tbuckley/cabot-search huggingface dataset:
Global Routine Vaccination Coverage — 2017
Authors: Kristin VanderEnde, Marta Gacic-Dobo, Mamadou S. Diallo, Laura M. Conklin, Aaron S. Wallace
Journal: MMWR Morbidity and Mortality Weekly Report (2018)

Endorsed by the World Health Assembly in 2012, the Global Vaccine Action Plan 2011-2020 (GVAP) (1) calls on all countries to reach ≥90% national coverage with all vaccines in the country's national immunization schedule by 2020. This report updates previous reports (2,3) and presents global, regional, and national vaccination coverage estimates and trends as of 2017. It also describes the number of infants surviving to age 1 year (surviving infants) who did not receive the third dose of diphtheria and tetanus toxoids and pertussis-containing vaccine (DTP3), a key indicator of immunization program performance (4,5), with a focus on the countries with the highest number of children who did not receive DTP3 in 2017. Based on the World Health Organization (WHO) and United Nations Children's Fund (UNICEF) estimates, global DTP3 coverage increased from 79% in 2007 to 84% in 2010, and has remained stable from 2010 to 2017 (84% to 85%). In 2017, among the 19.9 million children who did not receive DTP3 in the first year of life, 62% (12.4 million) lived in 10 countries. From 2007 to 2017, the number of children who had not received DTP3 decreased in five of these 10 countries and remained stable or increased in the other five. Similar to DTP3 coverage, global coverage with the first measles-containing vaccine dose (MCV1) increased from 80% in 2007 to 84% in 2010, and has remained stable from 2010 to 2017 (84% to 85%). Coverage with the third dose of polio vaccine (Pol3) has remained stable at 84%-85% since 2010. From 2007 to 2017, estimated global coverage with the second MCV dose (MCV2) increased from 33% to 67%, as did coverage with the completed series of rotavirus (2% to 28%), pneumococcal conjugate (PCV) (4% to 44%), rubella (26% to 52%), Haemophilus influenzae type b (Hib) (25% to 72%) and hepatitis B (HepB) (birth dose: 24% to 43%; 3-dose series: 63% to 84%) vaccines. Targeted, context-specific strategies are needed to reach and sustain high vaccination coverage, particularly in countries with the highest number of unvaccinated children.
THE ENHANCEMENT OF MACROPHAGE BACTERIOSTASIS BY PRODUCTS OF ACTIVATED LYMPHOCYTES
Authors: Robert E. Fowles, Ileana M. Fajardo, Jacques L. Leibowitch, John R. David
Journal: The Journal of Experimental Medicine (1973)

It was reported previously that the incubation of normal guinea pig macrophages with partially purified products of activated lymphocytes resulted in altered macrophage function including increased cell adherence to culture vessels, spreading, phagocytosis, and glucose carbon-1 oxidation. Studies reported here demonstrate that such macrophages also exhibit enhanced bacteriostasis. Lymphocytes were stimulated with concanavalin A, the culture supernatant was chromatographed over Sephadex G-100 and the fraction of mol wt 25,000-55,000, rich in lymphocyte mediators, was cultured with normal guinea pig macrophages for 1-3 days. Macrophages incubated with fractions from unstimulated lymphocyte cultures served as controls. The resulting macrophage monolayers were infected with Listeria monocytogenes. Macrophages incubated with mediator-rich fractions exhibited 2- to 10-fold enhanced bacteriostasis compared to controls. Further studies indicate that this enhancement was attributable to intrinsic changes in the macrophages and not simply a consequence of the number of macrophages on the monolayers. The studies support the concept that macrophage bacteriostasis can be enhanced by lymphocyte mediators. However, macrophages, which have been preincubated directly with sensitive lymphocytes and antigen exhibit even greater bacteriostasis and sometimes bactericidal capacity, suggesting that either a labile lymphocyte factor or direct lymphocyte macrophage interaction may also be involved in bactericidal activity.
Ethnic Differences in the Relationship Between Albuminuria and Calcified Atherosclerotic Plaque
Authors: Jasmin Divers, Lynne E. Wagenknecht, Donald W. Bowden, J. Jeffrey Carr, R. Caresse Hightower, Jianzhao Xu, Carl D. Langefeld, Barry I. Freedman
Journal: Diabetes Care (2009)

Despite higher rates of nephropathy, calcified atherosclerotic plaque is less prevalent in African Americans with diabetes relative to European Americans. We explored ethnicity-specific relationships between albuminuria and calcified plaque involving the infrarenal aorta, coronary artery, and carotid artery in 835 European American and 393 African American subjects with type 2 diabetes.Generalized estimating equations with exchangeable correlation and the sandwich estimator of the variance were used to test for association between the principal component of calcified plaque in the three vascular beds and urine albumin-to-creatinine ratio (ACR).Mean +/- SD ages of African American and European American participants were 56.7 +/- 9.6 and 61.7 +/- 9.1 years, respectively, with diabetes duration of 10.4 +/- 7.4 and 10.0 +/- 7.3 years and median urine ACR of 17.5 and 13.4 mg/g. In African American and European American participants, respectively, median calcified plaque mass scores were 53.5 and 291 for coronary artery, 3 and 35.5 for carotid artery, and 761 and 3,237 for aorta. With adjustment for age, sex, glomerular filtration rate, and BMI, albuminuria was significantly associated with calcified plaque in European Americans (P = 3.4 x 10(-8)) but not in African Americans (P = 0.33), with significant ethnic interaction (P = 0.01). Ethnic differences in this relationship persisted after adjustment for blood pressure, smoking, lipids, and use of ACE inhibitors or angiotensin receptor blockers.Albuminuria is strongly associated with severity of calcified plaque in European Americans with diabetes but not in African Americans. Disparities in this relationship may contribute to ethnic differences in the rates of cardiovascular disease that are observed in subjects with type 2 diabetes.
Of measles and flu
Authors: Fiona Godlee
Journal: BMJ (2006)

When was the last time you saw a case of measles? If you're in a developed country and are under 40, the answer may be never. But that might be about to change, provided of course that you recognise what you see. The number of cases is increasing steeply in the UK, bringing predictions of the re-emergence of endemic measles. Meanwhile, as Perviz Asaria and Eithne MacMahon point out (p 890), clinical experience of measles has declined. They offer a reminder of the clinical features, complications, and management strategies.

They also call for increased measles vaccine coverage if the UK is …
Time-dependent increase in left ventricular contractility following acute volume loading in the dog.
Authors: W Y Lew
Journal: Circulation Research (1988)

Acute volume alterations were produced in eight anesthetized dogs to determine if the contractility of the left ventricle is partially volume-dependent. Pressures were measured in the left ventricle with a micromanometer and regional ventricular function was measured with sonomicrometers implanted in the midwall of the anterior, lateral, and posterior left ventricle. Regional end-systolic pressure-length relations (ESPLR) were determined with transient venae cavae occlusions. The ESPLR data were fitted to a quadratic equation, then end-systolic lengths were compared at matched end-systolic pressures at multiple time periods after the acute load alterations. Bilateral vagotomy, carotid sinus denervation, and stellate ganglion denervation were performed to prevent reflex alterations in contractility. The heart was paced at a constant rate. In seven animals, dextran was infused intravenously over 77 +/- 23 seconds (+/- SD) to increase left ventricular end-diastolic pressure from 5 +/- 2 to 13 +/- 3 mm Hg and peak pressures from 113 +/- 11 to 147 +/- 18 mm Hg. The end-diastolic lengths increased 14 +/- 6% in the anterior, 9 +/- 2% in the lateral, and 12 +/- 4% in the posterior segments. The ESPLR was measured immediately (77 +/- 23 seconds), early (3 +/- 1 minutes), and late (10 +/- 2 minutes) after initiation of the volume load. In all three regions, there was a significant time-dependent leftward shift in the ESPLR. From 1 to 10 minutes after the volume load, the regional end-systolic lengths decreased by a mean of 4-6% when compared at a matched end-systolic pressure of 96 +/- 10 mm Hg, and decreased by 7-9% when compared at a matched pressure of 139 +/- 20 mm Hg. The end-systolic lengths immediately after the volume load were not significantly different from the control value (compared at a matched end-systolic pressure) but were significantly shorter 10 minutes after the volume load. The leftward shift of the ESPLR represented a true increase in contractility and not merely a recovery from a transient myocardial depression. A similar leftward shift in the ESPLR occurred in four animals after release of a partial venae cavae occlusion, producing an acute volume load without acute hemodilution. Acute volume loads in four animals treated with propranolol also produced a leftward shift in the ESPLR, ruling out the possibility that a time-dependent increase in circulating catecholamines was responsible for the alterations in contractility. In five animals, the ESPLR shifted to the right after a transient (1-2 minutes) decrease in venous return.(ABSTRACT TRUNCATED AT 400 WORDS)
SDF-1 restores angiogenesis synergistically with VEGF upon LDL exposure despite CXCR4 internalization and degradation
Authors: Fengyan Jin, Nina Hagemann, Simon T. Schäfer, Ulf Brockmeier, Anil Zechariah, Dirk M. Hermann
Journal: Cardiovascular Research (2013)

Angiogenesis is compromised under conditions of hypercholesterolaemia. Since disturbed angiogenesis predisposes to ischaemic injuries, efforts have been made to promote angiogenesis by delivery of growth factors. How stromal cell-derived growth factor (SDF)-1 influences angiogenesis under conditions reflecting hypercholesterolaemia was unknown. We investigated the effects of SDF-1, administered alone or in combination with vascular endothelial growth factor (VEGF), on angiogenesis using proliferation, transwell migration, and Matrigel-based tube formation assays with human umbilical vein endothelial cells that were exposed to low-density lipoprotein (LDL). We observed that SDF-1 dose-dependently enhanced angiogenesis, but only partly reversed the LDL-mediated suppression of angiogenesis. Reduced abundance of SDF-1's receptor, CXCR4, was noted on the surface of LDL-exposed endothelial cells. In subcellular localization studies combined with pharmacological experiments, we showed that the loss of CXCR4 resulted from its internalization and degradation. SDF-1 synergistically increased angiogenesis when combined with VEGF. As a consequence, angiogenesis was fully restored. SDF-1 reduced oxidized LDL formation and increased the anti-oxidant capacity of endothelial cells, most strongly when administered together with VEGF. Combination therapies of growth factors, specifically SDF-1 and VEGF, might enhance angiogenesis more successfully than monotherapies under conditions of hypercholesterolaemia.
Exenatide twice daily versus glimepiride for prevention of glycaemic deterioration in patients with type 2 diabetes with metformin failure (EUREXA): an open-label, randomised controlled trial
Authors: Baptist Gallwitz, Juan Guzman, Francesco Dotta, Bruno Guerci, Rafael Simó, Bruce R Basson, Andreas Festa, Jacek Kiljański, Hélène Sapin, Michael Trautmann, Guntram Schernthaner
Journal: The Lancet (2012)
Mediastinal cavernous haemangioma in a patient with Klippel-Trenaunay syndrome
Authors: P-H Kuo
Journal: Thorax (2003)

The Klippel-Trenaunay syndrome (KTS) is a rare syndrome characterised by the triad of varicose veins, bony and soft tissue hypertrophy, and cutaneous haemangioma. A 30 year old man with KTS with a right mediastinal mass which progressively enlarged over 5 years is described. Computed tomography, magnetic resonance imaging, and bronchial angiography revealed a vascular lesion in the azygous area. After complete excision of the mass, histological examination revealed cavernous haemangioma. To our knowledge, this is the first report of intrathoracic haemangioma in KTS.
Extra 2bn for NHS will mean 30 000 more staff, MPs hear
Authors: A. O'Dowd
Journal: BMJ (2014)

Extra money recently announced for the NHS could help to fund 30 000 additional new clinical staff despite some cuts in staffing elsewhere as the NHS becomes more efficient, MPs have been told.

England’s health secretary, Jeremy Hunt, giving evidence to the parliamentary health committee, said that providers would be able to recruit many more staff once the extra money started to filter into the new system. 

George Osborne, chancellor of the exchequer, last week announced a £2bn boost for next year’s spending on UK health services,1 of which £1.7bn is set to be invested in frontline care. During an evidence session for the health committee’s inquiry into public spending on health and social care, MPs …
A Critical Appraisal of Neuroimaging Studies of Bipolar Disorder: Toward a New Conceptualization of Underlying Neural Circuitry and a Road Map for Future Research
Authors: Mary L. Phillips, Holly A. Swartz
Journal: American Journal of Psychiatry (2014)

In this critical review, the authors appraise neuroimaging findings in bipolar disorder in emotion-processing, emotion-regulation, and reward-processing neural circuitry in order to synthesize the current knowledge of the neural underpinnings of bipolar disorder and provide a neuroimaging research road map for future studies.The authors examined findings from all major studies in bipolar disorder that used functional MRI, volumetric analysis, diffusion imaging, and resting-state techniques, integrating findings to provide a better understanding of larger-scale neural circuitry abnormalities in bipolar disorder.Bipolar disorder can be conceptualized, in neural circuitry terms, as parallel dysfunction in prefrontal cortical (especially ventrolateral prefrontal cortical)-hippocampal-amygdala emotion-processing and emotion-regulation circuits bilaterally, together with an "overactive" left-sided ventral striatal-ventrolateral and orbitofrontal cortical reward-processing circuitry, resulting in characteristic behavioral abnormalities associated with bipolar disorder: emotional lability, emotional dysregulation, and heightened reward sensitivity. A potential structural basis for these functional abnormalities is gray matter volume decreases in the prefrontal and temporal cortices, the amygdala, and the hippocampus and fractional anisotropy decreases in white matter tracts connecting prefrontal and subcortical regions.Neuroimaging studies of bipolar disorder clearly demonstrate abnormalities in neural circuits supporting emotion processing, emotion regulation, and reward processing, although there are several limitations to these studies. Future neuroimaging research in bipolar disorder should include studies adopting dimensional approaches; larger studies examining neurodevelopmental trajectories in youths with bipolar disorder or at risk for bipolar disorder; multimodal neuroimaging studies using integrated systems approaches; and studies using pattern recognition approaches to provide clinically useful individual-level data. Such studies will help identify clinically relevant biomarkers to guide diagnosis and treatment decision making for individuals with bipolar disorder.
Lymphocyte membrane IgG and secreted IgG are structurally and allotypically distinct.
Authors: V T Oi, V M Bryan, L A Herzenberg, L A Herzenberg
Journal: The Journal of Experimental Medicine (1980)

We have demonstrated that there are structurally distinct membrane and secreted IgG2a immunoglobulin molecules. The membrane heavy chain is both larger and more acidic than the secreted molecule. This difference is not a result of different N-glycosidic-linked oligosaccharide chains. The membrane heavy chain also is antigenically different from its secreted homologue. This is based on the fact that secreted IgG2a molecules express an allotypic determinant absent on membrane molecules. We discussed the genetic control and gene organization of membrane and secreted immunoglobulin heavy chain sequences and suggest mechanisms controlling the expression of the simian virus 40 genome as models for alternate gene expression of membrane and secreted heavy chain polypeptide chains from the same DNA sequence. The possible biological significance of the membrane immunoglobulin acting as a recognition site for regulatory T cells also is discussed. The difference between membrane and secreted immunoglobulin is proposed as a possible explanation for the manner in which T cells interact with IgG on memory B cells in the presence of a large excess of IgG present in body fluids.
Serum alpha-fetoprotein, albumin, and gamma-G-globulin in the human conceptus.
Authors: D Gitlin, M Boesman
Journal: Journal of Clinical Investigation (1966)

Serum concentrations of alpha fetoprotein (AFP) in the human conceptus were investigated and compared to the concentrations of albumin and gamma G-globulin.  Determinations were made immunochemically over gestational periods from 6.6-39 weeks and in the 1st 3 weeks of newborn life.  Serum concentation of AFP increased from 6.6 weeks reaching maximal at about 13 weeks at which time the level decreased rapidly to levels less than 2% of maximum by 34 weeks.  Newborn at term had detectable AFP but that disappeared from serum with an average half-life of 5 days during the 1st week of life and with an average half-life of 3 days after the 1st week.  Serum albumin levels reached a plateau by 22-24 weeks of gestation remaining at these levels throughout the neonatal period.  Average concentrations of albumin in neonatancy were slightly higher than those in mothers.  Gamma G-globulin serum concentrations from 6.6-22 weeks of gestation were less than .2 gm/100 ml.  After 22 weeks gamma G-globulin increased to levels seen in term infants by 26 weeks.  Albumin:AFP ratios in amniotic fluid were much higher than those in bladder urine from 11-13.2 weeks of gestation which indicates the possible existence of an additional source of amniotic fluid albumin besides urine.  Clearance of albumin into urine was greater than that of AFP.  By gel filtration and ultracentrifugation the molecular size of AFP was similar to that of albumin.  Sera of pregnant women did not contain detectable amounts of AFP.
Endometriosis and pelvic pain: epidemiological evidence of the relationship and implications
Authors: A. Fauconnier, C. Chapron
Journal: Human Reproduction Update (2005)

The relationship between chronic pelvic pain symptoms and endometriosis is unclear because painful symptoms are frequent in women without this pathology, and because asymptomatic forms of endometriosis exist. Our comprehensive review attempts to clarify the links between the characteristics of lesions and the semiology of chronic pelvic pain symptoms. Based on randomized trials against placebo, endometriosis appears to be responsible for chronic pelvic pain symptoms in more than half of confirmed cases. A causal association between severe dysmenorrhoea and endometriosis is very probable. This association is independent of the macroscopic type of the lesions or their anatomical locations and may be related to recurrent cyclic micro-bleeding in the implants. Endometriosis-related adhesions may also cause severe dysmenorrhoea. There are histological and physiopathological arguments for the responsibility of deeply infiltrating endometriosis (DIE) in severe chronic pelvic pain symptoms. DIE-related pain may be in relation with compression or infiltration of nerves in the sub-peritoneal pelvic space by the implants. The painful symptoms caused by DIE present particular characteristics, being specific to involvement of precise anatomical locations (severe deep dyspareunia, painful defecation) or organs (functional urinary tract signs, bowel signs). They can thus be described as location indicating pain. A precise semiological analysis of the chronic pelvic pain symptoms characteristics is useful for the diagnosis and therapeutic management of endometriosis in a context of pain.
Altered cardiac excitation–contraction coupling in mutant mice with familial hypertrophic cardiomyopathy
Authors: Wei Dong Gao, Nestor Gustavo Pérez, Christine E. Seidman, Jonathan G. Seidman, Eduardo Marbán
Journal: Journal of Clinical Investigation (1999)

Excitation-contraction coupling in cardiac muscle of familial hypertrophic cardiomyopathy (FHC) remains poorly understood, despite the fact that the genetic alterations are well defined. We characterized calcium cycling and contractile activation in trabeculae from a mutant mouse model of FHC (Arg403Gln knockin, alpha-myosin heavy chain). Wild-type mice of the same strain and age ( approximately 20 weeks old) served as controls. During twitch contractions, peak intracellular Ca2+ ([Ca2+]i) was higher in mutant muscles than in the wild-type (P < 0.05), but force development was equivalent in the two groups. Ca2+ transient amplitude increased dramatically in both groups as stimulation rate increased from 0.2 to 4 Hz. Nevertheless, developed force fell at the higher stimulation rates in the mutants but not in controls (P < 0.05). The steady-state force-[Ca2+]i relationship was less steep in mutants (Hill coefficient, 2.94 +/- 0.27 vs. 5.28 +/- 0.64; P > 0.003), with no changes in the [Ca2+]i required for 50% activation or maximal Ca2+-activated force. Thus, calcium cycling and myofilament properties are both altered in FHC mutant mice: more Ca2+ is mobilized to generate force, but this does not suffice to maintain contractility at high stimulation rates.
Effect of ryanodine on ventricular fibrillation induced by myocardial ischaemia
Authors: M. D Lappi, G. E Billman
Journal: Cardiovascular Research (1993)

Objective: Myocardial ischaemia can provoke a rise in cytosolic calcium which may in turn trigger malignant ventricular arrhythmias. Recently, inhibition of calcium entry has been shown to prevent these lethal arrhythmias. However, the contributions of calcium release from cytosolic stores to these disruptions in cardiac rhythm have not been investigated. This study examines the role of calcium release from the sarcoplasmic reticulum in the initiation of lethal ventricular arrhythmias. Methods: Mongrel dogs were chronically instrumented to measure left ventricular pressure, coronary blood flow, and cardiac electrical activity (ventricular electrocardiogram). The left anterior descending coronary artery was ligated during the surgery to produce a myocardial infarction. In addition, a hydraulic occluder was placed around the left circumflex artery. The susceptibility to ventricular fibrillation was then evaluated by the combination of acute myocardial ischaemia and exercise. Results: Ventricular fibrillation was induced in 10 animals during the exercise plus ischaemia test. On a subsequent day the exercise plus ischaemia test was repeated after pretreatment with ryanodine (10 μg·kg−1, n = 10), a drug which impairs calcium efflux from the sarcoplasmic reticulum. Ryanodine failed to prevent ventricular fibrillation induced by ischaemia. Ryanodine significantly (p<0.01) increased heart rate [control 115.3(SEM 6.3) v ryanodine 156.4(14.7) beats·min−1] but reduced left ventricular systolic pressure [control 141.8(4.9) v ryanodine 111.1(12.7) mm Hg] and positive left ventricular dP/dt [3312.9(217.4) v ryanodine 1462.9(226.3) mm Hg·s−1] both at rest and during exercise. In contrast, this drug abolished ventricular tachycardia induced by ouabain toxicity (n = 10, 40 μg·kg−1 bolus followed by 0.076 μg·kg−1·min−1 for 1 h, then 20 μg·kg−1 bolus, intravenously). Conclusions: These data suggest that calcium release from ryanodine sensitive channels in the sarcoplasmic reticulum may contribute significantly to the arrhythmias induced by ouabain toxicity but not to ventricular fibrillation provoked by ischaemia. Cardiovascular Research 1993;27:2152-2159