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Neutrophils are key first responders to Clostridioides difficile infection (CDI). Excessive tissue and blood neutrophils are associated with worse histopathology and adverse outcomes, however their functional role during CDI remains poorly defined. Utilizing intestinal epithelial cell (IEC)-neutrophil co-cultures and a pre-clinical animal model of CDI, we show that neutrophils exacerbate C. difficile -induced IEC injury. We utilized cutting-edge single-cell transcriptomics to illuminate neutrophil subtypes and biological pathways that could exacerbate CDI-associated IEC damage. As such, we have established the first transcriptomics atlas of bone marrow (BM), blood, and colonic neutrophils after CDI. We found that CDI altered the developmental trajectory of BM and blood neutrophils towards populations that exhibit gene signatures associated with pro-inflammatory responses and neutrophil-mediated tissue damage. Similarly, the transcriptomic signature of colonic neutrophils was consistent with hyper-inflammatory and highly differentiated cells that had amplified expression of cytokine-mediated signaling and degranulation priming genes. One of the top 10 variable features in colonic neutrophils was the gene for neutrophil glycoprotein, Olfactomedin 4 (OLFM4). CDI enhanced OLFM4 mRNA and protein expression in neutrophils, and OLFM4 + cells aggregated to areas of severe IEC damage. Compared to uninfected controls, both humans and mice with CDI had higher concentrations of circulating OLFM4; and in mice, OLFM4 deficiency resulted in faster recovery and better survival after infection. Collectively, these studies provide novel insights into neutrophil-mediated pathology after CDI and highlight the pathogenic role of OLFM4 + neutrophils in regulating CDI-induced IEC damage. One Sentence Summary: Utilizing single-cell transcriptomics, IEC-epithelial co-cultures, and pre-clinical models of CDI, we have identified a subset of neutrophils that are marked by OLFM4 expression as pathogenic determinants of IEC barrier damage after CDI.
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Adipogenesis is a complex process controlled by intrinsic and extrinsic factors that regulate preadipocyte proliferation, adipogenic capacity and maturation of metabolic function. Here we show that insulin and IGF-1 receptors are essential for mature adipocyte survival and that deletion of both IR and IGF1R specifically in fat using a tamoxifen inducible-AdipoQ-Cre (Ai-DKO) leads to rapid and severe loss of adipocytes in all depots, associated with a metabolic syndrome characterized by hypertriglyceridemia, hyperglycemia, hyperinsulinemia, fatty liver, and pancreatic beta cell proliferation. In this model, this pathological phenotype reverses over a few weeks, in large part, due to preadipocyte proliferation and adipose tissue regeneration. Incubation of preadipocytes with serum from the Ai-DKO mice in vitro stimulates cell proliferation, and this effect can be mimicked by conditioned media from liver slices of Ai-DKO mice, but not by media of cultured Ai-DKO adipocytes, indicating a hepatic origin of the growth factor. Proteomic analysis of serum reveals apolipoprotein C3 (APOC3), a protein secreted by liver, as one of the most upregulated proteins in the Ai-DKO mice. In vitro, purified and delipidated APOC3 stimulates preadipocyte proliferation, however, knockdown of hepatic APOC3 in vivo in Ai-DKO mice is not sufficient to block adipose regeneration. Thus, lipodystrophy is associated with presence of increased preadipocyte-stimulating growth factors in serum. Our study indicates that APOC3 is one contributing factor to preadipocyte proliferation, however, other still-unidentified circulating growth factors are also likely present in Ai-DKO mice. Identification of these factors may provide a new approach to regulation of adipose mass in health and disease.
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Lipodistrofia , Proteómica , Adipogénesis , Animales , Apolipoproteína C-III , Proliferación Celular , RatonesRESUMEN
The presence of an adenocarcinoma and non-Hodgkin's lymphoma in an individual is an uncommon finding. In this case report, we discuss the case of an elderly man presenting with a synchronous moderately differentiated colonic adenocarcinoma alongside a distal ileal extranodal marginal zone lymphoma, on a background of ulcerative colitis. He underwent an elective open panproctocolectomy with an end ileostomy for the management of his malignancy.
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Adenocarcinoma/patología , Colitis Ulcerosa , Neoplasias del Colon/patología , Neoplasias del Íleon/patología , Linfoma no Hodgkin/patología , Neoplasias Primarias Múltiples/patología , Anciano , Humanos , MasculinoRESUMEN
BACKGROUND: Cryopreservation of semen is a valuable technique; however, it is also known to be detrimental to the structure of spermatozoa and fertility due to cryo-injury and subsequent generation of reactive oxidants. OBJECTIVE: To determine the time-dependent impact of reactive oxidants on seminal attributes, mitochondrial membrane potential (MMP), lipid peroxidation status (LPO) and early capacitation like changes. MATERIALS AND METHODS: Semen samples were collected by artificial vagina technique from six Karan-Fries (KF) bulls and subsequently examined at 0 h (before cryopreservation) and at 24 hours, 15 days and 2-months of storage for various seminal attributes, MMP, and early capacitation-like changes. Simultaneously, LPO (TBARS) was determined in fresh and post-thaw seminal plasma. RESULTS: A sharp decrease (P < 0.01) in semen quality was observed only after 24 h of cryopreservation except for viability and acrosomal integrity. Sperm viability and acrosome integrity reduced significantly up to 2 months of cryopreservation. The lipid peroxidation status was found to be lower in fresh seminal plasma (2.6 ±0.2 vs. 3.5 ± 0.3 units/mL) as compared to post-thaw. Furthermore, the active MMP of fresh semen showed a significant (P < 0.01) decrease after 24 hours (77.9 ± 0.4 vs. 54.5 ±0.3%) of cryopreservation, while there was a non-significant decrease in active MMP after 15 d and 2-months (53.7 ± 0.1 and 52.8 ± 0.2%). Moreover, significant (P. < 0.01) early capacitation-like changes were found in post-thaw spermatozoa (25.7 ± 0.1 vs. 9.1 ± 0.2%) as compared to fresh ejaculate. CONCLUSION: Spermatozoa incur the majority of damages during the early phase of cryopreservation, however the damage associated by different stressors cannot be neglected. doi.org/10.54680/fr22410110212.
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Preservación de Semen , Semen , Femenino , Masculino , Animales , Bovinos , Análisis de Semen , Criopreservación/veterinaria , Criopreservación/métodos , Oxidantes/farmacología , Peroxidación de Lípido , Potencial de la Membrana Mitocondrial , Motilidad Espermática , Espermatozoides , Preservación de Semen/veterinaria , Preservación de Semen/métodosRESUMEN
The presence of an adenocarcinoma and non-Hodgkin's lymphoma in an individual is an uncommon finding. In this case report, we discuss the case of an elderly man presenting with a synchronous moderately differentiated colonic adenocarcinoma alongside a distal ileal extranodal marginal zone lymphoma, on a background of ulcerative colitis. He underwent an elective open panproctocolectomy with an end ileostomy for the management of his malignancy.
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Adenocarcinoma , Colitis Ulcerosa , Neoplasias del Colon , Linfoma no Hodgkin , Neoplasias Primarias Múltiples , Adenocarcinoma/diagnóstico , Adenocarcinoma/etiología , Adenocarcinoma/cirugía , Anciano , Colitis Ulcerosa/complicaciones , Neoplasias del Colon/diagnóstico , Neoplasias del Colon/etiología , Neoplasias del Colon/cirugía , Humanos , Linfoma no Hodgkin/complicaciones , Linfoma no Hodgkin/diagnóstico , Linfoma no Hodgkin/patología , Masculino , Neoplasias Primarias Múltiples/diagnóstico , Neoplasias Primarias Múltiples/patología , Neoplasias Primarias Múltiples/cirugíaRESUMEN
BACKGROUND: Surgical site infections (SSI) are the commonest healthcare associated infections. They severely compromise patient safety, are a significant burden on healthcare resources and have an adverse impact on patient quality of life. The incidence of SSIs can be as high as 10% after colorectal procedures. The laparoscopic approach is being increasingly used to undertake colorectal procedures. It provides advantages over the traditional open approach with smaller incisions, shorter hospital stay and equal oncological outcomes. The aim of this meta-analysis was to evaluate whether the laparoscopic approach for colorectal procedures reduces the incidence of SSI compared to the open approach. METHODS: Randomised controlled trials (RCTs) comparing the two approaches published since 2000 were included in the review. Revman 5.3 software was used to carry out the review. Data were pooled and the results were shown as risk ratios with 95% confidence intervals using the fixed effects model. RESULTS: Sixteen RCT's were included in the analysis comprising 5797 patients. These covered a range of colorectal pathologies including colon cancer, rectal cancer, inflammatory bowel disease and familial adenomatous polyposis syndrome. Analysis showed significantly lower wound infection rates (RR: 0.72, 95% confidence interval: 0.60-0.88, p = 0.001) and lower abdominal abscess rates (RR: 0.88, 95% CI 0.62-1.27, p = 0.51). The combined SSI rate was significantly lower in laparoscopic compared to open surgery (RR: 0.76, 95% CI 0.64-0.90, p = 0.001). CONCLUSIONS: Laparoscopic colorectal surgery significantly lowers the incidence of SSI compared to open surgery.
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Procedimientos Quirúrgicos del Sistema Digestivo , Laparoscopía , Neoplasias del Recto , Procedimientos Quirúrgicos del Sistema Digestivo/efectos adversos , Humanos , Incidencia , Neoplasias del Recto/cirugía , Infección de la Herida Quirúrgica/epidemiología , Infección de la Herida Quirúrgica/etiología , Infección de la Herida Quirúrgica/prevención & controlRESUMEN
Antineutrophil cytoplasmic antibody (ANCA)-associated glomerulonephritis in a patient of scleroderma is very rare. Very few cases have been reported in English literature. We report a case of a 58-year-old male with long-standing limited cutaneous scleroderma (Scl-70 positive) presenting with normotensive scleroderma renal crisis. Perinuclear ANCA with antimyeloperoxidase antibody was found to be strongly positive. Renal biopsy showed pauci immune-necrotizing crescentic glomerulonephritis. We believe that this case report will be helpful in understanding clinical features of normotensive ANCA-associated glomerulonephritis in scleroderma patients.
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Myringoplasty is one of the commonest operations performed on the middle ear. Our aim was to compare the results of endoscopic permeatal myringoplasty with that of conventional myringoplasty by post aural approach using operating microscope. A total of 120 patients having central perforation of tympanic membrane were randomly divided into two equal groups of 60 patients each. In the first group, endoscope was used and in the second group microscope was used to do myringoplasty. Temporalis fascia was used as a graft material. The patients were kept in follow-up for 1 year. The pre-operative and post-operative audiograms, post-operative pain, graft uptake and time taken for surgery were compared in both the groups. The graft uptake rate was 91.67% in the endoscopic group, whereas it was 93.3% in the microscopic group. Post-operative pain was significantly less in the endoscopic group as compared with microscopic group and not much difference was found in the gain in A-B gap in either group. The mean ABG gain was 16.16 dB (SD = 4.68) in endoscopic group and 19.54 dB (SD = 3.45) in microscopic group. On applying the Mann-Whitney U test, this finding was statistically significant (p value = 0.0001). In our study success rate was equal between endoscopic and microscopic technique. In terms of morbidity and postoperative recovery endoscope produced better results. Endoscopic tympanoplasty can be a good alternative of microscopic tympanoplasty.
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Schwannomas are benign neoplasms of the peripheral nerves originating in the Schwann cells. They are rare and usually solitary, with clearly delimited capsules. They occur in the head and neck region in only 25 % of the cases, and may be associated with Von Recklinghausen's disease. Schwannomas are always a diagnostic dilemma as they are asymptomatic for long time and histopathology is the gold standard for diagnosis. The present study retrospectively analysed data of 4 patients with schwannomas and reviewed the literature on the subject. Retrospective study at ENT & Head and Neck Surgery Department of Navodaya Medical College, Raichur. Data of 4 patients between 2008 and 2014 were reviewed. The sites of cervical schwannomas and the intraoperative, histopathological and postoperative clinical status of these cases were studied. Diagnostic methods, type of surgery and associated nerve of origin (NOO) were evaluated. The patients' age ranged from 18 to 50 years. None of them had type I neurofibromatosis or Von Recklinghausen's disease. The nerves affected included the brachial plexus, vagus nerve, sympathetic chain and lingual nerve. The nerve of origin was identified based on intra-operative findings and post-operative neurological deficits. Tumour was removed by debulk operation with the preservation of NOO method. Schwannomas are generally benign, and rarely recur. An accurate preoperative workup with the identification of NOO is very important not only for a correct diagnosis, but also for surgical planning and informing the patient about the possible complications.
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BACKGROUND AND OBJECTIVE: Epilepsy, the most common neurological disorder, has treatment failure rate of 20 to 25%. Inter-individual variability in drug response can be attributed to genetic polymorphism in genes encoding different drug metabolizing enzymes, drug transporters (P-gp), and enzymes involved in sodium channel biosynthesis. The present study attempted to evaluate association of polymorphisms of CYP2C9, CYP2C19, and ABCB1, and P-gp activity with treatment response in patients with epilepsy. MATERIALS AND METHODS: Patients with epilepsy on phenytoin and/or phenobarbital and/or carbamazepine were categorized into responders and non-responders as per the International League Against Epilepsy. Plasma drug concentration was estimated by high-performance liquid chromatography. P-gp activity was measured by flow cytometry using rhodamine efflux. The polymerase chain reaction (PCR-RFLP) was used to study polymorphisms of ABCB1 (C3435T), CYP2C9 (416 C > T, and 1061 A > T), and CYP2C19 (681 G > A and 636 G > A). RESULTS: Of total 117 patients enrolled in this study, genotype data was available for 115 patients. P-gp activity was higher in non-responders (n = 68) compared to responders (n = 47) (P<0.001). No association of 416 C > T and 1061 A > T in CYP2C9 or 681 G > A and 636 G > A in CYP2C19 was observed with response phenotype in genotypic analysis. Significant genotypic (odds ratio, OR = 4.5; 95% CI, 1.04 to 20.99) and allelic association (OR = 1.73; 95% CI, 1.02 to 2.95) was observed with ABCB1 C3435T and response phenotype. CONCLUSIONS: The response to antiepileptics seems to be modulated by C3435T in ABCB1 or P-gp activity. At present, role of other genetic factors in treatment responsiveness in epilepsy appears limited, warranting analysis in a larger cohort.
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Transportador 1 de Casete de Unión a ATP/genética , Miembro 1 de la Subfamilia B de Casetes de Unión a ATP/genética , Anticonvulsivantes/farmacología , Citocromo P-450 CYP2C19/genética , Citocromo P-450 CYP2C9/genética , Resistencia a Medicamentos/genética , Epilepsia/tratamiento farmacológico , Adolescente , Adulto , Anciano , Anticonvulsivantes/administración & dosificación , Carbamazepina/administración & dosificación , Carbamazepina/farmacología , Estudios Transversales , Epilepsia/genética , Epilepsia/metabolismo , Femenino , Frecuencia de los Genes , Variación Genética , Genotipo , Humanos , Modelos Logísticos , Masculino , Persona de Mediana Edad , Farmacogenética , Polimorfismo de Longitud del Fragmento de Restricción , Adulto JovenRESUMEN
The role of non-invasive methods in the investigation of acute effects of traffic-related air pollution is not clearly established. We evaluated the usefulness of non-invasive biomarkers in detecting acute air pollution effects according to the age of participants, the disease status, their sensitivity compared with lung function tests and their specificity for a type of pollutant. Search terms lead to 535 titles, among them 128 had potentially relevant abstracts. Sixtynine full papers were reviewed, while 59 articles were excluded as they did not meet the selection criteria. Methods used to assess short-term effects of air pollution included analysis of nasal lavage (NAL) for the upper airways, and induced sputum (IS), exhaled breath condensate (EBC) and exhaled nitric oxide (FeNO) for central and lower airways. There is strong evidence that FeNO evaluation is useful independently from subject age, while IS analysis is suitable almost for adults. Biomarker changes are generally observed upon pollutant exposure irrespective of the disease status of the participants. None of the biomarkers identified are specific for a type of pollutant exposure. Based on experimental exposure studies, there is moderate evidence that IS analysis is more sensitive than lung function tests, whereas this is not the case for biomarkers obtained by NAL or EBC. Cells and some cytokines (IL-6, IL-8 and myeloperoxidase) have been measured both in the upper respiratory tract (NAL) and in the lower airways (IS). Overall, the response to traffic exposure seems different in the two compartments. In conclusion, this survey of current literature displays the complexity of this research field, highlights the significance of short-term studies on traffic pollution and gives important tips when planning studies to detect acute respiratory effects of air pollution in a non-invasive way.
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Contaminación del Aire/efectos adversos , Enfermedades Respiratorias/etiología , Enfermedades Respiratorias/metabolismo , Emisiones de Vehículos , Biomarcadores , Pruebas Respiratorias , Espiración , Humanos , Líquido del Lavado Nasal , Óxido Nítrico/metabolismo , Enfermedades Respiratorias/diagnóstico , Esputo/metabolismoRESUMEN
BACKGROUND: To assess the plaque and salivary pH changes at different time intervals in vivo after consumption of a carbonated beverage modified with sodium fluoride and calcium phosphate. MATERIALS AND METHODS: Twenty-four subjects aged 18-25 years were recruited and randomly assigned to three groups (group A, original drink Sprite; group B, Sprite with sodium fluoride; group C, Sprite with calcium phosphate). Collection of pooled plaque and unstimulated saliva was done before and after the drinks were consumed by the subjects at 5-, 10-, 20- and 30-minute intervals. RESULTS: The pH rise was higher with group C for plaque and group B for saliva. CONCLUSIONS: Modification of the test carbonated beverage with calcium phosphate and fluoride may exert some protective potential, especially in high caries risk candidates.
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Fosfatos de Calcio/administración & dosificación , Bebidas Gaseosas , Placa Dental/fisiopatología , Saliva/efectos de los fármacos , Fluoruro de Sodio/administración & dosificación , Adolescente , Adulto , Fosfatos de Calcio/análisis , Bebidas Gaseosas/análisis , Comportamiento del Consumidor , Índice CPO , Método Doble Ciego , Femenino , Estudios de Seguimiento , Humanos , Concentración de Iones de Hidrógeno , Masculino , Fluoruro de Sodio/análisis , Gusto/fisiología , Adulto JovenRESUMEN
BACKGROUND: Fungal sensitization is common in severe asthma, but the clinical relevance of this and the relationship with airway colonization by fungi remain unclear. The range of fungi that may colonize the airways in asthma is unknown. OBJECTIVE: To provide a comprehensive analysis on the range of filamentous fungi isolated in sputum from people with asthma and report the relationship with their clinico-immunological features of their disease. METHODS: We recruited 126 subjects with a diagnosis of asthma, 94% with moderate-severe disease, and 18 healthy volunteers. At a single stable visit, subjects underwent spirometry; sputum fungal culture and a sputum cell differential count; skin prick testing to both common aeroallergens and an extended fungal panel; specific IgE to Aspergillus fumigatus. Fungi were identified by morphology and species identity was confirmed by sequencing. Four patients had allergic bronchopulmonary aspergillosis. RESULTS: Forty-eight percent of asthma subjects were IgE-sensitized to one fungal allergen and 22% to ≥ 2. Twenty-seven different taxa of filamentous fungi were isolated from 54% of their sputa, more than one species being detected in 17%. This compared with 3 (17%) healthy controls culturing any fungus (P < 0.01). Aspergillus species were most frequently cultured in isolation followed by Penicillium species. Post-bronchodilator FEV (1) (% predicted) in the subjects with asthma was 71(± 25) in those with a positive fungal culture vs. 83 (± 25) in those culture-negative, (P < 0.01). CONCLUSION AND CLINICAL RELEVANCE: Numerous thermotolerant fungi other than A. fumigatus can be cultured from sputum of people with moderate-to-severe asthma; a positive culture is associated with an impaired post-bronchodilator FEV (1) , which might be partly responsible for the development of fixed airflow obstruction in asthma. Sensitization to these fungi is also common.
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Asma/microbiología , Asma/fisiopatología , Hongos/aislamiento & purificación , Esputo/microbiología , Corticoesteroides/uso terapéutico , Adulto , Anciano , Anciano de 80 o más Años , Antiasmáticos/uso terapéutico , Asma/tratamiento farmacológico , Broncodilatadores/uso terapéutico , Femenino , Volumen Espiratorio Forzado , Hongos/inmunología , Humanos , Inmunoglobulina E/sangre , Macrófagos/inmunología , Masculino , Persona de Mediana Edad , Fagocitosis/efectos de los fármacos , Fagocitosis/inmunología , Adulto JovenRESUMEN
The stress either physical or mental, leads to cardiovascular morbidity. Newly admitted medical students are likely to be exposed to various stresses like change of environment, demanding medical education and different teaching protocol in a medical college. Pranayama is known since ancient times to relieve stress and stabilize autonomic function of the body. Therefore it was decided to study effect of Pranayama on stress and cardiovascular autonomic function. The subjects were first M.B.B.S students and the sample size was 59 consisting of 27 males and 32 females. The group of students thus selected was briefed about the study. After the orientation session, informed written consent was taken, stress questionnaire was put and the autonomic function tests were done. This was followed by practice of Pranayama for 2 months, 1 hour/day for 5 days/week and again stress questionnaire was put and the autonomic function tests were performed on the study group. The above tests were done before and after the practice of Pranayama. The results obtained were analyzed using SPSS software. The stress level has reduced after 2 months of practicing various pranayama as evident by decrease in total stress score which is highly significant. VLF and LF in n.u have reduced significantly after practice of pranayama signifying reduction in sympathetic drive to heart. HF in n.u has increased significantly after practice of pranayama for 2 months showing the increase in parasympathetic output to the heart. LF/ HF ratio reduced significantly after 2 months of practice of pranayama indicating a better sympatho vagal balance with resting balance tilting toward better parasympathetic control.
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Sistema Nervioso Autónomo/fisiología , Ejercicios Respiratorios , Estrés Psicológico/fisiopatología , Adolescente , Adulto , Electrocardiografía , Femenino , Frecuencia Cardíaca , Humanos , MasculinoRESUMEN
BACKGROUND: Interdisciplinary communication is critically important to provide safe and effective care, yet it has been inadequately studied for hospitalised medical patients. Our objective was to characterise nurse-physician communication and their agreement on patients' plan of care. METHODS: During a one-month period, randomly selected hospitalised patients, their nurses and their physicians were interviewed. Nurses and physicians were asked to identify one another, whether communication had occurred, and about six aspects of the plan of care. Two internists rated nurse-physician agreement on aspects of the plan of care as none, partial or complete agreement. Measures included the percentage of nurses and physicians able to identify one another and reporting communication and the percentage of nurse-physician pairs in agreement on aspects of the plan of care. RESULTS: 310 (91%) and 301 (88%) of 342 eligible nurses and physicians completed interviews. Nurses correctly identified patients' physicians 71% of the time and reported communicating with them 50% of the time. Physicians correctly identified the patients' nurses 36% of the time and reported communicating with them 62% of the time. Physicians and nurses showed no agreement on aspects of the plan of care ranging from 11% for planned procedures to 42% for medication changes. CONCLUSIONS: Nurses and physicians did not reliably communicate with one another and were often not in agreement on the plan of care for hospitalised medical patients.
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Comunicación Interdisciplinaria , Enfermeras y Enfermeros/psicología , Planificación de Atención al Paciente , Relaciones Médico-Enfermero , Médicos/psicología , Adulto , Chicago , Estudios Transversales , Disentimientos y Disputas , Hospitalización , Hospitales Universitarios , Humanos , Entrevistas como Asunto , Enfermeras y Enfermeros/estadística & datos numéricos , Médicos/estadística & datos numéricos , Evaluación de Procesos, Atención de Salud/normasRESUMEN
OBJECTIVE: The purpose of this study was to use microarray technology to: (1) understand the early molecular events underlying the damage of articular cartilage initiated by this surgical procedure, and (2) determine whether these changes mimic those that are occurring in human osteoarthritic (OA) cartilage. DESIGN: Cartilage was harvested from both medial and lateral sides of the tibial plateaus and femoral condyles of both meniscal tear (MT) and sham surgery groups on days 3, 7 and 21 post-surgery. mRNA prepared from these rat cartilage samples was used for microarray analysis. RESULTS: Statistical analysis identified 475 genes that were differentially expressed between the sham and MT groups, at one or more of the time points that were analyzed. By integrating these genes with OA-related genes reported previously in a rat OA model and in human OA array studies, we identified 20 commonly changed genes. Six out of these 20 genes (Col5A1, Col6A2, INHBA, LTBP2, NBL1 and SERPINA1) were differentially expressed in two animal models and in human OA. Pathway analysis identified some key features of OA pathology, namely cartilage extracellular matrix remodeling, angiogenesis, and chondrocyte cell death that were recapitulated in the animal models. The rat models suggested increased inflammation and cholesterol metabolic pathways may play important role in early cartilage degeneration. CONCLUSION: We identified a large number of differentially expressed genes in the articular cartilage of the MT model. While there was lack of overall identity in cartilage gene expression between the rat models and human OA, several key biological processes were recapitulated in the rat MT OA model.
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Lesiones del Ligamento Cruzado Anterior , Artritis Experimental/metabolismo , Cartílago Articular/metabolismo , Osteoartritis/metabolismo , Lesiones de Menisco Tibial , Animales , Fémur/metabolismo , Humanos , Masculino , Análisis por Micromatrices , Modelos Animales , Ratas , Ratas Endogámicas Lew , Tibia/metabolismoRESUMEN
The therapeutic goal of increasing bone mass by co-treatment of parathyroid hormone (PTH) and an osteoclast inhibitor has been complicated by the undefined contribution of osteoclasts to the anabolic activity of PTH. To determine whether active osteoclasts are required at the time of PTH administration, we administered a low dose of the transient osteoclast inhibitor salmon calcitonin (sCT) to young rats receiving an anabolic PTH regimen. Co-administration of sCT significantly blunted the anabolic effect of PTH as measured by peripheral quantitative computer tomography (pQCT) and histomorphometry in the femur and tibia, respectively. To determine gene targets of sCT, we carried out quantitative real time PCR and microarray analysis of metaphyseal samples 1.5, 4 and 6.5h after administration of a single injection of PTH, sCT or PTH+sCT. Known targets of PTH action, IL-6, ephrinB2 and RANKL, were not modified by co-administration with sCT. Surprisingly, at all time points, we noted a significant upregulation of sclerostin mRNA by sCT treatment, as well as down-regulation of two other osteocyte gene products, MEPE and DMP1. Immunohistochemistry confirmed that sCT administration increased the percentage of osteocytes expressing sclerostin, suggesting a mechanism by which sCT reduced the anabolic effect of PTH. Neither mRNA for CT receptor (Calcr) nor labeled CT binding could be detected in sclerostin-enriched cells differentiated from primary calvarial osteoblasts. In contrast, osteocytes freshly isolated from calvariae expressed a high level of Calcr mRNA. Furthermore immunohistochemistry revealed co-localization of CT receptor (CTR) and sclerostin in some osteocytes in calvarial sections. Taken together these data indicate that co-treatment with sCT can blunt the anabolic effect of PTH and this may involve direct stimulation of sclerostin production by osteocytes. These data directly implicate calcitonin as a negative regulator of bone formation through a previously unsuspected mechanism.
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Proteínas Morfogenéticas Óseas/genética , Calcitonina/farmacología , Marcadores Genéticos/genética , Osteocitos/metabolismo , Hormona Paratiroidea/farmacología , Animales , Células Cultivadas , Biología Computacional , Proteínas de la Matriz Extracelular/genética , Femenino , Fémur/efectos de los fármacos , Fémur/metabolismo , Humanos , Inmunohistoquímica , Interleucina-6/genética , Ratones , Ratones Endogámicos C57BL , Análisis de Secuencia por Matrices de Oligonucleótidos , Osteocitos/efectos de los fármacos , Fosfoproteínas/genética , Ratas , Ratas Sprague-Dawley , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Tibia/efectos de los fármacos , Tibia/metabolismoRESUMEN
Measurements of the local susceptibility and 3d spin relaxation rate for single Fe impurities embedded in a nanocrystalline Nb host indicates the emergence of a local moment on Fe at and below a critical size of 11 nm. Our ab initio electronic structure calculations show that the moment formation occurs due to Stoner enhancement arising from a size dependent lattice expansion and a consequent shift in the Fermi level. We also show that a size-induced positive host spin polarization of the Nb-4d band electrons strongly influences the fluctuation rate of the Fe moment.
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BACKGROUND: The burning of biomass fuels results in exposure to high levels of indoor air pollution, with consequent health effects. Possible interventions to reduce the exposure include changing cooking practices and introduction of smoke-free stoves supported by health education. Social, cultural and financial constraints are major challenges to implementation and success of interventions. The objective of this study is to determine awareness of women in Gondar, Ethiopia to the harmful health effects of cooking smoke and to assess their willingness to change cooking practices. METHODS: We used a single, administered questionnaire which included questions on household circumstances, general health, awareness of health impact of cooking smoke and willingness to change. We interviewed 15 women from each of rural, urban-traditional and middle class backgrounds. RESULTS: Eighty percent of rural women cooked indoors using biomass fuel with no ventilation. Rural women reported two to three times more respiratory disease in their children and in themselves compared to the other two groups. Although aware of the negative effect of smoke on their own health, only 20% of participants realised it caused problems in children, and 13% thought it was a cause for concern. Once aware of adverse effects, women were willing to change cooking practices but were unable to afford cleaner fuels or improved stoves. CONCLUSION: Increasing the awareness of the health-effects of indoor biomass cooking smoke may be the first step in implementing a programme to reduce exposure.