Getting to the heart of the matter: diagnostic tools and therapeutic approach to cardiac involvement in Behçet syndrome A Tunisian case series.

The aim was to investigate the frequency and spectrum of cardiac involvement (CI) in patients with Behçet syndrome (BS) in the Tunisian context, and to assess the clinical and imaging features, treatment, and outcomes. We retrospectively retrieved the medical records of patients with CI among 220 BS patients admitted to the hospital internal medicine department between February 2006 and April 2019, who fulfilled the International Study Group diagnostic criteria for BS. Ten patients (8 men, 2 women) were eligible for the study. Mean age was 37.3 years. Three patients had 2 isolated episodes of cardiac BS. The different types of CI were coronary artery disease (5/10), intracardiac thrombus (4/10), pericarditis (1/10), myocarditis (1/10), and myocardial fibrosis (1/10). Five patients had associated vascular involvement (50%). Medical treatment was based on corticosteroids and colchicine in all patients (100%), anticoagulants in 8 (80%), and cyclophosphamide followed by azathioprine in 9 (90%). The clinical course was favorable in 9 patients; 1 patient died. CI remains an important feature of BS because of its association with increased risk of mortality and morbidity. Therefore, early screening and detection with imaging methods are paramount. Also, better cooperation between rheumatologists and cardiologists could improve outcomes.

Anti-cardiolipin and anti-beta 2-glycoprotein I antibodies in celiac disease.

AIMS: To determine the frequency of anti-cardiolipin (aCL) and anti-ß2-glycoprotein I antibodies (aß2GPI) in celiac disease (CD) patients. PATIENTS AND METHODS: Sixty-three untreated CD patients and 40 healthy blood donors (HBD) were studied. IgG, IgA and IgM aCL and aß2GPI were detected by Elisa. RESULTS: The frequency of antiphospholipid antibodies (aPL) (aCL and/or aß2GPI) was significantly higher in CD patients (12 out of 63) than in HBD (two out of 40) (19% vs 5%, P=0.04). Six CD patients out of 63 (9.5%) and one HBD out of 40 (2.5%) had aCL. Ten CD patients (15.9%) and two HBD (5%) had aß2GPI. Only aß2GPI-IgA was significantly more frequent in CD patients than in HBD (14.3% vs 2.5%, P=0.048). In CD patients, aß2GPI-IgA (nine out of 63) was significantly more frequent (14.3%) than aß2GPI-IgG (1.6%) and IgM (1.6%) (P=0.008). In CD patients, the frequency of aCL-IgA and IgM was 6.3% (four out of 63) and aCL-IgG were not detected. Simultaneous presence of positive antibodies was found in four CD patients: one patient had four aPL, one had three aPL and two had two aPL. The four patients who had aCL-IgA had also aß2GPI-IgA and three of them had a titer higher than 50 units. Among nine patients with aß2GPI-IgA, four had a titer higher than 100 units. The highest titers were found in adults. CONCLUSIONS: aPL and particularly aß2GPI-IgA are frequent in CD. The significance of these antibodies has to be determined.

Hierarchical carbon nanostructure design: ultra-long carbon nanofibers decorated with carbon nanotubes.

Hierarchical carbon nanostructures based on ultra-long carbon nanofibers (CNF) decorated with carbon nanotubes (CNT) have been prepared using plasma processes. The nickel/carbon composite nanofibers, used as a support for the growth of CNT, were deposited on nanopatterned silicon substrate by a hybrid plasma process, combining magnetron sputtering and plasma-enhanced chemical vapor deposition (PECVD). Transmission electron microscopy revealed the presence of spherical nanoparticles randomly dispersed within the carbon nanofibers. The nickel nanoparticles have been used as a catalyst to initiate the growth of CNT by PECVD at 600°C. After the growth of CNT onto the ultra-long CNF, SEM imaging revealed the formation of hierarchical carbon nanostructures which consist of CNF sheathed with CNTs. Furthermore, we demonstrate that reducing the growth temperature of CNT to less than 500°C leads to the formation of carbon nanowalls on the CNF instead of CNT. This simple fabrication method allows an easy preparation of hierarchical carbon nanostructures over a large surface area, as well as a simple manipulation of such material in order to integrate it into nanodevices.

IgA anti-actin antibodies in celiac disease.

AIMS: The purpose of this study was to determine the sensitivity and specificity of IgA anti-actin antibodies (IgA-AAA) for celiac disease (CD), to investigate their usefulness as a marker of compliance in CD patients to the gluten-free diet (GFD), and to assess the relationship between their presence in the sera of CD patients and severity of intestinal mucosal damage. PATIENTS AND METHODS: A total of 182 patients with CD were studied: 63 patients were untreated; 50 patients were following a strict GFD; and 69 patients were non-compliant with a GFD. IgA-AAA was detected using a homemade enzyme-linked immunosorbent assay (ELISA). RESULTS: IgA-AAA showed a sensitivity of 41.3% and a specificity of 71.4% for a diagnosis of CD. In children, the frequency of IgA-AAA detection was lower in those following a strict GFD (23.1%) compared with untreated patients (39.4%) and those not complying with a GFD (32.5%). In patients following a strict GFD, IgA-AAA detection was significantly less frequent in children than in adults (23.1% vs. 58.3%, respectively; P<0.001). IgA-AAA was found in 17 out of 52 CD patients with total villous atrophy (32.7%), and in one out of 11 patients with subtotal villous atrophy (9%). CONCLUSION: IgA-AAA cannot replace anti-endomysium and anti-tissue transglutaminase antibodies in the diagnosis algorithm of CD, but it can serve as a reliable marker of severe intestinal mucosal damage in CD patients.

Outcomes of a primary care mental health implementation program in rural Rwanda: A quasi-experimental implementation-effectiveness study.

INTRODUCTION: To address the know-do gap in the integration of mental health care into primary care in resource-limited settings, a multi-faceted implementation program initially designed to integrate HIV/AIDS care into primary care was adapted for severe mental disorders and epilepsy in Burera District, Rwanda. The Mentoring and Enhanced Supervision at Health Centers (MESH MH) program supported primary care-delivered mental health service delivery scale-up from 6 to 19 government-run health centers over two years. This quasi-experimental study assessed implementation reach, fidelity, and clinical outcomes at health centers supported by MESH MH during the scale up period. METHODS: MESH MH consisted of four strategies to ensure the delivery of the priority care packages at health centers: training; supervision and mentorship; audit and feedback; and systems-based quality improvement (QI). Implementation reach (service use) across the 19 health centers supported by MESH MH during the two year scale-up period was described using routine service data. Implementation fidelity was measured at four select health centers by comparing total clinical supervisory visits and checklists to target goals, and by tracking clinical observation checklist item completion rates over a nine month period. A prospective before and after evaluation measured clinical outcomes in consecutive adults presenting to four select health centers over a nine month period. Primary outcome assessments at baseline, 2 and 6 months included symptoms and functioning, measured by the General Health Questionnaire (GHQ-12) and the World Health Organization Disability Assessment Scale (WHO-DAS Brief), respectively. Secondary outcome assessments included engagement in income generating work and caregiver burden using a quantitative scale adapted to context. RESULTS: A total of 2239 mental health service users completed 15,744 visits during the scale up period. MESH MH facilitated 70% and 76% of supervisory visit and clinical checklist utilization target goals, respectively. Checklist item completion rates significantly improved overall, and for three of five checklist item subgroups examined. 121 of 146 consecutive service users completed outcome measurements six months after entry into care. Scores improved significantly over six months on both the GHQ-12, with median score improving from 26 to 10 (mean within-person change 12.5 [95% CI: 10.9-14.0] p< 0.0001), and the WHO-DAS Brief, with median score improving from 26.5 to 7 (mean within-person change 16.9 [95% CI: 14.9-18.8] p< 0.0001). Over the same period, the percentage of surveyed service users reporting an inability to work decreased significantly (51% to 6% (p < 0.001)), and the proportion of households reporting that a caregiver had left income-generating work decreased significantly (41% to 4% (p < 0.001)). CONCLUSION: MESH MH was associated with high service use, improvements in mental health care delivery by primary care nurses, and significant improvements in clinical symptoms and functional disability of service users receiving care at health centers supported by the program. Multifaceted implementation programs such as MESH MH can reduce the evidence to practice gap for mental health care delivery by nonspecialists in resource-limited settings. The primary limitation of this study is the lack of a control condition, consistent with the implementation science approach of the study. STUDY REGISTRATION: ISRCTN #37231.

Cloning, expression, purification, crystallization and preliminary X-ray analysis of the pilus-associated sortase C from Streptococcus pneumoniae.

The pilus-associated sortase C from Streptococcus pneumoniae (SrtC or Srt-2) acts as a polymerase for the pilus subunit proteins RrgA and RrgB. Here, the crystallization and preliminary X-ray diffraction analysis of three crystal forms of SrtC are reported. One crystal form belongs to space group P2(1)2(1)2(1), with unit-cell parameters a = 48.9, b = 96.9, c = 98.9 A, alpha = beta = gamma = 90 degrees . The other two crystal forms belong to space group P222, with unit-cell parameters a = 48.8, b = 97.2, c = 99.2 A, alpha = beta = gamma = 90 degrees and a = 48.6, b = 96.5, c = 98.8 A, alpha = beta = gamma = 90 degrees , respectively. Preliminary analysis indicates the presence of two molecules in the asymmetric unit of the crystal for all three forms.

[Antineutrophil cytoplasmic antibodies and associated diseases]. / Anticorps anticytoplasme des polynucléaires neutrophiles et pathologies associées.

Antineutrophil cytoplasmic antibodies are classical serological markers of small-vessels vasculitis. However, they have been described in many other pathological situations. The aim of this study was to determine through our experience, the main antineutrophil cytoplasmic antibodies-associated diseases and to investigate antigen targets of these antibodies. Forty complete observations of antineutrophil cytoplasmic antibodies (ANCA) positive patients either by indirect immunofluorescence or by enzyme immunoassay were analysed. Only five (12.5%) patients have small-vessels vasculitis. Among these, antineutrophil cytoplasmic antibodies were detected only by Elisa in one patient and they were exclusively directed against bactericidal permeability increasing protein in another one. Our study confirms the presence of antineutrophil cytoplasmic antibodies in different diseases. It demonstrates that antineutrophil cytoplasmic antibodies should be investigated by Elisa when indirect immunofluorescence is negative. In small-vessels vasculitis, Proteinase 3 and myeloperoxidase are mainly but not exclusively the antigenic targets of antineutrophil cytoplasmic antibodies.

Short- and long-term follow-up of living kidney donors.

Living-donor kidney transplantation is a well-established treatment of end-stage renal disease in Tunisia. Over the years, concerns have increased about the harmlessness of kidney donation. This longitudinal single center study was carried out to evaluate the safety of nephrectomy as well as further medical and surgical outcomes among donors. We collected and analyzed clinical, biological, biochemical and kidney size data at the time of nephrectomy and at M1, M3, M6, Y1, Y2, and Y4 after donation measured by ultrasound. All donor nephrectomies performed in the nephrology and transplantation unit of Sahloul Hospital of Sousse since October 2006 were included. Criteria of exclusion were lost to follow-up or lack of complete data. Of the 106 donors (66 females and 40 males), 92 donors were included in the follow-up analysis after following exclusion criteria. The mean age at the time of nephrectomy was 42.8 ± 10 years with the sex ratio 0.6. and 27% of our donors were mothers. Twenty-two percent of the donors were obese and 4% were hypertensive. The median initial glomerular filtration rate (GFR) was 105 mL/min/1.73 m2. The surgical approach was costal lumbotomy in 96% of cases and laparoscopy for four cases. The kidneys were removed from the left side in 93% of cases. Postoperative mortality was zero and early postoperative morbidity was low. The median duration of hospital stay was nine days. During follow-up, 14% attended all recommended visits. The median follow-up duration was 26 months. After two years post donation, the prevalence of HTN was 28% and obesity was 26%. The prevalence of GFR decline (50-59 mL/min) was 14% using formula by modification of diet in renal disease. None of our donors reached stage 4 or 5 CKD. Twelve had proteinuria and one donor had diabetes, a comparable prevalence of morbidities to the general population.

Recombinant human erythropoietin prevents etoposide- and methotrexate-induced toxicity in kidney and liver tissues via the regulation of oxidative damage and genotoxicity in Wistar rats.

Etoposide (ETO) and methotrexate (MTX) are two effective chemotherapeutic drugs. However, the clinical use of these drugs is limited by its toxicity in normal tissues, especially in kidney and in liver tissues. Recombinant human erythropoietin (rhEPO), erythropoietin hormone, has also been shown to exert tissue protective effects. The purpose of this study was to explore the protective effect of rhEPO against oxidative stress and genotoxicity induced by ETO and MTX in vivo. Adult male Wistar rats were divided into 10 groups (6 animals each): control group, rhEPO alone group, ETO alone group, MTX alone group and rhEPO + ETO/MTX groups. In rhEPO + ETO/MTX groups, three doses of pretreatment with rhEPO were performed: 1000, 3000 and 6000 IU/kg. Our results showed that rhEPO pretreatment protects liver and kidney tissues against oxidative stress induced by the anticancer drugs. The glycoprotein decreased malondialdehyde (MDA) levels, reduced catalase activity and ameliorated glutathione depletion. Furthermore, we showed that rhEPO administration prevented drug-induced DNA damage accessed by comet test. Altogether, our results suggested a protective role of rhEPO, especially at 3000 IU/kg, against ETO- and MTX-induced oxidative stress and genotoxicity in vivo.

[Evaluation of plasmatic homocysteine determination by gas chromatography-mass spectrometry]. / Evaluation d'un transfert de méthode : dosage de l'homocystéine plasmatique par chromatographie en phase gazeuse couplée à la spectrométrie de masse.

Total plasma homocysteine emerged in the past few years as an independent risk factor for cardiovascular diseases. This test is now currently prescribed for the diagnosis of unexplained thrombosis in young adults or recurrent thrombosis in patients with arteriopathy. This sulphured amino-acid is an important intermediate in transsulfuration and remethylation pathways of methionine metabolism. Within the context of a collaboration between Monastir and Grenoble Universities and because a gas chromatograph mass spectrometer (GC-MS) instrument was available in Monastir, we proposed to transpose a GC-MS method previously developed in Grenoble's hospital for this parameter and to validate it by comparison with the liquid chromatography tandem mass spectrometry (LC-MS-MS) method, used at present. Analytical performances were good: detection limit 0.4 micromol/L and linear range up to 4 mg/L (29.6 micromol/L), and between-run and within-run precision with coefficients of variation < 5% and < 8 %, respectively. The comparison with LC-MS-MS method showed a good correlation (y = 0.9874 x -0.208; r(2) = 0.84). Mean difference from LC-MS-MS was -0.4 micromol/L. Plasma concentrations of homocysteine (mean + SD) determined among Tunisian adults, 29 men, 27 women, of the same age were respectively: 11.6 +/- 2.4 micromol/L and 10.1 +/- 2.7 micromol/L, p = 0.025. This method is now currently used to evaluate tHcy concentration in patients with risk factors for cardiovascular disease.

Clinical impact of NK-cell reconstitution after reduced intensity conditioned unrelated cord blood transplantation in patients with acute myeloid leukemia: analysis of a prospective phase II multicenter trial on behalf of the Société Française de Greffe de Moelle Osseuse et Thérapie Cellulaire and Eurocord.

Unrelated cord blood transplantation (UCBT) after a reduced intensity conditioning regimen (RIC) has extended the use of UCB in elderly patients and those with co-morbidities without an HLA-identical donor, although post-transplant relapse remains a concern in high-risk acute myeloid leukemia (AML) patients. HLA incompatibilities between donor and recipient might enhance the alloreactivity of natural killer (NK) cells after allogeneic hematopoietic stem-cell transplantation (HSCT). We studied the reconstitution of NK cells and KIR-L mismatch in 54 patients who underwent a RIC-UCBT for AML in CR in a prospective phase II clinical trial. After RIC-UCBT, NK cells displayed phenotypic features of both activation and immaturity. Restoration of their polyfunctional capacities depended on the timing of their acquisition of phenotypic markers of maturity. The incidence of treatment-related mortality (TRM) was correlated with low CD16 expression (P=0.043) and high HLA-DR expression (P=0.0008), whereas overall survival was associated with increased frequency of NK-cell degranulation (P=0.001). These features reflect a general impairment of the NK licensing process in HLA-mismatched HSCT and may aid the development of future strategies for selecting optimal UCB units and enhancing immune recovery.

Evaluating process and clinical outcomes of a primary care mental health integration project in rural Rwanda: a prospective mixed-methods protocol.

INTRODUCTION: Integrating mental healthcare into primary care can reduce the global burden of mental disorders. Yet data on the effective implementation of real-world task-shared mental health programmes are limited. In 2012, the Rwandan Ministry of Health and the international healthcare organisation Partners in Health collaboratively adapted the Mentoring and Enhanced Supervision at Health Centers (MESH) programme, a successful programme of supported supervision based on task-sharing for HIV/AIDS care, to include care of neuropsychiatric disorders within primary care settings (MESH Mental Health). We propose 1 of the first studies in a rural low-income country to assess the implementation and clinical outcomes of a programme integrating neuropsychiatric care into a public primary care system. METHODS AND ANALYSIS: A mixed-methods evaluation will be conducted. First, we will conduct a quantitative outcomes evaluation using a pretest and post-test design at 4 purposively selected MESH MH participating health centres. At least 112 consecutive adults with schizophrenia, bipolar disorder, depression or epilepsy will be enrolled. Primary outcomes are symptoms and functioning measured at baseline, 8 weeks and 6 months using clinician-administered scales: the General Health Questionnaire and the brief WHO Disability Assessment Scale. We hypothesise that service users will experience at least a 25% improvement in symptoms and functioning from baseline after MESH MH programme participation. To understand any outcome improvements under the intervention, we will evaluate programme processes using (1) quantitative analyses of routine service utilisation data and supervision checklist data and (2) qualitative semistructured interviews with primary care nurses, service users and family members. ETHICS AND DISSEMINATION: This evaluation was approved by the Rwanda National Ethics Committee (Protocol #736/RNEC/2016) and deemed exempt by the Harvard University Institutional Review Board. Results will be submitted for peer-reviewed journal publication, presented at conferences and disseminated to communities served by the programme.

Prevalence of metabolic abnormalities in the Tunisian adults: a population based study.

AIMS: To estimate the prevalence of individual metabolic abnormalities and the cluster of metabolic abnormalities in a representative sample of the Tunisian adult population and to identify their relationship with gender, age and residency. The definition used is an adaptation of the NCEP ATP III definition, using total cholesterol>or=5.2 mmol/l instead of HDL-cholesterol. MATERIALS AND METHODS: We used a sample of the Tunisian National Nutrition Survey (TNNS), a cross-sectional health survey conducted in 1996, to estimate the nutritional status of the population. The TNNS included 2 927 adults aged 20 years or older who had measurements of height, body weight, waist circumference, blood pressure, fasting plasma glucose, total cholesterol and triglycerides. The cluster of metabolic abnormalities was defined as the presence of three or more metabolic abnormalities. RESULTS: The prevalence of abdominal obesity, hypertriglyceridemia, high total cholesterol, high blood pressure and high fasting plasma glucose was, respectively, 9%, 23%, 24%, 45% and 15% in men and 33%, 19%, 29%, 44% and 15% in women. The prevalence of the cluster was more frequent in women than in men (18% versus 13%, P<0.001) and in those living in urban communities (21% in women, 16% in men) rather than rural communities (11% in women, 8% in men) (P<0.001). The prevalence also increased significantly with age (P<0.001). CONCLUSION: The cluster of metabolic abnormalities and its components are common in the Tunisian adult population and prevalence increases significantly with female sex, urban residency and age.

Effect of recombinant human erythropoietin on mitomycin C-induced oxidative stress and genotoxicity in rat kidney and heart tissues.

Mitomycin C (MMC) is an antineoplastic agent used for the treatment of several human malignancies. Nevertheless, the prolonged use of the drug may result in a serious heart and kidney injuries. Recombinant human erythropoietin (rhEPO) has recently been shown to exert an important cytoprotective effect in experimental brain injury and ischemic acute renal failure. The aim of the present work is to investigate the cardioprotective and renoprotective effects of rhEPO against MMC-induced oxidative damage and genotoxicity. Our results showed that MMC induced oxidative stress and DNA damage. rhEPO administration in any treatment conditions decreased oxidative damage induced by MMC. It reduced malondialdehyde and protein carbonyl levels. rhEPO ameliorated reduced glutathione plus oxidized glutathione modulation and the increased catalase activity after MMC treatment. Furthermore, rhEPO restored DNA damage caused by MMC. We concluded that rhEPO administration especially in pretreatment condition protected rats against MMC-induced heart and renal oxidative stress and genotoxicity.

Are CD4 and Fas peptide identities of gp120 relevant to the molecular basis of AIDS pathogenesis?

The release of virions from HIV-1-infected CD4 cells, although occurring readily as a result of immune activation, does not appear to be the only mechanism mediating T-cell loss in AIDS. Three other interacting HIV-1-induced immune disorders in association with viral release (the source of gp120 molecules) may also account for the constitutive T-cell depletion and functional immune suppression: 1. gp120-induced CD4(+) cell anergy, which can be reproduced in cultures of immune activated normal T-cells in the presence of gp120 or gp120 peptide containing the SLWDQ sequence identity to the CD4 molecule; 2. overproduction of IFNalpha and gamma, 3. activation-driven apoptosis of non infected T-cells. Apoptosis of T-cells could also be: 1. induced by effector components - particularly CTL and lymphotoxins produced by helper T-cells of the anti-Fas autoimmune reaction triggered by gp120 epitopes shared with the Fas/APO-1 molecule; 2. enhanced by IFN overproduction. These molecular mechanisms stress the importance in the progression to AIDS of both the viral load and HIV-induced cytokine dysregulation, including overproduction of IFNalpha, which should be considered as targets in the development of strategies for AIDS prophylaxis and immunotherapy.

Altered MHC class I presented peptide repertoire is not sufficient to induce NK cell mediated F1-hybrid resistance.

Murine NK cells are known to mediate F1-hybrid anti-parental graft rejection responses. This phenomenon has been linked to the MHC, and in particular, to the alpha 1/alpha 2 domains of the MHC class I molecules. Here, we have addressed the role of MHC class I bound peptides in NK cell mediated F1-hybrid anti-parental rejection by studying the resistance of F1-hybrids between B6 and different bm mutant strains to B6-derived RBL-5 lymphoma cell line. Tumor development occurred at a similar frequency in all combinations of (B6 x bm)F1 mice and control B6 mice. These results suggest that absence of a specific MHC class I presented peptide repertoire on grafted cells is not sufficient to induce NK cell mediated F1-hybrid anti-parental rejection responses.

[Incidence of surgical wound infections a prospective study in the Rabat Mohamed-V military hospital, Morocco]. / Incidence des infections du site opératoire étude prospective à l'hôpital militaire d'instruction Mohamed-V de Rabat, Maroc.

OBJECTIVES: The authors had for aim to determine prospectively the incidence of surgical site infections (SSI) in a visceral surgery department, in the Mohamed V military hospital (Rabat), and to identify risk factors. PATIENTS AND METHODS: All patients who had undergone surgery between April 1 and September 30, 2002 and were then admitted in the visceral surgery unit were included in this study. Patients were assessed within the following month. For each patient, data including perioperative factors, type of procedure, and SSI occurrence were collected on a standardized form. RESULTS: During the study, 310 patients were operated. The number of surgical wound infections was 16 (5.2%). This analysis pointed out: 11 superficial wounds, 5 deep wounds, and 1 organ/site wound. Emergency, age, ASA score, Altemeier classification, and procedure duration were found to be risk factors for SSI in visceral surgery. According to the NNIS index, SSI rates increase from 2.7% for patients with a risk index of 0 to 10.2% for patients with a risk index of 3. CONCLUSION: The high incidence of SSI emphasizes the importance of implementing SSI surveillance in surgery to obtain standardized incidence ratios necessary for adapted control measures.