Miracle-dz/UniFAR-FTUs huggingface dataset:
Autoantibody-Mediated Pulmonary Alveolar Proteinosis in Rasgrp1-Deficient Mice

Pulmonary alveolar proteinosis (PAP) is a rare lung syndrome caused by the accumulation of surfactants in the alveoli. The most prevalent clinical form of PAP is autoimmune PAP (aPAP) whereby IgG autoantibodies neutralize GM-CSF. GM-CSF is a pleiotropic cytokine that promotes the differentiation, survival, and activation of alveolar macrophages, the cells responsible for surfactant degradation. IgG-mediated neutralization of GM-CSF thereby inhibits alveolar macrophage homeostasis and function, leading to surfactant accumulation and innate immunodeficiency. Importantly, there are no rodent models for this disease; therefore, underlying immune mechanisms regulating GM-CSF–specific IgG in aPAP are not well understood. In this article, we identify that autoimmune-prone Rasgrp1-deficient mice develop aPAP: 1) Rasgrp1-deficient mice exhibit reduced pulmonary compliance and lung histopathology characteristic of PAP; 2) alveolar macrophages from Rasgrp1-deficient mice are enlarged and exhibit reduced surfactant degradation; 3) the concentration of GM-CSF–specific IgG is elevated in both serum and bronchoalveolar lavage fluid from Rasgrp1-deficient mice; 4) GM-CSF–specific IgG is capable of neutralizing GM-CSF bioactivity; and 5) Rasgrp1-deficient mice also lacking CD275/ICOSL, a molecule necessary for conventional T cell–dependent Ab production, have reduced GM-CSF–specific autoantibody and do not develop PAP. Collectively, these studies reveal that Rasgrp1-deficient mice, to our knowledge, represent the first rodent model for aPAP.
Oxidative stress in patients with cardiovascular disease and chronic renal failure

Abstract Oxidative response regulates many physiological response in human health, but if not properly regulated it could also lead to a number of deleterious effects. The importance of oxidative stress injury depends on the molecular target, the severity of the stress, and the mechanism by which the oxidative stress is imposed: it has been implicated in several diseases including cancer, neurodegenerative diseases, malaria, rheumatoid arthritis and cardiovascular and kidney disease. Most of the common diseases, such as hypertension, atherosclerosis, heart failure, and renal dysfunction, are associated with vascular functional and structural alterations including endothelial dysfunction, altered contractility, and vascular remodeling. Common to these processes is increased bioavailability of reactive oxygen species (ROS), decreased nitric oxide (NO) levels, and reduced antioxidant capacity. Oxidative processes are up-regulated also in patients with chronic renal failure (CRF) and seem to be a cause of elevated risk of morbidity and mortality in these patients. In this review, we highlight the role of oxidative stress in cardiovascular and renal disease.
The experiences of individuals with a traumatic brain injury, families, physicians and health professionals regarding care provided throughout the continuum

Primary objective: To investigate the experiences of individuals who had sustained a traumatic brain injury, their families and the physicians and health professionals involved, from the critical care episodes and subsequent rehabilitation. Research design: Semi-structured interviews were conducted with individuals who had sustained a TBI (n = 8) and their families (n = 8) as well as with the health professionals (or service providers) (n = 22) and physicians (n = 9) who provided them care. Main outcomes and results: Results revealed the difficulties encountered by the different people involved, from the standpoint of the readjustment of the individual with the TBI and their family, the relationships among the various actors and the continuity of care. Conclusions: This study brings to light the importance of including the family and the person with a TBI in the care process by calling for their participation and by setting up suitable structures that prioritize a meaningful partnership among the key individuals.
Rapid subglacial erosion beneath Pine Island Glacier, West Antarctica

We present measurements of ice thickness, gravimetry and surface elevation on Pine Island Glacier, West Antarctica, separated by a period of 49 years. At one station, on the main trunk of the glacier we measured a surface elevation lowering with no significant change in ice thickness. We interpret these as indicating subglacial erosion of 31.8 ± 13.4 m at this location, at a mean rate over the measurement period of 0.6 ± 0.3 m a−1, and suggest that a current erosion rate of ∼1 m a−1is possible. Our results emphasize that locally, basal processes can have a significant effect on ice sheet changes, particularly where fast‐flowing ice has an easily erodible bed.
Renal cell carcinoma metastatic to the pancreas: clinical and radiological features.

OBJECTIVE To review the clinical features, computed tomographic (CT) appearance, and treatment outcomes in a case series of patients with renal cell carcinoma (RCC) metastatic to the pancreas. PATIENTS AND METHODS We retrospectively reviewed the records of 23 patients (15 men and 8 women) with RCC metastatic to the pancreas, detected by CT examination between 1986 and 1996. All patients had undergone a previous nephrectomy for RCC. RESULTS Isolated mild elevation in liver function test results (in 5 patients) or in serum amylase level (in 8 patients) was observed. New-onset diabetes was detected in 3 patients. The CT characteristics of the pancreatic metastases generally resembled those of primary RCC with well-defined margins and greater enhancement than normal pancreas with a central area of low attenuation. The mean interval between resection of the primary RCC and detection of the pancreatic metastases was 116 months (range, 1-295 months). In 18 patients (78%), the pancreatic metastases were diagnosed more than 5 years after nephrectomy. The pancreas was the initial metastatic site in 12 patients (52%). Survival was shortened with higher tumor grade (mean survival time of 41 months and 10 months in patients with grade 2 and 3, respectively). Surgical resection was carried out in 11 patients (7 distal and 3 total pancreatectomies and 1 distal pancreatectomy followed 4 years later by total pancreatectomy), with 8 patients alive at a mean follow-up of 4 years, 6 of whom remained free of recurrence. Overall, 12 patients (52%) were alive at a mean of 42 months after diagnosis of metastatic disease. CONCLUSIONS The appearance of metastatic RCC lesions in the pancreas closely resembles the appearance of primary RCC on CT images. Pancreatic metastases from RCC are frequently detected many years after nephrectomy. Patient survival correlates with tumor grade. Histologic analysis of pancreatic masses in patients with a history of resected primary RCC is important since the prognosis for RCC metastatic to the pancreas is much better than that for primary pancreatic adenocarcinoma.
Urinary Excretion of Albumin and Retinol Binding Protein in Systemic Lupus Erythematosus

We have measured the urinary excretion of total protein, albumin and retinol binding protein (RBP) in random urine specimens obtained from 40 female patients with systemic lupus erythematosus (SLE). Thirty-three of these patients had no clinical evidence of any renal impairment (non-renal SLE); seven had overt renal disease (renal SLE). RBP: creatinine ratios were significantly higher in non-renal SLE patients compared with female controls (P = 0·002). There was no significant difference between urine total protein concentrations, albumin: creatinine or total protein: creatinine ratios in non-renal SLE patients when compared with controls, despite approximately 20% of these patients having elevated excretion of total protein or albumin. All seven renal SLE patients had elevated albumin: creatinine ratios but only four of them had an increased RBP: creatinine ratio. Of 29 non-renal SLE patients who had urinary total protein concentrations below 0·2 g/L, (i.e. approximating to a negative protein dipstick), 14 had increases in either albumin : or RPB: creatinine ratios. Only two patients had increases in both. In the absence of clinical evidence of renal disease, increases in urinary albumin or RBP excretion could indicate subclinical nephropathy and measurements may have a role in the early diagnosis and subsequent monitoring of renal disease in SLE.
In vitro antistaphylococcal activities of two investigative fluoroquinolones, CI-960 and WIN 57273, compared with those of ciprofloxacin, mupirocin (pseudomonic acid), and peptide-class antimicrobial agents

By using broth microdilution, 373 clinical isolates of staphylococci were studied to determine their susceptibilities to CI-960, WIN 57273, ciprofloxacin, mupirocin, vancomycin, teicoplanin, and ramoplanin. Test strains comprised 179 strains of Staphylococcus aureus and 194 strains of coagulase-negative species. Strains of S. aureus were susceptible to CI-960, which had a mode MIC of 0.032 micrograms/ml and an MIC for 90% of the strains of 2 micrograms/ml. CI-960 was equally active against methicillin-susceptible and -resistant S. aureus strains as well as ciprofloxacin-resistant strains. Similarly, WIN 57273 was highly active, with a mode MIC of 0.008 micrograms/ml and an MIC for 90% of the strains of 1 micrograms/ml. No cross-resistance to CI-960 and WIN 57273 among ciprofloxacin-resistant strains was detected. Mupirocin was four- to eightfold more active than ramoplanin, vancomycin, and teicoplanin. With regard to coagulase-negative staphylococci, CI-960 and WIN 57273 were the most active of the test compounds, inhibiting all strains at 0.5 and 1 micrograms/ml, respectively. Against the same strains, mupirocin was fourfold more active than ramoplanin and eightfold more active than vancomycin. Five strains of S. haemolyticus were found to be resistant to ciprofloxacin, while resistance to teicoplanin was found among strains of S. epidermidis, S. haemolyticus, S. hominis, S. saprophyticus, S. simulans, S. warneri, and S. xylosus.
Public Perception of Climate Change: The Importance of Knowledge and Cultural Worldviews

The importance of knowledge for lay people's climate change concerns has been questioned in recent years, as it had been suggested that cultural values are stronger predictors of concern about climate change than knowledge. Studies that simultaneously measured knowledge related to climate change and cultural values have, however, been missing. We conducted a mail survey in the German‐speaking part of Switzerland (N = 1,065). Results suggested that cultural worldviews and climate‐related knowledge were significantly related with people's concern about climate change. Also, cultural worldviews and climate‐relevant knowledge appeared important for people's willingness to change behaviors and to accept climate change policies. In addition, different types of knowledge were found to have different impacts on people's concern about climate change, their willingness to change behaviors, and their acceptance of policies about climate change. Specifically, causal knowledge significantly increased concern about climate change and willingness to support climate‐friendly policies. We therefore concluded that risk communication should focus on causal knowledge, provided this knowledge does not threaten cultural values.
Reflections on Transnational Transferability of Improvement Technologies—A Comparison of Factors for Successful Change in the United States and Northern Europe

Two reliable models for predicting the success of change initiatives have been developed through the same research process. One model represents what is important in order to conduct successful improvements in the United States. The other model has been developed to predict successful improvement initiatives in Sweden. Through qualitative comparison between two reliable models we found some similarities and differences framing the underlying management heuristics for driving improvement initiatives. These findings are important pieces in transnational knowledge acquirement on quality improvements. They contribute a basis for discussions on transferability of management change concepts, and prompts for areas in need of considerations of adaptation before using different improvement ideas in other contexts than those for which they were developed.
Roundabout is required in the visceral mesoderm for proper microvillus length in the hindgut epithelium

Introduction: In this study we examined Roundabout signaling in the Drosophila embryonic hindgut. Results: Slit and its receptors Roundabout (Robo) and Roundabout 2 (Robo2) localize to discrete regions in the hindgut epithelium and surrounding visceral mesoderm. Loss of robo, robo2 or slit did not disrupt overall hindgut patterning. However, slit and robo mutants showed a decrease in microvillus length on the boundary cells of the hindgut epithelium. Rescue and overexpression analysis revealed that robo is specifically required in the visceral mesoderm for correct microvillus length in the underlying hindgut epithelium. Expression of robo in the visceral mesoderm of robo mutant embryos restored normal microvillus length, while overexpression of robo resulted in an increase in microvillus length. Microvillus length was also increased in robo2 mutants suggesting that robo2 may antagonize robo function in the hindgut. Conclusion: Together, these results establish a novel, dose‐dependent role for Robo in regulating microvilli growth and provide in vivo evidence for the role of the visceral mesoderm in controlling morphological changes in the underlying intestinal epithelium. Developmental Dynamics 241:759–769, 2012. © 2012 Wiley Periodicals, Inc
Emotional Awareness, Relationship Quality, and Satisfaction in Patients With Parkinson’s Disease and Their Spousal Caregivers

Abstract This study aimed to evaluate the relationship quality and satisfaction in couples, in which one partner had PD, obtaining the perspective of both patients and partner and to examine the impact of alexithymia, empathy, depression, and anxiety on ratings of relationship quality and satisfaction. Fifteen PD patients and partners completed the following scales: the Dyadic Adjustment Scale; Couple Satisfaction Index (CSI); the 20-item Toronto Alexithymia Scale; the Empathy Quotient; the Hamilton Depression and the Hamilton Anxiety Rating Scale (HAM-A). We evaluated patients' motor functions by means of Unified Parkinson's Disease Rating Scale and patients' quality of life by means of the PD Questionnaire. Patients were significantly less satisfied with the relationship than their partners as revealed by CSI (p = 0.031) and they were more depressed (p = 0.003) and anxious (p = 0.015). A negative correlation between measures of relationship quality and satisfaction and alexithymia was found in the patients group. No correlations were found between measures of relationship quality and satisfaction (both of patients and partners) and any other demographical and clinical variables. CSI and HAM-A were predictors of patient's social support evaluation. The presence of alexithymia in PD is an important factor affecting relationship quality and satisfaction.
Auditory Efferent Function Is Affected in Multiple Sclerosis

Objective: This study evaluated efferent medial olivocochlear (MOC) function in patients with multiple sclerosis (MS). Various afferent auditory abnormalities have been described in MS, but there is a paucity of data on efferent function. The brain stem is a site of predilection for MS plaques and the efferent MOC pathway may be affected at this level. Methods: The study included 30 patients who had normal hearing. According to MRI findings, they were divided into two groups: those with an identifiable brain stem lesion (n = 10) and those with MS lesions in other parts of the central nervous system but without demonstrable MS plaques in the brain stem (n = 20). MOC function was evaluated by the olivocochlear suppression test, using transient evoked otoacoustic emissions. All subjects underwent standard auditory tests, including pure-tone audiometry and recording of auditory brain stem evoked responses. Twenty-two healthy subjects with normal hearing, matched for age and gender, served as a reference group for the auditory data. Results: The results showed that 66.6% of all patients had reduced MOC function, particularly those (90%) with identified lesions of the brain stem on MRI. Furthermore, abnormal MOC function was found in 55% patients without evidence of a brain stem lesion on MRI. Conclusions: This study provides the evidence for a deficit of efferent auditory function in the majority of patients with MS. Taking into consideration the possible roles of the MOC system in processing of auditory information, abnormal MOC suppression in patients with MS may explain a variety of auditory presentations that are currently largely overlooked. This study also highlights the diagnostic value of the MOC suppression test as a site-of-lesion diagnostic test in MS and in identifying subtle brain stem lesions undetected by MRI, suggesting that subtle brain stem lesions may exist and that the MOC suppression test is sufficiently sensitive to detect them. Accordingly, the MOC suppression test may provide a tool for an early diagnosis of MS.
Differential inhibition of catecholamine secretion by amitriptyline through blockage of nicotinic receptors, sodium channels, and calcium channels in bovine adrenal chromaffin cells

We investigated the effects of amitriptyline, a tricyclic antidepressant, on [3H]norepinephrine ([3H]NE) secretion and ion flux in bovine adrenal chromaffin cells. Amitriptyline inhibited [3H]NE secretion induced by 1,1‐dimethyl‐4‐phenylpiperazinium iodide (DMPP) and 70 mM K+. The half maximal inhibitory concentration (IC50) was 2 μM and 9 μM, respectively. Amitriptyline also inhibited the elevation of cytosolic calcium ([Ca2+]i) induced by DMPP and 70 mM K+ with IC50 values of 1.1 μM and 35 μM, respectively. The rises in cytosolic sodium ([Na+]i) and [Ca2+]i induced by the Na+ channel activator veratridine were also inhibited by amitriptyline with IC50 values of 7 μM and 30 μM, respectively. These results suggest that amitriptyline at micromolar concentrations inhibits both voltage‐sensitive calcium (VSCCs) and sodium channels (VSSCs). Furthermore, submicromolar concentrations of amitriptyline significantly inhibited DMPP‐induced [3H]NE secretion and [Ca2+]i rise, but not veratridine‐ or 70 mM K+‐induced responses, suggesting that nicotinic acetylcholine receptors (nAChR) as well as VSCCs and VSSCs can be targeted by amitriptyline. DMPP‐induced [Na+]i rise was much more sensitive to amitriptyline than the veratridine‐induced rise, suggesting that the influx of Na+ and Ca2+ through the nAChR itself is blocked by amitriptyline. Receptor binding competition analysis showed that binding of [3H]nicotine to chromaffin cells was significantly affected by amitriptyline at submicromolar concentrations. The data suggest that amitriptyline inhibits catecholamine secretion by blocking nAChR, VSSC, and VSCC. Synapse 29:248–256, 1998. © 1998 Wiley‐Liss, Inc.
Enlarged Vestibular Aqueduct Syndrome in the Pediatric Population

Objective To correlate clinical and audiometric findings with the radiologic appearance in patients with enlarged vestibular aqueduct. Design A retrospective review of data from enlarged vestibular aqueduct patients identified in a pediatric hearing-impaired database of 1,200 patients. Setting A tertiary care pediatric referral center. Patients Subjects were included for study with a radiographic diagnosis of enlarged vestibular aqueducts in at least one ear by a pediatric neuroradiologist. Main Outcome Measures Audiometric evaluations and radiographic temporal bone measurements. Results Seventy-seven patients were identified with an enlarged vestibular aqueduct with a male-to-female ratio of 1:1.5. Patients were followed for a mean of 34 months (range, 0–179 months). Hearing loss was bilateral in 87% of cases. Vestibular symptoms were present in only three (4%) of the patients. Three patients (4%) suffered a sudden decrease in hearing after mild head trauma. Borderline enlargement of the vestibular aqueduct was associated with varying degrees of sensorineural hearing loss. Ninety-seven percent (64 of 66) of ears in control subjects with no sensorineural hearing loss had normal vestibular aqueduct measurements at the midpoint and operculum. Overall, the audiogram remained stable in 51% of ears, fluctuated in 28%, and progressively worsened in 21%. Measurements of the vestibular aqueduct at the midpoint and the operculum did not correlate with the audiometric threshold or the audiogram configuration. However, mean vestibular aqueduct size at the operculum was significantly larger in those with a progressive loss when compared with those with a fluctuating or stable hearing outcome. Conclusions Overall, audiometric thresholds remained generally stable, with sudden deterioration of hearing after head trauma seen in only three male patients. Progression of hearing loss after head trauma was not a significant finding in our patient population. Vestibular aqueduct opercular size alone showed a direct correlation with the audiometric outcome. Borderline enlarged vestibular aqueduct measurements appear to be associated with sensorineural hearing loss.
Repeated Injections of IL‐2 Break Renal Allograft Tolerance Induced via Mixed Hematopoietic Chimerism in Monkeys

Tolerance of allografts achieved in mice via stable mixed hematopoietic chimerism relies essentially on continuous elimination of developing alloreactive T cells in the thymus (central deletion). Conversely, while only transient mixed chimerism is observed in nonhuman primates and patients, it is sufficient to ensure tolerance of kidney allografts. In this setting, it is likely that tolerance depends on peripheral regulatory mechanisms rather than thymic deletion. This implies that, in primates, upsetting the balance between inflammatory and regulatory alloimmunity could abolish tolerance and trigger the rejection of previously accepted renal allografts. In this study, six monkeys that were treated with a mixed chimerism protocol and had accepted a kidney allograft for periods of 1–10 years after withdrawal of immunosuppression received subcutaneous injections of IL‐2 cytokine (0.6–3 × 106 IU/m2). This resulted in rapid rejection of previously tolerated renal transplants and was associated with an expansion and reactivation of alloreactive pro‐inflammatory memory T cells in the host's lymphoid organs and in the graft. This phenomenon was prevented by anti‐CD8 antibody treatment. Finally, this process was reversible in that cessation of IL‐2 administration aborted the rejection process and restored normal kidney graft function.
Social constraints, loss-related factors, depression, and posttraumatic stress in a treatment-seeking suicide bereaved sample.

OBJECTIVE Negative social responses that inhibit disclosure in the suicide bereaved may pose an obstacle to recovery. However, such social constraints have not been evaluated in this population. The purpose of this study was to evaluate extent, types, and correlates of social constraints in treatment-seeking community-based participants recently bereaved by suicide. METHOD This cross-sectional study investigated social constraints and adjustment in a treatment-seeking sample of community-based participants (N = 33) recently bereaved by suicide; pretreatment, baseline data from a graduate school-based research clinic were analyzed. RESULTS Participants endorsed a moderate level of social constraints; subtle negative social responses appeared more common than overt negative reactions. Social constraints were unrelated to kinship with the deceased or to finding the body. Constraints were positively associated with depression (r = .54, p = .001) and posttraumatic stress (r = .43, p = .012). CONCLUSION Findings highlight the importance of the interpersonal context of adjustment in suicide postvention. (PsycINFO Database Record