Characterization of Natural Killer Cell Phenotype and Function during Recurrent Human HSV-2 Infection

Human natural killer (NK) cell differentiation, characterized by a loss of NKG2A in parallel with the acquisition of NKG2C, KIRs, and CD57 is stimulated by a number of virus infections, including infection with human cytomegalovirus (CMV), hantavirus, chikungunya virus, and HIV-1. Here, we addressed if HSV-2 infection in a similar way drives NK cell differentiation towards an NKG2A-NKG2C+KIR+CD57+ phenotype. In contrast to infection with CMV, hantavirus, chikungunya virus, and HIV-1, recurrent HSV-2 infection did not yield an accumulation of highly differentiated NK cells in human peripheral blood. This outcome indicates that human HSV-2 infection has no significant imprinting effect on the human NK cell repertoire

Diphosphanylmetallocenes of Main-Group Elements

Several 1,1’-diphosphanyl-substituted metallo cenes of magnesium (magnesocenes) were synthesized, structurally characterized, and their reactivity and coordina tion chemistry were investigated. Transmetalation of these magnesocenes gives access to group 14 metallocenes (tetre locenes), as well as to group 15 stibonocenes. These s- and p-block metallocenes represent a novel class of bis(phos phanyl) ligands, exhibiting Lewis-amphiphilic character. Their coordination chemistry towards different transition-metal and main-group fragments was investigated and different complexes are presented

Making cough count in tuberculosis care

Cough assessment is central to the clinical management of respiratory diseases, including tuberculosis (TB), but strategies to objectively and unobtrusively measure cough are lacking. Acoustic epidemiology is an emerging field that uses technology to detect cough sounds and analyze cough patterns to improve health outcomes among people with respiratory conditions linked to cough. This field is increasingly exploring the potential of artificial intelligence (AI) for more advanced applications, such as analyzing cough sounds as a biomarker for disease screening. While much of the data are preliminary, objective cough assessment could potentially transform disease control programs, including TB, and support individual patient management. Here, we present an overview of recent advances in this field and describe how cough assessment, if validated, could support public health programs at various stages of the TB care cascade

Validation of rapid, molecular testing for COVID-19 and integration with TB diagnostics

COVID-19 and tuberculosis (TB) are currently the top two infectious diseases by mortality. Universally, personnel and financial resources from existing disease control programs have been diverted to the COVID-19 response. For TB, this has resulted in a steep decline in case notifications, and, for the first time since 2015, annual mortality increased. Strategies to simultaneously address both diseases could help recover missing TB cases and ensure people suffering from either disease receive appropriate care. We have undertaken two initiatives towards integrating testing for COVID-19 and TB in Lima, Peru. First, we investigated rapid testing for COVID-19 and TB in one clinical encounter using a molecular multi-disease testing platform that is available through Peru. Second, we are evaluating the use of cough classification artificial intelligence models, with data collected using a smartphone. Clinical and qualitative aspects of the intervention are being assessed. The findings from our studies will likely be generalizable to other urban settings with high TB burdens

Tuberculosis treatment monitoring tests during routine practice : study design guidance

Funding: CMD reports project-specific funding from WHO; grants for various projects on TB diagnostics development and evaluation support from FIND, Geneva; grants for Rapid Research in Diagnostics Development (R2D2) for TB network from National Institutes of Health (NIH) US; grants for various projects on TB diagnostics development and evaluation from German Center for Infectious Disease Research (DZIF). EL-HM reports support for this project from the New Diagnostics Working GroupdBiomarkers Taskforce. Funding for the study was provided by the New Diagnostics Working Group-Biomarkers Taskforce. The New Diagnostics Working Group was supported by funding received from the Stop TB Partnership and USAID.Scope The current tools for tuberculosis (TB) treatment monitoring, smear microscopy and culture, cannot accurately predict poor treatment outcomes. Research into new TB treatment monitoring tools (TMT) is growing, but data are unreliable. In this document, we aim to provide guidance for studies investigating and evaluating TB TMT for use during routine clinical care. Here, a TB TMT would guide treatment during the course of therapy, rather test for cure at the regimen’s end. This document does not cover the use of TB TMTs as surrogate endpoints in the clinical trial context. Methods Guidelines were initially informed by experiences during a systematic review of TB TMTs. Subsequently, a small content expert group was consulted for feedback on initial recommendations. After revision, feedback from substantive experts across sectors was sought. Questions addressed by the guideline and Recommendations The proposed considerations and recommendations for studies evaluating TB TMTs for use during treatment in routine clinical care fall into eight domains. We provide specific recommendations regarding study design and recruitment; outcome definitions; reference standards; participant follow-up; clinical setting; study population; treatment regimen reporting; and index tests and data presentation. Overall, TB TMTs should be evaluated in a manner similar to diagnostic tests, but TB TMT accuracy must be assessed at multiple timepoints throughout the treatment course, and TB TMTs should be evaluated in study populations who have already received a diagnosis of TB. Study design and outcome definitions must be aligned with the developmental phase of the TB TMT under evaluation. There is no gold standard for TB treatment response, so different reference standards and comparator tests have been proposed, the selection of which will vary depending on the developmental phase of the TMT under assessment. The use of comparator tests can assist in generating evidence. Clarity is required when reporting of timepoints, TMT read-outs, and analysis results. Implementing these recommendations will lead to higher quality TB TMT studies which will allow data to be meaningfully compared, thereby facilitating the development of novel tools to guide individual TB therapy and improve treatment outcomes.Peer reviewe

Transcriptional regulation of the sodium channel gene (SCN5A) by GATA4 in human heart

Aberrant expression of the sodium channel gene (SCN5A) has been proposed to disrupt cardiac action potential and cause human cardiac arrhythmias, but the mechanisms of SCN5A gene regulation and dysregulation still remain largely unexplored. To gain insight into the transcriptional regulatory networks of SCN5A, we surveyed the promoter and first intronic regions of the SCN5A gene, predicting the presence of several binding sites for GATA transcription factors (TFs). Consistent with this prediction, chromatin immunoprecipitation (ChIP) and sequential ChIP (Re-ChIP) assays show co-occupancy of cardiac GATA TFs GATA4 and GATA5 on promoter and intron 1 SCN5A regions in freshfrozen human left ventricle samples. Gene reporter experiments show GATA4 and GATA5 synergism in the activation of the SCN5A promoter, and its dependence on predicted GATA binding sites. GATA4 and GATA6 mRNAs are robustly expressed in fresh-frozen human left ventricle samples as measured by highly sensitive droplet digital PCR (ddPCR). GATA5 mRNA is marginally but still clearly detected in the same samples. Importantly, GATA4 mRNA levels are strongly and positively correlated with SCN5A transcript levels in the human heart. Together, our findings uncover a novel mechanism of GATA TFs in the regulation of the SCN5A gene in human heart tissue. Our studies suggest that GATA5 but especially GATA4 are main contributors to SCN5A gene expression, thus providing a new paradigm of SCN5A expression regulation that may shed new light into the understanding of cardiac disease

Utilisation de l'analyse automatisée de la parole et des mesures des émotions faciales sur des vidéos pour évaluer les effets des dispositifs de relaxation: une étude pilote

International audienceRapid relaxation installations in order to reduce stress appear more and more in public or work places. However, the effects of such devices on physiological and psychological parameters have not been scientifically tested yet. This pilot study (N=40) evaluates the variations of vocal speech and facial emotions parameters in 3-minute videos of participant recorded just before and after relaxation, on four different groups, three of them using a different rapid (15 minutes) sensorial immersion relaxation devices and a control group using no device. Vocal speech parameters included sound duration, pause mean duration, sound duration ratio, mean vocal frequency (F0), standard deviation of F0, minimum and maximum of F0, jitter and shimmer. Facial emotion analysis included neutral, happy, sad, surprised, angry, disgusted, scared, contempt, valence and arousal. The objective of this study is to evaluate different parameters of the automated vocal and facial emotions analysis that could be of use to evaluate the relaxation effect of different devices and to measure their variations in the different experimental groups. We identified significant parameters that can be of use for evaluating rapid relaxation devices, particularly voice prosody and minimum vocal frequency, and some facial emotion such as happy, sad, the valence and arousal. Those parameters allowed us to discriminate distinct effects of the different devices used: in G1 (control) and G2 (spatialized sounds), we observed a slowdown in voice prosody; in G3 (Be-Breathe) a decrease in minimum vocal frequency and an increase of arousal; while in G4 (3D-video) we found an increase in facial emotion valence (happy increasing and sad decreasing). Other parameters tested were not affected by relaxation.Les installations de relaxation rapide afin de réduire le stress apparaissent de plus en plus dans les lieux publics ou de travail. Cependant, les effets de ces dispositifs sur les paramètres physiologiques et psychologiques n'ont pas encore été testés scientifiquement. Cette étude pilote (N = 40) évalue les variations des paramètres de la parole vocale et des émotions faciales dans des vidéos de 3 minutes de participant enregistrées juste avant et après la relaxation, sur quatre groupes différents, trois d'entre eux utilisant une immersion sensorielle rapide (15 minutes) différente. des appareils de relaxation et un groupe témoin n'utilisant aucun appareil. Les paramètres de la parole vocale comprenaient la durée du son, la durée moyenne de la pause, le rapport de durée du son, la fréquence vocale moyenne (F0), l'écart type de F0, le minimum et le maximum de F0, la gigue et le miroitement. L'analyse des émotions faciales comprenait la neutralité, la joie, la tristesse, la surprise, la colère, le dégoût, la peur, le mépris, la valence et l'excitation. L'objectif de cette étude est d'évaluer différents paramètres de l'analyse automatisée des émotions vocales et faciales qui pourraient être utiles pour évaluer l'effet de relaxation de différents appareils et mesurer leurs variations dans les différents groupes expérimentaux. Nous avons identifié des paramètres significatifs qui peuvent être utiles pour évaluer les dispositifs de relaxation rapide, en particulier la prosodie de la voix et la fréquence vocale minimale, et certaines émotions faciales telles que le bonheur, la tristesse, la valence et l'excitation. Ces paramètres nous ont permis de discriminer des effets distincts des différents appareils utilisés: pour G1 (contrôle) et G2 (sons spatialisés), nous avons observé un ralentissement de la prosodie vocale; dans le groupe G3 (Be-Breathe) une diminution de la fréquence vocale minimale et une augmentation de l'éveil; enfin, pour G4 (vidéo 3D), nous avons trouvé une augmentation de la valence des émotions faciales (augmentation de la joie et diminution de la tristesse). Les autres paramètres testés n'ont pas été affectés par la relaxation