PAPILOMAVIRUS INFECTION IN WOMEN WITH HIV

We developed diagnostic protocol and studied cervical diseases in 733 women with HIV. There were found high incidence of sexual transmitted diseases and multifocal papilloma in these patients. We describe colposcopical signs of cervical papilloma virus infection in HIV-positive women. We suppose that low information content of cervical cytology could be connected with concomitant infections. We also found that HIV is not eliminated but cause to dysplasia of cervical epithelium. That is why we suppose to optimal to pay an attention to cervical neoplasms in women with HIV-PVI association. Severity of observed cervical changes was depended on the associations with sexual transmitted infections, CD4+ lymphocytes level and total virus load

О теоретических основах аэролимнологии: изучение пресных водоемов и прибрежных территорий с применением воздушных робототехнических средств

Интеграция методологического базиса нескольких разных наук при междисциплинарных исследованиях является характерной чертой новых механизмов решения современных прикладных задач. Формируемые теоретические основы аэролимнологии, как нового научного направления, рассматриваются с точки зрения вклада в нее трех ключевых наук: лимнологии, информатики и робототехники. Приведены классификации методов и способов лимнологических исследований, воздушных робототехнических средств, информационных технологий, перспективных для решения задач в области аэролимнологии. Задача научного направления аэролимнологии формулируется как изучение возможностей и ограничений комбинированных способов дистанционного сенсорного измерения, роботизированного пробоотбора и аналитического исследования параметров экосистем пресных водоемов для мониторинга и предсказания динамики их развития. Среди основных направлений аэролимнологических исследований выделены: построение ортофотопланов и фотограмметрических пространственных моделей рельефа дна и отдельных элементов донного ландшафта и прибрежной зоны разного масштаба; геолого-геофизическое картирование подводной части береговой зоны; изучение фитопланктона, в частности «цветения» воды, вызванного цианобактериями; исследование распределения и миграций крупных представителей гидрофауны; изучение температурных полей и процессов перераспределения водных масс. Обсуждаются ограничения, накладываемые на использование беспилотных летательных аппаратов (БпЛА) при пробоотборе и мониторинге прибрежных водных территорий, прежде всего погодно-климатические, временные, пространственные, технические. Преимущество использования беспилотных летательных аппаратов в аэролимнологии обосновывается увеличением скорости получения данных, возможностью подлета к труднодоступным и территориально удаленным объектам, снижением влияния человеческого фактора. Научная новизна представленного исследования состоит в попытке интеграции междисциплинарных знаний при использовании беспилотных летательных аппаратов и обработке полученных данных на основе технологий искусственного интеллекта при изучении лимнологических объектов и процессов. Отмечается важная роль геоинформационных систем и приводятся примеры карт типизации берегов и геоморфологии Ладожского озера, размещенные на сайте Центра коллективного пользования научным оборудованием «Северо-Западный центр мониторинга и прогнозирования развития территорий» СПБ ФИЦ РАН. Рассматриваются основные этапы методологии проведения аэролимнологических исследований с применением междисциплинарных подходов на основе лимнологии, информатики и робототехнических средств, функционирующих в разных средах

Non-Penetrance for Ocular Phenotype in Two Individuals Carrying Heterozygous Loss-of-Function ZEB1 Alleles

ZEB1 loss-of-function (LoF) alleles are known to cause a rare autosomal dominant disorder—posterior polymorphous corneal dystrophy type 3 (PPCD3). To date, 50 pathogenic LoF variants have been identified as disease-causing and familial studies have indicated that the PPCD3 phenotype is penetrant in approximately 95% of carriers. In this study, we interrogated in-house exomes (n = 3616) and genomes (n = 88) for the presence of putative heterozygous LoF variants in ZEB1. Next, we performed detailed phenotyping in a father and his son who carried a novel LoF c.1279C>T; p.(Glu427*) variant in ZEB1 (NM_030751.6) absent from the gnomAD v.2.1.1 dataset. Ocular examination of the two subjects did not show any abnormalities characteristic of PPCD3. GnomAD (n = 141,456 subjects) was also interrogated for LoF ZEB1 variants, notably 8 distinct heterozygous changes presumed to lead to ZEB1 haploinsufficiency, not reported to be associated with PPCD3, have been identified. The NM_030751.6 transcript has a pLI score ≥ 0.99, indicating extreme intolerance to haploinsufficiency. In conclusion, ZEB1 LoF variants are present in a general population at an extremely low frequency. As PPCD3 can be asymptomatic, the true penetrance of ZEB1 LoF variants remains currently unknown but is likely to be lower than estimated by the familial led approaches adopted to date

Phenotype Variability in Czech Patients Carrying PAX6 Disease-Causing Variants

The aim of this study was to report PAX6 disease-causing variants in six Czech families, to describe the associated phenotypes, and to perform functional assessment of the splice site variants. Detailed ophthalmic examination was performed. The PAX6 coding region was directly sequenced in three probands. Two probands were analysed by exome sequencing and one by genome sequencing. The effect of two variants on pre-mRNA splicing was evaluated using an exon trapping assay. Six different heterozygous PAX6 variants were identified, with c.111_120del and c.1183+1G˃T being novel. Both c.1183+1G˃T and c.1032+1G>A were proved to cause aberrant splicing with exon skipping and subsequent frameshift. The phenotypic features were variable between and within families. One individual, aged 31 years, presented with mild unilateral ptosis accompanied by aniridia in the right eye, partial aniridia in the left eye, and bilateral congenital cataracts, without marked foveal hypoplasia. Bilateral microcornea, partial aniridia, congenital cataracts, and a large posterior segment coloboma were found in another proband, aged 32 years. One child, aged 8 years, had bilateral high myopia, optic nerve colobomas, anterior polar cataracts, but no iris defects. Another individual, aged 46 years, had bilateral congenital ptosis, iris hypoplasia, keratopathy with marked fibrovascular pannus, anterior polar cataract, and foveal hypoplasia combined with impaired glucose tolerance. However, his daughter, aged 11 years, showed classical features of aniridia. Our study extends the genetic spectrum of PAX6 disease-causing variants and confirms that the associated phenotypic features may be very broad and different to the 'classical' aniridia

Should patients with kearns-sayre syndrome and corneal endothelial failure be genotyped for a TCF4 trinucleotide repeat, commonly associated with fuchs endothelial corneal dystrophy?

The aim of this study was to describe the ocular phenotype in a case with Kearns-Sayre syndrome (KSS) spectrum and to determine if corneal endothelial cell dysfunction could be attributed to other known distinct genetic causes. Herein, genomic DNA was extracted from blood and exome sequencing was performed. Non-coding gene regions implicated in corneal endothelial dystrophies were screened by Sanger sequencing. In addition, a repeat expansion situated within an intron of TCF4 (termed CTG18.1) was genotyped using the short tandem repeat assay. The diagnosis of KSS spectrum was based on the presence of ptosis, chronic progressive external ophthalmoplegia, pigmentary retinopathy, hearing loss, and muscle weakness, which were further supported by the detection of ~6.5 kb mtDNA deletion. At the age of 33 years, the proband’s best corrected visual acuity was reduced to 0.04 in the right eye and 0.2 in the left eye. Rare ocular findings included marked corneal oedema with central corneal thickness of 824 and 844 µm in the right and left eye, respectively. No pathogenic variants in the genes, which are associated with corneal endothelial dystrophies, were identified. Furthermore, the CTG18.1 genotype was 12/33, which exceeds a previously determined critical threshold for toxic RNA foci appearance in corneal endothelial cells

Features of intensive organ-sparing therapy for massive postpartum hemorrhage

Bleeding in pregnancy, childbirth and the postpartum period is one of the leading causes of maternal morbidity and mortality worldwide. There is no doubt that obstetric bleeding demands the development of improved methods for its diagnostics and treatment. We assessed the effectiveness of the treatment strategy for massive postpartum hemorrhage (PPH) with preservation of reproductive function, applied in the Perinatal Center of Irkutsk. We performed a retrospective analysis of 24 delivery cases, complicated by massive bleeding and successfully treated with preservation of reproductive organs. The massive nature of bleeding (> 30 % of blood volume) was registered in 15 (62.5 %) cases, mild (> 20 % bu

Brittle cornea syndrome: A systemic review of disease-causing mutations in ZNF469 and two novel variants identified in a patient followed for 26 years

AIMS: Brittle cornea syndrome (BCS) is a rare autosomal recessive disorder. The aim of this study was to review ZNF469 mutations associated with BCS type 1 to date and to describe an additional case of Czech/Polish background. METHODS: Whole genome sequencing was undertaken to identify the molecular genetic cause of disease in the proband. Sequence variants in ZNF469 previously reported as BCS type 1-causing were searched in the literature, manually curated and aligned to the reference sequence NM_001127464.2. RESULTS: The proband has been reviewed since childhood with progressive myopia and hearing loss. Aged 13 years had been diagnosed with Stickler syndrome. Aged 16.5 years, he developed acute hydrops in the left eye managed by corneal transplantation. At the age of 26, he experienced right corneal rupture after blunt trauma, also managed by grafting. He had a number of secondary complications and despite regular follow-up and timely management, the right eye became totally blind and the left eye had light perception at the last follow-up visit, aged 42. He was found to be a compound heterozygote for two novel mutations c.1705C>T; p.(Gln569*) and c.1402_1411del; p.(Pro468Alafs*31) in ZNF469. In total 22 disease-causing variants in ZNF469 have been identified, mainly in consanguineous families or endogamous populations. Only four probands, including the case described in the current study, harboured compound heterozygous mutations. CONCLUSION: BCS occurs very rarely in outbred populations which may cause diagnostic errors due to poor awareness of the disease. Investigation into the underlying molecular genetic cause in patients with connective tissue disorders may lead to a re-evaluation of their clinical diagnosis

Novel disease-causing variants and phenotypic features of X-linked megalocornea

Purpose: The aim of the study was to describe the phenotype and molecular genetic causes of X-linked megalocornea (MGC1). We recruited four British, one New Zealand, one Vietnamese and four Czech families. // Methods: All probands and three female carriers underwent ocular examination and Sanger sequencing of the CHRDL1 gene. Two of the probands also had magnetic resonance imaging (MRI) of the brain. // Results: We identified nine pathogenic or likely pathogenic and one variant of uncertain significance in CHRDL1, of which eight are novel. Three probands had ocular findings that have not previously been associated with MGC1, namely pigmentary glaucoma, unilateral posterior corneal vesicles, unilateral keratoconus and unilateral Fuchs heterochromic iridocyclitis. The corneal diameters of the three heterozygous carriers were normal, but two had abnormally thin corneas, and one of these was also diagnosed with unilateral keratoconus. Brain MRI identified arachnoid cysts in both probands, one also had a neuroepithelial cyst, while the second had a midsagittal neurodevelopmental abnormality (cavum septum pellucidum et vergae). // Conclusion: The study expands the spectrum of pathogenic variants and the ocular and brain abnormalities that have been identified in individuals with MGC1. Reduced corneal thickness may represent a mild phenotypic feature in some heterozygous female carriers of CHRDL1 pathogenic variants

Phenotypic features of CRB1-associated early-onset severe retinal dystrophy and the different molecular approaches to identifying the disease-causing variants

PURPOSE: The aim of this study was to determine the molecular genetic basis of an early-onset severe retinal dystrophy in three unrelated consecutive patients of Czech origin and to describe their ocular phenotype. METHODS: DNA samples from two probands were analyzed using a genotyping microarray (Asper) followed by either target analysis of 43 genes implicated in retinal disorders by next generation sequencing or whole-exome sequencing, respectively. The third proband underwent conventional Sanger sequencing of CRB1 based on her ocular findings. RESULTS: All three probands harboured a known disease-causing mutation c.2843G>A; p.(Cys948Tyr) in the CRB1 gene. One individual was homozygous for this mutation, while in the other two probands c.2308G>A; p.(Gly770Ser) and c.3121A>G; p.(Met1041Val) were also identified in the heterozygous state, respectively. Both variants were novel and evaluated by in silico analysis as pathogenic. A false-negative result was observed in one of the two samples examined by the genotyping microarray. Disease onset in all patients was before the age of 7 years. Hypermetropic refractive error, bilateral nummular retinal pigmentation, retinal thickening and cystoid spaces in the macula were observed in two probands, aged 6 and 7 years. The third proband, aged 28 years, had bone spicule-like pigmentary changes associated with increased retinal nerve fiber layer. CONCLUSIONS: The first study reporting on the molecular genetic cause of non-syndromic early-onset severe retinal dystrophy in Czech patients identified one homozygous and two compound heterozygote probands with CRB1 mutations. Retina nerve fibre layer measurements should be considered an integral part of the clinical evaluation of retinal dystrophies. Detailed clinical examination and imaging can both direct molecular screening and help to confirm or refute disease causation of identified variants

Schnyder corneal dystrophy and associated phenotypes caused by novel and recurrent mutations in the UBIAD1 gene

BACKGROUND: The purpose of this study was to identify the genetic cause and describe the clinical phenotype of Schnyder corneal dystrophy (SCD) in six unrelated probands. METHODS: We identified two white Czech, two white British and two South Asian families with a clinical diagnosis of SCD. Ophthalmic assessment included spectral domain optical coherence tomography (SD-OCT) of one individual with advanced disease, and SD-OCT and confocal microscopy of a child with early stages of disease. UBIAD1 coding exons were amplified and Sanger sequenced in each proband. A fasting serum lipid profile was measured in three probands. Paternity testing was performed in one family. RESULTS: A novel heterozygous c.527G>A; p.(Gly176Glu) mutation in UBIAD1 was identified in one Czech proband. In the second Czech proband, aged 6 years when first examined, a previously described de novo heterozygous c.289G>A; p.(Ala97Thr) mutation was found. Two probands of South Asian descent carried a known c.305G>A; p.(Asn102Ser) mutation in the heterozygous state. Previously reported heterozygous c.361C>T; p.(Leu121Phe) and c.308C>T; p.(Thr103Ile) mutations were found in two white British families. Although crystalline deposits were present in all probands the affected area was small in some individuals. Corneal arcus and stromal haze were the most prominent phenotypical feature in two probands. In the Czech probands, SD-OCT confirmed accumulation of reflective material in the anterior stroma. Crystalline deposits were visualized by confocal microscopy. Mild dyslipidemia was found in all three individuals tested. CONCLUSION: Although de novo occurrence of mutations in UBIAD1 is extremely rare, SCD should be considered in the differential diagnosis of bilateral corneal haze and/or crystal deposition, especially in children