Clinical Spectrum and Prognosis of Atypical Autosomal Dominant Polycystic Kidney Disease Caused by Monoallelic Pathogenic Variants of IFT140.

Rationale & Objective: Monoallelic predicted Loss-of-Function (pLoF) variants in IFT140 have recently been associated with an autosomal dominant polycystic kidney disease (ADPKD)-like phenotype. This study sought to enhance the characterization of this phenotype.

Study Design: Case series.

Improving the reliability of small- and wide-angle X-ray scattering measurements of anisotropic precipitates in metallic alloys using sample rotation.

Nanometric precipitates in metallic alloys often have highly anisotropic shapes. Given the large grain size and non-random texture typical of these alloys, performing small- and wide-angle X-ray scattering (SAXS/WAXS) measurements on such samples for determining their characteristics (typically size and volume fraction) results in highly anisotropic and irreproducible data. Rotations of flat samples during SAXS/WAXS acquisitions are presented here as a solution to these anisotropy issues.

Elastic strain mapping of plastically deformed materials by TEM.

A method for mapping elastic strains by TEM in plastically deformed materials is presented. A characteristic feature of plastically deformed materials, which cannot be handled by standard strain measurement method, is the presence of orientation gradients. To circumvent this issue, we couple orientation and strain maps obtained from scanning precession electron diffraction datasets.

Monoallelic pathogenic ALG5 variants cause atypical polycystic kidney disease and interstitial fibrosis.

Disorders of the autosomal dominant polycystic kidney disease (ADPKD) spectrum are characterized by the development of kidney cysts and progressive kidney function decline. PKD1 and PKD2, encoding polycystin (PC)1 and 2, are the two major genes associated with ADPKD; other genes include IFT140, GANAB, DNAJB11, and ALG9. Genetic testing remains inconclusive in ∼7% of the families.

Lipoprotein Proteomics and Aortic Valve Transcriptomics Identify Biological Pathways Linking Lipoprotein(a) Levels to Aortic Stenosis.

Lipoprotein(a) (Lp(a)) is one of the most important risk factors for the development of calcific aortic valve stenosis (CAVS). However, the mechanisms through which Lp(a) causes CAVS are currently unknown. Our objectives were to characterize the Lp(a) proteome and to identify proteins that may be differentially associated with Lp(a) in patients with versus without CAVS.

A Comparative Analysis of the Lipoprotein(a) and Low-Density Lipoprotein Proteomic Profiles Combining Mass Spectrometry and Mendelian Randomization.

Background: Lipoprotein(a) (Lp[a]), which consists of a low-density lipoprotein (LDL) bound to apolipoprotein(a), is one of the strongest genetic risk factors for atherosclerotic cardiovascular diseases. Few studies have performed hypothesis-free direct comparisons of the Lp(a) and the LDL proteomes. Our objectives were to compare the Lp(a) and the LDL proteomic profiles and to evaluate the effect of lifelong exposure to elevated Lp(a) or LDL cholesterol levels on the plasma proteomic profile.

Interaction of Autotaxin With Lipoprotein(a) in Patients With Calcific Aortic Valve Stenosis.

Our objectives were to determine whether autotaxin (ATX) is transported by lipoprotein(a) [Lp(a)] in human plasma and if could be used as a biomarker of calcific aortic valve stenosis (CAVS). We first found that ATX activity was higher in Lp(a) compared to low-density lipoprotein fractions in isolated fractions of 10 healthy participants. We developed a specific assay to measure ATX-Lp(a) in 88 patients with CAVS and 144 controls without CAVS.

Pathogenic and likely pathogenic variants in at least five genes account for approximately 3% of mild isolated nonsyndromic thrombocytopenia.

Background: Thrombocytopenia has a variety of different etiologies, both acquired and hereditary. Inherited thrombocytopenia may be associated with other symptoms (syndromic forms) or may be strictly isolated. To date, only about half of all the familial forms of thrombocytopenia have been accounted for in terms of well-defined genetic abnormalities.

Acute and Chronic Impact of Biliopancreatic Diversion with Duodenal Switch Surgery on Plasma Lipoprotein(a) Levels in Patients with Severe Obesity.

Background: Elevated lipoprotein(a) (Lp(a)) level is an independent risk factor for cardiovascular diseases. Lifestyle intervention studies targeting weight loss revealed little to no significant changes in Lp(a) levels. The impact of interventions that induce substantial weight loss, such as bariatric surgery, on Lp(a) levels is currently unclear.

Clinical spectrum, prognosis and estimated prevalence of DNAJB11-kidney disease.

Monoallelic mutations of DNAJB11 were recently described in seven pedigrees with atypical clinical presentations of autosomal dominant polycystic kidney disease. DNAJB11 encodes one of the main cofactors of the endoplasmic reticulum chaperon BiP, a heat-shock protein required for efficient protein folding and trafficking. Here we conducted an international collaborative study to better characterize the DNAJB11-associated phenotype.

Lipoprotein(a), Oxidized Phospholipids, and Aortic Valve Microcalcification Assessed by 18F-Sodium Fluoride Positron Emission Tomography and Computed Tomography.

Background: Lipoprotein(a) (Lp[a]) is the preferential lipoprotein carrier of oxidized phospholipids (OxPLs) and a well-established genetic risk factor for calcific aortic valve stenosis (CAVS). Whether Lp(a) predicts aortic valve microcalcification in individuals without CAVS is unknown. Our objective was to estimate the prevalence of elevated Lp(a) and OxPL levels in patients with CAVS and to determine if individuals with elevated Lp(a) but without CAVS have higher aortic valve microcalcification.

Genetic Variation in LPA, Calcific Aortic Valve Stenosis in Patients Undergoing Cardiac Surgery, and Familial Risk of Aortic Valve Microcalcification.

Importance: Genetic variants at the LPA locus are associated with both calcific aortic valve stenosis (CAVS) and coronary artery disease (CAD). Whether these variants are associated with CAVS in patients with CAD vs those without CAD is unknown.

Objective: To study the associations of LPA variants with CAVS in a cohort of patients undergoing heart surgery and LPA with CAVS in patients with CAD vs those without CAD and to determine whether first-degree relatives of patients with CAVS and high lipoprotein(a) (Lp[a]) levels showed evidence of aortic valve microcalcification.

Air stepping in response to optic flows that move Toward and Away from the neonate.

To shed further light on the perceptual regulation of newborn stepping, we compared neonatal air stepping in response to optic flows simulating forward or backward displacement with stepping forward on a surface. Twenty-two 3-day-olds performed four 60 s trials in which they stepped forward on a table (Tactile) or in the air in response to a pattern that moved toward (Toward) or away (Away) from them or was static (Static). Significantly more steps were taken in the Tactile and Toward conditions than the Static condition.

Common variants at SCN5A-SCN10A and HEY2 are associated with Brugada syndrome, a rare disease with high risk of sudden cardiac death.

Brugada syndrome is a rare cardiac arrhythmia disorder, causally related to SCN5A mutations in around 20% of cases. Through a genome-wide association study of 312 individuals with Brugada syndrome and 1,115 controls, we detected 2 significant association signals at the SCN10A locus (rs10428132) and near the HEY2 gene (rs9388451). Independent replication confirmed both signals (meta-analyses: rs10428132, P = 1.

Neonatal stepping in relation to terrestrial optic flow.

This experiment examined whether newborn stepping, a primitive form of bipedal locomotion, could be modulated by optical flow. Forty-eight 3-day-old infants were exposed to optical flows that were projected onto a horizontal surface above which the infants were suspended. Significantly more air steps were elicited by exposure to a terrestrial optical flow specifying forward translation than by a rotating optical flow or a static optical pattern.

Safety of Oxygreen, an ozone treatment on wheat grains. Part 2. Is there a substantial equivalence between Oxygreen-treated wheat grains and untreated wheat grains?

The Oxygreen process is a new process based on wheat grain treatment by ozone (produced in situ), in a closed sequential batch reactor. The Oxygreen process offers a close, homogeneous, and controlled contact between the gas and the grain. It is proposed for use for wheat grain decontamination (insects, fungi, bacteria, mycotoxins, pesticides).

An ALARA approach to the radiological control of foodstuffs following an accidental release.

This article presents a methodology based on two complementary approaches, thus allowing a selection of maximal concentration in foodstuffs for determining appropriate countermeasures. The first approach is based on a minimal and maximal per capita intervention level and takes into account the annual intake of each product. The second one is based on a cost-benefit analysis, comparing the advantages of a countermeasure concerning those products presenting a contamination higher than a given maximal concentration (in terms of reduction of cost of the detriment associated with the risk), with its drawbacks (in terms of cost of the products) in order to select the "ALARA" maximal concentration.

[Exposure of industrial origin. Transfer to the environment].

The purpose of this paper is to show how to assess the consequences of gaseous and liquid releases. The following points are studied successively: --atmospheric dispersion and depletion process, in order to evaluate wet and dry deposition; --marine diffusion in order to evaluate the contamination of aquatic products; --the different models permitting to assess the contamination of vegetal and animal products; --the models used for the doses calculations resulting from external exposure due to the plume or the deposit. The calculation of the individual and collective effective dose equivalents is presented for each pathway to man.