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Background: The WHO 2016 antenatal care (ANC) policy recommends at least eight antenatal contacts during pregnancy. This study assessed ANC8 uptake following policy implementation and explored the relationship between ANC attendance and intermittent preventive treatment in pregnancy (IPTp) coverage in sub-Saharan Africa following the rollout of the World Health Organization (WHO) 2016 ANC policy, specifically, to assess differences in IPTp uptake between women attending eight versus four ANC contacts., Methods: A secondary analysis of data from 20 sub-Saharan African countries with available Demographic Health and Malaria Indicator surveys from 2018 to 2023 was performed. The key variables were the number of ANC contacts and IPTp doses received during a participant's last completed pregnancy in the past two years. Pooled crude and multivariable logistic regression models were used to explore factors associated with attendance of at least four or eight ANC contacts as well as receipt of at least three doses of IPTp during pregnancy., Results: Overall, only a small proportion of women (median = 3.9%) completed eight or more ANC contacts (ANC8 +). Factors significantly associated with increased odds of ANC8 + included early ANC attendance (AOR: 4.61: 95% CI 4.30-4.95), literacy (AOR: 1.20; 95% CI 1.11-1.29), and higher wealth quintile (AOR: 3.03; 95% CI 2.67-3.44). The pooled estimate across all countries showed a very slight increase in the odds of IPTp3 + among women with eight (AOR: 1.06; 95% CI 1.00-1.12) compared to those with four contacts. In all but two countries, having eight instead of four ANC contacts did not confer significantly greater odds of receiving three or more doses of IPTp (IPTp3 +), except in Ghana (AOR: 1.67; 95% CI 1.38-2.04) and Liberia (AOR: 1.43; 95% CI 1.18-1.72)., Conclusion: Eight years after the WHO ANC policy recommendation, all countries still had sub-optimal ANC8 + coverage rates. This paper is a call to action to actualize the vision of the WHO and the global malaria community of a malaria free world. Policies to improve ANC and IPTp coverage should be operationalized with clear actionable guidance and local ownership. Study findings can be used to inform multi-level policy, programmatic, and research recommendations to optimize ANC attendance and malaria in pregnancy prevention, thus improving maternal and child health outcomes, including the reduction of malaria in pregnancy., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Evidence suggests that bi-annual mass drug administration (MDA) of single-dose azithromycin to 1-11 month-old children reduces child mortality in high child-mortality settings. Several countries conduct annual MDAs to distribute azithromycin to individuals ages 6 months and older to prevent trachoma infection. This study examined the feasibility and acceptability of reaching 1-11 months-old children during a trachoma MDA in Côte d'Ivoire by extending azithromycin distribution to infants 1-5 months old during the campaign. In November 2020, the study piloted single-dose azithromycin for 1-5 month-olds during a trachoma MDA in one health district. Monitoring data included the number of children reached and occurrences of adverse drug reactions. Feasibility, the extent to which the target population received the intervention (coverage), was assessed through a population-based, household survey with parents/caregivers of eligible children conducted after the MDA. Acceptability was explored through in-depth interviews (IDIs) with parents/caregivers of eligible children, focus group discussions (FGDs) with community drug distributors (CDDs), and IDIs with their supervisors. CDD FGDs and supervisor IDIs also documented implementation challenges and recommendations for scale-up. 1,735 1-5 month-olds received azithromycin during the pilot activity (estimated population coverage of 90.2%). Adverse drug reactions were reported for 1% (n = 18) infants; all were mild and self-limited. The post-MDA coverage survey interviewed 267 parents/caregivers; survey-based intervention coverage was 95.4% of 1-5 month-olds. Qualitative data revealed high intervention acceptability among parents, CDDs, and supervisors. Implementation challenges included the need to weigh babies to calculate dosage for 1-5 month-olds and the need to obtain written informed consent from parents to provide the drug to 1-5 month-olds. CDDs also indicated the need for more information on azithromycin and possible side effects during training. Delivering azithromycin to younger infants appears acceptable to parents and implementers; >90% coverage indicates feasibility to integrate into a trachoma MDA. (Clinicaltrials.gov ID number: NCT04617626)., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Dulli et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Outpatient treatment of acute malnutrition is usually centralized in health centers and separated into different programs according to case severity. This complicates case detection, care delivery, and supply chain management, making it difficult for families to access treatment. This study assessed the impact of treating severe and moderate cases in the same program using a simplified protocol and decentralizing treatment outside health centers through community health workers (CHWs)., Methods: A three-armed cluster randomized controlled trial under a non-inferiority hypothesis was conducted in the Gao region of Mali involving 2,038 children between 6 and 59 months of age with non-complicated acute malnutrition. The control arm consisted of 549 children receiving standard treatment in health centers from nursing staff. The first intervention arm consisted of 800 children treated using the standard protocol with CHWs added as treatment providers. The second intervention arm consisted of 689 children treated by nurses and CHWs under the ComPAS simplified protocol, considering mid-upper arm circumference as the sole anthropometric criterion for admission and discharge and providing a fixed dose of therapeutic food for severe and moderate cases. Coverage was assessed through cross-sectional surveys using the sampling evaluation of access and coverage (SLEAC) methodology for a wide area involving several service delivery units., Results: The recovery rates were 76.3% in the control group, 81.8% in the group that included CHWs with the standard protocol, and 92.9% in the group that applied the simplified protocol, confirming non-inferiority and revealing a significant risk difference among the groups. No significant differences were found in the time to recovery (6 weeks) or in anthropometric gain, whereas the therapeutic food expenditure was significantly lower with the simplified combined program in severe cases (43 sachets fewer than the control). In moderate cases, an average of 35 sachets of therapeutic food were used. With the simplified protocol, the CHWs had 6% discharge errors compared with 19% with the standard protocol. The treatment coverage increased significantly with the simplified combined program (SAM +42.5%, MAM +13.8%)., Implications: Implementing a simplified combined treatment program and adding CHWs as treatment providers can improve coverage while maintaining non-inferior effectiveness, reducing the expenditure on nutritional intrants, and ensuring the continuum of care for the most vulnerable children., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 López-Ejeda, Charle-Cuéllar, Samake, Dougnon, Sánchez-Martínez, Samake, Bagayoko, Bunkembo, Touré, Vargas and Guerrero.)

Background: An estimated 21,000 children 0-14 years of age were living with HIV in Côte d'Ivoire in 2020, of whom only 49% have been diagnosed and are receiving antiretroviral therapy (ART). Retention in HIV care and treatment is key to optimize clinical outcomes. We evaluated pediatric retention in select care and treatment centers (CTCs) in Côte d'Ivoire., Methods: We retrospectively reviewed medical records using 2-stage cluster sampling for children under 15 years initiated on ART between 2012 and 2016. Kaplan-Meier time-to-event analysis was done to estimate cumulative attrition rates per total person-years of observation. Cox proportional hazard regression was performed to identify factors associated with attrition., Results: A total of 1198 patient records from 33 CTCs were reviewed. Retention at 12, 24, 36, 48 and 60 months after ART initiation was 91%, 84%, 74%, 72% and 70%, respectively. A total of 309 attrition events occurred over 3169 person-years of follow-up [266 children were lost to follow-up (LTFU), 29 transferred to another facility and 14 died]. LTFU determinants included attending a "public-private" CTC [adjusted hazard ratio (aHR) 6.05; 95% confidence interval (CI): 4.23-8.65], receiving care at a CTC without an on-site laboratory (aHR: 4.01; 95% CI: 1.70-9.46) or attending a CTC without an electronic medical record (EMR) system (aHR: 2.22; 95% CI: 1.59-3.12)., Conclusions: In Cote d'Ivoire, patients attending a CTC that is public-private, does not have on-site laboratory or EMR system were likely to be LTFU. Decentralization of laboratory services and scaling use of EMR systems could help to improve pediatric retention., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Reports on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spread across Africa have varied, including among healthcare workers (HCWs). This study assessed the comparative SARS-CoV-2 burden and associated risk factors among HCWs in three African countries., Methods: A multicentre study was conducted at regional healthcare facilities in Côte d'Ivoire (CIV), Burkina Faso (BF) and South Africa (SA) from February to May 2021. HCWs provided blood samples for SARS-CoV-2 serology and nasopharyngeal/oropharyngeal swabs for testing of acute infection by polymerase chain reaction and completed a questionnaire. Factors associated with seropositivity were assessed with logistic regression., Results: Among 719 HCWs, SARS-CoV-2 seroprevalence was 34.6% (95% confidence interval 31.2 to 38.2), ranging from 19.2% in CIV to 45.7% in BF. A total of 20 of 523 (3.8%) were positive for acute SARS-CoV-2 infection. Female HCWs had higher odds of SARS-CoV-2 seropositivity compared with males, and nursing staff, allied health professionals, non-caregiver personnel and administration had higher odds compared with physicians. HCWs also reported infection prevention and control (IPC) gaps, including 38.7% and 29% having access to respirators and IPC training, respectively, in the last year., Conclusions: This study was a unique comparative HCW SARS-CoV-2 investigation in Africa. Seroprevalence estimates varied, highlighting distinctive population/facility-level factors affecting COVID-19 burden and the importance of established IPC programmes to protect HCWs and patients., (© The Author(s) 2022. Published by Oxford University Press on behalf of Royal Society of Tropical Medicine and Hygiene.)

Background: Social deprivation could act as a barrier to peritoneal dialysis (PD). The objective of this study was to assess the association between social deprivation estimated by the European deprivation index (EDI) and PD uptake and to explore the potential mediators of this association., Methods: From the Renal Epidemiology and Information Network registry, patients who started dialysis in 2017 were included. The EDI was calculated based on the patient's address. The event of interest was the proportion of PD 3 months after dialysis initiation. A mediation analysis with a counterfactual approach was carried out to evaluate the direct and indirect effect of the EDI on the proportion of PD., Results: Among the 9588 patients included, 1116 patients were on PD; 2894 (30.2%) patients belonged to the most deprived quintile (Q5). PD was associated with age >70 years (odds ratio (OR) 0.79 [95% confidence interval (CI): 0.69-0.91]), male gender (0.85 [95% CI: 0.74-0.97]), cardiovascular disease (OR 0.86 [95% CI: 0.86-1.00]), chronic heart failure (OR 1.34 [95% CI: 1.13-1.58]), active cancer (OR 0.67 [95% CI: 0.53-0.85]) and obesity (OR 0.75 [95% CI: 0.63-0.89]). In the mediation analysis, Q5 had a direct effect on PD proportion OR 0.84 [95% CI: 0.73-0.96]. The effect of Q5 on the proportion of PD was mediated by haemoglobin level at dialysis initiation (OR 0.96 [95% CI: 0.94-0.98]) and emergency start (OR 0.98 [95% CI: 0.96-0.99])., Conclusion: Social deprivation, estimated by the EDI, was associated with a lower PD uptake. The effect of social deprivation was mediated by haemoglobin level, a proxy of predialysis care and emergency start.

A growing number of studies have used virtual reality (VR) for the assessment and treatment of body image disturbances (BIDs). This study, conducted in a community sample of adolescents, documents the convergent and discriminant validity between (a) the traditional paper-based Figure Rating Scale (paper-based FRS), (b) the VR-based Body Rating Scale ( e LoriCorps-IBRS 1.1), and (c) the mobile app-based Body Rating Scale ( e LoriCorps-IBRS 1.1-Mobile). A total of 93 adolescents (14 to 18 years old) participated in the study. Body dissatisfaction and body distortion were assessed through the paper-based FRS, the e LoriCorps-IBRS 1.1 and the e LoriCorps-IBRS 1.1-Mobile. Eating disorder symptoms, body image avoidance, and social physique anxiety were also measured. Correlation analyses were performed. Overall, the results showed a good and statistically significant convergence between allocentric perspectives as measured by the paper-based FRS, the e LoriCorps-IBRS 1.1 and the e LoriCorps-IBRS 1.1-Mobile. As expected, the egocentric perspective measured in VR produced different results from the allocentric perspective, and from cognitive-attitudinal-affective dimensions of BIDs, with the exception of body distortion. These differences support the discriminant validity of the egocentric perspective of e LoriCorps-IBRS 1.1 and are consistent with emerging evidence, highlighting a difference between experiencing the body from an egocentric (i.e., the body as a subject) and allocentric (i.e., the body as an object) perspective. The egocentric perspective could reflect a perceptual-sensory-affective construction of BIDs, whereas allocentric measures seem to be more related to a cognitive-affective-attitudinal construction of BIDs. Moreover, the results support the validity of the e LoriCorps-IBRS 1.1-Mobile with promising perspectives of implementation among young populations.

Background: Thymomas have been associated with a broad spectrum of autoimmune diseases. Minimal change disease (MCD) is the most frequent pathological lesion reported. Pathophysiological mechanisms involved in secondary MCD, and linking MCD to thymoma are not yet fully explained, although the hypothesis of T cell dysfunction has been suggested. The fundamental therapeutic principles are steroids and surgical treatment of thymoma, but failures and relapses often require immunosuppressant combinations., Case Presentation: A 62-year-old female was admitted in our unit for a nephrotic syndrome associated with a thymoma. The diagnosis of thymoma associated MCD was confirmed by kidney biopsy. After surgical resection of the thymoma and steroid therapy, no remission was observed. Immunosuppressive therapy was then intensified with introduction of rituximab. Here, we report a steroid-resistant nephrotic syndrome secondary to MCD associated thymoma, which achieved complete remission after rituximab therapy. To the best of our knowledge, this is the first report of the use and efficacy of rituximab therapy in this pathology., Conclusions: Our case report suggests that primary and secondary MCD may share similar pathophysiological mechanisms. It does not allow us to draw any conclusions about the mechanism of action of rituximab, but we believe this report argues for the safety and efficacy of rituximab use in thymoma-associated MCD, and therefore constitutes a rationale for future studies., (© 2021. The Author(s).)

Background: Kidney transplant recipients and patients receiving hemodialysis are immunocompromised populations that are prioritized for COVID-19 vaccination but were excluded from clinical trials of SARS-CoV-2 mRNA vaccines. Antibody titers and rates of seroconversion after vaccination are lower among patients with CKD and those taking immunosuppressants compared with controls. Data are lacking regarding their humoral response to vaccination to prevent COVID-19., Methods: This investigation of early serological response after COVID-19 vaccination with the Pfizer/BioNTech (BNT162b2) mRNA vaccine included 78 patients undergoing hemodialysis, 74 kidney transplant recipients, and seven healthy controls. We recorded data from the medical file for various clinical parameters, including response to hepatitis B vaccination, and measured antibody titers against SARS-CoV-2 at 0, 14, 28, 36, and 58 days after the first injection., Results: In controls, we detected antibodies at a positive level (>13 arbitrary units per ml; AU/ml) at day 14 postinjection, which increased progressively to peak at day 36 (1082 AU/ml; interquartile range [IQR], 735.0-1662.0). Patients undergoing hemodialysis had lower titers that peaked at day 58 (276 AU/ml; IQR, 83.4-526.0). We detected a positive antibody level in only three transplant recipients at day 36. In patients on hemodialysis, those aged <75 years had a higher antibody response versus those aged >75 years, and serum albumin and Kt/V were positively correlated with serological response ( P <0.04 and P <0.0, respectively); nonresponders to HBV vaccine had the lowest anti-SARS-CoV-2 antibody titers., Conclusions: Our results suggest that the postvaccination humoral response is strongly inhibited by immunosuppressant therapy in kidney transplant recipients, and is reduced by the uremic condition in patients undergoing hemodialysis., (Copyright © 2021 by the American Society of Nephrology.)

Peripheral arterial disease occurs more frequently and has a worse prognosis in patients with chronic kidney disease (CKD). The receptor for advanced glycation end products (RAGE) is involved in multiple aspects of uremia-associated vasculopathy. Previous data suggest that the RAGE pathway may promote soluble fms-like tyrosine kinase 1 (sFlt1) production, an anti-angiogenic molecule. Thus, we tested the hypothesis that the deletion of AgeR would decrease sFlt1 production and improve post-ischemic revascularization in uremic condition. We used a well-established CKD model (5/6 nephrectomy) in WT and AgeR -/- C57/Bl6 mice. Hindlimb ischemia was induced by femoral artery ligation. Revascularization was evaluated by complementary approaches: ischemic limb retraction, LASCA imagery, and capillary density. The production of sFlt1 was assessed at both RNA and protein levels. After hindlimb ischemia, uremic mice showed slower functional recovery (p < 0.01), decreased reperfusion (p < 0.01), lower capillary density (p = 0.02), and increased circulating sFlt1 levels (p = 0.03). AgeR deletion restored post-ischemic angiogenesis and was protective from sFlt1 increase in uremic mice. These findings show the main role of RAGE in post-ischemic angiogenesis impairment associated with CKD. RAGE may represent a key target for building new therapeutic approaches to improve the outcome of CKD patients with PAD.

Arterial stiffness is a complex process affecting the aortic tree that significantly contributes to cardiovascular diseases (systolic hypertension, coronary artery disease, heart failure or stroke). This process involves a large extracellular matrix remodeling mainly associated with elastin content decrease and collagen content increase. Additionally, various chemical modifications that accumulate with ageing have been shown to affect long-lived assemblies, such as elastic fibers, that could affect their elasticity. To precisely characterize the fiber changes and the evolution of its elasticity with ageing, high resolution and multimodal techniques are needed for precise insight into the behavior of a single fiber and its surrounding medium. In this study, the latest developments in atomic force microscopy and the related nanomechanical modes are used to investigate the evolution and in a near-physiological environment, the morphology and elasticity of aorta cross sections obtained from mice of different ages with an unprecedented resolution. In correlation with more classical approaches such as pulse wave velocity and fluorescence imaging, we demonstrate that the relative Young's moduli of elastic fibers, as well as those of the surrounding areas, significantly increase with ageing. This nanoscale characterization presents a new view on the stiffness process, showing that, besides the elastin and collagen content changes, elasticity is impaired at the molecular level, allowing a deeper understanding of the ageing process. Such nanomechanical AFM measurements of mouse tissue could easily be applied to studies of diseases in which elastic fibers suffer pathologies such as atherosclerosis and diabetes, where the precise quantification of fiber elasticity could better follow the fiber remodeling and predict plaque rupture.

Background:  Chronic kidney disease (CKD) is associated with a high cardiovascular mortality due to increased rates of vascular lesions and thrombotic events, as well as serum accumulation of uremic toxins. A subgroup of these toxins (advanced glycation end products [AGEs] and S100 proteins) can interact with the receptor for AGEs (RAGE). In this study, we analyzed the impact of CKD on platelet function and arterial thrombosis, and the potential role of RAGE in this process., Methods:  Twelve weeks after induction of CKD in mice, platelet function and time to complete carotid artery occlusion were analyzed in four groups of animals (sham-operated, CKD, apolipoprotein E [Apoe] -/- , and Apoe -/- /Ager -/- mice)., Results:  Analysis of platelet function from whole blood and platelet-rich plasma showed hyperactivation of platelets only in CKD Apoe -/- mice. There was no difference when experiments were done on washed platelets. However, preincubation of such platelets with AGEs or S100 proteins induced RAGE-mediated platelet hyperactivation. In vivo, CKD significantly reduced carotid occlusion times of Apoe -/- mice (9.2 ± 1.1 vs. 11.1 ± 0.6 minutes for sham, p  < 0.01). In contrast, CKD had no effect on occlusion times in Apoe -/- /Ager -/- mice. Moreover, carotid occlusion in Apoe -/- CKD mice occurred significantly faster than in Apoe -/- /Ager -/- CKD mice ( p  < 0.0001)., Conclusion:  Our results show that CKD induces platelet hyperactivation, accelerates thrombus formation in a murine model of arterial thrombosis, and that RAGE deletion has a protective role. We propose that RAGE ligands binding to RAGE is involved in CKD-induced arterial thrombosis., Competing Interests: None declared., (Thieme. All rights reserved.)

Community pharmacists (CPs) have traditionally had limited access to patients' estimated glomerular filtration rate (eGFR) during the medication-dispensing process. The increasing access to shared electronic health records is making eGFR available, but the skills needed to detect and manage clinically relevant drug-related problems (DRPs) are poorly documented. The primary objective of this study was to investigate the role of CPs in the medication-dispensation process for elderly patients with renal impairment. A total of 70 CPs participated in this 6 month study. Community pharmacists asked all patients ≥65 years to bring their laboratory test values for the next medication-dispensing process. Drug-related problem detection rates were compared between CPs (prospective period) and expert pharmacists (retrospectively). The clinical relevance of each DRP was assessed by nephrologists and general practitioners using an appropriate tool. Community pharmacists recruited n = 442 patients with eGFR < 60 mL/min/1.73 m 2 and detected n = 99 DRPs, whereas expert pharmacists detected n = 184 DRPs. The most frequently detected DRPs were dosage problems and contraindications. According to assessment by clinicians, CPs and expert pharmacists identified 54.0% and 84.7% of clinically relevant DRPs, respectively. This study suggests a positive impact of the systematic availability of eGFR to CPs on the detection of several DRPs with clinical relevance.

Introduction: Peritoneal dialysis (PD) is reported to be underused in the autosomal dominant polycystic kidney disease (ADPKD) population because doctors fear technical failure caused by reduced abdominal space and high intraperitoneal pressure (IPP)., Methods: We designed a multicenter retrospective study to be carried out in 15 French centers recruiting 60 patients with ADPKD treated with PD to identify factors associated with IPP. Inclusion criteria were start of PD between 2010 and 2017, available tomodensitometry, and IPP measurement in the first year of dialysis. The clinical and radiological data for each patient were reviewed by the same operator. Total kidney volume (TKV), liver volume, and the volume of the abdominal cavity were measured using contouring., Results: TKV and the volume of the abdominal cavity in women and men were, respectively, 2397 ml versus 3758 ml and 9402 ml versus 12,920 ml. In the univariate analysis, IPP was significantly and positively associated with body surface area ( P  = 0.0024), body mass index (BMI) ( P  < 0.0001), the volume of the abdominal cavity ( P  = 0.0005), and the volume of the dialysate infused in the peritoneal cavity (IPV) ( P  = 0.0108). In the multivariate analysis, only BMI was still significantly associated with IPP ( P  = 0.0004)., Conclusions: Our results identified BMI as the main factor linked to IPP in patients with ADPKD. Despite a reliable assessment of the volume of their organs we did not find any correlation between liver and kidney volumes and IPP. To our knowledge, this is the first study designed to identify factors associated with IPP in patients with ADPKD on PD., (© 2020 International Society of Nephrology. Published by Elsevier Inc.)

Background: Autosomal dominant polycystic kidney disease (ADPKD) is a common genetic disorder associated with progressive enlargement of the kidneys and liver. ADPKD patients may require renal volume reduction, especially before renal transplantation. The standard treatment is unilateral nephrectomy. However, surgery incurs a risk of blood transfusion and alloimmunization. Furthermore, when patients are treated with peritoneal dialysis (PD), surgery is associated with an increased risk of temporary or definitive switch to haemodialysis (HD). Unilateral renal arterial embolization can be used as an alternative approach to nephrectomy., Methods: We performed a multicentre retrospective study to compare the technique of survival of PD after transcatheter renal artery embolization with that of nephrectomy in an ADPKD population. We included ADPKD patients treated with PD submitted to renal volume reduction by either surgery or arterial embolization. Secondary objectives were to compare the frequency and duration of a temporary switch to HD in both groups and the impact of the procedure on PD adequacy parameters., Results: More than 700 patient files from 12 centres were screened. Only 37 patients met the inclusion criteria (i.e. treated with PD at the time of renal volume reduction) and were included in the study (21 embolized and 16 nephrectomized). Permanent switch to HD was observed in 6 embolized patients (28.6%) versus 11 nephrectomized patients (68.8%) (P = 0.0001). Renal artery embolization was associated with better technique survival: subdistribution hazard ratio (SHR) 0.29 [95% confidence interval (CI) 0.12-0.75; P = 0.01]. By multivariate analysis, renal volume reduction by embolization and male gender were associated with a decreased risk of switching to HD. After embolization, a decrease in PD adequacy parameters was observed but no embolized patients required temporary HD; the duration of hospitalization was significantly lower [5 days [interquartile range (IQR) 4.0-6.0] in the embolization group versus 8.5 days (IQR 6.0-11.0) in the surgery group., Conclusions: Transcatheter renal artery embolization yields better technique survival of PD in ADPKD patients requiring renal volume reduction., (© The Author(s) 2019. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.)

Background: Chronic kidney disease (CKD) is associated with increased cardiovascular mortality, frequent vascular calcification (VC) and accumulation of uraemic toxins. Advanced glycation end products and S100 proteins interact with the receptor for advanced glycation end products (RAGE). In the present work, we aimed to investigate the role(s) of RAGE in the CKD-VC process., Methods: Apoe-/- or Apoe-/-Ager (RAGE)-/- male mice were assigned to CKD or sham-operated groups. A high-phosphate diet was given to a subgroup of Apoe-/-and Apoe-/-Ager-/- CKD mice. Primary cultures of Ager+/+ and Ager-/- vascular smooth muscle cells (VSMCs) were established and stimulated with either vehicle, inorganic phosphate (Pi) or RAGE ligands (S100A12; 20 µM)., Results: After 12 weeks of CKD we observed a significant increase in RAGE ligand (AGE and S100 proteins) concentrations in the serum of CKD Apoe-/- mice. Ager messenger RNA (mRNA) levels were 4-fold higher in CKD vessels of Apoe-/- mice. CKD Apoe-/- but not CKD Apoe-/- or Ager-/- mice displayed a marked increase in the VC surface area. Similar trends were found in the high-phosphate diet condition. mRNA levels of Runx2 significantly increased in the Apoe-/- CKD group. In vitro, stimulation of Ager+/+VSMCs with Pi or S100A12 induced mineralization and osteoblast transformation, and this was inhibited by phosphonoformic acid (Pi co-transporters inhibitor) and Ager deletion. In vivo and in vitro RAGE was necessary for regulation of the expression of Pit-1, at least in part through production of reactive oxygen species., Conclusion: RAGE, through the modulation of Pit-1 expression, is a key molecule in the genesis of VC., (© The Author(s) 2019. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.)

Background: To improve the care and treatment of HIV-exposed children, early infant diagnosis (EID) using dried blood spot (DBS) sampling has been performed in Senegal since 2007, making molecular diagnosis accessible for patients living in decentralized settings. This study aimed to determine the evolution of the HIV transmission rate in children from 2008 to 2015 and to analyze associated factors, particularly the mother's treatment status and/or child's prophylaxis status and the feeding mode., Methods: The data were analyzed using EID reports from the reference laboratory. Information related to sociodemographic characteristics, HIV profiles, the mother's treatment status, the child's prophylaxis status, and the feeding mode was included. Descriptive statistics were calculated, and bivariate and multivariate logistic regression analyses were performed., Results: During the study period, a total of 5418 samples (5020 DBS and 398 buffy coat) from 168 primary prevention of HIV mother-to-child transmission (PMTCT) intervention sites in Senegal were tested. The samples were collected from 4443 children with a median age of 8 weeks (1-140 weeks) and a sex ratio (M/F) of 1.1 (2309/2095). One-third (35.2%; N = 1564) of the children were tested before 6 weeks of age. Twenty percent (N = 885) underwent molecular diagnostic testing more than once. An increased number of mothers receiving treatment (57.4%; N = 2550) and children receiving prophylaxis (52.1%; N = 2315) for protection against HIV infection during breastfeeding was found over the study period. The transmission rate decreased from 14.8% (95% confidence interval (CI): 11.4-18.3) in 2008 to 4.1% (95% CI: 2.5-7.5) in 2015 (p < 0.001). However, multivariate logistic regression analysis revealed that independent predictors of HIV mother-to-child transmission included lack of mother's treatment (adjusted odd ratio (aOR) = 3.8, 95% CI: 1.9-7.7; p˂0.001), lack of child's prophylaxis (aOR = 7.8, 95% CI: 1.7-35.7; p = 0.009), infant age at diagnosis (aOR = 2.2, 95% CI: 1.1-4.3 for ≤6 weeks versus 12-24 weeks; p = 0.025) and protective effect of breastfeeding on ART against formula feeding (aOR = 0.4, 95% CI: 0.2, 0.7; p = 0.005)., Conclusion: This study demonstrates the effectiveness of PMTCT interventions in Senegal but indicates also that increased efforts should be continued to reduce the MTCT rate to less than 2%., Competing Interests: The authors have declared that no competing interests exist.

Background: Pathological features of autosomal dominant polycystic kidney disease (ADPKD) include enlarged kidney volume, higher frequency of digestive diverticulitis and abdominal wall hernias. Therefore, many nephrologists have concerns about the use of peritoneal dialysis (PD) in ADPKD patients. We aimed to analyse survival and technique failure in ADPKD patients treated with PD., Methods: We conducted two retrospective studies on patients starting dialysis between 2000 and 2010. We used two French registries: the French Renal Epidemiology and Information Network (REIN) and the French language Peritoneal Dialysis Registry (RDPLF). Using the REIN registry, we compared the clinical features and outcomes of ADPKD patients on PD (n = 638) with those of ADPKD patients on haemodialysis (HD) (n = 4653); with the RDPLF registry, those same parameters were determined for ADPKD patients on PD (n = 797) and compared with those of non-ADPKD patients on PD (n = 12 059)., Results: A total of 5291 ADPKD patients and 12 059 non-ADPKD patients were included. Analysis of the REIN registry found that ADPKD patients treated with PD represented 10.91% of the ADPKD population. During the study period, PD was used for 11.2% of the non-ADPKD population. Compared with ADPKD patients on HD, ADPKD patients on PD had higher serum albumin levels (38.8 ± 5.3 versus 36.8 ± 5.7 g/dL, P < 0.0001) and were less frequently diabetic (5.31 versus 7.71%, P < 0.03). The use of PD in ADPKD patients was positively associated with the occurrence of a kidney transplantation but not with death [hazard ratio 1.15 (95% confidence interval 0.84-1.58)]. Analysis of the RDPLF registry found that compared with non-ADPKD patients on PD, ADPKD patients on PD were younger and had fewer comorbidities and better survival. ADPKD status was not associated with an increased risk of technique failure or an increased risk of peritonitis., Conclusions: According to our results, PD is proposed to a selected population of ADPKD patients, PD does not have a negative impact on ADPKD patients' overall survival and PD technique failure is not influenced by ADPKD status. Therefore PD is a reasonable option for ADPKD patients.

Background: Polycystic kidney disease (PKD) is the most frequent hereditary cause of chronic kidney disease. Peritoneal dialysis (PD) is often avoided for patients with PKD because of the suspected risk of mechanical and infectious complications. Only a few studies have analyzed the outcome of PKD patients on PD with sometimes conflicting results. The purpose of this meta-analysis was to investigate outcomes of patients with PKD treated by PD., Methods: A systematic review and meta-analysis were performed examining all studies which included "Polycystic kidney disease" and "Peritoneal dialysis" in their titles, excluding commentaries, letters to the authors and abstracts. PubMed, Embase, Google scholar and Scopus were searched to December 31st 2017. The primary outcome was overall patient survival. Additional outcomes were PD technique survival, incidence of peritonitis and incidence of abdominal wall hernia., Results: 9 studies published between 1998 and 2016 were included for analysis with a total of 7,197 patients including 882 PKD patients. Overall survival of PKD patients was found to be better compared to non-PKD patients (HR = 0.70 [95% CI, 0.54-0.92]). There were no statistical differences between PKD and non-PKD patients in terms of peritonitis (OR = 0.86 [95% CI, 0.66-1.12]) and technical survival (HR = 0.98 [95% CI, 0.83-1.16]). There was an increased risk of hernia in PKD patients (OR = 2.28 [95% CI, 1.26-4.12])., Conclusions: PKD is associated with a better global survival, an increased risk of abdominal hernia, but no differences in peritonitis rate or technical survival were found. PD is a safe dialysis modality for PKD patients. Properly designed controlled studies are needed to determine whether all PKD patients are eligible for PD or whether some specific criteria should be determined., Competing Interests: The authors have declared that no competing interests exist.

Unfortunately, the original article [1] contained some errors. The table title of Tables 4, 5, 6, 7 were interchanged by mistake and displayed incorrectly in the article. The correct table titles of Tables 4, 5, 6, 7 can be found below.

Background: During the 2014-2016 Ebola epidemic in West Africa, a key epidemiological feature was disease transmission within healthcare facilities, indicating a need for infection prevention and control (IPC) training and support., Methods: IPC training was provided to frontline healthcare workers (HCW) in healthcare facilities that were not Ebola treatment units, as well as to IPC trainers and IPC supervisors placed in healthcare facilities. Trainings included both didactic and hands-on components, and were assessed using pre-tests, post-tests and practical evaluations. We calculated median percent increase in knowledge., Results: From October-December 2014, 20 IPC courses trained 1,625 Guineans: 1,521 HCW, 55 IPC trainers, and 49 IPC supervisors. Median test scores increased 40% (interquartile range [IQR]: 19-86%) among HCW, 15% (IQR: 8-33%) among IPC trainers, and 21% (IQR: 15-30%) among IPC supervisors (all P<0.0001) to post-test scores of 83%, 93%, and 93%, respectively., Conclusions: IPC training resulted in clear improvements in knowledge and was feasible in a public health emergency setting. This method of IPC training addressed a high demand among HCW. Valuable lessons were learned to facilitate expansion of IPC training to other prefectures; this model may be considered when responding to other large outbreaks.

Background: Malaria, filariasis, and intestinal parasitic infections (IPIs) are common and frequently overlap in developing countries. The prevalence and predictors of these infections were investigated in three different settlements (rural, semi-urban, and urban) of Gabon., Methods: During cross-sectional surveys performed from September 2013 to June 2014, 451 individuals were interviewed. In addition, blood and stool samples were analysed for the presence of Plasmodium, filarial roundworm, intestinal protozoan, and helminth infections., Results: Intestinal parasitic infections (61.1%), including intestinal protozoa (56.7%) and soil-transmitted helminths (STHs) (22.2%), predominated, whereas Plasmodium falciparum (18.8%), Loa loa (4.7%), and Mansonella perstans (1.1%) were less prevalent. Filariasis and STHs were mainly found in rural settlements, whereas a higher plasmodial infection prevalence rate was observed in the periurban area. The most common IPI was blastocystosis (48.6%), followed by ascaridiasis (13.7%), trichuriasis (11.8%), amoebiasis (9.3%), giardiasis (4.8%), and strongyloidiasis (3.7%). Hookworm was detected in one adult from rural Dienga. Adults had a higher prevalence of Blastocystis hominis and STHs, whereas Giardia duodenalis was more frequently observed among children aged below 5 years (P < 0.01). The polyparasitism rate was 41.5%, with 7.0% Plasmodium-IPIs and 1.8% Plasmodium-STH co-infections. The multivariate analysis showed that living in a suburban area, belonging to the age group of 5-15 years, having none or a secondary education, or having an open body water close to home were significant risk factors for malaria (P ≤ 0.01). For STH infections, identified risk factors were drinking untreated water and living in a rural area (P ≤ 0.04). No significant predictors were identified for IPIs and malaria-IPI co-infection., Conclusions: This study reports a high prevalence of IPIs and intestinal protozoa, but a low rate of malaria-IPI co-infections in the study sites. Improvements in the living conditions of the population such as adequate water supply and proper health education and sanitation should be integrated into control strategies for malaria, STHs, and IPIs.

Background: Homocitrulline (HCit) is a carbamylation-derived product (CDP) that has been identified as a valuable biomarker of morbidity and mortality in patients with chronic kidney disease (CKD). The aim of this study was to determine whether initiation of hemodialysis therapy (HD) could induce variations of HCit concentrations in CKD patients., Methods: Serum HCit concentrations were determined by LC-MS/MS in CKD patients (n=108) just before (M0) and six months (M6) after the initiation of HD therapy., Results: Mean HCit concentrations reached 1000μmol/mol Lysine before initiation of HD therapy and decreased by 50% within 6months after HD onset. HCit concentrations remained stable over time as assessed during a 24-months follow-up period. HCit was mostly found in its protein-bound form in HD patients. HCit concentrations obtained at M0 were positively correlated with urea (r=0.58) and carbamylated hemoglobin (r=0.41), and are likely to be promising predictive markers of mortality. However, no correlations were found between HCit concentrations and Kt/V values, suggesting that HCit is not a marker of HD efficiency., Conclusion: HCit concentrations reflect the intensity of protein carbamylation and are stable over time during HD treatment, making HCit a reliable biomarker in the follow-up of CKD patients., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Tubulointerstitial nephritis and uveitis (TINU) syndrome is a rare disease, defined by the association of idiopathic acute TINU. The aim of our work was to determine the characteristics of adult TINU syndrome in France, and to assess factors (including treatment) influencing medium-term prognosis.We conducted a nationwide study including 20 French hospitals. Clinical, laboratory, and renal histopathologic data of 41 biopsy-proven TINU syndromes were retrospectively collected. The patients were diagnosed between January 1, 1999 and December 1, 2015.Twenty-five females and 16 males were included (F/M ratio: 1.6:1). The median age at disease onset was 46.8 years (range 16.8-77.4) with a median serum creatinine level at 207 μmol/L (range 100-1687) and a median estimated glomerular filtration rate (eGFR) at 27 mL/min per 1.73 m (range 2-73). Twenty-nine patients (71%) had a bilateral anterior uveitis and 24 (59%) had deterioration in general health at presentation. Moderate proteinuria was found in 32 patients (78%) (median proteinuria 0.52 g/24 h; range 0.10-2.10), aseptic leukocyturia in 25/36 patients (70%). The evaluation of renal biopsies revealed 41 patients (100%) with an acute tubulointerstitial nephritis, 19/39 patients (49%) with light to moderate fibrosis and 5 patients (12%) with an acute tubular necrosis. Thirty-six patients (88%) were treated with oral corticosteroids. After 1 year of follow-up, the median eGFR was 76 mL/min per 1.73 m (range 17-119) and 32% of the patients suffered from moderate to severe chronic kidney disease. Serum creatinine (P < 0.001, r = -0.54), serum bicarbonate and phosphate levels (respectively, P = 0.01, r = 0.53; and P = 0.04, r = 0.46), and age (P = 0.03, r = -0.37) at the 1st symptoms were associated with eGFR after 1 year. During the 1st year 40% of patients had uveitis relapses. The use of oral corticosteroids was not associated with a better kidney function but was associated with fewer uveitis relapses (P = 0.44 and 0.02, respectively).In our study, 32% of patients were suffering from moderate to severe chronic kidney disease after 1 year of follow-up, and 40% had uveitis relapses during this follow-up. This work also suggests that oral corticosteroids are effective for the treatment of TINU syndrome's uveitis.

Objective: Cardiovascular disease is the leading cause of death in patients with end-stage renal disease. Serum amyloid A (SAA) is an acute phase protein and a binding partner for the multiligand receptor for advanced glycation end products (RAGE). We investigated the role of the interaction between SAA and RAGE in uremia-related atherogenesis., Approach and Results: We used a mouse model of uremic vasculopathy, induced by 5 of 6 nephrectomy in the Apoe(-/-) background. Sham-operated mice were used as controls. Primary cultures of Ager(+/+) and Ager(-/-) vascular smooth muscle cells (VSMCs) were stimulated with recombinant SAA, S100B, or vehicle alone. Relevance to human disease was assessed with human VSMCs. The surface area of atherosclerotic lesions at the aortic roots was larger in uremic Apoe(-/-) than in sham-operated Apoe(-/-) mice (P<0.001). Furthermore, atherosclerotic lesions displayed intense immunostaining for RAGE and SAA, with a pattern similar to that of α-SMA. Ager transcript levels in the aorta were 6× higher in uremic animals than in controls (P<0.0001). Serum SAA concentrations were higher in uremic mice, not only after 4 weeks of uremia but also at 8 and 12 weeks of uremia, than in sham-operated animals. We investigated the functional role of RAGE in uremia-induced atherosclerosis further, in animals lacking RAGE. We found that the induction of uremia in Apoe(-/-) Ager(-/-) mice did not accelerate atherosclerosis. In vitro, the stimulation of Ager(+/+) but not of Ager(-/-) VSMCs with SAA or S100B significantly induced the production of reactive oxygen species, the phosphorylation of AKT and mitogen-activated protein kinase-extracellular signal-regulated kinases and cell migration. Reactive oxygen species inhibition with N-acetyl cysteine significantly inhibited both the phosphorylation of AKT and the migration of VSMCs. Similar results were obtained for human VSMCs, except that the phosphorylation of mitogen-activated protein kinase-extracellular signal-regulated kinases, rather than of AKT, was subject to specific redox-regulation by SAA and S100B. Furthermore, human aortic atherosclerotic sections were positively stained for RAGE and SAA., Conclusions: Uremia upregulates SAA and RAGE expression in the aortic wall and in atherosclerotic lesions in mice. Ager(-/-) animals are protected against the uremia-induced acceleration of atherosclerosis. SAA modulates the functions of murine and human VSMCs in vitro in a RAGE-dependent manner. This study, therefore, identifies SAA as a potential new uremic toxin involved in uremia-related atherosclerosis through interaction with RAGE., (© 2016 American Heart Association, Inc.)

IgA nephropathy (IgAN), the most common primary glomerulonephritis worldwide, frequently leads to end-stage renal disease and kidney transplantation. However, disease recurrence often occurs after transplantation. Here we evaluated the predictive value of three markers for IgAN recurrence: the presence of galactose-deficient IgA1, IgG anti-IgA autoantibodies, and IgA-soluble (s) CD89 complexes. This was analyzed in 38 kidney transplant recipients with IgAN recurrence and compared with 22 patients transplanted for IgAN but without recurrence and with 17 healthy controls. Pre-transplantation galactose-deficient IgA1 serum levels were significantly higher in the recurrence compared with the no recurrence or control groups. IgA-IgG complexes were significantly elevated in the recurrence group. Both the recurrence and no recurrence groups had increased values of IgA-sCD89 complexes compared with healthy controls, but values were significantly lower in patients with recurrence compared with no recurrence. Areas under the receiver operating curve of the markers in pre-transplantation sera were 0.86 for galactose-deficient-IgA, 0.82 for IgA-IgG, and 0.78 for sCD89-IgA; all significant. Disease recurrence was associated with decreased serum galactose-deficient IgA1 and appearance of mesangial-galactose-deficient IgA1 deposits, whereas increased serum IgA-sCD89 complexes were associated with mesangial sCD89 deposits. Thus, galactose-deficient-IgA1, IgG autoantibodies, and IgA-sCD89 complexes are valuable biomarkers to predict disease recurrence, highlighting major pathogenic mechanisms in IgAN.

Bacterial bloodstream infections (BSI) account for considerable morbidity worldwide, but epidemiological data from resource-constrained tropical settings are scarce. We analysed 293 blood cultures from patients presenting to a regional referral hospital in Bouaké, central Côte d'Ivoire, to determine the aetiology of community-onset BSI. The prevalence of bacteraemia was 22.5%, with children being most commonly affected. Enterobacteriaceae (predominantly Klebsiella pneumoniae and Salmonella enterica) accounted for 94% of BSI. Staphylococcus aureus was the only relevant Gram-positive pathogen. Clinical signs and symptoms were not significantly associated with blood culture positivity after controlling for malaria.

The receptor for advanced glycation end products (RAGE) is a pattern recognition receptor that interacts with advanced glycation end products, but also with C3a, CpG DNA oligonucleotides, and alarmin molecules such as HMGB1 to initiate a proinflammatory reaction. Systemic lupus erythematosus is an autoimmune disorder associated with the accumulation of RAGE ligands. We generated mice invalidated for RAGE in the lupus-prone B6-MRL Fas lpr/j background to determine the role of RAGE in the pathogenesis of systemic lupus erythematosus. We compared the phenotype of these mice with that of their wild-type and B6-MRL Fas lpr/j littermates. Lymphoproliferative syndrome, production of anti-dsDNA Abs, lupus nephritis, and accumulation of CD3(+)B220(+)CD4(-)CD8(-) autoreactive T cells (in the peripheral blood and the spleen) were significantly increased in B6-MRL Fas lpr/j RAGE(-/-) mice compared with B6-MRL Fas lpr/j mice (respectively p < 0.005, p < 0.05, p < 0.001, and p < 0.001). A large proportion of autoreactive T cells from B6-MRL Fas lpr/j mice expressed RAGE at their surface. Time course studies of annexin V expression revealed that autoreactive T cells in the spleen of B6-MRL Fas lpr/j-RAGE(-/-) mice exhibited a delay in apoptosis and expressed significantly less activated caspase 3 (39.5 ± 4.3%) than T cells in B6-MRL Fas lpr/j mice (65.5 ± 5.2%) or wild-type mice (75.3 ± 2.64%) (p = 0.02). We conclude that the deletion of RAGE in B6-MRL Fas lpr/j mice promotes the accumulation of autoreactive CD3(+)B220(+)CD4(-)CD8(-) T cells, therefore exacerbating lymphoproliferative syndrome, autoimmunity, and organ injury. This suggests that RAGE rescues the apoptosis of T lymphocytes when the death receptor Fas/CD95 is dysfunctional., (Copyright © 2015 by The American Association of Immunologists, Inc.)

We describe a new method for determining the concentration of total Ca in whole skeletal muscle samples ([CaT]WM in units of mmoles/kg wet weight) using the Ca-dependent UV absorbance spectra of the Ca chelator BAPTA (1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid). Muscle tissue was homogenized in a solution containing 0.15 mM BAPTA and 0.5% sodium dodecyl sulfate (to permeabilize membranes and denature proteins) and then centrifuged. The solution volume was adjusted so that BAPTA captured essentially all of the Ca. [CaT]WM was obtained with Beer's law from the absorbance change produced by adding 1 mM EGTA to capture Ca from BAPTA. Results from mouse, rat, and frog muscles were reasonably consistent with results obtained using other methods for estimating total [Ca] in whole muscles and in single muscle fibers. Results with external Ca removed before determining [CaT]WM indicate that most of the Ca was intracellular, indicative of a lack of bound Ca in the extracellular space. In both fast-twitch (extensor digitorum longus, EDL) and slow-twitch (soleus) muscles from mice, [CaT]WM increased approximately linearly with decreasing muscle weight, increasing approximately twofold with a twofold decrease in muscle weight. This suggests that the Ca concentration of smaller muscles might be increased relative to that in larger muscles, thereby increasing the specific force to compensate for the smaller mass. Knocking out the high capacity Ca-binding protein calsequestrin (CSQ) did not significantly reduce [CaT]WM in mouse EDL or soleus muscle. However, in EDL muscles lacking CSQ, muscle weights were significantly lower than in wild-type (WT) muscles and the values of [CaT]WM were, on average, about half the expected WT values, taking into account the above [CaT]WM versus muscle weight relationship. Because greater reductions in [CaT]WM would be predicted in both muscle types, we hypothesize that there is a substantial increase in Ca bound to other sites in the CSQ knockout muscles., (© 2015 Lamboley et al.)

The endogenous phospholipid lysophosphatidic acid (LPA) regulates fundamental cellular processes such as proliferation, survival, motility, and invasion implicated in homeostatic and pathological conditions. Hence, delineation of the full range of molecular mechanisms by which LPA exerts its broad effects is essential. We report avid binding of LPA to the receptor for advanced glycation end products (RAGE), a member of the immunoglobulin superfamily, and mapping of the LPA binding site on this receptor. In vitro, RAGE was required for LPA-mediated signal transduction in vascular smooth muscle cells and C6 glioma cells, as well as proliferation and migration. In vivo, the administration of soluble RAGE or genetic deletion of RAGE mitigated LPA-stimulated vascular Akt signaling, autotaxin/LPA-driven phosphorylation of Akt and cyclin D1 in the mammary tissue of transgenic mice vulnerable to carcinogenesis, and ovarian tumor implantation and development. These findings identify novel roles for RAGE as a conduit for LPA signaling and suggest targeting LPA-RAGE interaction as a therapeutic strategy to modify the pathological actions of LPA.

Rationale: The mammalian diaphanous-related formin (mDia1), governs microtubule and microfilament dynamics while functioning as an effector for Rho small GTP-binding proteins during key cellular processes such as adhesion, cytokinesis, cell polarity, and morphogenesis. The cytoplasmic domain of the receptor for advanced glycation endproducts binds to the formin homology 1 domain of mDia1; mDia1 is required for receptor for advanced glycation endproducts ligand-induced cellular migration in transformed cells., Objective: Because a key mechanism in vascular remodeling is the induction of smooth muscle cell migration, we tested the role of mDia1 in this process., Methods and Results: We report that endothelial denudation injury to the murine femoral artery significantly upregulates mDia1 mRNA transcripts and protein in the injured vessel, particularly in vascular smooth muscle cells within the expanding neointima. Loss of mDia1 expression significantly reduces pathological neointimal expansion consequent to injury. In primary murine aortic smooth muscle cells, mDia1 is required for receptor for advanced glycation endproducts ligand-induced membrane translocation of c-Src, which leads to Rac1 activation, redox phosphorylation of AKT/glycogen synthase kinase 3β, and consequent smooth muscle cell migration., Conclusions: We conclude that mDia1 integrates oxidative and signal transduction pathways triggered, at least in part, by receptor for advanced glycation endproducts ligands, thereby regulating pathological neointimal expansion.

Background: Advanced glycation end-products (AGEs) have been implicated in diverse pathological settings including diabetes, inflammation and acute ischemia/reperfusion injury in the heart. AGEs interact with the receptor for AGEs (RAGE) and transduce signals through activation of MAPKs and proapoptotic pathways. In the current study, adult cardiomyocytes were studied in an in vitro ischemia/reperfusion (I/R) injury model to delineate the molecular mechanisms underlying RAGE-mediated injury due to hypoxia/reoxygenation (H/R)., Methodology/principal Findings: Cardiomyocytes isolated from adult wild-type (WT), homozygous RAGE-null (RKO), and WT mice treated with soluble RAGE (sRAGE) were subjected to hypoxia for 30 minutes alone or followed by reoxygenation for 1 hour. In specific experiments, RAGE ligand carboxymethyllysine (CML)-AGE (termed "CML" in this manuscript) was evaluated in vitro. LDH, a marker of cellular injury, was assayed in the supernatant in the presence or absence of signaling inhibitor-treated cardiomyocytes. Cardiomyocyte levels of heterogeneous AGEs were measured using ELISA. A pronounced increase in RAGE expression along with AGEs was observed in H/R vs. normoxia in WT cardiomyocytes. WT cardiomyocytes after H/R displayed increased LDH release compared to RKO or sRAGE-treated cardiomyocytes. Our results revealed significant increases in phospho-JNK in WT cardiomyocytes after H/R. In contrast, neither RKO nor sRAGE-treated cardiomyocytes exhibited increased phosphorylation of JNK after H/R stress. The impact of RAGE deletion on GSK-3beta phosphorylation in the cardiomyocytes subjected to H/R revealed significantly higher levels of phospho-GSK-3beta/total GSK-3beta in RKO, as well as in sRAGE-treated cardiomyocytes versus WT cardiomyocytes after H/R. Further investigation established a key role for Akt, which functions upstream of GSK-3beta, in modulating H/R injury in adult cardiomyocytes., Conclusions/significance: These data illustrate key roles for RAGE-ligand interaction in the pathogenesis of cardiomyocyte injury induced by hypoxia/reoxygenation and indicate that the effects of RAGE are mediated by JNK activation and dephosphorylation of GSK-3beta. The outcome in this study lends further support to the potential use of RAGE blockade as an adjunctive therapy for protection of the ischemic heart.

Cardiac tissue engineering will remain only a prospect unless large numbers of therapeutic cells can be provided, either from small samples of cardiac cells or from stem cell sources. In contrast to most adult cells, cardiomyocytes are terminally differentiated and cannot be expanded in culture. We explored the feasibility of enabling the in vitro expansion of primary neonatal rat cardiomyocytes by lentivector-mediated cell immortalization, and then reverting the phenotype of the expanded cells back to the cardiomyocyte state. Primary rat cardiomyocytes were transduced with simian virus 40 large T antigen (TAg), or with Bmi-1 followed by the human telomerase reverse transcriptase (hTERT) gene; the cells were expanded; and the transduced genes were removed by adenoviral vector expressing Cre recombinase. The TAg gene was more efficient in cell transduction than the Bmi-1/hTERT gene, based on the rate of cell proliferation. Immortalized cells exhibited the morphological features of dedifferentiation (increased vimentin expression, and reduced expression of troponin I and Nkx2.5) along with the continued expression of cardiac markers (alpha-actin, connexin-43, and calcium transients). After the immortalization was reversed, cells returned to their differentiated state. This strategy for controlled expansion of primary cardiomyocytes by gene transfer has potential for providing large amounts of a patient's own cardiomyocytes for cell therapy, and the cardiomyocytes derived by this method could be a useful cellular model by which to study cardiogenesis.

AGEs (advanced glycation end-products) accumulate in collagen molecules during uraemia and diabetes, two diseases associated with high susceptibility to bacterial infection. Because neutrophils bind to collagen during their locomotion in extravascular tissue towards the infected area we investigated whether glycoxidation of collagen (AGE-collagen) alters neutrophil migration. Type I collagen extracted from rat tail tendons was used for in vitro glycoxidation (AGE-collagen). Neutrophils were obtained from peripheral blood of healthy adult volunteers and were used for the in vitro study of adhesion and migration on AGE- or control collagen. Glycoxidation of collagen increased adhesion of neutrophils to collagen surfaces. Neutrophil adhesion to AGE-collagen was inhibited by a rabbit anti-RAGE (receptor for AGEs) antibody and by PI3K (phosphoinositide 3-kinase) inhibitors. No effect was observed with ERK (extracellular-signal-regulated kinase) or p38 MAPK (mitogen-activated protein kinase) inhibitors. AGE-collagen was able to: (i) induce PI3K activation in neutrophils, and (ii) inhibit chemotaxis and chemokinesis of chemoattractant-stimulated neutrophils. Finally, we found that blocking RAGE with anti-RAGE antibodies or inhibiting PI3K with PI3K inhibitors restored fMLP (N-formylmethionyl-leucyl-phenylalanine)-induced neutrophil migration on AGE-collagen. These results show that RAGE and PI3K modulate adhesion and migration rate of neutrophils on AGE-collagen. Modulation of adhesiveness may account for the change in neutrophil migration rate on AGE-collagen. As neutrophils rely on their ability to move to perform their function as the first line of defence against bacterial invasion, glycoxidation of collagen may participate in the suppression of normal host defence in patients with diabetes and uraemia.

Plasmodium falciparum infection can lead to a life threatening disease and the pathogenetic mechanisms of severe manifestations are not fully understood. Here, we investigated the capacity of P. falciparum-parasitized red blood cells (PRBC) from 45 children with clinical malaria to induce endothelial cell (EC) apoptosis. In all subjects, PRBC that cytoadhered to ECs could be found albeit to a variable degree. By contrast, PRBC that induce EC apoptosis were found only in nine (20%) subjects. Interestingly, children with neurological manifestations were significantly more likely to harbour apoptogenic strains. There was no quantitative relationship between the capacity of these isolates to cytoadhere and apoptosis induction. We hypothesize that P. falciparum-encoded molecules could be responsible for apoptosis induction and therefore suggest new insights in the pathogenesis of P. falciparum malaria. Further investigations are currently in progress to determine whether these results can be confirmed and to identify putative parasite apoptogenic factors.

Introduction: Post-operative Peritonitis (PPO) put some diagnostic and therapeutic problems to surgeons. The aim of the study was: first, to analyze the epidemiological, diagnostic, and therapeutic factors of post-operative peritonitis; then, to define a strategy to improve their prognosis., Material and Method: We did a retrospective study carried out at department of general surgery of the Aristide Le Dantec hospital from January 2001 to March 2007 on cases of PPO. Fifteen cases were included. It was about 12 men and 3 women of middle age of 38.2 years with extremes of 17 and 70 years., Results: Clinical signs were dominated by the abdominal pain (73.3%) and the fever (66.7%). Abdominal collections were multi-microbial. The digestive suture failure was the dominant reason. All patients have been managed in the 48 hours that followed the diagnosis of PPO. The treatment consisted, essentialy in temporary digestive derivation, washing and drainage of the abdominal cavity framed by an adequate resuscitation. The recovery was 67.7%. Morbidity rate is 33.3%. Mortality concerned 5 patient (33.3%) especially carriers of 2 or 3 visceral failings. Criteria of precocious re-laparotomy have been specified., Conclusion: The improvement of the prognosis passes indeed by a precocious diagnosis and a coherent multidisci lina a roach.

Carbamylation is a post-translational modification of proteins characterized by the binding of cyanate to amino groups, increased in renal failure. Pathophysiological consequences of carbamylation and adverse effects of carbamylated proteins on cell functions are poorly understood. We studied the influence of carbamylated albumin on polymorphonuclear neutrophil (PMN) O(2)(-) production. Carbamylated albumin significantly decreased O(2)(-) production in PMNs stimulated by type I collagen, but not by phorbol 12-myristate 13-acetate or tumor necrosis factor-alpha. This effect was related to inhibition of p(125)FAK phosphorylation. Such an alteration of neutrophil oxidative functions might explain characteristic complications of renal failure, such as increased occurrence of inflammation or infections.

Background: An epidemic of aseptic peritonitis related to the presence of peptidoglycan contaminant in some batches of icodextrin solution (Extraneal, Baxter Healthcare Corporation) occurred in Europe in the first six months of 2002., Methods: By case-control study we examined the clinical and biologic features of 5 patients with icodextrin-induced peritonitis (group AP) and compared them with 7 patients with bacterial peritonitis (group BP) recruited in our clinical center between January and June 2002., Results: Diagnosis of icodextrin-induced peritonitis was confirmed in all cases by a positive reintroduction test with contaminated batches of icodextrin. No recurrence was observed on re-exposure to icodextrin free of peptidoglycan. Skin tests were positive with contaminated icodextrin in 2 of 5 patients, while they were negative with icodextrin solution free of peptidoglycan (<0.6 ng/mL). During peritonitis, serum level of C-reactive protein (CRP) was lower in group AP (42.4 +/- 34 mg/L) than in group BP (135 +/- 59 mg/L) (P= 0.01). Leukocyte number in peritoneal dialysis effluent was lower in group AP (284 +/- 101/mm3), with a lower neutrophil/monocyte ratio (N/M = 0.67) than in group BP (1410 +/- 973/mm3; N/M = 4) (P < 0.05). A low number of peritoneal fluid eosinophilia (11 +/- 8%) was detected in group AP., Conclusion: Icodextrin-induced peritonitis was associated with a burst of intraperitoneal cytokines. The phenotype of peritoneal neutrophils was different between aseptic and bacterial peritonitis, indicating that inflammatory stimuli that activate neutrophils in both types of peritonitis are clearly distinct. Finally, peritoneal injury measured by weight gain, peritoneal permeability, and CA125 concentration seemed to be less severe during icodextrin-induced peritonitis than during bacterial peritonitis.

To assess the relationships between variations of Plasmodium falciparum transmission and those of peripheral parasitaemia prevalence or malaria attack incidence rates in regions with limited fluctuations of transmission, we conducted a follow-up in two Gabonese populations. Entomological surveys were carried out from May 1995 to April 1996 in Dienga, and from May 1998 to April 1999 in Benguia. In Dienga, malaria transmission was seasonal, being not detected during two 3-month periods. Mean entomological inoculation rate (EIR) was 0.28 infective bite/person/night. In Benguia, malaria transmission was perennial with seasonal fluctuations, mean EIR being 0.76 infective bite/person/night. In Dienga, 301 schoolchildren were followed from October 1995 to March 1996. Clinical malaria attack was defined as fever associated with >5000 parasites/microl of blood. P. falciparum prevalence varied from 28 to 42%, and monthly malaria attack incidence from 30 to 169 per thousand. In Benguia, the entire population (122 persons) was followed from November 1998 to April 1999. Prevalence varied from 22 to 50%, and monthly malaria attack incidence from 52 to 179 per thousand. In each area, entomological variations were not related to parasite prevalence, but preceded malaria attack incidence with 1- or 2-month time lag, corresponding to the pre-patency period that differs in the two populations, possibly according to differences in immunity related to parasite transmission.

We have designed primers to the conserved region of the erythrocyte binding antigen (EBA)-175 gene which amplify specifically the two alleles by polymerase chain reaction (PCR) and by nested PCR. This approach provides a specific, sensitive and rapid method for genotype determination in a large number of Plasmodium falciparum field isolates.

Pasteurella dagmatis was identified as the etiologic agent of peritonitis in a continuous ambulatory peritoneal dialysis patient by utilizing a molecular kit in our hospital's clinical laboratory. This method would appear a useful approach to identify a species of Pasteurella not included in the existing database of commercial identification kits when discrepancies exist between phenotypic tests.

Mandrills (Mandrillus sphinx) experimentally infected with human Loa loa usually remain microfilaremic for a long period of time. Nevertheless some control their microfilaremia while still harboring adults worms, and therefore become occult-infected. A nested polymerase chain reaction (PCR) assay, targeted on the repeat 3 region of the gene coding for the L. loa 15-kD protein (15r3-PCR), has been evaluated in mandrills infected with third-stage larvae (L3) of L. loa. The results of this assay were negative during the prepatency period (4 months after inoculation), but became positive when microfilariae appeared in the blood, and remained positive in all mandrills, even in those that became amicrofilaremic. These results show that the positivity of the 15r3-PCR assay is linked to the appearance of microfilariae in peripheral blood and demonstrated that L. loa-specific DNA can be detected in blood from occult-infected mandrills.

We have previously demonstrated that peptide immunization restimulates the memory CD4 T-cell response, but fails to induce cytotoxic T lymphocyte (CTL) in cynomolgus macaques. To examine the nature of protective immunity to simian immunodeficiency virus (SIV) in this study, freshly isolated peripheral blood mononuclear cells (PBMC) from four infected juvenile cynomolgus macaques and from three uninfected control macaques were assessed for CTL activity monthly for 9 consecutive months, beginning 1 month after detection of infection. Target cells consisted of major histocompatibility (MHC) haploidentical parental PBMC which were stimulated with mitogen and then pulsed with heat-killed SIVcyn. CTL activity was demonstrated in PBMCs from all four infected animals. The effector cells are T cells which mediate cytotoxicity against SIVcyn-pulsed target cells in an MHC-restricted manner. Furthermore, the cytotoxicity is virus specific and predominantly, if not exclusively, mediated by CD8+ T cells; it is also MHC class I restricted. Incubation of target cells with pepstatin A during antigen pulsing prior to the cytotoxic assay inhibited target cell generation, suggesting that viral antigens are processed via an endocytic pathway.

Natural killer (NK) cell activity is impaired in Chlamydia trachomatis-infected patients. The mechanisms behind the altered NK functions are not clear, but data concerning NK and antibody-dependent cellular cytotoxicity (ADCC) activity have been reported. To investigate whether this impairment is related to a defect at the target cell binding and/or the postbinding level, we evaluated highly purified NK cells obtained from 125 C. trachomatis-infected patients and compared them with 101 normal controls for their ability to kill K-562 and U-937 cell lines using a 51Cr release assay; release tumour necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma); and kill anti-IgM preincubated P-815 cell line (ADCC activity). We found a decrease in the lytic capability of NK cells from C. trachomatis-infected patients against target cell lines; decreased ability to kill bound target cells; and low levels of released TNF-alpha and INF-gamma after incubation with U-937 cells. Taken together, these findings suggest that the impaired NK cell reaction during chlamydial infection is related to defects both at the target and postbinding levels. However, the precise mechanisms remain to be determined. The inability to restore normal NK activity after long-term culture in the presence of high levels of recombinant IL-2 support the hypothesis of an anergic process during chlamydial infection.

By evaluating the diagnostic methods developed in our laboratory, the prevalence of loaiosis was estimated among 201 individuals from the province of Haut Ogooué in Gabon using IgG4 serology and nested-PCR. The study showed that the prevalence of loaiosis was higher than that described using standard microscopy. IgG4-based ELISA (Enzyme Linked Immunosorbant Assay) using crude extract of Loa loa microfilariae showed that 80% (35/44) of microfilaraemic individuals (MF') and 56% (88/157) of amicrofilaraemics (AMF) presented antibodies. By contrast, L. loa specific DNA amplified by nested-PCR was detected in all MF and in 68% (106/157) of AMF. Among the 201 samples tested, 95 (47%) gave positive results in both tests. These results indicate that the presence of IgG4 antibodies directed against crude extract of L. loa microfilariae is not linked to the positivity of nested-PCR assay (chi 2 for paired data = 8.78; P < 0.02). We conclude that the PCR assay is more sensitive than the detection of IgG4 antibodies (directed against crude extract of L. loa microfilariae) in detecting loaiosis, and particularly occult loaiosis (infection without circulating microfilariae).

The development of control strategies for loiasis is of crucial importance in endemic areas and depends heavily on the accurate identification of occult-infected individuals. A polymerase chain reaction (PCR) and nested polymerase chain reaction (nested PCR) were developed and based on sequences of the repeat 3 region (15r3) of the gene encoding a Loa loa 15-kD protein. The assays was performed on 20 blood samples from occult-infected subjects and 30 from field-collected amicrofilaremic individuals. The size of the initial PCR product was 396 basepairs (bp). When this initial amplification using primers 15r3(1) and 15r3(2) was carried out for 30 cycles, the PCR products from three of the 20 occult-infected and five of the 30 amicrofilaremic individuals were visualized after electrophoresis by staining the gel with ethidium bromide. Subsequent Southern blotting and hybridization with the specific probe revealed hybridization in 19 of 20 occult-infected and 23 of 30 amicrofilaremic samples but only after two days of exposure of the blot to the x-ray film. When the nested PCR was carried out (product size = 366 bp, primers 15r3(3) and 15r3(4)), 19 of 20 occult-infected and 23 of 30 amicrofilaremic samples that were positive by Southern hybridization of the initial PCR products were strongly positive by staining with ethidium bromide. Qualitative Southern blotting of the nested PCR products using the same probe previously described confirmed the ethidium bromide staining results after a very short exposure time of 4 hr. These results demonstrate that the nested PCR amplification product is specific and that its sensitivity in detecting occult loiasis is 95%. This approach has significant promise for the screening of large human populations for active loiasis without the requirement for blotting and hybridization of the PCR products.

A nested polymerase chain reaction (nested PCR) assay, targeted on the repeat 3 region (15r3) of the gene coding for a Loa loa 15 kD polyprotein, was developed to detect L. loa infection. The assay has a sensitivity of 95% and is 100% specific with regard to sympatric filarial parasites: Mansonella perstans, Onchocerca volvulus and Wuchereria bancrofti. In this field study in a mixed filarial (L. loa and M. perstans) endemic region of Gabon, 157 L. loa amicrofilaraemic blood samples (AMF; diagnosed by leucoconcentration followed by standard microscopic examination) from the residents from four villages were screened by the 15r3-nested PCR assay. The assay detected 106 occult infected subjects among the 157 AMF individuals (68%), including 59 of 87 adults (68%) and 47 of 70 children (67%). In each village the prevalence of occult infection was, respectively, 38%, 52%, 79% and 80% for Moyabi, Djoutou, N'djokaye and Okoumbi. The annual transmission potential (ATP) of loiasis has been estimated to be 250 infective larvae (L 3) per man per year for Moyabi and Djoutou, 1800 for N'djokaye and 433000 L3/man/year for Okoumbi. This implies a correlation between occult infection of loiasis and the intensity of transmission. By contrast, the prevalence of L. loa microfilariae was 21% for Okoumbi, 22%, for N'djokaye and 19% for Djoutou and Moyabi. These results show that the prevalence of loiasis in this region of Gabon is higher than previously described by standard microscopic examination and that the application of this assay will be significant in the development of control strategies for loiasis.

Human filariasis due to Loa loa differs from other filariasis in that the majority of infected subjects are without circulating microfilariae (occult loiasis). In search for alternative diagnostic methods, which do not depend on circulating microfilariae or the (rather infrequent) eye-passage of adult worms, it was shown earlier that IgG4 antibodies directed against Loa loa adult worm antigen are apparently a good marker of occult loiasis and specific with regard to the sympatrically occurring Mansonella perstans. In this study we evaluated an IgG4 antibody-based ELISA using crude extract of Loa loa microfilariae (which is easier to obtain than adult worm) to estimate the prevalence of loiasis in 3 villages in South-East Gabon. Of 222 examined individuals (80 children < 16 years, 142 adults) 44 (20%) carried Loa loa microfilariae and 170 (77%) M. perstans. Using the mean OD-value + 1 standard deviation of 9 sera from patients solely infected with M. perstans (from the Gambia, where Loa loa is not endemic) as a cut-off, 35 of the 44 microfilaraemic Loa loa patients and 2 of the 9 Gambian controls were positive. This shows that our method had a sensitivity of 80% and a specificity of 78%. Among the remaining 178 subjects who had no microfilariae of Loa loa, as many as 97 (55%) had significant levels of specific IgG4 antibodies against Loa loa, suggesting that they carried occult loiasis. The mean IgG4 level in these putatively occult loiasis patients was slightly but significantly lower than in microfilaraemic subjects (P < 0.03). In conclusion, despite the limited sensitivity and specificity of our method, IgG4- ELISA at present is a very useful tool in estimating the real prevalence of loiasis in epidemiological surveys and at the individual level can confirm the diagnosis of L. loa amicrofilaraemic subjects with clinical signs suggesting loiasis.