Olfactory transport efficiency of the amorphous and crystalline manganese oxide nanoparticles

The ability to deliver particulated xenobiotics and therapeutic drugs directly from the nasal cavity to the central nervous system, bypassing the hemato-encephalic barrier, determines a high importance of investigation of factors influencing this process. It was shown that the bioavailability of solid particles is influenced by their size and surface charge. At the same time, the impact of a crystal structure (crystalline/amorphous) has been poorly investigated. In this study, using sexually mature male C57BL/6J mice, we analyzed the efficiency of the nose-to-brain transport of crystalline and amorphous manganese oxide nanoparticles. T1-weighted magnetic resonance imaging (MRI) was used to evaluate the accumulation of manganese nanoparticles in olfactory bulb (OB) and olfactory epithelium (OE). So, it has been established that amorphous particles have higher accumulation rate in OE and OB in comparison with crystalline particles after their intranasal administration. The unequal ability of amorphous and crystalline particles to overcome the mucosal layer covering the OE may be one of the possible reasons for the different nose-to-brain transport efficiency of particulated matter. Indeed, the introduction of mucolytic (dithiothreitol) 20 minutes prior to intranasal particle application did not influence the accumulation of amorphous particles in OE and OB, but enhanced the efficiency of crystalline nanoparticle entry. Data on the different intake of amorphous and crystalline nanoparticles from the nasal cavity to the brain, as well as the evidence for the key role of the mucosal layer in differentiating the penetrating power of these particles will be useful in developing approaches to assessing air pollution and optimizing the methods of inhalation therapy

Geographical Distribution, Incidence, Malignancies, and Outcome of 136 Eastern Slavic Patients With Nijmegen Breakage Syndrome and NBN Founder Variant c.657_661del5

Nijmegen breakage syndrome (NBS) is a DNA repair disorder characterized by combined immunodeficiency and a high predisposition to lymphoid malignancies. The majority of NBS patients are identified with a homozygous five base pair deletion in the Nibrin (NBN) gene (c.657_661del5, p.K219fsX19) with a founder effect observed in Caucasian European populations, especially of Slavic origin. We present here an analysis of a cohort of 136 NBS patients of Eastern Slav origin across Belarus, Ukraine, Russia, and Latvia with a focus on understanding the geographic distribution, incidence of malignancy, and treatment outcomes of this cohort. Our analysis shows that Belarus had the highest prevalence of NBS (2.3 per 1,000,000), followed by Ukraine (1.3 per 1,000,000), and Russia (0.7 per 1,000,000). Of note, the highest concentration of NBS cases was observed in the western regions of Belarus and Ukraine, where NBS prevalence exceeds 20 cases per 1,000,000 people, suggesting the presence of an “Eastern Slavic NBS hot spot.” The median age at diagnosis of this cohort ranged from 4 to 5 years, and delay in diagnosis was more pervasive in smaller cities and rural regions. A total of 62 (45%) patients developed malignancies, more commonly in males than females (55.2 vs. 34.2%; p=0.017). In 27 patients, NBS was diagnosed following the onset of malignancies (mean age: 8 years). Malignancies were mostly of lymphoid origin and predominantly non-Hodgkin lymphoma (NHL) (n=42, 68%); 38% of patients had diffuse large B-cell lymphoma. The 20-year overall survival rate of patients with malignancy was 24%. However, females with cancer experienced poorer event-free survival rates than males (16.6% vs. 46.8%, p=0.036). Of 136 NBS patients, 13 underwent hematopoietic stem cell transplantation (HSCT) with an overall survival of 3.5 years following treatment (range: 1 to 14 years). Indications for HSCT included malignancy (n=7) and immunodeficiency (n=6). Overall, 9% of patients in this cohort reached adulthood. Adult survivors reported diminished quality of life with significant physical and cognitive impairments. Our study highlights the need to improve timely diagnosis and clinical management of NBS among Eastern Slavs. Genetic counseling and screening should be offered to individuals with a family history of NBS, especially in hot spot regions. © Copyright © 2021 Sharapova, Pashchenko, Bondarenko, Vakhlyarskaya, Prokofjeva, Fedorova, Savchak, Mareika, Valiev, Popa, Tuzankina, Vlasova, Sakovich, Polyakova, Rumiantseva, Naumchik, Kulyova, Aleshkevich, Golovataya, Minakovskaya, Belevtsev, Latysheva, Latysheva, Beznoshchenko, Akopyan, Makukh, Kozlova, Varabyou, Ballow, Ong, Walter, Kondratenko, Kostyuchenko and Aleinikova.We thank all doctors for clinical help for patients. We also appreciate the support of patient and their parents for agreeing to take part in this study. TP thanks Sergey?Nikulshin, Marika Grutupa, and Zanna Kovalova. We thank Joseph Dasso for editing this manuscript, primarily for proper English

Long-term outcome of LRBA deficiency in 76 patients after various treatment modalities as evaluated by the immune deficiency and dysregulation activity (IDDA) score

Background: Recent findings strongly support hematopoietic stem cell transplantation (HSCT) in patients with severe presentation of LPS-responsive beige-like anchor protein (LRBA) deficiency, but long-term follow-up and survival data beyond previous patient reports or meta-reviews are scarce for those patients who do not receive a transplant.Objective: This international retrospective study was conducted to elucidate the longitudinal clinical course of patients with LRBA deficiency who do and do not receive a transplant.Method: We assessed disease burden and treatment responses with a specially developed immune deficiency and dysregulation activity score, reflecting the sum and severity of organ involvement and infections, days of hospitalization, supportive care requirements, and performance indices.Results: Of 76 patients with LRBA deficiency from 29 centers (median follow-up, 10 years; range, 1-52), 24 underwent HSCT from 2005 to 2019. The overall survival rate after HSCT (median follow-up, 20 months) was 70.8% (17 of 24 patients); all deaths were due to nonspecific, early, transplant-related mortality. Currently, 82.7% of patients who did not receive a transplant (43 of 52; age range, 3-69 years) are alive. Of 17 HSCT survivors, 7 are in complete remission and 5 are in good partial remission without treatment (together, 12 of 17 [70.6%]). In contrast, only 5 of 43 patients who did not receive a transplant (11.6%) are without immunosuppression. Immune deficiency and dysregulation activity scores were significantly lower in patients who survived HSCT than in those receiving conventional treatment (P = .005) or in patients who received abatacept or sirolimus as compared with other therapies, and in patients with residual LRBA expression. Higher disease burden, longer duration before HSCT, and lung involvement were associated with poor outcome.Conclusion: The lifelong disease activity, implying a need for immunosuppression and risk of malignancy, must be weighed against the risks of HSCT.Transplantation and immunomodulatio

Characteristics of the Microvascular Bed of Rats' Testis Exposed to Electromagnetic Field and Using Immunomodulator.

As a result at studies performed there were defined morphofunctional changes in the structyre of microvascular bed of rats' testes, exposed to electromagnetic field during 30-45 days, later they were receiving 7% Echinacea purple tincture. It was established that in these experimental terms the structure of testicular vessels was significantly different by morphologic structure. On the day 30 in the structure of micro­hemocirculatory bed of testes there was defined an insignificant blood-filling of the venous bed. There were neither spasms of arteries, which formed cellular structure in the testicular tissue, no edematous signs. On the day 45 of the experiment in the testes of the irradiated rats there was noted more expressed bifurcation of arterial vessels and decrease of blood-filling of veins without expressed venous stasis. With the increase of irradiation term by electromagnetic field up to 45 days and usage of Echinacea purpura tincture there were noted reverse phenomena in hemacicrulatory bed of rats' testes in the form of widening of arterial chain of vessels and narrowing of venons chain of the vessels; this led to increase of index of medium diameter of seminal tubules and subsequently, to the increase of the total area of spermatogenous tissue of rats

Oxytocinergic regulation in pathogenesis of pelvic pain caused by adenomyosis

Objective: The aim of the study was to expand the understanding of pathogenesis of adenomyosis-associated pelvic pain. Material and Methods: We studied 30 (n = 30) biopsy samples obtained after hysterectomy in women with diffuse adenomyosis of grade II-III, accompanied by severe pain syndrome, who did not receive hormonal therapy. The morphologic comparison group comprised 30 (n = 30) biopsy samples obtained from women with adenomyosis, without pain syndrome, operated on for abnormal uterine bleeding, who also did not receive hormone therapy. Results: The total density of immunological OTR labeling in the adenomyotic lesion foci was 73.7 ± 1.8%, and in the morphological control group it was 35.2 ± 1.4% (p <0.05), which indicates a significant effect of oxytocin as a ureterotonic peptide. Processes of local neurogenesis and growth of nerve fibers was established due to an increase in the expression of the nervous system growth factor NGF in the myometrium stroma, in comparison with biopsy samples of morphological control. Conclusion: Pelvic pain pathogenesis in women with diffuse adenomyosis compared with the painless form of the disease is an increase in the activity of ureterotonic factors of OTR oxytocin. Compared to the painless form of adenomyosis, the myometrial innervation apparatus of patients with pelvic pain is characterized by a significantly higher expression of nerve growth factor. © 2020 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group on behalf of the UR MED GRUPP (LLC)

A FIND OF THE NORTH-CAUCASIAN CERAMICS IN THE ELITE BURIAL OF THE ISAKOVKA I BURIAL GROUND (WESTERN SIBERIA)

We present the results of a multi-disciplinary analysis of a jug and its contents from the elite burial complex of the Sargat culture in Middle Irtysh Basin (burial Isakovka I, mound 3, burial 6). The burial, along with military equipment and various metallic import, contained a ceramic jug, the closest analogies to which are found in the production centers of the settled population of the foothill zone of the central and partially eastern regions of the North Caucasus, as well as the steppe territory (the basin of the Kuma River). The studied piece is distinguished by its massive form and traces of repair of the upper part. The jug was placed in the burial filled with a granular substance with fragments of light and gray-black color. Laboratory analysis found no traces of tartrates, i.e. the jug was not used for cooking or transporting beverages of grape juice. The detected fractions of biogenic apatite could possibly originate from fish bones and scales, used for the production of glue, which was added for clarification of wine, beer and mead. At the same time, the composition of the filling contains organic substances related to the production of a low-alcohol drink based on honey, fermented with the addition of cereal grains (local wild or coming from agricultural centers). There are two versions for defining this drink: either it was beer – one of the oldest ritual drinks, the use of which in pastoral cultures is confirmed by texts of the Nart sagas and is confirmed by similar forms of words of Iranian origin; or an infusion of herbs/cereals based on honey, also common in the ritual practices of ancient and traditional cultures. This find is considered exceptional, since the North Caucasian antiquities of the Early Iron Age have been previously unknown in the forest-steppe monuments of the Trans-Urals and Western Siberia. It is possible that the area of the Sargat culture is so far the easternmost territory of distribution of such ceramics. © 2022 Kola Science Centre of the Russian Academy of SciencesRussian Foundation for Basic Research, РФФИ; Ministry of Education and Science of the Russian Federation, Minobrnauka: 075-15-2021-680; Ural Branch, Russian Academy of Sciences, UB RAS: АААА-А18-118053090045-8Acknowledgment. The article was prepared within the framework of the state order No. 121102500121-8 and the RFBR project No. 20-09-00194; laboratory studies were carried out at the Center for Collective Use “Geoanalyst” of the Institute of Geology and Geochemistry of the Ural Branch of RAS and supported by the state order No. АААА-А18-118053090045-8. The retrofitting and integrated development of the Center for Collective Use “Geoanalyst” of the Institute of Geology and Geochemistry of the Ural Branch of RAS is carried out with the financial support of the Ministry of Science and Higher Education of the Russian Federation, project No. 075-15-2021-680