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Background\ud \ud One of the main barriers of the management of household tuberculosis child contacts is the necessity for parents to bring healthy children to the facility. We assessed the feasibility of a community intervention for tuberculosis (TB) household child contact management and the conditions for its evaluation in a cluster randomized controlled trial in Cameroon and Uganda.\ud \ud \ud \ud Methods\ud \ud We assessed three dimensions of feasibility using a mixed method approach: (1) recruitment capability using retrospective aggregated data from facility registers; (2) acceptability of the intervention using focus group discussions with TB patients and in-depth interviews with healthcare providers and community leaders; and (3) adaptation, integration, and resources of the intervention in existing TB services using a survey and discussions with stakeholders.\ud \ud \ud \ud Results\ud \ud Reaching the sample size is feasible in all clusters in 15 months with the condition of regrouping 2 facilities in the same cluster in Uganda due to decentralization of TB services. Community health worker (CHW) selection and training and simplified tools for contact screening, tolerability, and adherence of preventive therapy were key elements for the implementation of the community intervention. Healthcare providers and patients found the intervention of child contact investigations and TB preventive treatment management in the household acceptable in both countries due to its benefits (competing priorities, transport cost) as compared to facility-based management. TB stigma was present, but not a barrier for the community intervention. Visit schedule and team conduct were identified as key facilitators for the intervention.\ud \ud \ud \ud Conclusions\ud \ud This study shows that evaluating a community intervention for TB child contact management in a cluster randomized trial is feasible in Cameroon and Uganda.\ud \ud \ud \ud Trial registration\ud \ud Clini calTr ials. gov NCT03832023. Registered on February 6th 2019.

Nowadays, ticks and tick-borne pathogens (TBPs) are an increasing One Health problem. The main tick-borne diseases in Europe are Lyme borreliosis, granulocytic anaplasmosis and tick-borne encephalitis. Their vector is Ixodes ricinus, which has a wide geographical distribution and can feed on many different vertebrate hosts. It can acquire and/or transmit more than one pathogen to animals including humans at each blood-feeding stage. Tick co-infections and co-transmissions of pathogens by ticks have been demonstrated in diverse studies. For example, co-infections in ticks are common in the wild. In humans, a study of patients with chronic Lyme disease (confirmed by medical diagnosis) has demonstrated that among them 23.5 % of the patients show at least one co-infection with other tick borne pathogens like Babesia, Bartonella, Ehrlichia, and Anaplasma and 30% report two or more co-infections with those pathogens by laboratory diagnosis. The outcome of these co-infections and co-transmissions deserves to be considered with great interest because they are likely to lead to synergy and/or competition between pathogens. Those interactions could have ,consequences for individual pathogen fitness in mammalian hosts. In particular, individual infection ,rates can be reduced if pathogens directly compete for resources or via toxin production. Conversely, the down-regulation of the host immune response can result in an increased pathogen burden and facilitate transmission from host to vector. Thus, these interactions can potentially have a major impact on public health, both clinically and in terms of therapeutic applications. The small number of co-infection or multiple infection models to study the complex interactions between TBPs in co-infected ticks, and co-infected vertebrate hosts prompted us to establish co-infection models using two bacteria (Borrelia afzelii and Anaplasma phagocytophilum) and a virus (Tick-Borne Encephalitis ,Virus (TBEV)) in ticks (I. ricinus) and mammals (mice). Ticks were co-infected using different techniques (artificial feeding system, capillary feeding and micro-injection), whereas the mice were co-infected by inoculation of the different pathogens (intraperitoneal/subcutaneous/intradermal). Our preliminary results obtained: (i) in mice, single and co-infection with TBEV and B. afzelii were established using different concentrations/amounts of each pathogen; (ii) in ticks, single infections and co-infection were set up using an artificial feeding system with B. afzelii and TBEV; (iii) in ticks, single infections and co-infections were set up by capillary feeding and microinjection by B. afzelii, TBEV and A. phagocytophilum. These preliminary results are the first steps to studying the transmission success of these pathogens from co-infected ticks to non-infected mice and from co-infected mice to non-infected ticks.

As part of our continuing study of apoptosis-inducing saponins from CameroonianAlbiziagenus, one new triterpenoid saponin, named adianthifolioside J (1), together with the known gummiferaoside E (2), were isolated fromAlbizia adianthifoliastems. The structure of the new saponin (1), was established on the basis of extensive analysis of 1 D and 2 D NMR (H-1-,C-13-NMR, DEPT, COSY, TOCSY, NOESY, HSQC, HSQC-TOCSY and HMBC) and HRESIMS experiments, and by chemical evidence as 3-O-[beta-D-xylopyranosyl-(1 -> 2)-beta-D-fucopyranosyl-(1 -> 6)-beta-D-glucopyranosyl]-21-O-{(2E,6S)-2-(hydroxymethyl)-6-methyl-6-O-{4-O-[(2E,6S)-2,6-dimethyl-6-O-(beta-D-quinovopyranosyl)octa-2,7-dienoyl]-(beta-D-quinovopyranosyl)octa-2,7-dienoyl]}acacic acid-28-O-beta-D-glucopyranosyl-(1 -> 3)-[5-O-acetyl-alpha-L-arabinofuranosyl-(1 -> 4)]-alpha-L-rhamnopyranosyl-(1 -> 2)-beta-D-glucopyranosyl ester (1).The pro-apoptotic activity of the new isolated saponin1was evaluated, using Annexin V-FITC binding assay, on the A431 human epidermoid cancer cell. The result showed that adianthifolioside J (1) displayed weak pro-apoptotic activity.

In our continuing studies on saponins from Cameroonian medicinal plants, phytochemical investigation of Chytranthus klaineanus stem barks led to the isolation of three new oleanane-type saponins, named Klaineanosides A-C(1-3). Their structures were established by extensive analysis of their spectral data, mainly 1D(H-1, C-13 NMR, and DEPT) and 2D (COSY, HSQC, NOESY, HSQC-TOCSY, and HMBC) NMR experiments, and mass spectrometry as 3-O-beta-D-glucopyranosyl-(1 -> 3)-beta-D-xylopyranosyl-(1 -> 4)[-beta-D-xylopyranosyl(1 -> 3)-beta-D-xylopyranosyl(1 -> 3)-alpha-L-rhamnopyranosyl-(1 -> 2)]-alpha-L-arabinopyranosylhederagenin(1), 3-O-beta-D-glucopyr-anosyl-(1 -> 3)-beta-D-xylopyranosyl-(1 -> 4)[ beta-D-xylopyranosyl(1 -> 3)-alpha-L-rhamnopyranosyl-(1 -> 2)]-alpha-L-arabinopyr-anosylhederagenin(2), and 3-O-beta-D-xylopyranosyl(1 -> 4)-beta-D-glucopyranosyl-(1 -> 3)-alpha-L-rhamnopyranosyl-(1 -> 2)-alpha-L-arabinopyranosylhederagenin(3). These triterpene saponins 1-3 have hederagenin as aglycone with a-(3)Rha-(2)Ara-(3)hederagenin oligosaccharidic sequence usually found in Sapindaceae family.

Serum protein S100B determinations have been recently suggested as markers of traumatic brain injury. However, little is known about the effects of extracranial injuries on S100B levels in trauma patients.We studied 224 patients with head trauma (54 of whom also had extracranial injuries), 155 patients with various types of extracranial injuries, and 8 healthy pilots exposed to high Gz forces. The head trauma patients had either no brain injury (n = 35), mild brain injury (n = 165), or moderate to severe brain injury (n = 24). The extracranial injuries were divided into small and large injuries. Serum protein S100B levels were determined from samples taken within 6 hours after the trauma event.The head trauma patients had a significantly higher median S100B (0.17 microg/L) than the patients with extracranial injuries (0.07 microg/L) (p0.001). Serum S100B levels also correlated with the severity of brain injury (p0.001), the highest values occurring in the patients with moderate to severe brain injury (1.27 microg/L). However, large extracranial injuries also elevated S100B levels (0.35 microg/L), whereas small extracranial injuries in the absence of head trauma did not significantly affect S100B levels (0.07 microg/L). Above the cutoff level of 0.13 microg/L, there were 61% of the head trauma patients and 26% of those with extracranial injuries (Pearson chi test, p0.001). However, only 4% of the patients with purely extracranial injuries had a concentration of S100B above the cutoff level of 0.50 microg/L, whereas the head trauma patients with moderate to severe brain injury exceeded this cutoff in 67% of the cases. Exposure to high Gz forces did not influence serum S100B levels in healthy individuals.We conclude that serum S100B is a sensitive marker of brain injury, which correlates with the severity of the injury. Large extracranial injuries also elevate S100B levels. However, S100B has a high negative predictive power, and the finding of a normal S100B value shortly after trauma should thus exclude significant brain injury with a high accuracy.

Positive pressure breathing for G-protection (PBG) reduces the need for fighter pilots to use the fatiguing anti-G straining maneuver (AGSM) so that they can better endure high acceleration (+Gz). The aim of the study was to determine the differences in cerebral blood flow during flight with an extended-coverage anti-G suit (ECGS) with AGSM or with PBG.Subjects were eight male members of the Finnish Air Force. Each was studied in the laboratory at +1 Gz and then during two identical flights in the back seat of the BAe Hawk Mk 51 jet trainer at +6 Gz, first with AGSM and second with PBG (24 mmHg). Regional cerebral blood flow (rCBF) was measured by injecting (99 m) Tc-ECD for deposition at +6 Gz, then scanning the subject in the laboratory an hour later using single photon emission computed tomography (SPECT).The rCBF was 30% below baseline for both the AGSM and PBG.PBG maintained CBF at +6 Gz without the need for the fatiguing AGSM.