The gastric acid pocket is attenuated in H. pylori infected subjects

Objective Gastric acid secretory capacity in different anatomical regions, including the postprandial acid pocket, was assessed in Helicobacter pylori positive and negative volunteers in a Western population. Design We studied 31 H. pylori positive and 28 H. pylori negative volunteers, matched for age, gender and body mass index. Jumbo biopsies were taken at 11 predetermined locations from the gastro-oesophageal junction and stomach. Combined high-resolution pH metry (12 sensors) and manometry (36 sensors) was performed for 20 min fasted and 90 min postprandially. The squamocolumnar junction was marked with radio-opaque clips and visualised radiologically. Biopsies were scored for inflammation and density of parietal, chief and G cells immunohistochemically. Results Under fasting conditions, the H. pylori positives had less intragastric acidity compared with negatives at all sensors >1.1 cm distal to the peak lower oesophageal sphincter (LES) pressure (p<0.01). Postprandially, intragastric acidity was less in H. pylori positives at sensors 2.2, 3.3 and 4.4 cm distal to the peak LES pressure (p<0.05), but there were no significant differences in more distal sensors. The postprandial acid pocket was thus attenuated in H. pylori positives. The H. pylori positives had a lower density of parietal and chief cells compared with H. pylori negatives in 10 of the 11 gastric locations (p<0.05). 17/31 of the H. pylori positives were CagA-seropositive and showed a more marked reduction in intragastric acidity and increased mucosal inflammation. Conclusions In population volunteers, H. pylori positives have reduced intragastric acidity which most markedly affects the postprandial acid pocket

Predictors of excellent early outcome after total hip arthroplasty

<p>Abstract</p> <p>Background</p> <p>Not all patients gain the same degree of improvement from total hip replacement and the reasons for this are not clear. Many investigators have assessed predictors of general outcome after hip surgery. This study is unique in its quest for the predictors of the best possible early outcome.</p> <p>Methods</p> <p>We prospectively collected data on 1318 total hip replacements. Prior to surgery patient characteristics, demographics and co-morbidities were documented. Hip function and general health was assessed using the Harris Hip score (HHS) and the Short-Form 36 respectively. The HHS was repeated at three years. We took a maximal HHS of 100 to represent an excellent outcome (102 patients). Multiple logistic regression analysis was used to identify independent predictors of excellent outcome.</p> <p>Results</p> <p>The two strongest predictive factors in achieving an excellent result were young age and a high pre-operative HHS (p = 0.001).</p> <p>Conclusions</p> <p>It was the young and those less disabled from their arthritis that excelled at three years. When making a decision about the timing of hip arthroplasty surgery it is important to take into account the age and pre-operative function of the patient. Whether these patients continue to excel however will be the basis of future research.</p

The Soft-Excess in Mrk 509: Warm Corona or Relativistic Reflection?

We present the analysis of the first NuSTAR observations ($\sim 220$ ks), simultaneous with the last SUZAKU observations ($\sim 50$ ks), of the active galactic nucleus of the bright Seyfert 1 galaxy Mrk 509. The time-averaged spectrum in the $1-79$ keV X-ray band is dominated by a power-law continuum ($\Gamma\sim 1.8-1.9$), a strong soft excess around 1 keV, and signatures of X-ray reflection in the form of Fe K emission ($\sim 6.4$ keV), an Fe K absorption edge ($\sim 7.1$ keV), and a Compton hump due to electron scattering ($\sim 20-30$ keV). We show that these data can be described by two very different prescriptions for the soft excess: a warm ($kT\sim 0.5-1$ keV) and optically thick ($\tau\sim10-20$) Comptonizing corona, or a relativistically blurred ionized reflection spectrum from the inner regions of the accretion disk. While these two scenarios cannot be distinguished based on their fit statistics, we argue that the parameters required by the warm corona model are physically incompatible with the conditions of standard coronae. Detailed photoionization calculations show that even in the most favorable conditions, the warm corona should produce strong absorption in the observed spectrum. On the other hand, while the relativistic reflection model provides a satisfactory description of the data, it also requires extreme parameters, such as maximum black hole spin, a very low and compact hot corona, and a very high density for the inner accretion disk. Deeper observations of this source are thus necessary to confirm the presence of relativistic reflection, and to further understand the nature of its soft excess.Comment: Accepted for publication in ApJ, 18 pages, 7 figure

Efficacy and safety of elinzanetant, a selective neurokinin-1,3 receptor antagonist for vasomotor symptoms: a dose-finding clinical trial (SWITCH-1)

OBJECTIVE: Neurokinin (NK)-3 and NK-1 receptors have been implicated in the etiology of vasomotor symptoms (VMS) and sleep disturbances associated with menopause. This phase 2b, adaptive, dose-range finding study aimed to assess the efficacy and safety of multiple doses of elinzanetant (NT-814), a selective NK-1,3 receptor antagonist, in women experiencing VMS associated with menopause, and investigate the impact of elinzanetant on sleep and quality of life. METHODS: Postmenopausal women aged 40 to 65 years who experienced seven or more moderate-to-severe VMS per day were randomized to receive elinzanetant 40, 80, 120, or 160 mg or placebo once daily using an adaptive design algorithm. Coprimary endpoints were reduction in mean frequency and severity of moderate-to-severe VMS at weeks 4 and 12. Secondary endpoints included patient-reported assessments of sleep and quality of life. RESULTS: Elinzanetant 120 mg and 160 mg achieved reductions in VMS frequency versus placebo from week 1 throughout 12 weeks of treatment. Least square mean reductions were statistically significant versus placebo at both primary endpoint time points for elinzanetant 120 mg (week 4: -3.93 [SE, 1.02], P \u3c 0.001; week 12: -2.95 [1.15], P = 0.01) and at week 4 for elinzanetant 160 mg (-2.63 [1.03]; P = 0.01). Both doses also led to clinically meaningful improvements in measures of sleep and quality of life. All doses of elinzanetant were well tolerated. CONCLUSIONS: Elinzanetant is an effective and well-tolerated nonhormone treatment option for postmenopausal women with VMS and associated sleep disturbance. Elinzanetant also improves quality of life in women with VMS

Exposure-age constraints on the extent, timing and rate of retreat of the last Irish Sea ice stream

We report 23 cosmogenic isotope exposure ages (10Be and 36Cl) relating to the maximum extent and deglaciation chronology of the Irish Sea Ice Stream (ISIS), which drained the SW sector of the last British-Irish Ice Sheet. These show that the ISIS failed to reach the Preseli Hills of North Pembrokeshire yet extended southwards to impinge on northern Isles of Scilly (50°N) during the last glacial maximum. Four samples from western Anglesey demonstrate deglaciation of the southern Irish Sea Basin by c. 20-18 ka, and two from the Llŷn Peninsula in northwest Wales, if valid, suggest deglaciation by c. 23-22 ka followed by gradual oscillatory northwards retreat of the ice margin for over 3000 years. An alternative interpretation of our data suggests that ice reached Scilly as late as 22-21 ka then retreated 450 km northwards within the following three millennia, possibly in response to sea level rise and/or intrinsic reorganisation within the last British-Irish Ice Sheet. Samples from upland source areas of the ISIS in NW England and SW Scotland produced exposure ages ≤14.3 ka, suggesting possible persistence of ice in such areas into the Lateglacial Interstade of 14.7-12.9 ka

Implications of the Warm Corona and Relativistic Reflection Models for the Soft Excess in Mrk 509

We present the analysis of the first Nuclear Spectroscopic Telescope Array observations (~220 ks), simultaneous with the last Suzaku observations (~50 ks), of the active galactic nucleus of the bright Seyfert 1 galaxy Mrk 509. The time-averaged spectrum in the 1–79 keV X-ray band is dominated by a power-law continuum (Γ ~ 1.8–1.9), a strong soft excess around 1 keV, and signatures of X-ray reflection in the form of Fe K emission (~6.4 keV), an Fe K absorption edge (~7.1 keV), and a Compton hump due to electron scattering (~20–30 keV). We show that these data can be described by two very different prescriptions for the soft excess: a warm (kT ~ 0.5–1 keV) and optically thick (τ ~ 10–20) Comptonizing corona or a relativistically blurred ionized reflection spectrum from the inner regions of the accretion disk. While these two scenarios cannot be distinguished based on their fit statistics, we argue that the parameters required by the warm corona model are physically incompatible with the conditions of standard coronae. Detailed photoionization calculations show that even in the most favorable conditions, the warm corona should produce strong absorption in the observed spectrum. On the other hand, while the relativistic reflection model provides a satisfactory description of the data, it also requires extreme parameters, such as maximum black hole spin, a very low and compact hot corona, and a very high density for the inner accretion disk. Deeper observations of this source are thus necessary to confirm the presence of relativistic reflection and further understand the nature of its soft excess

Associations Between High-Density Lipoprotein Particles and Ischemic Events by Vascular Domain, Sex, and Ethnicity A Pooled Cohort Analysis

Background: High-density lipoprotein (HDL) cholesterol concentration (HDL-C) is an established atheroprotective marker, in particular for coronary artery disease; however, HDL particle concentration (HDL-P) may better predict risk. The associations of HDL-C and HDL-P with ischemic stroke and myocardial infarction (MI) among women and Blacks have not been well studied. We hypothesized that HDL-P would consistently be associated with MI and stroke among women and Blacks compared with HDL-C. Methods: We analyzed individual-level participant data in a pooled cohort of 4 large population studies without baseline atherosclerotic cardiovascular disease: DHS (Dallas Heart Study; n=2535), ARIC (Atherosclerosis Risk in Communities; n=1595), MESA (Multi-Ethnic Study of Atherosclerosis; n=6632), and PREVEND (Prevention of Renal and Vascular Endstage Disease; n=5022). HDL markers were analyzed in adjusted Cox proportional hazard models for MI and ischemic stroke. Results: In the overall population (n=15 784), HDL-P was inversely associated with the combined outcome of MI and ischemic stroke, adjusted for cardiometabolic risk factors (hazard ratio [HR] for quartile 4 [Q4] versus quartile 1 [Q1], 0.64 [95% CI, 0.52-0.78]), as was HDL-C (HR for Q4 versus Q1, 0.76 [95% CI, 0.61-0.94]). Adjustment for HDL-C did not attenuate the inverse relationship between HDL-P and atherosclerotic cardiovascular disease, whereas adjustment for HDL-P attenuated all associations between HDL-C and events. HDL-P was inversely associated with the individual end points of MI and ischemic stroke in the overall population, including in women. HDL-P was inversely associated with MI among White participants but not among Black participants (HR for Q4 versus Q1 for Whites, 0.49 [95% CI, 0.35-0.69]; for Blacks, 1.22 [95% CI, 0.76-1.98];P-interaction=0.001). Similarly, HDL-C was inversely associated with MI among White participants (HR for Q4 versus Q1, 0.53 [95% CI, 0.36-0.78]) but had a weak direct association with MI among Black participants (HR for Q4 versus Q1, 1.75 [95% CI, 1.08-2.83];P-interactio

Midlife Determinants of Healthy Cardiovascular aging: the atherosclerosis Risk in Communities (Aric) Study

BACKGROUND AND AIMS: Risk factor cutoffs are derived from associations with clinical cardiovascular disease (CVD), but how these risk factors associate with preserved cardiovascular health into old age is not well studied. We investigated midlife determinants of healthy versus nonhealthy cardiovascular aging in the Atherosclerosis Risk in Communities (ARIC) study. METHODS: ARIC participants were categorized by cardiovascular status in older age (mean age 75.8 ± 5.3 years, range 66-90): healthy, subclinical disease (assessed by biomarkers and left ventricular function), clinical CVD (coronary heart disease, stroke, or heart failure), or prior death. We examined associations of midlife (mean age 52.1 ± 5.1 years) systolic and diastolic blood pressure (SBP, DBP), low-density lipoprotein cholesterol (LDL-C), triglycerides, hemoglobin A1c (HbA1c), and body mass index (BMI) with cardiovascular status in older age using multinomial logistic regression analyses. RESULTS: Compared with healthy status, odds for subclinical disease (odds ratio [OR] 1.30, 95% confidence interval [CI] 1.09-1.55) and clinical CVD (OR 1.87, 95% CI 1.53-2.29) at older age increased starting with midlife SBP 120-129 mmHg, whereas odds for death increased starting with SBP 110-119 mmHg (OR 1.29, 95% CI 1.10-1.52); findings were similar for DBP. Odds for subclinical disease increased for HbA1c ≥ 6.5% and BMI starting at 30-/m CONCLUSIONS: More-stringent levels of modifiable risk factors in midlife beyond current clinical practice and guidelines were associated with preserved cardiovascular health in older age

Chromosome Xq23 Is Associated with Lower Atherogenic Lipid Concentrations and Favorable Cardiometabolic Indices

Autosomal genetic analyses of blood lipids have yielded key insights for coronary heart disease (CHD). However, X chromosome genetic variation is understudied for blood lipids in large sample sizes. We now analyze genetic and blood lipid data in a high-coverage whole X chromosome sequencing study of 65,322 multi-ancestry participants and perform replication among 456,893 European participants. Common alleles on chromosome Xq23 are strongly associated with reduced total cholesterol, LDL cholesterol, and triglycerides (min P = 8.5 × 10−72), with similar effects for males and females. Chromosome Xq23 lipid-lowering alleles are associated with reduced odds for CHD among 42,545 cases and 591,247 controls (P = 1.7 × 10−4), and reduced odds for diabetes mellitus type 2 among 54,095 cases and 573,885 controls (P = 1.4 × 10−5). Although we observe an association with increased BMI, waist-to-hip ratio adjusted for BMI is reduced, bioimpedance analyses indicate increased gluteofemoral fat, and abdominal MRI analyses indicate reduced visceral adiposity. Co-localization analyses strongly correlate increased CHRDL1 gene expression, particularly in adipose tissue, with reduced concentrations of blood lipids