A call to action: Addressing the reproductive health needs of women with drug-resistant tuberculosis

Although there is substantial risk to maternal and neonatal health in the situation of pregnancy during treatment for rifampicin-resistant tuberculosis (RR-TB), there is little evidence to guide clinicians as to how to manage this complexity. Of the 49 680 patients initiated on RR-TB treatment from 2009 to 2014 in South Africa, 47% were women and 80% of them were in their reproductive years (15 - 44). There is an urgent need for increased evidence of the safety of RR-TB treatment during pregnancy, increased access to contraception during RR-TB treatment, and inclusion of reproductive health in research on the prevention and treatment of TB

Biallelic VARS variants cause developmental encephalopathy with microcephaly that is recapitulated in vars knockout zebrafish

Aminoacyl tRNA synthetases (ARSs) link specific amino acids with their cognate transfer RNAs in a critical early step of protein translation. Mutations in ARSs have emerged as a cause of recessive, often complex neurological disease traits. Here we report an allelic series consisting of seven novel and two previously reported biallelic variants in valyl-tRNA synthetase (VARS) in ten patients with a developmental encephalopathy with microcephaly, often associated with early-onset epilepsy. In silico, in vitro, and yeast complementation assays demonstrate that the underlying pathomechanism of these mutations is most likely a loss of protein function. Zebrafish modeling accurately recapitulated some of the key neurological disease traits. These results provide both genetic and biological insights into neurodevelopmental disease and pave the way for further in-depth research on ARS related recessive disorders and precision therapies

The chemokine RANTES is secreted by human melanoma cells and is associated with enhanced tumour formation in nude mice

Modulation of tumour cell growth by tumour-infiltrating leucocytes is of high importance for the biological behaviour of malignant neoplasms. In melanoma, tumour-associated macrophages (TAM) and tumour-infiltrating lymphocytes (TIL) are of particular interest as inhibitors or enhancers of cell growth. Recruitment of leucocytes from the peripheral blood into the tumour site is mediated predominantly by chemotaxins, particularly by the group of chemokines

Macrophages Homing to Metastatic Lymph Nodes Can Be Monitored with Ultrasensitive Ferromagnetic Iron-Oxide Nanocubes and a 1.5T Clinical MR Scanner

Background: Due to the ability of macrophages to specifically home to tumors, their potential use as a delivery vehicle for cancer therapeutics has been suggested. Tracking the delivery and engraftment of macrophages into human tumors with a 1.5T clinical MR scanner requires the development of sensitive contrast agents for cell labeling. Therefore, this study aimed to determine whether intravenously injected macrophages could target a primary tumor as well as metastatic LNs, and whether these cells could be detected in vivo by MRI. Methodology: Peritoneal macrophages were obtained from BALB/c nude mice. The viability, phagocytotic capacity and migratory activity of the macrophages were assessed. MR imaging was performed using a clinical 1.5 T MR scanner and we estimated the T2 * of the labeled macrophages. Metastatic lymph nodes were produced in BALB/c nude mice. We administrated 2610 6 macrophages labeled with 50 mg Fe/mL FIONs intravenously into the mice. In the 3D T2 * GRE MR images obtained one day after the injection of the labeled macrophages or FION solution, the percentages of pixels in the tumors or LNs below the minimum normalized SI (signal intensity) threshold were summated and reported as the black pixel count (%) for the FION hypointensity. Tumors in the main tumor model as well as the brachial, axillary and inguinal lymph nodes in the metastatic LN models were removed and stained. For all statistical analyses, single-group data were assessed using t test or the Mann-Whitney test. Repeated measurements analysis of variance (ANOVA) with Tukey–Krame

COVID-19: Rapid antigen detection for SARS-CoV-2 by lateral flow assay: A national systematic evaluation of sensitivity and specificity for mass-testing

Background Lateral flow device (LFD) viral antigen immunoassays have been developed around the world as diagnostic tests for SARS-CoV-2 infection. They have been proposed to deliver an infrastructure-light, cost-economical solution giving results within half an hour. Methods LFDs were initially reviewed by a Department of Health and Social Care team, part of the UK government, from which 64 were selected for further evaluation from 1st August to 15th December 2020. Standardised laboratory evaluations, and for those that met the published criteria, field testing in the Falcon-C19 research study and UK pilots were performed (UK COVID-19 testing centres, hospital, schools, armed forces). Findings 4/64 LFDs so far have desirable performance characteristics (orient Gene, Deepblue, Abbott and Innova SARS-CoV-2 Antigen Rapid Qualitative Test). All these LFDs have a viral antigen detection of >90% at 100,000 RNA copies/ml. 8951 Innova LFD tests were performed with a kit failure rate of 5.6% (502/8951, 95% CI: 5.1–6.1), false positive rate of 0.32% (22/6954, 95% CI: 0.20–0.48). Viral antigen detection/sensitivity across the sampling cohort when performed by laboratory scientists was 78.8% (156/198, 95% CI 72.4–84.3). Interpretation Our results suggest LFDs have promising performance characteristics for mass population testing and can be used to identify infectious positive individuals. The Innova LFD shows good viral antigen detection/sensitivity with excellent specificity, although kit failure rates and the impact of training are potential issues. These results support the expanded evaluation of LFDs, and assessment of greater access to testing on COVID-19 transmission. Funding Department of Health and Social Care. University of Oxford. Public Health England Porton Down, Manchester University NHS Foundation Trust, National Institute of Health Research

Mobile Payload Element (MPE): Concept study for a sample fetching rover for the ESA Lunar Lander Mission

In late 2010, the DLR Space Administration invited the German industry to submit a proposal for a study about a Mobile Payload Element (MPE), which could be a German national contribution to the ESA Lunar Lander Mission. Several spots in the south polar region of the moon come into consideration as landing site for this mission. All possible spots provide sustained periods of solar illumination, interrupted by darkness periods of several 10 h. The MPE is outlined to be a small, autonomous, innovative vehicle in the 10 kg class for scouting and sampling the environment in the vicinity of the lunar landing site. The novel capabilities of the MPE will be to acquire samples of lunar regolith from surface, subsurface as well as shadowed locations, define their geological context and bring them back to the lander. This will enable access to samples that are not contaminated by the lander descent propulsion system plumes to increase the chances of detecting any indigenous lunar volatiles contained within the samples. Kayser-Threde, as prime industrial contractor for Phase 0/A, has assembled for this study a team of German partners with relevant industrial and institutional competence in space robotics and lunar science. The primary scientific objective of the MPE is to acquire clearly documented samples and to bring them to the lander for analysis with the onboard Lunar Dust Analysis Package (L-DAP) and Lunar Volatile Resources Analysis Package (L-VRAP). Due to the unstable nature of volatiles, which are of particular scientific interest, the MPE design needs to provide a safe storage and transportation of the samples to the lander. The proposed MPE rover concept has a four-wheeled chassis configuration with active suspension, being a compromise between innovation and mass efficiency. The suspension chosen allows a compact stowage of the MPE on the lander as well as precise alignment of the solar generators and instruments. Since therefore no further complex mechanics are necessary, the active suspension significantly contributes to the lightweight MPE design. The thermal control system enables the MPE to operate in shaded areas for about 2 h and hibernate darkness periods of about 14 h. Increasing the hibernation capability requires additional battery capacity and thus increases the MPE mass. As operational modes teleoperations from earth and autonomous navigation are foreseen. The MPE payload includes navigation cameras, a close-up imager and a mole as sampling device. The MPE phase 0/A study finished in early 2012. This article describes the resulting MPE rover concept with focus on its scientific benefit for the Lunar Lander Mission