Aberrant mTOR/autophagy/Nurr1 signaling is critical for TSC-associated tumor development.

Tuberous sclerosis complex (TSC), an inherited neurocutaneous disease, is caused by mutations in either the TSC1 or TSC2 gene. This genetic disorder is characterized by the growth of benign tumors in the brain, kidneys, and other organs. As a member of the orphan nuclear receptor family, nuclear receptor related 1 (Nurr1) plays a vital role in some neuropathological diseases and several types of benign or malignant tumors. Here, we explored the potential regulatory role of TSC1/2 signaling in Nurr1 and the effect of Nurr1 in TSC-related tumors. We found that Nurr1 expression was drastically decreased by the disruption of the TSC1/2 complex in Tsc2-null cells, genetically modified mouse models of TSC, cortical tubers of TSC patients, and kidney tumor tissue obtained from a TSC patient. Deficient TSC1/2 complex downregulated Nurr1 expression in an mTOR-dependent manner. Moreover, hyperactivation of mTOR reduced Nurr1 expression via suppression of autophagy. In addition, Nurr1 overexpression inhibited cell proliferation and suppressed cell cycle progression. Therefore, TSC/mTOR/autophagy/Nurr1 signaling is partially responsible for the tumorigenesis of TSC. Taken together, Nurr1 may be a novel therapeutic target for TSC-associated tumors, and Nurr1 agonists or reagents that induce Nurr1 expression may be used for the treatment of TSC.

Identification and characterization of heat-responsive microRNAs at the booting stage in two rice varieties, 9311 and Nagina 22.

MicroRNAs (miRNAs) are small, non-coding, regulatory RNAs that play important roles in abiotic stress responses in plants, but their regulatory roles in the adaptive response to heat stress at the booting stage in two rice varieties, 9311 and Nagina 22, remain largely unknown. In this study, 464 known miRNAs and 123 potential novel miRNAs were identified. Of these miRNAs, a total of 90 differentially expressed miRNAs were obtained with 9311 libraries as the control group, of which 54 were upregulated and 36 were downregulated. To gain insight into functional significance, 2773 potential target genes of these 90 differentially expressed miRNAs were predicted. GO enrichment analysis showed that the predicted target genes of differentially expressed miRNAs included NACs, LACs, CSD, and Hsp40. KEGG pathway analysis showed that the target genes of these differentially expressed miRNAs were significantly enriched in the plant hormone signal transduction pathway. The expression levels of 10 differentially expressed miRNAs and their target genes obtained by qRT-PCR were largely consistent with the sequencing results. This study lays a foundation for the elucidation of the miRNA-mediated regulatory mechanisms in rice at elevated temperatures.

Vaccinomics-driven proteome-wide screening of Haemophilus influenzae for the prediction of common putative vaccine candidates.

Haemophilus influenzae colonizes the respiratory tract and is associated with life-threatening invasive infections. The recent rise in its global prevalence, even in the presence of multiple vaccines, indicates an urgent need to develop effective cross-strain vaccine strategies. Our work focused on identifying the universally conserved antigenic regions of H. influenzae that can be used to develop new vaccines. A variety of bioinformatics tools were applied for the comprehensive geno-proteomic analysis of H. influenzae type a strain, as reference serotype, through which subcellular localization, essentiality, virulence, and non-host homology were determined. B and T cell epitope mapping of the 3D protein structures were performed. Thereafter, molecular docking with HLA_DRB1*0101 and comparative genome analysis established the candidature of the identified regions. Based on the established vaccinomics criteria, five target proteins were predicted as novel vaccine candidates. Among these, nine epitopic regions that could regulate lymphocyte activity through strong protein-protein interactions were identified. Comparative genomic analysis revealed that the identified regions were highly conserved among the different strains of H. influenzae. Based on multiple immunogenic factors, five prioritized proteins and their predicted epitopes were identified as ideal common putative vaccine candidates against typeable strains.

miR-628-5p promotes growth and migration of osteosarcoma by targeting IFI44L.

This study investigated the role of miR-628-5p and interferon-induced protein 44-like (IFI44L) in osteosarcoma (OS) and determined whether miR-628-5p modulated OS growth by regulating IFI44L. Based on the data downloaded from Gene Expression Omnibus (GEO) database, we revealed that the expression of IFI44L was downregulated in OS and low expression of IFI44L was correlated with better prognosis of patients with OS. Biological prediction of its upstream regulatory miRNAs on the miRWalk website found that miR-628-5p is a possible upstream regulatory miRNA of IFI44L. Luciferase activity assay demonstrated that miR-628-5p could bind to the 3' untranslated region (UTR) of IFI44L, which proved the above prediction. The expression of miR-628-5p is upregulated in OS and high expression of miR-628-5p is correlated with poor prognosis of patients with OS. The results of RT-qPCR showed that the expression of miR-628-5p in MG-63, U2OS, Saos-2, and SW1353 cells was significantly higher than that in the hFOB1.19 cells. Downregulation of miR-628-5p by miR-628-5p inhibitor significantly inhibited the proliferation, migration, and invasion of MG-63 cells. By rescue assay, we found that knockdown of IFI44L rescued the proliferation and motility of miR-628-5p depleted MG-63 cells. Collectively, our present data illustrated that miR-628-5p promoted the growth and motility of OS at least partly by targeting IFI44L. Moreover, miR-628-5p and IFI44L might be proposed as promising biomarkers in OS diagnosis and treatment.

Phagocytosis: what's on the menu? 1.

Phagocytosis is an evolutionarily conserved process. In Protozoa, phagocytosis fulfills a feeding mechanism, while in Metazoa, phagocytosis diversified to play multiple organismal roles, including immune defence, tissue homeostasis, and remodeling. Accordingly, phagocytes display a high level of plasticity in their capacity to recognize, engulf, and process targets that differ in composition and morphology. Here, we review how phagocytosis adapts to its multiple roles and discuss in particular the effect of target morphology in phagocytic uptake and phagosome maturation.

Hemoglobin oxygen saturation targets in the neonatal intensive care unit: Is there a light at the end of the tunnel? 1.

The optimal oxygenation target needed to prevent the extremes of hypoxia and oxygen toxicity in premature and sick newborns has been the subject of much research and debate. The advent of the pulse oximeter has allowed the continuous monitoring of oxyhemoglobin saturation and the delivery of oxygen with greater precision. Well-run, large clinical trials to determine the safest oxygen concentration have led to several revisions in guidelines for neonatal care. However, monitoring of oxyhemoglobin saturation has its limitations and does not provide a comprehensive assessment of tissue oxygenation. To identify optimal oxygen therapy, various other factors (partial pressure of arterial carbon dioxide, hemoglobin concentration, blood pH, and tissue metabolic demand) that influence perfusion and tissue oxygenation need to be considered.

Inhibition of miR-182-5p protects cardiomyocytes from hypoxia-induced apoptosis by targeting CIAPIN1.

Myocardial infarction (MI), a type of ischemic heart disease, is generally accompanied by apoptosis of cardiomyocytes. MicroRNAs play the vital roles in the development and physiology of MI. Here, we established a downregulation model of miR-182-5p in H9c2 cells under hypoxic conditions to investigate the potential molecular mechanisms for miR-182-5p in hypoxia-induced cardiomyocyte apoptosis (HICA). RT-qPCR indicated that miR-182-5p levels exhibit a time-dependent increase in the rate of apoptosis induced by hypoxia. The results from the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) and LDH (lactate dehydrogenase) assays indicated that cardiomyocyte injury noticeably increased after exposure to hypoxia. Meanwhile, hypoxia dramatically increased the apoptosis rate [which was reflected in the results from the annexin V - propidium iodide (PI) assay], enhanced caspase-3 activity, and reduced the expression of Bcl-2. Downregulation of miR-182-5p can significantly reverse hypoxia-induced cardiomyocyte injury or apoptosis. Importantly, bioinformatic analysis and dual-luciferase reporter assay revealed that CIAPIN1 (cytokine-induced apoptosis inhibitor 1) was a direct functional target of miR-182-5p, and that inhibition of miR-182-5p can lead to an increase in CIAPIN1 expression at both the mRNA and protein levels. Furthermore, the knockdown of CIAPIN1 with small interfering RNAs (siRNAs) efficiently abolished the protective effects of miR-182-5p inhibitor on HICA, demonstrating that miR-182-5p plays a pro-apoptotic role in cardiomyocytes under hypoxic conditions by downregulating CIAPIN1. Collectively, our results demonstrate that miR-182-5p may serve an underlying target to prevent cardiomyocytes from hypoxia-induced injury or apoptosis.

[Targeted newborn screening for sickle-cell anemia: Sickling test (Emmel test) boundaries in the prenatal assessment in West African area]. / Dépistage néonatal ciblé de la drépanocytose : limites du test de falciformation (test d'Emmel) dans le bilan prénatal en zone ouest africaine.

BACKGROUND: Newborn screening for sickle cell anemia is necessary in Africa where the disease is more frequent. Hemoglobin electrophoresis is used for screening, but is limited by a high cost and difficult access. Sickling test (Emmel test), which is more affordable and technically more accessible, is often requested for prenatal assessment of pregnant women in West African areas to reserve screening for newborns from mothers in whom the positive sickling test attests the presence of hemoglobin S. This study aims to evaluate the number of undetected sickle cell anemia newborns by a screening policy targeting only newborns from mothers in whom a sickling test would have been positive. METHODS: From 2010 to 2012, in Bamako, Mali, West Africa, 2489 newborns were routinely screened for sickle cell anemia at the umbilical cord or heel by isoelectrofocusing and, if necessary, by high-performance liquid chromatography. These newborns were born from 2420 mothers whose hemoglobin was studied by isoelectrofocusing. The data was recorded and processed using Excel software version 14.0.0. We calculated the frequency of the sickle cell gene in mothers and newborns as well as the number of SCA newborns from heterozygous or C homozygous mothers. RESULTS: Of the 2489 newborns, 16 had sickle cell anemia (6 SS and 10 SC); 198 had the sickle cell trait; 139 were AC and 1 was CC. Of the 10 newborns with SC profile, 3 were born from mothers not carrying the S gene but the C gene of hemoglobin and in which an Emmel test would have been negative. CONCLUSION: Targeted newborn screening, based on the results of sickling test in pregnant women, would misdiagnose more than one of six sickle cell anemia newborns who would not benefit from early care. Cost-effectiveness studies of routine newborn screening for sickle cell anemia should lead to a better screening strategy in contexts where hemoglobin S and other hemoglobin defect genes coexist.

Herbicide targets and detoxification proteins in sugarcane: from gene assembly to structure modelling.

In a genome context, sugarcane is a classic orphan crop, in that no genome and only very few genes have been assembled. We have devised a novel exome assembly methodology that has allowed us to assemble and characterize 49 genes that serve as herbicide targets, safener interacting proteins, and members of herbicide detoxification pathways within the sugarcane genome. We have structurally modelled the products of each of these genes, as well as determining allelic, genomic, and RNA-Seq based polymorphisms for each gene. This study provides the largest collection of sugarcane structures modelled to date. We demonstrate that sugarcane genes are highly polymorphic, revealing that each genotype is evolving both uniquely and independently. In addition, we present an exome assembly system for orphan crops that can be executed on commodity infrastructure, making exome assembly practical for any group. In terms of knowledge about herbicide modes of action and detoxification, we have advanced sugarcane from a crop where no information about any herbicide-associated gene was available to the situation where sugarcane is now a species with the single largest collection of known and annotated herbicide-associated genes.

Investigation of orthologous pathogen recognition gene-rich regions in solanaceous species.

Pathogen receptor proteins such as receptor-like protein (RLP), receptor-like kinase (RLK), and nucleotide-binding leucine-rich repeat (NLR) play a leading role in plant immunity activation. The genome architecture of such genes has been extensively investigated in several plant species. However, we still know little about their elaborate reorganization that arose during the plant speciation process. Using recently released pepper and eggplant genome sequences, we were able to identify 1097 pathogen recognition genes (PRGs) in the cultivated pepper Zunla-1 and 775 in the eggplant line Nakate-Shinkuro. The retrieved genes were analysed for their tendency to cluster, using different methods to infer the means of grouping. Orthologous relationships among clustering loci were found, and interesting reshuffling within given loci was observed for each analysed species. The information obtained was integrated into a comparative map to highlight the evolutionary dynamics in which the PRG loci were involved. Diversification of 14 selected PRG-rich regions was also explored using a DNA target-enrichment approach. A large number of gene variants were found as well as rearrangements of sequences encoding single protein domain and changes in chromosome gene order among species. Gene duplication and transposition activity have clearly influenced plant genome R-gene architecture and diversification. Our findings contribute to addressing several biological questions concerning the parallel evolution that occurred between genomes of the family Solanaceae. Moreover, the integration of different methods proved a powerful approach to reconstruct the evolutionary history in plant families and to transfer important biology findings among plant genomes.

[Current and upcoming treatments of adult atopic dermatitis]. / L'actuel et le futur du traitement de la dermatite atopique de l'adulte.

The treatment of atopic dermatitis in adults is based on the use of topical steroids and emollients. When AD is resistant to a well-conducted topical treatment, phototherapy or systemic treatments can be used: ciclosporin, methotrexate, azathioprine or mycophenolate mofetil. The therapeutic landscape of adult AD is about to change and even be revolutionized by the imminent arrival of new treatments: topical phosphodiesterase 4 inhibitors, topical or systemic JAK inhibitors, anti-IL-4 and/or antiIL-13 biotherapies (dupilumab, tralokinumab, lebrikizumab), anti-IL-31 (nemolizumab), anti-TSLP.

[Professional practice and nursing records]. / Pratique professionnelle et dossier de soins.

Nursing record-keeping has evolved over the ages and has several functions. It is an act which provides proof of the professional's responsibility. These records reinforce notably the competencies of the caregivers and the collaboration of the patient.

Appropriate targeting of artemisinin-based combination therapy by community health workers using malaria rapid diagnostic tests: findings from randomized trials in two contrasting areas of high and low malaria transmission in south-western Uganda.

OBJECTIVE: To compare the impact of malaria rapid diagnostic tests (mRDTs), used by community health workers (CHWs), on the proportion of children <5 years of age receiving appropriately targeted treatment with artemisinin-based combination therapy (ACT), vs. presumptive treatment. METHODS: Cluster-randomized trials were conducted in two contrasting areas of moderate-to-high and low malaria transmission in rural Uganda. Each trial examined the effectiveness of mRDTs in the management of malaria and targeting of ACTs by CHWs comparing two diagnostic approaches: (i) presumptive clinical diagnosis of malaria [control arm] and (ii) confirmatory diagnosis with mRDTs followed by ACT treatment for positive patients [intervention arm], with village as the unit of randomisation. Treatment decisions by CHWs were validated by microscopy on a reference blood slide collected at the time of consultation, to compare the proportion of children <5 years receiving appropriately targeted ACT treatment, defined as patients with microscopically-confirmed presence of parasites in a peripheral blood smear receiving artemether-lumefantrine or rectal artesunate, and patients with no malaria parasites not given ACT. RESULTS: In the moderate-to-high transmission area, ACT treatment was appropriately targeted in 79.3% (520/656) of children seen by CHWs using mRDTs to diagnose malaria, vs. 30.8% (215/699) of children seen by CHWs using presumptive diagnosis (P < 0.001). In the low transmission area, 90.1% (363/403) children seen by CHWs using mRDTs received appropriately targeted ACT treatment vs. 7.8% (64/817) seen by CHWs using presumptive diagnosis (P < 0.001). Low mRDT sensitivity in children with low-density parasitaemia (<200 parasites/µl) was identified as a potential concern. CONCLUSION: When equipped with mRDTs, ACT treatments delivered by CHWs are more accurately targeted to children with malaria parasites. mRDT use could play an important role in reducing overdiagnosis of malaria and improving fever case management within iCCM, in both moderate-to-high and low transmission areas. Nonetheless, missed treatments due to the low sensitivity of current mRDTs in patients with low parasite density are a concern. For community-based treatment in areas of low transmission and/or non-immune populations, presumptive treatment of all fevers as malaria may be advisable, until more sensitive diagnostic assays, suitable for routine use by CHWs in remote settings, become available.

Targeted clinical audits immediately following the establishment of clinical practice guidelines for multiple sclerosis in 17 neurology departments: A pragmatic and collaborative study.

UNLABELLED: Following the publication practice guidelines for multiple sclerosis by a group of neurologists (multiple sclerosis study group [GRESEP]), the primary objective of this study was to compare the reality of practice to the guidelines according to the targeted clinical audit (TCA) method. The study was conducted at 17 neurology sites and was administered during two periods of MS care (diagnostic - TCA-DIAG, and disease course - TCA-EVOL). Two complementary surveys were done on the record keeping and the root causes of the deviations. The percentages of compliance ranged from 8 to 98% for the TCA-DIAG, and from 15 to 99% for the TCA-EVOL, with wide disparity between sites. The audits were able to identify causes of the flaws in traceability or accessibility. At the end of the study, despite its limitations, we think that the sharing of the results from different sites provided interesting approaches for the use of the assessment criteria defined by GRESEP in a complete audit cycle. This study is to our knowledge the first report of an experiment in which guidelines were created, and subsequently followed by the development of assessment criteria and then the performance of targeted clinical audits using them, all by the same participants. CONTEXT: Clinical practice guidelines (CPGs) are intended to help practitioners and patients make informed treatment choices, but their integration into actual practice remains problematic. This study was done immediately following the publication of CPGs for multiple sclerosis (MS) by the multiple sclerosis study group [GRESEP]. The primary objective was to generate quality criteria, to test them within the same group, and to analyze the observed deviations. MATERIALS AND METHODS: The study was conducted in the 17 voluntary departments that had participated in the development of the CPGs. The targeted clinical audit method was administered during two periods of MS care (diagnostic - TCA-DIAG, and disease course - TCA-EVOL). All the files were evaluated by a clinical research technician using digital format, which ensured thoroughness of the collection. Two complementary surveys were done on the record keeping and the potential causes of the deviations. RESULTS: The percentages of compliance to the criteria ranged from 8 to 98% (out of 240 files) for the TCA-DIAG, and from 15 to 99% (221 files) for the TCA-EVOL, with wide disparity between sites (interquartile distance ranges: TCA-DIAG between 0% and 55%; TCA-EVOL between 0% and 70%). The mean percentage of compliance with all the criteria as measured by the TCA-DIAG was 83.9% for the sites with digital files vs. 76.4% for those with only paper files (P<0.01). For the TCA-EVOL, the difference was not significant. Explanations for the observed deviations were suggested (1 to 9 according to the participants). DISCUSSION AND CONCLUSION: The quantified results could not be compared to other studies given the unique nature of the experiment. The importance of the traceability of practices in the patient files was discussed and assessed with regard to continuity and safety of care, as well as the medical-legal perspectives. Causes of lack of compliance were suggested (particularly the absence of reminders, the lack of means and/or time). Despite the limitations of the study, we think it is advisable that when a group becomes involved in the development of CPGs that they follow with the development of assessment criteria in order to evaluate the validity as well as their character as intermediate indicators of the quality of practices.

[Proposal for the delineation of postoperative primary clinical target volumes in maxillary sinus and nasal cavity cancers]. / Proposition de délinéation des volumes cibles anatomocliniques postopératoires de la tumeur primitive des cancers du sinus maxillaire et des cavités nasales.

In this article, we propose a consensus delineation of postoperative clinical target volumes for the primary tumour in maxillary sinus and nasal cavity cancers. These guidelines are developed based on radioanatomy and the natural history of those cancers. They require the fusion of the planning CT with preoperative imaging for accurate positioning of the initial GTV and the combined use of the geometric and anatomical concepts for the delineation of clinical target volume for the primary tumour. This article does not discuss the indications of external radiotherapy (nor concurrent systemic treatment) but focuses on target volumes when there is an indication for radiotherapy.

Factors Associated With Attainment of Glycemic Targets Among Adults With Type 1 and Type 2 Diabetes in Canada: A Cross-sectional Study Using Primary and Specialty Care Electronic Medical Record Data.

OBJECTIVE: Using a new database combining primary and specialty care electronic medical record (EMR) data in Canada, we determined attainment of glycemic targets and associated predictors among adults with diabetes. METHODS: We conducted a cross-sectional observational study combining primary and specialty care EMR data in Canada. Adults with diabetes whose primary care provider contributed to the National Diabetes Repository or who were assessed at a diabetes specialty clinic (LMC Diabetes and Endocrinology) between July 3, 2015, and June 30, 2019, were included. Diabetes type was categorized as type 2 diabetes (T2D) not prescribed insulin, T2D prescribed insulin, and type 1 diabetes (T1D). Covariates were age, sex, income quintile, province, rural/urban location, estimated glomerular filtration rate, medications, and insulin pump use. Associations between predictors and the outcome (glycated hemoglobin [A1C] of ≤7.0%) were assessed by multivariable logistic regressions. RESULTS: Among 122,106 adults, consisting of 91,366 with T2D not prescribed insulin, 25,131 with T2D prescribed insulin, and 5,609 with T1D, attainment of an A1C of ≤7.0% was 60%, 25%, and 23%, respectively. Proportions with an A1C of ≤7.5% and ≤8.0% were 75% and 84% for those with T2D not prescribed insulin, 41% and 57% for those with T2D prescribed insulin, and 37% and 53% for those with T1D. Highest vs lowest income quintile was associated with greater odds of meeting the A1C target (adjusted odds ratio [95% confidence interval] for each diabetes category: 1.15 [1.10 to 1.21], 1.21 [1.10 to 1.33], and 1.29 [1.04 to 1.60], respectively). Individuals in Alberta and Manitoba had less antihyperglycemic medication use and attainment of A1C target than other provinces. CONCLUSIONS: Attainment of glycemic targets among adults with diabetes was poor and differed by income and geographic location, which must be addressed in national diabetes strategies.

Care Endpoints in Adults With Type 2 Diabetes: Screening and Therapeutic Targets at a Canadian Tertiary Diabetes Care Centre.

OBJECTIVES: Although national diabetes guidelines recommend targets for various health parameters, studies have demonstrated a gap between recommendations and real-life practice. The objectives of the present study were to 1) assess measurements in type 2 diabetes (T2DM) care performed by diabetologists in tertiary care, 2) determine whether these measurements were within recommended targets by Canadian guidelines, and 3) identify how these measurements compare with previously published Canadian studies. METHODS: A retrospective chart review analyzed electronic medical records of patients seen by diabetes specialists at the McGill University Health Centre (MUHC). Patients 18 to 75 years of age and diagnosed with T2DM were assessed for blood pressure <130/80 mmHg, low-density lipoprotein cholesterol (LDL-C) ≤2 mmol/L and glycated hemoglobin (A1C) ≤7%. Urinary albumin:creatinine ratio (uACR) was also assessed. Comparisons were made with existing literature data. RESULTS: The percentages of patients with recent screening of A1C, LDL-C, blood pressure and uACR were higher compared with the earlier studies. The calculated means for A1C, LDL-C and blood pressure were comparable with those studies. The percentage of measurements achieving target was comparable with subspecialty care data but differed from primary care data. CONCLUSIONS: Patients with T2DM at the MUHC receive guideline-based measurements of health parameters more frequently than at other institutions. Achievement of target values was closer to that seen by Canadian specialists than by primary care. Although further analyses are necessary to help implement effective strategies for improvement, quality assurance is nonetheless an essential part of ensuring the standards of tertiary care.

[Study of arterial pressure levels at consultation in treated hypertensive Algerian patients]. / Étude du niveau de pression artérielle en consultation chez l'hypertendu algérien traité (PACT II).

BACKGROUND: Hypertension is responsible for 8.5 million deaths from stroke, ischemic heart disease and other vascular and kidney diseases. In Algeria, hypertension (HTN) is the most common chronic disease with an estimated prevalence of 23,6%. METHODS: The PACT II study is a national, observational, descriptive, cross-sectional, multicenter and non-interventional study of therapeutic strategy, conducted in Algeria on hypertensive patients treated for at least 3 months, followed by 100 specialists or general practitioners. The primary objective is to describe the hypertension management in Algeria through the distribution of patients treated for HTN through predefined levels of arterial pressure (AP) reached under treatment. RESULTS: 2000 eligible patients were recruited in the study. 63.5% and 36.4% of patients were female and male respectively. The average age was 62.4 years ± 10.7. The most affected age group (65.2%) was between 55 to 75 years old. Most of the patients had an elevated blood pressure (BP) with 49.30 % at level III AP (130 - 139 mmHg of SBP or 80 - 89 mmHg of DBP), with 49.6% for diabetic patients and 48.8% for non-diabetic patients, then followed by 20.35% at the level IV AP (140 - 159 mmHg of SBP or 90 - 99 mmHg of DBP) with 21.4% for diabetic and 18.3% for non-diabetic patients. Also, 47.32% were at AP level III in patients with Renal failure. Regarding the achievement of the BP target, it was 17.4% for the overall population with 18,3% for diabetic's patients and only 12.64% for Renal failure patients. Additionally, the risk of cardiovascular disease (CVD) was at very high level for most patients, corresponding to 38,4 % of the overall study population. At last, PACT II study data were collected on analysis of blood pressure levels in the overall population and in cardiovascular risk (CVR) population groups such as diabetes (65%), sedentary lifestyle (53%), dyslipidemia (50%), obesity (44%), and renal failure (11.3%). CONCLUSION: PACT II has made it possible to update national data relating to hypertension in Algeria. It confirmed the low level of achievement of the BP target, even if the average arterial pressure level obtained was acceptable in 76% patients with a BP level which was lower than 140 mmHg for SBP and less than 90 mmHg for DBP. Many efforts must be made, according to WHO recommendations, to improve the management of hypertensive patients and BP control in Algeria.

French protocol for the diagnosis and management of familial Mediterranean fever.

Familial Mediterranean fever is the most common monogenic auto-inflammatory disease in the world. It mainly affects people originating from the Mediterranean region. The mutated gene is MEFV, which codes for pyrin. Transmission is autosomal recessive. Patients present with recurrent attacks of fever since childhood associated with abdominal and/or thoracic pain lasting an average of 2-3days and a biological inflammatory syndrome. Other symptoms include arthralgia or arthritis in large joints such as the knees and ankles, myalgia in the lower limbs and pseudo-erysipelas in the ankles. The most serious complication is inflammatory amyloidosis, which can lead to kidney failure. Treatment is based on colchicine, which helps to prevent flares and the onset of renal amyloidosis. This paper proposes national guidelines for the diagnosis, management and follow-up of familial Mediterranean fever in France, where we estimate there are between 5000 and 10,000 patients with the disease at all stages of life. The diagnosis is suspected on the basis of clinical and anamnestic factors and confirmed by genetic analysis. These guidelines also suggest a "treat-to-target" approach to disease management, particularly in case of suspected colchicine resistance - a very rare situation that should remain a diagnosis of elimination, especially after colchicine compliance has been verified. Two special situations are also addressed in these guidelines: kidney failure and pregnancy.