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Targeted-therapy failure in treating nonsmall cell lung cancer (NSCLC) frequently occurs because of the emergence of drug resistance and genetic mutations. The same mutations also result in aerobic glycolysis, which further antagonizes outcomes by localized increases in lactate, an immune suppressor. Recent evidence indicates that enzymatic lowering of lactate can promote an oncolytic immune microenvironment within the tumour. Here, we review factors relating to lactate expression in NSCLC and the utility of lactate oxidase (LOX) for governing therapeutic delivery, its role in lactate oxidation and turnover, and relationships between lactate depletion and immune cell populations. The lactate-rich characteristic of NSCLC provides an exploitable property to potentially improve NSCLC outcomes and design new therapeutic strategies to integrate with conventional therapies Refereed/Peer-reviewed

Purpose: The concept of time perspective (TP) implies that a mental focus on past, present, or future affect a person makes decisions and take action. Inability to plan their life for a sufficiently long time perspective due to the COVID-19 pandemic appeared to have a pronounced impact on a human’s lifestyle influencing their thoughts, feelings, and behaviors, including eating behavior. This study tested two hypotheses: (a) that during COVID-19 isolation, the incidence rate of food addiction is increased, and (b) people with present TP are more likely exhibited signs of food addiction (FA). Methods: The final study sample included 949 people, mean age 21.8 ± 7.8 years (range: 17–71 years, women: 78.3%). Each participant indicated their personal data and completed Yale Food Addiction Scale and the Zimbardo Time Perspective Inventory. Results: There was an increased incidence rate of FA (OR = 1.678, 95% CI = 1.324, 2.148, p = 0.000) during COVID-19 isolation. Individuals with balanced, future, and past positive TP were less likely to exhibit symptoms of FA. Persons with past negative, and present hedonistic TP were more likely to exhibit signs of FA. Conclusion: There was an increased incidence rate of FA during COVID-19 isolation. Persons with shortened time horizon are more likely to exhibit symptoms of FA. Level of evidence: Level V, cross-sectional descriptive study. © 2022, The Author(s), under exclusive licence to Springer Nature Switzerland AG.

Lung cancer is the primary cause of cancer-related death worldwide. 85%–90% of cases are non-small cell lung cancer (NSCLC) which characteristically exhibits altered epidermal growth factor receptor (EGFR) signaling is a major driver pathway. Unfortunately, therapeutic outcomes in treating NSCLC are compromised by the emergence of drug resistance in response to EGFR-tyrosine kinase inhibitor (TKI) targeted therapy due to the acquired resistance mutation EGFR T790M or activation of alternative pathways. There is current need for a new generation of TKIs to be developed to treat EGFR-TKI-resistant NSCLC. To overcome the above problems and improve clinical efficacy, nanotechnology with targeting abilities and sustained release has been proposed for EGFR-TKI-resistant NSCLC treatment and has already achieved success in in vitro or in vivo models. In this review, we summarize and illustrate representative nano-formulations targeting EGFR-TKI-resistant NSCLC. The described advances may pave the way to better understanding and design of nanocarriers and multifunctional nanosystems for efficient treatment for drug resistant NSCLC. Refereed/Peer-reviewed

BACKGROUND The United States Chronic Thromboembolic Pulmonary Hypertension Registry (US-CTEPH-R) was designed to characterize the demographic characteristics, evaluation, clinical course, and outcomes of surgical and nonsurgical therapies for patients with chronic thromboembolic pulmonary hypertension. RESEARCH QUESTION What are the differences in baseline characteristics and 1-year outcomes between operated and nonoperated subjects? STUDY DESIGN AND METHODS This study describes a multicenter, prospective, longitudinal, observational registry of patients newly diagnosed (< 6 months) with CTEPH. Inclusion criteria required a mean pulmonary artery pressure ≥ 25 mm Hg documented by right heart catheterization and radiologic confirmation of CTEPH. Between 2015 and 2018, a total of 750 patients were enrolled and followed up biannually until 2019. RESULTS Most patients with CTEPH (87.9%) reported a history of acute pulmonary embolism. CTEPH diagnosis delays were frequent (median, 10 months), and most patients reported World Health Organization functional class 3 status at enrollment with a median mean pulmonary artery pressure of 44 mm Hg. The registry cohort was subdivided into Operable patients undergoing pulmonary thromboendarterectomy (PTE) surgery (n = 566), Operable patients who did not undergo surgery (n = 88), and those who were Inoperable (n = 96). Inoperable patients were older than Operated patients; less likely to be obese; have a DVT history, non-type O blood group, or thrombophilia; and more likely to have COPD or a history of cancer. PTE resulted in a median pulmonary vascular resistance decline from 6.9 to 2.6 Wood units (P < .001) with a 3.9% in-hospital mortality. At 1-year follow-up, Operated patients were less likely treated with oxygen, diuretics, or pulmonary hypertension-targeted therapy compared with Inoperable patients. A larger percentage of Operated patients were World Health Organization functional class 1 or 2 at 1 year (82.9%) compared with the Inoperable (48.2%) and Operable/No Surgery (56%) groups (P < .001). INTERPRETATION Differences exist in the clinical characteristics between patients who exhibited operable CTEPH and those who were inoperable, with the most favorable 1-year outcomes in those who underwent PTE surgery. CLINICAL TRIAL REGISTRATION ClinicalTrials.gov; No.: NCT02429284; URL: www.clinicaltrials.gov.

BACKGROUND: Currently, several types of designs of support rings of M. Muller, Burch-Schneider, rings of the company Protek (Switzerland), implanted in the BB are widely used, which are used in the surgical treatment of long-standing fractures of the BB, as a rule, as a device that strengthens the walls of the BB. AIM: Study of the deformation properties of the repositional-fixing ring. MATERIALS AND METHODS: For carrying out mechanical tests, a ring with an external diameter of 52 mm was made by the method of sequential sintering using additive technologies by the company Konmet LLC, Moscow. Laboratory mechanical tests were carried out by the Testing Laboratory of Medical Devices and Materials of the N.N. Priorov National Medical Research Center of Traumatology and Orthopedics. RESULTS: As a result of static testing of the ring for compression, tension, torsion, and joint stretching and twisting of the edges of the ring connector, its deformation properties are studied. Load corresponding to the deformation of 2 mm, kN: compression 0.180; tension 0.061; torsion (torque corresponding to the angle of rotation of 5 degrees, Nm) 2.653; joint tension with twisting of the edges of the ring connector (load corresponding to the deformation of 10 mm, kN) 0.048. CONCLUSION: The results of the initial study of the deformation behavior of the ring structure show that it is necessary to refine the ring design and further study the deformation and strength characteristics of the ring.

Orbital metastasis may be the initial manifestation of a malignancy of unknown origin. The primary locations of orbital metastasis are usually the lung, prostate, gastrointestinal tract, skin, kidney, eye, or thyroid gland. Metastasis of gastric carcinoma to an extraocular eye muscle is extremely rare. A solitary thickening in an extraocular eye muscle with no inflammatory features is suspect for a tumor. Symptoms such as diplopia, proptosis, ptosis, vision loss, or pain may be associated with an orbital malignancy. Our patient, a 67-year-old man known with radically resected prostate cancer, presented with complaints of vertigo with a tendency to fall, headache, and diplopia when looking to the right. As a coincidental finding, swelling of the rectus lateralis muscle of the left eye was observed on imaging. Extensive additional investigations showed that a gastric carcinoma with intraorbital and leptomeningeal metastasis was the cause. In conclusion, a solitary thickened extraocular eye muscle should be recognized in time and examined further.

Background: Panretinal photocoagulation (PRP) (also called scatter laser treatment) remains one of the effective methods of treatment, and it can help to prevent blindness and low vision in diabetic retinopathy (DR). The aim of this study was to investigate the efficacy of local prolonged conservative therapy after PRP and the effect of somatic polymorbidity on visual functions in patients with diabetic neuropathy (DN) at the stage of clinical manifestations based on monitoring the clinical, functional and morphometric parameters of the macular region of the retina. Methods and Results: The study included 78 patients with type 2 diabetes (T2D) who underwent PRP for DR using a VISULAS® 532s solid-state laser (ZEISS). The patients were divided into two groups depending on the presence or absence of DN. Group 1 (n=60, 120 eyes) included patients with DN (stage of clinical manifestations), Group 2 (n=18, 36 eyes) included patients without DN. All patients underwent standard ophthalmological examination: visometry, tonometry, perimetry, biomicroscopy of the anterior segment of the eye and vitreous body, and fundus ophthalmoscopy. Thickness map of the retina was obtained using the RTVue-100 OCT (Optovue, Fremont, CA) EMM5 scan protocol and the Stratus OCT (Carl Zeiss Meditec, USA) radial scan protocol. After laser treatment, all patients, regardless of the treatment stage, were prescribed topically Broxinac® ( Bromfenac ophthalmic solution 0.09%), 1 drop twice a day for a month. In the presence of macular edema, a carbonic anhydrase inhibitor (Dorzolamide 2% solution) was added to the Broxinac® solution (1 drop twice a day) for up to 1 month after each PRP stage. The dynamics of CVA parameters and the retinal thickness of the macular region were assessed before PRP and 3 months after the complex treatment. Based on the monitoring of the clinical, functional and morphometric parameters of the macular region of the retina after PRP in T2D patients, we found a local, prolonged, 3-month conservative therapy to be effective, using the instillation of Broxinac® supplemented with Dorzolamide 2% solution in the presence of macular edema. Conversely, there is a negative effect of somatic polymorbidity (stage 3 chronic kidney disease), aspartate aminotransferase >40U/L) on corrected visual acuity (CVA) and morphometric parameters of the macular region of the retina during PRP in T2D patients with DN at the stage of clinical manifestations.

The impact of solvent polarity on the kinetics, reducing capacity, antioxidant activity, and mineral composition of black locust (Robinia pseudoacacia) flowers extracts obtained by ultrasound-assis...

Differential types of reflexivity (as human activities aimed at understanding their own actions) were studied in 66 persons against the background of the COVID-19 epidemic in order to effectively carry out medical, psychological and social interventions in order to maintain epidemiological well-being in society during the current epidemic. It was established that in all examined persons the indicators of scales, the methodology used do not significantly differ from the data obtained earlier by its authors. The surveyed contingent is reliably dominated by systemic reflexion (the indicators of which are comparable to those of those years when there were no such significant global shocks) with a lower (compared to the control group) level of introspection and quasi-reflexion. The bigger variability of data, received by D.A. Leontyev and E.N. Osin, in comparison with our data is caused probably by temporary aspect, various professional contingent of the examined persons, and the relevant processes flowing nowadays in society. Thus, the absence of significant differences from the data obtained earlier is probably due to the cultural and age characteristics of the examined. This indicates the possibility of adequate medical and psychological support for this category of persons against the background of the current COVID-19 pandemic.

The changes in the content of the giant sarcomeric cytoskeletal proteins titin (3000–3700 kDa) and nebulin (770 kDa) in skeletal muscles (m. soleus, m. gastrocnemius), and titin in the left ventricular myocardium, as well as of the submembrane cytoskeletal protein dystrophin (427 kDa) in m. soleus and m. extensor digitorum longus (EDL), have been studied in the edible dormouse Glis glis during hibernation. The animals were divided into two experimental groups: “Summer activity” and “Hypothermia”. It was found that the development of atrophic changes in the skeletal muscles of hibernating animals is accompanied by a decrease in the dystrophin content. Specifically, the fluorescence intensity in skeletal muscle cross sections labeled with primary antibodies to dystrophin and Alexa Fluor® 488 conjugated secondary antibodies decreased in animals of the “Hypothermia” group by 2.7 times (p < 0.05) and 2.0 times (p < 0.05) in m. soleus and m. EDL, respectively. SDS electrophoresis of proteins in agarose-strengthened macroporous 2.2%-polyacrylamide gel revealed an insignificant decrease (by 15%, p ≤ 0.01) in the titin content compared to the myosin heavy chain content in m. gastrocnemius of animals of the “Hypothermia” group. The titin content in m. soleus and cardiac muscle, as well as the nebulin content in m. soleus and m. gastrocnemius, did not decrease during hibernation. These results are consistent with our previous data for other hibernators: long-tailed ground squirrel, brown and Himalayan black bears. It can be assumed that during evolution, hibernating animals developed the molecular mechanisms responsible for maintaining a stable level of giant sarcomeric cytoskeletal proteins during hibernation.

Changes in titin alternative splicing in the rat soleus after seven-day gravitational unloading (the hindlimb unloading model) were studied by long-fragment PCR and nanopore sequencing. An increase in the proportion of shorter titin mRNA transcripts was found in m. soleus of the hindlimb suspended rats, which may have led to the translation of shorter variants of the N2A isoform of this protein. In the nuclear fraction of m. soleus of control and hindlimb suspended rats, no significant differences were found in the content of Rbm20, an RNA-binding protein involved, as is shown earlier, in the regulation of titin alternative splicing in mammalian cardiac muscle. It can be assumed that Rbm20 is not involved in the regulation of titin alternative splicing in the rat soleus muscle.

Objective This study investigates the influence of timing of surgery among infants with congenital heart disease and active respiratory tract infections in a contemporary Western Canadian cohort. Methods This was a retrospective matched cohort study of infants aged 1 week to 6 months undergoing surgical repair of congenital heart disease between 2014 and 2017. Case patients had active respiratory tract infections preoperatively and were matched to control patients based on primary heart lesion. The primary outcome was time to extubation. Results We identified 20 cases (median age, 3.4 months [range, 2.4-4.3 months]) that were matched to 40 controls (1:2 ratio). In case patients, surgery occurred at a median of 1 day after the positive viral testing. There were no statistically significant differences between cases and controls in time to extubation (59 vs 34 hours [P = .12]), postoperative vasoactive scores at 24 hours (0 vs 0 [P = .53]), 48 hours (0 vs 0 [P = .23]), maximum vasoactive score in postoperative period (5 vs 5.5 [P = .54]), or time to hospital discharge (13 vs 12 days [P = .39]). Case patients had increased duration of total respiratory support (including noninvasive ventilation, 3.5 vs 2 days [P = .02]) and postoperative intensive care unit length of stay (5.5 vs 3 days [P = .01]). Conclusions Cardiac surgery on infants with congenital heart disease during an acute viral respiratory tract infection may yield a clinically relevant prolongation in time to extubation.

Background: In 2020, the pandemic caused by novel coronavirus infection has become one of the most critical global health challenges during the past century. The lack of a vaccine, as the most effective way to control the novel infection, has prompted the development of a large number of preventive products by the scientific community. We have developed a candidate vaccine (EpiVacCorona) against novel coronavirus infection caused by SARS-CoV-2 that is based on chemically synthesized peptides conjugated to a carrier protein and adsorbed on aluminum hydroxide and studied the specific activity of the developed vaccine. Aims: Study of the immunogenicity and protectivity of the peptide candidate vaccine EpiVacCorona. Materials and methods: the work was performed using standard molecular biological, virological and histological methods. Results: It was demonstrated that EpiVacCorona, when administered twice, spaced 14 days apart, to hamsters, ferrets, and non-human primates (African green monkeys, rhesus macaques) at a dose of 260 g, which is equal to one inoculation dose for humans, induces virus-specific antibodies in 100% of the animals. Experiments in hamsters showed this vaccine to be associated with the dose-dependent immunogenicity. The vaccine was shown to accelerate the elimination of the virus from the upper respiratory tract in ferrets and prevent the development of pneumonia in hamsters and non-human primates following a respiratory challenge with novel coronavirus. Conclusions: The results of a preclinical specific activity study indicate that the use of EpiVacCorona has the potential for human vaccination.

Background Children with congenital heart disease (CHD) are at risk of adverse long-term neurodevelopmental outcomes, believed to be, in part, secondary to prenatal insults. Placental pathology and altered fetal middle cerebral arterial (MCA) flow suggestive of brain sparing have been documented in fetal CHD. In the present study we investigated the relationship between MCA and umbilical arterial (UA) flow patterns in fetal transposition of the great arteries (d-TGA) and hypoplastic left heart syndrome (HLHS) and growth and 2-year neurodevelopmental outcomes. Methods We included children with d-TGA and HLHS who had third-trimester fetal echocardiograms between 2004 and 2014, at which time umbilical artery (UA) and MCA pulsatility indices (PIs) were measured, and who underwent 2-year growth and neurodevelopmental assessments. Results We identified 24 children with d-TGA and 36 with HLHS. Mean age at fetal echocardiography was 33.8 ± 3.5 weeks. At 2-year follow-up, head circumference z score (standard deviation [SD]) was –0.09 (1.07) and 0.17 (1.7) for the d-TGA and HLHS groups, respectively. Bayley III mean (SD) cognitive, language, and motor scores were 97.7 (10.8), 94.7 (13.4), and 98.6 (8.6) for the d-TGA group and 90.3 (13.9), 87.2 (17.5), and 85.3 (16.2) for the HLHS group. On multivariate linear regression analysis, UA-PI was associated (effect sizes [95% CI]) with length (–1.45 [–2.7, –0.17], P = 0.027), weight (–1.46 [–2.6 to –0.30], P = 0.015) and cognitive scores (–14.86 [–29.95 to 0.23], P = 0.05) at 2 years of age. MCA PI showed no statistically significant correlation. Conclusions In fetal d-TGA and HLHS, a higher UA-PI in the third trimester, suggestive of placental insufficiency—but not MCA-PI—is associated with worse 2-year growth and neurodevelopment.

Modification of vaccine carriers by decoration with glycans can enhance binding to and even targeting of dendritic cells (DCs), thus augmenting vaccine efficacy. To find a specific glycan-“vector” it is necessary to know glycan-binding profile of DCs. This task is not trivial; the small number of circulating blood DCs available for isolation hinders screening and therefore advancement of the profiling. It would be more convenient to employ long-term cell cultures or even primary DCs from murine blood. We therefore examined whether THP-1 (human monocyte cell line) and DC2.4 (immature murine DC-like cell line) could serve as a model for human DCs. These cells were probed with a set of glycans previously identified as binding to circulating human CD14low/-CD16+CD83+ DCs. In addition, we tested a subpopulation of murine CD14low/-CD80+СD11c+CD16+ cells reported as relating to the human CD14low/-CD16+CD83+ cells. Manα1–3(Manα1–6)Manβ1–4GlcNAcβ1–4GlcNAcβ bound to both the cell lines and the murine CD14low/-CD80+СD11c+CD16+ cells. Primary cells, but not the cell cultures, were capable of binding GalNAcα1–3Galβ (Adi), the most potent ligand for binding to human circulating DCs. In conclusion, not one of the studied cell lines proved an adequate model for DCs processes involving lectin binding. Although the glycan-binding profile of BYRB-Rb (8.17)1Iem mouse DCs could prove useful for assessing human DCs, important glycan interactions were missing, a situation which was aggravated when employing cells from the BALB/c strain. Accordingly, one must treat results from murine work with caution when seeking vaccine targeting of human DCs, and certainly should avoid cell lines such as THP-1 and DC2.4 cells.

Background The Coronavirus disease 2019 (COVID‐19) pandemic is having a major global impact, and the resultant response in the development of new diagnostics is unprecedented. The detection of antibodies against severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) has a role in managing the pandemic. We evaluated the feasibility of using SARS‐CoV‐2 peptide Kode Technology‐modified red cells (C19‐kodecytes) to develop an assay compatible with existing routine serologic platforms. Study Design and Methods A panel of eight unique red cells modified using Kode Technology function‐spacer‐lipid constructs and bearing short SARS‐CoV‐2 peptides was developed (C19‐kodecyte assay). Kodecytes were tested against undiluted expected antibody‐negative and ‐positive plasma samples in manual tube and three column agglutination technology (CAT) platforms. Parallel analysis with the same peptides in solid phase by enzyme immunoassays was performed. Evaluation samples included >120 expected negative blood donor samples and >140 COVID‐19 convalescent plasma samples, with independent serologic analysis from two centers. Results Specificity (negative reaction rate against expected negative samples) in three different CAT platforms against novel C19‐kodecytes was >91%, which correlated with published literature. Sensitivity (positive reaction rate against expected positive convalescent, PCR‐confirmed samples) ranged from 82% to 97% compared to 77% with the Abbott Architect SARS‐CoV‐2 IgG assay. Manual tube serology was less sensitive than CAT. Enzyme immunoassay results with some Kode Technology constructs also had high sensitivity. Conclusions C19‐kodecytes are viable for use as serologic reagent red cells for the detection of SARS‐CoV‐2 antibody with routine blood antibody screening equipment.

OBJECTIVE. The purpose of our study was to assess potential disparities in the utilization of advanced imaging during emergency department (ED) visits. MATERIALS AND METHODS. This retrospective study was conducting using 5% Research Identifiable Files. All CT and MRI (together defined as "advanced imaging") examinations associated with ED visits in 2015 were identified for continuously enrolled Medicare beneficiaries. Individuals with medical claims 30 days before the index ED event were excluded, and encounters that occurred in hospitals without advanced imaging capabilities were also excluded. Patient characteristics were identified using Medicare files and hospital characteristics using the American Hospital Association Annual Survey of Hospitals. Multivariate logistic regression was used for the analysis. RESULTS. Of 86,976 qualifying ED encounters, 52,833 (60.74%) ED encounters were for female patients; 29.03% (n = 25,245) occurred at rural hospitals and 15.81% (n = 13,750) at critical access hospitals. Race distribution was 83.13% White, 11.05% Black, and 5.82% Other. Compared with ED patients at urban hospitals, those at rural and critical access hospitals were 6.9% less likely (odds ratio [OR] = 0.931, p = 0.015) and 18.0% less likely (OR = 0.820, p < 0.0001), respectively, to undergo advanced imaging. Compared with White patients, Black patients were 31.6% less likely (OR = 0.684, p < 0.0001) to undergo advanced imaging. Relative to their urban counterparts, both White (OR = 0.941, p = 0.05) and Black (OR = 0.808, p = 0.047) rural ED patients were less likely to undergo advanced imaging. CONCLUSION. Among Medicare beneficiaries receiving care in U.S. EDs, significant disparities exist in advanced imaging utilization. Although imaging appropriateness was not investigated, these findings suggest inequity. Further research is necessary to understand why consistent health benefits do not translate into consistent imaging access among risk-adjusted ED patients.

Objective The aim: The identification and determination of needs that the population of older age groups have in medical and social services on the basis of health data and the results of a survey. Patients and methods Material and methods: Because of bibliographic, epidemiological, medical-statistical, analytical methods the research has investigated the problems of healthy aging, tendencies in population health of the population of Ukraine of senior age groups during 2000-2017, features and tendencies of health of a sample contingent of urban population of elderly age according to appeals in health care facilities during 2009-2019. The use of the sociological method, the self-evaluation of elderly people of their own health, characteristics of lifestyle and medical activity are determined, the needs of older people in medical and social services were assessed. Results Results: Negative tendencies to increase during 2000-2017 the prevalence of pathology among the population older than working age by 22.8%, including blood diseases in 2 times, endocrine system - in 1.8 times, urogenital system - by 1.5 times, digestive organs - by 1.4 times, tumors and nervous system - by 1.3 times. Among the urban elderly population, the prevalence of sensory diseases, including ear and eye diseases, endocrine disorders, injuries and poisonings, has increased, and mental health indicators have deteriorated. The sociological survey found a low level of self-esteem (31.5±3.5 per 100 had health problems, 10.1±2.3 are significant). Self-medication was practiced by 76.4±3.2 per 100 respondents, 74.2±3.3 were not followed or they violated the doctor's recommendations. 56.2 ±3.7 per 100 respondents had physical examinations in the non-right time 29.7±3.4 had not it.There was a significant prevalence of risk factors, including hypodynamics (21.9±3.1 per 100), tobacco use (29.8±3.4), malnutrition (37.1±3.6), overweight (obesity) (32, 6±3.5), arterial hypertension (37.6±3.6), hypercholesterolemia (28.7±3.4), glucosemia 16.3±2.8). The research has discovered the needs of older people in health care and social services, inter alia in preventive counseling (65.2±3.6 per 100), the introduction of electronic technologies in health care (68.5±3.5), information educational services on health issues (67.4±3.5), provision of services in hospitals at home (66.3±3.5), in increasing the availability of rehabilitation (43.8±3.7), specialized counseling (34.3±3.6) and emergency medical care (16.2±2.8), improvement of socio-economic determinants (78.0±3.1), introduction of activities (48.3±3.7), joint training programs for older people (42.1±3.7), the development of certain skills, the use of technical means, assistive devices (67.4±3.5), the formation of a conducive to better health environment (58, 4±3.7). Conclusion Conclusions: The low level of the elderly people's health, the tendency to increase the burden of disease, the prevalence of risk factors for disease and low medical activity lead tosignificant needs for medical and social services of preventive, treatment-diagnostic, rehabilitation, improving socio-economic determinants, measures to reduce social isolation.

Background: Mouse neutralization test is widely used to determine the level of anti-rabies antibodies, but it is labor-intensive and time consuming. Alternative methods for determining the neutralizing activity of anti-rabies sera and immunoglobulin in cell cultures are also known. Methods such as FAVN and RFFIT involve the use of fluorescent diagnostics. Determination of Cytopathic Effect (CPE) is often complicated due to features of rabies virus replication in cells. Atomic Force Microscopy (AFM) is able to detect the interaction of the virus with the cell at an early stage. Therefore, in this study, a method has been developed for determining the specific activity of anti-rabies sera and immunoglobulin using AFM of cell cultures. Methods: The method is based on the preliminary interaction of rabies virus with samples of rabies sera or immunoglobulin drug, adding the specified reaction mixture to cell culture (Vero or BHK-21), and then measuring the surface roughness of the cells using AFM. AFM was carried out in the intermittent contact mode by the mismatch method in the semi-contact mode. The results were compared with the values obtained in the mouse neutralization test. The consistency of the results obtained by both methods was evaluated by Bland-Altman method. Results: The increment in the surface roughness of the cells is a consequence of the damaging effect of the virus, which is weakened as a result of its neutralization by rabies antibodies. A dilution allowing 50% suppression of the increase in the surface roughness of cells was selected as the titer of rabies sera or immunoglobulin. In this case, the recommended range for determining the antibody titer is from 1:100 to 1:3000. Conclusion: For the first time, a new methodological approach in virology and pharmaceutical research is presented in this study. The use of the proposed methodological technique will reduce the time from 21 to 2 days to obtain results in comparison with the mouse neutralization test; also, fewer laboratory animals are required in this approach which is in agreement with 3 R Principle.

Background The treatment, genotyping, and phenotyping of patients with World Health Organization Group 1 pulmonary arterial hypertension (PAH) have evolved dramatically in the last decade. Research Question The United States Pulmonary Hypertension Scientific Registry was established as the first US PAH patient registry to investigate genetic information, reproductive histories, and environmental exposure data in a contemporary patient population. Study Design and Methods Investigators at 15 US centers enrolled consecutively screened adults diagnosed with Group 1 PAH who had enrolled in the National Biological Sample and Data Repository for PAH (PAH Biobank) within 5 years of a cardiac catheterization demonstrating qualifying hemodynamic criteria. Exposure and reproductive histories were collected by using a structured interview and questionnaire. The biobank provided genetic data. Results Between 2015 and 2018, a total of 499 of 979 eligible patients with clinical diagnoses of idiopathic PAH (IPAH) or familial PAH (n = 240 [48%]), associated PAH (APAH; n = 256 [51%]), or pulmonary venoocclusive disease/pulmonary capillary hemangiomatosis (n = 3 [1%]) enrolled. The mean age was 55.8 years, average BMI was 29.2 kg/m2, and 79% were women. Mean duration between symptom onset and diagnostic catheterization was 1.9 years. Sixty-six percent of patients were treated with more than one PAH medication at enrollment. Past use of prescription weight loss drugs (16%), recreational drugs (27%), and oral contraceptive pills (77%) was common. Women often reported miscarriage (37%), although PAH was rarely diagnosed within 6 months of pregnancy (1.9%). Results of genetic testing identified pathogenic or suspected pathogenic variants in 13% of patients, reclassifying 18% of IPAH patients and 5% of APAH patients to heritable PAH. Interpretation Patients with Group 1 PAH remain predominately middle-aged women diagnosed with IPAH or APAH. Delays in diagnosis of PAH persist. Treatment with combinations of PAH-targeted medications is more common than in the past. Women often report pregnancy complications, as well as exposure to anorexigens, oral contraceptives, and/or recreational drugs. Results of genetic tests frequently identify unsuspected heritable PAH.

OBJECTIVE The aim: Of work is to determine changes in blood flow in the vessels of the anterior abdominal wall that occur after plastic surgeries in order to improve the results of operations and to develop new methods for the prevention of complications. PATIENTS AND METHODS Materials and methods: The study was conducted in 132 patients. Patients were divided into 2 groups: main group 64 and control group 68 patients. Main group has patients who underwent abdominoplasty in combination with liposuction; control group has patients who underwent abdominoplasty without liposuction. In both groups we make different simultaneous operations. Laser Doppler Flowmetry and Ultrasonic Doppler Flowmetry were performed to determine the blood flow indices in the flaps. RESULTS Results: Liposuction volumes averaged 3.57 ± 0.74 liters of lipoaspirate. In the main group there were totaly 4 complications, in the control group complications developed in 9 patients. Comparing daily indicators between the two groups, no statistically significant difference in the dynamics of MI changes was found during the entire study period (p = 0.767). Increase in caliber of vessels, on average, from 1.55 ± 0.8 mm in the preoperative period to 1.68 ± 0.75 mm on the 14th day of the postoperative period was statistically significant (p < 0.05). CONCLUSION Conclusions: The combination of abdominoplasty with liposuction and simultaneous operations does not lead to greater development of complications and allows to achieve good aesthetic results.

Skeletal muscle is characterized by its three-dimensional (3D) anisotropic architecture composed of highly aligned and electrically-excitable muscle fibers that enable normal movement. Biomaterial-based tissue engineering approaches to repair skeletal muscle are limited due to difficulties combining 3D structural alignment (to guide cell/matrix organization) and electrical conductivity (to enable electrically-excitable myotube assembly and maturation). In this work we successfully produced aligned and electrically conductive 3D collagen scaffolds using a freeze-drying approach. Conductive polypyrrole (PPy) nanoparticles were synthesized and directly mixed into a suspension of type I collagen and chondroitin sulfate followed by directional lyophilization. Scanning electron microscopy (SEM), energy-dispersive spectroscopy (EDS), and confocal microscopy showed that directional solidification resulted in scaffolds with longitudinally aligned pores with homogeneously-distributed PPy content. Chronopotentiometry verified that PPy incorporation resulted in a five-fold increase in conductivity compared to non-PPy-containing collagen scaffolds without detrimentally affecting myoblast metabolic activity. Furthermore, the aligned scaffold microstructure provided contact guidance cues that directed myoblast growth and organization. Incorporation of PPy also promoted enhanced myotube formation and maturation as measured by myosin heavy chain (MHC) expression and number of nuclei per myotube. Together these data suggest that aligned and electrically conductive 3D collagen scaffolds could be useful for skeletal muscle tissue engineering.