Miracle-dz/UniFAR-FTUs huggingface dataset:
T cell vaccination in multiple sclerosis patients with autologous CSF‐derived activated T cells: results from a pilot study

Myelin‐reactive T cells are considered to play an essential role in the pathogenesis of multiple sclerosis (MS), an autoimmune disease of the central nervous system. We have previously studied the effects of T cell vaccination (TCV), a procedure by which MS patients are immunized with attenuated autologous myelin basic protein (MBP)‐reactive T cell clones. Because several myelin antigens are described as potential autoantigens for MS, T cell vaccines incorporating a broad panel of antimyelin reactivities may have therapeutic effects. Previous reports have shown an accumulation of activated T cells recognizing multiple myelin antigens in the cerebrospinal fluid (CSF) of MS patients. We conducted a pilot clinical trial of TCV with activated CD4+ T cells derived from CSF in five MS patients (four RR, one CP) to study safety, feasibility and immune effects of TCV. CSF lymphocytes were cultured in the presence of rIL‐2 and depleted for CD8 cells. After 5–8 weeks CSF T cell lines (TCL) were almost pure TCRαβ+CD4+ cells of the Th1/Th0 type. The TCL showed reactivity to MBP, MOG and/or PLP as tested by Elispot and had a restricted clonality. Three immunizations with irradiated CSF vaccines (10 million cells) were administered with an interval of 2 months. The vaccinations were tolerated well and no toxicity or adverse effects were reported. The data from this small open‐label study cannot be used to support efficacy. However, all patients remained clinically stable or had reduced EDSS with no relapses during or after the treatment. Proliferative responses against the CSF vaccine were observed in 3/5 patients. Anti‐ergotypic responses were observed in all patients. Anti‐MBP/PLP/MOG reactivities remained low or were reduced in all patients. Based on these encouraging results, we recently initiated a double‐blind placebo‐controlled trial with 60 MS patients to study the effects of TCV with CSF‐derived vaccines in early RR MS patients.
Rapid warming accelerates tree growth decline in semi‐arid forests of Inner Asia

Forests around the world are subject to risk of high rates of tree growth decline and increased tree mortality from combinations of climate warming and drought, notably in semi‐arid settings. Here, we assess how climate warming has affected tree growth in one of the world's most extensive zones of semi‐arid forests, in Inner Asia, a region where lack of data limits our understanding of how climate change may impact forests. We show that pervasive tree growth declines since 1994 in Inner Asia have been confined to semi‐arid forests, where growing season water stress has been rising due to warming‐induced increases in atmospheric moisture demand. A causal link between increasing drought and declining growth at semi‐arid sites is corroborated by correlation analyses comparing annual climate data to records of tree‐ring widths. These ring‐width records tend to be substantially more sensitive to drought variability at semi‐arid sites than at semi‐humid sites. Fire occurrence and insect/pathogen attacks have increased in tandem with the most recent (2007–2009) documented episode of tree mortality. If warming in Inner Asia continues, further increases in forest stress and tree mortality could be expected, potentially driving the eventual regional loss of current semi‐arid forests.
Renal Denervation vs. Spironolactone in Resistant Hypertension: Effects on Circadian Patterns and Blood Pressure Variability

BACKGROUND Sympathetic renal denervation (SRD) has been proposed as a therapeutic alternative for patients with resistant hypertension not controlled on pharmacological therapy. Two studies have suggested an effect of SRD in reducing short-term blood pressure variability (BPV). However, this has not been addressed in a randomized comparative trial. We aimed to compare the effects of spironolactone and SRD on circadian BP and BPV. METHODS This is a post-hoc analysis of a randomized trial in 24 true resistant hypertensive patients (15 men, 9 women; mean age 64 years) comparing 50mg of spironolactone (n = 13) vs. SRD (n = 11) on 24-hour BP. We report here the comparative effects on daytime (8 AM–10 PM) and nighttime (0 AM–6 AM) BP, night-to-day ratios and BP and heart rate variabilities (SD and coefficient of variation of 24-hour, day and night, as well as weighted SD and average real variability (ARV)). RESULTS Spironolactone was more effective than SRD in reducing daytime systolic (P = 0.006), daytime diastolic (P = 0.006), and nighttime systolic (P = 0.050) BP. No differences were observed in the night-to-day ratios. In contrast, SRD-reduced diastolic BPV (24 hours, daytime, nighttime, weighted, and ARV; all P < 0.05) with respect to spironolactone, without significant differences in systolic BPV. CONCLUSION Spironolactone is more effective than SRD in reducing ambulatory BP. However, BPV is significantly more reduced with SRD. This effect could be important in terms of potential prevention beyond BP reduction and deserves further investigation.
Surgical management of paraclinoid aneurysms via frontal lateral approach

Objective: Towards exploring minimally invasive techniques in paraclinoid aneurysms clipping via a frontal lateral approach. Methods: 118 patients by frontal lateral approach in the last 2.5 y in Beijing Tiantan Hospital were analysed retrospectively. Clinical data and follow-up outcomes of the patients were reviewed. Digital Subtraction Angiography (DSA) was performed among all patients to categorize the paraclinoid aneurysms. The microsurgery through frontal lateral approach was performed in 118 patients. According to various subtypes of paraclinoid aneurysms, summarize and compare the surgical skills and outcome of the treatment. Outcomes: Out of the 126 aneurysms, 116 got trimmed effectively, 5 was trapped. Numerous aneurysms in 3 incidents got cured in one craniotomy. Anterior clinoidectomy was removed in 110 cases. Aneurysm residues were found after 1 giant aneurysms clipping. One case lost his sight with preoperative visual light perception and in eight cases cerebral infarction occurred. Type I (dorsal projection) aneurysms constituted 47.5%, Type II aneurysms (34.7%) followed by Type III aneurysms constituted 17.8%. All the others had a good recovery. Conclusions: The paraclinoid aneurysm can be exposed and treated very well by microsurgery through frontal lateral approach which has the advantages such as minimal invasion, less effect on the patient’s look and simple procedure. The lateral transfrontal approach is safe and effective in surgery for paraclinoid aneurysm. Among the 3 types, type I can reach better prognosis.
Survival of women with surgical stage II endometrial cancer.

OBJECTIVE The aim of this study was to report survival and determine prognostic factors and results of therapy in women with surgical stage II endometrial cancer. METHODS Forty-eight consecutive women with surgical stage II endometrial cancer treated at the University of Vermont between March 1984 and March 1998 were reviewed. Patients' characteristics, surgical procedure, postoperative treatment and its complications, and tumor recurrence and its treatment were recorded. In addition, a formal review of their pathological material for confirmation of the diagnosis was performed. RESULTS The median duration of follow-up was 6.2 years. Three patients (6.3%) had tumor recurrence and two (4.2%) died of their disease. The estimated 5-year overall survival and disease-free survivals were 92.1% (SE = 5.5%, 95% confidence interval: 81.3, 100%) and 89.9% (SE = 5.8%, 95% confidence interval: 78.5%, 100%), respectively. None of the patients treated by total abdominal hysterectomy followed by both whole pelvic and vaginal cuff radiation therapy (the main line of treatment for patients in whom cervical involvement was diagnosed following hysterectomy, n = 20) or by radical hysterectomy (the main line of treatment for patients in whom cervical involvement was known before hysterectomy, n = 11) had tumor recurrence. Three of 17 (17.6%) patients treated with total abdominal hysterectomy followed by either whole pelvic (n = 13) or vaginal cuff (n = 4) radiation therapy had tumor recurrence. The difference between those two groups was statistically significant (0/31 versus 3/17, P = 0.02). There was no difference in survival among women with stage IIA and IIB or women who underwent radical abdominal hysterectomy and those who underwent total abdominal hysterectomy with postoperative pelvic and vaginal cuff radiation. Morbidity secondary to therapy was mild. Age, depth of myometrial invasion, tumor histology, and grade were not significantly related to recurrence. CONCLUSIONS Survival of women with surgical stage II endometrial cancer is excellent especially among those treated with total abdominal hysterectomy followed by both pelvic and vaginal cuff radiotherapy or by radical abdominal hysterectomy.
LEGO Engineer and RoboLab: Teaching Engineering with LabVIEW from Kindergarten to Graduate School*

For the past 6 years, faculty members at Tufts University have developed two different softwarepackages between LabVIEWTMand LEGOTMdata acquisition systems. These packages allow usto teach engineering with both LEGO bricks and LabVIEW to students from 5 to 50 years old. Theversatility of the hardware and software allow a wide variety of possibilities in what students canbuild and program–from robots and remote sensing devices to kinetic sculptures. As studentsdesign and build their projects, they are motivated to learn the math and science they need tooptimise their project. Both college students and kindergartners respond to this motivator. In thepaper, we explain how we designed software to complement these projects in allowing automationand animation. The software uses LabVIEW, extending its capabilities to kindergartners andLEGO bricks. Finally, we will show how we have used LabVIEW and LEGO data acquisition toteach elementary school science, freshman engineering, instrumentation and experimentation, andhow college seniors and graduate students have used both the hardware and software to solvevarious data acquisition problems.
Decreased Superoxide Production in Macrophages of Long-lived p66Shc Knock-out Mice*

A decrease in reactive oxygen species (ROS) production has been associated with extended life span in animal models of longevity. Mice deficient in the p66Shc gene are long-lived, and their cells are both resistant to oxidative stress and produce less ROS. Our microarray analysis of p66Shc(−/−) mouse tissues showed alterations in transcripts involved in heme and superoxide production and insulin signaling. Thus, we carried out analysis of ROS production by NADPH oxidase (PHOX) in macrophages of control and p66Shc knock-out mice. p66Shc(−/−) mice had a 40% reduction in PHOX-dependent superoxide production. To confirm whether the defect in superoxide production was a direct consequence of p66Shc deficiency, p66Shc was knocked down with siRNA in the macrophage cell line RAW264, and a 30% defect in superoxide generation was observed. The pathway of PHOX-dependent superoxide generation was investigated. PHOX protein levels were not decreased in mutant macrophages; however, the rate and extent of phosphorylation of p47phox was decreased in mutants, as was membrane translocation of the complex. Consistently, phosphorylation of protein kinase Cδ, Akt, and ERK (the kinases responsible for phosphorylation of p47phox) was decreased. Thus, p66Shc deficiency causes a defect in activation of the PHOX complex that results in decreased superoxide production. p66Shc-deficient mice have recently been observed to be resistant to atherosclerosis and to oxidant injury in kidney and brain. Because phagocyte-derived superoxide is often a component of oxidant injury and inflammation, we suggest that the decreased superoxide production by PHOX in p66Shc-deficient mice could contribute significantly to their relative protection from oxidant injury and consequent longevity.
Does social capital affect the incidence of functional disability in older Japanese? A prospective population-based cohort study

Background Recent increases in numbers of older people have been accompanied by increases in those with functional disability. No study has examined the association between community social capital and the onset of functional disability. Methods The association between community social capital and the onset of functional disability was examined using data from the Aichi Gerontological Evaluation Study, a prospective cohort established in 2003 in Japan. Perceptions of community social capital (indicators of social cohesion such as trust of others and extent of social participation) in 6953 men and 7636 women aged 65 years or older were surveyed. Multilevel survival analysis using the discrete-time hazard model was applied. Results During 4-year follow-up, onset of functional disability occurred in 759 men and 1146 women. Women living in communities with higher mistrust had 1.68 (95% CI 1.14 to 2.49) times higher OR of onset of disability, even after adjusting for covariates. Mediators did not substantially change this association. Lack of social participation seemed to affect the health of women, though the effect was marginal (OR for covariates adjusted model =1.12 (95% CI 0.96 to 1.31)). There were no significant ORs among men. Conclusions Lower community social capital was associated with higher incidence of onset of functional disability among older women but not among men. Community-based interventions to promote social capital may be useful for preventing functional disability of older Japanese women.
Disturbed calcium metabolism in renal failure--pathogenesis and therapeutic strategies.

Absolute or relative deficiency of 1,25(OH)2 vitamin D3 is thought to play a key role in the genesis of secondary (renal) hyperparathyroidism. Elevated concentrations of PTH and--less consistently--diminished concentrations of 1,25(OH)2 vitamin D3 are demonstrable in a considerable proportion of patients with incipient renal failure. Increased PTH concentrations counteract to some extent the trend of 1,25(OH)2 vitamin D3 production to decrease. When iPTH is elevated, prophylactic administration of 1,25(OH)2 vitamin D3 is a logical procedure, even when patients have not yet reached end-stage renal failure. With the use of low doses, the incidence of side effects is low, and excessive lowering of PTH and bone turnover presumably can be avoided. Acute administration of 1,25(OH)2 vitamin D3 to achieve brief episodes of peak plasma levels causes prolonged suppression of pre-pro-PTH mRNA in the parathyroid cell. This provides a rationale to treat symptomatic hyperparathyroidism with intermittent high dose 1,25(OH)2 vitamin D3, either per os or i.v.
Nurse Staffing and Quality of Care of Nursing Home Residents in Korea.

PURPOSE To investigate the relationship between nurse staffing and quality of care in nursing homes in Korea. METHODS This study used a cross-sectional design to describe the relationship between nurse staffing and 15 quality-of-care outcomes. Independent variables were hours per resident day (HPRD), skill mix, and turnover of each nursing staff, developed with the definitions of the Centers for Medicare & Medicaid Services and the American Health Care Association. Dependent variables were prevalence of residents who experienced more than one fall in the recent 3 months, aggressive behaviors, depression, cognitive decline, pressure sores, incontinence, prescribed antibiotics because of urinary tract infection, weight loss, dehydration, tube feeding, bed rest, increased activities of daily living, decreased range of motion, use of antidepressants, and use of restraints. Outcome variables were quality indicators from the U.S. Centers for Medicare & Medicaid and 2013 nursing home evaluation manual by the Korean National Health Insurance Service. FINDINGS The effects of registered nurse (RN) HPRD was supported in fall prevention, decreased tube feeding, decreased numbers of residents with deteriorated range of motion, and decreased aggressive behavior. Higher turnover of RNs related to more residents with dehydration, bed rest, and use of antipsychotic medication. CONCLUSIONS Study results supported RNs' unique contribution to resident outcomes in comparison to alternative nurse staffing in fall prevention, decreased use of tube feeding, better range of motion for residents, and decreased aggressive behaviors in nursing homes in Korea. More research is required to confirm the effects of nurse staffing on residents' outcomes in Korea. CLINICAL RELEVANCE We found consistency in the effects of RN staffing on resident outcomes acceptable. By assessing nurse staffing levels and compositions of nursing staffs, this study contributes to more effective long-term care insurance by reflecting on appropriate policies, and ultimately contributes to the stable settlement of the long-term care insurance system for elders.
Cryptococcal meningitis in non-HIV-infected patients.

There are few reports on cryptococcal meningitis in non-HIV-infected patients in subtropical areas. We reviewed 94 non-HIV-infected patients microbiologically diagnosed with cryptococcal meningitis and hospitalized at National Taiwan University Hospital, 1977-1996. Forty-two patients (44.7%) had underlying diseases. The main initial manifestations were headache (86.2%), vomiting (72.3%) and fever (69. 1%). The 30 patients with T-cell suppression had more acute illnesses (median duration of symptoms: 14 days vs. 29 days), less typical presentations of meningitis, and reduced inflammatory responses compared with the 64 without T cell suppression. There was no statistical difference between patients who received amphotericin B treatment for 10 weeks and those received amphotericin B with subsequent fluconazole treatment, in terms of mortality rate and recurrence rate. Seventy-five patients (79.8%) had satisfactory clinical responses, and two relapsed. Eighteen patients died (19.1%) and 10 of these died within 2 weeks of hospitalization. Patients in this series had outcomes comparable with those from temperate and even tropical countries with high percentages of immunocompetent hosts. Factors significantly associated with death were lymphoma, semicoma, leukocytosis, and initial high titres of cryptococcal antigen in cerebral spinal fluid (especially >/=1 : 512). On multivariate analysis, lymphoma and initial high cryptococcal antigen titres were independent predictors of mortality.
Esophageal pH-Impedance Monitoring and Symptom Analysis in GERD: A Study in Patients off and on Therapy

INTRODUCTION:Combined esophageal pH-impedance monitoring allows detection of nearly all gastroesophageal reflux episodes, acid as well as nonacid. However, the role of nonacid reflux in the pathogenesis of symptoms is poorly known. The aim of this study was to evaluate the diagnostic yield of this technique in patients with suspected reflux symptoms while on or off PPI therapy.PATIENTS AND METHODS:The recordings of 150 patients recruited at seven academic centers with symptoms possibly related to gastroesophageal reflux were analyzed. Reflux events were detected visually using impedance (Sandhill, CO) and then characterized by pHmetry as acid or nonacid reflux. The temporal relationship between symptoms and reflux episodes was analyzed: a symptom association probability (SAP) ≥95% was considered indicative of a positive association.RESULTS:One hundred fifty patients were included, 102 women (mean age 52 ± 14 yr, range 16–84). Among the 79 patients off PPI, five did not report any symptom during the recording period. A positive SAP was found in 41 of the 74 symptomatic patients (55.4%), including acid reflux in 23 (31.1%), nonacid reflux in three (4.1%), and acid and nonacid in 15 (20.3%). In the group of patients on PPI (N = 71, 46 women, mean age 51 ± 15 yr), 11 were asymptomatic during the study, SAP was positive in 22 of the 60 symptomatic patients (36.7%), including acid reflux in three (5.0%), nonacid reflux in 10 (16.7%), and acid and nonacid in nine (15.0%). The symptoms most frequently associated with nonacid reflux were regurgitation and cough.CONCLUSION:Adding impedance to pH monitoring improves the diagnostic yield and allows better symptom analysis than pHmetry alone, mainly in patients on PPI therapy. The impact of this improved diagnostic value on gastroesophageal reflux disease management remains to be investigated by outcome studies.
SANS Study of the Effects of Water Vapor Sorption on the Nanoscale Structure of Perfluorinated Sulfonic Acid (NAFION) Membranes

Several poly(perfluorosulfonic acid) membranes (NAFION, EW = 1100) with the same sulfonic acid content were systematically investigated with SANS under in-situ water vapor sorption and/or with bulk water to quantify the effects of relative humidity (RH), membrane processing (melt-extruded and solution-casting), prehistory (pretreated at 80 °C and as-received), and thickness on the nanoscale structure at room temperature. The sorption isotherm (water uptake vs RH) of the membranes showed a strong correlation between the interionic domain distance (Lion) and RH. The melt-extruded membranes showed evidence of partial alignment of better organized ionic domains than those solution-cast. Pretreating the membranes resulted in a larger Lion and a broader scattering over the entire range of RH. The ionic peak of the melt-extruded membranes (as-received and pretreated) became more symmetric and narrower with sorption time. Diffusion coefficients of water vapor, based on structural evolution and Fick's second law, .
Coping with stress: its influence on periodontal disease.

BACKGROUND Various forms of stress behavior were documented and in patients with periodontitis their relationship with periodontal disease was investigated. METHODS Eighty-nine patients with different forms of chronic periodontitis were included in this retrospective case-control study. They were all undergoing periodontal treatment at the Department of Dental Prosthetics, University of Graz, or a private dental practice. The control group consisted of 63 persons employed in health care at the Clinic of Graz. All participants completed a stress coping questionnaire of 114 items and 19 actional and intrapsychic stress coping modes. The questionnaire served as a psychodiagnostic survey aimed at collecting data on stress coping strategies. Clinical attachment loss (CAL) served as the clinical parameter. RESULTS With the help of a factor analysis with a factorization and Varimax rotation, 5 factors were extracted from the 19 subtests. The reliability of the questionnaire was less than 0.70 only for subtests "escape" and "pharmaceutical drugs. " Otherwise the internal consistency ranged between 0.74 and 0.92, and the retest reliability between 0.72 and 0.84. Subsequent assessment with the t test for independent random samples at the 5% level showed that patients differ significantly from controls in regard of factor 2 (active coping, P = 0.40) and 3 (distractive coping, P = 0.033), and that they differ very significantly from controls in regard of factor 4 (defensive coping, P = 0.000) and 5 (coping through aggression and pharmaceutical drugs, P = 0.007). In the statistical analysis of factors with regard to the severity of periodontal disease, the patients were divided into 2 groups (mild to moderate and severe). The t test for independent random samples showed significance for factor 4 (defensive coping) in that patients with a defensive coping style had greater attachment loss (pF4 = 0.04). CONCLUSIONS The data corroborate the thesis that periodontitis patients with inadequate stress behavior strategies (defensive coping) are at greater risk for severe periodontal disease. However, further investigations are required to confirm the significance of inappropriate coping styles with respect to the advancement of periodontal disease.