Stem-like T cells are associated with the pathogenesis of ulcerative colitis in humans.

To understand the role of T cells in the pathogenesis of ulcerative colitis (UC), we analyzed colonic T cells isolated from patients with UC and controls. Here we identified colonic CD4+ and CD8+ T lymphocyte subsets with gene expression profiles resembling stem-like progenitors, previously reported in several mouse models of autoimmune disease. Stem-like T cells were increased in inflamed areas compared to non-inflamed regions from the same patients. Furthermore, TCR sequence analysis indicated stem-like T cells were clonally related to proinflammatory T cells, suggesting their involvement in sustaining effectors that drive inflammation. Using an adoptive transfer colitis model in mice, we demonstrated that CD4+ T cells deficient in either BCL-6 or TCF1, transcription factors that promote T cell stemness, had decreased colon T cells and diminished pathogenicity. Our results establish a strong association between stem-like T cell populations and UC pathogenesis, highlighting the potential of targeting this population to improve clinical outcomes.

Cytotoxic CD4+ tissue-resident memory T cells are associated with asthma severity.

BACKGROUND: Patients with severe uncontrolled asthma represent a distinct endotype with persistent airway inflammation and remodeling that is refractory to corticosteroid treatment. CD4+ TH2 cells play a central role in orchestrating asthma pathogenesis, and biologic therapies targeting their cytokine pathways have had promising outcomes. However, not all patients respond well to such treatment, and their effects are not always durable nor reverse airway remodeling. This observation raises the possibility that other CD4+ T cell subsets and their effector molecules may drive airway inflammation and remodeling. METHODS: We performed single-cell transcriptome analysis of >50,000 airway CD4+ T cells isolated from bronchoalveolar lavage samples from 30 patients with mild and severe asthma. FINDINGS: We observed striking heterogeneity in the nature of CD4+ T cells present in asthmatics' airways, with tissue-resident memory T (TRM) cells making a dominant contribution. Notably, in severe asthmatics, a subset of CD4+ TRM cells (CD103-expressing) was significantly increased, comprising nearly 65% of all CD4+ T cells in the airways of male patients with severe asthma when compared to mild asthma (13%). This subset was enriched for transcripts linked to T cell receptor activation (HLA-DRB1, HLA-DPA1) and cytotoxicity (GZMB, GZMA) and, following stimulation, expressed high levels of transcripts encoding for pro-inflammatory non-TH2 cytokines (CCL3, CCL4, CCL5, TNF, LIGHT) that could fuel persistent airway inflammation and remodeling. CONCLUSIONS: Our findings indicate the need to look beyond the traditional T2 model of severe asthma to better understand the heterogeneity of this disease. FUNDING: This research was funded by the NIH.

Detection of porcine circovirus type 2 (PCV2) in the Philippines and the complexity of PCV2-associated disease diagnosis.

Porcine circovirus type 2 (PCV2), an important pig viral pathogen, can cause porcine circovirus-associated disease (PCVAD), resulting in economic losses associated with decreased growth and mortalities. The diagnosis of PCVAD is complex requiring clinical, pathological and virological approaches. This study assessed PCV2 infection using histopathology and immunohistochemistry (IHC) on tissue samples and quantitative polymerase chain reaction (qPCR) on serum samples from 47 grower-finisher pigs allocated in three clinical groups in the Philippines. Typical PCV2 histopathological lesions were observed in mediastinal lymph nodes (MLN) of eight of 47 pigs. Lymphoid depletion was seen in all eight pigs and granulomatous inflammation in one of these pigs. Four of these eight pigs were PCV2 positive by both IHC and qPCR. IHC revealed PCV2 antigen in 8 pigs in at least one of the following tissues: MLN (5/8), spleen (3/8), tonsils (4/8) and lungs (5/8). PCV2 antigen was observed in 3/8 MLN with lymphoid depletion and in one MLN with depletion and granulomatous inflammation. The qPCR test showed that 33 sera had a non-detectable level, twelve had < 106 and two had > 106 PCV2 DNA copies/ml serum. One pig with lymphoid depletion had > 106 PCV2 DNA copies/ml serum, and another pig without MLN lesions also had > 106 PCV2 DNA copies/ml serum. These findings suggest that PCVAD is present in the Philippines and confirm the challenges of PCVAD diagnosis as different patterns of results were obtained from the different tests.

GABAA Receptors are Selectively Expressed in NG2 Glia of the Cerebellar White Matter.

The cerebellum is involved in the coordination of movement. Its cellular composition is dominated by GABAergic neuronal types, and glial cells are known to express functional receptors. GABAergic signaling regulates cell proliferation, differentiation, and migration during neurodevelopment. However, little is known about the functional expression of GABA receptors in the cerebellar white matter (WM). Thus, the aim of this study was to test whether glial cells express functional GABA receptors during postnatal development (P7-P9) of cerebellar WM. Immunofluorescence showed that half of the astrocytes express GAD67, suggesting that glial cells synthesize GABA. Calcium imaging in cerebellar slices revealed that GABA and the GABAA agonist muscimol evoked calcium transients in sulforhodamine B negative cells, whereas the GABAB agonist baclofen failed to evoke responses in cerebellar WM. Whole-cell patch-clamp recordings of GFAP+ cells showed dye coupling and a passive current-voltage relation typical of astrocytes. Surprisingly, these cells did not respond to muscimol. Two additional populations were identified as GFAP- cells. The first population showed dye coupling, slow decaying inward and outward currents with no voltage dependence, and did not respond to GABAA agonists. The second population showed an outward-rectifying current-voltage relationship and responded to muscimol, but dye coupling was absent. These cells received synaptic input and were NG2+, but evoked calcium waves failed to modulate the frequency of spontaneous postsynaptic currents (sPSCs) or signaling into NG2 glia. We conclude that GABAA receptor-mediated signaling is selective for NG2 glia in the WM of the cerebellum.

Anorexia increases microglial density and cytokine expression in the hippocampus of young female rats.

Anorexia by osmotic dehydration is an adaptive response to hypernatremia and hyperosmolaemia induced by ingestion of a hypertonic solution. Dehydration-induced anorexia (DIA) reproduces weight loss and avoidance of food, despite its availability. By using this model, we previously showed increased reactive astrocyte density in the rat dorsal hippocampus, suggesting a pro-inflammatory environment where microglia may play an important role. However, whether such anorexic condition increases a pro-inflammatory response is unknown. The aim of this study was to test if DIA increases microglial density in the dorsal hippocampus, as well as the expression of pro-inflammatory cytokines tumor necrosis factor alpha (TNF-α), interleukin 6 (IL-6) and interleukin 1 beta (IL-1ß) in the hippocampus of young female rats. Our results showed that DIA significantly increased microglial density in CA2-CA3 and dentate gyrus (DG) but not in CA1. However, forced food restriction (FFR) only increased microglial density in the DG. Accordingly, the activated/resting microglia ratio was significantly increased in CA2-CA3 and DG, in DIA and FFR groups. Finally, western blot analysis showed increased expression of IBA1, TNF-α, IL-6 and IL-1ß in the hippocampus of both experimental groups. We conclude that anorexia triggers increased reactive microglial density and expression of TNF-α, IL-6 and IL-1ß; this environment may result in hippocampal neuroinflammation.

Gasto familiar del tratamiento con hemodiálisis en Tuxtla Gutiérrez, Chiapas, para población abierta y afiliada a los servicios de salud / Familiar health expenditures of haemodialysis treatment in Tuxtla Gutierrez, Chiapas, for open and health-affiliated populations

Resumen: Objetivo: Identificar los gastos que realizan los pacientes que reciben hemodiálisis con diferentes esquemas de cobertura en salud, en la ciudad de Tuxtla Gutiérrez, en el contexto de una entidad altamente marginada como el estado de Chiapas, en México durante los meses de agosto-septiembre de 2017. Métodos: Estudio etnográfico, observacional, descriptivo a partir de una muestra no probabilística intencional de 21 casos abordados mediante entrevistas individuales. Los criterios de selección fueron la etiología de la enfermedad renal crónica, el sexo, el tiempo que tenía el paciente en hemodiálisis, el esquema de financiamiento del tratamiento, el lugar de residencia y la edad. Resultados: Se identificaron cuatro modalidades de financiamiento del tratamiento. Considerando los gastos en medicamentos, transporte, viáticos, consultas médicas, estudios de laboratorio, dieta y hemodiálisis. El grupo que reporta menor gasto es el de pacientes institucionales que destinan en promedio $308.90 USD mensuales, seguido de los pacientes subrogados que destinaron en promedio $337.94 USD mensuales. Los pacientes semiprivados invierten $768.89 USD cada mes y el grupo con el mayor gasto es el de los pacientes privados que destinan en promedio $1,530.61 USD mensualmente. Conclusiones: El tratamiento de la ERC por medio de hemodiálisis tiene un costo mensual por paciente que va desde los $308.9 USD hasta los $1,530.61 USD, por lo tanto, las posibilidades de que un hogar asuma los costos del tratamiento están en función del esquema de seguridad social al que tienen acceso, del capital físico y financiero que posean y de las redes de apoyo que construyan.

Abstract: Objective: To identify the costs incurred by hemodialysis patients under different health coverage schemes in the city of Tuxtla Gutiérrez, in the context of a highly marginalized entity such as the state of Chiapas, Mexico. During the months of August-September 2017. Methods:Ethnographic, observational, descriptive study based on an intentional non-probabilistic sample of 21 cases addressed through individual interviews. The selection criteria were Chronic kidney disease etiology, sex, time spent on hemodialysis, treatment financing scheme, place of residence, and age. Results: Four modalities of treatment financing were identified. Considering expenses for medication, transportation, travel expenses, medical consultations, laboratory studies, diet and hemodialysis. The group that reports the lower spending is institutional patients with an average of 308.94 USD per month, followed by surrogate patients who spend an average of $337.94 USD per month. Semi-private patients invest $768.89 USD each month and the group with the highest spending is private patients who spend an average of $1,530.61 USD monthly. Conclusions: The treatment of chronic kidney disease through hemodialysis has a monthly cost per patient that ranges from $308.9 USD to $1,530.61 USD, therefore, the chances that a household can assume the costs of treatment are based on the social security system they have access to, the physical and financial capital they have and the support networks they build.

Anorexia Reduces GFAP+ Cell Density in the Rat Hippocampus.

Anorexia nervosa is an eating disorder observed primarily in young women. The neurobiology of the disorder is unknown but recently magnetic resonance imaging showed a volume reduction of the hippocampus in anorexic patients. Dehydration-induced anorexia (DIA) is a murine model that mimics core features of this disorder, including severe weight loss due to voluntary reduction in food intake. The energy supply to the brain is mediated by astrocytes, but whether their density is compromised by anorexia is unknown. Thus, the aim of this study was to estimate GFAP+ cell density in the main regions of the hippocampus (CA1, CA2, CA3, and dentate gyrus) in the DIA model. Our results showed that GFAP+ cell density was significantly reduced (~20%) in all regions of the hippocampus, except in CA1. Interestingly, DIA significantly reduced the GFAP+ cells/nuclei ratio in CA2 (-23%) and dentate gyrus (-48%). The reduction of GFAP+ cell density was in agreement with a lower expression of GFAP protein. Additionally, anorexia increased the expression of the intermediate filaments vimentin and nestin. Accordingly, anorexia increased the number of reactive astrocytes in CA2 and dentate gyrus more than twofold. We conclude that anorexia reduces the hippocampal GFAP+ cell density and increases vimentin and nestin expression.

Dehydration-Induced Anorexia Reduces Astrocyte Density in the Rat Corpus Callosum.

Anorexia nervosa is an eating disorder associated with severe weight loss as a consequence of voluntary food intake avoidance. Animal models such as dehydration-induced anorexia (DIA) mimic core features of the disorder, including voluntary reduction in food intake, which compromises the supply of energy to the brain. Glial cells, the major population of nerve cells in the central nervous system, play a crucial role in supplying energy to the neurons. The corpus callosum (CC) is the largest white matter tract in mammals, and more than 99% of the cell somata correspond to glial cells in rodents. Whether glial cell density is altered in anorexia is unknown. Thus, the aim of this study was to estimate glial cell density in the three main regions of the CC (genu, body, and splenium) in a murine model of DIA. The astrocyte density was significantly reduced (~34%) for the DIA group in the body of the CC, whereas in the genu and the splenium no significant changes were observed. DIA and forced food restriction (FFR) also reduced the ratio of astrocytes to glial cells by 57.5% and 22%, respectively, in the body of CC. Thus, we conclude that DIA reduces astrocyte density only in the body of the rat CC.

Depression among patients with end-stage renal disease in hemodialysis.

Depression is frequent in end-stage renal disease (ESRD) and predicts mortality in dialysis patients. The aim of this study was to investigate the occurrence of depression among patients on hemodialysis. We conducted an observational cross-sectional study at two hemodialysis centres in the metropolitan area of Fortaleza, Ceará, Brazil, between September and October 2010. The occurrence of depression was evaluated according to Beck Depression Inventory II. Among 148 patients interviewed, the mean age was 46 ± 13 years and 54% were male. The average time on dialysis was 5.3 ± 5.2 years. Depression was found in 101 (68.2%) cases. Depression was classified as mild (49.5%), moderate (41.5%) and severe (9%). Only 15.5% had prior depression diagnosis. Follow-up with Psychologist was being done in only 32.4% of cases. Patients with depression had a higher frequency of antidepressant use (20.7% vs. 4.2%, p=.01) and benzodiazepines (33.6% vs. 8.5%, p=.001). Among patients using antidepressant, improvement of symptoms was reported by 81.6%. Depression is one potentially modifiable risk factor in ESRD. The investigation and multidisciplinary approach of depression should be part of routine evaluation of patients on dialysis.

Percepção de estudantes de enfermagem acerca da profissão / Nursing student’s perception about the profession

O objetivo do estudo é identificar as percepções de alunos recém-admitidos ao curso de graduação em Enfermagem acerca da profissão. Estudo qualitativo, realizado no período de março a maio de 2008, junto a 38 estudantes do primeiro semestre de uma universidade pública do Ceará. A coleta de dados ocorreu por meio de cinco encontros, anotações em diário de campo e técnica do desenho projetivo, baseada no questionamento: Para você, o que é Enfermagem? Os resultados evidenciam valorização do hospital como campo de atuação, seguido do cuidado na atenção primária à saúde. Os estudantes reconhecem a Enfermagem como possibilidade de ascensão financeira, e enfatizam a relevância do apoio, ajuda e solidariedade junto ao paciente. O estudo permite identificar as percepções dos discentes de enfermagem e fazer uma reflexão acerca da necessidade de novas posturas e reconhecimento do papel do enfermeiro, independentemente do cenário de atuação.