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1.
JAMA Surg ; 2024 Apr 17.
Artículo en Inglés | MEDLINE | ID: mdl-38630452

RESUMEN

Importance: Care of patients with diverticulitis is undergoing a paradigm shift. This narrative review summarizes the current evidence for left-sided uncomplicated and complicated diverticulitis. The latest pathophysiology, advances in diagnosis, and prevention strategies are also reviewed. Observations: Treatment is moving to the outpatient setting, physicians are forgoing antibiotics for uncomplicated disease, and the decision for elective surgery for diverticulitis has become preference sensitive. Furthermore, the most current data guiding surgical management of diverticulitis include the adoption of new minimally invasive and robot-assisted techniques. Conclusions and Relevance: This review provides an updated summary of the best practices in the management of diverticulitis to guide colorectal and general surgeons in their treatment of patients with this common disease.

2.
J Taibah Univ Med Sci ; 19(2): 304-312, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38283381

RESUMEN

Objectives: To explore healthcare undergraduates' views on how to design effective IPE. The need for interprofessional education implementation in undergraduate healthcare education is gaining wide recognition globally. Students' views about their learning experiences can offer useful insights to advance teaching and learning courses. Thus, in the IPE literature, students' views on how to effectively design IPE can help shape future IPE plans. Methods: Purposeful sampling was used to recruit healthcare students who attended IPE events across three UK institutions. Virtual focus groups were conducted, and audio recorded. Transcripts were thematically analysed and relevant themes were presented under three subheadings, pre, during and post IPE session. Results: Twenty-five students from medicine, nursing, pharmacy, midwifery and other disciplines participated in six focus groups. Students thought IPE should be offered consistently across the programme's years of study to ensure learning continuity. Students from programmes with higher placement hours (nursing and midwifery), suggested more IPE in placement. Pre-IPE sessions, introducing IPE to students attending for the first time was perceived to be important as the lack of awareness/understanding of IPE could adversely impact their willingness to attend and their engagement. During IPE, interaction with other students was perceived as the core of an effective IPE session. Students reported difficulties in communication with other students via online IPE sessions and thought they were less engaged compared to face-to-face sessions. Post-IPE, students valued reflective exercises, whereas traditional formal assessment was seen as a barrier to engagement with the learning. Conclusion: Students considered IPE valuable to prepare for future practice. However, students felt that IPE experiences could be enhanced with proper planning to ensure regular compulsory IPE exposure. For better IPE experiences, IPE design and delivery should be in line with each healthcare programme's unique learning and training curriculum.

3.
J Interprof Care ; 38(2): 273-282, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38079371

RESUMEN

Interprofessional education (IPE) can help prepare future graduates to work collaboratively in healthcare teams. Using a multiple-case study approach, we explored IPE across four United Kingdom (UK) Higher Education Institutions (HEIs) to identify factors affecting IPE implementation and outcomes. For each site, educators involved with IPE were surveyed and interviewed to explore IPE implementation. To examine outcomes, students took part in focus groups and accreditation reports published by professional regulators were explored. A total of five IPE courses were surveyed, six IPE leads were interviewed, three focus groups were conducted with students, and sixteen reports were reviewed. Regulators' standards mandating IPE and directives by the Deans were the main triggers for IPE initiation. In sites where the regulator's standards were perceived by educators as non-mandating IPE, some staff were less inclined to engage with IPE initiation, which adversely affected IPE planning and delivery. Students from such sites were less satisfied with their IPE experiences and uncertain about the purpose of IPE. Senior management (i.e. Dean) commitment and support is needed to establish IPE initiatives across the institution and cultivate a collaborative culture. The presence of a collaborative culture was associated with positive feedback from regulators and students regarding IPE.


Asunto(s)
Educación Interprofesional , Relaciones Interprofesionales , Humanos , Atención a la Salud , Estudiantes , Grupos Focales
4.
Int J Pharm Pract ; 31(5): 504-511, 2023 Sep 30.
Artículo en Inglés | MEDLINE | ID: mdl-37548434

RESUMEN

OBJECTIVES: Community pharmacists (CPs) are the last healthcare professional to check the clinical appropriateness of prescribed medicines before being dispensed to patients. This process is known as 'clinical checking' and is intended to ensure the prescribed medications are safe and effective. This study aims to explore how CPs carry out clinical checking in practice, and the main factors affecting their clinical decisions. METHODS: The study was qualitative in nature, and data were collected by means of semi-structured interviews. The interview questions aimed to explore how CPs carry out clinical checking in practice. A purposive sampling strategy was employed to recruit a sample representative of CPs in England. Interview transcripts were subjected to thematic template analysis. KEY FINDINGS: Twelve CPs of various professional backgrounds participated in the interviews. The analysis yielded three overarching themes, namely: pharmacists' perception of the clinical checking process; clinical checking as a naturalistic decision-making process and barriers to effective clinical checking. Interviewees described being faced with a trade-off between examining each prescription thoroughly and maintaining the throughput of prescriptions, due to the highly pressurised environment they work within. A number of factors inform this trade-off: (1) assuming the safety of repeat medicines; (2) lacking access to sufficient clinical information and (3) working under challenging circumstances (such as a lack of resources). CONCLUSIONS: Clinical checking is a complex, variable and experience-driven process which is heavily influenced by the surrounding environment and information accessibility. Further research should investigate the cognitive process involved in clinical checking and explore the practicalities and potential benefits of the recommendations identified in this study.

5.
J Immunol ; 211(3): 389-402, 2023 08 01.
Artículo en Inglés | MEDLINE | ID: mdl-37272847

RESUMEN

The impact of endemic parasitic infection on vaccine efficacy is an important consideration for vaccine development and deployment. We have examined whether intestinal infection with the natural murine helminth Heligmosomoides polygyrus bakeri alters Ag-specific Ab and cellular immune responses to oral and parenteral vaccination in mice. Oral vaccination of mice with a clinically relevant, live, attenuated, recombinant Salmonella vaccine expressing chicken egg OVA (Salmonella-OVA) induced the accumulation of activated, OVA-specific T effector cells rather than OVA-specific regulatory T cells in the GALT. Intestinal helminth infection significantly reduced Th1-skewed Ab responses to oral vaccination with Salmonella-OVA. Activated, adoptively transferred, OVA-specific CD4+ T cells accumulated in draining mesenteric lymph nodes of vaccinated mice, regardless of their helminth infection status. However, helminth infection increased the frequencies of adoptively transferred OVA-specific CD4+ T cells producing IL-4 and IL-10 in the mesenteric lymph node. Ab responses to the oral Salmonella-OVA vaccine were reduced in helminth-free mice adoptively transferred with OVA-specific CD4+ T cells harvested from mice with intestinal helminth infection. Intestinal helminth infection also significantly reduced Th2-skewed Ab responses to parenteral vaccination with OVA adsorbed to alum. These findings suggest that vaccine-specific CD4+ T cells induced in the context of helminth infection retain durable immunomodulatory properties and may promote blunted Ab responses to vaccination. They also underscore the potential need to treat parasitic infection before mass vaccination campaigns in helminth-endemic areas.


Asunto(s)
Helmintiasis , Parasitosis Intestinales , Ratones , Animales , Eficacia de las Vacunas , Linfocitos T CD4-Positivos , Vacunas Sintéticas , Ovalbúmina , Ratones Endogámicos BALB C
6.
Nat Ecol Evol ; 7(6): 903-913, 2023 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-37188966

RESUMEN

Butterflies are a diverse and charismatic insect group that are thought to have evolved with plants and dispersed throughout the world in response to key geological events. However, these hypotheses have not been extensively tested because a comprehensive phylogenetic framework and datasets for butterfly larval hosts and global distributions are lacking. We sequenced 391 genes from nearly 2,300 butterfly species, sampled from 90 countries and 28 specimen collections, to reconstruct a new phylogenomic tree of butterflies representing 92% of all genera. Our phylogeny has strong support for nearly all nodes and demonstrates that at least 36 butterfly tribes require reclassification. Divergence time analyses imply an origin ~100 million years ago for butterflies and indicate that all but one family were present before the K/Pg extinction event. We aggregated larval host datasets and global distribution records and found that butterflies are likely to have first fed on Fabaceae and originated in what is now the Americas. Soon after the Cretaceous Thermal Maximum, butterflies crossed Beringia and diversified in the Palaeotropics. Our results also reveal that most butterfly species are specialists that feed on only one larval host plant family. However, generalist butterflies that consume two or more plant families usually feed on closely related plants.


Asunto(s)
Mariposas Diurnas , Filogenia , Animales , Evolución Biológica , Mariposas Diurnas/genética
8.
Cureus ; 15(4): e37668, 2023 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-37206532

RESUMEN

Enteroatmospheric fistula (EAF) is a relatively rare complication of patients undergoing open abdomen (OA) for damage control surgery. Mortality rates are high due to the increased risk of peritonitis, intraabdominal abscess, sepsis, and new perforations. There are a wide range of EAF management therapies in the literature, however, there are limited options on cases involving fistula-vaccum assisted closure (VAC) therapy. This case describes the treatment course of a 57-year-old, male admitted for blunt abdominal trauma secondary to a motor vehicle accident. Upon admission the patient underwent damage control surgery. The surgeons elected to have the patient's abdomen open, applying a mesh to promote healing. After several weeks of hospitalization an EAF was discovered in the abdominal wound subsequently managed by utilizing a fistula-VAC technique. Based on the successful outcome of this patient, fistula-VAC was shown as an effective way to promote wound healing while reducing the chances of complications.

9.
Ann Surg Oncol ; 30(8): 4631-4635, 2023 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-37067741

RESUMEN

BACKGROUND: The Centers for Medicare & Medicaid Services (CMS) mandate that every US hospital provide public online pricing information for services rendered. This allows patients to compare prices across hospital systems before establishing care. The goal of this project was to evaluate hospital compliance and patient-level accessibility to price transparency for common breast cancer surgical procedures. METHODS: A sample case of a 62-year-old female with a T2N0 breast cancer was chosen. The patient would have the option of undergoing a partial mastectomy or mastectomy, both with sentinel lymph node biopsy (SLNB). Eight Massachusetts academic medical centers were evaluated. Searches were performed by authors for each hospital system and procedure using the sample case. RESULTS: Every hospital had a cost calculator on its website. The average success rate of establishing a cost for partial mastectomy, mastectomy, and SLNB was 58, 35, and 25%, respectively. The median time to reach the cost calculator tool was 32 s (range 25-37 s). In successful attempts, the median pre-insurance estimated cost of a partial mastectomy was $16,509 (range $11,776-22,169), compared with $24,541 (range $16,921-25,543) for mastectomy and $12,342 (range $4034-20,644) for SLNB. SLNB costs varied significantly across hospitals (p = 0.025), but no statistically significant difference was observed for partial mastectomy or mastectomy. CONCLUSION: Despite new regulatory requirements by CMS for increased price transparency for surgical procedures, our results demonstrate poor success rates in obtaining cost estimates and significant variability of reported hospital charges. Further efforts to improve the quality of hospital cost estimate calculators are necessary for informed decision-making for patients with breast cancer.


Asunto(s)
Neoplasias de la Mama , Anciano , Femenino , Humanos , Estados Unidos , Persona de Mediana Edad , Neoplasias de la Mama/cirugía , Neoplasias de la Mama/patología , Mastectomía , Medicare , Biopsia del Ganglio Linfático Centinela , Costos y Análisis de Costo
10.
PLoS One ; 18(2): e0269828, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36757947

RESUMEN

INTRODUCTION: Chronic Pelvic Pain (CPP) is a complex, multifaceted condition that affects both women and men. There is limited literature on the cost utilization the healthcare system and CPP patients incur. The purpose of this analysis is to characterize the overall healthcare utilization, cost burden, and quality-of-life restrictions experienced by CPP patients using data from an outpatient pelvic rehabilitation practice. METHODS: Healthcare utilization data was gathered by systematically reviewing and analyzing data from new patient visit progress notes stored in the clinic's electronic health records (EHR). We obtained in-network costs by using the FAIR Health Consumer online database. Overall costs were then calculated as the utilization times the per-unit costs from the FAIR database. Additionally, data on patients' visual analogue scale (VAS), absenteeism, presenteeism emergency room visits, usage of common pain medications, use of diagnostics, and participation in common treatment modalities was gathered. RESULTS: Data from 607 patients was used. The overall cost burden per patient for all surgeries combined was $15,750 for in-network services. The cost burden for diagnostics was $5,264.22 and treatments was $8,937 per patient for in-network treatments. CONCLUSION: Chronic Pelvic Pain was found to have a large cost burden of $29,951 for in-network services which includes treatments, diagnostics, and surgeries. This analysis sets the stage for future investigations involving data on costs of medications that patients have tried prior to presenting to us and costs associated with work hours lost.


Asunto(s)
Dolor Crónico , Calidad de Vida , Masculino , Humanos , Femenino , Pacientes Ambulatorios , Aceptación de la Atención de Salud , Dimensión del Dolor , Dolor Pélvico/terapia , Dolor Crónico/terapia
11.
J Natl Med Assoc ; 115(1): 90-98, 2023 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-36470707

RESUMEN

BACKGROUND: Colorectal cancer screening has been shown effective at reducing stage at presentation, but there is differential uptake of screening based on insurance status. We sought to determine the population-level effect of Medicare and screening guidelines on colorectal screening by race and region. METHODS: Data on Black and white patients with colorectal cancer were obtained from the SEER database. Regression discontinuity was used to assess the causal effect of near-universal health insurance (represented by age 65) and United States Preventive Services Task Force guidelines (age 50) on the proportion of people presenting at advanced stage. This was stratified by race and region. RESULTS: In the Southern United States, Black patients saw a significant decrease in advanced stage at presentation at age 65 (coefficient -0.12, p = 0.003), while white patients did not (coefficient -0.03, p = 0.09). At age 50, neither Black (coefficient 0.09, p = 0.10) nor white patients (coefficient -0.04, p = 0.1) saw a significant decrease in advanced stage. In the Western U.S., neither Black (coefficient 0.02, p = 0.72) or white patients (coefficient -0.02, p = 0.09) saw a significant decrease in advanced stage at age 65; however, both Black (coefficient -0.20, p = 0.008) and white patients (coefficient -0.05, p = 0.03) saw a significant decrease at age 50. CONCLUSIONS: Our data highlight the significant impact that near-universal insurance has on reducing colorectal cancer stage at presentation in areas with poor baseline insurance coverage, particularly for Black patients. To reduce disparities in advanced stage at presentation for colorectal cancer, state-level insurance coverage should be addressed.


Asunto(s)
Neoplasias Colorrectales , Medicare , Humanos , Anciano , Estados Unidos/epidemiología , Persona de Mediana Edad , Detección Precoz del Cáncer , Neoplasias Colorrectales/diagnóstico , Neoplasias Colorrectales/prevención & control , Población Negra , Disparidades en Atención de Salud , Blanco
12.
Immunity ; 55(11): 2027-2043.e9, 2022 11 08.
Artículo en Inglés | MEDLINE | ID: mdl-36243007

RESUMEN

T helper 17 (Th17) cells regulate mucosal barrier defenses but also promote multiple autoinflammatory diseases. Although many molecular determinants of Th17 cell differentiation have been elucidated, the transcriptional programs that sustain Th17 cells in vivo remain obscure. The transcription factor RORγt is critical for Th17 cell differentiation; however, it is not clear whether the closely related RORα, which is co-expressed in Th17 cells, has a distinct role. Here, we demonstrated that although dispensable for Th17 cell differentiation, RORα was necessary for optimal Th17 responses in peripheral tissues. The absence of RORα in T cells led to reductions in both RORγt expression and effector function among Th17 cells. Cooperative binding of RORα and RORγt to a previously unidentified Rorc cis-regulatory element was essential for Th17 lineage maintenance in vivo. These data point to a non-redundant role of RORα in Th17 lineage maintenance via reinforcement of the RORγt transcriptional program.


Asunto(s)
Encefalomielitis Autoinmune Experimental , Miembro 3 del Grupo F de la Subfamilia 1 de Receptores Nucleares , Diferenciación Celular , Encefalomielitis Autoinmune Experimental/metabolismo , Regulación de la Expresión Génica , Miembro 3 del Grupo F de la Subfamilia 1 de Receptores Nucleares/genética , Miembro 3 del Grupo F de la Subfamilia 1 de Receptores Nucleares/metabolismo , Células Th17/metabolismo , Factores de Transcripción/metabolismo
13.
MMWR Morb Mortal Wkly Rep ; 71(32): 1005-1010, 2022 Aug 12.
Artículo en Inglés | MEDLINE | ID: mdl-35951486

RESUMEN

Self-tests* to detect current infection with SARS-CoV-2, the virus that causes COVID-19, are valuable tools that guide individual decision-making and risk reduction† (1-3). Increased self-test use (4) has likely contributed to underascertainment of COVID-19 cases (5-7), because unlike the requirements to report results of laboratory-based and health care provider-administered point-of-care COVID-19 tests,§ public health authorities do not require reporting of self-test results. However, self-test instructions include a recommendation that users report results to their health care provider so that they can receive additional testing and treatment if clinically indicated.¶ In addition, multiple manufacturers of COVID-19 self-tests have developed websites or companion mobile applications for users to voluntarily report self-test result data. Federal agencies use the data reported to manufacturers, in combination with manufacturing supply chain information, to better understand self-test availability and use. This report summarizes data voluntarily reported by users of 10.7 million self-tests from four manufacturers during October 31, 2021-June 11, 2022, and compares these self-test data with data received by CDC for 361.9 million laboratory-based and point-of-care tests performed during the same period. Overall trends in reporting volume and percentage of positive results, as well as completeness of reporting demographic variables, were similar across test types. However, the limited amount and quality of data reported from self-tests currently reduces their capacity to augment existing surveillance. Self-tests provide important risk-reduction information to users, and continued development of infrastructure and methods to collect and analyze data from self-tests could improve their use for surveillance during public health emergencies.


Asunto(s)
COVID-19 , COVID-19/diagnóstico , COVID-19/epidemiología , Prueba de COVID-19 , Humanos , SARS-CoV-2 , Autoevaluación , Estados Unidos/epidemiología
15.
Health Promot Int ; 37(1)2022 Feb 17.
Artículo en Inglés | MEDLINE | ID: mdl-33948640

RESUMEN

This project is an exploratory survey of the ways in which living in the UK has affected the health-related behaviours of Saudi Arabian undergraduate students. The study identifies changes in exercise behaviours, dietary and smoking habits and experiences of stress after their move to the UK. In addition, it identifies what the students perceive to be the drivers of these changes. To achieve this, an online questionnaire was developed collecting quantitative data. This was distributed via Facebook groups specifically for Saudi students in the UK. The results demonstrate that a majority of Saudi Arabian undergraduates felt that their behaviours had become healthier since their move to the UK, mainly as a result of a more active lifestyle, derived from reduced reliance on cars, increased daily walking, and a heightened focus on health promoted by their independence, the availability of healthy foods and exposure to a more health-promoting culture. Although these results are based on a relatively small sample, they are surprising since they contradict previous studies on international students, which have generally found negative lifestyle changes during their studies, including increased stress, poorer dietary habits and a decline in physical activity. Although the exploratory nature of the study means that concrete recommendations cannot be made, it nonetheless offers an impetus for further research into how Saudi Arabian students may be encouraged to adopt healthier lifestyles while studying in the UK.


Asunto(s)
Conductas Relacionadas con la Salud , Estudiantes , Conducta Alimentaria , Humanos , Arabia Saudita , Reino Unido
16.
Ann Surg ; 275(3): 546-550, 2022 03 01.
Artículo en Inglés | MEDLINE | ID: mdl-34954755

RESUMEN

OBJECTIVE: To determine the impact of income mobility on racial disparities in colorectal cancer. BACKGROUND: There are well-documented disparities in colorectal cancer treatment and outcomes between Black and White patients. Socioeconomic status, insurance, and other patient-level factors have been shown important, but little has been done to show the discriminatory factors that lead to these outcomes. METHODS: Data were obtained from the Surveillance Epidemiology and End-Results database for Black and White patients with colorectal cancer between 2005 and 2015. County level measures of Black (BIM) and White income mobility (WIM) were obtained from the Opportunity Atlas as a measure of intergenerational poverty and social mobility. Regression models were created to assess the relative risk of advanced stage at diagnosis (Stage IV), surgery for localized disease (Stage I/II), and cancer-specific mortality. RESULTS: There was no significant association of BIM or WIM on advanced stage at diagnosis in Black or White patients. An increase of $10,000 of BIM was associated with a 9% decrease in hazards of death for both Black (hazard ratio 0.91, 95% confidence interval 0.86,0.95) and White (0.91, 95%CI 0.90,0.93) patients, while the same increase in WIM was associated with no significant difference in hazards among Black patients (hazard ratio 0.99, 95% confidence interval 0.97,1.02). There were no predicted racial differences in hazards of death at high levels of BIM. CONCLUSIONS: Increased Black income mobility significantly improves survival for both Black and White patients. Interventions aimed at increasing economic and social mobility could significantly decrease mortality in both Black and White patients while alleviating disparities in outcomes.


Asunto(s)
Negro o Afroamericano , Neoplasias Colorrectales/mortalidad , Renta , Movilidad Social , Población Blanca , Anciano , Anciano de 80 o más Años , Estudios Transversales , Femenino , Humanos , Masculino , Persona de Mediana Edad , Tasa de Supervivencia
17.
Pediatr Qual Saf ; 6(5): e473, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34589647

RESUMEN

Improving the discharge process is an area of focus throughout healthcare organizations. Capacity constraints, efficiency improvement, patient safety, and quality care are driving forces for many discharge process workgroups. METHODS: Following the Pareto principle, we focused on improving the discharge process on the medical-surgical units that received the most patients admitted from the emergency department. Increased demand for medical-surgical beds, renovations, and diminished bed capacity made it imperative to improve efficiency using quality improvement techniques. A core team of frontline staff decreased the time between computer entry of discharge orders and patient's departure from the unit to less than 60 minutes, with 80% compliance. The team developed a daily dashboard that detailed the process and outcome measures to create situational awareness and daily visual management. Additional observations of staff workflow uncovered excessive walking for printer use. Printers were placed at the point of use to reduce transport times. Next, using survey results provided by patients on discharge quality, a Treasure Map that aided with teach-back and Team Discharge were implemented to level the staff's workload. Finally, physicians discharged patients earlier in the day. They standardized their discharge criteria to remove subjectivity from the discharge process and enable better team involvement. RESULTS: After implementing 4 interventions, the average time between computer entry of discharge orders and patient's departure from the unit decreased (94.26 versus 65.98 minutes; P < 0.001), simultaneously reducing our average length of stay from 5.62 to 4.81 days (P < 0.001). CONCLUSIONS: In conclusion, hardwiring proven interventions and complementing them with daily visual management led to significant, sustained results.

18.
Sci Rep ; 11(1): 17220, 2021 08 26.
Artículo en Inglés | MEDLINE | ID: mdl-34446743

RESUMEN

Primary cilia protrude from the apical surface of many cell types and act as a sensory organelle that regulates diverse biological processes ranging from chemo- and mechanosensation to signaling. Ciliary dysfunction is associated with a wide array of genetic disorders, known as ciliopathies. Polycystic lesions are commonly found in the kidney, liver, and pancreas of ciliopathy patients and mouse models. However, the pathogenesis of the pancreatic phenotype remains poorly understood. Chibby1 (Cby1), a small conserved coiled-coil protein, localizes to the ciliary base and plays a crucial role in ciliogenesis. Here, we report that Cby1-knockout (KO) mice develop severe exocrine pancreatic atrophy with dilated ducts during early postnatal development. A significant reduction in the number and length of cilia was observed in Cby1-KO pancreta. In the adult Cby1-KO pancreas, inflammatory cell infiltration and fibrosis were noticeable. Intriguingly, Cby1-KO acinar cells showed an accumulation of zymogen granules (ZGs) with altered polarity. Moreover, isolated acini from Cby1-KO pancreas exhibited defective ZG secretion in vitro. Collectively, our results suggest that, upon loss of Cby1, concomitant with ciliary defects, acinar cells accumulate ZGs due to defective exocytosis, leading to cell death and progressive exocrine pancreatic degeneration after birth.


Asunto(s)
Proteínas Portadoras/genética , Cilios/metabolismo , Páncreas Exocrino/metabolismo , Páncreas/metabolismo , Pancreatitis/genética , Células Acinares/metabolismo , Animales , Atrofia , Proteínas Portadoras/metabolismo , Ciliopatías/genética , Ciliopatías/metabolismo , Exocitosis/genética , Ratones de la Cepa 129 , Ratones Endogámicos C57BL , Ratones Noqueados , Microscopía Electrónica de Transmisión , Páncreas/patología , Páncreas/ultraestructura , Páncreas Exocrino/patología , Pancreatitis/metabolismo , Vesículas Secretoras/metabolismo
19.
Immunity ; 54(8): 1745-1757.e7, 2021 08 10.
Artículo en Inglés | MEDLINE | ID: mdl-34348118

RESUMEN

Environmental enteric dysfunction (EED) is a gastrointestinal inflammatory disease caused by malnutrition and chronic infection. EED is associated with stunting in children and reduced efficacy of oral vaccines. To study the mechanisms of oral vaccine failure during EED, we developed a microbiota- and diet-dependent mouse EED model. Analysis of E. coli-labile toxin vaccine-specific CD4+ T cells in these mice revealed impaired CD4+ T cell responses in the small intestine and but not the lymph nodes. EED mice exhibited increased frequencies of small intestine-resident RORγT+FOXP3+ regulatory T (Treg) cells. Targeted deletion of RORγT from Treg cells restored small intestinal vaccine-specific CD4 T cell responses and vaccine-mediated protection upon challenge. However, ablation of RORγT+FOXP3+ Treg cells made mice more susceptible to EED-induced stunting. Our findings provide insight into the poor efficacy of oral vaccines in EED and highlight how RORγT+FOXP3+ Treg cells can regulate intestinal immunity while leaving systemic responses intact.


Asunto(s)
Toxinas Bacterianas/inmunología , Vacunas contra Escherichia coli/inmunología , Enfermedades Gastrointestinales/inmunología , Intestino Delgado/inmunología , Linfocitos T Reguladores/inmunología , Administración Oral , Animales , Línea Celular , Modelos Animales de Enfermedad , Drosophila , Escherichia coli/inmunología , Femenino , Factores de Transcripción Forkhead/metabolismo , Enfermedades Gastrointestinales/microbiología , Enfermedades Gastrointestinales/patología , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Transgénicos , Miembro 3 del Grupo F de la Subfamilia 1 de Receptores Nucleares/metabolismo , Vacunación
20.
Clin Colon Rectal Surg ; 34(2): 79-80, 2021 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-33642945
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