Spectrum of pathogenic variants and high prevalence of pathogenic BBS7 variants in Russian patients with Bardet-Biedl syndrome.

Introduction: Bardet-Biedl syndrome is a rare condition characterized by obesity, retinitis pigmentosa, polydactyly, development delay, and structural kidney anomalies. This syndrome has an autosomal recessive type of inheritance. For the first time, molecular genetic testing has been provided for a large cohort of Russian patients with Bardet-Biedl syndrome. Materials and methods: Genetic testing was provided to 61 unrelated patients using an MPS panel that includes coding regions and intronic areas of all genes (n = 21) currently associated with Bardet-Biedl syndrome. Results: The diagnosis was confirmed for 41% of the patients (n = 25). Disease-causing variants were observed in BBS1, BBS4, BBS7, TTC8, BBS9, BBS10, BBS12, and MKKS genes. In most cases, pathogenic and likely pathogenic variants were localized in BBS1, BBS10, and BBS7 genes; recurrent variants were also observed in these genes. Discussion: The frequency of pathogenic and likely pathogenic variants in the BBS1 and BBS10 genes among Russian patients matches the research data in other countries. The frequency of pathogenic variants in the BBS7 gene is about 1.5%-2% of patients with Bardet-Biedl syndrome, while in the cohort of Russian patients, the fraction is 24%. In addition, the recurrent pathogenic variant c.1967_1968delinsC was detected in the BBS7 gene. The higher frequency of this variant in the Russian population, as well as the lack of association of this pathogenic variant with Bardet-Biedl syndrome in other populations, suggests that the variant c.1967_1968delinsC in the BBS7 gene is major and has a founder effect in the Russian population. Results provided in this article show the significant role of pathogenic variants in the BBS7 gene for patients with Bardet-Biedl syndrome in the Russian population.

Generation of two iPSC lines from patient with Mucopolysaccharidosis IV B type and autosomal recessive non-syndromic hearing loss 12.

We generated two human induced pluripotency stem cell (hiPSC) lines, RCMGi011-A and 11-B, from skin fibroblast from patient with Mucopolysaccharidosis IV B type and autosomal recessive non-syndromic hearing loss 12 using non-integrating, viral CytoTune™-iPS 2.0 Sendai Reprogramming Kit. We verified variant c.808 T > G and insertion in GLB1 gene, as well as two mutations, c.6992 T > C and c.805C > T, in CDH23 gene which lead to autosomal recessive hearing loss type 12. We have demonstrated normal karyotype of hiPSCs and capacity for cell differentiation into three germ layers.

A checklist of bat-associated macronyssid mites (Acari: Gamasina: Macronyssidae) of Russia, with new host and geographical records.

The family Macronyssidae (Acari: Mesostigmata) comprises mostly obligate blood-sucking ectoparasites of bats (Mammalia: Chiroptera) and some other animals, such as small mammals, reptiles and birds. Here, we document and curate previously known data, and, based on our extensive survey, provide this article of bat-associated macronyssid mites of the Russian Federation. We record a total of 24 mite species belonging to 4 genera (Ichoronyssus, Macronyssus, Steatonyssus, and Cryptonyssus). Twenty-seven new host-parasite associations are reported. In addition, were provide data on five major Russian regions, for which bat-associated mite records were lacking.

Ectoparasites and Pathogens of Kuhl's Pipistrelle Pipistrellus kuhlii (Kuhl, 1817) (Chiroptera: Vespertilionidae): Our Own and Published Data Review.

Here we report the results of our own survey and literary published data on the ectoparasite fauna and pathogens of the alien bat species, the Kuhl's pipistrelle Pipistrellus kuhlii (Kuhl, 1817) (Chiroptera: Vespertilionidae). This bat is a host of 36 species of parasitic mites, ticks and insects (including accidental findings) and 13 species of pathogens (protozoa, bacteria, viruses). The flea Ischnopsyllus variabilis is re-corded on this host for the first time. We have found that outside of the host ancestral range, the core of the bat parasite fauna is significantly different due to the loss of host species-specific ectoparasites. Particularly, in Russia, only 6 species of parasitic arthropods have been recorded for Kuhl's pipistrelle and all of them are host genus-specific. At the same time, the features of ecology and occasional finds of extrinsic parasites allow to suggest that P. kuhlii has wide contacts with animals which are the reservoirs of zoonotic infec-tions, that in combination with the fact of isolation of several pathogens from this species (including two coronaviruses) points to a possible medical importance of Kuhl's pipistrelle.

Accumulation of Circulating Cell-Free CpG-Enriched Ribosomal DNA Fragments on the Background of High Endonuclease Activity of Blood Plasma in Schizophrenic Patients.

INTRODUCTION: Schizophrenia (SZ) increases the level of cell death, leading to an increase in the concentration of circulating cell-free DNA (cfDNA). Ribosomal DNA (rDNA) contains many unmethylated CpG motifs that stimulate TLR9-MyD88-NF-κB signaling and the synthesis of proinflammatory cytokines. The number of rDNA copies in the genomes of SZ patients is increased; therefore, we expect that the concentration of cell-free rDNA in the plasma of the SZ patients also increases. This may be one of the explanations of the proinflammatory cytokine increase that is often observed in SZ. The major research question is what is the rDNA copy number in cfDNA (cf-rDNA CN) and its putative role in schizophrenia? Materials and Methods. We determined cfDNA concentration (RNase A/proteinase K/solvent extraction; fluorescent dye PicoGreen) and endonuclease activity (NA) of blood plasma (radial diffusion method) in the untreated male SZ group (N = 100) and in the male healthy control group (HC) (N = 96). Blood leukocyte DNA and cfDNA rDNA CN were determined with nonradioactive quantitative hybridization techniques. Plasma concentration of cf-rDNA was calculated. RESULTS: In the subjects from the SZ group, the mean cfDNA plasma concentration was twofold higher and NA of the plasma was fourfold higher than those in the healthy controls. rDNA CN in the blood leukocyte genome and in the cfDNA samples in the SZ group was significantly higher than that in the HC group. cf-rDNA concentration was threefold higher in the SZ group. CONCLUSION: Despite the abnormally high endonuclease activity in the blood plasma of SZ patients, the circulating cfDNA concentration is increased. Fragments of cf-rDNA accumulate in the blood plasma of SZ patients. Potentially, SZ patients' cfDNA should be a strong stimulating factor for the TLR9-MyD88-NF-κB signaling pathway.

Historic and geographic surveillance of Pseudogymnoascus destructans possible from collections of bat parasites.

Specimens archived in wet collections represent valuable material for scientific research. Here, we show that bat fly (Diptera, Nycteribiidae) samples contain DNA of Pseudogymnoascus destructans, a fungus pathogenic to bats. Using dual-probe quantitative PCR, we detected P. destructans DNA on bat flies collected in the Samara, Sverdlovsk and Irkutsk regions of Russia between 2005 and 2017. Fungal load was significantly lower on bat flies from wet collections than on freshly collected mites in the Czech Republic. The bat pathogen was present in the Samara region (European part of Russia) in 2005, that is, a year before recognition of white-nose syndrome in North America. As Samara and Irkutsk regions were identified as new positive locations of P. destructans, our data expand the known geographic distribution of P. destructans. We conclude that ethanol-stored ectoparasites can be used to identify the presence of pathogens in historic bat populations and understudied geographical regions.

Patterns of Abundance and Host Specificity of Bat Ectoparasites in the Central Balkans.

Bats are hosts to a number of ectoparasites-acarines (ticks, chiggers, other mites), bat flies, and fleas. Bat ectoparasites might have significant ecological and public health importance as they may be potential vectors of zoonotic agents. It is important to identify their distribution, diversity, and host-parasite associations. Bat ectoparasites in the central Balkans have been largely understudied. The present research was conducted in 45 localities at the territory of Bosnia and Herzegovina, former Yugoslav Republic of Macedonia, Montenegro, and Serbia. In total, 1,143 individuals of 18 species of bats have been examined for the presence and abundance of ectoparasite species during 3 yr of research. In total, 21 ectoparasite species have been identified: three species of ticks, seven species of mites (including one species of chigger), eight species of bat flies, and three species of fleas. In total, 80 host-parasite associations have been identified. The largest number of ectoparasites parasitized primarily only one host species. The highest total number of hosts was identified for ectoparasite species Ixodes vespertilionis Koch, Nycteribia schmidlii Schiner, and Spinturnix myoti Kolenati. The spinturnicid mite Spinturnix psi Kolenati was the most abundant ectoparasite species and together with Penicilidia dufouri Westwood the most widely distributed species of bat ectoparasite, being present at 21 localities in the central Balkans. The presented data include the first systematic records of patterns of prevalence, mean intensity, mean abundance, and host specificity for bat ectoparasites in the central Balkans.

Prevalence of thymidylate synthase gene 5'-untranslated region variants in an Argentinean sample.

Thymidylate synthase (TYMS) is a key enzyme in nucleotide synthesis and therefore, an important target of many chemotherapeutic agents. Expression of TYMS mRNA is thought to be modulated by a 28-bp tandem repeat polymorphism within its 5'-untranslated region, raising the question of this variant's utility in predicting the efficacy and toxicity of cancer treatment regimens. The aim of the present research was to describe the distribution of this TYMS polymorphism in the Argentinean population. A total of 199 randomly selected DNA samples from healthy volunteers were analyzed using polymerase chain reaction and polyacrylamide gel electrophoresis. The 2R and 3R alleles were present in 47.74 and 52.26% of samples, respectively, with frequencies of 21.6 (43), 52.3 (104), and 26.1% (52) recorded for the 2R/2R, 2R/3R, and 3R/3R genotypes, respectively. No significant difference regarding gender was observed. Our prevalence data are similar to those reported for other Caucasian populations. This opens a discussion concerning the reference population valid for comparisons and the clinical importance of this genotyping test as an additional tool in personalized medicine.

[The Nonlinear Effect of the Composite Influence of Red and Blue Light on Bacteria Escherichia coli Viability].

A non-linear dependence of the inhibition of E. coli cells is found when irradiated simultaneously with the blue and red regions of the spectrum at a power density of 100 mW/cm2. Such dependence is explained by the assumption of a cascade two-photon absorption of light by DNA molecules with an intermediate resonance at cellular chromophores, causing excitation and subsequent DNA damage similar to damage when exposed to UV radiation.

A genome-wide association study of pulmonary tuberculosis in Morocco.

Although epidemiological evidence suggests a human genetic basis of pulmonary tuberculosis (PTB) susceptibility, the identification of specific genes and alleles influencing PTB risk has proven to be difficult. Previous genome-wide association (GWA) studies have identified only three novel loci with modest effect sizes in sub-Saharan African and Russian populations. We performed a GWA study of 550,352 autosomal SNPs in a family-based discovery Moroccan sample (on the full population and on the subset with PTB diagnosis at <25 years), which identified 143 SNPs with p < 1 × 10(-4). The replication study in an independent case/control sample identified four SNPs displaying a p < 0.01 implicating the same risk allele. In the combined sample including 556 PTB subjects and 650 controls these four SNPs showed suggestive association (2 × 10(-6) < p < 4 × 10(-5)): rs358793 and rs17590261 were intergenic, while rs6786408 and rs916943 were located in introns of FOXP1 and AGMO, respectively. Both genes are involved in the function of macrophages, which are the site of latency and reactivation of Mycobacterium tuberculosis. The most significant finding (p = 2 × 10(-6)) was obtained for the AGMO SNP in an early (<25 years) age-at-onset subset, confirming the importance of considering age-at-onset to decipher the genetic basis of PTB. Although only suggestive, these findings highlight several avenues for future research in the human genetics of PTB.

[NEW FINDINGS OF RARE SPECIES OF THE MITE GENUS SPINTURNIX VON HEYDEN, 1826 (MESOSTIGMATA: GAMASINA: SPINTURNICIDAE) IN RUSSIA AND TADJIKISTAN].

The article reports new findings of rare and poorly known mite species of the genus Spinturnix von Heyden, 1826 (Gamasina: Spinturnicidae) parasitizing bats of the genera Myotis and Barbastella in Russia and Tadjikistan.

[Fauna of Rare and Poorly Studied Ectoparasites of bats in Southern Siberia].

Forty-six chiropteran specimens from seven species have been captured on the territory of Southern Siberia. From them, 676 ectoparasites of 16 species (gamasid mites and insects) were collected. The bat fly Basilia mongolensis mongolensis Theodor, 1966 was found in Russia for the first time. The gamasid mites Spinturnix maedai Uchikawa et Wada, 1979 and Macronyssus hosonoi Uchikawa, 1979 have not previously been registered in Siberia. Several species have been recorded on new hosts. Three species of gamasid mites out of the genus Macronyssus are, probably, new to science. New data on the ecology of low-abundant and understudied bat species belonging to the Siberian-Far Eastern complex have been provided.

[NEW FINDINGS OF BAT ECTOPARASITES (CHIROPTERA: VESPERTILIONIDAE) IN SOUTHERN SIBERIA].

The data on new findings of ectoparasites (mites and insects) of bats (Chiroptera: Vespertilionidae) in the Western Sayan and Tuva are represented. The bat fly Basilia mongolensis mongolensis Theodor, 1966 was discovered in the territory of Russia for the first time. Gamasid mite Spinturnix bregetovae Stanyukovich, 1995 is new for the region. New hosts were described for some ectoparasites.

Three New Bat Ectoparasite Species of the Genus Macronyssus from Western Siberia (with an Identification Key for Females of the Genus Macronyssus from the Palearctic Boreal Zone).

Three new gamasid mite species belonging to the genus Macronyssus Kolenati, 1858 (Acari: Macronyssidae), namely, Macronyssus sibiricus n. sp., Macronyssus stanyukovichi n. sp., and Macronyssus tigirecus n. sp., are described (females only; males, protonymphs, and larvae remain unknown). All species are known from Western Siberia and belong to the Siberian-Far Eastern bat ectoparasite fauna complex. The parasite hosts are the eastern water bat Myotis petax Hollister, 1912, and Hilgendorf's tube-nosed bat Murina hilgendorfi Peters, 1880 (Chiroptera: Vespertilionidae). An identification key for females of the genus Macronyssus Kolenati, 1858, in the boreal Palearctic region is presented.

[HIV infection risk perception and stigmatizing attitude: Results of surveys of dwellers from the Central Administrative District of Moscow].

AIM: To study human immunodeficiency virus (HIV) infection risk perception and stigmatizing attitudes in the dwellers of the Central Administrative District of Moscow. SUBJECTS AND METHODS: An anonymous survey was conducted using specially developed questionnaires. A total of 893 people were interviewed. Each of the given indicators was used to ask 98 to 254 respondents. Among the survey participants, there were 92 healthcare workers, including 66 physicians and 26 representatives of middle-level and junior medical staff. According to their replies, the respondents were divided into 2 groups: 1) healthcare workers; 2) representatives of the so-called general population. RESULTS: 91.3% of the healthcare workers gave a negative reply to the question: "Should contacts (intercourse) with people living with HIV (AIDS) be avoided to escape infection?". In Group 2, 58.8 and 23.5% of the respondents answered negatively and positively, respectively; and 17.6% had difficulty answering the question. In the general population group, 44.10% of the respondents answered negatively and 32.2% had difficulty answering the question: "Would you agree to live in the same room with anybody whom you know or suspect to be HIV positive?"; 23.8% agreed to do this. Among the healthcare workers, there were 46.7% of the respondents who answered positively. When the question: "Would you agree to send your child (grandson) to the kindergarten if you would learn that a HIV-infected child goes there?" was asked, 48.6 and 18.7% of the respondents in the general population group answered negatively and positively, respectively; 32.7% had difficulty answering. In the group of healthcare workers, 66.7% answered positively. Among both the healthcare workers and the representatives of the general population, more than 60% of the respondents agreed with the statement that "HIV-infected people lead a loose life". CONCLUSION: The specific features of perceiving a HIV infection risk and showing stigmatizing attitudes towards HIV-infected patients make the forming less dangerous behaviors difficult and restrict an access to care and support in infected patients. The training of healthcare workers in issues related to HIV infection should involve the identification of stigmatizing attitudes and the application of destigmatization strategies.

[Epidemiology of chronic critical limb ischemia].

Peripheral artery diseases amount to more than 20% of all types of cardiovascular diseases, which corresponds to 2-3% of the total population. 15 to 30% of the population of Russian Federation over 65 years have signs of obliterating arteriopathy. Advance of arterial insufficiency in some cases leads to development of special state - chronic critical limb ischemia (CLI). This article presents a review of statistical data from different sources, showing high prevalence of this severe issue, as well as data of amputations rate, performed in different countries due to CLI, reflecting the extreme relevance of the search for new methods of CLI treatment.

[Cardiosynchronized sequential antegrade pneumocompression in treatment of patients with multifocal atherosclerosis].

The work was aimed at assessing efficacy and safety of indications for and contraindications to a promising method of treatment for multifocal atherosclerosis - enforced external counterpulsation, suggesting a new noninvasive method of treatment of chronic obliterating diseases of lower-limb arteries - cardiosynchronized sequential antegrade pneumocompression.

[New records of ectoparasites of the eastern water bat Myotis petax Hollister, 1912 (Vespertilionidae, Chiroptera) and the revision of the previous material collected from Myotis daubentonii s. lato in Eastern Palaearctic].

New findings of ectoparasites from the eastern water bat Myotis petax Hollister, 1912, belonging to the Siberian-Russian Far Eastern complex and earlier attributed as a subspecies of the Daubenton's bat Myotis daubentonii s. lato, is given. Fourteen species of bloodsucking arthropods feed on M. petax; these species include 4, 3, and 7 species of gamasid mites, fleas, and bloodsucking flies, respectively.

[Possibilities for identification of cryptic species of Chiroptera using host-specific ectoparasites].

The possibility of identification of the sibling species of Chiroptera by the example of Myotis daubentonii Kuhl, 1817 and Myotis petax Hollister, 1912 by their host-specific ectoparasitic fauna is discussed. Their habitat limits are defined.

Host genomics and control of tuberculosis infection.

Tuberculosis (TB), caused by the human pathogenic bacterium Mycobacterium tuberculosis, poses a major global health problem. The tubercle bacillus is transmitted from person to person by aerosol, but only a proportion of those in contact with infectious aerosol particles will become infected. If infection occurs, less than 10% of those infected will develop clinical signs of TB, while the majority will develop latent TB infection (LTBI). The identification and treatment of LTBI persons is a major aspect of TB control, especially in low-incidence, highly developed nations. In the absence of a gold standard test for latent TB, infection is inferred with the help of either the in vivo tuberculin skin test or in vitro interferon gamma release assays of anti-mycobacterial immunity. Recent work has observed high heritability of these immune assays indicating the critical role of the host genetic background on the establishment of infection and latency. Additional genetic studies have identified the host genetic background as an important covariate for the proper interpretation of the results obtained from LTBI assays. Taken together, these data suggest TB surveillance and control can likely be improved by including host genetic information into the interpretation of these widely used assays.