[Clinical and genetic description of neuronal ceroid lipofuscinosis 6 type in the yakut family]. / Kliniko-geneticheskoe opisanie neironal'nogo tseroidnogo lipofustsinoza 6 tipa v yakutskoi sem'e.

Neuronal ceroid lipofuscinosis type 6 (NCL 6) is a rare progressive neurodegenerative disease that belongs to the group of lysosomal storage diseases. A clinical and genetic description of NCL 6 in a Yakut family was carried out. The proband and her sibling showed characteristic clinical signs, including myoclonic epilepsy, ataxia, psychomotor regression, dementia, and visual impairment. The onset of the disease in the age range from 3-4 years. The disease is caused by the frameshift mutation c.396dupT (p.Val133CysfsTer18) in exon 4 of the CLN6 in a homozygous state, which was detected using targeted next generation sequencing. Diagnosis of NCL is difficult due to the pronounced genetic heterogeneity of the disease, as well as the similarity with other hereditary metabolic diseases in clinical manifestations. The method of DNA diagnostics of NCL type 6 using NGS and direct sequencing according to Sanger has been introduced into the practice of medical genetic counseling.

REACTIVE ARTHRITIS IN CHILDREN (REVIEW).

Reactive arthritis is an aseptic inflammatory arthritis that is associated with intestinal, urogenital, and nasopharyngeal infections, and represents a systemic clinical presentation of these infections. Reactive arthritis among children still remains an issue in pediatric rheumatology. The variety of the clinical manifestations makes it difficult to diagnose and detect reactive arthritis. Moreover, there is a risk that reactive arthritis without a proper treatment can lead to chronic destructive joint diseases. As the articles' analysis has shown, this topic in pediatrics has been neglected over the past 10 years. Thus, the paper presents data on the epidemiology, pathophysiology, clinical presentation and diagnosis of this disease, as well as recommendations for further studies.

DNA insecticides: Data on the trial in the field.

This data article is related to the research articles entitled "The RING for gypsy moth control: topical application of fragment of its nuclear polyhedrosis virus anti-apoptosis gene as insecticide" (Oberemok et al., 2016), "Molecular alliance of Lymantria dispar multiple nucleopolyhedrovirus and a short unmodified antisense oligonucleotide of its anti-apoptotic IAP-3 gene: a novel approach for gypsy moth control" (Oberemok et al., 2017), and "Topical treatment of LdMNPV-infected gypsy moth caterpillars with 18 nucleotides long antisense fragment from LdMNPV IAP-3 gene triggers higher levels of apoptosis in infected cells and mortality of the pest" (Oberemok et al., 2017). This data article reports on the significant decrease of survival of L. dispar larvae after contact application of 18 nucleotides long antisense oligoRING fragment in the field experiment and supports perspective of use of DNA insecticides in forests.

Systemic lupus erythematosus and associated healthcare resource consumption in selected cities from the Russian Federation, Republic of Kazakhstan and Ukraine: the ESSENCE study.

OBJECTIVES: To evaluate healthcare resource (HR) consumption associated with Systemic Lupus Erythematosus (SLE) management in adult patients with active autoantibody positive disease in the Russian Federation, Republic of Kazakhstan, and Ukraine. METHODS: The ESSENCE was a retrospective, observational study, and included data on patients' clinical characteristics and SLE-related HR use (laboratory, biopsy, imaging tests, medications, visits to specialists, outpatient visits, hospitalizations) during 2010 from the 12 specialized rheumatologic centers. RESULTS: A total of 436 SLE patients were included in the analyses, with 232 patients being enrolled in Russia, 110 in Kazakhstan, and 94 in Ukraine. The mean age was 36-42 years and median SLE duration was 3-6.8 years across the countries. Extrapolation to total country population showed that, in 2010, visits to specialists (who assign treatment for organs involved/damaged by SLE) were the most frequently used HR (from 13,439 visits in Kazakhstan to 23,510 in Russia), followed by hospitalizations (from 2,950 in Kazakhstan to 6,267 in Russia) and outpatient visits (from 1,654 visits in Russia to 8,064 in Kazakhstan). Compared to chronic active patients (SLE persistent during last year), patients with relapsing-remitting SLE (at least one flare alternated by one remission per year) had a higher rate of visits to specialists (100% vs 60.8%, p < .001) and hospitalizations (98.9% vs 60.8%, p < .001). Compared to patients without flares, patients experiencing flares had a higher rate of unplanned visits to specialists (86.2% vs 6.3%, p < .001), were more often hospitalized (both ICU and non-ICU) (100.0% vs 50.0%, p < .001), and had a longer duration of ICU hospitalization (25.9 days vs 17.5 days, p < .001). CONCLUSIONS: Specialist visits are the most frequently consumed SLE-related healthcare recourse in the Commonwealth of Independent States (CIS) countries. A relapsing-remitting SLE profile and the occurrence of flares significantly raise healthcare resource consumption.

[A case of gynandroblastoma in a 16-year old girl and review of literature].

An ovarian tumor (gynandroblastoma) in a 16-year old girl is reported. Clinical presentation include abdominal pain, signs of virilization and irregular menstrual cycles. Ultrasound scan examination reveals a cystic mass in a left ovary. The patient underwent a left ovariosalpingectomy. Grossly, a cystic mass (73 x 42 x 36 mm) with smooth outer surface and with many cysts was found in the left ovary. The intraoperative diagnosis was ovarian adenocarcinoma. Postoperative histological examination reveals that the tumor was presented by two patterns- nodules and nests of juvenile granulose cell pattern admixed with Sertoli-Leydig pattern as tubules and cyst and scanty Sertoli cells. On immunohistochemical staining the Granulosa cells were negative for cytokeratin AE1-AE3 and positive for Vimentin. The Sertoli cells were androgen receptor positive. A year after operation the patient had no abdominal pain, the menstrual cycles are regular but the virilization persist. Histogenesis and differential diagnosis are discussed.

Standard medical care of patients with systemic lupus erythematosus (SLE) in large specialised centres: data from the Russian Federation, Ukraine and Republic of Kazakhstan (ESSENCE).

OBJECTIVES: To describe disease characteristics and treatment regimens for adult patients with systemic lupus erythematosus (SLE) with autoantibody positive disease in three countries (the Russian Federation, Ukraine and Republic of Kazakhstan). METHODS: The Efficacy and Safety of Subcutaneous Enoxaparin in Non-Q wave Coronary Events (ESSENCE) study was a 1-year, retrospective, multicentre, observational study. Data included patients' characteristics, disease activity and severity, and healthcare resource use in 2010. RESULTS: Twelve centres enrolled 436 eligible patients: 232 in Russia, 110 in Kazakhstan and 94 in Ukraine. Mean age ranged from 36 to 42 years and median SLE duration from 3 to 6.8 years. According to study definitions, 69.2% of patients in Russia, 72.7% in Kazakhstan and 55.4% in Ukraine had severe disease at diagnosis. SLE activity (Nasonova classification, 1972) decreased from diagnosis to the last visit in 2010 in all countries. At the last visit, mean (SD) Safety of Estrogens in Lupus Erythematosus National Assessment-Systemic Lupus Erythematosus Disease Activity Index score was 13.8 (10.5) in Russia, 19.4 (16.9) in Kazakhstan and 7.2 (6.8) in Ukraine, and Systemic Lupus International Collaborative Clinics/American College of Rheumatology damage index was 2.0 (2.2), 3.3 (3.2) and 2.2 (2.0), respectively. Treatment regimens included predominantly glucocorticoids (96.7-99.1%), immunosuppressants or cytotoxic drugs, for example, azathioprine and cyclophosphamide (20.7-53.2%), and antimalarial drugs (18.3-40.8%). CONCLUSIONS: The study provides reliable insight into the SLE clinical profiles in the referenced countries. Patients were 4-10 years younger in the study and had 3-7 years shorter SLE duration than in Western European countries and both SLE activity and severity were higher with higher rate of hospitalisations, but decreased during treatment. Local and international scales demonstrated correlation in SLE activity and organ damage evaluation. There were differences in clinical characteristics and healthcare features across the countries.

[A case of gynandroblastoma in a 16-year old girl and review of literature].

An ovarian tumor (gynandroblastoma) in a 16-year old girl is reported. Clinical presentation include abdominal pain, signs of virilization and irregular menstrual cycles. Ultrasound scan examination reveals a cystic mass in a left ovary. The patient underwent a left ovariosalpingectomy Grossly, a cystic mass (73x 42 x 36 mm) with smooth outersurface and with many cysts was found in the left ovary The intraoperative diagnosis was ovarian adenocarcinoma. Postoperative histological examination reveals that the tumor was presented by two patterns - nodules and nests of juvenile granulose cell pattern admixed with Sertoli-Leydig pattern as tubules and cyst and scanty Sertoli cells. On immunohistochemical staining the Granulosa cells were negative for cytokeratin AE1-AE3 and positive for Vimentin. The Sertoli cells were androgen receptor positive. A yar after operation the patient had no abdominal pain, the menstrual cycles are regular, but virilization persist. Histogenesis and differential diagnosis are discussed.

The prevalence and incidence of systemic lupus erythematosus (SLE) in selected cities from three Commonwealth of Independent States countries (the Russian Federation, Ukraine and Kazakhstan).

We assessed the prevalence and incidence of Systemic Lupus Erythematosus (SLE) in 2010 in adults from four cities in Russia, Kazakhstan and Ukraine. Individuals with SLE were identified retrospectively from the medical records of specialized centers. Prevalent SLE patients were nondeceased city residents, diagnosed prior to December 31, 2010; incident patients were residents newly diagnosed between January 1 and December 31, 2010. Population size was obtained from official census data. The observed prevalence rates (per 100,000, 95% CI) were 9.0 (7.1-11.2) in Kursk and Yaroslavl, Russian Federation; 20.6 (15.4-27.0) in Semey, Kazakhstan; and 14.9 (10.9-19.9) in Vinnitsa, Ukraine. The cumulative incidence rates (per 100,000, 95% CI) were 1.4 (0.7-2.4); 1.6 (0.4-4.1) and 0.3 (0.0-1.8), correspondingly. All rates were higher among females compared to males, and incidence peaked in the population aged 25-44. These rates appear slightly lower than those reported from Western Europe and the USA. This could be because of study design (case-ascertainment), local health care practices or true differences in disease risk. Case age and sex distribution was similar to the known epidemiology of SLE. The rates were highest in Kazakhstan, likely because of a predominantly ethnic Asian population.

Doppler parameters of hepatic and renal hemodynamics in patients with liver cirrhosis.

Introduction. There are limited studies on simultaneous evaluation of liver and renal blood flow using Doppler methods. We evaluated and compared the changes of liver and renal Doppler US parameters in patients with liver cirrhosis according to the degree of liver disease. Material and Methods. We assessed a large spectrum of liver and renal Doppler US parameters in 67 patients with liver cirrhosis. Results. Significant differences between Child's classes or score, as well as MELD score, were observed in all investigated intrarenal blood flow Doppler US parameters, except renal artery peak systolic velocity, but only in some of the hepatic ones. The deviations of renal Doppler US parameters were also related with the complications of liver cirrhosis, as well as serum urea and creatinine levels. There was relationship between Doppler US parameters of hepatic artery and the corresponding renal artery Doppler US parameters. The changes of Doppler US parameters were age independent. Conclusion. Our results show, renal Doppler US parameters correlate with the severity and complications of liver cirrhosis. Because of dynamic deviations of renal Doppler US parameters with advance of liver cirrhosis, we recommend Doppler US of renal artery as a part of follow up of these patients.

[Experimental quality assessment of APTT-control reagent kits in the study of heparin-containing plasma in therapeutic ranges].

Investigation of activated partial thromboplastin time (APTT) in the plasma samples containing different levels of heparin determines the following parameters of the quality of APTT-control reagent kits: coefficient of variation, linearity, sensitivity, and detection. The kit is shown to meet GOST P 51352-99 requirements. The determination of the validity coefficient of approximation has proven a directly proportional functional relationship of the APTT values to the level of heparin in therapeutic ranges in the logarithmic coordinate system. The kit may be used to monitor heparin therapy.

[Experimental quality assessment of APTT-control reagent kits in the study of plasma with varying Factor VIII activity].

An investigation into activated partial thromboplastin time (APTT) in the plasma samples with varying Factor VIII activities has determined the following parameters of the quality of APTT-control reagent kits: coefficient of variation, linearity, sensitivity, and detection. The kit is shown to meet GOST P 51352-99 requirements. The determination of the validity coefficient of approximation has proven a directly proportional functional relationship of the APTT values to the Factor VIII activity in the bilogarithmic coordinate system. The kit may be used to diagnose hemophilia A and Willebrand disease.

Healthcare-associated infective endocarditis: an undesirable effect of healthcare universalization.

Invasive medical technology has led to an increase in the incidence of healthcare-associated infective endocarditis (HAIE). A prospective multicentre cohort study was conducted at seven hospitals in Andalusia, Spain, to establish the characteristics of HAIE and to compare them with those of community-acquired infective endocarditis (CAIE). HAIE was defined as either infective endocarditis (IE) manifesting >48 h after admission to hospital, or IE associated with a significant invasive procedure performed in the 6 months before diagnosis. Seven hundred and ninety-three cases of IE were investigated, and HAIE accounted for 127 (16%). As compared with patients with CAIE, patients with HAIE were older (60.1 ± 14.4 years vs. 53.6 ± 17.5 years) and had more comorbidities (Charlson index 3.3 ± 2.3 vs. 1.8 ± 2.3) and staphylococcal infections (58.3% vs. 24.8%). Vascular manipulation was the main cause of bacteraemia responsible for HAIE (63%). Peripheral vein catheter-associated bacteraemia accounted for 32.8% of the catheter-related bacteraemias. In-hospital mortality (44.9% vs. 24.2%) was higher in the HAIE group. Septic shock (OR 2.2, 95% CI 2.9-30.2) and surgery not performed because of high surgical risk (OR 1.6, 95% CI 1.2-20) were independent predictors of mortality in HAIE. The present study demonstrates that HAIE is a growing health problem associated with high mortality. Careful management of vascular devices is essential to minimize the risk of bacteraemias leading to HAIE.

Multiple relapses of hyperthyroidism after thyroid surgeries in a patient with long term follow-up of sporadic non-autoimmune hyperthyroidism.

Constitutively activating thyrotropin receptor (TSHR) germline mutations have been identified as a molecular cause of congenital hyperthyroidism. Patients with relapsing hyperthyroidism were previously treated with surgery and radioiodine. We report on a 22-year-old male patient who was treated for his multiple relapses of hyperthyroidism by repeated subtotal thyroidectomies (STE). During the 22 years of follow-up, the patient developed several relapses of hyperthyroidism, four of them after thyroid surgeries. Sequencing of the TSHR gene revealed a gain-of-function mutation with an amino acid exchange of aspartate to tyrosine in codon 633 which is located in the sixth transmembrane domain of the TSH receptor. The absence of the mutation in all other family members identifies the patient's TSHR mutation as a sporadic germline mutation. In this patient, thyroid tissue growth and hyperthyroidism could repeatedly be controlled only for limited periods by near total thyroidectomy. Therefore, this case confirms that early combined treatment with near-total thyroidectomy plus radioiodine therapy seems to be the treatment of choice for patients with sporadic non-autoimmune hyperthyroidism.

Solubilization of Morocco phosphorite by Aspergillus niger.

Phosphorus containing fertilizers have an important role in agriculture. Conventionally phosphate fertilizers are obtained by rock phosphate (RP) dissolution using mineral acids. Biotechnological methods can be a promising alternative in RP processing. The influence of Aspergillus niger strain, the composition of a nutritive medium, Morocco phosphorite (MP) concentration in the liquid medium, the time of bioconversion and the preliminary mechanical activation (PMA) of MP on the phosphorite microbial solubilization has been presented. The phosphorus concentration (as P2O5), citric acid production, glucose concentration and pH in the cultural medium were monitored. The phosphate concentration was expressed as water soluble - alpha1 (in the native cultural liquid), citrate soluble - alpha2 (after treating the biomass and remaining mineral mass with citric acid) and biomass available phosphorus - alpha3. Phosphate dissolution was not strongly correlated both with the citric acid production and the incubation period. When the fungi were grown without water soluble phosphorus compounds the MP solubilization had higher values. A maximum of 94.80% total P2O5 extraction was achieved. The PMA activity does not facilitate MP dissolution during the bioconversion.

Serological and molecular detection of Borrelia burgdorferi sensu lato and Anaplasmataceae in rodents.

The presence of Anaplasma spp. and Borrelia burgdorferi sensu lato in rodents from Eastern Slovakia were followed by serological and molecular methods. The seroprevalence for Borrelia was detected in 16.6 %, for Anaplasmataceae (APT) in 13.2 % and co-occurrence of Borrelia and APT in 7.5 %. Out of 110 ear biopsies of rodents, 5 were B. afzelii-positive. Five biopsies tested positive with the Ehr521-Ehr747 primers amplifying all the members of the family APT. A. phagocytophilum was detected in 1.8 %, 2.7 % were infected with Anaplasma-like organisms. Co-occurrence of Borrelia and Anaplasma in ear biopsies was found in 1.8 %. The circulation of both Borrelia and Anaplasma in the region of Eastern Slovakia was confirmed.

[Peculiarities of maternal mortality in the University Hospital of Pleven for period 1977-2001].

The authors report retrospective investigation of causes for maternal mortality in the Department of Obstetric and Gynecology in Hospital in Pleven for the period 1977-2001 and comparison between indexes for a different period of time. Objects of investigation were patient histories necropsy report and forensic expertise. Vital births were 73922 for a period of 25 years in Pleven. Dead pregnant and maternity were 45 and the rate of maternal mortality was 60,07/per 100 000 vital births. Causes of maternal mortality were divided in immediate 40 cases (88,88%) and indirect--5 cases (11,11%). The hemorrhage was the most common cause of maternal mortality--18 cases (45%). The authors mention that the absolute number of maternal losses is comparatively constant but the rate of maternal mortality in creases because of tendency of decrease of birthrate and concentration of pathology in Department of Obstetric and Gynecology in Pleven.

[Characteristics of maternal mortality in the university hospital of Pleven for the period of 1977-2001 years]. / Osobennosti na maichinata smurtnost v MBAL na gr. Pleven prez peroida 1977-2001 godina.

The authors report retrospective investigation of causes for maternal mortality in the Department of Obstetric and Gynecology in Hospital in Pleven for the period 1977-2001 and comparison between indexes for a different period of time. Objects of investigation were patient histories necropsy report and forensic expertise. Vital births were 73922 for a period of 25 years in Pleven. Dead pregnant and materinity were 45 and the rate of maternal mortality was 60,07/per 100 000 vital births. Causes of maternal mortality were divided in immediate 40 cases (88,88%) and indirect - 5 cases (11,11%). The hemorrhage was the most common cause of maternal mortality - 18 cases (45%). The authors mention that the absolute number of maternal losses is comparatively constant but the rate of maternal mortality in creases because of tendency of decrease of birthrate and concentration of pathology in Department of Obstertic and Gynecology in Pleven.

Genomic analysis of Th1-Th2 cytokine genes in an AIDS cohort: identification of IL4 and IL10 haplotypes associated with the disease progression.

Polymorphisms of Th1-Th2 cytokine genes have previously been implicated in the rate of progression to AIDS in seropositive patients. To evaluate further the impact of these genes in the development of AIDS, we have performed an extensive genetic analysis of IL2, IL4, IL6, IL10, IL12p35 and p40, IL13 and IFNgamma. The coding regions and promoters of these genes were sequenced in a Caucasian cohort of 337 HIV-1 seropositive extreme patients (the GRIV cohort) consisting of patients with slow progression and rapid progression, and up to 470 healthy controls. In all, 64 single nucleotide polymorphisms (SNPs) and four deleterious polymorphisms with frequency >1% were identified and evaluated for their association with disease. Statistically significant associations were observed with haplotypes of the IL4 and IL10 genes, but no relation was found with variants of other genes. The catalogue of SNP and haplotypes presented here will facilitate further genetic investigations of Th1-Th2 cytokines in AIDS and other immune-related disorders.