Gender differences in the use of cardiovascular interventions in HIV-positive persons; the D:A:D Study

Peer reviewe

Calcium-binding protein immunoreactivity in Gudden's tegmental nuclei and the hippocampal formation: differential co-localization in neurons projecting to the mammillary bodies

The principal projections to the mammillary bodies arise from just two sites, Gudden’s tegmental nuclei (dorsal and ventral nuclei) and the hippocampal formation (subiculum and pre/postsubiculum). The present study sought to compare the neurochemical properties of these mammillary body inputs in the rat, with a focus on calcium-binding proteins. Neuronal calretinin (CR) immunoreactivity was sparse in Gudden’s tegmental nuclei and showed no co-localization with neurons projecting to the mammillary bodies. In contrast, many of the ventral tegmental nucleus of Gudden cell that project to the mammillary bodies were parvalbumin (PV)-positive whereas a smaller number of mammillary inputs stained for calbindin (CB). Only a few mammillary body projection cells in the dorsal tegmental nucleus of Gudden co-localized with PV and none co-localized with CB. A very different pattern was found in the hippocampal formation. Here, a large proportion of postsubiculum cells that project to the mammillary bodies co-localized with CR, but not CB or PV. While many neurons in the dorsal and ventral subiculum projected to the mammillary bodies, these cells did not co-localize with the immunofluorescence of any of the three tested proteins. These findings highlight marked differences between hippocampal and tegmental inputs to the rat mammillary bodies as well as differences between the medial and lateral mammillary systems. These findings also indicate some conserved neurochemical properties in Gudden’s tegmental nuclei across rodents and primates

Surgical site infection after gastrointestinal surgery in high-income, middle-income, and low-income countries: a prospective, international, multicentre cohort study

Background: Surgical site infection (SSI) is one of the most common infections associated with health care, but its importance as a global health priority is not fully understood. We quantified the burden of SSI after gastrointestinal surgery in countries in all parts of the world. Methods: This international, prospective, multicentre cohort study included consecutive patients undergoing elective or emergency gastrointestinal resection within 2-week time periods at any health-care facility in any country. Countries with participating centres were stratified into high-income, middle-income, and low-income groups according to the UN's Human Development Index (HDI). Data variables from the GlobalSurg 1 study and other studies that have been found to affect the likelihood of SSI were entered into risk adjustment models. The primary outcome measure was the 30-day SSI incidence (defined by US Centers for Disease Control and Prevention criteria for superficial and deep incisional SSI). Relationships with explanatory variables were examined using Bayesian multilevel logistic regression models. This trial is registered with ClinicalTrials.gov, number NCT02662231. Findings: Between Jan 4, 2016, and July 31, 2016, 13 265 records were submitted for analysis. 12 539 patients from 343 hospitals in 66 countries were included. 7339 (58·5%) patient were from high-HDI countries (193 hospitals in 30 countries), 3918 (31·2%) patients were from middle-HDI countries (82 hospitals in 18 countries), and 1282 (10·2%) patients were from low-HDI countries (68 hospitals in 18 countries). In total, 1538 (12·3%) patients had SSI within 30 days of surgery. The incidence of SSI varied between countries with high (691 [9·4%] of 7339 patients), middle (549 [14·0%] of 3918 patients), and low (298 [23·2%] of 1282) HDI (p < 0·001). The highest SSI incidence in each HDI group was after dirty surgery (102 [17·8%] of 574 patients in high-HDI countries; 74 [31·4%] of 236 patients in middle-HDI countries; 72 [39·8%] of 181 patients in low-HDI countries). Following risk factor adjustment, patients in low-HDI countries were at greatest risk of SSI (adjusted odds ratio 1·60, 95% credible interval 1·05–2·37; p=0·030). 132 (21·6%) of 610 patients with an SSI and a microbiology culture result had an infection that was resistant to the prophylactic antibiotic used. Resistant infections were detected in 49 (16·6%) of 295 patients in high-HDI countries, in 37 (19·8%) of 187 patients in middle-HDI countries, and in 46 (35·9%) of 128 patients in low-HDI countries (p < 0·001). Interpretation: Countries with a low HDI carry a disproportionately greater burden of SSI than countries with a middle or high HDI and might have higher rates of antibiotic resistance. In view of WHO recommendations on SSI prevention that highlight the absence of high-quality interventional research, urgent, pragmatic, randomised trials based in LMICs are needed to assess measures aiming to reduce this preventable complication

Development and Validation of a Risk Score for Chronic Kidney Disease in HIV Infection Using Prospective Cohort Data from the D:A:D Study

Ristola M. on työryhmien DAD Study Grp ; Royal Free Hosp Clin Cohort ; INSIGHT Study Grp ; SMART Study Grp ; ESPRIT Study Grp jäsen.Background Chronic kidney disease (CKD) is a major health issue for HIV-positive individuals, associated with increased morbidity and mortality. Development and implementation of a risk score model for CKD would allow comparison of the risks and benefits of adding potentially nephrotoxic antiretrovirals to a treatment regimen and would identify those at greatest risk of CKD. The aims of this study were to develop a simple, externally validated, and widely applicable long-term risk score model for CKD in HIV-positive individuals that can guide decision making in clinical practice. Methods and Findings A total of 17,954 HIV-positive individuals from the Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) study with >= 3 estimated glomerular filtration rate (eGFR) values after 1 January 2004 were included. Baseline was defined as the first eGFR > 60 ml/min/1.73 m2 after 1 January 2004; individuals with exposure to tenofovir, atazanavir, atazanavir/ritonavir, lopinavir/ritonavir, other boosted protease inhibitors before baseline were excluded. CKD was defined as confirmed (>3 mo apart) eGFR In the D:A:D study, 641 individuals developed CKD during 103,185 person-years of follow-up (PYFU; incidence 6.2/1,000 PYFU, 95% CI 5.7-6.7; median follow-up 6.1 y, range 0.3-9.1 y). Older age, intravenous drug use, hepatitis C coinfection, lower baseline eGFR, female gender, lower CD4 count nadir, hypertension, diabetes, and cardiovascular disease (CVD) predicted CKD. The adjusted incidence rate ratios of these nine categorical variables were scaled and summed to create the risk score. The median risk score at baseline was -2 (interquartile range -4 to 2). There was a 1: 393 chance of developing CKD in the next 5 y in the low risk group (risk score = 5, 505 events), respectively. Number needed to harm (NNTH) at 5 y when starting unboosted atazanavir or lopinavir/ritonavir among those with a low risk score was 1,702 (95% CI 1,166-3,367); NNTH was 202 (95% CI 159-278) and 21 (95% CI 19-23), respectively, for those with a medium and high risk score. NNTH was 739 (95% CI 506-1462), 88 (95% CI 69-121), and 9 (95% CI 8-10) for those with a low, medium, and high risk score, respectively, starting tenofovir, atazanavir/ritonavir, or another boosted protease inhibitor. The Royal Free Hospital Clinic Cohort included 2,548 individuals, of whom 94 individuals developed CKD (3.7%) during 18,376 PYFU (median follow-up 7.4 y, range 0.3-12.7 y). Of 2,013 individuals included from the SMART/ESPRIT control arms, 32 individuals developed CKD (1.6%) during 8,452 PYFU (median follow-up 4.1 y, range 0.6-8.1 y). External validation showed that the risk score predicted well in these cohorts. Limitations of this study included limited data on race and no information on proteinuria. Conclusions Both traditional and HIV-related risk factors were predictive of CKD. These factors were used to develop a risk score for CKD in HIV infection, externally validated, that has direct clinical relevance for patients and clinicians to weigh the benefits of certain antiretrovirals against the risk of CKD and to identify those at greatest risk of CKD.Peer reviewe

The stratigraphic architecture and evolution of the Burdigalian carbonate—siliciclastic sedimentary systems of the Mut Basin, Turkey

This study describes the coeval development of the depositional environments in three areas across the Mut Basin (Southern Turkey) throughout the Late Burdigalian (early Miocene). Antecedent topography and rapid high-amplitude sea-level change are the main controlling factors on stratigraphic architecture and sediment type. Stratigraphic evidence is observed for two high-amplitude (100–150 m) sea-level cycles in the Late Burdigalian to Langhian. These cycles are interpreted to be eustatic in nature and driven by the long-term 400-Ka orbital eccentricity-cycle-changing ice volumes in the nascent Antarctic icecap. We propose that the Mut Basin is an exemplary case study area for guiding lithostratigraphic predictions in early Miocene shallow-marine carbonate and mixed environments elsewhere in the world. The Late Burdigalian in the Mut Basin was a time of relative tectonic quiescence, during which a complex relict basin topography was flooded by a rapid marine transgression. This area was chosen for study because it presents extraordinary large-scale 3D outcrops and a large diversity of depositional environments throughout the basin. Three study transects were constructed by combining stratal geometries and facies observations into a high-resolution sequence stratigraphic framework. 3346 m of section were logged, 400 thin sections were studied, and 145 biostratigraphic samples were analysed for nannoplankton dates (Bassant, P., 1999. The high-resolution stratigraphic architecture and evolution of the Burdigalian carbonate-siliciclastic sedimentary systems of the Mut Basin, Turkey. PhD Thesis. GeoFocus 3. University of Fribourg, 277 p.). The first transect (Alahan) is on the northwestern basin margin. Here, the siliciclastic input is high due to the presence of a river system. The siliciclastic depocentre migrates landwards during transgressions, creating an ecological window allowing carbonates to develop in the distal part of the delta. Carbonate production shuts down during the regression when siliciclastics return. The second transect (Pirinç) is also situated on the northern basin margin 12 km to the east of the Alahan section. It shows a complete platform-to-basin transition. An isolated carbonate platform complex develops during the initial flooding, which is drowned during a time of rapid sea-level rise and environmental stress, associated with prograding siliciclastics. The shelf margin then retrogrades forming large-scale clinoform geometries and progrades before a major sea-level fall provokes slumping collapse, followed by rebuilding of the shelf margin as sea level rises again. The third transect (Silifke) has a steep asymmetric Pre-Miocene valley-topography, forming a narrow strait, linking the Mut Basin to the Mediterranean. Strong tidal currents are generated in this strait area. Siliciclastic input is low and localised. Eighty metres of cross-bedded bioclastic sands are deposited in a tidal regime at the base. Subsequently, carbonate platforms backstep against the shallow-dipping northern flank, while platforms only develop on the steep southern flank when a firm wide shallow-marine substrate is provided by a bench on the footwall block. The energy of the environment decreases with increased flooding of the strait area. Third-order sequences and higher-order parasequences have been identified in each transect and correlated between transects. Correlations were made using biostratigraphic data and high-resolution sequence stratigraphy in combination with the construction of the relative sea-level curve for each site. The third-order highstands are stacked in a proximal position and separated by exposure surfaces, while the lowstands, deposited in a distal setting, are separated by deep-marine (offshore or subphotic) deposits. The parasequences produce dominantly aggradational and progradational geometries with transgressive ravinement surfaces and exposure surfaces developing at times. Reconstruction of the depositional profile shows that the third-order sequences are driven by relative sea-level oscillations of 100–150 m, and that these may be attributed to 400-Ka orbital eccentricity cycles. The parasequences are driven by eustatic 20–30 m sea-level oscillations, which may be attributed to the 100-Ka orbital eccentricity cycles. The isolated carbonate build-ups in the Pirinç and Alahan transects develop at the same time as bioclastic tidal deposits in the Silifke area during the transgression of sequence 1. This is caused by a difference in hydrodynamic regime: a direct result of basin morphology funneling tidal currents in the Silifke area. We also demonstrate how during the highstands a siliciclastic delta system progrades in the Alahan area, while only 12 km to the east, a fringing carbonate platform develops, showing how siliciclastic input can have a very localised effect on carbonate environments. The exceptional quality of the outcrops with its variety of environments and its location at the Tethyan margin make this site a good candidate for a reference model for Burdigalian reef and platform architectures

Aging of memory mechanisms

International audienceHuman amnesia cases (after surgical removal of the hippocampi or brain anoxia) have clearly established the critical role of the hippocampal formation in anterograde amnesia. Other parts of the brain may also contribute to anterograde amnesia (mammillary bodies, medial thalamus). In neurodegenerative diseases (and specially in Alzheimer's disease) amnesia is often the prominent symptom, but the brain lesions are not restricted to the hippocampal formation. In Alzheimer's disease they involve also the cerebral cortex and several subcortical nuclei. Physiological brain aging is also associated with some degree of memory impairment, but much less severe than in Alzheimer's disease. The issue of the nature and the mechanisms of the memory impairment associated with age and with Alzheimer's disease is very important, because the frequency of these problems increases dramatically as the populations of the world is growing older. There is some evidence that neuronal loss and alterations in neurotransmitter systems occur in the aged subject, but the relationship between such changes and the age-related memory deficit is far from being clear. In Alzheimer's disease, the loss of memory is likely to be due to neuronal loss in cerebral cortex and hippocampal formation, along with alterations in neurotransmitter systems (specially cholinergic, monoaminergic and aminoacidergic systems). The work in experimental animals has largely confirmed the critical role of the hippocampal formation, as well as identified other critical structures. The mechanisms of the age-related memory impairment can be to some extent investigated in aged animals. In the aged rat there is evidence that several neurotransmitter networks are altered. Alteration in the dopaminergic and cholinergic systems have been extensively studied, but the involvement of other systems is likely. Learning and memory deficits are consistently observed in a sub-population of aged rodents (as well as in other species including non-human primates). For instance some aged rats do have a deficit in the performance of a spatial learning task such as the "water maze". There is some evidence that this deficit is due, at least in part, to alterations in the functions of the hippocampal formation. In other words, if aged rats have a spatial memory deficit, it might be due to changes in hippocampal neuronal circuitry. The study of age-related alterations in hippocampal neuronal networks, using electrophysiological techniques have shown that several neuronal properties such as resting membrane potential, membrane resistance or sodium spike amplitude are not altered in the aged rat hippocampus.(ABSTRACT TRUNCATED AT 400 WORDS

Mut basin, Turkey: Miocene carbonate depositional styles

The Mut Basin in southcentral Turkey contains a rich variety of Cenozoic carbonate deposits that developed on a complex pre-Miocene topography and can be studied in seismic-scale, threedimensional outcrops. These include open and rimmed carbonate shelves with steep slopes, small isolated platforms, and mixed carbonate-siliciclastic systems showing reciprocal sedimentation. The exceptional preservations of the stratal geometries make it possible to easily link large-scale depositional geometry to depositional facies in a variety of platform types and depositional environments. The Mut Basin provides a better understanding of (1) the control of antecedent topography on carbonate platform development, (2) the influence of icehouse conditions (e.g., highamplitude, high-frequency sea level fluctuations) on the carbonate system, (3) the link between faunal evolution and the style of carbonate platforms and stratigraphic architecture, (4) lateral and reciprocal carbonate and siliciclastic sedimentation, (5) platform asymmetry and local controls on stratal geometries, and (6) the architecture of steep carbonate margin and associated gravitational collapse deposits. These concepts are directly applicable to time-equivalent Cenozoic carbonate reservoir systems in Southeast Asia, the southern Caribbean, and the eastern Mediterranean. Copyright © 2017The American Association of Petroleum Geologists. All rights reserved

[Aging of memory mechanisms].

International audienceHuman amnesia cases (after surgical removal of the hippocampi or brain anoxia) have clearly established the critical role of the hippocampal formation in anterograde amnesia. Other parts of the brain may also contribute to anterograde amnesia (mammillary bodies, medial thalamus). In neurodegenerative diseases (and specially in Alzheimer's disease) amnesia is often the prominent symptom, but the brain lesions are not restricted to the hippocampal formation. In Alzheimer's disease they involve also the cerebral cortex and several subcortical nuclei. Physiological brain aging is also associated with some degree of memory impairment, but much less severe than in Alzheimer's disease. The issue of the nature and the mechanisms of the memory impairment associated with age and with Alzheimer's disease is very important, because the frequency of these problems increases dramatically as the populations of the world is growing older. There is some evidence that neuronal loss and alterations in neurotransmitter systems occur in the aged subject, but the relationship between such changes and the age-related memory deficit is far from being clear. In Alzheimer's disease, the loss of memory is likely to be due to neuronal loss in cerebral cortex and hippocampal formation, along with alterations in neurotransmitter systems (specially cholinergic, monoaminergic and aminoacidergic systems). The work in experimental animals has largely confirmed the critical role of the hippocampal formation, as well as identified other critical structures. The mechanisms of the age-related memory impairment can be to some extent investigated in aged animals. In the aged rat there is evidence that several neurotransmitter networks are altered. Alteration in the dopaminergic and cholinergic systems have been extensively studied, but the involvement of other systems is likely. Learning and memory deficits are consistently observed in a sub-population of aged rodents (as well as in other species including non-human primates). For instance some aged rats do have a deficit in the performance of a spatial learning task such as the "water maze". There is some evidence that this deficit is due, at least in part, to alterations in the functions of the hippocampal formation. In other words, if aged rats have a spatial memory deficit, it might be due to changes in hippocampal neuronal circuitry. The study of age-related alterations in hippocampal neuronal networks, using electrophysiological techniques have shown that several neuronal properties such as resting membrane potential, membrane resistance or sodium spike amplitude are not altered in the aged rat hippocampus.(ABSTRACT TRUNCATED AT 400 WORDS