tbuckley/cabot-search huggingface dataset:
Genetic diversity in India and the inference of Eurasian population expansion
Authors: Jinchuan Xing, W Scott Watkins, Ya Hu, Chad D Huff, Aniko Sabo, Donna M Muzny, Michael J Bamshad, Richard A Gibbs, Lynn B Jorde, Fuli Yu
Journal: Genome biology (2010)

Genetic studies of populations from the Indian subcontinent are of great interest because of India's large population size, complex demographic history, and unique social structure. Despite recent large-scale efforts in discovering human genetic variation, India's vast reservoir of genetic diversity remains largely unexplored.To analyze an unbiased sample of genetic diversity in India and to investigate human migration history in Eurasia, we resequenced one 100-kb ENCODE region in 92 samples collected from three castes and one tribal group from the state of Andhra Pradesh in south India. Analyses of the four Indian populations, along with eight HapMap populations (692 samples), showed that 30% of all SNPs in the south Indian populations are not seen in HapMap populations. Several Indian populations, such as the Yadava, Mala/Madiga, and Irula, have nucleotide diversity levels as high as those of HapMap African populations. Using unbiased allele-frequency spectra, we investigated the expansion of human populations into Eurasia. The divergence time estimates among the major population groups suggest that Eurasian populations in this study diverged from Africans during the same time frame (approximately 90 to 110 thousand years ago). The divergence among different Eurasian populations occurred more than 40,000 years after their divergence with Africans.Our results show that Indian populations harbor large amounts of genetic variation that have not been surveyed adequately by public SNP discovery efforts. Our data also support a delayed expansion hypothesis in which an ancestral Eurasian founding population remained isolated long after the out-of-Africa diaspora, before expanding throughout Eurasia.
How much vitamin D should I take?
Authors: Cathleen S. Colón-Emeric, Kenneth W. Lyles
Journal: Journal of Clinical Investigation (2012)

Clinical vignette: A 68-year-old woman consults you after a recent bone mineral density screening revealed osteopenia, total hip T score of –1.8. Further evaluation shows her only other abnormal lab value is a serum 25-hydroxyvitamin D [25(OH)D] level of 13 ng/ml (normal 30–80). You find no evidence of malabsorption. What vitamin D supplement regimen should you recommend to reduce her risk of fractures?
Gene correction in the evolution of the T cell receptor beta chain.
Authors: E Jouvin-Marche, M Heller, S Rudikoff
Journal: The Journal of Experimental Medicine (1986)

Mutational mechanisms operating at the T cell receptor beta chain locus have been examined by comparison of the CT beta 1 and CT beta 2 gene sequences from Mus pahari, believed to be the oldest living species in the genus Mus, with those of inbred mice. Results indicate that a gene correction event independent of that suggested to have occurred in inbred mice has homogenized the M. pahari CT beta exon 1 sequences, minimizing diversity in this region of the molecule. These observations suggest that correction events such as gene conversion may occur frequently, even in pauci-gene families with as few as two members, and therefore play a significant role in gene diversification or homogenization of small as well as large gene families.
Topological Requirements and Signaling Properties of T Cell–activating, Anti-CD28 Antibody Superagonists
Authors: Fred Lühder, Yun Huang, Kevin M. Dennehy, Christine Guntermann, Ingrid Müller, Erna Winkler, Thomas Kerkau, Shinji Ikemizu, Simon J. Davis, Thomas Hanke, Thomas Hünig
Journal: The Journal of Experimental Medicine (2003)

Full activation of naive T cells requires both engagement of the T cell antigen receptor (TCR; signal 1) and costimulatory signaling by CD28 (signal 2). We previously identified two types of rat CD28-specific monoclonal antibodies (mAbs): “conventional,” TCR signaling–dependent costimulatory mAbs and “superagonistic” mAbs capable of inducing the full activation of primary resting T cells in the absence of TCR ligation both in vitro and in vivo. Using chimeric rat/mouse CD28 molecules, we show that the superagonists bind exclusively to the laterally exposed C′′D loop of the immunoglobulin-like domain of CD28 whereas conventional, costimulatory mAbs recognize an epitope close to the binding site for the natural CD80/CD86 ligands. Unexpectedly, the C′′D loop reactivity of a panel of new antibodies raised against human CD28 could be predicted solely on the basis of their superagonistic properties. Moreover, mouse CD28 molecules engineered to express the rat or human C′′D loop sequences activated T cell hybridomas without TCR ligation when cross-linked by superagonistic mAbs. Finally, biochemical analysis revealed that superagonistic CD28 signaling activates the nuclear factor κB pathway without inducing phosphorylation of either TCRζ or ZAP70. Our findings indicate that the topologically constrained interactions of anti-CD28 superagonists bypass the requirement for signal 1 in T cell activation. Antibodies with this property may prove useful for the development of T cell stimulatory drugs.
Repair of bone erosions in rheumatoid arthritis treated with tumour necrosis factor inhibitors is based on bone apposition at the base of the erosion
Authors: S. Finzel, J. Rech, S. Schmidt, K. Engelke, M. Englbrecht, C. Stach, G. Schett
Journal: Annals of the Rheumatic Diseases (2011)

<h3>Objectives</h3> To investigate whether bone erosions in patients with rheumatoid arthritis (RA) show evidence of repair. <h3>Methods</h3> 127 erosions were identified in metacarpophalangeal joints 2–4 of the right hands of 30 RA patients treated with tumour necrosis factor inhibitors (TNFi) and 21 sex, age and disease activity-matched patients treated with methotrexate. All erosions were assessed for their exact maximal width and depth by high-resolution µCT imaging at baseline and after 1 year. <h3>Results</h3> All erosions detected at baseline could be visualised at follow-up after 1 year. At baseline, the mean width of bone erosions in the TNFi group was 2.0 mm; their mean depth was 2.3 mm, which was not significantly different from the methotrexate-treated group (width 2.4 mm; depth 2.4 mm). Mean depth of erosions significantly decreased after 1 year of treatment with TNFi (−0.1 mm; p=0.016), whereas their width remained unchanged. In contrast, mean depth and width of erosive lesions increased in the methotrexate-treated group. The reduction in the depth of lesions was confined to erosions showing evidence of sclerosis at the base of the lesion. Moreover, deeper lesions in the TNFi group were particularly prone to repair (−0.4 mm; p=0.02) compared with more shallow lesions. <h3>Conclusions</h3> Bone erosions in RA patients treated with TNFi show evidence of limited repair in contrast to bone erosions in patients treated with methotrexate. Repair is associated with a decrease in the depth of lesions and sclerosis at the bases of the lesions. Repair thus emerges from the endosteal rather than periosteal bone compartment and probably involves the bone marrow.
The Epidemic of Gang-Related Homicides in Los Angeles County From 1979 Through 1994
Authors: H. Range Hutson
Journal: JAMA (1995)

<h3>Objective.</h3> —To determine trends in gang homicides and the population at greatest risk for homicide by reviewing all gang-related homicides in Los Angeles County, California, from January 1979 to December 1994. <h3>Design.</h3> —Homicide files of the Los Angeles Police Department and the Los Angeles County Sheriff's Department from 1979 to 1994 involving violent street gang activity were reviewed. Gang files were reviewed for demographic data, weapons used, homicides by drive-by shootings, and times and geographic areas of occurrence. <h3>Setting.</h3> —Los Angeles County from January 1, 1979, to December 31, 1994. <h3>Main Outcome Measures.</h3> —Age, race, and sex of gang-related homicide victims; frequency of weapon use; and the change in gang-related homicide rates during the study period. <h3>Results.</h3> —A total of 7288 gang-related homicides occurred in Los Angeles County from 1979 through 1994; 5541 of these homicides occurred in Los Angeles Police Department and Los Angeles County Sheriff's Department jurisdictions. During the study period, the proportion of all homicides that were gang related increased from 18.1% to 43.0% (<i>P</i>&lt;.001). Of the 5541 gang-related homicide victims, 4580 (85.6%) were aged 15 to 34 years, 93.3% were African American or Hispanic, 5157 (93.2%) were male, 3559 (64.2%) were gang members, and 1408 (25.4%) occurred during drive-by shootings. Firearms were used in an increasing proportion of homicides, from 71.4% in 1979 to 94.5% in 1994. Homicides by semiautomatic handguns dramatically increased during the study period. Gang-related homicide rates for African-American males aged 15 to 19 years increased from 60.50 per 100 000 population per year in 1979 to 1981 to 192.41 per 100 000 population per year in 1989 to 1991. <h3>Conclusions.</h3> —Gang-related homicides in Los Angeles County have reached epidemic proportions and are a major public health problem. To prevent gang violence, the root causes of violent street gang formation must be alleviated, the cycle of violent street gang involvement must be broken, and access to firearms must be limited. (<i>JAMA</i>. 1995;274:1031-1036)
Effects of an Intervention to Increase Bed Alarm Use to Prevent Falls in Hospitalized Patients
Authors: Ronald I. Shorr, A. Michelle Chandler, Lorraine C. Mion, Teresa M. Waters, Minzhao Liu, Michael J. Daniels, Lori A. Kessler, Stephen T. Miller
Journal: Annals of Internal Medicine (2012)

Background: Bed alarm systems intended to prevent hospital falls have not been formally evaluated. Objective: To investigate whether an intervention aimed at increasing bed alarm use decreases hospital falls and related events. Design: Pair-matched, cluster randomized trial over 18 months. Nursing units were allocated by computer-generated randomization on the basis of baseline fall rates. Patients and outcome assessors were blinded to unit assignment; outcome assessors may have become unblinded. (ClinicalTrials.gov registration number: NCT00183053) Setting: 16 nursing units in an urban community hospital. Patients: 27 672 inpatients in general medical, surgical, and specialty units. Intervention: Education, training, and technical support to promote use of a standard bed alarm system (intervention units); bed alarms available but not formally promoted or supported (control units). Measurements: Pre–post difference in change in falls per 1000 patient-days (primary end point); number of patients who fell, fall-related injuries, and number of patients restrained (secondary end points). Results: Prevalence of alarm use was 64.41 days per 1000 patient-days on intervention units and 1.79 days per 1000 patient-days on control units (P = 0.004). There was no difference in change in fall rates per 1000 patient-days (risk ratio, 1.09 [95% CI, 0.85 to 1.53]; difference, 0.41 [CI, −1.05 to 2.47], which corresponds to a greater difference in falls in control vs. intervention units) or in the number of patients who fell, injurious fall rates, or the number of patients physically restrained on intervention units compared with control units. Limitation: The study was conducted at a single site and was slightly underpowered compared with the initial design. Conclusion: An intervention designed to increase bed alarm use in an urban hospital increased alarm use but had no statistically or clinically significant effect on fall-related events or physical restraint use. Primary Funding Source: National Institute on Aging.
Regression of Atherosclerosis in Monkeys Reduces Vascular Superoxide Levels
Authors: Christopher A. Hathaway, Donald D. Heistad, Donald J. Piegors, Francis J. Miller
Journal: Circulation Research (2002)

Superoxide (O 2 ·− ) in arteries may contribute to atherosclerosis in part by inactivation of nitric oxide. We hypothesized that regression of atherosclerosis in nonhuman primates is associated with a decrease in vascular NAD(P)H oxidase, decreased O 2 ·− levels, and improved endothelium-dependent relaxation. Cynomolgus monkeys (n=28) were fed an atherogenic diet for 47±10 (mean±SE) months. In carotid arteries (containing advanced lesions), femoral arteries (moderate lesions), and saphena arteries (minimal lesions), we examined O 2 ·− levels and vasomotor function. Compared with vessels from normal monkeys (n=8), O 2 ·− levels (measured by lucigenin-enhanced chemiluminescence) were 3.3-fold higher in carotid, 1.7-fold higher in femoral, and not different in saphena arteries from atherosclerotic monkeys. Dihydroethidium staining also demonstrated increased O 2 ·− levels throughout the vessel wall in femoral and carotid arteries from atherosclerotic monkeys. Components of the NAD(P)H oxidase (p22 phox and p47 phox ) were increased in atherosclerotic arteries, and immunohistochemistry demonstrated colocalization primarily to areas of macrophage infiltration. Relaxation to acetylcholine was impaired in carotid and femoral, but not saphena, arteries from atherosclerotic monkeys. After 8 months of regression diet (n=9), serum cholesterol decreased to normal, and O 2 ·− levels (basal and NAD(P)H-stimulated), as well as expression of NAD(P)H oxidase, returned toward normal. Relaxation to acetylcholine improved in femoral arteries, but not in the more diseased carotid arteries. We conclude that, in a primate model of moderately severe atherosclerosis and regression of atherosclerosis, changes in endothelial function are inversely related to O 2 ·− and NAD(P)H oxidase levels. Reduction in vascular O 2 ·− during regression of atherosclerosis may contribute to improvement in vasomotor function.
Open Mandibular Fracture with Malocclusion
Authors: Joseph R Shiber, Kelly Carter
Journal: New England Journal of Medicine (2008)

A 21-year-old healthy man presented to the emergency department with mouth pain and bleeding, after being struck with a gun on his right lower jaw. Physical examination revealed upward displacement of the left half of his mandible with malocclusion on biting and mild bleeding from the fracture line between his central incisors (Panel A). He had no other intraoral lacerations or fractures of the teeth. Computed tomography showed a comminuted fracture of the left mandible just lateral to the symphysis mentalis, extending vertically through the alveolar ridge near the midline (Panel B), and a comminuted fracture of the right mandibular . . .
Cardiac Actions of Glucagon
Authors: BENEDICT R. LUCCHESI, Jeanne Brown, Barbara Laidlaw, Deonna Rockiki
Journal: Circulation Research (1968)

Glucagon increased heart rate and contractile force in the anesthetized dog and increased isometric tension in the isolated dog papillary muscle. The positive inotropic and chronotropic responses were not abolished or reduced by previous administration of the beta-receptor blocking agent propranolol, in doses of 0.5 mg/kg. Glucagon increased the force and rate of cardiac contraction even when cardiac-depressant doses of propranolol, 2 mg/kg, had been given. Previous treatment with reserpine (1.0 mg/kg on each of 3 consecutive days) failed to diminish the positive inotropic and chronotropic effects of glucagon. However, previous administration of tyramine, 0.05 mg/kg, which resulted in a positive inotropic response in the dog, significantly reduced the glucagon-induced positive inotropic response. Theophylline, 10 mg/kg, likewise prevented the inotropic action of glucagon without preventing the positive inotropic effect of calcium chloride. The increase in isometric tension produced by glucagon in the isolated dog papillary muscle was prevented during simultaneous exposure of the muscles to acetylcholine. The results of these studies are discussed in reference to the known metabolic actions of glucagon and the catecholamines and the possibility that they both share a common mechanism of action mediated through an increase in the intracellular concentration of cyclic 3',5' AMP.
Rigid bronchoscopy induces bacterial translocation: an experimental study in rats
Authors: A. Nayci, S. Atis, D.U. Talas, G. Ersoz
Journal: European Respiratory Journal (2003)

Bronchoscopy has the potential to propagate infections. Bacterial translocation was hypothesised to be the cause of infections observed following bronchoscopy and this study was designed to assess the risk of bacterial translocation following rigid bronchoscopy in rats. A total of 30 rats were evaluated. The study group (n=15) underwent rigid bronchoscopy. Arterial blood gas analysis was performed in all rats. Blood and tissue cultures from the ileum, caecum, mesenteric lymph nodes, liver, spleen, mediastinal lymph nodes and lung were obtained 24 h following bronchoscopy. Bacterial translocation to the mesenteric lymph nodes was found in seven of 15 rats (46.7%) that underwent bronchoscopy, compared with none of the controls. Of the seven positives, three rats (42.8%) also demonstrated other organ involvement, such as the liver and spleen. Escherichia coli , Salmonella typhymirium , S. enteritidis and Pseudomonas spp. were found as translocating bacteria. In the study group, pH and arterial oxygen tension were significantly lower and arterial carbon dioxide tension was higher, compared with controls. This study shows that rigid bronchoscopy may induce bacterial translocation in rats. Further investigations aimed at understanding the clinical consequences of this phenomenon are warranted.
Prevalence of and Racial Disparities in Risk Factor Control in Older Adults With Diabetes: The Atherosclerosis Risk in Communities Study
Authors: Christina M. Parrinello, Ina Rastegar, Job G. Godino, Michael D. Miedema, Kunihiro Matsushita, Elizabeth Selvin
Journal: Diabetes Care (2015)

OBJECTIVE Controversy surrounds appropriate risk factor targets in older adults with diabetes. We evaluated the proportion of older adults with diabetes meeting different targets, focusing on possible differences by race, and assessed whether demographic and clinical characteristics explained disparities. RESEARCH DESIGN AND METHODS We conducted a cross-sectional study of 5,018 participants aged 67–90 years (1,574 with and 3,444 without diagnosed diabetes) who attended visit 5 of the Atherosclerosis Risk in Communities (ARIC) study (2011–2013). Risk factor targets were defined using both stringent (and less stringent) goals: hemoglobin A1c (HbA1c) &amp;lt;7%, &amp;lt;53 mmol/mol (&amp;lt;8%, &amp;lt;64 mmol/mol); LDL cholesterol (LDL-c) &amp;lt;100 mg/dL (&amp;lt;130 mg/dL); and blood pressure (BP) &amp;lt;140/90 mmHg (&amp;lt;150/90 mmHg). We used Poisson regression to obtain prevalence ratios (PRs). RESULTS Most older adults with diabetes met stringent (and less stringent) targets: 72% (90%) for HbA1c, 63% (86%) for LDL-c, and 73% (87%) for BP; but only 35% (68%) met all three. A higher proportion of whites than blacks met targets, however defined. Among people treated for risk factors, racial disparities in prevalence of meeting stringent targets persisted even after adjustment: PRs (whites vs. blacks) were 1.03 (95% CI 0.91, 1.17) for HbA1c, 1.21 (1.09, 1.35) for LDL-c, 1.10 (1.00, 1.21) for BP, and 1.28 (0.99, 1.66) for all three. Results were similar but slightly attenuated using less stringent goals. Black women were less likely than white women to meet targets for BP and all three risk factors; this disparity was not observed in men. CONCLUSIONS Black-white disparities in risk factor control in older adults with diabetes were not fully explained by demographic or clinical characteristics and were greater in women than men. Further study of determinants of these disparities is important.
New lane in the information highway: alternative reading frame peptides elicit T cells with potent antiretrovirus activity
Authors: Jonathan W. Yewdell, Heather D. Hickman
Journal: The Journal of Experimental Medicine (2007)

CD8(+) T cells rapidly recognize virus-infected cells due to the generation of antigenic peptides from defective ribosomal products (DRiPs) that are encoded by standard open reading frames (ORFs). New data now show that alternative reading frame (ARF) DRiPs can also induce robust CD8(+) T cell responses. ARF-specific T cells control retroviral replication and select for viral escape in monkeys, providing the most compelling evidence to date for the biological relevance of ARF immunosurveillance.
Contractile State of the Heart Characterized by Force-Velocity Relations in Variably Afterloaded and Isovolumic Beats
Authors: John Ross, James W. Covell, Edmund H. Sonnenblick, Eugene Braunwald
Journal: Circulation Research (1966)

Relations between tension and the velocity of shortening in the intact left ventricle of the dog were examined in a manner analogous to that employed in isolated muscle, i.e., by serial, reproducible variations in the afterload alone, from a constant end diastolic volume. Sudden increases or decreases in the aortic pressure during diastole were produced, and ejection rate was measured with an electromagnetic flowmeter; LV wall tension and the shortening velocities of the myocardial fibers and the contractile elements were then calculated. By analyzing isovolume points early in ejection, effects resulting from two other determinants of shortening velocity, duration of active state and instantaneous muscle length, were minimized. Shifts in the basic force-velocity relation with alterations in V max , obtained by extrapolation, and maximum tension were clearly demonstrated. Norepinephrine and paired electrical stimulation caused a shift in this relation to the right, with increases in velocity at any tension, and acute heart failure produced a shift to the left, with decreases in velocity at any tension. Similar shifts were also apparent in curves relating tension to velocity, calculated during single isovolumic contractions. It was suggested that determination of these relations expands traditional definitions of ventricular performance, and that estimation of changes in maximum velocity as well as maximum strength relative to muscle length provides direct information concerning alterations in the contractile state of the intact heart.