[After the pandemic is before the pandemic: And how interdisciplinary research can help here]. / Nach der Pandemie ist vor der Pandemie: Und wie interdisziplinäre Forschung hier helfen kann.

Aviation is among the social sectors most impacted by the COVID-19 pandemic, and at the same time has contributed to the rapid global spread of the SARS-CoV-2 virus. SARS-CoV-2 is one of the coronaviruses that have led to outbreaks such as MERS-CoV in the past. This group of pathogens, as well as others that may be unknown at this time, will continue to challenge our society in the future. In order to be able to react better, a research training group was established at DLR in cooperation with 6 institutes, which will develop interdisciplinary approaches to researching and combating current and future pandemics. Engineers, physicists, software developers, biologists and physicians are working closely together on new concepts and the development of interdisciplinary knowledge in order to better control and contain future pandemics and to be able to react in a more targeted manner. One focus is the reduction of germ contamination in airplanes but also in other means of public transport such as buses and trains. In this review, we provide an overview of the baseline situation and possible approaches to address future pandemic challenges.

Discovery of the Potent and Selective ATR Inhibitor Camonsertib (RP-3500).

ATR is a key kinase in the DNA-damage response (DDR) that is synthetic lethal with several other DDR proteins, making it an attractive target for the treatment of genetically selected solid tumors. Herein we describe the discovery of a novel ATR inhibitor guided by a pharmacophore model to position a key hydrogen bond. Optimization was driven by potency and selectivity over the related kinase mTOR, resulting in the identification of camonsertib (RP-3500) with high potency and excellent ADME properties. Preclinical evaluation focused on the impact of camonsertib on myelosuppression, and an exploration of intermittent dosing schedules to allow recovery of the erythroid compartment and mitigate anemia. Camonsertib is currently undergoing clinical evaluation both as a single agent and in combination with talazoparib, olaparib, niraparib, lunresertib, or gemcitabine (NCT04497116, NCT04972110, NCT04855656). A preliminary recommended phase 2 dose for monotherapy was identified as 160 mg QD given 3 days/week.

Discovery of an Orally Bioavailable and Selective PKMYT1 Inhibitor, RP-6306.

PKMYT1 is a regulator of CDK1 phosphorylation and is a compelling therapeutic target for the treatment of certain types of DNA damage response cancers due to its established synthetic lethal relationship with CCNE1 amplification. To date, no selective inhibitors have been reported for this kinase that would allow for investigation of the pharmacological role of PKMYT1. To address this need compound 1 was identified as a weak PKMYT1 inhibitor. Introduction of a dimethylphenol increased potency on PKMYT1. These dimethylphenol analogs were found to exist as atropisomers that could be separated and profiled as single enantiomers. Structure-based drug design enabled optimization of cell-based potency. Parallel optimization of ADME properties led to the identification of potent and selective inhibitors of PKMYT1. RP-6306 inhibits CCNE1-amplified tumor cell growth in several preclinical xenograft models. The first-in-class clinical candidate RP-6306 is currently being evaluated in Phase 1 clinical trials for treatment of various solid tumors.

Neonatal and postneonatal tetanus at a referral hospital in Kamsar, Guinea: a retrospective audit of paediatric records (2014-2018).

BACKGROUND: Tetanus is a vaccine-preventable disease caused by the bacterium Clostridium tetani. In 2018, all of Guinea was considered to be at risk of the disease and the country is currently in the elimination phase. METHODS: A 5-y audit (1 January 2014-31 December 2018) of all admissions to the neonatal and general paediatric units of Kamsar Hospital (Western Guinea) was undertaken to identify cases of neonatal tetanus (NNT) and postneonatal tetanus (PNNT). RESULTS: There were 5670 admissions during the study period, of which 39 (0.7%) were due to tetanus (22 NNT and 17 PNNT). Among NNT patients, the bacterial entry site was the umbilical cord (n=20) or wound following circumcision (n=2). For PNNT, the entry site was surface wound (n=12), limb fracture (n=1) or could not be established (n=4). A majority of the patients (36/39, 92.3%) were born to unvaccinated mothers or those who received suboptimal vaccination during pregnancy. Overall, 21 (53.8%) children died within 7 d of admission with a higher mortality observed among neonates (16/22, 72.7%) compared with postneonates (5/17, 29.4%). CONCLUSIONS: Tetanus was a rare cause of admission at Kamsar Hospital with a very high case fatality rate. The disease primarily occurred among children born to mothers who were unvaccinated/inadequately vaccinated during pregnancy.

Infections respiratoires aigües virales chez les enfants de moins de 15 ans à Conakry: étiologies et prise en charge / Acute viral respiratory infections of children aged 0-15 years in the city of Conakry: aetiologies and management

Introduction. Les infections respiratoires aiguës (IRA) sont des pathologies ubiquitaires très fréquentes, touchant aussi bien les adultes que les enfants. L'inclusion des vaccins conjugués, contre les pneumocoques et l'Haemophilus influenzae type B a modifié l'épidémiologie en réduisant la prévalence de ces bactéries dans les atteintes infectieuses respiratoires, la prédominance virale est devenue la règle. Notre travail avait pour objectif d'identifier les principaux virus responsables d'IRAS chez les enfants au service de pédiatrie de Donka de décrire la prise en charge des enfants. Patients et méthodes. Étude descriptive prospective de 6 mois allant du 01 Avril au 30 Septembre 2022 incluant les enfants admis au service pour IRAS dont une PCR a été réalisée sur prélèvement nasopharyngé. Résultats. Une proportion de 3,3% des 1584 enfants avaient une IRA virale. 51,1% avaient moins de 5 ans. La proportion des filles était de 63,05% et 76,09% des enfants étaient vaccinés selon le programme élargi de vaccination (PEV). Les motifs de consultation les plus fréquents étaient : fièvre, difficulté respiratoire, asthénie physique, myalgie et toux. La bronchiolite était le diagnostic le plus fréquent. Le diagnostic clinique et radiologique était dominé par la bronchiolite, la bronchopneumonie et la pneumonie. La PCR était positive dans 3,26% des cas dont 2/3 pour le virus influenza et 1/3 pour le coronavirus. Le paracétamol, l'oxygénation, l'antibiothérapie et le sérum physiologique dominaient le traitement. Conclusion. La prévalence des IRA reste élevée avec une faible implication virale. Une étude plus poussée comprenant la microbiologie des prélèvements nasopharyngés et la PCR est nécessaire

Introduction. Acute respiratory infections (ARI) are very common ubiquitous pathologies, affecting both adults and children. The inclusion of conjugate vaccines, against pneumococci and Haemophilus influenzae type b, has changed the epidemiology by reducing the prevalence of these bacteria in respiratory infectious diseases, viral predominance has become the rule. The aim of our study was to identify the main viruses responsible for ARI in children at the Donka Pediatric Department and to secribe the management of patients. Patients and methods. This was a prospective descriptive study of 6 months from 01 April to 30 September 2022 including children admitted to the service for IRAS whose PCR was performed on nasopharyngeal swab. Results. A proportion of 3.3% of the 1584 children had viral SARI. 51.1% were under 5 years of age. The proportion of girls was 63.05% and 76.09% of children were vaccinated according to the EPI. The most common reasons for consultations were fever, difficulty breathing, physical asthenia, myalgia and cough. Bronchiolitis was the most common diagnosis, Clinical and radiological diagnosis was dominated by bronchiolitis, bronchopneumonia and pneumonia. PCR was positive in 3.26% of cases including 2/3 for influenza virus and 1/3 for coronavirus. Paracetamol, oxygenation, antibiotic therapy and saline dominated treatment. Conclusion. The prevalence of SARI remains high with low viral involvement. Further study including bacteriology of nasopharyngeal specimens and PCR is needed

Multiple criteria decision analysis approach to consider therapeutic innovations in the emergency department: The methoxyflurane organizational impact in acute trauma pain.

BACKGROUND: Acute trauma pain is poorly managed in the emergency department (ED). The reasons are partly organizational: ED crowding and rare trauma care pathways contribute to oligoanalgesia. Anticipating the organizational impact of an innovative care procedure might facilitate the decision-making process and help to optimize pain management. METHODS: We used a multiple criteria decision analysis (MCDA) approach to consider the organizational impact of methoxyflurane (self-administered) in the ED, introduced alone or supported by a trauma care pathway. A MCDA experiment was designed for this specific context, 8 experts in emergency trauma care pathways (leading physicians and pharmacists working in French urban tertiary hospitals) were recruited. The study involved four steps: (i) Selection of organizational criteria for evaluating the innovation's impact; (ii) assessment of the relative weight of each criterion; (iii) choice of appropriate scenarios for exploring the organizational impact of MEOX under various contexts; and (iv) software-assisted simulation based on pairwise comparisons of the scenarios. The final outcome measure was the expected overall organizational impact of methoxyflurane on a 0-to-100 scale (score >50: positive impact). RESULTS: Nine organizational criteria were selected. "Mean length of stay in the ED" was the most weighted. Methoxyflurane alone obtained 59 as a total score, with a putative positive impact for eight criteria, and a neutral effect on one. When a trauma care pathway was introduced concomitantly, the impact of methoxyflurane was greater overall (score: 75) and for each individual criterion. CONCLUSIONS: Our model highlighted the putative positive organizational impact of methoxyflurane in the ED-particularly when supported by a trauma care pathway-and the relevance of expert consensus in this particular pharmacoeconomic context. The MCDA approach could be extended to other research fields and healthcare challenges in emergency medicine.

[Epidemiological and clinical profile of children with Coronavirus disease (COVID-19) at the Center for the Treatment of Epidemics and Infection Prevention (CTEIP) of the University Hospital of Donka in Conakry]. / Profil épidémiologique et clinique des enfants atteints de la maladie à coronavirus (COVID-19) au Centre de Traitement des Epidémies et Prévention des Infections (CTEPI) du CHU de Donka à Conakry.

COVID-19 is caused by SARS-CoV-2 virus, which is genetically similar to severe acute respiratory syndrome (SARS) virus. In pediatrics, it has a benign clinical course. Since the outbreak of COVID-19 pandemic in Guinea, whose epicenter was Conakry, pediatric cases have been reported at the CTEIP in Donka. The purpose of this study was to determine their epidemiological profile. We conducted a descriptive cross-sectional study of children aged 0-16 years admitted to the CTEIP, Donka, over a period of four months. Out of 7308 patients, coming predominantly from 5 communes of Conakry and hospitalized in the CTEPI, 189 were aged between 0 and 16 years (2 .59%). The majority of patients were within the age-group 0-4-years (38.62%) with a sex-ratio (F/M) of 1.52; 62.96% were students, 70% of children lived in Conakry, 28.57% of mothers were traders and contact persons (39.68%); 37.57% of fathers were civil servants, 2.65% of children had a history of sickle cell disease and 1.59% had allergic rhinitis. Asymptomatic patients accounted for 52.38% of cases and diagnosed patients were 74.6%. Symptoms included fever, rhinorrhea, headache, cough, abdominal pain, sneezing, diarrhea, physical asthenia. The incidence of COVID-19 among children hospitalized in the CTEIP of Donka is low. Children aged 5 years and older are more affected and nearly 50% are asymptomatic. Common symptoms are fever, headache, rhinorrhea, cough, abdominal pain, sneezing, diarrhea, physical asthenia.

Néoplasies intraépithéliales du col utérin chez la congolaise à Kinshasa : intérêt des biomarqueurs immunohistochimiques

Contexte et objectif.Bien que le cancer du col utérin soit le deuxième cancer plus fréquent chez la femme en Afrique, le recours aux biomarqueurs immunohistochimiques reste exceptionnel en Afrique subsaharienne. La présente étude avait pour objectif de montrer l'apport des biomarqueurs p16 et Ki-67 dans le diagnostic des néoplasies intra-épithéliales du col utérin. Méthodes. C'était une étude rétrospective réalisée dans cinq laboratoires d'Anatomie Pathologique de Kinshasa. Des lames biopsiques ont été relues et reclassées par au moins deux pathologistes indépendants aux Cliniques Universitaires de Kinshasa en suivant la nomenclature de Bethesda/OMS. L'immunomarquage (p16 et Ki-67) a été réalisé avec un contrôle qualité externe en Europe. Résultats. 70 cas ont été inclus. Les 24 cas des néoplasies intra-épithéliales de haut grade (CIN2, CIN3 et CIS) étaient marquées positivement par p16 et Ki-67 alors que celles de bas grade étaient marquées positivement pour 41 cas de CIN1 et négativement pour 5 cas (3 de CIN1 et 2 de CP). Certaines lésions ont été requalifiées. L'immunomarquage était significativement associé au grade des néoplasies pour la p16 (p=0,001) et pour le Ki-67 (p=0,004). Conclusion. P16 et Ki-67 sont des biomarqueurs spécifiques et efficaces pour un diagnostic optimal des néoplasies intra-épithéliales du col utérin

Fréquence des néphropathies congénitales au Centre hospitalier universitaire de Donka à Conakry

Contexte et objectif. L'ampleur réelle des néphropathies congénitales est peu connue en Afrique et notamment en Guinée. L'objectif de cette étude était de déterminer la fréquence des néphropathies congénitales rencontrées. Méthodes. Cette étude documentaire de type descriptif sur la néphropathie congénitale, a été conduite entre les 1er janvier 2007 et 30 juin 2012, dans les services de pédiatrie et de chirurgie pédiatrique de Donka. Les paramètres d'intêret englobaient les données épidémiologiques, cliniques et paracliniques. Résultats. Parmi les 34.448 dossiers colligés, 26 présentaient une néphropathie congénitale. Il s'agissait des néphroblastomes (n=17), des syndromes de jonction pyélo-urétérale (n=6), d'une hydronéphrose sur rein multikystique gauche (n=1), d'un rein multikystique en ptose (n=1) et d'une ectopie rénale (n=1). Le sexe masculin était prépondérant (21/26) avec un sexe ratio de 4,2/1. Les enfants de 29 jours à 2 ans étaient les plus touchés. Conclusion. Les néphropathies congénitales sont paraissent moins fréquentes dans cette institution hospitalière, à cause du manque d'un plateau technique diagnostique optimal. Le diagnostic précoce des néphropathies congénitales devrait être fait dans la période prénatale ce qui permettrait une meilleure prise en charge des enfants affectés