Prognostic factors and overall survival of breast cancer in Benin: a hospital-based study.

BACKGROUND: In Benin, a country in West Africa, breast cancer is the leading cancer in women, both in terms of incidence and mortality. However, evidence on the mortality of breast cancer and its associated factors is lacking in this country. Our aim was to describe and analyze the clinical, histopathological, and prognostic aspects of breast cancer in Benin. METHODS: A descriptive and analytical study was carried out at the CNHU-HKM and the CHU-MEL, two major tertiary referral hospitals for breast cancer management located in Cotonou, the capital city of Benin. All breast cancer medical records with histological evidence and immunohistochemistry studies were retrospectively collected between January 1, 2014, and September 30, 2020, in these two tertiary referral hospitals and analyzed in the current study. RESULTS: Finally, 319 medical records were included. The mean age at diagnosis was 48.74 years. The tumors were most frequently classified as T4 (47.6%) with lymph node involvement N2 (34.5%), and metastases were clinically noted in 21.9% of cases. Stage was reported in the medical records of 284 patients. Tumors were diagnosed at very late AJCC stages: stage III (47.5%) and stage IV (24.7%). Grades SBR 2 (49.2%) and SBR 3 (32.6%) were the most frequent grades. Triple-negative breast cancer (31.3%) was the most common molecular type. The overall 5-year survival was 48.49%. In multivariable analysis, the poor prognostic factors were lymph node invasion (HR = 2.63; p = 0.026; CI: [1.12, 6.17]), the presence of metastasis (HR = 3.64; p < 0.001); CI: [2.36, 5.62] and the immunohistochemical profile (HR = 1.29; p < 0.001; CI: [1.13, 1.48]). CONCLUSIONS: Breast cancer in Beninese is predominant in young adults and is often diagnosed at a late stage. The survival of breast cancer patients in Benin can be improved by enhancing early diagnosis and multidisciplinary management.

Negative association between ascaris lumbricoides seropositivity and Covid-19 severity: insights from a study in Benin.

Introduction: The COVID-19 pandemic has had devastating effects worldwide, but the trajectory of the pandemic has been milder in Low-and-Middle-Income Countries (LMICs), including those in Africa. Co-infection with helminths, such as Ascaris lumbricoides, has been suggested as a possible factor contributing to the reduced severity observed in these regions. Methods: The present study investigated the association between Ascaris-specific antibody levels and COVID-19 severity in 276 SARS-CoV-2-infected individuals in Benin. Participants were categorized into asymptomatic (n=100), mild (n=150), and severe (n=26) groups based on clinical disease severity. Sera were collected and analyzed using ELISA to measure Ascaris and SARS-CoV-2-specific antibodies, while Luminex was used to assess cytokines and SARS-CoV-2-specific neutralizing antibody expression. Results and discussion: The results demonstrated that asymptomatic SARS-CoV-2 seropositive individuals expressed, on average, 1.7 and 2.2-times higher levels of Ascaris antibodies compared to individuals with mild and severe COVID-19, respectively. This finding suggests an inverse correlation between Ascaris antibody levels and COVID-19 severity. Notably, logistic regression analysis showed that Ascaris seropositivity was significantly associated with a reduced risk of severe COVID-19 (OR = 0.277, p = 0.021). Interestingly, COVID-19 patients with comorbidities such as type 2 diabetes and high blood pressure showed lower expression of Ascaris antibodies. Strikingly, no correlation was observed between Ascaris antibody levels and SARS-CoV-2-specific neutralizing antibodies. On the other hand, individuals seronegative for Ascaris displayed significantly higher levels of systemic pro-inflammatory markers compared to seropositive individuals. These findings suggest that higher expression of Ascaris antibodies is associated with asymptomatic SARS-CoV-2 infections and may contribute to the reduction of the risk to develop severe COVID-19. The beneficial effect of Ascaris seropositivity on COVID-19 outcomes in Benin may be attributed to a decrease in comorbidities and pro-inflammatory markers. These observations provide valuable insights into the milder COVID-19 trajectory observed in Africa and may have implications for future therapeutic strategies.

Phylogeography of Sub-Saharan Mitochondrial Lineages Outside Africa Highlights the Roles of the Holocene Climate Changes and the Atlantic Slave Trade.

Despite the importance of ancient DNA for understanding human prehistoric dispersals, poor survival means that data remain sparse for many areas in the tropics, including in Africa. In such instances, analysis of contemporary genomes remains invaluable. One promising approach is founder analysis, which identifies and dates migration events in non-recombining systems. However, it has yet to be fully exploited as its application remains controversial. Here, we test the approach by evaluating the age of sub-Saharan mitogenome lineages sampled outside Africa. The analysis confirms that such lineages in the Americas date to recent centuries-the time of the Atlantic slave trade-thereby validating the approach. By contrast, in North Africa, Southwestern Asia and Europe, roughly half of the dispersal signal dates to the early Holocene, during the "greening" of the Sahara. We elaborate these results by showing that the main source regions for the two main dispersal episodes are distinct. For the recent dispersal, the major source was West Africa, but with two exceptions: South America, where the fraction from Southern Africa was greater, and Southwest Asia, where Eastern Africa was the primary source. These observations show the potential of founder analysis as both a supplement and complement to ancient DNA studies.

Aqueous extract of Pedalium murex D. Royen ex L. leafy stem protects against lead induced testicular toxicity in Wistar rats.

OBJECTIVES: Lead exposure seriously impairs male reproductive function. The protective capacity of Pedalium murex leafy stem and fruit aqueous extracts against lead testicular toxicity is evaluated to find herbals drugs able to improve semen quality. METHODS: Phytochemical screening were performed according to classical methods. Twenty four male rats were divided into four groups of six rats each and received the following treatments via oral route: distilled water; 0.2% lead acetate in drinking water; 0.2% lead acetate in drinking water with 400 mg/kg P. murex aqueous leafy stem extract; 0.2% leaded water with 400 mg/kg P. murex aqueous fruit extract. Treatments were administered for 70 days. Body and reproductive organs weights, sperm parameters and testicular histological sections of each group were examined. RESULTS: Flavonoids, tannins, coumarins, alkaloids, and lignans were found in both extracts. Lead intoxication reduced sperm motility and count but increased the percentage of morphologically abnormal sperms. The germinal epithelium of seminiferous tubules histoarchitecture was disorganized by lead. The leafy stem extract was effective in reducing lead induced testicular disruption whereas fruit has not shown any beneficial effect. CONCLUSIONS: P. murex leafy stem aqueous extract is effective against semen alterations caused by lead.

A 90-Day Oral Toxicity Study of an Ethanolic Root Extract of Caesalpinia bonduc (L.) Roxb. in Wistar Rats.

BACKGROUND: Plant medicine is the oldest form of health care known to mankind; hence, studies on their safety for use are essential for the control of adverse drug effects. In Benin, Caesalpinia bonduc is one of many medicinal plants used as aphrodisiac, and for treatment of various ailments including prostatic hyperplasia. Despite its numerous ethnomedicinal benefits, toxicological information associated with its chronic use is currently limited. OBJECTIVE: The present study therefore assessed the toxicity of an ethanolic root extract of Caesalpinia bonduc in Wistar rats. METHODS: Caesalpinia bonduc root extract was administered by oral gavage at doses of 31.25, 125, and 500 mg/kg/day for 90 days to male Wistar rats, after which body weight changes, food consumption, urinary parameters, hematological and blood biochemical parameters, organ weights changes, gross pathology, and histopathology of vital organs were assessed. RESULTS: There were no death or abnormal clinical signs, no significant changes in body weight gain or urinary parameters, and no changes in necropsy and histopathology findings of vital organs associated with extract treatment. However, some indices such as erythrocytes, total cholesterol, and aspartate amino transferase increased in rats treated with high doses of the extract, as well as relative weight of testes, followed by a decrease in food intake and prostate relative weight. CONCLUSION: The results indicate that an ethanolic root extract of Caesalpinia bonduc does not cause significant adverse effects and suggest its tolerability up to 500 mg/kg for daily administration of 90 days.

A hotspot of Toxoplasma gondii Africa 1 lineage in Benin: How new genotypes from West Africa contribute to understand the parasite genetic diversity worldwide.

Through international trades, Europe, Africa and South America share a long history of exchanges, potentially of pathogens. We used the worldwide parasite Toxoplasma gondii to test the hypothesis of a historical influence on pathogen genetic diversity in Benin, a West African country with a longstanding sea trade history. In Africa, T. gondii spatial structure is still non-uniformly studied and very few articles have reported strain genetic diversity in fauna and clinical forms of human toxoplasmosis so far, even in African diaspora. Sera from 758 domestic animals (mainly poultry) in two coastal areas (Cotonou and Ouidah) and two inland areas (Parakou and Natitingou) were tested for T. gondii antibodies using a Modified Agglutination Test (MAT). The hearts and brains of 69 seropositive animals were collected for parasite isolation in a mouse bioassay. Forty-five strains were obtained and 39 genotypes could be described via 15-microsatellite genotyping, with a predominance of the autochthonous African lineage Africa 1 (36/39). The remaining genotypes were Africa 4 variant TUB2 (1/39) and two identical isolates (clone) of Type III (2/39). No difference in terms of genotype distribution between inland and coastal sampling sites was found. In particular, contrarily to what has been described in Senegal, no type II (mostly present in Europe) was isolated in poultry from coastal cities. This result seems to refute a possible role of European maritime trade in Benin despite it was one of the most important hubs during the slave trade period. However, the presence of the Africa 1 genotype in Brazil, predominant in Benin, and genetic analyses suggest that the triangular trade was a route for the intercontinental dissemination of genetic strains from Africa to South America. This supports the possibility of contamination in humans and animals with potentially imported virulent strains.

In Vitro and In Vivo Toxicity Studies on Cymbopogon giganteus Chiov. Leaves Essential Oil from Benin.

Cymbopogon giganteus Chiov. (Poaceae) is a medicinal plant used to treat various diseases in traditional medicine in several African countries. The present study aims to evaluate the oral and inhalation toxicity as well as the mutagenic effects of the essential oil of Cymbopogon giganteus leaves (EOCG) from a sample collected in Benin. Mutagenic potential was assessed by the Ames test using Salmonella typhimurium strains TA98 and TA100. Oral acute toxicity was carried out by administration of a single dose of 2000 mg/kg b.w. to Wistar rats while oral subacute toxicity was assessed by daily administration of 50 and 500 mg/kg of EOCG for 28 days. Finally, inhalation toxicity was assessed by administration of a single dose of 0.125%, 0.5%, 2% or 5% v/v of EOCG emulsions in 0.05% v/v lecithin solution in sterile water for the first experiment, and in a second one by administration of single dose of 0.125% or 0.5% v/v. A broncho-alveolar lavage was performed after 3 h or 24 h, respectively. The results show that EOCG is not mutagenic on Salmonella typhimurium strains at the highest concentration tested (200 µg/plate). In the acute oral toxicity study, EOCG induce neither mortality nor toxicity, showing that the LD50 is greater than 2000 mg/kg. The subacute oral toxicity study at both doses did not show any significant difference in body weight, relative organ weight, hematological and/or biochemical parameters or histopathology as compared to the control group. EOCG induced mortality and inflammation in lungs 3 h after administration of a single dose of 5% or 2% v/v. Single doses of 0.125% or 0.5% v/v did not induce inflammation, cell recruitment nor cytotoxicity in lungs 3 h or 24 h after administration, suggesting safety at these concentrations. This first report on the in vivo toxicity will be useful to guide safe uses of EOCG.

Evaluation de la toxicité de «anteprost »: médicament traditionnel amelioré, utilisé contre l'hypertrophie benigne de la prostate

Objectif : Evaluer la toxicité du phytomédicament 'Antéprost' chez les animaux de laboratoire. Méthode : Après une extraction hydro-alcoolique, un criblage phytochimique a été réalisé. Ensuite une dose unique de 5000 mg/kg de poids corporel a été administrée aux cobayes dans l'étude de toxicité aiguë avec une surveillance des animaux pendant 15 jours. Au cours de l'étude de toxicité subchronique, trois différentes doses (153,6 mg/kg/jr, 307,2 mg/jr et 614.4 mg/kg) ont été administrées quotidiennement pendant 90 jours à des rats Wistar des deux sexes. Ils ont été surveillés pour tout signe de toxicité et les données relatives aux poids corporels, consommations alimentaires, para-mètres biologiques ainsi qu'à l'histologie des organes ont été relevées. Résultats : Plusieurs composés phytochimiques ont été mis en évidence dans notre extrait. Nous n'avons enregistré ni de mortalité ni de signes de toxicité aussi bien dans le comportement des co-bayes que dans leur consommation alimentaire au terme des quinze jours d'observation. L'étude de toxicité subchronique n'a révélé aucun signe de toxicité. Le poids corporel des animaux ainsi que la consommation alimentaire, les paramètres biochimiques, hématologiques et histologiques n'ont pas été significativement modifiés. Conclusion : Cette étude a permis de montrer que la DL50 d u médicament traditionnel amélioré''Antéprost'' est supérieure à 5g/kg chez le cobaye. Aucune toxicité n'a été observée au cours de l'étude de la toxicité subchronique de 90 jours. Toutes ces données suggèrent que le produit est rela-tivement non toxique aux doses étudiées

Evidence of Immunosuppressive and Th2 Immune Polarizing Effects of Antidiabetic Momordica charantia Fruit Juice.

The mechanism of action of the antidiabetic capacity of Momordica charantia is still under investigation. Here, we assessed phytochemical compositions, antioxidant activity, and effects of total and filtered fruit and leafy stem juices of Momordica charantia on human T cell proliferation and differentiation through quantification of Th1/Th2 cytokines. In the absence of stimulation, total fruit and leafy stem juices induced significant T cell proliferation. Under PHA stimulation, both juices potentiated plant-induced T cell proliferation. However, the filtered fruit and leafy stem juices significantly inhibited PHA-stimulated T cell proliferation, while neither juice influenced T cell proliferation. Moreover, total and filtered fruit juice increased IL-4 secretion, while total and filtered leafy stem juice enhanced IFN-γ production. Phytochemical screening revealed the presence of tannins, flavonoids, anthocyans, steroids, and triterpenoids in both juices. Alkaloids, quinone derivatives, cardenolides, and cyanogenic derivatives were undetectable. The saponins present in total juices were undetectable after filtration. Moreover, both juices had appreciable antioxidant capacity. Our study supports the type 1 antidiabetic effect of filtered fruit juice of M. charantia which may be related to its immunosuppressive and T-helper 2 cell inducing capacities. Due to their immune-stimulatory activities and their ability to increase T-helper 1 cell cytokines, total fruit and leafy stem juices may serve in the treatment of immunodeficiency and certain infections.

HLA Class II Allele, Haplotype, and Genotype Associations with Type 1 Diabetes in Benin: A Pilot Study.

BACKGROUND: Several studies have reported the implication of HLA-DR/DQ loci in the susceptibility to type 1 diabetes (T1D). Since no such study has yet been performed in Benin, this pilot one aimed at assessing HLA class II allele, haplotype, and genotype associations with T1D. MATERIAL AND METHODS: Class II HLA genotyping was performed in 51 patients with T1D and 51 healthy unrelated controls by means of the PCR-SSP method. The diagnosis of T1D was set up according to American Diabetes Association criteria. Odds ratio (OR) and its 95% confidence interval (95% CI) were calculated to assess the associations between T1D and HLA alleles, haplotypes, and genotypes. RESULTS: Participants were aged 1-24 years. T1D was significantly associated with DR3, DQA1∗05:01, DQB1∗02:01, and DR3-DR4. No significant associations were observed with DR4, DQB1∗03:02, and DQB1∗06:02. CONCLUSION: Certain HLA class II alleles, haplotypes, and genotypes were related to T1D and may be used as genetic susceptibility markers to T1D in Benin.

Antimicrobial, antioxidant, toxicity and phytochemical assessment of extracts from Acmella uliginosa, a leafy-vegetable consumed in Bénin, West Africa.

BACKGROUND: Acmella uliginosa (Asteraceae) is a flowering plant whose leaves are consumed as a vegetable in Benin. They are also traditionally used as an antibiotic in the treatment of infectious diseases. To evaluate the therapeutic potential and toxicity effect of this leafy-vegetable, the antibacterial, antifungal, antioxidant activities and, toxicity and phytochemical constituents were investigated. METHODS: Dichloromethane, methanol and aqueous extracts of Acmella uliginosa were evaluated for their antimicrobial activity against six bacterial and six fungi strains. Antibacterial and antifungal activities were investigated by microdilution method and agar diffusion method respectively. Antioxidant activity was assessed using the 2,2-diphenyl-1-picryl-hydrazyl assay and phytochemical screening was carried out using standard procedures. Finally, oral acute toxicity at a dose of 2000 mg/kg was done according to the Organization for Economic Co-operation and Development guideline n° 423. RESULTS: The antibacterial activity was broad spectrum, inhibiting both Gram-positive and Gram-negative bacteria. The minimum inhibitory concentration ranged from 0.625 to 5 mg/ml. The antifungal evaluation show that all the extracts inhibited mycelial growth and sporulation of fungi with percentages of inhibition ranging from 9.39 to 75.67% and 22.04 to 99.77%, respectively. In DPPH radical scavenging assay, the effect on reducing free radicals increased in a dose dependent manner. The percentage of inhibition of DPPH ranged from 0.94 to 73.07%. Phytochemical screening revealed the presence of coumarin, flavonoid, naphtoquinone, anthracene derivative, saponin, lignan, triterpene and tannin. The dichloromethane and methanol extracts showed the best biological activities; they were also shown as the best extraction solvents of phytochemicals. In the acute toxicity evaluation, all animals were physically active and no deaths of rats were observed during the test. However, the aqueous extract promoted biochemical, hematological and histopathological alterations of treated rats at 2000 mg/kg body weight. CONCLUSION: A. uliginosa extracts contains antimicrobial, antioxidant agents and was not lethal for rats when ingested. However, according to the results obtained for biochemical, hematological, and histopathological analysis, caution is required regarding its consumption.

Polykystose renale autosomique dominante (PKAD) au CNHU-HKM de Cotonou: profil épidémiologique, clinique, biologique et intérêt du dépistage familial

Introduction: Étudier le profil épidémiologique, clinique et paraclinique de la PKAD chez des patients diagnostiqués au CNHU de Cotonou et évaluer l'intérêt d'un dépistage chez les patients à risque. Méthodes: Il s'agit d'une étude transversale comportant une revue de dossiers des patients cliniquement diagnostiqués PKAD à la clinique universitaire de néphrologie et d'hémodialyse du 1er janvier 2000 au 31 janvier 2011, et une enquête familiale chez les patients où le diagnostic de PKAD a été confirmé entre le 1er février et le 31 Août 2011.Un séquençage à la recherche de mutations dans les gènes de la Polycystine 1 et 2 a été réalisé chez les cas index. Résultats: L'incidence hospitalière de la PKAD était de 7,8 cas par an. Le dépistage familial avait permis d'examiner 99 membres de 22 familles et de confirmer 14 cas de PKAD. L'âge moyen des patients était de 45,6±12,8ans. Le signe physique le plus fréquent était l'hypertension artérielle (HTA (83%). Une insuffisance rénale chronique était observée dans 75% des cas. Le séquençage direct avait permis de mettre en évidence 7 nouvelles mutations dont 02 mutations dans les gènes PKD2 et 5 dans PKD1. Conclusion: La PKAD relativement fréquente, présente de nouvelles mutations chez les patients diagnostiqués au CNHU de Cotonou. Le conseil génétique est particulièrement indiqué dans les familles où la maladie rénale a débuté précocement

Phytochemical composition of Cymbopogon citratus and Eucalyptus citriodora essential oils and their anti-inflammatory and analgesic properties on Wistar rats.

Cymbopogon citratus and Eucalyptus citriodora are widely used herbs/plants as a source of ethnomedicines in tropical regions of the world. In this work, we studied the anti-inflammatory and gastroprotective effects of C. citratus and E. citriodora essential oils on formol-induced edema, and acetic acid induced abdominal cramps in Wistar rats. To fully understand the chemically induced anti-inflammatory properties of these plants, we first analyzed the chemical composition of the essential oils. A total of 16 chemical constituents accounting for 93.69 % of the oil, were identified in C. citratus among which, Geranial (27.04 %), neral (19.93 %) and myrcene (27.04 %) were the major constituents. For E. citriodora, 19 compounds representing 97.2 % of the extracted oil were identified. The dominant compound of E. citriodora essential oil was citronellal (83.50 %). In vivo analysis and histological assay showed that the two essential oils displayed significant dose dependent edema inhibition effect over time. They displayed strong analgesic and antipyretic properties similar to that induced by 50 mg/kg of acetylsalicylate of lysine. However, the E. citriodora essential oil was more effective than that of C. citratus. We identified significant numbers of aldehyde molecules in both essential oils mediating antioxidant activity that may contribute to the anti-inflammatory effects observed on the rats. Altogether, this work demonstrates the anti-inflammatory property of C. citratus and E. citriodora suggesting their potential role as adjuvant therapeutic alternatives in dealing with inflammatory-related diseases.

Hypokalaemic periodic paralysis due to the CACNA1S R1239H mutation in a large African family.

Hypokalaemic periodic paralysis (HypoKPP) is a skeletal muscle channelopathy caused by mutations in calcium (CACNA1S) and sodium (SCN4A) channel subunits. A small number of causative mutations have been found in European and Asian patients, but not in African patients yet. We have identified a large Beninese family in which HypoKPP segregated over five generations and was caused by the CACNA1S R1239H mutation. We report on the clinical and histopathological spectrum of the disorder in this family. A later age at onset (15.8+/-8.8years), and particular triggering factors due to specific African life conditions seem to be characteristic of our observation.

[Effects of physical activity on adipose tissue cellularity in premenopausal obese women in Bénin]. / Effets des exercices physiques sur la cellularité adipeuse des femmes obèses préménopausées.

The purpose of this article was to quantify the exercise load and investigate the influence of physical exercise on adipose tissue in obese women from Bénin. Twelve subjects participated at the study. Six of the subjects trained three times a week for six months. Each training session lasted forty-five minutes. The remaining six women constituted the control group. Biopsy samples of adipose tissue were taken from the same site in the gluteal iliac region at the end of six months and analyzed by histochemistry and electron microscopy. The results showed that all subjects suffered from severe central obesity; lipid content and number of adipocytes were higher among the sedentary woman than among those who exercised. Intense exercise in the latter used more lipids than carbohydrates. We conclude that regular, supervised physical exercise reduces lipid levels and thus induces weight loss.

Giant platelets in a case of deletion 11q24-qter confirmed by fluorescence in situ hybridization.

Here we report the association of giant platelets and an increase in platelet volume in a 19-month-old black female with de novo del 11q24-qter. The deletion, which was visible on karyotype, was further confirmed and more precisely localized by fluorescence in situ hybridization studies (FISH) that showed the deletion to lie distal to the MLL gene region (11q23). Clinically, the case presented less severe symptoms than Jacobsen syndrome-the well known partial deletion of the distal end of chromosome 11. Platelet glycoproteins CD 41, CD 42a, C 42b, CD 61, and PAC-1 were also assayed and found to be normally expressed. To our knowledge, giant platelets are described for the first time in the relevant deleted region.