Miracle-dz/UniFAR-FTUs huggingface dataset:
Transcranial magnetic stimulation-evoked inhibition of voluntary muscle activity (silent period) is impaired in patients with ischemic hemispheric lesion.

BACKGROUND AND PURPOSE Transcranial magnetic stimulation of the motor cortex is well established as a valuable method for noninvasive examination of the central motor system. In addition to exciting corticospinal cells and evoking a direct motor response, the magnetic stimulus delivered during voluntary activity produces a prolonged postexcitatory inhibition (silent period) of activity. We investigated silent period changes in patients with ischemic stroke of different clinical degrees. METHODS Standardized transcranial magnetic stimulation during sustained muscle contraction was performed at the vertex. Electromyographic activity was recorded via surface electrodes placed over the abductor digiti minimi muscle on both sides. We examined 50 patients with stroke (divided into three subgroups according to the degree of impairment) and 50 healthy control subjects. RESULTS In the control group we found no statistically significant interside difference in the duration of the silent period, whereas a marked interindividual variation was found. In patients with prior minor stroke who showed no residual motor disturbance, we found a significant prolongation of the postexcitatory inhibition recorded from the affected side compared with the healthy side. This interside discrepancy was even more pronounced in patients with minor hemiparesis and patients with moderate hemiparesis. CONCLUSIONS Our findings suggest that the measurement of the silent period elicited by transcranial magnetic stimulation is a useful and sensitive neurophysiological parameter in the management of stroke. Particularly in the subgroup of patients with no residual clinical signs of central motor impairment, it is capable of detecting subclinical motor function disturbances.
Cognitive modulation of the endocrine stress response to a pharmacological challenge in normal and panic disorder subjects.

CONTEXT The hypothalamic-pituitary-adrenal (HPA) axis may mediate the deleterious effects of stress on health. It is sensitive to cognitive and emotional aspects of organism-environment interactions, such as familiarity, control, and social support. Scientific study of how such factors moderate human HPA axis activity has been limited. Their relevance to HPA axis disturbances in psychiatric patients is largely unexplored. OBJECTIVE To determine whether cognitive manipulation can alter HPA axis activity in laboratory studies and whether patients with panic disorder are differentially sensitive to the manipulated factors. DESIGN Pharmacological activation paradigm (cholecystokinin-B agonist pentagastrin) by which we examined symptom and endocrine effects on subjects randomly assigned to a standard introduction or a cognitive intervention. SETTING Clinical research center. PARTICIPANTS Recruited from university clinic and newspaper advertisements. Fourteen patients with panic disorder and 14 controls, individually matched for age and sex. Intervention Half of each group received a 9-minute cognitive intervention designed to reduce novelty, increase cognitive coping, and provide a sense of control. MAIN OUTCOME MEASURES Corticotropin (ACTH) and cortisol levels. RESULTS The cognitive intervention significantly reduced cortisol (P = .02) and ACTH (P = .01) levels, despite pentagastrin's robust stimulation of both hormones (P<.001). The intervention effect was evident in patients and controls, who did not differ in basal HPA axis activity or response to pentagastrin. They did differ in panic symptom responses, which were unaffected by the intervention, and in ACTH effects of the intervention. Patients' exaggerated anxiety responses to pentagastrin were normalized by the intervention. CONCLUSIONS Cognitive/emotional manipulation can substantially modulate HPA axis responses to pharmacological activation in humans, and HPA disturbances in panic disorder may be secondary to manipulable cognitive/emotional sensitivities. Further study of such factors as novelty, control, and coping may help clarify the origins of HPA axis disturbance in psychiatric disorders and the mediators linking psychosocial stress to disease.
Semaphorin 3A – a marker for disease activity and a potential putative disease-modifying treatment in systemic lupus erythematosus

Semaphorin 3A (sema3A) and neuropilin-1 (NP-1) play a regulatory role in immune responses and have a demonstrated effect on the course of collagen-induced arthritis. Sema3A was also found to be involved in other immune-mediated diseases, e.g. psoriasis and allergic rhinitis. In this review we concentrated on the involvement of sema3A and NP-1 in the pathogenesis of systemic lupus erythematosus (SLE) and on the specific effect of sema3A on the auto-reactive properties of B cells in SLE patients. We demonstrated the expression of sema3A in renal biopsies from lupus glomerulonephritis patients. This expression was found to be inversely correlated with proteinuria and kidney function tests. Sema3A serum levels in SLE patients were found to be significantly lower than in RA patients (disease control) and lower yet than in normal individuals. Altered serum sema3A levels were found to be in inverse correlation with SLE disease activity, mainly with renal damage and the presence of anti-cardiolipin antibodies. The expression of both sema3A and NP-1 on B cells from SLE patients was significantly different in comparison with normal healthy individuals. Finally, we demonstrated that when sema3A was co-cultured with CpG-ODN-stimulated memory B cells of SLE patients, their TLR-9 expression was significantly reduced by almost 50% (p = 0.001). These findings, along with the observation of sema3A being reduced in SLE patients in correlation with disease severity and autoimmunity, and memory B cells being beneficially responsive to sema3A, suggest this regulatory molecule may be considered as a potential therapy for SLE. Such focused therapies will help in achieving the maintenance of self-tolerance and alter pro-inflammatory status in lupus.
Cell-intrinsic timers and thyroid hormone regulate the probability of cell-cycle withdrawal and differentiation of oligodendrocyte precursor cells.

During vertebrate development many types of precursor cells divide a limited number of times before they stop dividing and terminally differentiate. It is unclear what causes the cells to stop dividing when they do. We have been studying this problem in the oligodendrocyte cell lineage, which is responsible for myelination in the vertebrate central nervous system. Here we show for the first time that in clonal cultures of oligodendrocyte precursor cells purified from embryonic day 18 (E18) rat optic nerves the first oligodendrocytes develop within 3-4 days, equivalent to the time they first differentiate in the nerve, and that this timely differentiation depends on the presence of thyroid hormone. These findings suggest that a cell-intrinsic, thyroid-hormone-regulated timer determines when the first oligodendrocytes develop. Whereas the first oligodendrocytes develop asynchronously within clones, the vast majority develop after the first week in culture and do so more synchronously within clones. We show that beta1 thyroid hormone receptors in the precursor cells increase in clonal cultures in the absence of thyroid hormone in parallel with the increasing sensitivity of the cells to the cell-cycle-arresting activity of thyroid hormone; moreover, the increase in beta1 receptors, like the timer itself, is accelerated at 33 degrees C compared to 37 degrees C, suggesting that the increase in receptors may be part of the intrinsic timer. Finally, we show that the precursor cells do not divide indefinitely when stimulated to divide extensively in the absence of thyroid hormone but, instead, eventually stop dividing and either die or differentiate.
Brief Cognitive Assessment in the Early Stages of Parkinson Disease

Introduction:Cognitive dysfunction is an integral part of the Parkinson disease (PD) symptom spectrum. Early detection of cognitive dysfunction could help to delineate prevention strategies. Our main objective was to study the validity of brief cognitive tests, the Frontal Assessment Battery (FAB) and Mini-Mental State Examination (MMSE), as cognitive screening tools for detecting global and executive cognitive deficits in early stages of PD, as compared to a healthy control population. Methods:We evaluated 75 early-stage PD patients and 45 healthy age-matched and education-matched controls with the MMSE (global test) and FAB (frontal test), and compared total and subtest scores. We evaluated PD motor function with the Unified Parkinson Disease Rating Scale Part III. We assessed the relationship between cognitive and motor variables. Results:Frontal and global cognitive dysfunction was significantly more frequent in PD patients. PD patients scored significantly lower on FAB total and similarities, motor series, and conflicting instructions scores, and on the MMSE total, visuoconstructive, and memory scores. MMSE scores correlated significantly with Unified Parkinson Disease Rating Scale part III total score, speech, and bradykinesia scores. Conclusions:Early-stage PD patients present with frontal, memory, and visuoconstructive deficits in brief cognitive tests. Our results suggest that these brief bedside tests are useful for cognitive deficit screening in the early stages of PD. Our study did not account for the influence of depression in cognition. This constitutes a limitation, because many PD patients have depressive symptoms, which some studies have shown can be related to cognitive dysfunction.
Cardiovascular , Pulmonary and Renal Pathology Thrombotic Microangiopathy Associated with Humoral Rejection of Cardiac Xenografts from 1 , 3-Galactosyltransferase Gene-Knockout Pigs in Baboons

From the Transplantation Biology Research Center * and the Department of Pathology, Massachusetts General Hospital/Harvard Medical School, Boston, Massachusetts; the Department of Medicine, Transplant Center, Beth Israel Deaconess Medical Center/Harvard Medical School, Boston, Massachusetts; Immerge BioTherapeutics Incorporated, Cambridge, Massachusetts; and the Department of Pathology, Nippon Medical School, Tokyo, Japan
CD4 cell count recovery in HIV/TB co-infected patients versus TB uninfected HIV patients.

BACKGROUND There is lack of data comparing the improvement in CD4 count following antitubercular (ATT) and antiretroviral therapy (ART) in patients presenting with Human Immunodeficiency Virus/Tuberculosis (HIV/TB) dual infection compared with CD4 matched cohort of TB uninfected HIV patients initiated on ART. We sought to test the hypothesis; TB additionally contributes to reduction in CD4 count in HIV/TB co-infected patients and this would result in greater improvement in count following treatment compared with CD4 matched TB uninfected individuals. MATERIALS AND METHODS In a retrospective cohort study design we studied the change in CD4 cell counts in two groups of patients - those with CD4 cell count >100 cells / mm 3 (Group 1) and <100/mm 3 (Group 2) at presentation. In each group the change in CD4 cell count in dually infected patients following six-month ATT and ART was compared to cohorts of CD4 matched TB uninfected patients initiated on ART. RESULTS In Group 1 (52 patients) dually infected subjects' CD4 count improved from 150 cells/ mm 3 to 345 cells/mm 3 (P=0.001). In the control TB uninfected patients, the change was from 159 cells/mm 3 to 317 cells/mm 3 (P=0.001). Additional improvement in dually infected patients compared to the control group was not statistically significant (P=0.24). In Group 2 (65 patients) dually infected subjects count improved from 49 cells/mm3 to 249 cells/mm 3 (P=0.001) where as in control TB uninfected patients improvement was from 50 cells/ mm 3 to 205 cells/mm 3 (P=0.001), there being statistically significant additional improvement in dually infected subjects (P=0.01). CONCLUSION Greater increment in CD4 counts with ATT and ART in dually infected patients suggests that TB additionally influences the reduction of CD4 counts in HIV patients.
Response Entropy™ is not more sensitive than State Entropy™ in distinguishing the use of esmolol instead of remifentanil in patients undergoing gynaecological laparoscopy

Background: Monitoring of analgesia remains a challenge during general anaesthesia. Activation of Response Entropy™ (RE) to painful stimuli has been suggested to be a sign of inadequate analgesia. We evaluated the ability of RE to be more sensitive than State Entropy™ (SE) in measuring nociception in patients undergoing gynaecological laparoscopy. Our hypothesis was that while keeping SE at a predetermined level, RE would be higher in patients receiving a beta‐blocking agent (esmolol) instead of an opioid (remifentanil) during a propofol/nitrous oxide anaesthesia.
Interleukin-1alpha induction of tensile weakening associated with collagen degradation in bovine articular cartilage.

OBJECTIVE To determine whether interleukin-1alpha (IL-1alpha) induces tensile weakening of articular cartilage that is concomitant with the loss of glycosaminoglycans (GAGs) or the subsequent degradation of the collagen network. METHODS Explants of young adult bovine cartilage obtained from the superficial (including the articular surface), middle, and deep layers were cultured with or without IL-1alpha for 1 week or 3 weeks. Then, portions of the explants were analyzed for their tensile properties (ramp modulus, strength, and failure strain); other portions of explants and spent culture medium were analyzed for the amount of GAG and the amount of cleaved, denatured, and total collagen. RESULTS The effect of IL-1alpha treatment on cartilage tensile properties and content was dependent on the duration of culture and the depth of the explant from the articular surface. The tensile strength and failure strain of IL-1alpha-treated samples from the superficial and middle layers were lower after 3 weeks of culture, but not after 1 week of culture. However, by 1 week of culture, IL-1alpha had already induced release of the majority of tissue GAGs into the medium, without detectable loss or degradation of collagen. In contrast, after 3 weeks of culture, IL-1alpha induced significant collagen degradation, as indicated by the amount of total, cleaved, or denatured collagen in the medium or in explants from the superficial and middle layers. CONCLUSION IL-1alpha-induced degradation of cartilage results in tensile weakening that occurs subsequent to the depletion of GAG and concomitant with the degradation of the collagen network.
Lysophosphatidic Acid Induces Threonine Phosphorylation of Tiam1 in Swiss 3T3 Fibroblasts via Activation of Protein Kinase C*

The Rho family of GTPases plays an important role in the control of cell shape, adhesion, movement, and growth. Several guanine nucleotide exchange factors have been identified that activate Rho family GTPases by promoting the binding of GTP to these proteins. However, little is known concerning the regulation of these GDP/GTP exchange factors. In this study, we demonstrate that lysophosphatidic acid (LPA) induces a rapid, sustainable phosphorylation of the Rac1-specific nucleotide exchange factor Tiam1 in Swiss 3T3 fibroblasts. LPA stimulated Tiam1 phosphorylation in a dose-dependent manner, and the protein was phosphorylated on threonine, but not tyrosine or serine. Tiam1 phosphorylation was also induced by platelet-derived growth factor, endothelin-1, bombesin, and bradykinin but not by epidermal growth factor. Significantly, pretreatment of Swiss 3T3 fibroblasts with 1 μmphorbol 12-myristate 13-acetate for 24 h, or with the selective protein kinase C inhibitor Ro-31–8220, reduced LPA-stimulated phosphorylation of Tiam1 by approximately 75%. Moreover, acute stimulation with 100 nm phorbol 12-myristate 13-acetate was sufficient to induce Tiam1 phosphorylation in vivo, and protein kinase C could phosphorylate purified Tiam1 on threonine residues in vitro. These data indicate that agonist-induced phosphorylation of Tiam1 is a general mechanism and suggest that it is likely to be important in its regulation. Protein kinase C appears to play a key role in phosphorylation of Tiam1.
Student-led objective tutorials in Pharmacology: An interventional study

Objectives: Students learn in a better way if they are involved in active learning. Hence, the study was designed to introduce student-led objective tutorials (SLOTs) as an alternative to conventional tutorials (CTs) in pharmacology and to compare SLOT and CT on outcomes such as improved score in tests, active involvement of students, and faculty requirement of each. Materials and Methods: Didactic lectures taken on a topic in pharmacology were followed by a preintervention test for a batch of the 2nd year medical undergraduates. They were allotted either in SLOT or CT group. For a SLOT session, students of Group A (interventional group) were divided into teams and each team prepared five multiple choice questions on the given topic in PowerPoint format, which were presented to other teams and audience. The proceedings were facilitated by two lecturers. Group B undertook CT (controls). A postintervention test was then taken for both groups. Feedback was sought from students and teachers on SLOT. Results: The total marks for the test were 20. The mean marks in Group A improved by 31% (from 5.1 to 11.2). In Group B, they improved by 11% (from 5 to 7.2). Academic performance following SLOT was better than CT. Students (63%) favored SLOT as it stimulated their interest in the topic, improved self-learning skills, and teamwork. The teachers also favored SLOT for similar reasons. Conclusion: SLOT leads to greater satisfaction and better performance in tests. SLOT is an effective alternative to CT to promote active learning among students through group work. It helps overcome the logistic difficulties due to faculty shortage.
The Epstein-Barr virus (EBV) ORI1yt enhancer is not B-cell specific and does not respond synergistically to the EBV transcription factors R and Z

The Epstein-Barr virus DR promoter is located upstream of the PstI repeats, and in addition to the TATA box, it contains an upstream region (positions -69 to -220) responsive to EB1 (Z) (the BZLF1-encoded transcription factor) and an enhancer with two functionally distinct domains, A and B. Domain B has been described as a B-cell-specific EB1-responsive element (P. M. Lieberman, J. M. Hardwick, and S. D. Hayward, J. Virol. 63:3040-3050, 1989) activated synergistically by EB1 and R, an EBV early product encoded by the open reading frame BRLF1 (M. A. Cox, J. Leahy, and J. M. Hardwick, J. Virol. 64:313-321, 1990). We show here that domain B is an R-responsive element in HeLa cells and is therefore not an EB1-responsive B-cell-specific element. However, there is an EB1-binding site (ZRE-B) located within the R-responsive enhancer region. ZRE-B can be deleted without affecting the R-dependent enhancer activity. Moreover, there is no cooperation or synergy between R and EB1 when activating the B domain (ZRE-B plus the R-responsive element) positioned as an enhancer. ZRE-B is therefore not part of the R-inducible enhancer. We have tested several subregions of the DR enhancer B domain, either alone or in combination, for their capacity to transmit the R-activating signal to the rabbit beta-globin promoter. We found that the R-responsive element is composed of four protoenhancers that span the whole B domain. These protoenhancers alone are weakly or not responsive to R. One of the protoenhancers contains the overlapping palindromes 5'-TTGTCCcgtGGACAAaTGTCC-3'. However, one palindrome, either alone or duplicated, or the overlapping palindromes did not respond to R.
Kinematic differences between front crawl sprint and distance swimmers at a distance pace

Abstract The purpose of the study was to determine whether there are differences in kinematics between sprint and distance front crawl specialists when swimming at a distance pace using a six beat kick. Seven sprint and eight distance male specialists performed one maximum 400 m swim through a 6.75 m3 calibrated space recorded by six gen-locked cameras. The following variables were calculated: average swim velocity, stroke length, stroke frequency, upper limb and foot displacement, elbow angle, the shoulder and hip roll angle, duration of the stroke phases and time corresponding to particular events within the stroke cycle relative to hand entry. Differences between the groups were assessed by an independent t-test and effect size (d) calculations for each variable. The groups only differed significantly with respect to the average swim velocity, with the distance swimmers maintaining a greater velocity throughout the 400 m. However, effect sizes were moderate for elbow angle range during the pull phase (d = 0.78) and the total hip roll magnitude (d = 0.76). There was little evidence to suggest that sprint and distance swimmers using a six beat kick pattern differ in technique when swimming at a distance pace and therefore coaches should not encourage the development of different techniques between these groups.
Bone marrow reconversion in adults who are smokers: MR Imaging findings.

OBJECTIVE Conversion of bone marrow in the extremities from red to yellow is a normal maturation process. Marrow reconversion is present when expected yellow marrow is replaced with active red marrow, and it tends to occur at times of physiologic stress. The significance of this finding on MR imaging is not always clear. Accordingly, we studied the prevalence of bone marrow reconversion in adults undergoing MR imaging of the knee for reasons other than marrow disorders. Possible relationships between marrow reconversion and age, sex, weight, and smoking were sought. MATERIALS AND METHODS Fifty-nine outpatients over 24 years of age who had no evidence of hematopoietic disorders and for whom MR images of the knee were available for review were selected for study. Patients younger than 25 years old were eliminated to ensure that all patients in the study were old enough to have achieved normal adult marrow conversion. The 59 subjects were classified according to their smoking histories. Twenty-eight were nonsmokers, 10 were intermediate smokers, and 21 were heavy smokers. The MR images were classified as showing either red marrow (reconverted from yellow to red) or yellow marrow (converted) by two independent observers who had no knowledge of the patients' smoking histories. RESULTS MR images of six heavy smokers, two intermediate smokers, and one nonsmoker showed evidence of reconversion. A statistically significant association between marrow reconversion and heavy smoking (p = .02) was found. Reconversion also was found to be more prevalent in patients less than 39 years old and in obese women who smoked. No association was found between weight, sex, or obese male smokers and reconversion. CONCLUSION Our results show marrow reconversion at the knee is most prevalent in heavy smokers, younger patients, and especially obese women who smoke heavily. In these patients, marrow reconversion can be a normal finding on MR imaging. In other patients, other causes should be considered.