Miracle-dz/UniFAR-FTUs huggingface dataset:
Induction of Interferon-γ, Interleukin-4, and Transforming Growth Factor-β in Rats Orally Tolerized against Experimental Autoimmune Myasthenia Gravis

Oral administration of nicotinic acetylcholine receptor (AChR) to Lewis rats prior to myasthenogenic immunization with Torpedo AChR+complete Freund's adjuvant (CFA) results in the prevention of experimental autoimmune myasthenia gravis (EAMG) and the suppression of AChR-specific B cell responses and counteracts the development of AChR-reactive interferon-gamma (IFN-gamma) secreting T cells. To study the involvement of the T helper type 1 (Th1) cell-related lymphokine IFN-gamma, the Th2 cell-related interleukin-4 (IL-4), and transforming growth factor beta (TGF-beta) that suppresses the synthesis of IFN-gamma and IL-4, we used in situ hybridization with complementary DNA oligonucleotide probes to enumerate mononuclear cells (MNC) expressing mRNA for the cytokines IFN-gamma, IL-4, and TGF-beta. Upon in vivo recognition of AChR, popliteal, inguinal, and mesenteric lymph nodes, spleen and thymus of rats with EAMG contained higher levels of IFN-gamma, IL-4, and TGF-beta mRNA-expressing cells compared to CFA-injected control rats, implicating the involvement in EAMG of AChR-reactive Th1 and Th2 cells in parallel. TGF-beta was also upregulated in EAMG. Oral tolerance to EAMG was characterized by suppression of the levels of MNC expressing IFN-gamma and IL-4, but augmentation of cells expressing TGF-beta. The results suggest that IFN-gamma, IL-4, and TGF-beta are involved in the development of EAMG, and that TGF-beta is important in the induction of oral tolerance to EAMG.
Identification of a Variety of Mutations in Cancer Predisposition Genes in Patients With Suspected Lynch Syndrome.

BACKGROUND & AIMS Multigene panels are commercially available tools for hereditary cancer risk assessment that allow for next-generation sequencing of numerous genes in parallel. However, it is not clear if these panels offer advantages over traditional genetic testing. We investigated the number of cancer predisposition gene mutations identified by parallel sequencing in individuals with suspected Lynch syndrome. METHODS We performed germline analysis with a 25-gene, next-generation sequencing panel using DNA from 1260 individuals who underwent clinical genetic testing for Lynch syndrome from 2012 through 2013. All patients had a history of Lynch syndrome-associated cancer and/or polyps. We classified all identified germline alterations for pathogenicity and calculated the frequencies of pathogenic mutations and variants of uncertain clinical significance (VUS). We also analyzed data on patients' personal and family history of cancer, including fulfillment of clinical guidelines for genetic testing. RESULTS Of the 1260 patients, 1112 met National Comprehensive Cancer Network (NCCN) criteria for Lynch syndrome testing (88%; 95% confidence interval [CI], 86%-90%). Multigene panel testing identified 114 probands with Lynch syndrome mutations (9.0%; 95% CI, 7.6%-10.8%) and 71 with mutations in other cancer predisposition genes (5.6%; 95% CI, 4.4%-7.1%). Fifteen individuals had mutations in BRCA1 or BRCA2; 93% of these met the NCCN criteria for Lynch syndrome testing and 33% met NCCN criteria for BRCA1 and BRCA2 analysis (P = .0017). An additional 9 individuals carried mutations in other genes linked to high lifetime risks of cancer (5 had mutations in APC, 3 had bi-allelic mutations in MUTYH, and 1 had a mutation in STK11); all of these patients met NCCN criteria for Lynch syndrome testing. A total of 479 individuals had 1 or more VUS (38%; 95% CI, 35%-41%). CONCLUSIONS In individuals with suspected Lynch syndrome, multigene panel testing identified high-penetrance mutations in cancer predisposition genes, many of which were unexpected based on patients' histories. Parallel sequencing also detected a high number of potentially uninformative germline findings, including VUS.
YouTube as a source of information on rhinosinusitis: the good, the bad and the ugly

Abstract Objective: YouTube is an internet-based repository of user-generated content. This study aimed to determine whether YouTube represented a valid and reliable patient information resource for the lay person on the topic of rhinosinusitis. Methods: The study included the first 100 YouTube videos found using the search term ‘sinusitis’. Videos were graded on their ability to inform the lay person on the subject of rhinosinusitis. Results: Forty-five per cent of the videos were deemed to provide some useful information. Fifty-five per cent of the videos contained little or no useful facts, 27 per cent of which contained potentially misleading or even dangerous information. Videos uploaded by medical professionals or those from health information websites contained more useful information than those uploaded by independent users. Conclusion: YouTube appears to be an unreliable resource for accurate and up to date medical information relating to rhinosinusitis. However, it may provide some useful information if mechanisms existed to direct lay people to verifiable and credible sources.
Epidemiological Study of Glucose-6-phosphate Dehydrogenase Deficiency in Scheduled Caste Population of India

The aim of the present study was to determine the glucose-6-phostphate dehydrogenase (G6PD) deficiency in scheduled caste (SC) population of eastern Uttar Pradesh, India. After taking clearance certificate from the Institutional Ethics Committee, blood samples were collected from total 200 healthy individuals belonging to scheduled caste. G6PD deficiency analysis was done by methemoglobin test according to the method of Brewer et al. (1962). Out of 200 samples, 20 individuals were glucose-6-phosphate dehydrogenase deficient and 22 samples were heterozygous that is, carriers. The percentage of G6PD deficient (Gd
Genotype-by-environment interaction effects on blast disease severity and genetic diversity of advanced blast-resistant rice lines based on quantitative traits

Introduction Among the rice diseases, rice blast caused by the pathogen Magnaporthe oryzae is a major threat to the global rice cultivation. This experiment was aimed at investigating the genotype by environment interaction effects on the severity of blast disease and variability of the advanced blast resistant rice lines using quantitative characters. Materials and methods The experiment was laid out in randomized complete block design conducted at three locations. Data were collected on 21 traits which included vegetative, physiological, yield and yield components and were subjected to analysis of variance and variance component analysis. Cluster analysis was authenticated using principal component analysis for genotypes’ classification. Results and discussion All vegetative and yield traits showed highly significant variation among the advanced lines and the check. Seberang Prai showed the highest average yield (5.62t/ha), followed by Tanjung Karang (5.39t/ha) and UPM (4.97t/ha). All the advanced lines showed high resistance to blast disease. Evaluation across the three environments indicated that genotype G3, from MR219 based population, had the highest yield and resistance to blast infection. Genotype G21, from MR263 based population, performed best across the three environments studied and were selected for further breeding programme. The two selected lines, three and four clusters derived from MR219 and MR263 based populations, respectively, were recommended as new lines for further breeding programmes.
Cardiac sympathetic denervation correlates with clinical and pathologic stages of Parkinson's disease

Attention has been drawn to cardiac sympathetic denervation in Parkinson's disease (PD) based on clinical studies using [123I] metaiodobenzylguanidine scintigraphy; however, the histologic correlates and time course of cardiac sympathetic denervation are poorly understood. To address these issues, we used tyrosine hydroxylase (TH) immunohistochemistry to detect cardiac sympathetic nerve fibers in the epicardium of 4 normal controls, 11 cases with incidental Lewy bodies (iLBs), and 14 cases of PD. Cardiac sympathetic innervation was significantly less in PD than in normal controls and cases with iLBs (P < 0.05). There was also a decrease in TH‐immunoreactive fibers in iLB cases compared to normal controls (P < 0.01). TH‐immunoreactive fibers correlated with the PD stage (r = −0.75, P < 0.001), as well as with Hoehn & Yahr clinical stage (r = −0.61, P < 0.001), and disease duration (r = −0.63, P < 0.001). Immunohistochemistry for α‐synuclein showed neurites in epicardium in PD and iLB cases, but not in normal controls. The density of α‐synuclein neurites correlated with Braak PD stage (r = 0.38, P < 0.05), Hoehn & Yahr clinical stage (r = 0.44, P < 0.05), and disease duration (r = 0.42, P < 0.05). This study demonstrates that cardiac sympathetic degeneration and α‐synuclein pathology is present in presymptomatic phase of PD, and that both increase with disease duration and severity. © 2008 Movement Disorder Society.
American Gastroenterological Association Institute Guideline on the Diagnosis and Management of Lynch Syndrome.

Veterans Affairs Center for Clinical Management Research; Division of Gastroenterology, University of Michigan Medical School, Ann Arbor, Michigan; Division of Gastroenterology, St Paul’s Hospital, University of British Columbia, Vancouver, British Columbia, Canada; Departments of Family Medicine and Urology, University of Michigan Medical School, Ann Arbor, Michigan; and Division of Gastroenterology, McGill University, McGill University Health Centre, Montreal, Quebec, Canada
CHEMO-IMMUNOLOGICAL STUDIES ON CONJUGATED CARBOHYDRATE-PROTEINS

1. Azoprotein antigens containing glucuronic and galacturonic acids give rise in rabbits to specific antibodies. The immune sera show no serological crossing with antigens containing glucose or galactose. 2. The galacturonic acid antigen reacts in antipneumococcus horse serum Type I in high dilutions. 3. Azoprotein antigens containing galacturonic acid, benzene sulfonic and carboxylic acids precipitate in antipneumococcus horse sera of various types but not in normal horse serum. The mechanism underlying these cross reactions is discussed.
Three-dimensional temporal bone reconstruction from histological sections.

OBJECTIVE To produce a high-resolution, three-dimensional temporal bone model from serial sections, using a personal computer. METHOD Digital images were acquired from histological sections of the temporal bone. Image registration, segmentation and three-dimensional volumetric reconstruction were performed using a personal computer. The model was assessed for anatomical accuracy and interactivity by otologists. RESULTS An accurate, high-resolution, three-dimensional model of the temporal bone was produced, containing structures relevant to otological surgery. The facial nerve, labyrinth, internal carotid artery, jugular bulb and all of the ossicles were seen (including the stapes footplate), together with the internal and external auditory meati. Some projections also showed the chorda tympani nerve. CONCLUSION A high-resolution, three-dimensional computer model of the complete temporal bone was produced using a personal computer. Because of the increasing difficulty in procuring cadaveric bones, this model could be a useful adjunct for training.
Incidence and mortality of colorectal cancer in individuals with a family history of colorectal cancer.

BACKGROUND & AIMS Little is known about the change in risk conferred by family history of colorectal cancer (CRC) as a person ages. We evaluated the effect of family history on CRC incidence and mortality after 55 years of age, when the risk of early onset cancer had passed. METHODS We collected data from participants in the randomized, controlled Prostate, Lung, Colorectal and Ovarian cancer screening trial of flexible sigmoidoscopy versus usual care (55-74 years old, no history of CRC), performed at 10 US centers from 1993 to 2001. A detailed family history of colorectal cancer was obtained at enrollment, and subjects were followed for CRC incidence and mortality for up to 13 years. RESULTS Among 144,768 participants, 14,961 subjects (10.3%) reported a family of CRC. Of 2090 incident cases, 273 cases (13.1%) had a family history of CRC; among 538 deaths from CRC, 71 (13.2%) had a family history of CRC. Overall, family history of CRC was associated with an increased risk of CRC incidence (hazard ratio [HR], 1.30; 95% confidence interval [CI], 1.10-1.50; P<.0001) and increased mortality (HR, 1.31; 95% CI, 1.02-1.69; P = .03). Subjects with 1 first degree relative (FDR) with CRC (n = 238; HR, 1.23; 95% CI, 1.07-1.42) or ≥2 FDRs with CRC (n = 35; HR, 2.04; 95% CI, 1.44-2.86) were at increased risk for incident CRC. However, among individuals with 1 FDR with CRC, there were no differences in risk based on age at diagnosis in the FDR (for FDR <60 years of age: HR, 1.27; 95% CI, 0.97-1.63; for FDR 60-70 years of age: HR, 1.33; 95% CI, 1.06-1.62; for FDR >70 years of age: HR, 1.14; 95% CI, 0.93-1.45; P trend = .59). CONCLUSIONS After 55 years of age, subjects with 1 FDR with CRC had only a modest increase in risk for CRC incidence and death; age of onset in the FDR was not significantly associated with risk. Individuals with ≥2 FDRs with CRC had continued increased risk in older age. Guidelines and clinical practice for subjects with a family history of CRC should be modified to align CRC testing to risk. ClinicalTrials.gov number, NCT00002540.
Causal effect of polyunsaturated fatty acids on bone mineral density and fracture

Background Polyunsaturated fatty acids (PUFAs) are closely related to osteoporosis. To test their causal relationship, we conducted a Mendelian randomization (MR) analysis. Methods We analyzed the causal relationship between four PUFAs measures, n-3 PUFAs (n-3), n-6 PUFAs (n-6), the ratio of n-3 PUFAs to total fatty acids (n-3 pct), and the ratio of n-6 PUFAs to n-3 PUFAs (n-6 to n-3), and five measures of osteoporosis, including estimated bone mineral density (eBMD), forearm (FA) BMD, femoral neck (FN) BMD, lumbar spine (LS) BMD, and fracture, using two-sample MR analysis. In order to verify the direct effect between PUFAs and BMD, we chose interleukin-6 (IL-6), tumor necrosis factor-β (TNF-β), and bone morphogenetic proteins 7 (BMP-7), three markers or cytokines strongly related to BMD, as possible confounding factors, and analyzed the possible causal relationships between them and PUFAs or BMD by MR. Inverse variance weighting (IVW), MR-Egger, weighted and weighted median were conducted. MR Pleiotropy RESidual Sum and Outlier (MR-PRESSO) and MR-Egger regression methods were used to evaluate the potential pleiotropy of instrumental variables (IVs) and outliers were identified by MR-PRESSO. Cochran’s Q statistic was used to detect the heterogeneity among IVs. Leave-one-out sensitivity analysis was used to find SNPs that have a significant impact on the results. All results were corrected by the Bonferroni correction. Results The IVW results showed that n-3 PUFAs (OR = 1.030, 95% CI: 1.013, 1.047, P = 0.001) and n-6 PUFAs (OR = 1.053, 95% CI: 1.034, 1.072, P < 0.001) were positively correlated with eBMD, while n-6 to n-3 (OR = 0.947, 95% CI: 0.924, 0.970, P < 0.001) were negatively correlated with eBMD. These casual relationships still existed after Bonferroni correction. There were positive effects of n-3 PUFAs on FA BMD (OR = 1.090, 95% CI: 1.011, 1.176, P = 0.025) and LS BMD (OR = 1.056, 95% CI: 1.011, 1.104, P = 0.014), n-3 pct on eBMD (OR = 1.028, 95% CI: 1.002, 1.055, P = 0.035) and FA BMD (OR = 1.090, 95% CI: 1.011, 1.174, P = 0.025), n-6 to n-3 on LS BMD (OR = 1.071, 95% CI: 1.021, 1.124, P = 0.005); negative effects of n-3 pct on fracture (OR = 0.953, 95% CI: 0.918, 0.988, P = 0.009) and n-6 to n-3 on FA BMD (OR = 0.910, 95% CI: 0.837, 0.988, P = 0.025). However, these causal effects all disappeared after Bonferroni correction (all P > 0.0025). None of IL-6, TNF-β, and BMP-7 had a causal effect on PUFA and BMD simultaneously (all P > 0.05). Conclusion Evidence from this MR study supports the genetically predicted causal effects of n-3, n-6, n-3 pct, and n-6 to n-3 on eBMD. In addition, n-3 not only associate with FA BMD and LS BMD through its own level and n-6 to n-3, but also link to fracture through n-3 pct.
Helicobacter pylori infection and motor fluctuations in patients with Parkinson's disease

To investigate whether Helicobacter pylori (HP) infection affects the clinical response to levodopa and whether its eradication could improve motor fluctuation in patients with Parkinson's disease (PD). Using the [13C] urea breath test, we monitored HP infection in 65 patients with PD and motor fluctuations of the “wearing‐off” or delayed “on” types, with or without dyskinesia. We compared the clinical features and response to L‐dopa between HP noninfected (n = 30) and HP infected patients (n = 35) by reviewing home diaries kept for 72 hours. Among HP infected patients, we compared the differences in L‐dopa “onset” time, “on‐time” duration, and scores on the motor examination section of the Unified PD Rating Scale (UPDRS‐III) during the medication “on” phase before and after HP eradication. There were no differences in the age, disease duration, Hoehn and Yahr stage, UPDRS‐III score, L‐dopa daily dose, and frequency of dyskinesia between HP noninfected and HP infected groups. However, L‐dopa “onset” time was longer and “on‐time” duration was shorter in HP infected patients than in HP noninfected patients (78.4 ± 28.2 vs. 56.7 ± 25.1 and 210.0 ± 75.7 vs. 257.7 ± 68.9 min, respectively, P < 0.05). HP eradication improved the delay L‐dopa “onset” time and short “on‐time” duration (to 58.1 ± 25.6 and to 234.4 ± 66.5 min, respectively, P < 0.05). These data demonstrated that HP infection could interfere with the absorption of L‐dopa and provoke motor fluctuations. HP eradication can improve the motor fluctuations of HP infected patients with PD. © 2008 Movement Disorder Society
Bile acids as inflammatory mediators and modulators of intestinal permeability

Bile acids are critical for the digestion and absorption of lipids and fat-soluble vitamins; however, evidence continues to emerge supporting additional roles for bile acids as signaling molecules. After they are synthesized from cholesterol in the liver, primary bile acids are modified into secondary bile acids by gut flora contributing to a diverse pool and making the composition of bile acids highly sensitive to alterations in gut microbiota. Disturbances in bile acid homeostasis have been observed in patients with Inflammatory Bowel Diseases (IBD). In fact, a decrease in secondary bile acids was shown to occur because of IBD-associated dysbiosis. Further, the increase in luminal bile acids due to malabsorption in Crohn’s ileitis and ileal resection has been implicated in the induction of diarrhea and the exacerbation of inflammation. A causal link between bile acid signaling and intestinal inflammation has been recently suggested. With respect to potential mechanisms related to bile acids and IBD, several studies have provided strong evidence for direct effects of bile acids on intestinal permeability in porcine and rodent models as well as in humans. Interestingly, different bile acids were shown to exert distinct effects on the inflammatory response and intestinal permeability that require careful consideration. Such findings revealed a potential effect for changes in the relative abundance of different bile acids on the induction of inflammation by bile acids and the development of IBD. This review summarizes current knowledge about the roles for bile acids as inflammatory mediators and modulators of intestinal permeability mainly in the context of inflammatory bowel diseases.
Deep brain stimulation and the ethics of protection and caring for the patient with Parkinson's dementia

Deep brain stimulation (DBS) is an effective neurosurgical treatment for patients with advanced Parkinson's disease (PD) suffering from motor complications that are refractory to further medication management. DBS requires an invasive procedure of implanting brain electrodes while awake, followed by implantation of neurostimulators under general anesthesia. The neurostimulator requires battery monitoring and replacement approximately every 3 to 5 years. These two elements of the technology provide numerous decision points about continuing therapies that can involve ethical choices. Although motor function can be improved with subthalamic nucleus (STN) DBS, the long‐term risks of living with implanted hardware should be carefully evaluated for patients with diminishing cognitive capacity. We describe two cases where ethical dilemmas occurred postoperatively as a result of cognitive decline and describe salient ethical dimensions that illustrate the need for a proactive postoperative plan for supervision as a prerequisite for surgery to include neuropsychological testing to predict the likelihood of net benefit to the patient and family beyond just motor improvement. © 2008 Movement Disorder Society
Comparação de duas diferentes intensidades de alongamento na amplitude de movimento

O alongamento e uma pratica comum no treinamento da flexibilidade, porem existe uma deficiencia de informacoes especificas sobre os componentes da carga utilizados, em especial, sobre a intensidade do alongamento. O presente estudo teve como objetivo investigar o efeito agudo de duas diferentes intensidades de alongamento na amplitude de movimento (ADM) de extensao do joelho. Participaram deste estudo 14 voluntarios do sexo masculino. Os dois membros inferiores de cada participante foram avaliados, sendo que um membro executou o treinamento na intensidade submaxima de alongamento (TS, N=14) e o outro na intensidade maxima de alongamento (TM, N=14). O treinamento utilizou a tecnica passiva-estatica executando quatro repeticoes com duracao de 15 segundos. Foi encontrada diferenca estatisticamente significativa para os valores de ADM entre o pre-teste (68,0±10,5) e o pos-teste (74,0±10,0) no TM. Os valores de ADM para o pre-teste (68,9±14,0) e o pos-teste (71,0±14,4) no TS nao apresentaram diferenca significativa. Os resultados analisados atraves da ANOVA two-way apresentaram interacao significativa entre o grupo e o teste (F=1.26; df=8,62; p=0,007). O estudo demonstrou que o treinamento na intensidade maxima de alongamento promove aumento agudo da ADM. Dessa forma, os estudos que avaliam os componentes ideais da carga de treinamento na melhora da flexibilidade nao devem negligenciar o controle da intensidade do estimulo de alongamento.