Cerebral venous thrombosis in a sub-saharan African country: A preliminary monocentric study of a 70 case series at the neurology department of Fann teaching hospital in Dakar - Senegal.

INTRODUCTION: Cerebral venous thrombosis (CVT) are underdiagnosed in sub-saharan Africa where publications are uncommon. Our study aim was to describe the CVT diagnostic and therapeutic features through a senegalese case series. PATIENTS AND METHOD: A monocentric retrospective and prospective study was conducted at the adult Neurology department of Fann Teaching Hospital in Dakar (Senegal), between January 01, 2013 and April 30, 2020. It had included all CVT cases diagnosed by neurovascular imaging. RESULTS: Seventy CVT cases were collected including 48 women (68.6%). The average age of the patients was 35.2±14 years. The main neurological signs were headache (92.8%) and motor deficit (41.4%), with subacute onset in 67.2% of cases. The superior sagittal sinus (54.3%) and the transverse sinus (38.6%) were the most affected with multiple involvements in 27 patients (38.6%). Thirty patients (42.8%) had indirect parenchymal signs such as venous infarction (15.7%), cerebral edema (11.4%) or intracerebral hemorrhage (12.8%). The etiological factors were mostly infectious (41.4%) with meningoencephalitis (12.8%) and otorhinolaryngological infection (10%). Gyneco-obstetric factors (27%) and Behçet's disease (7%) were the main aseptic factors. In the short-term clinical course, curative anticoagulation (98.6%) had enabled a favourable outcome (mRS 0-1) in half of the patients. CONCLUSION: Our study, the largest series in sub-saharan Africa to this date, confirms that CVT is a young women disease. Infectious etiology is the most frequent at the Fann national teaching hospital (41.4% in Dakar against 6.5% in Germaine Bousser's series) even if the etiological assessment is limited by financial constraints (no coagulopathy/thrombophilia check-up).

Unfolding and displaying the influencing factors of advance directives from the stakeholder's perspective: A concept mapping approach.

AIMS: To develop a culturally relevant conceptual map to discover perceptions of a statutory form of advance directive (AD) for Hong Kong Chinese. DESIGN: This was the first study on AD using a concept mapping approach with two phases. METHODS: The data collection of the two phases was conducted from February 2016-February 2017. In Phase I, 96 participants were recruited using purposive sampling. In Phase II, multi-dimensional scaling and hierarchical cluster analysis were used to create a concept map based on quantitative data. RESULTS: The map depicted six clusters of factors affecting the acceptance of AD, with their importance rating in decreasing order: Conditional factor, value system, process of AD, physical and illness factor, personal situation factor, and socio-cultural factor. CONCLUSION: The study adopted a comprehensive approach to unfolding the multi-faceted factors affecting the acceptance of ADs by stakeholders. Strategies targeting the clusters could be developed to facilitate the discussion and completion of AD.

An intact helical domain is required for Gα14 to stimulate phospholipase Cß.

BACKGROUND: Stimulation of phospholipase Cß (PLCß) by the activated α-subunit of Gq (Gαq) constitutes a major signaling pathway for cellular regulation, and structural studies have recently revealed the molecular interactions between PLCß and Gαq. Yet, most of the PLCß-interacting residues identified on Gαq are not unique to members of the Gαq family. Molecular modeling predicts that the core PLCß-interacting residues located on the switch regions of Gαq are similarly positioned in Gαz which does not stimulate PLCß. Using wild-type and constitutively active chimeras constructed between Gαz and Gα14, a member of the Gαq family, we examined if the PLCß-interacting residues identified in Gαq are indeed essential. RESULTS: Four chimeras with the core PLCß-interacting residues composed of Gαz sequences were capable of binding PLCß2 and stimulating the formation of inositol trisphosphate. Surprisingly, all chimeras with a Gαz N-terminal half failed to functionally associate with PLCß2, despite the fact that many of them contained the core PLCß-interacting residues from Gα14. Further analyses revealed that the non-PLCß2 interacting chimeras were capable of interacting with other effector molecules such as adenylyl cyclase and tetratricopeptide repeat 1, indicating that they could adopt a GTP-bound active conformation. CONCLUSION: Collectively, our study suggests that the previously identified PLCß-interacting residues are insufficient to ensure productive interaction of Gα14 with PLCß, while an intact N-terminal half of Gα14 is apparently required for PLCß interaction.

[Pulmonary rehabilitation methods in the prevention of acute respiratory infections in patients with chronic obstructive pulmonary disease, the association with psycho-emotional state].

In patients with chronic obstructive pulmonary disease stage I GOLD we revealed a significant reduction of acute respiratory infections frequency after pulmonary rehabilitation using salt aerosol therapy; however, in patients with chronic obstructive pulmonary disease stage II GOLD such a reduction we have not seen. We didn't find marked reduction of acute respiratory infections frequency also in patients with chronic obstructive pulmonary disease stage I GOLD with higher depression level.

[Rehabilitation features in the prevention of asthma exacerbations in patients with different body weight].

Bronchial asthma patients with excessive body weight compared to persons with normal weight had more severe course of the disease, associating with more pronounced inflammation (increased level of the proinflammatory interleukin-6, interferon-gamma, tumor necrosis factor alpha). After the rehabilitation treatment including speleotherapy we observed the improvement of clinical manifestation and reduction of the studied immune parameters.

[Clinical and genetic features of APC- and MYH-mutation-negative patients with multiple polyposis of large bowel that tested by conventional methods].

The genealogic analysis, molecular and clinical investigations has been carried out in 19 probands with multiple colorectal adenomas (approximately 100 or more). Twelve of these patients (63.1%) were APC and MYH mutation-negative. Three (25%) probands have positive family history. The median of the disease manifestation age in APC-negative patients was intermediate between the median of the disease manifestation age in APC- and MYH-positive patients. Extraintestinal manifestations in the APC-negative probands are more rare than in APC-positive patients. A half of APC- and MYH-negative probands with multiple polyposis had colorectal cancer. APC- and MYH-negative patients formed a genetically heterogenous group.

[Role of enterosorbents in treatment of complicated varicose disease].

Results of treatment of 43 patients, suffering varicose disease, complicated by trophic disorders, were analyzed. To the patients a complex was prescribed, including sorpents, angioprotectors, locally - ointments. There were operated 14 patients.

Repurposing of triamterene as a histone deacetylase inhibitor to overcome cisplatin resistance in lung cancer treatment.

PURPOSE: Cisplatin is the core chemotherapeutic drug used for first-line treatment of advanced non-small cell lung cancer (NSCLC). However, drug resistance is severely hindering its clinical efficacy. This study investigated the circumvention of cisplatin resistance by repurposing non-oncology drugs with putative histone deacetylase (HDAC) inhibitory effect. METHODS: A few clinically approved drugs were identified by a computational drug repurposing tool called "DRUGSURV" and evaluated for HDAC inhibition. Triamterene, originally indicated as a diuretic, was chosen for further investigation in pairs of parental and cisplatin-resistant NSCLC cell lines. Sulforhodamine B assay was used to evaluate cell proliferation. Western blot analysis was performed to examine histone acetylation. Flow cytometry was used to examine apoptosis and cell cycle effects. Chromatin immunoprecipitation was conducted to investigate the interaction of transcription factors to the promoter of genes regulating cisplatin uptake and cell cycle progression. The circumvention of cisplatin resistance by triamterene was further verified in a patient-derived tumor xenograft (PDX) from a cisplatin-refractory NSCLC patient. RESULTS: Triamterene was found to inhibit HDACs. It was shown to enhance cellular cisplatin accumulation and potentiate cisplatin-induced cell cycle arrest, DNA damage, and apoptosis. Mechanistically, triamterene was found to induce histone acetylation in chromatin, thereby reducing the association of HDAC1 but promoting the interaction of Sp1 with the gene promoter of hCTR1 and p21. Triamterene was further shown to potentiate the anti-cancer effect of cisplatin in cisplatin-resistant PDX in vivo. CONCLUSION: The findings advocate further clinical evaluation of the repurposing use of triamterene to overcome cisplatin resistance.

Generation of an induced pluripotent stem cell line carrying biallelic deletions (SCTCi019-B) in ALDH7A1 using CRISPR/Cas9.

Biallelic pathogenic variants in ALDH7A1 are associated with pyridoxine-dependent epilepsy (PDE). ALDH7A1 encodes for the third enzyme of the lysine catabolism pathway. In this study a human isogenic ALDH7A1 knock-out iPSC line was created using CRISPR/Cas9 technology. One clone (SCTCi019-B) with biallelic deletions in ALDH7A1 was obtained and fully characterized, showing expression of pluripotency markers, a normal karyotype and no off-targets. Human-based models derived from this iPSC line will contribute to gain insights in the molecular mechanism of disease underlying PDE.

Generation of an induced pluripotent stem cell line carrying a biallelic deletion (SCTCi019-A) in GCDH using CRISPR/Cas9.

GCDH encodes for the enzyme catalyzing the sixth step of the lysine catabolism pathway. Biallelic pathogenic variants in GCDH have been associated with glutaric aciduria type 1 (GA1). In this study CRISPR/Cas9 technology was used to create an isogenic GCDH knock-out human iPSC line. One clone with a biallelic deletion (SCTCi019-A) in GCDH was obtained and fully characterized, revealing a normal karyotype, no off-targets detected and expression of pluripotency markers. This iPSC line can contribute to gain insights in the molecular mechanism of disease.

Acute renal failure in the postpartum due to calcified myoma: a case report.

BACKGROUND: It has been reported that delivery can be a cause of urine retention. This complication occurs especially in case which are associated with a pelvic mass like calcified uterine myoma. But this unusual aspect of myoma can make ultrasonographic traps. OBJECTIVE: To report an unusual case of calcified uterine myoma which was unnoticed during pregnancy and made so obstructive renal failure few days after the delivery. CASE REPORT: Seven days after delivery a Twenty-nine-year-old Senegalese woman was admitted at a private hospital for a slight alteration of consciousness(Glasgow Coma Scale at 12). Emergency check-up showed an acute obstructive renal failure. Biological investigations showed ascendancy of granulocytes, deterioration of renal function with creatinin in 78 mg / l and urea in 1.82 g/l. Ultrasonographic examination revealed bilateral dilatation of renal calyces and an interstitial calcified uterine myoma compressing the bladder. Management consisted on a urethral catheterization of bladder, correction of hydro-electrolytic troubles and antibiotherapy (ciprofloxacin).Global evolution leads to fast fully consciousness, with disappearance of biological and ultrasonographic disorders. CONCLUSION: Calcified myoma can look like cephalic pole during pregnancy. This unusual aspect can be sometimes source of acute obstructive renal failure requiring urinary drainage in emergency. Improvement of women's management during postpartum can prevent such complications.

Pneumophonic coordination impairments in parkinsonian dysarthria: importance of aerodynamic parameters measurements.

BACKGROUND: Among Parkinsonian axial signs, dysarthria represents an important disabling symptom able to lead towards a significant reduction of oral communication. Several methods of dysarthria assessment have been used but aerodynamic evaluation is rare in the literature. OBJECTIVE: To highlight the importance of aerodynamic parameters measurements in assessment of parkinsonian dysarthria. PATIENTS AND METHODS: Using a dedicated system (EVA2), 24 parkinsonian patients were recorded after withdrawal of L-dopa for at least 12 h (condition called OFF DOPA) in order to evaluate intra-oral pressure (IOP), mean oral air flow (MOAF) and laryngeal resistance (LR) on six /p/ during realization of the sentence "Papa ne m'a pas parle' de beau-papa" ("Daddy did not speak to me about daddy-in-law") which corresponds to a breath group. 50 control subjects were recorded in parallel in order to define reference measurements. RESULTS: It appeared that there is in Parkinson's disease aerodynamic impairments which were evidenced by the fall in IOP and that of MOAF in patients compared with control subjects. The difference between the two groups was statistically significant. In addition a greater instability of LR in patients compared with control subjects was also noted. CONCLUSION: Our results show that measurements of aerodynamics parameters, by reflecting the dysfunction induced by disease, may well be relevant factors in parkinsonian dysarthria evaluation.

[Investigation of the influence of intracameral injection of domestic lidocaine on the corneal thickness during phacoemulsification of cataract].

Influence of intracameral injection of 0.5 % solution of lidocaine hydrochloride on the cornea was investigated. It was proved that 0.5 % solution of lidocaine hydrochloride being preservative-free, has not any adverse effect on the corneal thickness measured by keratopachimetry before and after injection of medicine.

[Seroprevalence of HBsAgs in patients with rheumatoid arthiritis in a hospital setting in Senegal]. / Séroprévalence de l'antigène HBs au cours de la polyarthrite rhumatoïde en milieu hospitalier Sénégalais.

PURPOSE: Rheumatoid arthritis is the most common chronic inflammatory joint disease in adults. In Senegal, where biotherapy is unavailable, treatment of RA relies on a combination of glucocorticoids and disease-modifying antirheumatic drugs (DMARD). Since DMARD, particularly methotrexate, induce hepatotoxicity pretreatment assays of serum transaminase and albumin levels, as well as serological tests for the hepatitis B and C viruses is recommended. Hepatitis B virus (HBV) infection is endemic in Africa, particularly in Senegal. The purpose of this study was to assess the seroprevalence of the HBV surface antigen (HBsAg) for HBV in 258 patients with RA in Senegal as a basis for defining the least hepatotoxic DMARD for these patients and ensuring the most suitable monitoring. METHOD: This retrospective study was based on a review of the medical records of patients examined between January 2005 and December 2009 at the rheumatology outpatient clinic of the Aristide Le Dantec Teaching Hospital in Dakar, Senegal. All patients met the American College of Rheumatology criteria for RA. RESULTS: A total of 258 patients were tested for HBsAg. Tests were positive in 6 for a seroprevalence of 2.3%. All 6 positive patients were women with a mean age of 48.7 years (range, 16-79 years). Transaminase levels were normal in 5 patients. In the remaining patient, ASAT level elevation were twice normal and ALAT was normal. No patients had clinical evidence of liver disease. CONCLUSION: HBsAg seroprevalence in our population of patients with RA was lower than in the general population of Senegal: 2.3% versus 15%-18%. No evidence indicated that HBVinfection produced specific features in patients with RA. Based on these findings, widespread use of methotrexate in optimal dosages appears safe in patients with RA in Senegal. Treatment should be accompanied by careful attention to HBV prevention.

[Hematologic and immunologic signs of lupus: the experience of the hospital of Dakar]. / Les manifestations hématologiques et immunologiques de la maladie lupique: l'expérience du centre hospitalo-universitaire de Dakar.

INTRODUCTION: The systemic erythematosus lupus (SEL) or lupic disease is a systemic auto-immune pathology, characterized primarily by the presence of antibodies directed against native antibodies anti-DNA. The circumstances of discovery are variable and polymorphic. The hematologic signs and the immunological disorders constitute criteria of diagnosis of lupic disease. METHODOLOGY: It is a multicentric retrospective study from January 1, 1997 to September 30, 2006. Patients were followed up in Internal medicine of Dakar. We appreciate the hematologic and immunological aspects appreciate their prognosis prevalence and their implications with the course the lupic disease. RESULTS: 142 lupic patients were included with 125 women and 17 men; the sex ratio is 0.13. The average age was 34 years with extremes of 6 and 72 years. Our patients had hematologic manifestations average in 32,4 % of the cases and immunological in 76,8 % of the cases. The immunological tests showed the presence, of antinuclear antibodies in 97,9 % of the cases, of native antibody anti-DNA in 45,7 % of the cases, the anti-ECT in 86,95 % (with the anti-RNP in 78,3 % of the cases, anti-Sm in 56,5 % and of anti-SSA in 87 % of the cases). Antibodies anti-DNA and anti-ECT were associated with the hematologic demonstrations respectively in 92,0 % and 95 % of the cases (p = 0,08). Total survival in 96 % of the cases is estimated to 7 years. CONCLUSION: The circumstances of discovery of the lupic disease are variable. The hematologic signs constitute criteria diagnosis of lupic disease. The accessibility of the hematologic and immunological assessment is necessary for an early diagnosis and an early treatment.

[Systemic vasculitis: study of 27 cases in Senegal]. / Vascularites systémiques: 27 observations au Sénégal.

Studies on vasculitis in black Africa are rare. The purpose of this report is to describe a retrospective study of systemic vasculitis managed in the internal medicine, ORL and cardiolology departments of the Aristide le Dantec University Hospital in Dakar, Senegal from 1995 to 2007. A series of 27 cases involving 7 men and 20 women with a mean age of 49 years was compiled. Primary vasculitis included Horton disease in 3 cases, Wegener disease in 2, Takayasu disease in 1, and Buerger disease in 1. Secondary vasculitis included mixed cryoglobulinemia with Gougerot Sjögren syndrome in 7 cases, primary Goujeröt syndrome in 4, rheumatoid arthritis in 3, nodosa periarteritis with hepatitis B in 2, SHARP syndrome in 1, and polymyositis in 1. The remaining two cases involved abdominal periaortitis including one associated with retrosperitoneal fibrosis and tuberculosis and the other with spondylarthropathy. Corticotherapy in combination with anticoagulants, immunosuppressive therapy, and surgery, when necessary, allowed effective management in 24 cases. The findings of this study show that systemic vasculitis can have numerous etiologies and indicate that secondary forms are the most common. Appropriate care modalities are needed to prevent severe outcome in Senegalese hospitals.

[Radiation induced modification of human somatic cells chromosome sensitivity in testing mutagenic effect of bleomycin].

The voluntary investigation of hidden chromosome instability in 53 persons with different intensity of radiation exposure had been carried pout using modified "G2-bleomycin sensitivity assay". In all examined groups the individual levels of chromosome injuries under identical bleomycin exposure varied in wide range and didnrt depend on their initial values in the intact cultures. Among control donors and individuals with low radiation exposure approximately 33% hypersensitive persons had been identified that can be considered as genetically caused phenomenon. In patients recovered from acute radiation syndrome (57.9%) persons expressed hidden chromosome instability. The data permit to assume that high doses of ionizing radiation can modify inherited human chromosomes susceptibility to mutagen exposure.

[Biofilm on a metal surface as a factor of microbial corrosion].

Main attention was given in the present review to the research methods, phases of biofilm's forming, exopolymer compounds of bacteria as main biofilm forming factor. A microbial corrosion as a result of interaction between the biofilm and metal surface was considered. The interaction was displayed in biomineralization. The future trends of biofilms study were bound with research of their architecture. That architecture was determined by the structure and function of biofilms compounds: biopolymers and biominerals.

[Genetic counseling and prognosis of the development of complications in patients with syndromes of hereditary polyposis of the colon].

Physical examinations, genealogic analysis and genetic consulting were done for 14 probands and their family members with most frequent syndromes of hereditary polyposis of large bowel during 4 generations. These syndromes include familial adenomatous polyposis, Gardner syndrome and Peutz-Jeghers syndrome. 46 relatives of probands with the same pathology were affected (from 1 to 9 of affected relatives within families). We have found the congenital abnormalities in 13 (28.2%) patients with syndromes of hereditary polyposis. 29 (63%) patients have malignant neoplasia. In families with high risk for hereditary polyposis we recommend regular medical and genetic consultation for early prophylaxis of illness and for genetic risk of possible complications in their members.

An integrative approach to product development-A skin-care cream.

An integrative approach, involving marketing and management issues on the business side, and product design and prototyping on the technical side, is proposed for the development of chemical-based products. For the former, objective-time chart, RAT2IO modules and workflow diagrams are used for project management. For the latter, the integration of experiments, modeling and synthesis expedites product conceptualization and prototyping. Tasks for which chemical engineers are expected to play a key or a supporting role are discussed. An industrial application - the development of a skin-care cream is described alongside the procedure in order to illustrate the myriad issues in product development. In addition to the traditional engineering problems such as process and equipment design, product characterization, performance evaluation, and stability tests are also included as an integral part of this approach.