Additive Interaction Between Insulin Resistance, Chronic Low-Grade Inflammation and Vitamin D Deficiency on the Risk of Type 2 Diabetes Mellitus: A Cohort Study.

OBJECTIVES: The aim of this study was to explore, on an additive scale, the combined effect of the association between insulin resistance (IR), chronic low-grade inflammation (CLGI) and vitamin D deficiency (VDD) on the risk of type 2 Diabetes Mellitus (T2DM). METHODS: This is a cohort study, including 1484 non-diabetic subjects, followed for a period of four years. 25 hydroxy-vitamin D (25OHD), hypersensitive C-reactive protein (HsCRP) and triglyceride-glucose index were assessed. Based on VDD and CLGI, the population was subdivided into 4 exposure groups. Analysis was performed both in the case of IR and without IR. Cox proportional regression and additive interaction were applied to explore cumulative effects of exposure. RESULTS: At follow-up, 162 newly diagnosed cases of T2DM were identified. TYG index (RR = 4.0[2.8-5.6]), HsCRP (RR = 1.6 [1.4-1.7]) and 25OHD (RR = 0.96 [0.39-0.98]) were all significantly associated with the risk of T2DM (p < 0.01). The highest excess risk was recorded in patients cumulating simultaneously IR, CLGI and VDD (RR= 8.4[3.6-19.8], p < 0.0001). The additive interaction was significant, the excess risk linked to the interaction RERI = 10.5[1.43-19.7], the proportion attributable to the combined effect: AP = 0.61[0.37-0.85], and the interaction was synergistic: synergy index: 2.8[1.42-5.69]. CONCLUSION: Baseline levels of TYG index, 25OHD and HsCRP are strongly predictive of future T2DM, and their joint effects are additive and synergistic. Interventional studies are therefore warranted in order to evaluate whether vitamin D supplementation, combined with appropriate anti-inflammatory therapies, is effective as a preventive strategy to reduce the risk of T2DM.

Racial and ethnic disparities in psychological care for individuals with FASD: a dis/ability studies and critical race theory perspective toward improving prevention, assessment/diagnosis, and intervention.

Fetal alcohol spectrum disorders (FASD) are among the most common neurodevelopmental disorders and substantially impact public health. FASD can affect people of all races and ethnicities; however, there are important racial and ethnic disparities in alcohol-exposed pregnancy prevention, assessment and diagnosis of FASD, and interventions to support individuals with FASD and their families. In this article we use the Dis/Ability Studies and Critical Race Theory (Dis/Crit) framework to structure the exploration of disparities and possible solutions within these three areas (prevention, diagnosis, intervention). Dis/Crit provides a guide to understanding the intersection of dis/ability and race, while framing both as social constructs. Following the Dis/Crit framework, the systemic, historical, and contemporary racism and ableism present in psychological care is further discussed. We aim to elucidate these racial and ethnic disparities within the fields of psychology and neuropsychology through the Dis/Crit framework and provide potential points of action to reduce these disparities.

Prediction of body fat percentage: Development and validation of new anthropometric equations.

INTRODUCTION: The aim of this study was to test the validity of existing equations, retrieved from the literature, in the Algerian adult population. To develop, and validate, new predictive equations for body fat percentage (%BF) using simple and easy-to-measure anthropometric parameters. METHODS: This is a cross-sectional study including 877 Algerian adults who underwent a body composition assessment by the direct segmental multi-frequency bioelectrical impedance technique (Inbody-770). Participants were randomly divided into two groups: the development group (n = 577) and the validation group (n = 300). To develop the equations, multiple linear regression models were analyzed. The predictive performance of the developed equations was compared with the direct technique. The following validation tests were used: Student's t-test for paired samples, correlation, and Bland-Altman diagram. Diagnostic accuracy has also been assessed. RESULTS: Four existing equations were tested, and all showed statically significant bias. Four new equations were developed; all had satisfactory predictive performance, with a correlation coefficient ranging from 0.72 to 0.94 in men and 0.87 to 0.93 in women. The best-fitting equation was based on body mass index, waist-to-hip ratio, and chest circumference. The diagnostic accuracy of this equation was 96.7% in men and 95.3% in women. CONCLUSION: The newly developed equations based on anthropometric parameters can serve as a simple tool for the accurate prediction of BF% in adult subjects, at both individual and epidemiological levels.

Reconsidering vitamin D optimal values based on parathyroid hormone levels in a North Algerian cohort: stratification by gender and season.

"Health-based threshold value" is used to define the optimal cutoff of vitamin D. This approach is based on the hypothesis of a secondary hyperparathyroidism associated with hypovitaminosis D. We define the optimal values in a North Algerian population. The optimal value is 25.0 ng/ml in men and 30.0 ng/ml in women. PURPOSE/INTRODUCTION: There is no consensus defining the vitamin D optimal values. The aim of this study is to establish vitamin D optimal values in the Northern Algerian population, based on its skeletal effects as represented by the inverse relationship between 25-hydroxy vitamin D (25(OH) D) and parathyroid hormone (PTH). METHODS: 451 healthy volunteers of both genders, aged 19 to 79 years, were enrolled in a cross-sectional study conducted at the medical analysis laboratory of the University Hospital of Blida, Algeria. 25(OH) D was assessed by a sequential competitive immuno-fluoroassay technique. Determination of vitamin D optimal values was performed based on the kinetic relationship between 25(OH) D and PTH, as explored by inverse nonlinear regression on a spline plots curve. The optimal value represents the 25(OH) D level at which PTH ceases to increase and reaches a virtual plateau. RESULTS: In men and women, respectively, the 25 (OH) D thresholds are estimated at 25.0 ng/ml and 30 ng/ml, above this value, PTH stabilizes in a virtual plateau, estimated at 22.3 pg/ml and 26.8 pg/ml. In warm and cold seasons, respectively, the 25 (OH) D cut-offs are estimated at 30.0 ng/ml and 25.0 ng/ml, from these values, the PTH stabilizes in a virtual plateau, estimated at 21.5 pg/ml and 27.7 pg/ml. CONCLUSION: In this study, the optimal values of 25(OH) D were defined for the first time in a North Algerian adult population. The optimal value is 25.0 ng/ml in men and 30.0 ng/ml in women.

Association and interaction between vitamin D level and metabolic syndrome for non-alcoholic fatty liver disease.

INTRODUCTION/OBJECTIVES: Previous studies have shown conflicting results regarding the association between hypovitaminosis D and non-alcoholic fatty liver disease (NAFLD). The aim of this study is to explore the individual and combined effect of hypovitaminosis D and metabolic syndrome (MS) on NAFLD. MATERIALS AND METHODS: In this cross-sectional study, 874 subjects were enrolled. 25(OH)D was assessed by a sequential competitive immuno-fluoro-assay method. The Fatty Liver Index (FLI) was used for NAFLD screening. Binary logistic regression and additive interaction were performed to investigate the association between vitamin D status, MS and NAFLD. RESULTS: Severe vitamin D deficiency was found to be positively related to NAFLD, with a higher risk in women than in men (OR = 6.4, 95% CI [2.8-15], p < 0.0001 vs. OR = 5.8, 95% CI [1.9-17.7], p = 0.002). In men, this association was partially masked by obesity. The additive interaction with MS was significant in women but not in men, the relative excess risk due to interaction was of 7.2, 95% CI [1.3-12.9], p = 0.02), the attributable proportion due to the combined effect was of 0.6, 95% CI [0.4-0.8], p < 0.0001. The interaction mechanism is synergistic; the synergy index: was of 2.9, 95% CI [1.6-5.3], p = 0.0006. CONCLUSION: A positive association has been found between severe vitamin D deficiency and NAFLD. Moreover, an excess risk in women combining both MS and severe vitamin D deficiency was quantified.

Combined effect of obesity and metabolic profile on glomerular dysfunction in hypertensive subjects.

AIM: The aim of this study is to explore the individual and combined effects of obesity and metabolic profile on the impairment of glomerular function among hypertensive subjects. METHODS: This is a cross-sectional study enrolling 499 hypertensive subjects. Based on body mass index values and metabolic profile, they were assigned to one of four metabolic phenotype groups: MHNO: metabolically healthy non-obese, MHO: metabolically healthy but obese, MUHNO: metabolically unhealthy but non-obese, and MUHO: metabolically unhealthy and obese. The effect of the interaction between obesity and metabolic profile was tested on an additive scale, for both microalbuminuria and reduced estimated glomerular filtration rate (eGFR). RESULTS: After adjustment for confounding factors, the highest risk of both microalbuminuria and decreased eGFR was found among patients of the MUHO group (OR = 6.0 [2.13], p < 0.0001, OR = 5.4 [1.26], p = 0.03, respectively). Analysis of the additive interaction indicates that 51% and 53% of the risk of microalbuminuria and its combination with low eGFR respectively is explained by the co-occurrence of obesity and metabolic disorder. The mechanism of this interaction is synergistic (synergy index = 2.6, [1.5.3]). CONCLUSION: The decline of glomerular function in hypertensive subjects is significantly exacerbated by the interaction between obesity and metabolic disorders. The management of such high-risk subjects requires, in addition to the therapeutic regimen, an adequate dietary and physical program in order to preserve glomerular function.

Development and validation of a laboratory risk score for the early prediction of COVID-19 severity and in-hospital mortality.

BACKGROUND AND AIMS: Coronavirus Disease 2019 is characterized by a spectrum of clinical severity. This study aimed to develop a laboratory score system to identify high-risk individuals, to validate this score in a separate cohort, and to test its accuracy in the prediction of in-hospital mortality. METHODS: In this cohort study, biological data from 330 SARS-CoV-2 infected patients were used to develop a risk score to predict progression toward severity. In a second stage, data from 240 additional COVID-19 patients were used to validate this score. Accuracy of the score was measured by the area under the receiver operating characteristic curve (AUC). RESULTS: In the development cohort, a step-wise decrease in the average survival duration was noted with the increment of the risk score (pANOVA < 0.0001). A similar trend was confirmed when analyzing this association in the validation cohort (p < 0.0001). The AUC was 0.74 [0.66-0.82] and 0.90 [0.87-0.94], p < 0.0001, respectively for severity and mortality prediction. CONCLUSION: This study provides a useful risk score based on biological routine parameters assessed at the time of admission, which has proven its effectiveness in predicting both severity and short-term mortality of COVID-19. Improved predictive scores may be generated by including other clinical and radiological features.

Vitamin D Deficiency and Low Serum Calcium as Predictors of Poor Prognosis in Patients with Severe COVID-19.

BACKGROUND: The severity of Coronavirus Disease 2019 (COVID-19) is a multifactorial condition. An increasing body of evidence argues for a direct implication of vitamin D deficiency, low serum calcium on poor outcomes in COVID-19 patients. This study was designed to investigate the relationship between these two factors and COVID-19 in-hospital mortality. MATERIALS: This is a prospective study, including 120 severe cases of COVID-19, admitted at the department of Reanimation-Anesthesia. Vitamin D was assessed by an immuno-fluoroassay method. Total serum calcium by a colorimetric method, then, corrected for serum albumin levels. The association with in-hospital mortality was assessed using the Kaplan-Meier survival curve, proportional Cox regression analyses and the receiver operating characteristic curve. RESULTS: Hypovitaminosis D and hypocalcemia were very common, occurring in 75% and 35.8% of patients. When analyzing survival, both were significantly associated with in-hospital mortality in a dose-effect manner (pLog-Rank = 0.009 and 0.001 respectively). A cutoff value of 39 nmol/l for vitamin D and 2.05 mmol/l for corrected calcemia could predict poor prognosis with a sensitivity of 76% and 84%, and a specificity of 69% and 60% respectively. Hazard ratios were (HR = 6.9, 95% CI [2.0-24.1], p = 0.002 and HR = 6.2, 95% CI [2.1-18.3], p = 0.001) respectively. CONCLUSION: This study demonstrates the high frequency of hypocalcemia and hypovitaminosis D in severe COVID-19 patients and provides further evidence of their potential link to poor short-term prognosis. It is, therefore, possible that the correction of hypocalcemia, as well as supplementation with vitamin D, may improve the vital prognosis.

[Management of a global health crisis: first COVID-19 disease feedback from Overseas and French-speaking countries medical biologists]. / Gestion d'une crise sanitaire mondiale : premiers retours d'expérience de biologistes médicaux d'Outre-mer et de francophonie face au COVID-19.

The French society of clinical biology "Biochemical markers of COVID-19" has set up a working group with the primary aim of reviewing, analyzing and monitoring the evolution of biological prescriptions according to the patient's care path and to look for markers of progression and severity of the disease. This study covers all public and private sectors of medical biology located in metropolitan and overseas France and also extends to the French-speaking world. This article presents the testimonies and data obtained for the "Overseas and French-speaking countries" sub-working group made up of 45 volunteer correspondents, located in 20 regions of the world. In view of the delayed spread of the SARS-CoV-2 virus, the overseas regions and the French-speaking regions have benefited from feedback from the first territories confronted with COVID-19. Thus, the entry of the virus or its spread in epidemic form could be avoided, thanks to the rapid closure of borders. The overseas territories depend very strongly on air and/or sea links with the metropolis or with the neighboring continent. The isolation of these countries is responsible for reagent supply difficulties and has necessitated emergency orders and the establishment of stocks lasting several months, in order to avoid shortages and maintain adequate patient care. In addition, in countries located in tropical or intertropical zones, the diagnosis of COVID-19 is complicated by the presence of various zoonoses (dengue, Zika, malaria, leptospirosis, etc.).

Usefulness of biological markers in the early prediction of corona virus disease-2019 severity.

Coronavirus Disease 2019 is a very fast-spreading infectious disease. Severe forms are marked by a high mortality rate. The objective of this study is to identify routine biomarkers that can serve as early predictors of the disease progression. This is a prospective, single-center, cohort study involving 330 SARS-CoV-2 infected patients who were admitted at the University Hospital of Blida, Algeria in the period between the 27th of March and 22nd of April 2020. The ROC curve was used to evaluate the predictive performance of biomarkers, assessed at admission, in the early warning of progression toward severity. Multivariate logistic regression was used to quantify the independent risk for each marker. After an average follow-up period of 13.9 ± 3.5 days, 143 patients (43.3%) were classified as severe cases. Six biological abnormalities were identified as potential risk markers independently related to the severity: elevated urea nitrogen (>8.0 mmol/L, OR = 9.3 [2.7-31.7], p < .00001), elevated CRP (>42mg/L, OR = 7.5 [2.4-23.3], p = .001), decreased natremia (<133. 6 mmol/L, OR = 6.0 [2.0-17.4], p = .001), decreased albumin (<33.5 g/L, OR = 5.2 [1.7-16.6], p = .003), elevated LDH (>367 IU/L, OR = 4.9 [1.7-14.2], p = .003) and elevated neutrophil to lymphocyte ratio (>7.99, OR = 4.2, [1.4-12.2], p = .009). These easy-to-measure, time-saving and very low-cost parameters have been shown to be effective in the early prediction of the COVID-19 severity. Their use at the early admission stage can improve the risk stratification and management of medical care resources in order to reduce the mortality rate.

Diversity of the Genes Implicated in Algerian Patients Affected by Usher Syndrome.

Usher syndrome (USH) is an autosomal recessive disorder characterized by a dual sensory impairment affecting hearing and vision. USH is clinically and genetically heterogeneous. Ten different causal genes have been reported. We studied the molecular bases of the disease in 18 unrelated Algerian patients by targeted-exome sequencing, and identified the causal biallelic mutations in all of them: 16 patients carried the mutations at the homozygous state and 2 at the compound heterozygous state. Nine of the 17 different mutations detected in MYO7A (1 of 5 mutations), CDH23 (4 of 7 mutations), PCDH15 (1 mutation), USH1C (1 mutation), USH1G (1 mutation), and USH2A (1 of 2 mutations), had not been previously reported. The deleterious consequences of a missense mutation of CDH23 (p.Asp1501Asn) and the in-frame single codon deletion in USH1G (p.Ala397del) on the corresponding proteins were predicted from the solved 3D-structures of extracellular cadherin (EC) domains of cadherin-23 and the sterile alpha motif (SAM) domain of USH1G/sans, respectively. In addition, we were able to show that the USH1G mutation is likely to affect the binding interface between the SAM domain and USH1C/harmonin. This should spur the use of 3D-structures, not only of isolated protein domains, but also of protein-protein interaction interfaces, to predict the functional impact of mutations detected in the USH genes.

A novel biallelic splice site mutation of TECTA causes moderate to severe hearing impairment in an Algerian family.

Congenital deafness is certainly one of the most common monogenic diseases in humans, but it is also one of the most genetically heterogeneous, which makes molecular diagnosis challenging in most cases. Whole-exome sequencing in two out of three Algerian siblings affected by recessively-inherited, moderate to severe sensorineural deafness allowed us to identify a novel splice donor site mutation (c.5272+1G > A) in the gene encoding α-tectorin, a major component of the cochlear tectorial membrane. The mutation was present at the homozygous state in the three affected siblings, and at the heterozygous state in their unaffected, consanguineous parents. To our knowledge, this is the first reported TECTA mutation leading to the DFNB21 form of hearing impairment among Maghrebian individuals suffering from congenital hearing impairment, which further illustrates the diversity of the genes involved in congenital deafness in the Maghreb.

The CD2 isoform of protocadherin-15 is an essential component of the tip-link complex in mature auditory hair cells.

Protocadherin-15 (Pcdh15) is a component of the tip-links, the extracellular filaments that gate hair cell mechano-electrical transduction channels in the inner ear. There are three Pcdh15 splice isoforms (CD1, CD2 and CD3), which only differ by their cytoplasmic domains; they are thought to function redundantly in mechano-electrical transduction during hair-bundle development, but whether any of these isoforms composes the tip-link in mature hair cells remains unknown. By immunolabelling and both morphological and electrophysiological analyses of post-natal hair cell-specific conditional knockout mice (Pcdh15ex38-fl/ex38-fl Myo15-cre+/-) that lose only this isoform after normal hair-bundle development, we show that Pcdh15-CD2 is an essential component of tip-links in mature auditory hair cells. The finding, in the homozygous or compound heterozygous state, of a PCDH15 frameshift mutation (p.P1515Tfs*4) that affects only Pcdh15-CD2, in profoundly deaf children from two unrelated families, extends this conclusion to humans. These results provide key information for identification of new components of the mature auditory mechano-electrical transduction machinery. This will also serve as a basis for the development of gene therapy for deafness caused by PCDH15 defects.

EPS8, encoding an actin-binding protein of cochlear hair cell stereocilia, is a new causal gene for autosomal recessive profound deafness.

BACKGROUND: Almost 90% of all cases of congenital, non-syndromic, severe to profound inherited deafness display an autosomal recessive mode of transmission (DFNB forms). To date, 47 causal DFNB genes have been identified, but many others remain to be discovered. We report the study of two siblings born to consanguineous Algerian parents and affected by isolated, profound congenital deafness. METHOD: Whole-exome sequencing was carried out on these patients after a failure to identify mutations in the DFNB genes frequently involved. RESULTS: A biallelic nonsense mutation, c.88C > T (p.Gln30*), was identified in EPS8 that encodes epidermal growth factor receptor pathway substrate 8, a 822 amino-acid protein involved in actin dynamics. This mutation predicts a truncated inactive protein or no protein at all. The mutation was also present, in the heterozygous state, in one clinically unaffected sibling and in both unaffected parents, and was absent from the other two unaffected siblings. It was not found in 120 Algerian normal hearing control individuals or in the Exome Variant Server database. EPS8 is an F-actin capping and bundling protein. Mutant mice lacking EPS8 (Eps8-/- mice), which is present in the hair bundle, the sensory antenna of the auditory sensory cells that operate the mechano-electrical transduction, are also profoundly deaf and have abnormally short hair bundle stereocilia. CONCLUSION: This new DFNB form is likely to arise from abnormal hair bundles resulting in compromised detection of physiological sound pressures.