofilms in the wound that impede bacterial eradication by the host's immune mechanisms and limit efficacy of systemic antibiotics. Thus, non-antibiotic approaches to limit the growth and biofilm formation of this wound pathogen would be an advance in the treatment of chronic wounds. Prior work has demonstrated that the growth of other microbial species can be modulated by catecholamine agonists and antagonists of the adrenergic receptors (ARs). Here, we demonstrate that not only can the growth of this common wound pathogen be modulated by catecholamines, but also that the beta-AR antagonists can significantly decrease their growth, and importantly, limit their ability to form biofilms. These findings suggest that beta adrenergic antagonists may have a therapeutic role in the treatment of chronic skin wounds.

Parenting in the Midst of Adversity: Tailoring a Culturally Adapted Parent Training Intervention According to the Parenting Experiences of Mexican-Origin Caregivers.

Although parent training (PT) interventions are considered the gold standard for preventing externalizing behaviors in children and youth, their dissemination in low-income Latina/o immigrant communities continues to be scarce throughout the United States (US). An alternative to address this gap in service delivery consists of implementing culturally adapted PT interventions characterized by cultural and contextual relevance. Thus, the main objective of this qualitative study was to document salient immigration-related experiences, as well as parenting needs and challenges, as reported by 30 low-income Mexican-origin immigrant caregivers residing in an urban setting in the Southern United States. The research methodology was guided by the tenets of the Thematic Analysis approach, which involved collecting data through a series of focus group interviews. Qualitative research findings highlight the importance of culturally and contextually tailoring adapted PT prevention interventions, prior to their delivery in contexts that differ from those in which interventions were originally adapted. Specifically, parents in the current investigation provided detailed accounts of immigration-related stressors that are highly relevant to inform recruitment procedures, intervention curriculum, and intervention delivery activities.

Aunque las intervenciones de capacitaciones para padres se consideran la norma de oro para prevenir los comportamientos de externalización en los niños y los jóvenes, su difusión en las comunidades de inmigrantes latinos de bajos recursos continúa siendo escasa en todo Estados Unidos. Una alternativa para minimizar esta brecha en la prestación del servicio consiste en implementar intervenciones de capacitación para padres adaptadas culturalmente que se caractericen por la relevancia cultural y contextual. Por lo tanto, el objetivo principal de este estudio cualitativo fue documentar las experiencias destacadas relacionadas con la inmigración, así como las necesidades y las dificultades de la crianza, según lo informado por 30 cuidadores inmigrantes de origen mexicano y de bajos recursos que viven en un entorno urbano en el sur de EE. UU. La metodología de investigación estuvo guiada por los principios del método del análisis temático, que consistió en recopilar datos mediante una serie de entrevistas a grupos de análisis. Los resultados de la investigación cualitativa destacan la importancia de amoldar culturalmente y contextualmente las intervenciones preventivas y adaptadas de capacitación para padres antes de su implementación en contextos distintos a aquellos a los que fueron adaptadas originalmente. Específicamente, los padres de la investigación actual explicaron detalladamente los factores de estrés relacionados con la inmigración que son sumamente relevantes para preparar los procedimientos de captación, el currículo de intervención y las actividades de implementación de la intervención.

Phase-variable capsular polysaccharides and lipoproteins modify bacteriophage susceptibility in Bacteroides thetaiotaomicron.

A variety of cell surface structures dictate interactions between bacteria and their environment, including their viruses (bacteriophages). Members of the human gut Bacteroidetes characteristically produce several phase-variable capsular polysaccharides (CPSs), but their contributions to bacteriophage interactions are unknown. To begin to understand how CPSs have an impact on Bacteroides-phage interactions, we isolated 71 Bacteroides thetaiotaomicron-infecting bacteriophages from two locations in the United States. Using B. thetaiotaomicron strains that express defined subsets of CPSs, we show that CPSs dictate host tropism for these phages and that expression of non-permissive CPS variants is selected under phage predation, enabling survival. In the absence of CPSs, B. thetaiotaomicron escapes bacteriophage predation by altering expression of eight distinct phase-variable lipoproteins. When constitutively expressed, one of these lipoproteins promotes resistance to multiple bacteriophages. Our results reveal important roles for Bacteroides CPSs and other cell surface structures that allow these bacteria to persist under bacteriophage predation, and hold important implications for using bacteriophages therapeutically to target gut symbionts.

Topical Fluoxetine as a Novel Therapeutic That Improves Wound Healing in Diabetic Mice.

Diabetic foot ulcers represent a significant source of morbidity in the U.S., with rapidly escalating costs to the health care system. Multiple pathophysiological disturbances converge to result in delayed epithelialization and persistent inflammation. Serotonin (5-hydroxytryptamine [5-HT]) and the selective serotonin reuptake inhibitor fluoxetine (FLX) have both been shown to have immunomodulatory effects. Here we extend their utility as a therapeutic alternative for nonhealing diabetic wounds by demonstrating their ability to interact with multiple pathways involved in wound healing. We show that topically applied FLX improves cutaneous wound healing in vivo. Mechanistically, we demonstrate that FLX not only increases keratinocyte migration but also shifts the local immune milieu toward a less inflammatory phenotype in vivo without altering behavior. By targeting the serotonin pathway in wound healing, we demonstrate the potential of repurposing FLX as a safe topical for the challenging clinical problem of diabetic wounds.

A tractable, simplified ex vivo human skin model of wound infection.

The prevalence of infection in chronic wounds is well documented in the literature but not optimally studied due to the drawbacks of current methodologies. Here, we describe a tractable and simplified ex vivo human skin model of infection that addresses the critical drawbacks of high costs and limited translatability. Wounds were generated from excised abdominal skin from cosmetic procedures and cultured, inoculated with Staphylococcus aureus strain UAMS-1, or under aseptic conditions. After three days, the infected wounds exhibited biofilm formation and significantly impaired reepithelialization compared to the control. Additionally, promigratory and proreparative genes were significantly downregulated, while proinflammatory genes were significantly upregulated, demonstrating molecular characterizations of impaired healing as in chronic wounds. This model allows for a simplified and versatile tool for the study of wound infection and subsequent development of novel therapies.

Deep Brain Stimulation Surgery for Parkinson Disease Coexisting With Communicating Hydrocephalus: A Case Report.

We report a successful bilateral globus pallidus internus-deep brain stimulation (GPi-DBS) for a Parkinson disease (PD) patient with idiopathic normal pressure hydrocephalus (INPH) and an unusually long anterior commissure-posterior commissure (AC-PC) line. A 54-year-old man presented with a history of 3 months of severe shuffling gait, rigidity, slow movements of the left side limbs, and difficulty managing finances. A brain MRI revealed marked ventriculomegaly (Evans index = 0.42). The patient was diagnosed with INPH and a ventriculoperitoneal shunt was placed. Cognitive impairment improved, but walking disturbances, slowness, and rigidity persisted. Then treatment with levodopa was added, and the patient experienced a sustained improvement. He was diagnosed with PD. After 7 years, the patient developed gait freezing and severe levodopa-induced dyskinesia. The patient underwent bilateral GPi-DBS. We used MRI/CT fusion techniques for anatomical indirect targeting. Indirect targeting is based on standardized stereotactic atlas and on a formula-derived method based on AC-PC landmarks. The AC-PC line was 40 mm (the usual length is between 19 and 32 mm). Intraoperative microelectrode recording was a non-expendable test, but multiple recordings were avoided to reduce the surgical risk of ventricular involvement. There was a 71% decrease in the UPDRS III score during the on-stimulation state (28 to 8). The patient's dyskinesias resolved dramatically with a UdysRS of 15 (88% improvement) during the on-stimulation condition. The observed motor benefits and the improvement of his daily activities have persisted 6 months after surgery. Deep brain stimulation surgery in PD with ventriculomegaly is a challenge. This procedure can result in a greater chance of breaching the ventricle, with risks of intraventricular hemorrhage and migration of cerebrospinal fluid into the brain parenchyma with target displacement. Furthermore, clinical judgment is paramount when recent onset of shuffling gait coexists with ventriculomegaly because the most common dilemma is differentiating between PD and INPH. For these reasons, neurologists and surgeons may refuse to operate on PD patients with ventriculomegaly. However, DBS should be considered for PD patients with motor complications when responsiveness to levodopa is demonstrated, even in the context of marked ventriculomegaly.

Combination therapy of autologous adipose mesenchymal stem cell-enriched, high-density lipoaspirate and topical timolol for healing chronic wounds.

Chronic venous leg ulcers are profoundly debilitating and result in billions in health care expenditure. Thus, there is a quest for engineered and innovative approaches. Herein we present a 63-year-old patient with a 30 year history of venous stasis and left lower extremity ulcers, which have been refractory to standard of care, anticoagulation and venous stripping. The medial ulcer was treated with transplantation of autologous adipose mesenchymal stem cell (AMSC)-enriched, high-density lipoaspirate (HDL) on OASIS wound matrix and compression therapy. The lateral ulcer was treated as a control with standard debridement and compression therapy. Four weeks later, both ulcers received daily topical timolol. Three months later, the test ulcer was completely epithelized and remains healed for over 15 months. However, the control showed minimal signs of improvement. In companion studies in our laboratory, human AMSC were cultured in Minimum Essential Medium Eagle Alpha Modifications (MEMα) with fetal bovine serum (FBS). Timolol was administered to AMSC prior to treatment with epinephrine and 104 bacteria/ml heat-killed Staphylococcus aureus. The MEMα with FBS devoid of AMSC served as a background control. After 24 h, cell culture supernatants and protein lysates were collected to determine cytokine production. There was a statistical significant decrease in pro-inflammatory interleukin-6 and -8 induced by the bacteria (to model the wound environment) in AMSC in the presence of timolol compared with control (p < 0.5). This is the first case of a successful combination of autologous AMSC-enriched, HDL with topical timolol for the healing of chronic venous leg ulcers. Copyright © 2016 John Wiley & Sons, Ltd.

Fractions of aqueous and methanolic extracts from tomato (Solanum lycopersicum L.) present platelet antiaggregant activity.

Cardiovascular disease (CVD) is the leading cause of death worldwide. Its prevention emphasizes three aspects: not smoking, physical activity and a healthy diet. Recently, we screened the antithrombotic activity of a selected group of fruits and vegetables. Among them, tomato showed an important effect. The aim of this study was to evaluate and characterize the platelet antiaggregatory activity of tomato (Solanum lycopersicum L.). For this, we obtained aqueous and methanolic tomato extracts and evaluated the effect of pH (2 and 10) and temperature (22, 60 and 100°C) on this activity. Furthermore, in order to isolate the antiaggregant principle, we separated tomato extracts into several fractions (A-D) by size exclusion chromatography. In addition, we evaluated the platelet antiaggregating activity ex vivo in Wistar rats. Aqueous and methanolic extracts of tomato treated at 22, 60 and 100°C and pH 2 and 10 still inhibited platelet aggregation (in vitro). Moreover, it was noted that one of the fractions (fraction C), from both aqueous and methanolic extracts, presented the highest activity (∼70% inhibition of platelet aggregation) and concentration dependently inhibited platelet aggregation significantly compared with control (P < 0.05). These fractions did not contain lycopene but presented two peaks of absorption, at 210 and 261 nm, compatible with the presence of nucleosides. In rats treated with tomato macerates, a mild platelet antiaggregating effect ex vivo was observed. Further studies are required to identify the molecules with platelet antiaggregating activity and antiplatelet mechanisms of action.

Imperativos y estrategias para la acción: prevención de zoonosis en sector ganadero / Imperatives and strategies for the action: prevention of zoonosis in cattle sector

El trabajo presenta los resultados de un proyecto de investigación que utiliza metodología científica aplicada al estudio prospectivo del conocimiento que poseen los trabajadores usuarios o expuestos a riesgos biológicos presentes en el sector agropecuario del sur de Chile, y la relación que este conocimiento tiene con el grado de peligrosidad que estos riesgos representan para la salud de los mismos trabajadores expuestos. Se aplicaron encuestas de conocimientos sobre cinco zoonosis: hidatidosis, carbunco, triquinilosis, tuberculosis y brucelosis a trabajadores del sector agropecuario del llano central de la provincia de Osorno. Del análisis de los resultados obtenidos se concluye que es bajo el nivel de conocimiento que ellos poseen, respecto de la zoonosis a las que se encuentran expuestos, o a las que eventualmente podrían estarlo. Esta situación constituye un alto riesgo para estos trabajdores y sus familias, considerando el hábitat rural o entorno laboral donde se desempeñam