Prevalence of potential underlying aetiology of macrocytic anaemia in Dutch general practice

Background: Macrocytic anaemia (MCV \xe2\x89\xa5 100 fL) is a relatively common finding in general practice. However, literature on the prevalence of the different causes in this population is limited. The prevalence of macrocytic anaemia and its underlying aetiology were analysed in a general practice population. The potential effect of the different aetiology on survival was also evaluated. Methods: Between the 1st of February 2007 and the 1st of February 2015, patients aged 50 years or older and presenting to their general practitioner with a newly diagnosed anaemia, were included in the study. Anaemia was defined as haemoglobin level below 13.7 g/dL in men and below 12.1 g/dL in women. A broad range of laboratory tests was performed for each patient. The causes of anaemia were consequently determined by two independent observers based on the laboratory results. Results: Of the 3324 included patients, 249 (7.5 %) displayed a macrocytic anaemia and were subsequently analysed. An underlying explanation could be established in 204 patients (81.9 %) with 27 patients (13.2 %) displaying multiple causes. Classic aetiology (i.e. alcohol abuse, vitamin B12/folic acid deficiency, haemolysis and possible bone marrow disease) was found in 115 patients. Alternative causes (i.e. anaemia of chronic disease, iron deficiency, renal anaemia and other causes) were encountered in 101 patients. In addition, a notable finding was the median gamma GT of 277 U/L in patients diagnosed with alcohol abuse (N = 24, IQR 118.0-925.5) and 23 U/L in the remaining cohort (N = 138, IQR 14.0-61.0). The distribution of gamma GT values was statistically different (P < 0.001). Five year survival rates were determined for six categories of causes, ranging from 39.9 % (95 % CI 12.9-66.9) for renal anaemia to 76.2 % (95 % CI 49.4-103.0) for the category multiple causes. Conclusion: In addition to classic explanations for macrocytosis, alternative causes are frequently encountered in patients with macrocytic anaemia in general practice

Structure of the Vesicular Stomatitis Virus N0-P Complex

Replication of non-segmented negative-strand RNA viruses requires the continuous supply of the nucleoprotein (N) in the form of a complex with the phosphoprotein (P). Here, we present the structural characterization of a soluble, heterodimeric complex between a variant of vesicular stomatitis virus N lacking its 21 N-terminal residues (NΔ21) and a peptide of 60 amino acids (P60) encompassing the molecular recognition element (MoRE) of P that binds RNA-free N (N0). The complex crystallized in a decameric circular form, which was solved at 3.0 Å resolution, reveals how the MoRE folds upon binding to N and competes with RNA binding and N polymerization. Small-angle X-ray scattering experiment and NMR spectroscopy on the soluble complex confirms the binding of the MoRE and indicates that its flanking regions remain flexible in the complex. The structure of this complex also suggests a mechanism for the initiation of viral RNA synthesis

The steel–concrete interface

Although the steel–concrete interface (SCI) is widely recognized to influence the durability of reinforced concrete, a systematic overview and detailed documentation of the various aspects of the SCI are lacking. In this paper, we compiled a comprehensive list of possible local characteristics at the SCI and reviewed available information regarding their properties as well as their occurrence in engineering structures and in the laboratory. Given the complexity of the SCI, we suggested a systematic approach to describe it in terms of local characteristics and their physical and chemical properties. It was found that the SCI exhibits significant spatial inhomogeneity along and around as well as perpendicular to the reinforcing steel. The SCI can differ strongly between different engineering structures and also between different members within a structure; particular differences are expected between structures built before and after the 1970/1980s. A single SCI representing all on-site conditions does not exist. Additionally, SCIs in common laboratory-made specimens exhibit significant differences compared to engineering structures. Thus, results from laboratory studies and from practical experience should be applied to engineering structures with caution. Finally, recommendations for further research are made

Performance of a novel melting curve-based qPCR assay for malaria parasites in routine clinical practice in non-endemic setting

Abstract Background High-quality malaria diagnosis is essential for effective treatment and clinical disease management. Microscopy and rapid diagnostic tests are the conventional methods performed as first-line malaria diagnostics in non-endemic countries. However, these methods lack the characteristic to detect very low parasitaemia, and accurate identification of the Plasmodium species can be difficult. This study evaluated the performance of the MC004 melting curve-based qPCR for the diagnosis of malaria in routine clinical practice in non-endemic setting. Methods and results Whole blood samples were collected from 304 patients with clinical suspicion of malaria and analysed by both the MC004 assay and conventional diagnostics. Two discrepancies were found between the MC004 assay and microscopy. Repeated microscopic analysis confirmed the qPCR results. Comparison of the parasitaemia of nineteen Plasmodium falciparum samples determined by both microscopy and qPCR showed the potential of the MC004 assay to estimate the parasite load of P. falciparum. Eight Plasmodium infected patients were followed after anti-malarial treatment by the MC004 assay and microscopy. The MC004 assay still detected Plasmodium DNA although no parasites were seen with microscopy in post-treatment samples. The rapid decline in Plasmodium DNA showed the potential for therapy-monitoring. Conclusion Implementation of the MC004 assay in non-endemic clinical setting improved the diagnosis of malaria. The MC004 assay demonstrated superior Plasmodium species identification, the ability to indicate the Plasmodium parasite load, and can potentially detect submicroscopic Plasmodium infections

Peptides That Mimic the Amino-Terminal End of the Rabies Virus Phosphoprotein Have Antiviral Activity▿

We wanted to develop a therapeutic approach against rabies disease by targeting the lyssavirus transcription/replication complex. Because this complex (nucleoprotein N-RNA template processed by the L polymerase and its cofactor, the phosphoprotein P) is similar to that of other negative-strand RNA viruses, we aimed to design broad-spectrum antiviral drugs that could be used as a complement to postexposure vaccination and immunotherapy. Recent progress in understanding the structure/function of the rabies virus P, N, and L proteins predicts that the amino-terminal end of P is an excellent target for destabilizing the replication complex because it interacts with both L (for positioning onto the N-RNA template) and N (for keeping N soluble, as needed for viral RNA encapsidation). Thus, peptides mimicking various lengths of the amino-terminal end of P have been evaluated, as follows: (i) for binding properties to the N-P-L partners by the two-hybrid method; (ii) for their capacity to inhibit the transcription/replication of a rabies virus minigenome encoding luciferase in BHK-21-T7 cells; and (iii) for their capacity to inhibit rabies virus infection of BHK-21-T7 cells and of two derivatives of the neuronal SK-N-SH cell line. Peptides P60 and P57 (the first 60 and first 57 NH2 residues of P, respectively) exhibited a rapid, strong, and long-lasting inhibitory potential on luciferase expression (>95% from 24 h to 55 h). P42 was less efficient in its inhibition level (75% for 18 to 30 h) and duration (40% after 48 h). The most promising peptides were synthesized in tandem with the Tat sequence, allowing cell penetration. Their inhibitory effects were observed on BHK-21-T7 cells infected with rabies virus and Lagos bat virus but not with vesicular stomatitis virus. In neuronal cells, a significant inhibition of both nucleocapsid inclusions and rabies virus release was observed

Widespread closure of HIV prevention and care services places youth at higher risk during the COVID-19 pandemic.

BackgroundCentral to measuring the impact of the COVID-19 pandemic on HIV is understanding the role of loss of access to essential HIV prevention and care services created by clinic and community-based organization closures. In this paper, we use a comprehensive list of HIV prevention services in four corridors of the US heavily impacted by HIV, developed as part of a large RCT, to illustrate the potential impact of service closure on LGBTQ+ youth.MethodsWe identified and mapped LGBTQ+ friendly services offering at least one of the following HIV-related services: HIV testing; STI testing; PrEP/PEP; HIV treatment and care; and other HIV-related services in 109 counties across four major interstate corridors heavily affected by HIV US Census regions: Pacific (San Francisco, CA to San Diego, CA); South-Atlantic (Washington, DC to Atlanta, GA); East-North-Central (Chicago, IL to Detroit, MI); and East-South-Central (Memphis, TN to New Orleans, LA).ResultsThere were a total of 831 LGBTQ+ youth-friendly HIV service providers across the 109 counties. There was a range of LGBTQ+ youth-friendly HIV-service provider availability across counties (range: 0-14.33 per 10,000 youth aged 13-24 (IQR: 2.13), median: 1.09); 9 (8.26%) analyzed counties did not have any LGBTQ+ youth-friendly HIV service providers. The Pearson correlation coefficient for the correlation between county HIV prevalence and LGBTQ+ youth-friendly HIV service provider density was 0.16 (p = 0.09), suggesting only a small, non-statistically significant linear relationship between a county's available LGBTQ+ youth-friendly HIV service providers and their HIV burden.ConclusionsAs the COVID-19 pandemic continues, we must find novel, affordable ways to continue to provide sexual health, mental health and other support services to LGBTQ+ youth

Constructing a web-based health directory for adolescent men who have sex with men: Strategies for development and resource verification

Online health directories are increasingly used to locate health services and community resources, providing contact and service information that assists users in identifying resources that may meet their health and wellness needs. However, service locations require additional vetting when directories plan to refer vulnerable populations. As a tool included as part of a trial of a mobile life skills intervention for cisgender adolescent men who have sex with men (AMSM; ages 13–18), we constructed and verified resources for an online resource directory focused on linking young people to LGBTQ+ friendly and affirming local health and community social services resources. We collected information for 2301 individual directory listings through database and internet searches. To ensure the listings aligned with the project\u27s focus of supporting young sexual minority men, we developed multiple data verification assessments to ensure community appropriateness resulting in verification of 1833 resources suitable for inclusion in our locator tool at project launch (March 2018). We offer lessons learned and future directions for researchers and practitioners who may benefit from adapting our processes and strategies for building culturally-tailored resource directories for vulnerable populations

Preferences for and Experiences of an HIV-Prevention Mobile App Designed for Transmasculine People: Pilot Feasibility Trial and Qualitative Investigation

BackgroundTransmasculine people are at risk for HIV; yet few HIV prevention interventions have been developed for this population. We adapted an existing HIV prevention smartphone app for cisgender men who have sex with men to meet the sexual health needs of transmasculine people. ObjectiveThis study aims to assess the acceptability of the adapted app, Transpire, among transmasculine people living in Atlanta, Georgia, and Washington, DC, via in-depth interviews of participants in a pilot feasibility trial. MethodsParticipants used the Transpire app for 3 months as part of a pilot study of the app. Eligible participants were aged 18-34 years. There were no eligibility criteria with respect to race and ethnicity, and most participants were non-Hispanic White. At the end of the follow-up, participants were invited to participate in web-based in-depth interviews to discuss their experiences using the app and feedback on design and content. Interviews were transcribed and coded using a constant comparative approach. Three main themes were identified: sexual behavior, app experiences and feedback, and pre-exposure prophylaxis. ResultsOverall, participants found the app acceptable and thought that it would be a useful tool for themselves and their peers. Participants reported appreciating having a comprehensive information source available to them on their phones and reported learning more about HIV, sexually transmitted infections, and pre-exposure prophylaxis via the app. They also reported appreciating the inclusive language that was used throughout the app. Although the app included some resources on mental health and substance use, participants reported that they would have appreciated more resources and information in these areas as well as more comprehensive information about other health concerns, including hormone therapy. Representative quotes are presented for each of the identified themes. ConclusionsThere is a desire to have greater access to reliable sexual health information among transmasculine people. Mobile apps like Transpire are an acceptable intervention to increase access to this information and other resources. More evidence is needed, however, from more racially and ethnically diverse samples of transmasculine people