Miracle-dz/UniFAR-FTUs huggingface dataset:
Mechanistic independence of Nef and cyclophilin A enhancement of human immunodeficiency virus type 1 infectivity.

Optimal HIV-1 infectivity requires the presence of both the viral factor Nef and the cellular protein cyclophilin A (CyPA) during virion assembly. These two proteins are integral components of HIV-1 particles. Both CyPA and Nef facilitate a step in the viral life cycle occurring between penetration and reverse transcription, suggesting a common mechanism of action. Experiments were performed to test the potential interplay of Nef- and CyPA-mediated enhancement of HIV-1 infectivity. In single-cycle infection assays, nef-defective virions were partially resistant to cyclosporin A (CsA), a drug that inhibits the binding of CyPA to the HIV-1 Gag precursor and CyPA incorporation into virions. Genetic dissection of the relative contributions of Nef and the cyclophilin A-Gag interaction to HIV-1 infectivity demonstrated the independence of these two effects. Nef was not required for incorporation of CyPA into HIV-1 virions and vice-versa. Surprisingly, CyPA-deficient virions remained sensitive to inhibition by CsA, in a manner that depended strongly on the presence of a functional nef gene. These results demonstrate that Nef and CyPA act independently to render HIV-1 particles fully infectious. They further suggest that in addition to blocking the CyPA-Gag interaction, CsA can also inhibit HIV-1 replication through a novel mechanism involving suppression of Nef-directed enhancement of virus infectivity.
Obesity and the Built Environment: Does the Density of Neighborhood Fast-Food Outlets Matter?

Purpose. Examine variation in obesity among older adults relative to the joint influences of density of neighborhood fast food outlets and residents' behavioral, psychosocial, and sociodemographic characteristics. Design. Cross-sectional and multilevel design. Setting. Census block groups, used as a proxy for neighborhoods, within the metropolitan region's Urban Growth Boundary in Portland, Oregon. Subjects. A total of 1221 residents (mean age, 65 years) recruited randomly from 120 neighborhoods (48% response rate). Measures. A geographic information system-based measure of fast food restaurant density across 120 neighborhoods was created. Residents within the sampled neighborhoods were assessed with respect to their body mass indices (BMI), frequency of visits to local fast food restaurants, fried food consumption, levels of physical activity, self-efficacy of eating fruits and vegetables, household income, and race/ethnicity. Analyses. Multilevel logistic regression analyses. Results. Significant associations were found between resident-level individual characteristics and the likelihood of being obese (BMI ≥ 30) for neighborhoods with a high-density of fast food restaurants in comparison with those with a low density: odds ratios for obesity, 95% confidence intervals (CI), were 1.878 (CI, 1.006–3.496) for weekly visits to local fast food restaurants; 1.792 (CI, 1.006–3.190) for not meeting physical activity recommendations; 1.212 (CI, 1.057–1.391) for low confidence in eating healthy food; and 8.057 (CI, 1.705–38.086) for non-Hispanic black residents. Conclusion. Increased density of neighborhood fast food outlets was associated with unhealthy lifestyles, poorer psychosocial profiles, and increased risk of obesity among older adults.
NFATx, a novel member of the nuclear factor of activated T cells family that is expressed predominantly in the thymus

The nuclear factor of activated T cells (NFAT) regulates cytokine gene expression in T cells through cis-acting elements located in the promoters of cytokine genes. Here, we report the cDNA cloning, chromosomal localization, and initial characterization of a transcription factor related to NFATp and NFATc. The novel molecule, designated NFATx, exhibits in its middle a region very similar to the Rel homology domain in NFATc and NFATp. The amino-terminal region of NFATx also shows significant similarities to corresponding sequences in NFATc and NFATp and contains three copies of a conspicuous 17-residue motif of unknown function. We provide evidence showing that NFATx can reconstitute binding to the NFAT-binding site from the interleukin 2 promoter when combined with AP1 (c-Fos/c-Jun) polypeptides and that NFATx is capable of activating transcription of the interleukin 2 promoter in COS-7 cells when stimulated with phorbol ester and calcium ionophore. NFATx mRNA is preferentially and remarkably found in the thymus and at lower levels in peripheral blood leukocytes. The expression pattern of NFATx, together with its functional activity, strongly suggests that NFATx plays a role in the regulation of gene expression in T cells and immature thymocytes.
Giant cell tumor of the distal end of the radius treated by the resection and free vascularized iliac crest graft.

Juxtaarticular giant cell tumor involving the distal radius presents a special problem of reconstruction after tumor excision. A tailored block of vascularized iliac crest graft with its feeding artery (i.e., the deep circumflex iliac artery) joined to the ulnar artery was used as a replacement for the resected distal radius, thereby creating a new wrist joint. Excellent graft survivals were observed in all four cases. The wrists, when assessed 24-48 months after surgery, were found to have good ranges of movement, although with mild dorsal subluxation. These results compared well with other means of wrist reconstruction (i.e., the vascularized fibular graft). Although conventional means of arthrodesis give acceptable hand function, the absence of wrist motion is unacceptable to the young and active, who may prefer the method described in this article.
Alterations in the circadian rhythm of salivary melatonin begin during middle‐age

Abstract: To investigate whether free melatonin may be better suited to reveal age‐related changes, we studied the circadian rhythm alterations in saliva melatonin levels during aging. Special attention was paid to the question as to how the free melatonin rhythms change in aging and when such changes take place. A total of 52 healthy volunteers participated in the study consisting of young, middle‐aged, old and the oldest groups. In each subject, a total of 12 time‐point salivary melatonin samples was taken over 24 hr. Of the 52 data sets, 51 exhibited significant circadian rhythm over 24 hr by using the base cosine function analysis to fit the data. A clear circadian rhythm of salivary melatonin was present in all age groups. The decline in nocturnal peak levels (amplitude) in salivary melatonin was found in old and the oldest subjects. Both the old and the oldest subjects showed an increased daytime (baseline) melatonin levels. The off‐set melatonin levels were more than two times higher in the oldest group than that in the other groups indicating a delayed phase of salivary melatonin. Most strikingly, we found that a step‐wise decrease in the circadian rhythms of saliva melatonin occurred early in life, around 40 yr of ages. The middle‐aged subjects had only 60% of the amplitude of the young subjects. In addition, the middle‐aged subjects showed the longest peak levels duration and the lowest daytime melatonin levels. The present study showed that the alterations in the circadian rhythms of salivary melatonin begin during middle‐age. Our results showed that salivary melatonin measurement is a reliable, sensitive and easy method to monitor changes in the circadian rhythms of melatonin during the course of aging.
Biological aggressiveness of prostate cancer in the Finnish screening trial

Prostate cancer aggressiveness was evaluated based on pathologic characterization of cases detected in the Finnish prostate cancer screening trial. The trial population consists of 80,458 men aged 55–67 years. A total of 32,000 men were randomized to the screening arm. The remaining 48,000 men formed the control arm. The interval cases and cancers among nonparticipants and in the control arm were identified from the Finnish Cancer Registry. Random samples were selected from screen‐detected cases (126 of 543 in the first and 133 of 508 in the second round) and control arm cancers (133 out of 863), in addition to all 92 interval cancers and 106 cases among nonparticipants. All the biopsies were regraded according to the Gleason system. The expression of the proliferation antigen Ki‐67 was determined in 479 cases (72%). More than half of the tumors diagnosed in the first round of screening were high‐grade cancers (Gleason 7 or higher). In the second round, the proportion of low‐grade cancers increased from 47% to 70%. Cancers in the screening arm were more commonly focal and fewer bilateral cancers were detected. The cancers among nonparticipants were the most aggressive group. The aggressiveness of the interval cancers was between the cancers detected in the first and the second round. Our results indicate that prostate cancers detected through screening are less biologically aggressive. This was most notable after the first screening round. Nonparticipants had more aggressive cancers. © 2008 Wiley‐Liss, Inc.
Lumbar discogenic pain: state-of-the-art review.

OBJECTIVE To test the null hypotheses that: lumbar intervertebral discs cannot be a source of pain; discs are not a source of pain; painful lumbar discs cannot be diagnosed; and there is no pathology that causes discogenic pain. METHODS Philosophical essay and discourse with reference to the literature. RESULTS Anatomic and physiologic evidence denies the proposition that disc cannot be a source of pain. In patients with back pain, discs can be source of pain. No studies have refuted the ability of disc stimulation to diagnose discogenic pain. Studies warn only that disc stimulation may have a false-positive rate of 10% or less. Internal disc disruption is the leading cause of discogenic pain. Discogenic pain correlates with altered morphology on computerized tomography scan, with changes on magnetic resonance imaging, and with internal biophysical features of the disc. The morphological and biophysical features of discogenic pain have been produced in biomechanics studies and in laboratory animals. CONCLUSIONS All of the null hypotheses that have been raised against the concept of discogenic pain and its diagnosis have each been refuted by one or more studies. Although studies have raised concerns, none has sustained any null hypothesis. Discogenic pain can occur and can be diagnosed if strict operational criteria are used to reduce the likelihood of false-positive results.
Cheerleading-related injuries in the United States: a prospective surveillance study.

CONTEXT Cheerleading injuries are on the rise and are a significant source of injury to females. No published studies have described the epidemiology of cheerleading injuries by type of cheerleading team and event. OBJECTIVE To describe the epidemiology of cheerleading injuries and to calculate injury rates by type of cheerleading team and event. DESIGN Prospective injury surveillance study. SETTING Participant exposure and injury data were collected from US cheerleading teams via the Cheerleading RIO (Reporting Information Online) online surveillance tool. PATIENTS OR OTHER PARTICIPANTS Athletes from enrolled cheerleading teams who participated in official, organized cheerleading practices, pep rallies, athletic events, or cheerleading competitions. MAIN OUTCOME MEASURE(S) The numbers and rates of cheerleading injuries during a 1-year period (2006-2007) are reported by team type and event type. RESULTS A cohort of 9022 cheerleaders on 412 US cheerleading teams participated in the study. During the 1-year period, 567 cheerleading injuries were reported; 83% (467/565) occurred during practice, 52% (296/565) occurred while the cheerleader was attempting a stunt, and 24% (132/563) occurred while the cheerleader was basing or spotting 1 or more cheerleaders. Lower extremity injuries (30%, 168/565) and strains and sprains (53%, 302/565) were most common. Collegiate cheerleaders were more likely to sustain a concussion (P = .01, rate ratio [RR] = 2.98, 95% confidence interval [CI] = 1.34, 6.59), and All Star cheerleaders were more likely to sustain a fracture or dislocation (P = .01, RR = 1.76, 95% CI = 1.16, 2.66) than were cheerleaders on other types of teams. Overall injury rates for practices, pep rallies, athletic events, and cheerleading competitions were 1.0, 0.6, 0.6, and 1.4 injuries per 1000 athlete-exposures, respectively. CONCLUSIONS We are the first to report cheerleading injury rates based on actual exposure data by type of team and event. These injury rates are lower than those reported for other high school and collegiate sports; however, many cheerleading injuries are preventable.
Age at menopause in Latin America

Objective: To assess the age at menopause (AM) in Latin America urban areas. Design: A total of 17,150 healthy women, aged 40 to 59 years, accompanying patients to healthcare centers in 47 cities of 15 Latin American countries, were surveyed regarding their age, educational level, healthcare coverage, history of gynecological surgery, smoking habit, presence of menses, and the use of contraception or hormone therapy at menopause. The AM was calculated using logit analysis. Results: The mean age of the entire sample was 49.4 ± 5.5 years. Mean educational level was 9.9 ± 4.5 years, and the use of hormone therapy and oral contraception was 22.1% and 7.9%, respectively. The median AM of women in all centers was 48.6 years, ranging from 43.8 years in Asuncion (Paraguay) to 53 years in Cartagena de Indias (Colombia). Logistic regression analysis determined that women aged 49 living in cities at 2,000 meters or more above sea level (OR = 2.0, 95% CI: 1.4-2.9, P < 0.001) and those with lower educational level (OR = 1.9, 95% CI: 1.3-2.8, P < 0.001) or living in countries with low gross national product (OR = 2.1, 95% CI: 1.5-2.9, P < 0.001) were more prone to an earlier onset of menopause. Conclusions: The AM varies widely in Latin America. Lower income and related poverty conditions influence the onset of menopause.
Non‐hodgkin's lymphoma of the heart in patients infected with human immunodeficiency virus

A case of HIV‐associated cardiac non‐Hodgkin's lymphoma (NHL) is described, and the epidemiologic and clinicopathologic features of 21 cases previously reported in the literature are analyzed. All patients were homosexual males, and the cardiac NHL was the first acquired immune deficiency syndrome‐defining condition in the majority. Patients were referred with nonspecific clinical findings including dyspnea and tachycardia, but rapid progression of cardiac dysfunction was frequent after symptoms appeared. Echocardiography constitutes the most useful noninvasive procedure in the diagnosis of cardiac NHL. Most of the patients had disseminated disease at initial presentation; pathologically, the lymphomas were of B lymphocyte origin and of high‐grade subtypes. Prognosis of HIV‐associated cardiac NHL is generally poor, although clinical remission has been observed with combination chemotherapy. Cardiac lymphomas in HIV‐associated patients are typically high‐grade and often disseminate early. Although the prognosis is poor, patients in whom dissemination has not occurred could have longer survival under systemic chemotherapy.
Granulocyte colony‐stimulating factor ameliorates coronary artery elastin breakdown in a mouse model of Kawasaki disease

Background Coronary artery damage from Kawasaki disease (KD) is closely linked to the dysfunction of the endothelial progenitor cells (EPCs). The aim of the present study was to evaluate the modulatory effect of granulocyte colony‐stimulating factor (G‐CSF) on EPCs and elastin breakdown of coronary arteries in a KD mouse model. Methods A Lactobacillus casei cell wall extract (LCWE)‐induced KD model was established in C57BL/6 mice that were subsequently administrated with recombinant human G‐CSF (rhG‐CSF). Nù‐nitro‐L‐arginine methyl ester (L‐NAME) was administrated for the negative intervention. Evaluations included coronary artery lesions, EPC number and functions, and the plasma concentration of nitric oxide (NO). Results Elastin breakdown was found in the coronary arteries of model mice 56 days after injection of LCWE. The number of circulating EPCs, plasma concentration of NO, and functions of bone marrow EPCs, including proliferation, adhesion, and migration abilities, were all lower in the KD model group compared with those in the control group. After administration of rhG‐CSF, the number of circulating EPCs and plasma concentration of NO were increased significantly compared with those in the KD model group. There were also increases in the functional indexes of EPCs. Furthermore, rhG‐CSF administration improved the elastin breakdown effectively. However, these protective effects of rhG‐CSF on coronary arteries were attenuated by L‐NAME. Conclusion The present study indicated that the administration of G‐CSF prevents elastin breakdown of the coronary arteries by enhancing the number and functions of EPCs via the NO system, and then accelerates the repair of coronary artery lesions in the KD.
Indications, diagnostic yields and complications of transbronchial biopsy over 5 years in the State of Qatar.

OBJECTIVES To review the indications, diagnostic yields and complications of transbronchial biopsy (TBB) in a tertiary hospital in the State of Qatar. METHODS A retrospective review of our records revealed 1006 adult flexible fibre optic bronchoscopies (FFB) at Hamad General Hospital, State of Qatar between January 1999 and December 2003. A total of 85 (8.4%) TBB were performed, but complete data were available for 71/85 (83.5%), which were reviewed for indications, diagnostic yields and complications. RESULTS Adequate samples were obtained in 58/71 TBBs (81.7%), while 13/71 TBBs (18.3%) yielded bronchial mucosa. The main indications in 16/71 (22.5%) TBBs for radiographic localized pulmonary disease were to rule out tuberculosis (TB) in 13 cases, and malignancy in 3 cases. Tuberculosis was verified in 3 (23%) of the 13 cases with localized disease. Fifty-five out of 71 (77.5%) TBBs were performed for radiographic diffuse pulmonary disease: 16/55 (29%) for miliary shadows, while 39/55 (70.9%) were carried out for reticular/reticulonodular infiltrates. Histopathology showed granulomatous lesions consistent with TB in 10/16 (62.5%) cases of miliary shadow. In the other pattern of diffuse disease, the histopathological diagnosis were obtained in 25/39 (64%) cases. It showed non-specific pulmonary fibrosis in 13 cases, sarcoidosis in 4 cases, connective tissue disease associated interstitial fibrosis in 4 cases, bronchiolitis obliterans organizing pneumonia (BOOP) in one case, eosinophilic pneumonia in one case, amiodarone toxicity in one case and lymphangitis carcinomatosis in one case. The main complications were minor bleeding <50 cc in 17 cases (23.9%), pneumothorax in 7 cases (9.8%)) and one case had sepsis. CONCLUSION Our experience substantiates previous reports of the value and safety of transbronchial biopsy in the rapid diagnosis of smear-negative miliary TB. In diffuse lung diseases of a non-infectious nature, other than sarcoidosis, lymphangitis carcinomatosis and few other conditions, a pathological diagnosis are much less likely to be reliably made on small pieces of tissue such as those provided by TBB.
Endothelial cells stimulate osteogenic differentiation of mesenchymal stem cells on calcium phosphate scaffolds

The interaction of mesenchymal stem cells (MSCs) with endothelium in vivo is significant for regenerative processes in organisms. To design concepts for tissue engineering for bone regeneration based on this interaction, the osteogenic differentiation of human bone marrow‐derived MSCs in a co‐culture with human dermal microvascular endothelial cells (HDMECs) was studied. The experiments were focussed on the regulation of MSCs in a co‐culture with HDMECs on different calcium phosphate scaffolds. Alkaline phosphatase (ALP) activity and mRNA expression of various osteogenic markers increased significantly when cells were co‐cultured on materials with calcium phosphate scaffolds compared to tissue culture polystyrene or when MSCs were cultured alone. In addition, it was observed that the expression of osteopontin and osteocalcin was highly sensitive to the substrate for cell adhesion. Whereas these late osteogenic markers were down‐regulated in co‐cultures on polystyrene, they were up‐regulated on calcium phosphate and moreover, were differentially expressed on the three calcium phosphate scaffolds tested. To enhance the osteogenic differentiation of MSCs in a co‐culture, direct cell‐cell interactions were required. Concerning molecular mechanisms in the interactions between both cell types, it was found that connexin 43 was expressed in contact sites and more apparently, endothelial cells grew over the MSCs, which facilitated direct cellular interactions mediated by various adhesion receptors. This study revealed significant findings for the design of implant materials suitable for regeneration of bone by stimulating the functional interaction of MSCs with endothelial cells. Copyright © 2012 John Wiley & Sons, Ltd.
Overall and single-kidney clearance in children with urinary tract infection and damaged kidneys.

UNLABELLED The overall and single-kidney clearance in children with acute urinary tract infection was investigated retrospectively using the combination of the relative 99mTc-dimercaptosuccinic acid (DMSA) uptake and the 51Cr-ethylenediaminetetraacetic acid clearance. METHODS There were 180 patients with both normal kidneys, 56 with clear unilateral abnormalities on DMSA scintigraphy and 11 with two abnormal kidneys. Half of the patients were younger than 2 y, and because of the progressive maturation of the renal function, they were not considered in the analysis of the absolute overall and single-kidney clearance; nevertheless, they were included in the analysis of the relative DMSA percentage uptake. RESULTS When only one kidney was affected on DMSA scintigraphy, the clearance of the affected kidney was lower than on the normal side and often abnormally low. In these unilaterally affected kidneys, contralateral compensation mechanisms tended to occur, resulting in preservation of overall clearance. This compensation was probably not present only on the contralateral side. On the abnormal side, the clearance was normal in about half of the cases, probably because of intrarenal compensation occurring in regions not damaged by the infection. In addition to these compensation mechanisms, hyperfiltration was probably present in many cases of acute urinary tract infection with intact or unilaterally damaged kidneys.