Miracle-dz/UniFAR-FTUs huggingface dataset:
Regulatory role of natural killer (NK) cells on antibody responses to Brucella abortus

Our previous studies have indicated an important regulatory role for natural killer (NK) cells, a major constituent of the innate immune system in modulating antigen-specific responses. Herein, we have investigated the possible participation of these cells in regulating the polyclonal response as well. For these studies we have utilized heat-killed Brucella abortus (HKBA). Brucella abortus is a facultative intracellular bacterium that is pathogenic for both humans and animals. An outstanding feature of the infectious process is the rapid production of polyclonal antibodies, particularly of the IgG2c subclass, that bypasses the requirement for clonally specific antigen recognition. We report here that NK-cell depletion profoundly reduced the production of these polyclonal antibodies suggesting that activation of B cells by HKBA requires help from NK cells. This help may not be solely derived from NK-cell amplification of the cytokine circuit initiated by HKBA but may involve direct NK—B-cell interactions as suggested by results of in vitro analyses of NK induction of γ2a mRNA by B cells. These findings have therapeutic implications in that the induction of polyclonal Ig production may be more important for altering the chronic phase rather than the acute stage of infection by B. abortus.
The Ljubljana Classification: A Practical Strategy for the Diagnosis of Laryngeal Precancerous Lesions

Summary: There is no internationally accepted classification of epithelial hyperplastic laryngeal lesions (EHLL). The majority of current classifications follow criteria similar to those commonly used for cervical epithelial lesions. However, the different etiology of laryngeal cancer and its particular clinical and histologic features necessitate a grading system more appropriate to this region. The Ljubljana classification of EHLL was devised in 1971 to cater to this requirement. Detailed criteria for histologic grading in this classification were formulated by a working group on EHLL of the European Society of Pathology in 1999. The system recognizes four grades: simple and abnormal hyperplasia are benign categories; atypical hyperplasia (“risky” epithelium) is potentially malignant, and carcinoma in situ actually malignant. The main features by which the proposed grading system differs from other classifications are: 1. the distinction between benign and potentially malignant lesions: 2. the positive separation of carcinoma in situ from atypical hyperplasia; 3. the lack of prognostic significance for any surface keratin layer. The eventual outcome of EHLL patients so graded justifies the proposal for separating the lesions into a benign group, showing malignant transformation in only 0.9% of cases, from a potentially malignant group showing malignant transformation in 11% of cases. For diagnostically difficult cases, supplementary techniques such as those using morphometry, immunohistochemical and molecular biology are advised to improve the accuracy of diagnosis and predictions of their biological behavior.
Occupational Blood Exposure among Health Care Personnel and Hospital Trainees

Blood and body fluid Exposure is a major occupational safety problems for health care workers. Therefore, we conducted a descriptive and retrospective study to identify the characteristics of blood exposure accidents in health care settings which lasted five years (2005-2009) at the two university hospitals of Sfax. We have 593 blood exposure accidents in health care settings 152 (25.6%) health personnel and 441 (74.4%) trainees' doctors, nurses and health technicians. The mechanism of blood and body fluid exposure was accidental needle-stick injury in 78.9% of health staff, and 81% of trainees, accidental cut in 14.7% of health workers and 10.2% of trainees. The increasing severity of blood exposure accidents is linked to the lack of safe behavior against this risk.
Anatomically based guidelines for systematic investigation of the central somatosensory system and their application to a spinocerebellar ataxia type 2 (SCA2) patient

Dysfunctions of the somatosensory system are among the clinical signs that characterize a variety of polyglutamine or CAG‐repeat diseases. Deficits within this system may hinder the perception of potential threats, be detrimental to somatomotor functions, and result in uncoordinated movements, ataxia, and falls. Despite the considerable clinical relevance of such deficits, however, no systematic pathoanatomical studies of the central somatosensory system in polyglutamine diseases are currently available. The present paper has two goals: (1) re‐commendation of an economical tissue sampling method and optimized histological processing of this tissue to allow rapid and reliable evaluation of the structural integrity of all known relay stations and interconnecting fibre tracts within this complex system, and (2) the proposal of guidelines for a rapid and detailed pathoanatomical investigative procedure of the human central somatosensory system. In so doing, we draw on the current state of neuroanatomic research and apply the methods and guidelines proposed here to a 25‐year‐old female patient with spinocerebellar ataxia type 2 (SCA2). The use of 100 µm serial sections through the SCA2 patient's central somatosensory components showed that obvious neuronal loss occurred in nearly all of the relay stations of this system (Clarke's column; cuneate, external cuneate and gracile nuclei; spinal, principal and mesencephalic trigeminal nuclei; ventral posterior lateral and ventral posterior medial nuclei of the thalamus), whereas the majority of interconnecting fibre tracts (dorsal spinocerebellar tract; cuneate and gracile fascicles; medial lemniscus; spinal trigeminal tract, trigeminal nerve and mesencephalic trigeminal tract) displayed signs of atrophy accompanied by demyelinization. These pathological findings suffice to explain the patient's impaired senses of vibration, position and temperature. Moreover, together with the lesions seen in the motor cerebellothalamocortical feedback loop (pontine nuclei, deep cerebellar nuclei and cerebellar cortex, ventral lateral nucleus of the thalamus), they also account for the somatomotor deficits that were observed in the young woman (gait, stance, and limb ataxia, falls, and impaired writing). In proposing these new guidelines, we hope to enable others to study the hitherto unknown morphological counterparts of somatosensory dysfunctions in additional CAG‐repeat disease patients.
Hochu-ekki-to combined with interferon-gamma moderately enhances daily activity of chronic fatigue syndrome mice by increasing NK cell activity, but not neuroprotection

The purpose of this study was to evaluate the beneficial effect of Hochu-ekki-to (TJ-41) combined with interferon-gamma (IFNγ) on daily activity, immunological and neurological alternation in a mouse model of chronic fatigue syndrome (CFS). CFS was induced by 6 times of repeated injection of Brucella abortus antigen every 2 weeks. Both single TJ-41 and TJ-41 combined with IFNγ increased running activity and thymus weight of CFS mice, while thicker thymic cortex together with elevation of natural killer cell activity was only found in the combined treatment group. No significant improvement was observed in the atrophic brain and decreased expression level of brain-derived neurotrophic factor and Bcl-2 mRNA in hippocampus in both treatment groups. Our results suggest that TJ-41 combined with IFNγ might have a protective effect on the marked reduction in the activity in a model of CFS via normalization of host immune responses, but not neuroprotection.
Pain, Physical Function, and Health in Patients With Knee Osteoarthritis

Purpose: The aim of this study was to evaluate the associations between pain and physical functional limitation and health status in patients with knee osteoarthritis (OA). Design: A correlational study. Methods: In a convenience sample of 73 patients with knee OA, pain and physical function were assessed using the Western Ontario and McMaster University Osteoarthritis Index. Health status was evaluated using multiple instruments under the International Classification of Functioning, Disability, and Health framework. Findings: In the study of patients with knee OA, pain and physical functional limitation exhibited mild to strong associations with health status, including body function and structure (r = .26–.71), activities and participation (r = .24–.88), and personal and environmental factors (r = .24–.62). Conclusion: In patients with knee OA, health status is mildly to strongly associated with pain and physical functional limitation. Clinical Relevance: Reducing pain and physical functional limitation in patients with knee OA might improve their health status.
Motives of Belgian Adolescents for Using Sunscreen: The Role of Action Plans

The first objective of this study was to analyze the differences between adolescents who use sunscreen frequently and those who do not. The second objective was to explore the importance of specific action plans when planning sunscreen use. Data was gathered among 602 Belgian secondary school students. Frequent and infrequent users of sunscreen were compared on several determinants related with sunscreen use, and a regression analysis on sunscreen use was done. Frequent users of sunscreen measures had significantly higher scores on attitudes, social influence, self-efficacy, some awareness factors, intention, and action plans. The integrated model for exploring motivational and behavioral change (I-Change model) explained 57% of the total variance of using sunscreen every 2 hours. Frequent sunscreen use was most strongly predicted by action plans, followed by positive intentions to use sunscreen, wearing protective clothing, seeking shade, attitude toward sunscreen use, education, social influence, and exposure to the sun. Our results suggest that skin cancer prevention programs aimed at promoting sunscreen use need to emphasize the advantages of sunscreen to infrequent users and to increase feelings of self-efficacy. Moreover, support by friends and parents should be stimulated. Finally, developing specific action plans for the use of sunscreen should be promoted to more effectively translate general intentions into actual sunscreen use. (Cancer Epidemiol Biomarkers Prev 2006;15(7):1360–6)
Crystal Structure of Glucagon-like Peptide-1 in Complex with the Extracellular Domain of the Glucagon-like Peptide-1 Receptor*

GLP-1 (glucagon-like peptide-1) is an incretin released from intestinal L-cells in response to food intake. Activation of the GLP-1 receptor potentiates the synthesis and release of insulin from pancreatic β-cells in a glucose-dependent manner. The GLP-1 receptor belongs to class B of the G-protein-coupled receptors, a subfamily characterized by a large N-terminal extracellular ligand binding domain. Exendin-4 and GLP-1 are 50% identical, and exendin-4 is a full agonist with similar affinity and potency for the GLP-1 receptor. We recently solved the crystal structure of the GLP-1 receptor extracellular domain in complex with the competitive antagonist exendin-4(9–39). Interestingly, the isolated extracellular domain binds exendin-4 with much higher affinity than the endogenous agonist GLP-1. Here, we have solved the crystal structure of the extracellular domain in complex with GLP-1 to 2.1 Åresolution. The structure shows that important hydrophobic ligand-receptor interactions are conserved in agonist- and antagonist-bound forms of the extracellular domain, but certain residues in the ligand-binding site adopt a GLP-1-specific conformation. GLP-1 is a kinked but continuous α-helix from Thr13 to Val33 when bound to the extracellular domain. We supplemented the crystal structure with site-directed mutagenesis to link the structural information of the isolated extracellular domain with the binding properties of the full-length receptor. The data support the existence of differences in the binding modes of GLP-1 and exendin-4 on the full-length GLP-1 receptor.
Origin of endocrine‐metabolic changes in the weanling rat ventromedial syndrome

Destruction of the ventromedial hypothalamic nuclei (VMN) in the weanling rat without injury to the median eminence results in a series of somatic, endocrine, and metabolic changes that are characterized by normal food and water intake but decreased linear growth, normal body weight but increased carcass fat and reduced carcass protein, lean body mass, and water. The endocrine alterations comprise hyerinsulinemia in the face of normoglycemia, hypertrigly ceridemia and hypercholesterolemia and reduced growth hormone levels. The metabolic changes include greater oxidation of glucose and incorporation into lipid and reduced palmitate oxidation but increased incorporation into lipid.
[Lymphocytic alveolitis in the early stages of HIV infection: correlation with biological and prognostic factors].

Broncho-alveolar lavage was performed to assess the degree of pulmonary lymphocytic alveolitis in 32 asymptomatic patients who were infected with the Human Immunodeficiency Virus (VIH). The patients were stages II and III of the CDC classification and the aim of the study was to determine the frequency, nature and prognostic role of the findings. 62.5% of the subjects (20/32) presented with a lymphocytic alveolitis which consisted predominantly of CD8 lymphocyte (64.3 +/- 3.5%), in the absence of an opportunistic infection or broncho-pulmonary tumours. Two sub-populations of alveolar CD8 were shown at comparable levels, a) sub-population CD8+D44+ (22.1 +/- 5%), in whom we showed the possession of cytotoxic activity in particular specific for VIH; b) sub-population CD8+CD57+ (19.6 +/- 3%) which we have shown to be capable in vitro of inhibiting the effector phase of cytotoxic activity of CD8+D44+ alveolar cells specific for VIH. In this group of 32 patients the occurrence of an alveolitis was not correlated with the usual prognostic factors of infection by VIH measured simultaneously with broncho-alveolar lavage (the level of CD4+ blood lymphocytes, and the beta 2-plasma microglobulins and the presence of p24 antigenaemia). In addition the level of CD4 lymphocytes supperior to 400/mm3 and of beta 2-microglobulins less then 3 mg/l whether a lymphocytic alveolitis was there or not confirmed the relatively poorly developed state of the VIH infection in these asymptomatic patients. Also the occurrence of a lymphocytic alveolitis did not seem to be linked to progression of the disease in the group of patients studied. (ABSTRACT TRUNCATED AT 250 WORDS)
Compression stiffening of brain and its effect on mechanosensing by glioma cells

Many cell types, including neurons, astrocytes and other cells of the central nervous system, respond to changes in the extracellular matrix or substrate viscoelasticity, and increased tissue stiffness is a hallmark of several disease states, including fibrosis and some types of cancers. Whether the malignant tissue in brain, an organ that lacks the protein-based filamentous extracellular matrix of other organs, exhibits the same macroscopic stiffening characteristic of breast, colon, pancreatic and other tumors is not known. In this study we show that glioma cells, like normal astrocytes, respond strongly in vitro to substrate stiffness in the range of 100 to 2000 Pa, but that macroscopic (mm to cm) tissue samples isolated from human glioma tumors have elastic moduli in the order of 200 Pa that are indistinguishable from those of normal brain. However, both normal brain and glioma tissues increase their shear elastic moduli under modest uniaxial compression, and glioma tissue stiffens more strongly under compression than normal brain. These findings suggest that local tissue stiffness has the potential to alter glial cell function, and that stiffness changes in brain tumors might arise not from increased deposition or crosslinking of the collagen-rich extracellular matrix, but from pressure gradients that form within the tumors in vivo.
Body composition is distinctly altered in Turner syndrome: relations to glucose metabolism, circulating adipokines, and endothelial adhesion molecules.

BACKGROUND Body composition in Turner syndrome (TS) is altered with final height of TS decreased; anthropometry and bone mass distinctly changed. AIM To describe total and regional distribution of fat and muscle mass in TS and the relation to measures of glucose metabolism, sex hormones, IGFs, and markers of inflammation and vascular function. MATERIAL AND METHODS Fifty-four women with TS (mean age, 42.5 +/- 9.7 years) and an age-matched group of controls (n = 55) were examined by dual-energy X-ray absorptiometry scans with determination of regional body composition and estimation of visceral fat and skeletal muscle mass. We determined maximal oxygen uptake and assessed physical activity using a questionnaire. We measured serum adiponectin, ghrelin, IGF-I, IGF-binding protein-3 (IGFBP-3), estradiol, testosterone, sex hormone-binding globulin (SHBG), insulin, glucose, cytokines, vascular cell adhesion molecule-I, and intercellular cell adhesion molecule-I. Insulin sensitivity was estimated. Multiple linear regression models were used to examine the relationships between variables. RESULTS TS had lower total lean body mass (LBM), while body mass index (BMI) and total fat mass (FM) were increased. We found increased visceral FM, and decreased trunk LBM, appendicular LBM, and skeletal muscle mass. VO2max and physical activity were significantly lower in TS, as were most hormone levels, except increased leptin. In multiple linear regression models, status (i.e. TS or control) was a consistent contributing variable. CONCLUSION Profound changes are present in body composition in TS, with increased FM, and decreased skeletal muscle mass. Circulating hormones, VO2max, and insulin sensitivity influence body composition. The accumulation of visceral fat would predict a higher risk of development of the insulin resistance syndrome.
The glenolabral articular disruption lesion: MR arthrography with arthroscopic correlation.

OBJECTIVE The purpose of this study was to describe the MR arthrography appearance of the glenolabral articular disruption (GLAD) lesion. Proper diagnosis of this lesion is important because it can be a source of persistent shoulder pain that requires surgical repair and because it is often difficult to diagnose clinically. MATERIALS AND METHODS Findings on MR arthrography were retrospectively correlated with the clinical histories and physical examination findings of six patients in whom we saw the typical appearance of the GLAD lesion. Four of these patients underwent follow-up arthroscopy that included surgical proof of GLAD lesions. RESULTS Five of the six patients had a documented glenohumeral impaction injury associated with an abducted externally rotated shoulder. All six patients had persistent shoulder pain, but their shoulders were stable during routine examination. In all patients, MR arthrography showed a superficial tear of the anteroinferior labrum with an adjacent articular cartilage injury. The torn labrum remained firmly attached to the anterior scapular periosteum, and contrast material was seen to extend into the labral tear and cartilaginous defect. CONCLUSION The MR arthrography findings of GLAD lesions include a nondisplaced tear of the anteroinferior labrum with an adjacent chondral injury. The pattern of chondral injury can range from a cartilaginous flap tear to a depressed osteochondral injury of the articular cartilage and underlying bone.
Use of inspiratory strength training to wean six patients who were ventilator-dependent.

BACKGROUND AND PURPOSE Patients who are unable to wean from mechanical ventilation (MV) after resolution of critical illness or surgery risk increased morbidity and death and consume a disproportionate amount of intensive care unit resources. Decreased inspiratory muscle strength is often cited as a major factor contributing to prolonged MV. The purpose of this case report is to describe the rationale and application of inspiratory strength training (IST) as an adjunct to lengthen unassisted breathing trials and to ultimately wean patients with chronic mechanical ventilator dependency. CASE DESCRIPTION Six patients who had been ventilator-dependent for 18 to 221 days (mean of 72 days) after surgery and were diagnosed with "failure to wean" performed low-repetition, high-resistance breathing exercises that were coupled with increasing time off the ventilator. OUTCOMES All 6 patients were weaned from the ventilator in 9 to 28 days (mean of 17 days). The patients' training pressure increased from a mean of 9.3 cm/H2O to 27.5 cm/H2O, for an increase of 195%. The volitional maximum inspiratory pressure (MIP) increased from a mean of 22.5 cm/H2O to 54 cm/H2O, for a 140% gain in pressure. DISCUSSION Although it is not clear why the patients appeared to benefit from IST, possible explanations include: (1) addressing inspiratory muscle pump dysfunction, (2) standardization of breathing patterns, 3) routinization of the patients' unassisted breathing trials, and (4) nonspecific training effects. Future research should address these possibilities when attempting to understand the effects of IST in the weaning of patients with chronic ventilator dependency.
Topically Applied Eicosapentaenoic Acid Protects Against Local Immunosuppression Induced by UVB Irradiation, cis-Urocanic Acid and Thymidine Dinucleotides¶

Abstract UVB-induced immunosuppression, a promoter of photocarcinogenesis, involves the formation of pyrimidine dimers and cis-urocanic acid (cis-UCA), but reactive oxygen species (ROS) also plays an important role. Eicosapentaenoic acid (EPA) can inhibit photocarcinogenesis, but due to its polyunsaturated nature it is susceptible to oxidative damage by ROS. The antioxidant defense system may therefore be challenged upon ultraviolet-B (UVB) irradiation in the presence of EPA. We investigated whether topically applied EPA in mice could protect against local immunosuppression (contact hypersensitivity response to dinitrofluorobenzene) induced by UVB radiation (1.5 J/cm2), or topically applied cis-UCA (150 nmol/cm2) or thymidine dinucleotides (pTpT) (5 nmol/cm2). The influence of EPA on epidermal lipid peroxidation and antioxidant status was also measured. UVB irradiation, cis-UCA and pTpT all caused 70% immunosuppression. Topical pretreatment of mice with EPA partially protected against immunosuppression; the EPA dose needed to accomplish this was 10 nmol/cm2 for UVB irradiation, 100 nmol/cm2 for cis-UCA and 1000 nmol/cm2 for pTpT. Higher EPA doses caused higher UVB-induced lipid peroxidation and lower vitamin C levels. Glutathione only decreased with the highest EPA dose whereas vitamin E was not decreased after UVB irradiation. In conclusion, topically applied EPA protects against UVB-, cis-UCA- and pTpT-induced immunosuppression and maintenance of an adequate antioxidant defense seems to be an important prerequisite for the protective action by EPA.