Capacity Building in Sub-Saharan Africa as Part of the INTENSE-TBM Project During the COVID-19 Pandemic.

Tuberculous meningitis (TBM) is the most severe and disabling form of tuberculosis (TB), with at least 100,000 cases per year and a mortality rate of up to 50% in individuals co-infected with human immunodeficiency virus type 1 (HIV-1). To evaluate the efficacy and safety of an intensified anti-tubercular regimen and an anti-inflammatory treatment, the INTENSE-TBM project includes a phase III randomised clinical trial (TBM-RCT) in four countries in sub-Saharan Africa (SSA). Within this framework, we designed a comprehensive capacity-building work package ensuring all centres had, or would acquire, the ability to conduct the TBM-RCT and developing a network of skilled researchers, clinical centres and microbiology laboratories. Here, we describe these activities, identify strengths/challenges and share tools adaptable to other projects, particularly in low- and lower-middle income countries with heterogeneous settings and during the coronavirus disease 2019 (COVID-19) pandemic. Despite major challenges, TBM-RCT initiation was achieved in all sites, promoting enhanced local healthcare systems and encouraging further clinical research in SSA. In terms of certified trainings, the achievement levels were 95% (124/131) for good clinical practice, 91% (39/43) for good clinical laboratory practice and 91% (48/53) for infection prevention and control. Platform-based research, developed as part of capacity-building activities for specific projects, may be a valuable tool in fighting future infectious diseases and in developing high-level research in Africa.

The INTENSE-TBM project aimed to design a comprehensive work-package on capacity building, ensuring all centres would acquire the ability to conduct a phase III randomised clinical trial on TBM in sub-Saharan Africa, to reduce tuberculous meningitis mortality and morbidity in patients with/without HIV-1 co-infection. Therefore, the INTENSE-TBM project is an example of how an international clinical research consortium can provide opportunities to enhance local capacity building and promote centres without previous experience in clinical research. This article provides practical approaches for implementing effective capacity-building programmes. We highlight how to overcome limitations imposed by the COVID-19 pandemic to successfully complete clinics, laboratory set-ups and personnel training, so as to optimise resources and empower African institutions on a local level. At the same time, our experience shows how capacity-building programmes can deliver long-lasting impact that extends beyond the original aims of the project (e.g. HIV and TB), and support local health systems in fighting other infectious disease (e.g. COVID-19). Research projects in low- and lower-middle income countries with heterogeneous settings could stand to benefit the most.

Contemporary and historic factors influence differently genetic differentiation and diversity in a tropical palm.

Population genetics theory predicts loss in genetic variability because of drift and inbreeding in isolated plant populations; however, it has been argued that long-distance pollination and seed dispersal may be able to maintain gene flow, even in highly fragmented landscapes. We tested how historical effective population size, historical migration and contemporary landscape structure, such as forest cover, patch isolation and matrix resistance, affect genetic variability and differentiation of seedlings in a tropical palm (Euterpe edulis) in a human-modified rainforest. We sampled 16 sites within five landscapes in the Brazilian Atlantic forest and assessed genetic variability and differentiation using eight microsatellite loci. Using a model selection approach, none of the covariates explained the variation observed in inbreeding coefficients among populations. The variation in genetic diversity among sites was best explained by historical effective population size. Allelic richness was best explained by historical effective population size and matrix resistance, whereas genetic differentiation was explained by matrix resistance. Coalescence analysis revealed high historical migration between sites within landscapes and constant historical population sizes, showing that the genetic differentiation is most likely due to recent changes caused by habitat loss and fragmentation. Overall, recent landscape changes have a greater influence on among-population genetic variation than historical gene flow process. As immediate restoration actions in landscapes with low forest amount, the development of more permeable matrices to allow the movement of pollinators and seed dispersers may be an effective strategy to maintain microevolutionary processes.

Serotonergic-postsynaptic receptors modulate gripping-induced immobility episodes in male taiep rats.

The Taiep rat is a myelin mutant with a motor syndrome characterized by tremor, ataxia, immobility, epilepsy, and paralysis. The rat shows a hypomyelination followed by a progressive demyelination. During immobilities taiep rats show a REM-like sleep pattern and a disorganized sleep-wake pattern suggesting taiep rats as a model of narcolepsy-cataplexy. Our study analyzed the role of postsynaptic serotonin receptors in the expression of gripping-induced immobility episodes (IEs) in 8-month-old male taiep rats. The specific postsynaptic serotonin agonist +/-1-(2,5-dimethoxy-4-iodoamphetamine hydrochloride (+/-DOI) decreased the frequency of gripping-induced IEs, but that was not the case with alpha-methyl-serotonin maleate (alpha-methyl-5HT), a nonspecific postsynaptic agonist. Although the serotonin antagonists, ketanserine and metergoline, produced a biphasic effect, first a decrease followed by an increase with higher doses, similar effects were obtained with a mean duration of gripping-induced IEs. These findings correlate with the pharmacological observations in narcoleptic dogs and humans in which serotonin-reuptake inhibitors improve cataplexy, particularly in long-term treatment that could change the serotonin receptor levels. Polysomnographic recordings showed an increase in the awakening time and a decrease in the slow wave and rapid eye movement sleep concomitant with a decrease in immobilities after use of +/-DOI, this being stronger with the highest dose. Taken together, our results show that postsynaptic serotonin receptors are involved in the modulation in gripping-induced IEs caused by the changes in the organization of the sleep-wake cycle in taiep rats. It is possible that specific agonists, without side effects, could be a useful treatment in human narcoleptic patients.

Characterization of 10 microsatellite markers for the understorey Amazonian herb Heliconia acuminata.

We characterized 10 microsatellite loci for the plant Heliconia acuminata from the Biological Dynamics of Forest Fragments Project (Manaus, Brazil). Markers were screened in 61 individuals from one population and were found to be polymorphic with an average of eight alleles per locus. We found moderate to high levels of polymorphic information content, and observed and expected heterozygosities. All 10 markers are suitable for spatial genetic structure and parentage analyses and will be used for understanding H. acuminata dynamics across a fragmented landscape.

Enfermedad de Darier unilateral y segmentaria de tipo 1 / Unilateral type 1 segmental Darier disease

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The quality of reporting of randomized clinical trials published in Ophthalmology.

PURPOSE: To evaluate the quality of reporting of all the new randomized clinical trials published during 1999 in OPHTHALMOLOGY: using the CONSORT statement parameters. DESIGN: Descriptive series of published studies. STUDIES INCLUDED: Randomized clinical trials. METHODS: Eligible studies were all randomized clinical trials published in Volume 106 (1999) of OPHTHALMOLOGY: that reported the results of prospectively conducted studies in humans comparing two or more therapeutic options with regard to their effect on one or various outcomes, in which the authors stated that a process of randomization or quasi-randomization was performed before the interventions. Each study was evaluated by two independent observers establishing the specific report in the published manuscript of 57 CONSORT statement descriptors, and consensus was obtained between evaluators. MAIN OUTCOME MEASURES: Overall presence of CONSORT statement descriptors in published reports. RESULTS: The mean number of positive CONSORT descriptors for the 24 eligible randomized clinical trials was 33.42 (standard error of the mean [SEM] 1.57) of 57 possible. This score was significantly different (P: < 0.001) from the score of 16.6 (standard error of the mean 0.6) reported for OPHTHALMOLOGY: in the 1991 to 1994 study by Scherer and Crawley. Of the nine descriptors measuring the quality of abstract reporting, a mean of 6.25 (SEM 0.3) was included in the 24 study abstracts evaluated, significantly different from the Scherer and Crawley score (5.2, SEM 0.2. P: < 0.001). Four and six descriptors increased and decreased, respectively, their reporting in more than 20%. Key descriptors such as hypothesis postulation, primary outcome determination, sample size calculations, and a discussion of the limitations of the study such as bias, imprecision, and internal validity are still reported in less than 42% of clinical trials. CONCLUSIONS: This study describes for the first time after the adoption of the CONSORT statement recommendations the status on the quality of reporting of recently published randomized clinical trials in OPHTHALMOLOGY: Although not a direct measure of the intrinsic quality of a study, reporting quality provides the reader with useful tools for the evaluation of its validity. The quality of reporting of randomized clinical trials shows an overall improvement when compared with the period between 1991 and 1994. However, there is still significant room for improvement, especially in descriptors essential for the validation of clinical trial results that are still widely underreported.

Isozyme variation in Larrea ameghinoi and Larrea nitida (Zygophyllaceae): genetic diversity and its bearing on their relationship.

Electrophoretic variants for 11 isozyme systems were examined by horizontal polyacrilamide gel electrophoresis in natural populations of Larrea ameghinoi and L. nitida (section Larrea). The two taxa presented fixed alternative allelic variants at loci Adh-1, Gdh-1 and Mdh-1. Genetic variability estimates showed no statistically significant differences among populations of section Larrea (He: 0.097-0.167). However, these values were significantly lower than those reported for species of section Bifolium (L. divaricata, diploid L. tridentata) in a previous contribution (He: 0.17-0.29). Positive and highly significant Wright's fixation indices are in agreement with higher amounts of inbreeding for L. nitida and L. ameghinoi, as suggested on the basis of floral morphology by previous authors. Moreover, the higher levels of genetic differentiation obtained for conspecific populations of section Larrea as compared to those of section Bifolium are also consistent with these observations. Nei's genetic identity values obtained for sympatric (I = 0.80) and allopatric (I = 0.63-0.73) L. ameghinoi - L. nitida population pairs are concordant with those expected for different, but closely related congeneric species.

Isozymes in Larrea divaricata and Larrea tridentata (Zygophyllaceae): a study of two amphitropical vicariants and autopolyploidy.

Electrophoretic variants for seven isozyme systems - probably encoded by 18 structural gene loci - in diploid populations of Larrea divaricata and diploid and tetraploid populations of its North American vicariant derivative L. tridentata were assayed by polyacrilamide and starch gel electrophoresis. High molecular similarity of diploid and tetraploid cytotypes of L. tridentata supports the hypothesis of interracial autopolyploidy. The absence of fixed heterozygosity and additive profiles indicates a low level of divergence between the parental diploids and the tetraploids. The phenogram based on the I coefficient showed the similarities between the populations of diploid L. divaricata and also between the diploid populations of L. tridentata. Both groups of diploid populations were more distantly connected to tetraploid L. tridentata.

[The Saethre-Chotzen syndrome (acrocephalosyndactylia type III)]. / El síndrome de Saethre-Chotzen (acrocéfalosindactilia tipo III).

A ten year old girl with Saethre-Chozen's syndrome and normal intelligence is described and her phenotype is compared to previously reported cases.