Assessment of Vulnerability to the Covid-19 Pandemic in the Central African Sub-region.

OBJECTIVE: This study was aimed at examining the vulnerability of Central Africa to the COVID-19 pandemic. METHODS: Demographic, health, and socio-economic indicators were used to describe the vulnerability. The study period was from December 31st, 2019 to May 31st, 2020 (i.e. 5 months after the start of the pandemic). RESULTS: According to demographic indicators, African populations appear younger than in Europe, Asia, and North America, where evidence showed a higher lethality of COVID-19 and a higher frequency of hospitalization among the elderly. This highlights the protective effect of the age structure of Central African populations. Their populations face significant vulnerability from high morbidity and a considerable deficit in health care facilities and services. Poverty indicators are not in their favour for a sustainable implementation of effective pandemic control measures. Very low literacy rates in some countries, misinformation, and belief in conspiracy theories could affect the community involvement in the response. Several countries are weakened by other humanitarian crises, including conflicts and other epidemics. The early easing of lockdown restrictions in certain countries could worsen the situation. CONCLUSION: In this sub-region, where the largest proportion of the population lives in poverty, poor sanitary conditions, conflicts, and humanitarian crises, the question of standards of prevention could appear to be a luxurious idea relegated to the background. Central African countries need financial and logistical support for a sustainable and effective response. These observations could be easily extrapolated to other sub-Saharan sub-regions.

Inflammatory biomarkers and prediction of insulin resistance in Congolese adults.

Several studies have shown that low levels of adiponectin (ADP) and high levels of alpha tumor necrosis factor (NFT) increase the risk or severity of many cardiometabolic diseases associated with insulin resistance. The main objective of this study was to evaluate the association between plasma adipokines and IR measured by HOMA-IR. The secondary objective was to determine the biomarker of the potential inflammation to predict IR in Congolese melanoderm subjects residing in Brazzaville. This cross-sectional study was conducted on 234 apparently healthy participants over the age of 18. Socio-demographic and clinical data were collected. Biological data, including the total ADP and NFT dosage, were measured using the ELISA method. Participants were categorized into two groups according to HOMA-IR ≥ 2.5. Univariate and multivariate logistic regression analyses were conducted to identify risk factors for insulin resistance. An optimized model was obtained after the logistic regression. The analysis of the receptor's operating characteristics (OCR) was performed to determine the optimal threshold value and diagnostic characteristics, as well as the area under the curve (ASC). ADP averages were significantly low (11.49 ± 7.61 ng/mL; P < 0.001) while those of TNF were significantly higher (96.03 ± 44.09 pg/mL) in the HOMA-IR group ≥ 2.5. There was a positive and significant correlation (p < 0.05) between BMI, TT, CRPhs, TNF and HOMA-IR. And a negative and significant correlation was noted between ADP and HOMA-IR (r = - 0.39; P < 0.01). Similarly, a negative and significant correlation (p < 0.01) was noted between BMI, TT, TNF, CRPhs and ADP. The optimal threshold value of the total ADP for predicting IR was 17.52 ng/mL with a sensitivity of 89% [IC 95% (0.83-0.95)], 56% specificity [IC 95% (0.47-0.65)] and a CSA of 0.76 [IC 95% (0.69-0.81)]. After logistic regression, the CSA of the optimized model was 0.84 [IC 95% (0.79-0.89)]. ADP can be used as a highly plausible IR prediction biomarker.

Wnt/beta-catenin and PI3K/Akt/mTOR Signaling Pathways in Glioblastoma: Two Main Targets for Drug Design: A Review.

Glioblastoma (GBM) is the most common and malignant astrocytic glioma, accounting for about 90% of all brain tumors with poor prognosis. Despite recent advances in understanding molecular mechanisms of oncogenesis and the improved neuroimaging technologies, surgery, and adjuvant treatments, the clinical prognosis of patients with GBM remains persistently unfavorable. The signaling pathways and the regulation of growth factors of glioblastoma cells are very abnormal. The various signaling pathways have been suggested to be involved in cellular proliferation, invasion, and glioma metastasis. The Wnt signaling pathway with its pleiotropic functions in neurogenesis and stem cell proliferation is implicated in various human cancers, including glioma. In addition, the PI3K/Akt/mTOR pathway is closely related to growth, metabolism, survival, angiogenesis, autophagy, and chemotherapy resistance of GBM. Understanding the mechanisms of GBM's invasion, represented by invasion and migration, is an important tool in designing effective therapeutic interventions. This review will investigate two main signaling pathways in GBM: PI3K/Akt/mTOR and Wnt/beta-catenin signaling pathways.

The mental foramen in dry human mandibles of adult South Africans: an anatomical study / El foramen mental en mandíbulas humanas secas de adultos sudafricanos: un estudio anatómico

The objective of the study was to investigate the position, position symmetry, shape and number of the mental foramen in a heterogeneous South African population. Knowledge of the precise position of MF in maxillofacial surgery is critical for an accurate local anaesthesia; and can provide a landmark in forensic or medico legal cases. Dry adult human mandibles (n = 325) were selected and classified by ancestry. The sample comprised male-to-female ratio of 1.2:1. Observations were made for the position, position symmetry, shape and number of the mental foramen. There was a substantial to perfect agreement (p < 0.001) for most observations, except for the shape of the MF on the right side of the mandible that had a fair agreement (K = 0.25; P > 0.05). PIV of the MF is shown as the most prevalent position. PIII and IV were commonly observed in males and females respectively. PII was commonly observed in the males of European descent, while PIII was observed in male African and Mixed descents and female European descents. There was no significant difference in the symmetric analysis of MF amongst male and female (p = 0.059) and between ancestry (p = 0.455). But also, an oval shape of MF was the most common across subpopulations and ancestries, with 2 (2 %) and 3 (0.46 %) of the AMFs present. This study is the first comprehensive description of the MF in the South African population, and could be very useful in forensic anthropology in the South Africa population.

El objetivo de este estudio fue investigar, en una población sudafricana heterogénea, la posición, simetría de posición, forma y número de forámenes mentales (FM). El conocimiento de la localización exacta del FM en la cirugía maxilofacial es crítico para una anestesia local precisa y puede proporcionar un punto de referencia en casos legales forenses o médicos. Se seleccionaron 325 mandíbulas humanas secas adultas y clasificadas por ascendencia. La muestra relación hombre-mujer fue de 1,2:1. Las observaciones fueron realizadas para la posición, simetría de la posición, forma y el número forámenes mentales. Se alcanzó la perfección de concordancia (p < 0,001) para la mayoría de las observaciones, a excepción de la forma intermedia en el lado derecho de la mandíbula el cual presentó un acuerdo justo (K = 0,25; p > 0,05). La PIV de la MF se muestra como la posición más prevalente. PIII y IV fueron observados comúnmente en hombres y mujeres, respectivamente. La PII se observó comúnmente en los varones de ascendencia europea, mientras que el PIII se observó en descendientes africanos y mixtos masculinos y descendientes femeninos europeos. No hubo diferencias significativas en el análisis simétrico del FM entre hombres y mujeres (p = 0,059) y entre ascendencia (p = 0,455). Una forma ovalada de FM fue la más común a través de subpoblaciones y ancestros, con 2 (2 %) y 3 (46 %) del con la presencia de un foramen mental accesorio. Este estudio es la primera descripción comprensiva del FM en la población sudafricana, y podría ser muy útil en antropología forense en la población de Sudáfrica.

Early islets and mesenchyme from an injured adult pancreas improve syngeneic engraftments and islet graft function in diabetic rats.

A decrease in mass of isografts and a decline in islet function are major challenges in islet transplantations. Despite this, transplantation of 84 h harvested pancreatic duct ligation (PDL) tissues have been shown to have the same functional ability to foetal pancreata, but there was only 40% success in reverting hyperglycaemia. We tested the potential of early islets with mesenchymal stromal cells (MSCs) to promote isogeneic grafts survival and to restore normoglycemia in diabetic rats, in comparison with late islets. Islets were isolated from injured adult pancreata of donor rats at 24 h post ligation either with MSCs (24 h islet/MSC+) or without MSCs (24 h islet/MSC-), and at 84 h without MSCs (84 h islet/MSC-). These cells were transplanted under the renal capsule of syngeneic STZ-diabetic recipient rats. The islet grafts were monitored using the BGLs of recipients and the immunohistomorphology of the grafts were analysed using anti-insulin and anti-Ki67 antibodies. The mean BGL in 24 h islet/MSC+ recipients was reduced over time toward the control value. The curves of the mean BGLs in the control islet/MSC- and the 24 h islet/MSC- recipients dropped significantly below the control normal glucose group's levels to reach their nadirs on weeks 4 and 6, respectively. Both curves had a peak overshoot on week 9, with no statistical significant difference between them. Engrafted islets were evident in these recipients, lasted for 5 and 6 weeks and correspondingly survived failure. However, insulin+ cells were present in the isografts of all recipients; but, only isografts in the 24 h islet/MSC+ presented with a homogenous subcapsular beta cell mass. In addition, the tendency of 24 h islet/MSC- to restore normoglycaemia with its survival capacity was statistically highly significant compared to the 84 islet/MSC- recipients (80%; 20%; p = 0.001). Transplantation of early islets with MSCs from injured adult pancreata prolongs islet graft survival and improves isograft function in diabetic rats. This novel observation requires much further exploration for its clinical application, but this model already provides hope for new sources of donor islets for transplantation.

Immunohistomorphology of pancreatic islet microvasculature and the immunophenotypic analysis of CEPC in adult diabetic rats / Inmunohistomorfología de microvasculatura de islotes pancreatic y el análisis inmunofenotípico de CEPC en ratas diabéticas adultas

SUMMARY: Hyperglycaemia is one of the main causes for the endothelial cell (EC) damage in diabetic patients. Even though circulating endothelial progenitor cells (CEPC) could be used as a prognosis for microvascular complications, there is very little information on the islet microvasculature. We analysed by immunohistochemistry and by flow cytometric immunophenotyping, the expression of CD34 on EC and the expressions of CD31, CD34, CD45 and CD133 on CEPC in Streptozotocin (STZ)-induced diabetic rats. Peripheral blood and tissue specimens were obtained from rats of different treatment regimens: STZ treatment, control saline (NS) and sodium citrate (CB) treatments. Blood cells were exposed to flow cytometric immunophenotyping for CD133, CD31, CD34, CD45 and CD133. While tissues from the pancreas, liver and kidney were routinely processed and stained immunohistochemically for CD34. There was a tendency of an increased in CD45-/CD133+/CD31+/CD34+ cells (0.04 ± 0.11 %) in diabetic rats compared to the controls (CB: 0.03 ± 0.04 %; Saline: 0.01 ± 0.03 %). But there was no significant statistical difference between them. The expression pattern of CD34 on the EC in the organs' vascular beds including arterioles, venules, capillaries and sinusoids was extremely heterogeneous across and within treatment regimens. The ECs in the sinusoids of the liver presented similar CD34 expression patterns across different treatment regimens, while the expression of CD34 on the ECs of sinusoidal capillaries in the pancreas vary with the treatment regimen. We conclude that the degree of endothelial cell damage is not uniform across organs' vascular beds in the rat, contrary to mice and humans. Furthermore, the sinusoids in the pancreas and the kidney may have the same degree of endothelial damage when exposed to the same deleterious causes.

RESUMEN: La hiperglucemia es una de las principales causas del daño de las células endoteliales (EC) en pacientes diabéticos. A pesar de que las células progenitoras endoteliales circulantes (CEPC) podrían utilizarse como pronóstico de las complicaciones microvasculares, hay muy poca información sobre la microvasculatura de los islotes. Se analizaron por inmunohistoquímica y por inmunofenotipificación citométrica de flujo, la expresión de CD34 en EC y las expresiones de CD31, CD34, CD45 y CD133 en CEPC en ratas diabéticas inducidas por estreptozotocina (STZ). Se obtuvieron muestras de sangre y tejidos periféricos a partir de ratas de diferentes regímenes de tratamiento: tratamiento con STZ, solución salina control (NS) y citrato de sodio (CB). Las células sanguíneas fueron expuestas a inmunofenotipado por citometría de flujo para CD133, CD31, CD34, CD45 y CD133. Mientras que los tejidos del páncreas, el hígado y el riñón fueron rutinariamente procesados y teñidos inmunohistoquímicamente para CD34. Se observó una tendencia a un aumento en las células CD45- / CD133 + / CD31 + / CD34 + (0,04 ± 0,11 %) en ratas diabéticas en comparación con los controles (CB: 0,03 ± 0,04 %; Salino: 0,01 ± 0,03 %). Pero no hubo diferencias estadísticamente significativas entre ellos. El patrón de expresión de CD34 en la EC en los lechos vasculares de los órganos incluyendo arteriolas, vénulas, capilares y sinusoides fue extremadamente heterogéneo a través de y dentro de los regímenes de tratamiento. Las EC en los sinusoides del hígado presentaron patrones de expresión de CD34 similares a través de diferentes regímenes de tratamiento, mientras que la expresión de CD34 en las CE de capilares sinusoidales en el páncreas varía con el régimen de tratamiento. Concluimos que el grado de daño de las células endoteliales no es uniforme en los lechos vasculares de los órganos en la rata, en comparación de los ratones y los seres humanos. Además, los sinusoides en el páncreas y el riñón pueden tener el mismo grado de daño endotelial cuando se exponen a las mismas causas deletéreas.

Mesenchymal cells are required for epithelial duct cell-to-beta cell maturation and function in an injured adult pancreas in the rat.

The islet, the endocrine portion of the pancreas - develops from an invagination of the pancreatic duct epithelial cells (PDECs) into the surrounding tissue. The contact of the PDECs with mesenchymal cells (MSCs) may be an essential drive for endocrine cell fate. During pancreatic development, cells that express Neurogenin-3 (Ngn3) biomarker are precursors of insulin- producing beta cells. These precursors have been reported in the neogenesis of islets from adult tissues following the surgical ligation of the main pancreatic duct (PDL). But the capacity of these precursors to induce the appropriate signals to complete the entire neogenesis program has been questioned. We studied the fate of co-culture of PDECs and MSCs from the ligated adult pancreas and established the exact location of adult stem- or progenitor-like cells that give rise to beta cells. PDECs were cultured in direct contact with or without MSCs in serum-containing culture media. The cytomorphology of the cells in co-cultures was determined and the immunocytochemical study of the cells was carried out using anti-Ngn3, anti-insulin and anti-cytokeratin-7 (CK7) antibodies. Both the PDEC/MSC- and PDEC/MSC+ cultures showed out- pocketing from duct epithelium by the end of the second week, which are distinct as cell clusters only in PDEC/MSC+ cells later in week four, exhibiting numerous branching ducts. Co-expression of Ngn3 with insulin was observed in both cultures from the second week. However, characterizations of these Ngn3+ cells in the PDEC/MSC+ culture revealed that these cells also co-expressed a CK7 biomarker. This study provides new evidence of the ductal epithelial nature of beta cells in injured adult pancreata; and that the mesenchymal stromal cells are required to sustain Ngn3 expression for beta cell maturation and function.

Hyperbolic relation between beta-cell function and insulin sensitivity for type 2 diabetes mellitus, malaria, influenza, Helicobacter pylori, Chlamydia pneumoniae, and hepatitis C virus infection-induced inflammation/oxidative stress and temporary insulin resistance in Central Africans

Background/aim: We calculated the homeostatic model assessment (HOMA) for estimating insulin sensitivity and beta-cell function in normal, healthy nondiabetics with infections (malaria, influenza, HIV, Helicobacter pylori, Chlamydia pneumoniae, and hepatitis C virus), type 2 diabetic black patients, and healthy controls from Kinshasa, DR Congo. Materials and methods: A case-control study was carried out between 2006 and 2007 for black Central African participants managed for HOMA.Results: In total, 219 patients and 110 healthy controls were matched for sex and age. The hyperbolic product for 85 infected patients occupied an intermediate position between the hyperbolic product for 110 controls and that of 134 type 2 diabetics. Inflammation/oxidative stress was present in all infected patients, as well as in the type 2 diabetics. Of the patients, 39.3% and 49.8% had insulin resistance and metabolic syndrome, respectively. Insulin resistance was more prevalent in nondiabetics with inflammation/oxidative stress (47.1%; P = 0.041) than in type 2 diabetics (34.3%). Type 2 diabetics had higher insulin sensitivity and lower beta-cell function but a similar HOMA-IR score. Conclusion: We recommend the assessment of insulin resistance in Central African patients with severe infections and type 2 diabetes.

Feasibility of iFISH patterns in hematologic malignancies among Congolese patients at Kinshasa University clinics

Objective:To analyze the feasibility of detecting Ph1 in leukemia patients in the Kinshasa University Clinics in the Democratic Republic of Congo,at KU Leuven,Belgium.Methods:Bone marrow and peripheral blood samples with chronic myeloid leukemia,acute myeloid leukemia or acute leukocytes leukemia were obtained from 32 patients in Kinshasa University clinics in the Democratic Republic of Congo and transferred to KU Leuven in Belgium for iFISH feasibility.Ph1 was detected by using a remote analysis of interphase fluorescence in situ hybridization (iFISH).Results:Out of the 32 patients involved in this study,65.6％ (n =21) of the cases were successfully tested,of which 52.4％ (n =11) were iFISH positives for the variant t(9;22)(presence of Ph1) in chronic myeloid leukemia samples and 47.6％ (n =10) negatives in all subtypes of hematological malignancies.However,there was a female predominance in chronic myeloid leukemia samples Phi-positives by iFISH,whereas no sexual influence was observed on acute subtypes of leukemia.Conclusions:iFISH analysis is feasible on samples obtained from remote sites in the Democratic Republic of Congo.However,the optimization of the sample storage is necessary to further improve iFISH's performance.

Histomorphometric and radioimmunoassay studies of the rat endometrium following peanut oil treatment.

BACKGROUND: The pregnancy rate during in-vitro fertilization (IVF) following progesterone supplement still remains very low at around 20%. OBJECTIVE: To investigate the effects of peanut oil itself on the endometrial receptivity, the pregnancy success rate and fertility during the peri-implantation time in hyper stimulated and normal rats. MATERIALS AND METHODS: Thirty-six adult Sprague Dawley rats with at least four regular oestrus cycles were randomly divided into 4 groups: two groups were hyper stimulated by human chorionic gonadotropin (hCG) and treated with progesterone or with peanut oil; the two other groups were not hyper stimulated and treated with saline solution or peanut oil. On day 5.5 of pregnancy, the uterine horns were removed and blood was collected for histomorphometric and serum progesterone evaluation. 12 rats were allowed to continue the presumed pregnancy to term. Analysis of variance (ANOVA) and student t-test were used to compare the means of morphometric and radioimmunoassay data between groups. p-values less than 0.05 were considered statistically significant. RESULTS: The mean values of morphometric parameters and serum progesterone varied significantly between the groups (ANOVA, p<0.0001). The lowest values of progesterone parameters were observed in the hyperstimulated groups that did not deliver pups; both hyperstimulated groups had deleterious luminal epithelium with varying degrees of mucosal projections. There were isolated decidualised zones observed in hyper stimulated peanut oil group, whereas peanut oil group had the highest number of implantation sites and deliveries. CONCLUSION: The results show that hype stimulation reduces the endometrial receptivity, while peanut oil increases endometrial receptivity, pregnancy rates and fertility by triggering decidualisation.