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1.
bioRxiv ; 2024 Jan 23.
Artículo en Inglés | MEDLINE | ID: mdl-38328247

RESUMEN

Undernutrition in children commonly disrupts the structure and function of the small intestinal microbial community, leading to enteropathies, compromised metabolic health, and impaired growth and development. The mechanisms by which diet and microbes mediate the balance between commensal and pathogenic intestinal flora remain elusive. In a murine model of undernutrition, we investigated the direct interactions Giardia lamblia, a prevalent small intestinal pathogen, on indigenous microbiota and specifically on Lactobacillus strains known for their mucosal and growth homeostatic properties. Our research reveals that Giardia colonization shifts the balance of lactic acid bacteria, causing a relative decrease in Lactobacillus spp . and an increase in Bifidobacterium spp . This alteration corresponds with a decrease in multiple indicators of mucosal and nutritional homeostasis. Additionally, protein-deficient conditions coupled with Giardia infection exacerbate the rise of primary bile acids and susceptibility to bile acid-induced intestinal barrier damage. In epithelial cell monolayers, Lactobacillus spp . mitigated bile acid-induced permeability, showing strain-dependent protective effects. In vivo, L. plantarum, either alone or within a Lactobacillus spp consortium, facilitated growth in protein-deficient mice, an effect attenuated by Giardia , despite not inhibiting Lactobacillus colonization. These results highlight Giardia's potential role as a disruptor of probiotic functional activity, underscoring the imperative for further research into the complex interactions between parasites and bacteria under conditions of nutritional deficiency.

2.
Arq. bras. cardiol ; 120(12 supl.1): 21-21, dez. 2023. ilus.
Artículo en Portugués | CONASS, Sec. Est. Saúde SP, SESSP-IDPCPROD, Sec. Est. Saúde SP | ID: biblio-1518964

RESUMEN

INTRODUÇÃO: Em março de 2021 a Biotronik emitiu um comunicado sobre uma possível depleção prematura da bateria de cardiodesfibriladores implantáveis (CDI) e ressincronizadores cardíacos com desfibrilador (TRC-D). A empresa não orientou troca imediata das baterias e sugeriu o acompanhamento através de monitoramento remoto desses pacientes com dispositivos implantados em nosso serviço. Relatamos neste trabalho a taxa de recall. MÉTODOS: Estudo retrospectivo observacional com pacientes com CDI e TRC-D Biotronik suscetíveis a recall implantados no Instituto Dante Pazzanese de Cardiologia entre os anos de 2015 a 2021. Em consulta médica, os pacientes foram convidados a participar do monitoramento remoto com o uso do monitor CardioMessenger Smart, orientados quanto ao comunicado da empresa e sobre como manusear o aparelho. RESULTADOS: Foram identificados 76 pacientes com dispositivos passíveis de disfunção. Através de contato telefônico, observou-se que 34 pacientes já haviam falecido. Uma paciente foi submetida à troca do gerador previamente ao comunicado por desgaste da bateria. Dos 41 restantes, realizouse o monitoramento remoto de 73% (30), sendo 2 TRC-D e 28 CDI. Não ocorreu a monitorização de 10 pacientes devido à não disponibilização dos aparelhos pela empresa. Não foi possível contato com um paciente. Durante o follow-up de 2 anos, 6,6% dos casos (2) apresentaram depleção prematura da bateria, sendo submetidos à troca do gerador. CONCLUSÃO: A percentagem de recall encontrada neste estudo foi relevante e o monitoramento remoto foi fundamental para a detecção precoce e prevenção de uma situação potencialmente fatal.


Asunto(s)
Monitoreo del Ambiente , Desfibriladores Implantables
3.
Nat Commun ; 14(1): 2840, 2023 05 18.
Artículo en Inglés | MEDLINE | ID: mdl-37202423

RESUMEN

Giardia lamblia (Giardia) is among the most common intestinal pathogens in children in low- and middle-income countries (LMICs). Although Giardia associates with early-life linear growth restriction, mechanistic explanations for Giardia-associated growth impairments remain elusive. Unlike other intestinal pathogens associated with constrained linear growth that cause intestinal or systemic inflammation or both, Giardia seldom associates with chronic inflammation in these children. Here we leverage the MAL-ED longitudinal birth cohort and a model of Giardia mono-association in gnotobiotic and immunodeficient mice to propose an alternative pathogenesis of this parasite. In children, Giardia results in linear growth deficits and gut permeability that are dose-dependent and independent of intestinal markers of inflammation. The estimates of these findings vary between children in different MAL-ED sites. In a representative site, where Giardia associates with growth restriction, infected children demonstrate broad amino acid deficiencies, and overproduction of specific phenolic acids, byproducts of intestinal bacterial amino acid metabolism. Gnotobiotic mice require specific nutritional and environmental conditions to recapitulate these findings, and immunodeficient mice confirm a pathway independent of chronic T/B cell inflammation. Taken together, we propose a new paradigm that Giardia-mediated growth faltering is contingent upon a convergence of this intestinal protozoa with nutritional and intestinal bacterial factors.


Asunto(s)
Giardiasis , Enfermedades Inflamatorias del Intestino , Ratones , Animales , Giardia , Giardiasis/parasitología , Nutrientes , Inflamación/complicaciones , Aminoácidos
4.
Sci Total Environ ; 880: 163266, 2023 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-37028654

RESUMEN

In urban areas, exposure to greenspace has been found to be beneficial to human health. The biodiversity hypothesis proposed that exposure to diverse ambient microbes in greener areas may be one pathway leading to health benefits such as improved immune system functioning, reduced systemic inflammation, and ultimately reduced morbidity and mortality. Previous studies observed differences in ambient outdoor bacterial diversity between areas of high and low vegetated land cover but didn't focus on residential environments which are important to human health. This research examined the relationship between vegetated land and tree cover near residence and outdoor ambient air bacterial diversity and composition. We used a filter and pump system to collect ambient bacteria samples outside residences in the Raleigh-Durham-Chapel Hill metropolitan area and identified bacteria by 16S rRNA amplicon sequencing. Geospatial quantification of total vegetated land or tree cover was conducted within 500 m of each residence. Shannon's diversity index and weighted UniFrac distances were calculated to measure α (within-sample) and ß (between-sample) diversity, respectively. Linear regression for α-diversity and permutational analysis of variance (PERMANOVA) for ß-diversity were used to model relationships between vegetated land and tree cover and bacterial diversity. Data analysis included 73 ambient air samples collected near 69 residences. Analysis of ß-diversity demonstrated differences in ambient air microbiome composition between areas of high and low vegetated land (p = 0.03) and tree cover (p = 0.07). These relationships remained consistent among quintiles of vegetated land (p = 0.03) and tree cover (p = 0.008) and continuous measures of vegetated land (p = 0.03) and tree cover (p = 0.03). Increased vegetated land and tree cover were also associated with increased ambient microbiome α-diversity (p = 0.06 and p = 0.03, respectively). To our knowledge, this is the first study to demonstrate associations between vegetated land and tree cover and the ambient air microbiome's diversity and composition in the residential ecosystem.


Asunto(s)
Biodiversidad , Ecosistema , Humanos , ARN Ribosómico 16S/genética , Modelos Lineales , Bacterias , Árboles/genética
5.
PLoS One ; 18(2): e0281432, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36763596

RESUMEN

To date studies have not investigated the culture-independent microbiome of bile from dogs, a species where aseptic collection of bile under ultrasound guidance is somewhat routine. Despite frequent collection of bile for culture-based diagnosis of bacterial cholecystitis, it is unknown whether bile from healthy dogs harbors uncultivable bacteria or a core microbiota. The answer to this question is critical to understanding the pathogenesis of biliary infection and as a baseline to exploration of other biliary diseases in dogs where uncultivable bacteria could play a pathogenic role. A pressing example of such a disease would be gallbladder mucocele formation in dogs. This prevalent and deadly condition is characterized by excessive secretion of abnormal mucus by the gallbladder epithelium that can eventually lead to rupture of the gallbladder or obstruction of bile flow. The cause of mucocele formation is unknown as is whether uncultivable, and therefore unrecognized, bacteria play any systematic role in pathogenesis. In this study we applied next-generation 16S rRNA gene sequencing to identify the culture-negative bacterial community of gallbladder bile from healthy dogs and gallbladder mucus from dogs with mucocele formation. Integral to our study was the use of 2 separate DNA isolations on each sample using different extraction methods and sequencing of negative control samples enabling recognition and curation of contaminating sequences. Microbiota findings were validated by simultaneous culture-based identification, cytological examination of bile, and fluorescence in-situ hybridization (FISH) performed on gallbladder mucosa. Using culture-dependent, cytological, FISH, and 16S rRNA sequencing approaches, results of our study do not support existence of a core microbiome in the bile of healthy dogs or gallbladder mucus from dogs with mucocele formation. Our findings further document how contaminating sequences can significantly contribute to the results of sequencing analysis when performed on samples with low bacterial biomass.


Asunto(s)
Enfermedades de los Conductos Biliares , Enfermedades de los Perros , Enfermedades de la Vesícula Biliar , Microbiota , Mucocele , Perros , Animales , Vesícula Biliar/patología , Mucocele/veterinaria , ARN Ribosómico 16S/genética , Bilis/microbiología , Enfermedades de la Vesícula Biliar/veterinaria , Microbiota/genética , Enfermedades de los Perros/diagnóstico
6.
J Bronchology Interv Pulmonol ; 30(1): 60-65, 2023 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-35696591

RESUMEN

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can cause severe respiratory failure leading to prolonged mechanical ventilation. Data are just emerging about the practice and outcomes of tracheostomy in these patients. We reviewed our experience with tracheostomies for SARS-CoV-2. METHODS: We retrospectively reviewed the demographics, comorbidities, timing of mechanical ventilation, tracheostomy, and intensive care unit and hospital lengths of stay in SARS-CoV-2 patients who received tracheostomies performed by the interventional pulmonary team. A tertiary care, teaching hospital in Chicago, Illinois. From March 2020 to April 2021, our center had 473 patients intubated for SARS-CoV-2, and 72 (15%) had percutaneous bedside tracheostomy performed by the interventional pulmonary team. RESULTS: Median time from intubation to tracheostomy was 20 (interquartile range: 16 to 25) days. Demographics and comorbidities were similar between early and late tracheostomy, but early tracheostomy was associated with shorter intensive care unit lengths of stay and a shorter total duration of ventilation. To date, 39 (54%) patients have been decannulated, 17 (24%) before hospital discharge; median time to decannulation was 22 (IQR: 18 to 36) days. Patients that were decannulated were younger (56 vs. 69 y). The rate of decannulation for survivors was 82%. No providers developed symptoms or tested positive for SARS-CoV-2. CONCLUSION: Tracheostomy enhances care for patients with prolonged respiratory failure from SARS-CoV-2 since early tracheostomy is associated with shorter duration of critical care, and decannulation rates are high for survivors. It furthermore appears safe for both patients and operators.


Asunto(s)
COVID-19 , Insuficiencia Respiratoria , Humanos , SARS-CoV-2 , Traqueostomía/efectos adversos , Estudios Retrospectivos , Respiración Artificial , Insuficiencia Respiratoria/etiología , Insuficiencia Respiratoria/terapia , Unidades de Cuidados Intensivos
7.
bioRxiv ; 2023 Dec 14.
Artículo en Inglés | MEDLINE | ID: mdl-38168346

RESUMEN

Pathogen clearance and resolution of inflammation in patients with pneumonia require an effective local T cell response. Nevertheless, local T cell activation may drive lung injury, particularly during prolonged episodes of respiratory failure characteristic of severe SARS-CoV-2 pneumonia. While T cell responses in the peripheral blood are well described, the evolution of T cell phenotypes and molecular signatures in the distal lung of patients with severe pneumonia caused by SARS-CoV-2 or other pathogens is understudied. Accordingly, we serially obtained 432 bronchoalveolar lavage fluid samples from 273 patients with severe pneumonia and respiratory failure, including 74 unvaccinated patients with COVID-19, and performed flow cytometry, transcriptional, and T cell receptor profiling on sorted CD8+ and CD4+ T cell subsets. In patients with COVID-19 but not pneumonia secondary to other pathogens, we found that early and persistent enrichment in CD8+ and CD4+ T cell subsets correlated with survival to hospital discharge. Activation of interferon signaling pathways early after intubation for COVID-19 was associated with favorable outcomes, while activation of NF-κB-driven programs late in disease was associated with poor outcomes. Patients with SARS-CoV-2 pneumonia whose alveolar T cells preferentially targeted the Spike and Nucleocapsid proteins tended to experience more favorable outcomes than patients whose T cells predominantly targeted the ORF1ab polyprotein complex. These results suggest that in patients with severe SARS-CoV-2 pneumonia, alveolar T cell interferon responses targeting structural SARS-CoV-2 proteins characterize patients who recover, yet these responses progress to NF-κB activation against non-structural proteins in patients who go on to experience poor clinical outcomes.

8.
JMIR Cancer ; 8(3): e38722, 2022 Jul 05.
Artículo en Inglés | MEDLINE | ID: mdl-35788019

RESUMEN

BACKGROUND: Adult child caregivers of parents with cancer may face challenges when communicating with the patient and other family members, communicating during clinical interactions, and navigating web-based information seeking. OBJECTIVE: We developed and pilot-tested the Healthy Communication Practice program for adult child caregivers of parents with a blood cancer, which aims to help participants learn and implement communication skills central to caregiving. We assessed the feasibility and acceptability of the training. METHODS: Eligible participants completed a preprogram survey. We assessed the feasibility of participants completing the intervention in the allotted time. Participants had 2 weeks to complete the 2-part, 90-minute online program and completed a postprogram survey that included program evaluation items and the Acceptability of Intervention Measure (AIM) using a 1-5 rating scale (5=strongly agree). RESULTS: Of 50 caregivers who initially expressed interest, 34 consented, and 30 completed the program and both surveys (88% completion rate). Caregivers had a mean age of 45.07 (SD 11.96) years and provided care for parents who had a mean age of 73.31 (SD 9.38) years. Caregivers were primarily daughters (n=22, 73%). Overall, scores on the AIM scale were high (mean 4.48, SD 0.67). Specifically, caregivers felt the content met their communication needs (mean 4.58, SD 0.62) and their own needs as a caregiver of a parent with a blood cancer (mean 4.39, SD 0.72). CONCLUSIONS: We demonstrated the feasibility and acceptability of the Healthy Communication Practice program, which aims to enhance family and clinical communication skills among caregivers of a parent with a blood cancer. Future studies will examine the efficacy of the program and its impact on both caregiver and patient communication and health outcomes.

9.
J Law Med Ethics ; 49(2): 206-210, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34924042

RESUMEN

This article argues that because racial inequalities are embedded in American society, as well as in medicine, more evidence-based investigation of the effects and implications of affirmative action is needed. Residency training programs should also seek ways to recruit medical students from underrepresented groups and to create effective mentorship programs.


Asunto(s)
Educación Médica , Internado y Residencia , Diversidad Cultural , Humanos , Grupos Minoritarios , Política Pública , Factores Socioeconómicos , Estados Unidos
10.
Ethics Hum Res ; 43(5): 18-25, 2021 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-34496156

RESUMEN

This article provides pragmatic advice for organizations interested in creating a research ethics consultation service (RECS). A robust RECS has the potential to build capacity among investigators to identify and consider the ethical issues they encounter while conducting their research. Determining whether to establish an RECS should begin with an institutional-needs assessment that includes three key questions: What are the current resources available to research teams to navigate ethical concerns that arise from their research? Is there a demand or perceived need for more resources? Is there institutional support (financial and otherwise) to establish and maintain an RECS? If this results in the decision to establish the consultation service, relevant institutional stakeholders must be identified and consulted, and personnel with the requisite skills recruited. The next step is to establish an RECS and build the infrastructure to process and respond to requests. The RECS's long-term sustainability will depend on a stable source of funding and a mechanism to receive constructive feedback to ensure that the service is meeting the institutional needs it set out to address.


Asunto(s)
Consultoría Ética , Ética en Investigación , Humanos
11.
Am J Respir Crit Care Med ; 204(8): 921-932, 2021 10 15.
Artículo en Inglés | MEDLINE | ID: mdl-34409924

RESUMEN

Rationale: Current guidelines recommend patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pneumonia receive empirical antibiotics for suspected bacterial superinfection on the basis of weak evidence. Rates of ventilator-associated pneumonia (VAP) in clinical trials of patients with SARS-CoV-2 pneumonia are unexpectedly low. Objectives: We conducted an observational single-center study to determine the prevalence and etiology of bacterial superinfection at the time of initial intubation and the incidence and etiology of subsequent bacterial VAP in patients with severe SARS-CoV-2 pneumonia. Methods: Bronchoscopic BAL fluid samples from all patients with SARS-CoV-2 pneumonia requiring mechanical ventilation were analyzed using quantitative cultures and a multiplex PCR panel. Actual antibiotic use was compared with guideline-recommended therapy. Measurements and Main Results: We analyzed 386 BAL samples from 179 patients with SARS-CoV-2 pneumonia requiring mechanical ventilation. Bacterial superinfection within 48 hours of intubation was detected in 21% of patients. Seventy-two patients (44.4%) developed at least one VAP episode (VAP incidence rate = 45.2/1,000 ventilator days); 15 (20.8%) initial VAPs were caused by difficult-to-treat pathogens. The clinical criteria did not distinguish between patients with or without bacterial superinfection. BAL-based management was associated with significantly reduced antibiotic use compared with guideline recommendations. Conclusions: In patients with SARS-CoV-2 pneumonia requiring mechanical ventilation, bacterial superinfection at the time of intubation occurs in <25% of patients. Guideline-based empirical antibiotic management at the time of intubation results in antibiotic overuse. Bacterial VAP developed in 44% of patients and could not be accurately identified in the absence of microbiologic analysis of BAL fluid.

12.
Front Nutr ; 8: 640100, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33898497

RESUMEN

Complex dietary carbohydrate structures including ß(1-4) galacto-oligosaccharides (GOS) are resistant to digestion in the upper gastrointestinal (GI) tract and arrive intact to the colon where they benefit the host by selectively stimulating microbial growth. Studies have reported the beneficial impact of GOS (alone or in combination with other prebiotics) by serving as metabolic substrates for modulating the assembly of the infant gut microbiome while reducing GI infections. N-Acetyl-D-lactosamine (LacNAc, Galß1,4GlcNAc) is found in breast milk as a free disaccharide. This compound is also found as a component of human milk oligosaccharides (HMOs), which have repeating and variably branched lactose and/or LacNAc units, often attached to sialic acid and fucose monosaccharides. Human glycosyl-hydrolases do not degrade most HMOs, indicating that these structures have evolved as natural prebiotics to drive the proper assembly of the infant healthy gut microbiota. Here, we sought to develop a novel enzymatic method for generating LacNAc-enriched GOS, which we refer to as humanized GOS (hGOS). We showed that the membrane-bound ß-hexosyl transferase (rBHT) from Hamamotoa (Sporobolomyces) singularis was able to generate GOS and hGOS from lactose and N-Acetyl-glucosamine (GlcNAc). The enzyme catalyzed the regio-selective, repeated addition of galactose from lactose to GlcNAc forming the ß-galactosyl linkage at the 4-position of the GlcNAc and at the 1-position of D-galactose generating, in addition to GOS, LacNAc, and Galactosyl-LacNAc trisaccharides which were produced by two sequential transgalactosylations. Humanized GOS is chemically distinct from HMOs, and its effects in vivo have yet to be determined. Thus, we evaluated its safety and demonstrated the prebiotic's ability to modulate the gut microbiome in 6-week-old C57BL/6J mice. Longitudinal analysis of gut microbiome composition of stool samples collected from mice fed a diet containing hGOS for 5 weeks showed a transient reduction in alpha diversity. Differences in microbiome community composition mostly within the Firmicutes phylum were observed between hGOS and GOS, compared to control-fed animals. In sum, our study demonstrated the biological synthesis of hGOS, and signaled its safety and ability to modulate the gut microbiome in vivo, promoting the growth of beneficial microorganisms, including Bifidobacterium and Akkermansia.

13.
medRxiv ; 2021 Feb 25.
Artículo en Inglés | MEDLINE | ID: mdl-33655275

RESUMEN

BACKGROUND: SARS-CoV-2 can cause severe respiratory failure leading to prolonged mechanical ventilation. Data are just emerging about the practice and outcomes of tracheostomy in these patients. We reviewed our experience with tracheostomies for SARS-CoV-2 at our tertiary-care, urban teaching hospital. METHODS: We reviewed the demographics, comorbidities, timing of mechanical ventilation, tracheostomy, and ICU and hospital lengths-of-stay (LOS) in SARS-CoV-2 patients who received tracheostomies. Early tracheostomy was considered <14 days of ventilation. Medians with interquartile ranges (IQR) were calculated and compared with Wilcoxon rank sum, Spearman correlation, Kruskal-Wallis, and regression modeling. RESULTS: From March 2020 to January 2021, our center had 370 patients intubated for SARS-CoV-2, and 59 (16%) had percutaneous bedside tracheostomy. Median time from intubation to tracheostomy was 19 (IQR 17 - 24) days. Demographics and comorbidities were similar between early and late tracheostomy, but early tracheostomy was associated with shorter ICU LOS and a trend towards shorter ventilation. To date, 34 (58%) of patients have been decannulated, 17 (29%) before hospital discharge; median time to decannulation was 24 (IQR 19-38) days. Decannulated patients were younger (56 vs 69 years), and in regression analysis, pneumothorax was associated was associated with lower decannulation rates (OR 0.05, 95CI 0.01 - 0.37). No providers developed symptoms or tested positive for SARS-CoV-2. CONCLUSIONS: Tracheostomy is a safe and reasonable procedure for patients with prolonged SARS-CoV-2 respiratory failure. We feel that tracheostomy enhances care for SARS-CoV-2 since early tracheostomy appears associated with shorter duration of critical care, and decannulation rates appear high for survivors.

15.
Microbiome ; 9(1): 31, 2021 01 28.
Artículo en Inglés | MEDLINE | ID: mdl-33509277

RESUMEN

BACKGROUND: Prebiotic galacto-oligosaccharides (GOS) have an extensively demonstrated beneficial impact on intestinal health. In this study, we determined the impact of GOS diets on hallmarks of gut aging: microbiome dysbiosis, inflammation, and intestinal barrier defects ("leaky gut"). We also evaluated if short-term GOS feeding influenced how the aging gut responded to antibiotic challenges in a mouse model of Clostridioides difficile infection. Finally, we assessed if colonic organoids could reproduce the GOS responder-non-responder phenotypes observed in vivo. RESULTS: Old animals had a distinct microbiome characterized by increased ratios of non-saccharolytic versus saccharolytic bacteria and, correspondingly, a lower abundance of ß-galactosidases compared to young animals. GOS reduced the overall diversity, increased the abundance of specific saccharolytic bacteria (species of Bacteroides and Lactobacillus), increased the abundance of ß-galactosidases in young and old animals, and increased the non-saccharolytic organisms; however, a robust, homogeneous bifidogenic effect was not observed. GOS reduced age-associated increased intestinal permeability and increased MUC2 expression and mucus thickness in old mice. Clyndamicin reduced the abundance Bifidobacterium while increasing Akkermansia, Clostridium, Coprococcus, Bacillus, Bacteroides, and Ruminococcus in old mice. The antibiotics were more impactful than GOS on modulating serum markers of inflammation. Higher serum levels of IL-17 and IL-6 were observed in control and GOS diets in the antibiotic groups, and within those groups, levels of IL-6 were higher in the GOS groups, regardless of age, and higher in the old compared to young animals in the control diet groups. RTqPCR revealed significantly increased gene expression of TNFα in distal colon tissue of old mice, which was decreased by the GOS diet. Colon transcriptomics analysis of mice fed GOS showed increased expression of genes involved in small-molecule metabolic processes and specifically the respirasome in old animals, which could indicate an increased oxidative metabolism and energetic efficiency. In young mice, GOS induced the expression of binding-related genes. The galectin gene Lgals1, a ß-galactosyl-binding lectin that bridges molecules by their sugar moieties and is an important modulator of the immune response, and the PI3K-Akt and ECM-receptor interaction pathways were also induced in young mice. Stools from mice exhibiting variable bifidogenic response to GOS injected into colon organoids in the presence of prebiotics reproduced the response and non-response phenotypes observed in vivo suggesting that the composition and functionality of the microbiota are the main contributors to the phenotype. CONCLUSIONS: Dietary GOS modulated homeostasis of the aging gut by promoting changes in microbiome composition and host gene expression, which was translated into decreased intestinal permeability and increased mucus production. Age was a determining factor on how prebiotics impacted the microbiome and expression of intestinal epithelial cells, especially apparent from the induction of galectin-1 in young but not old mice. Video abstract.


Asunto(s)
Envejecimiento/fisiología , Microbioma Gastrointestinal/efectos de los fármacos , Oligosacáridos/farmacología , Prebióticos , Envejecimiento/efectos de los fármacos , Envejecimiento/genética , Animales , Femenino , Intestinos/efectos de los fármacos , Intestinos/microbiología , Intestinos/fisiología , Ratones , Ratones Endogámicos C57BL , Fosfatidilinositol 3-Quinasas/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo
16.
medRxiv ; 2021 Jan 15.
Artículo en Inglés | MEDLINE | ID: mdl-33469593

RESUMEN

BACKGROUND: Severe community-acquired pneumonia secondary to SARS-CoV-2 is a leading cause of death. Current guidelines recommend patients with SARS-CoV-2 pneumonia receive empirical antibiotic therapy for suspected bacterial superinfection, but little evidence supports these recommendations. METHODS: We obtained bronchoscopic bronchoalveolar lavage (BAL) samples from patients with SARS-CoV-2 pneumonia requiring mechanical ventilation. We analyzed BAL samples with multiplex PCR and quantitative culture to determine the prevalence of superinfecting pathogens at the time of intubation and identify episodes of ventilator-associated pneumonia (VAP) over the course of mechanical ventilation. We compared antibiotic use with guideline-recommended care. RESULTS: The 179 ventilated patients with severe SARS-CoV-2 pneumonia discharged from our hospital by June 30, 2020 were analyzed. 162 (90.5%) patients had at least one BAL procedure; 133 (74.3%) within 48 hours after intubation and 112 (62.6%) had at least one subsequent BAL during their hospitalization. A superinfecting pathogen was identified within 48 hours of intubation in 28/133 (21%) patients, most commonly methicillin-sensitive Staphylococcus aureus or Streptococcus species (21/28, 75%). BAL-based treatment reduced antibiotic use compared with guideline-recommended care. 72 patients (44.4%) developed at least one VAP episode. Only 15/72 (20.8%) of initial VAPs were attributable to multidrug-resistant pathogens. The incidence rate of VAP was 45.2/1000 ventilator days. CONCLUSIONS: With use of sensitive diagnostic tools, bacterial superinfection at the time of intubation is infrequent in patients with severe SARS-CoV-2 pneumonia. Treatment based on current guidelines would result in substantial antibiotic overuse. The incidence rate of VAP in ventilated patients with SARS-CoV-2 pneumonia are higher than historically reported.

17.
J Law Med Ethics ; 48(2): 275-278, 2020 06.
Artículo en Inglés | MEDLINE | ID: mdl-32631178

RESUMEN

Many studies have shown that marijuana can negatively affect the cognitive development of adolescents. For some individuals, marijuana use may also initiate opioid use, dose escalation, and opioid use disorder. States that legalize marijuana should help adolescents through regulation of advertising and availability of marijuana-infused edibles. Such policies may assist in protecting neurodevelopment of the adolescent and young adult brain. The federal government should also remove its prohibition of marijuana sales and use, leaving their regulation to state law-makers.


Asunto(s)
Fumar Marihuana , Uso de la Marihuana , Trastornos Relacionados con Opioides , Preparaciones Farmacéuticas , Adolescente , Comercio , Humanos , Estados Unidos , Adulto Joven
18.
Acad Med ; 94(12): 1851-1853, 2019 12.
Artículo en Inglés | MEDLINE | ID: mdl-31517683

RESUMEN

Trust plays a critical role in the assessment of learners in the clinical setting. In an ideal system, learners can be vulnerable and share their limitations and areas for improvement, while faculty possess the time and skill to provide specific feedback that enables learners to achieve competency in clinical skills. For medical students, a number of threats to the establishment of trust in the learning environment exist, including the interplay between feedback and grades, the existence of bias, and competing demands for faculty time. However, several strategies can help institutions to overcome these threats and foster a culture of trust related to assessment and assessment systems: Provide ungraded environments where learners are able to be vulnerable, cocreate assessments and assessment systems with faculty and learners, acknowledge and address bias, and provide faculty with adequate time and resources to employ best practices in assessment. By intentionally employing these strategies, our institutions can support trust in assessment systems and further learner growth and achievement.


Asunto(s)
Educación de Pregrado en Medicina/métodos , Evaluación Educacional/métodos , Docentes Médicos/psicología , Aprendizaje , Estudiantes de Medicina/psicología , Confianza , Competencia Clínica , Retroalimentación Formativa , Humanos , Relaciones Interpersonales , Apoyo Social , Estados Unidos
19.
J Public Health Manag Pract ; 25(3): 221-228, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-30933957

RESUMEN

CONTEXT: Opioid-related overdoses in the United States have increased by 33% over the past 5 years. America's opioid crisis is increasing across demographic groups and spreading geographically. South Carolina is one of the states in the southern region of the United States that experiences an unusually high rate of opioid-related deaths. In 2016, 616 deaths occurred in South Carolina from drug overdoses from prescription opioid drugs, up 9% from 2015. South Carolina residents filled nearly 4.5 million opioid prescriptions in 2015, which is greater than 1.5 times the national average. IMPLEMENTATION: In 2017, the governor of South Carolina declared a statewide public health emergency in response to the growing opioid crisis. In response, a committee of the South Carolina House of Representatives released a report in January 2018 on its opioid abuse prevention study and made recommendations on ways to reduce the number of opioid-related deaths. EVALUATION: This article examines the strengths and weaknesses of South Carolina's state action plan to combat opioid-related deaths in the context of what other states have done to address opioid abuse, as well as the scientific literature on pain management. Several state opioid action plans, including South Carolina's and West Virginia's, were identified and evaluated. DISCUSSION: This article describes (1) several legislative and nonlegislative strategies being considered in South Carolina for addressing the crisis, (2) an assessment of the strengths and weaknesses of these proposals and how they compare with other states that have also implemented response plans, and (3) an examination of the scientific literature to determine best practices for treating patients who are currently taking opioids, as well as discussing alternative approaches to pain management. The authors make several recommendations to improve upon South Carolina's opioid abuse prevention plan, such as engaging communities and encouraging multistakeholder collaboration to expand access to treatment, particularly among the most vulnerable populations.


Asunto(s)
Legislación como Asunto/tendencias , Trastornos Relacionados con Opioides/prevención & control , Trastornos Relacionados con Opioides/terapia , Humanos , South Carolina
20.
J Pain Symptom Manage ; 57(1): 100-107, 2019 01.
Artículo en Inglés | MEDLINE | ID: mdl-30315917

RESUMEN

INTRODUCTION: In 2013, the Centers for Medicare and Medicaid Services issued a mandate requiring that all patients undergoing destination therapy ventricular assist device (DT VAD) implantation have access to a palliative care team before surgery. Subsequently, many VAD programs implemented a mandatory preimplantation palliative care consultation for patients considering DT VAD. However, little is known about the quality of these consults. METHODS: All patients undergoing DT VAD implantation at Northwestern Memorial Hospital from October 30, 2013 (the Centers for Medicare and Medicaid Services decision date), through March 1, 2018, were included. Palliative care consultation notes were qualitatively analyzed for elements of "palliative care assessment" and preparedness planning. RESULTS: Sixty-eight preimplantation palliative care consultations were analyzed. Fifty-six percent of the consults occurred in the intensive care unit, and the median time from consult to VAD implant was six days. General palliative care elements were infrequently discussed. Furthermore, the elements of preparedness planning-device failure, post-VAD health-related quality of life, device complications, and progressive comorbidities-were discussed in only 10%, 54%, 49%, and 12% of consultations, respectively. CONCLUSIONS: One-time preimplantation palliative care consultations at our institution do not lead to completion of preparedness planning or even general palliative care assessment. Further work is needed to determine the most effective way to integrate palliative care into preimplantation care.


Asunto(s)
Insuficiencia Cardíaca/terapia , Corazón Auxiliar , Cuidados Paliativos , Cuidados Preoperatorios , Derivación y Consulta , Planificación Anticipada de Atención , Comorbilidad , Cuidados Críticos , Femenino , Insuficiencia Cardíaca/epidemiología , Insuficiencia Cardíaca/psicología , Humanos , Masculino , Persona de Mediana Edad , Morfolinas , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/psicología , Investigación Cualitativa , Calidad de la Atención de Salud , Calidad de Vida
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