Ischemic strokes revealing neurosyphilis: Study of six (6) observations at the neurology Department of the University Hospital of Conakry.

Introduction: In sub-Saharan Africa (SSA), stroke is a major public health problem and the etiological aspects are poorly studied and documented because of under-medicalization; the syphilitic etiology is rarely mentioned. Patients and methods: We performed a retrospective study of 472 patients hospitalized for ischemic stroke between 2016 and 2021 in the Neurology Department of the University Hospital of Conakry, confirmed by neuroradiological explorations (brain CT, MRI-Angio) and a biological workup including VDRL-TPHA serological reactions in blood and CSF. Results: Syphilitic etiology was retained for six (6) patients (4 men and 2 women) with a mean age of 43 years (extremes 36 and 49 years). The clinical picture was dominated by carotid syndromes: superficial and deep sylvian syndrome, anterior cerebral artery syndrome and vertebro-basilar syndromes and one case of lacunar syndrome.The diagnosis was based on the positivity of serological reactions (VDRL-TPHA) in blood and cerebrospinal fluid (CSF) and the presence of a predominantly lymphocytic hypercellularity and a hyperproteinorachy in the CSF in the absence of any other etiology. Conclusion: These neurological vascular syndromes consecutive to a cerebral treponematous attack are often the result of a still poorly conducted management of primary and secondary syphilis in our country.

[Cryptogenic stroke management : where are we ?] / Prise en charge de l'AVC cryptogénique : où en sommes-nous ?

Cryptogenic stroke is an old definition that designates an ischemic stroke with no identifiable cause. The term of the embolic stroke of undetermined source was then introduced to identify non-lacunar strokes in whom thromboembolism was the likely mechanism. This subgroup of cryptogenic strokes remains heterogeneous with many potential and possibly associated embolic causes. Covert atrial fibrillation is probably less often involved than initially expected, in contrast to intracranial and extracranial atherosclerosis. The cardiologist should be involved in the search of underlying causes of ischemic stroke by helping the neurologist to identify the most likely diagnosis. Further research is necessary to select populations that may benefit from more effective and individualized treatment.

Hypoxia enhances ILC3 responses through HIF-1α-dependent mechanism.

Group 3 innate lymphoid cells (ILC3) have a prominent role in the maintenance of intestine mucosa homeostasis. The hypoxia-inducible factor (HIF) is an important modulator of immune cell activation and a key mechanism for cellular adaptation to oxygen deprivation. However, its role on ILC3 is not well known. In this study, we investigated how a hypoxic environment modulates ILC3 response and the subsequent participation of HIF-1 signaling in this process. We found increased proliferation and activation of intestinal ILC3 at low oxygen levels, a response that was phenocopied when HIF-1α was chemically stabilized and was reversed when HIF-1 was blocked. The increased activation of ILC3 relied on a HIF-1α-dependent transcriptional program, but not on mTOR-signaling or a switch to glycolysis. HIF-1α deficiency in RORyt compartment resulted in impaired IL-17 and IL-22 production by ILC3 in vivo, which reflected in a lower expression of their target genes in the intestinal epithelium and an increased susceptibility to Clostridiodes difficile infection. Taken together, our results show that HIF-1α activation in intestinal ILC3 is relevant for their functions in steady state and infectious conditions.

The interplay among gut microbiota, hypertension and kidney diseases: The role of short-chain fatty acids.

The bacteria community living in the gut maintains a symbiotic relationship with the host and its unbalance has been associated with progression of a wide range of intestinal and extra intestinal conditions. Hypertension and chronic kidney disease (CKD) are closely associated diseases with high incidence rates all over the world. Increasing data have supported the involvement of gut microbiome in the blood pressure regulation and the impairment of CKD prognosis. In hypertension, the reduced number of short-chain fatty acids (SCFAs) producing bacteria is associated with modifications in gut environment, involving reduction of the hypoxic gut profile and worsening of the microbial balance, leading to a loss of epithelial barrier integrity, development of gut inflammation and the reduction of SCFAs plasma levels. These modifications compromise the blood pressure regulation and, as a consequence, favor the end organ damage, also affecting the kidneys. In CKD, impaired renal function leads to accumulation of high levels of uremic toxins that reach the intestine and cause alterations in bacteria composition and fecal metabolite profile, inducing a positive feedback that allows translocation of endotoxins into the bloodstream, which enhances local kidney inflammation and exacerbate kidney injury, compromising even more CKD prognosis. In line with these data, the use of prebiotics, probiotics and fecal microbiota transplantation are becoming efficient therapies to improve the gut dysbiosis aiming hypertension and CKD treatment. This review describes how changes in gut microbiota composition can affect the development of hypertension and the progression of kidney diseases, highlighting the importance of the gut microbial composition uncovering to improve human health maintenance and, especially, for the development of new alternative therapies.

Retrospective study of foreign body-associated pathology in stranded cetaceans, Canary Islands (2000-2015).

Marine pollution, overrepresented by plastic, is a growing concern worldwide. However, there is little knowledge on occurrence and detrimental impacts of marine debris in cetaceans. To partially fill in this gap of knowledge, we aimed to investigate the occurrence and pathologies associated with foreign bodies (FBs) in a large cohort of cetaceans (n = 465) stranded in the Canary Islands. The Canary Islands shelter the greatest cetacean biodiversity in Europe, with up to 30 different species, of which nine are regularly present year around. We found at least one ingested FB in 36 out of 465 (7.74%) studied cetaceans, involving 15 different species, including eight out of the nine (80%) cetacean species present year-round in the Canary Islands. Risso's dolphin was the species most affected, followed by sperm whale, beaked whale and mysticetes. Plastic FB were the most common item found (80.56%). FB was directly associated with death in 13/36 (36.11%) animals. Poor body condition and deep diving behavior were found to be risk factors for FB ingestion, whereas the adult age was a protective factor. To the authors knowledge this is the first study that use statistical analysis to investigate risk and protective factors for FB ingestion. This study also provides insights of the potential impact caused by ingested FBs on the animal's health and mortality. This knowledge is critical to better understand and assess the impact of FB in cetaceans setting the scientific basis for prospective impact monitoring and future conservation policies.

Prevalence of extended-spectrum beta-lactamase phenotypes in enterobacteria isolated from blood cultures of patients at admission to the University Hospital of Bamako.

The aim of our study was to determine the frequency of extended-spectrum beta-lactamase (ESBL) phenotypes among the enterobacteria present in blood cultures of patients at admission to two university hospitals of Bamako (Mali). During a period of three months, we isolated enterobacteria from blood cultures from patients upon admission to the Point G and Gabriel Toure University Hospitals. The ESBL-positive enterobacteria were initially identified by API 20E strips and VITEK®2 and then confirmed in France by MALDI-TOF mass spectrometry at the Bichat Hospital bacteriology laboratory. Antibiotic susceptibility was determined by the diffusion method as recommended by EUCAST. The species isolated were K. pneumoniae (14/40, 35.0 %), E. coli (11/40, 27.5 %), and E. cloacae (9/40, 22.5 %); 21/34 (61.8 %) had an ESBL phenotype, including 10/14 (71.4 %) K. pneumoniae, 8/11 (72.7 %) E. coli, and 3/9 (33 3 %), E. cloacae. The ESBL strains of K. pneumoniae, E. coli, and E. cloacae were associated, respectively, with resistance to the following antibiotics: gentamicin (10/10, 100 %; 6/8, 75%; 2/3, 67%), amikacin (2/10, 20 %; 0/8, 0%; 0/3, 0%), ofloxacin (8/10, 80. %; 7/8, 87%; 3/3, 100%), cotrimoxazole (10/10, 100 %; 6/8, 75%; 3/3, 100%). Almost two thirds (61.8%) of the enterobacteria isolated from blood cultures produced extended-spectrum beta-lactamases. They retained regular sensitivity only to carbapenems and amikacin.

Co-transplantation of Xenogeneic Bone Marrow-derived Mesenchymal Stem Cells Alleviates Rejection of Pancreatic Islets in Non-obese Diabetic Mice.

Bone marrow-mesenchymal stem cells (BM-MSCs) have generated a great perspective in the field of regenerative medicine, and also in the treatment of inflammatory and autoimmune diseases in the past decade due to their immunomodulatory and anti-inflammatory properties. Here, we investigated the effect of xenogeneic BM-MSCs and pancreatic islets co-transplantation obtained from Wistar rats in preventing rejection or inducing tolerance to islet transplantation in non-obese diabetic mice. Non-obese diabetic mice were treated with co-transplantation of pancreatic islets and BM-MSCs (islet + MSCs group) or pancreatic islets only (islet group). Compared to the islet group, islet + MSCs had a lower expression of inflammatory markers, such as, tumor necrosis factor- α (13.40 ± 0.57 vs. 9.90 ± 0.12, P = .01), monocyte chemoattractant protein 1 (51.30 ± 6.80 vs. 9.00 ± 1.80, P = .01), and interleukin 1ß (IL-1ß) (16.2 ± 1.65 vs. 6.80 ± 1.00, P = .04). Comparing the expression of immune tolerance markers, it is noted that animals receiving the co-transplantation showed a significantly higher expression than the islet group of IL-4 (25.60 ± 1.96 vs. 2.80 ± 0.20, P = .004), IL-10 (188.40 ± 4.60 vs. 4.55 ± 0.12, P = .0001), and forkhead box P3 (34.20 ± 1.3 vs. 1.30 ± 0.2, P = .004), respectively. These results suggest an immunomodulatory action of BM-MSC in islet xenotransplantation showing that these stem cells have the potential to mitigate the early losses of grafts, due to the regulation of the inflammatory process of transplantation.

SOCS1 favors the epithelial-mesenchymal transition in melanoma, promotes tumor progression and prevents antitumor immunity by PD-L1 expression.

Silencing of SOCS1 protein with shRNAi lentivirus (shR-SOCS1) led to partial reversion of the tumorigenic phenotype of B16F10-Nex2 melanoma cells. SOCS1 silencing inhibited cell migration and invasion as well as in vitro growth by cell cycle arrest at S phase with increased cell size and nuclei. Down-regulation of SOCS1 decreased the expression of epidermal growth factor receptor, Ins-Rα, and fibroblast growth factor receptors. The present work aimed at analyzing the SOCS1 cell signaling and expression of proteins relevant to tumor development. An RNA microarray analysis of B16F10-Nex2 melanoma cells with SOCS1 silenced by shRNAi-SOCS1 was undertaken in comparison with cells transduced with the empty vector. Among 609 differentially expressed genes, c-Kit, Met and EphA3 cytokine/tyrosine-kinase (TK) receptors were down regulated. A significant decrease in the expression of TK receptors, the phosphorylation of mediators of ERK1/2 and p38 pathways and STAT3 (S727) were observed. Subcutaneous immunization with shR-SOCS1-transduced viable tumor cells rendered protection against melanoma in a syngeneic model, with decreased expression of PD-L1 and of matrix metallo-proteinases (MMPs) and CD-10 in those cells. The present work shows the role of SOCS1 in murine melanoma development and the potential of SOCS1-silenced tumor cells in raising an effective anti-melanoma immune response.

Follicular helper T cell in immunity and autoimmunity.

The traditional concept that effector T helper (Th) responses are mediated by Th1/Th2 cell subtypes has been broadened by the recent demonstration of two new effector T helper cells, the IL-17 producing cells (Th17) and the follicular helper T cells (Tfh). These new subsets have many features in common, such as the ability to produce IL-21 and to express the IL-23 receptor (IL23R), the inducible co-stimulatory molecule ICOS, and the transcription factor c-Maf, all of them essential for expansion and establishment of the final pool of both subsets. Tfh cells differ from Th17 by their ability to home to B cell areas in secondary lymphoid tissue through interactions mediated by the chemokine receptor CXCR5 and its ligand CXCL13. These CXCR5+ CD4+ T cells are considered an effector T cell type specialized in B cell help, with a transcriptional profile distinct from Th1 and Th2 cells. The role of Tfh cells and its primary product, IL-21, on B-cell activation and differentiation is essential for humoral immunity against infectious agents. However, when deregulated, Tfh cells could represent an important mechanism contributing to exacerbated humoral response and autoantibody production in autoimmune diseases. This review highlights the importance of Tfh cells by focusing on their biology and differentiation processes in the context of normal immune response to infectious microorganisms and their role in the pathogenesis of autoimmune diseases.

[Clinical appearance and scalable profile Thiamine deficiency in prison in Guinea: study of thirty-eight observations]. / Aspect clinique et profil évolutif de la carence en thiamine en milieu carcéral en Guinée : étude de trente-huit observations.

Cardiovascular and neurological manifestations associated with thiamine deficiency in Guinean prisons are common but not reported.We performed a prospective study of 38 cases related to vitamin B1 deficiency over a period of 4 years. In this population, the literature of traditional data gathered: frequency peak after thirty (92.6%) and clear representation male (sex ratio M/F: 18/1). The clinical symptomatology remains essentially dominated by sensorimotor polyneuropathy and pure sensory (52.2%), overall heart failure (31.5%) and to a lesser degree by Gayet Wernicke's encephalopathy (7.8%) and shoshin beriberi with severe evolution (5.2%). The study of nutritional status by body mass index (BMI) of the World Health Organization, by the criteria of Detsky and biological markers including albumin, shows that these patients are severely malnourished.

Effects of acute aerobic exercise on leukocyte inflammatory gene expression in systemic lupus erythematosus.

UNLABELLED: Systemic lupus erythematosus (SLE) is an autoimmune disease with a persistent systemic inflammation. Exercise induced inflammatory response in SLE remains to be fully elucidated. The aim of this study was to assess the effects of acuteexercise on leukocyte gene expression in active (SLEACTIVE) and inactive SLE (SLEINACTIVE) patients and healthy controls(HC). METHODS: All subjects (n = 4 per group) performed a 30-min single bout of acute aerobic exercise (~70% of VO2peak) on a treadmill, and blood samples were collected for RNA extraction from circulating leukocyte at baseline, at the end of exercise, and after three hours of recovery. The expression of a panel of immune-related genes was evaluated by a quantitative PCR array assay. Moreover, network-based analyses were performed to interpret transcriptional changes occurring after the exercise challenge. RESULTS: In all groups, a single bout of acute exercise led to the down-regulation of the gene expression of innate and adaptive immunity at the end of exercise (e.g., TLR3, IFNG, GATA3, FOXP3, STAT4) with a subsequent up-regulation occurring upon recovery. Exercise regulated the expression of inflammatory genes in the blood leukocytes of the SLE patients and HC, although the SLE groups exhibited fewer modulated genes and less densely connected networks (number of nodes: 29, 40 and 58; number of edges: 29, 60 and 195; network density: 0.07, 0.08 and 0.12, for SLEACTIVE, SLEINACTIVE and HC, respectively). CONCLUSION: The leukocytes from the SLE patients, irrespective of disease activity, showed a down-regulated inflammatory geneexpression immediately after acute aerobic exercise, followed by an up-regulation at recovery. Furthermore, less organized gene networks were observed in the SLE patients, suggesting that they may be deficient in triggering a normal exercised-induced immune transcriptional response.

Single-crystalline ZnO sheet Source-Gated Transistors.

Due to their fabrication simplicity, fully compatible with low-cost large-area device assembly strategies, source-gated transistors (SGTs) have received significant research attention in the area of high-performance electronics over large area low-cost substrates. While usually based on either amorphous or polycrystalline silicon (α-Si and poly-Si, respectively) thin-film technologies, the present work demonstrate the assembly of SGTs based on single-crystalline ZnO sheet (ZS) with asymmetric ohmic drain and Schottky source contacts. Electrical transport studies of the fabricated devices show excellent field-effect transport behaviour with abrupt drain current saturation (IDS(SAT)) at low drain voltages well below 2 V, even at very large gate voltages. The performance of a ZS based SGT is compared with a similar device with ohmic source contacts. The ZS SGT is found to exhibit much higher intrinsic gain, comparable on/off ratio and low off currents in the sub-picoamp range. This approach of device assembly may form the technological basis for highly efficient low-power analog and digital electronics using ZnO and/or other semiconducting nanomaterial.

Follicular helper T cell in immunity and autoimmunity

The traditional concept that effector T helper (Th) responses are mediated by Th1/Th2 cell subtypes has been broadened by the recent demonstration of two new effector T helper cells, the IL-17 producing cells (Th17) and the follicular helper T cells (Tfh). These new subsets have many features in common, such as the ability to produce IL-21 and to express the IL-23 receptor (IL23R), the inducible co-stimulatory molecule ICOS, and the transcription factor c-Maf, all of them essential for expansion and establishment of the final pool of both subsets. Tfh cells differ from Th17 by their ability to home to B cell areas in secondary lymphoid tissue through interactions mediated by the chemokine receptor CXCR5 and its ligand CXCL13. These CXCR5+ CD4+ T cells are considered an effector T cell type specialized in B cell help, with a transcriptional profile distinct from Th1 and Th2 cells. The role of Tfh cells and its primary product, IL-21, on B-cell activation and differentiation is essential for humoral immunity against infectious agents. However, when deregulated, Tfh cells could represent an important mechanism contributing to exacerbated humoral response and autoantibody production in autoimmune diseases. This review highlights the importance of Tfh cells by focusing on their biology and differentiation processes in the context of normal immune response to infectious microorganisms and their role in the pathogenesis of autoimmune diseases.

Prevalence of extended-spectrum beta-lactamase-producing Enterobacteriaceae isolated from blood cultures in Africa.

Extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae have been isolated from many regions of the world. Epidemiological studies are being conducted in Europe, North America, and Asia. No study has however been conducted in Africa to determine the prevalence and distribution of ESBLs on the continent. This literature review aimed at describing the prevalence of ESBL-producing Enterobacteriaceae isolated from blood cultures, as well as the ESBL genes involved at the international level. Our focus was mainly on Africa. We conducted a literature review on PubMed. Articles related to our study field and published between 1996 and 2014 were reviewed and entirely read for most of them, while we only focused on the abstracts of some other articles. Relevant articles to our study were then carefully reviewed and included in the review. The prevalence of ESBL-producing Enterobacteriaceae differs from one country to another. The results of our literature review however indicate that class A ESBLs prevail over the other types. We took into consideration articles focusing on various types of samples to assess the prevalence of ESBL-producing Enterobacteriaceae, but information on isolates from blood cultures is limited. The worldwide prevalence of ESBL-producing Enterobacteriaceae has increased over time. Evidence of ESBL-producing Enterobacteriaceae can be found in all regions of the world. Studies conducted in Africa mainly focused on the Northern and Eastern parts of the continent, while only rare studies were carried out in the rest of the continent.

Inflammatory cytokine kinetics to single bouts of acute moderate and intense aerobic exercise in women with active and inactive systemic lupus erythematosus.

The aim of this study was to evaluate changes in the cytokines INF-γ, IL-10, IL-6, TNF-α and soluble TNF receptors (sTNFR1 and sTNFR2) in response to single bouts of acute moderate and intense exercise in systemic lupus erythematosus women with active (SLE(ACTIVE)) and inactive (SLE(INACTIVE)) disease. Twelve SLE(INACTIVE) women (age: 35.3 ± 5.7 yrs; BMI: 25.6±3.4 kg/m2), eleven SLE(ACTIVE) women (age: 30.4 ± 4.5 yrs; BMI: 26.1±4.8 kg/m2), and 10 age- and BMI-matched healthy control women (HC) performed 30 minutes of acute moderate (~50% of VO(2)peak) and intense (~70% of VO(2)peak) exercise bout. Cytokines and soluble TNF receptors were assessed at baseline, immediately after, every 30 minutes up to three hours, and 24 hours after both acute exercise bouts. In response to acute moderate exercise, cytokines and soluble TNF receptors levels remained unchanged in all groups (P>0.05), except for a reduction in IL-6 levels in the SLE(ACTIVE) group at the 60th and 180th minutes of recovery (P<0.05), and a reduction in sTNFR1 levels in the HC group at the 90th, 120th, 150th, 180th minutes of recovery (P<0.05). The SLE(INACTIVE) group showed higher levels of TNF-α, sTNFR1, and sTNFR2 at all time points when compared with the HC group (P<0.05). Also, the SLE(ACTIVE) group showed higher levels of IL-6 at the 60th minute of recovery (P<0.05) when compared with the HC group. After intense exercise, sTNFR1 levels were reduced at the 150th (P=0.041) and 180th (P=0.034) minutes of recovery in the SLE(INACTIVE) group, whereas the other cytokines and sTNFR2 levels remained unchanged (P>0.05). In the HC group, IL-10, TNF-α, sTNFR1, and sTNFR2 levels did not change, whilst INF-γ levels decreased (P=0.05) and IL-6 levels increased immediately after the exercise (P=0.028), returning to baseline levels 24 hours later (P > 0.05). When compared with the HC group, the SLE(INACTIVE) group showed higher levels of TNF-α and sTNFR2 in all time points, and higher levels of sTNFR1 at the end of exercise and at the 30th minute of recovery (P<0.05). The SLE(ACTIVE) group also showed higher levels of TNF-α at all time points when compared with the HC group (P<0.05), (except after 90 min, 120 min and 24 hours of recovery) (P>0.05). Importantly, the levels of all cytokine and soluble TNF receptors returned to baseline 24 hours after the end of acute exercise, irrespective of its intensity, in all three groups (P>0.05). This study demonstrated that both the single bouts of acute moderate and intense exercise induced mild and transient changes in cytokine levels in both SLE(INACTIVE) and SLE(ACTIVE) women, providing novel evidence that acute aerobic exercise does not trigger inflammation in patients with this disease.

[Pediatric multiple sclerosis: is it different from the adult form?]. / La SEP de l'enfant: est-elle différente de celle de l'adulte ?

INTRODUCTION: Multiple sclerosis (MS) is not uncommon in children. The aim of this study was to compare early onset MS (EOMS) with adult onset MS (AOMS). METHODS: A retrospective study including MS cases between 1997 and 2010. EOMS was defined by age at MS onset<18years. Data were collected using the EDMUS database (European Database of Multiple Sclerosis) including: sex, age at onset, disease duration, EDSS, score after relapse. The MSSS and the Progression Index were calculated. Patients with disease duration less than one year were excluded. MS symptoms at onset and at further relapses were also noted. These parameters were compared between the EOMS and the AOMS groups. RESULTS: Two hundred fifty-nine cases were included including 31 EOMS (11.96%). The mean follow-up was 96months. The relapsing-remittent form was significantly more frequent in the pediatric group (94% vs 79%). Mean EDSS and MSSS scores and the percentage of fast progressors (MSSS>5) were lower in the EOMS group. Analysis of neurological symptoms at the first MS attack and further neurological events showed a lower frequency of gait disturbances, motor symptoms and bladder symptoms in the EOMS group compared with the AOMS group. The 10-year mean EDSS score was 1.9 for EOMS and 4.1 for AOMS, after 25years it was 4.5, and 7.27 respectively. CONCLUSION: This study highlights the relative frequency of EOMS in our MS population. However, different severity scores showed less disability progression in EOMS patients compared with AOMS patient; irreversible disability was reached at an early age.

Impaired structural and functional regeneration of skeletal muscles from ß2-adrenoceptor knockout mice.

AIMS: ß2-adrenergic stimulation causes beneficial effects on structure and function of regenerating muscles; thus, the ß2-adrenoceptor may play an important role in the muscle regenerative process. Here, we investigated the role of the ß2 -adrenoceptor in skeletal muscle regeneration. METHODS: Tibialis anterior (TA) muscles from ß2-adrenoceptor knockout (ß2 KO) mice were cryolesioned and analysed after 1, 3, 10 and 21 days. The role of ß2-adrenoceptor on regenerating muscles was assessed through the analysis of morphological and contractile aspects, M1 and M2 macrophage profile, cAMP content, and activation of TGF-ß signalling elements. RESULTS: Regenerating muscles from ß2 KO mice showed decreased calibre of regenerating myofibres and reduced muscle contractile function at 10 days when compared with those from wild type. The increase in cAMP content in muscles at 10 days post-cryolesion was attenuated in the absence of the ß2 -adrenoceptor. Furthermore, there was an increase in inflammation and in the number of macrophages in regenerating muscles lacking the ß2-adrenoceptor at 3 and 10 days, a predominance of M1 macrophage phenotype, a decrease in TßR-I/Smad2/3 activation, and in the Smad4 expression at 3 days, while akirin1 expression increased at 10 days in muscles from ß2 KO mice when compared to those from wild type. CONCLUSIONS: Our results suggest that the ß2-adrenoceptor contributes to the regulation of the initial phases of muscle regeneration, especially in the control of macrophage recruitment in regenerating muscle through activation of TßR-I/Smad2/3 and reduction in akirin1 expression. These findings have implications for the future development of better therapeutic approaches to prevent or treat muscle injuries.