Monitoring recently acquired HIV infections in Amsterdam, The Netherlands:The attribution of test locations

Background:  Surveillance of recent HIV infections (RHI) using an avidity assay has been implemented at Dutch sexual health centres (SHC) since 2014, but data on RHI diagnosed at other test locations is lacking. Setting:  Implementation of the avidity assay in HIV treatment clinics for the purpose of studying RHI among HIV patients tested at different test locations. Methods: We retrospectively tested leftover specimens from newly diagnosed HIV patients in care in 2013–2015 in Amsterdam. Avidity Index (AI) values ≤0.80 indicated recent infection (acquired ≤6 months prior to diagnosis), and AI > 0.80 indicated established infection (acquired >6 months prior to diagnosis). An algorithm for RHI was applied to correct for false recency. Recency based on this algorithm was compared with recency based on epidemiological data only. Multivariable logistic regression analysis was used to identify factors associated with RHI among men who have sex with men (MSM).Results: We tested 447 specimens with avidity; 72% from MSM. Proportions of RHI were 20% among MSM and 10% among heterosexuals. SHC showed highest proportions of RHI (27%), followed by GPs (15%), hospitals (5%), and other/unknown locations (11%) (p < 0.001). Test location was the only factor associated with RHI among MSM. A higher proportion of RHI was found based on epidemiological data compared to avidity testing combined with the RHI algorithm. Conclusion:  SHC identify more RHI infections compared to other test locations, as they serve high-risk populations and offer frequent HIV testing. Using avidity-testing for surveillance purposes may help targeting prevention programs, but the assay lacks robustness and its added value may decline with improved, repeat HIV testing and data collection

Never injected, but hepatitis C virus-infected: a study among self-declared never-injecting drug users from the Amsterdam Cohort Studies

The aim of this study was to gain insight in transmission routes of hepatitis C virus (HCV) infection among never-injecting drug users (DU) by studying, incidence, prevalence, determinants and molecular epidemiology of HCV infection. From the Amsterdam Cohort Studies among DU, 352 never-injecting DU were longitudinally tested for HCV antibodies. Logistic regression was used to identify factors associated with antibody prevalence. Part of HCV NS5B was sequenced to determine HCV genotype and for phylogenetic analyses, in which sequences were compared with those from injecting DU. HCV antibody prevalence was 6.3% and HCV incidence was 0.49/1000 PY. HIV-positive status, female sex and starting injection drug use during follow-up (a putative marker of past injection drug use), were independently associated with HCV prevalence. The main genotypes found were genotype 3a (50%) and 1a (30%). Phylogenetic analysis revealed that HCV strains in never-injecting DU did not cluster together and did not differ from HCV strains circulating in injecting DU. We found a higher HCV prevalence in never-injecting DU than in the general population. Phylogenetic analysis shows a strong link with the injecting DU population. The increased risk could be related to underreporting of injecting drug use or to household or sexual transmission from injectors to noninjectors. Our findings stress the need for HCV testing of DU who report never injecting, especially given the potential to treat HCV infection effectively

Resonant X-Ray Magnetic Scattering from CoO

We analyze the recent experiment [W. Neubeck {\em et al.}, Phys. Rev. B \vol(60,1999,R9912)] for the resonant x-ray magnetic scattering (RXMS) around the K edge of Co in the antiferromagnet CoO. We propose a mechanism of the RXMS to make the $4p$ states couple to the magnetic order: the intraatomic exchange interaction between the $4p$ and the $3d$ states and the $p$-$d$ mixing to the $3d$ states of neighboring Co atoms. These couplings induce the orbital moment in the $4p$ states and make the scattering tensor antisymmetric. Using a cluster model, we demonstrate that this modification gives rise to a large RXMS intensity in the dipole process, in good agreement with the experiment. We also find that the pre-edge peak is generated by the transition to the $3d$ states in the quadrupole process, with negligible contribution of the dipole process. We also discuss the azimuthal angle dependence of the intensity.Comment: 15 pages, 8 figure

Lateral and Medial Ventral Occipitotemporal Regions Interact During the Recognition of Images Revealed from Noise

Several studies suggest different functional roles for the medial and the lateral sections of the ventral visual cortex in object recognition. Texture and surface information is processed in medial sections, while shape information is processed in lateral sections. This begs the question whether and how these functionally specialized sections interact with each other and with early visual cortex to facilitate object recognition. In the current research, we set out to answer this question. In an fMRI study, 13 subjects viewed and recognized images of objects and animals that were gradually revealed from noise while their brains were being scanned. We applied dynamic causal modeling (DCM) a method to characterize network interactions to determine the modulatory effect of object recognition on a network comprising the primary visual cortex (V1), the lingual gyrus (LG) in medial ventral cortex and the lateral occipital cortex (LO). We found that object recognition modulated the bilateral connectivity between LG and LO. Moreover, the feed-forward connectivity from Vito LG and LO was modulated, while there was no evidence for feedback from these regions to V1 during object recognition. In particular, the interaction between medial and lateral areas supports a framework in which visual recognition of objects is achieved by networked regions that integrate information on image statistics, scene content and shape rather than by a single categorically specialized region within the ventral visual cortex

Differences in clinical presentation of primary open-angle glaucoma between African and European populations

PURPOSE: Primary open‐angle glaucoma (POAG) has been reported to occur more frequently in Africans, and to follow a more severe course compared to Europeans. We aimed to describe characteristics of POAG presentation and treatment across three ethnic groups from Africa and one from Europe. METHODS: We ascertained 151 POAG patients from South African Coloured (SAC) and 94 South African Black (SAB) ethnicity from a university hospital in South Africa. In Tanzania, 310 patients were recruited from a university hospital and a referral hospital. In the Netherlands, 241 patients of European ancestry were included. All patients were over 35 years old and had undergone an extensive ophthalmic examination. Patients were diagnosed according to the ISGEO criteria. A biogeographic ancestry analysis was performed to estimate the proportion of genetic African ancestry (GAA). RESULTS: The biogeographic ancestry analysis showed that the median proportion of GAA was 97.6% in Tanzanian, 100% in SAB, 34.2% in SAC and 1.5% in Dutch participants. Clinical characteristics at presentation for Tanzanians, SAB, SAC and Dutch participants, respectively: mean age: 63, 57, 66, 70 years (p < 0.001); visual acuity in the worse eye: 1.78, 1.78, 0.3, 0.3 LogMAR (p < 0.001); maximum intraocular pressure of both eyes: 36, 34, 29, 29 mmHg (p (anova)  < 0.001); maximum vertical cup to disc ratio (VCDR) of both eyes: 0.90, 0.90, 0.84, 0.83 (p < 0.001); mean central corneal thickness: 506, 487, 511, 528 μm (p < 0.001). Fourteen percent of Tanzanian patients presented with blindness (<3/60 Snellen) in the better eye in contrast to only 1% in the Dutch. CONCLUSION: In this multi‐ethnic comparative study, Sub‐Saharan Africans present at a younger age with lower visual acuity, higher IOP, larger VCDR, than SAC and Dutch participants. This indicates the more progressive and destructive course in Sub‐Saharan Africans

Randomized Delayed-Start Trial of Levodopa in Parkinson's Disease

BACKGROUND Levodopa is the main treatment for symptoms of Parkinson's disease. Determining whether levodopa also has a disease-modifying effect could provide guidance as to when in the course of the disease the treatment with this drug should be initiated. METHODS In a multicenter, double-blind, placebo-controlled, delayed-start trial, we randomly assigned patients with early Parkinson's disease to receive levodopa (100 mg three times per day) in combination with carbidopa (25 mg three times per day) for 80 weeks (early-start group) or placebo for 40 weeks followed by levodopa in combination with carbidopa for 40 weeks (delayed-start group). The primary outcome was the between-group difference in the mean change from baseline to week 80 in the total score on the Unified Parkinson's Disease Rating Scale (UPDRS; scores range from 0 to 176, with higher scores signifying more severe disease). Secondary analyses included the progression of symptoms, as measured by the UPDRS score, between weeks 4 and 40 and the noninferiority of early initiation of treatment to delayed initiation between weeks 44 and 80, with a noninferiority margin of 0.055 points per week. RESULTS A total of 445 patients were randomly assigned: 222 to the early-start group and 223 to the delayed-start group. The mean (+/- SD) UPDRS score at baseline was 28.1 +/- 11.4 points in the early-start group and 29.3 +/- 12.1 points in the delayed-start group. The change in UPDRS score from baseline to week 80 was -1.0 +/- 13.1 points and -2.0 +/- 13.0 points, respectively (difference, 1.0 point; 95% confidence interval [CI], -1.5 to 3.5; P = 0.44); this finding of no significant between-group difference at week 80 implies that levodopa had no disease-modifying effect. Between weeks 4 and 40, the rate of progression of symptoms, as measured in UPDRS points per week, was 0.04 +/- 0.23 in the early-start group and 0.06 +/- 0.34 in the delayed-start group (difference, -0.02; 95% CI, -0.07 to 0.03). The corresponding rates between weeks 44 and 80 were 0.10 +/- 0.25 and 0.03 +/- 0.28 (difference, 0.07; two-sided 90% CI, 0.03 to 0.10); the difference in the rate of progression between weeks 44 and 80 did not meet the criterion for noninferiority of early receipt of levodopa to delayed receipt. The rates of dyskinesia and levodopa-related fluctuations in motor response did not differ significantly between the two groups. CONCLUSIONS Among patients with early Parkinson's disease who were evaluated over the course of 80 weeks, treatment with levodopa in combination with carbidopa had no disease-modifying effect

Direct-Acting Antiviral Treatment for Hepatitis C Genotypes Uncommon in High-Income Countries:A Dutch Nationwide Cohort Study

Background. The majority of hepatitis C virus (HCV) infections are found in low- and middle-income countries, which harbor many region-specific HCV subtypes. Nevertheless, direct-acting antiviral (DAA) trials have almost exclusively been conducted in high-income countries, where mainly epidemically spread HCV subtypes are present. Recently, several studies have demonstrated suboptimal DAA efficacy for certain nonepidemic subtypes, which could hamper global HCV elimination. Therefore, we aimed to evaluate DAA efficacy in patients treated for a nonepidemic HCV genotype infection in the Netherlands. Methods. We performed a nationwide retrospective study including patients treated with interferon-free DAAs for an HCV genotype other than 1a/1b/2a/2b/3a/4a/4d. The genotype was determined by NS5B region phylogenetic analysis. The primary end point was SVR-12. If stored samples were available, NS5A and NS5B sequences were obtained for resistance-associated substitutions (RAS) evaluation. Results. We included 160 patients, mainly infected with nonepidemic genotype 2 (41%) and 4 (31%) subtypes. Most patients were from Africa (45%) or South America (24%); 51 (32%) were cirrhotic. SVR-12 was achieved in 92% (140/152) of patients with available SVR-12 data. Only 73% (8/11) genotype 3-infected patients achieved SVR-12, the majority being genotype 3b patients with 63% (5/8) SVR. Regardless of SVR, all genotype 3b patients had 30K and 31M RAS. Conclusions. (T)he DAA efficacy we observed in most nonepidemic genotypes in the Netherlands seems reassuring. However, the low SVR-12 rate in subtype 3b infections is alarming, especially as it is common in several HCV-endemic countries. Alongside earlier results, our results indicate that a remaining challenge for global HCV elimination is confirming and monitoring DAA efficacy in nonepidemic genotypes

Efficacy of serology driven “test and treat strategy” for eradication of H. pylori in patients with rheumatic disease in the Netherlands

The treatment of choice of H. pylori infections is a 7-day triple-therapy with a proton pump inhibitor (PPI) plus amoxicillin and either clarithromycin or metronidazole, depending on local antibiotic resistance rates. The data on efficacy of eradication therapy in a group of rheumatology patients on long-term NSAID therapy are reported here. This study was part of a nationwide, multicenter RCT that took place in 2000–2002 in the Netherlands. Patients who tested positive for H. pylori IgG antibodies were included and randomly assigned to either eradication PPI-triple therapy or placebo. After completion, follow-up at 3 months was done by endoscopy and biopsies were sent for culture and histology. In the eradication group 13% (20/152, 95% CI 9–20%) and in the placebo group 79% (123/155, 95% CI 72–85%) of the patients were H. pylori positive by histology or culture. H. pylori was successfully eradicated in 91% of the patients who were fully compliant to therapy, compared to 50% of those who were not (difference of 41%; 95% CI 18–63%). Resistance percentages found in isolates of the placebo group were: 4% to clarithromycin, 19% to metronidazole, 1% to amoxicillin and 2% to tetracycline

A systems biology approach to understand gut microbiota and host metabolism in morbid obesity: design of the BARIA Longitudinal Cohort Study

Introduction: Prevalence of obesity and associated diseases, including type 2 diabetes mellitus, dyslipidaemia and non-alcoholic fatty liver disease (NAFLD), are increasing. Underlying mechanisms, especially in humans, are unclear. Bariatric surgery provides the unique opportunity to obtain biopsies and portal vein blood-samples. Methods: The BARIA Study aims to assess how microbiota and their metabolites affect transcription in key tissues and clinical outcome in obese subjects and how baseline anthropometric and metabolic characteristics determine weight loss and glucose homeostasis after bariatric surgery. We phenotype patients undergoing bariatric surgery (predominantly laparoscopic Roux-en-Y gastric bypass), before weight loss, with biometrics, dietary and psychological questionnaires, mixed meal test (MMT) and collect fecal-samples and intra-operative biopsies from liver, adipose tissues and jejunum. We aim to include 1500 patients. A subset (approximately 25%) will undergo intra-operative portal vein blood-sampling. Fecal-samples are analyzed with shotgun metagenomics and targeted metabolomics, fasted and postprandial plasma-samples are subjected to metabolomics, and RNA is extracted from the tissues for RNAseq-analyses. Data will be integrated using state-of-the-art neuronal networks and metabolic modeling. Patient follow-up will be ten years. Results: Preoperative MMT of 170 patients were analysed and clear differences were observed in glucose homeostasis between individuals. Repeated MMT in 10 patients showed satisfactory intra-individual reproducibility, with differences in plasma glucose, insulin and triglycerides within 20% of the mean difference. Conclusion: The BARIA study can add more understanding in how gut-microbiota affect metabolism, especially with regard to obesity, glucose metabolism and NAFLD. Identification of key factors may provide diagnostic and therapeutic leads to control the obesity-associated disease epidemic

Moderate and heavy metabolic stress interval training improve arterial stiffness and heart rate dynamics in humans

Traditional continuous aerobic exercise training attenuates age-related increases of arterial stiffness, however, training studies have not determined whether metabolic stress impacts these favourable effects. Twenty untrained healthy participants (n = 11 heavy metabolic stress interval training, n = 9 moderate metabolic stress interval training) completed 6 weeks of moderate or heavy intensity interval training matched for total work and exercise duration. Carotid artery stiffness, blood pressure contour analysis, and linear and non-linear heart rate variability were assessed before and following training. Overall, carotid arterial stiffness was reduced (p  0.05). This study demonstrates the effectiveness of interval training at improving arterial stiffness and autonomic function, however, the metabolic stress was not a mediator of this effect. In addition, these changes were also independent of improvements in aerobic capacity, which were only induced by training that involved a high metabolic stress