Diagnostics and treatment of ocular complications in infantile nephropathic cystinosis

Cystinosis, as a rare disease, faces many difficulties with regard to appropriate early diagnostics and treatment. The aim of our study is to present current methods of diagnostics and treatment of ocular complications in an infantile nephropathic type of cystinosis. It is the most severe type, causing many ocular and life-threatening systemic complications. Ocular severe complications are usually due to the presence of an infantile nephropathic form of cystinosis, long-term illness, delayed diagnosis, non-compliance, or inappropriate treatment. Slit-lamp biomicroscopy is a major examination detecting corneal cystine crystals and the main tool in cystinosis diagnostics. Anterior segment optical coherence tomography (AS-OCT) and in vivo confocal microscopy (IVCM) are other helpful devices in monitoring the accumulation of crystals in the cornea

Genetic Drivers of Kidney Defects in the DiGeorge Syndrome

Background The DiGeorge syndrome, the most common of the microdeletion syndromes, affects multiple organs, including the heart, the nervous system, and the kidney. It is caused by deletions on chromosome 22q11.2; the genetic driver of the kidney defects is unknown. Methods We conducted a genomewide search for structural variants in two cohorts: 2080 patients with congenital kidney and urinary tract anomalies and 22,094 controls. We performed exome and targeted resequencing in samples obtained from 586 additional patients with congenital kidney anomalies. We also carried out functional studies using zebrafish and mice. Results We identified heterozygous deletions of 22q11.2 in 1.1% of the patients with congenital kidney anomalies and in 0.01% of population controls (odds ratio, 81.5; P=4.5×10(-14)). We localized the main drivers of renal disease in the DiGeorge syndrome to a 370-kb region containing nine genes. In zebrafish embryos, an induced loss of function in snap29, aifm3, and crkl resulted in renal defects; the loss of crkl alone was sufficient to induce defects. Five of 586 patients with congenital urinary anomalies had newly identified, heterozygous protein-altering variants, including a premature termination codon, in CRKL. The inactivation of Crkl in the mouse model induced developmental defects similar to those observed in patients with congenital urinary anomalies. Conclusions We identified a recurrent 370-kb deletion at the 22q11.2 locus as a driver of kidney defects in the DiGeorge syndrome and in sporadic congenital kidney and urinary tract anomalies. Of the nine genes at this locus, SNAP29, AIFM3, and CRKL appear to be critical to the phenotype, with haploinsufficiency of CRKL emerging as the main genetic driver. (Funded by the National Institutes of Health and others.)

Le droit de l'environnement en Pologne, (2000 - 2005)

Sikora Przemyslaw. Le droit de l'environnement en Pologne, (2000 - 2005) . In: Revue Européenne de Droit de l'Environnement, n°3, 2006. pp. 289-294

Christoforos Petrou, Le régime de la protection de l'environnement dans le cadre de la Communauté européenne, 2000

Sikora Przemyslaw. Christoforos Petrou, Le régime de la protection de l'environnement dans le cadre de la Communauté européenne, 2000. In: Revue Européenne de Droit de l'Environnement, n°4, 2002. p. 497

Microbial communities associated with the anthropogenic, highly alkaline environment of a saline soda lime, Poland

Soda lime is a by-product of the Solvay soda process for the production of sodium carbonate from limestone and sodium chloride. Due to a high salt concentration and alkaline pH, the lime is considered as a potential habitat of haloalkaliphilic and haloalkalitolerant microbial communities. This artificial and unique environment is nutrient-poor and devoid of vegetation, due in part to semi-arid, saline and alkaline conditions. Samples taken from the surface layer of the lime and from the depth of 2 m (both having pH similar to 11 and ECe up to 423 dS m(-1)) were investigated using culture-based (culturing on alkaline medium) and culture-independent microbiological approaches (microscopic analyses and pyrosequencing). A surprisingly diverse bacterial community was discovered in this highly saline, alkaline and nutrient-poor environment, with the bacterial phyla Proteobacteria (representing 52.8% of the total bacterial community) and Firmicutes (16.6%) showing dominance. Compared to the surface layer, higher bacterial abundance and diversity values were detected in the deep zone, where more stable environmental conditions may occur. The surface layer was dominated by members of the genera Phenylobacterium, Chelativorans and Skermanella, while in the interior layer the genus Fictibacillus was dominant. The culturable aerobic, haloalkaliphilic bacteria strains isolated in this study belonged mostly to the genus Bacillus and were closely related to the species Bacillus pseudofirmus, B. cereus, B. plakortidis, B. thuringensis and B. pumilus

Ophthalmic Evaluation of Diagnosed Cases of Eye Cystinosis: A Tertiary Care Center’s Experience

Background: We aimed to identify diagnosed cases of ocular cystinosis and describe clinical, epidemiological and therapeutic characteristics. Methods: This is a descriptive and retrospective case series. All patients underwent a full check-up examination every 4–6 months by ophthalmologists, nephrologists and other required specialists. Results: Of the seven cases, six (85.7%) were females and one (14.2%) was male. The infantile nephropathic form of cystinosis was observed in five patients and the juvenile nephropathic form in two patients. No patients with the ocular form of cystinosis were identified. Corneal cystine crystals (CCC) were found in all analyzed patients. Severe ocular and general complications of the disease that had been standing for years, connected to the infantile nephropathic form, delayed diagnosis or inappropriate treatment, were observed only in two patients. All patients received topical therapy. No adverse events related to the therapy were observed. Conclusions: Cystinosis is a rare, progressive disease. Early diagnosis and treatment prevent serious complications from numerous systemic organs. Patients require constant systematic monitoring by various specialists

Chronic liver disease and hepatic calcium-oxalate deposition in patients with primary hyperoxaluria type I

Patients with primary hyperoxaluria type I (PH I) are prone to develop early kidney failure. Systemic deposition of calcium-oxalate (CaOx) crystals starts, when renal function declines and plasma oxalate increases. All tissue, but especially bone, heart and eyes are affected. However, liver involvement, as CaOx deposition or chronic hepatitis/fibrosis has never been reported. We examined liver specimen from 19 PH I patients (aged 1.5 to 52 years at sample collection), obtained by diagnostic biopsy (1), at autopsy (1), or transplantation (17). With polarization microscopy, birefringent CaOx crystals located in small arteries, but not within hepatocytes were found in 3/19 patients. Cirrhosis was seen in one, fibrosis in 10/19 patients, with porto-portal and nodular fibrosis (n = 1), with limitation to the portal field in 8 and/or to central areas in 5 patients. Unspecific hepatitis features were observed in 7 patients. Fiber proliferations were detectable in 10 cases and in one sample transformed Ito-cells (myofibroblasts) were found. Iron deposition, but also megakaryocytes as sign of extramedullary erythropoiesis were found in 9, or 3 patients, respectively. Overall, liver involvement in patients with PH I was more pronounced, as previously described. However, CaOx deposition was negligible in liver, although the oxalate concentration there must be highest

Still diagnosed too late and under-recognized? The first comprehensive report on primary hyperoxaluria in Poland

INTRODUCTION Primary hyperoxalurias (PHs) are rare disorders leading to overproduction and increased urinary excretion of oxalate. Three monogenic forms (PH1-PH3) were classified. PHs lead to urolithiasis and chronic kidney disease. There are only sparse data on patients with PH from Eastern European countries including Poland. OBJECTIVES The aim of the study was to evaluate the prevalence, genetic background, and clinical course of PH in the Polish population. PATIENTS AND METHODS This was a retrospective multicenter study including data of all identified and genetically confirmed Polish patients with PH. RESULTS Between 1998 and 2019, 21 patients with PH were identified, including 13 patients with PH1 (62%), 2 with PH2 (9%), and 6 with PH3 (29%). In those with PH1, the most common mutation was c.508G>A in AGXT and in PH3, c.700+5G>T in HOGA1. Nine patients (69%) developed end-stage renal disease at a median age of 13 years and 2 died. In 6 (46%) PH1 cases, the diagnosis was made only after patients had progressed to end-stage renal disease and received isolated kidney transplantation, followed by graft failure. Combined liver-kidney transplantation was performed in 6 patients with PH1. Two siblings with PH2 showed a milder course with slightly decreased renal function in one, at age of 11 years. Despite infantile onset of urolithiasis, all patients with PH3 at a median age of 10 years maintained normal renal function. CONCLUSIONS The prevalence of PH1 and PH2 in Poland seems to be much lower than in Western countries with PH3 constituting about 30% of all cases. The molecular findings and clinical course are typical, but the underdiagnosis is of concern

Design and Integration of the Optical Reference Module at 1.3 GHz for FLASH and the European XFEL

In this paper we present recent progress on the integration and implementation of the optical reference module (REFM-OPT) for the free-electron lasers FLASH and European XFEL. In order to achieve high energy stability and low arrival time jitter of the electron beam, the accelerator requires an accurate low-level RF (LLRF) field regulation and a sophisticated synchronization scheme for various devices along the facility. The REFM-OPT is a 19” module which is responsible for resynchronizing the 1.3 GHz reference signal for the LLRF distributed by coaxial cables to a phase-stable signal of the optical synchronization system. The module provides a 1.3 GHz output signal with low phase noise and high long-term stability. Several sub-components of the REFM-OPT designed specifically for this module are described in detail. The readout electronics of the high-precision Laser-to-RF phase detector are presented as well as the integration of this key component into the 19” module. Additionally, we focus on design solutions which assure phase stability and synchronization of the 1.3 GHz signal at several high power outputs of the module