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The unobliterated portion of embryological thyroglossal duct may present as cystic swelling later in life and may contain functional thyroid follicles. This cyst requires excision along with the entire thyroglossal duct remnant and adjacent portion of hyoid bone. At times, the excised specimen could demonstrate a focus of carcinomatous change inside the cyst wall. Very rarely, this thyroglossal duct cyst carcinoma could be associated with malignancy of native thyroid gland. This case report illustrates an interesting case of synchronous carcinoma of thyroglossal duct cyst and native thyroid gland. It also sheds light on the controversies related to the pathophysiology of such association and the dilemmas surrounding the management of thyroglossal duct cyst carcinoma, with or without concurrent carcinoma of thyroid gland.

A male in his 70s presented with a chronic malunited comminuted Galeazzi fracture dislocation, including angular malunion, radial shortening (1.3 cm ulnar-plus variance) and distal radioulnar joint (DRUJ) instability secondary to chronic dislocation with mechanical rotation block. A modified, single-stage radius corrective osteotomy with bone grafting technique to overcorrect radius length was employed, restoring normal DRUJ motion and stability by engaging the secondary DRUJ stabilisers without triangular fibrocartilage complex repair. DRUJ stability was restored via radius lengthening, engaging the DRUJ’s secondary stabilisers, bypassing the need for complex ligamentous reconstruction. The patient returned to full activity. We recommend our simple yet effective approach to treat chronic, malunited Galeazzi fractures with DRUJ instability.

A male in his 70s presented to the emergency department with sudden-onset abdominal pain and syncope. While in the emergency department, he developed worsening hypotension and anaemia. A CT angiogram was suggestive of abdominal apoplexy (spontaneous intraperitoneal haemorrhage), which was treated successfully with embolisation of the bleeding vessels. Spontaneous bleeding was thought to be related to his initiation of apixaban 1 week previously. The patient made an excellent recovery and was transitioned back to oral anticoagulation.

Each year in the United States, food banks receive more than one million kilograms of donated hunted game meat. The National Rifle Association’s (NRA’s) Hunters for the Hungry initiative has established programs in more than 40 states for hunters to take their harvested game animal to a meat processing facility and indicate intent to donate the resulting processed and packaged meat to a local food bank. Most donated game meat is ground deer meat (venison); other donated game includes wild hog and goose. Even though the presence of ammunition-derived metallic lead fragments in donated firearms-hunted meat has been recognized for more than a decade, most of the donated hunted meat is not inspected to discard meat containing lead fragments. An underlying lack of food safety standards for adulterated donated food increases risks to low-income recipients, who are already disproportionately affected by elevated blood lead levels (BLLs).2 Primary prevention is needed for this overlooked source of lead exposure.

Researchers are increasingly recognizing the importance of studying and addressing intersectional stigma within the field of HIV. Yet, researchers have, arguably, struggled to operationalize intersectional stigma. To ensure that future research and methodological innovation is guided by frameworks from which this area of inquiry has arisen, we propose a series of core elements for future HIV-related intersectional stigma research. These core elements include multidimensional, multilevel, multidirectional, and action-oriented methods that sharpen focus on, and aim to transform, interlocking and reinforcing systems of oppression. We further identify opportunities for advancing HIV-related intersectional stigma research, including reducing barriers to and strengthening investments in resources, building capacity to engage in research and implementation of interventions, and creating meaningful pathways for HIV-related intersectional stigma research to produce structural change. Ultimately, the expected payoff for incorporating these core elements is a body of HIV-related intersectional stigma research that is both better aligned with the transformative potential of intersectionality and better positioned to achieve the goals of Ending the HIV Epidemic in the United States and globally. (Am J Public Health. 2022;112(S4):S413–S419. https://doi.org/10.2105/AJPH.2021.306710 )

INTRODUCTION: In the 330-patient ADVOCATE trial of avacopan for the treatment of antineutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis, in which 81% of patients had renal involvement, estimated glomerular filtration rate (eGFR) increased on average 7.3 ml/min per 1.73 m(2) in the avacopan group and 4.1 ml/min per 1.73 m(2) in the prednisone group (P = 0.029) at week 52. This new analysis examines the results in the patient subgroup with severe renal insufficiency at enrollment into the trial, i.e., eGFR ≤20 ml/min per 1.73 m(2). METHODS: eGFR was determined at baseline and over the course of the trial. Changes in eGFR were compared between the 2 treatment groups. RESULTS: In ADVOCATE, 27 of 166 patients (16%) in the avacopan group and 23 of 164 patients (14%) in the prednisone group had a baseline eGFR ≤20 ml/min per 1.73 m(2). At week 52, eGFR increased on average 16.1 and 7.7 ml/min per 1.73 m(2) in the avacopan and prednisone groups, respectively (P = 0.003). The last eGFR value measured during the 52-week treatment period was ≥2-fold higher than baseline in 41% of patients in the avacopan group compared to 13% in the prednisone group (P = 0.030). More patients in the avacopan group versus prednisone group had increases in eGFR above 20, 30, and 45 ml/min per 1.73 m(2), respectively. Serious adverse events occurred in 13 of 27 patients (48%) in the avacopan group and 16 of 23 patients (70%) in the prednisone group. CONCLUSION: Among patients with baseline eGFR ≤20 ml/min per 1.73 m(2) in the ADVOCATE trial, eGFR improved more in the avacopan group than in the prednisone group.

BACKGROUND: Enrichment strategies from clinical trials for progressive systemic sclerosis-associated interstitial lung disease (SSc-ILD) have not been tested in a real-life cohort.RESEARCH QUESTION: Do enrichment strategies for progressive ILD impact efficacy, repre-sentativeness, and feasibility in patients with SSc-ILD from the European Scleroderma Trials and Research (EUSTAR) database?STUDY DESIGN AND METHODS: We applied the inclusion criteria of major recent SSc-ILD trials (Study of the Efficacy and Safety of Tocilizumab in Participants With Systemic Sclerosis [focuSSced], Scleroderma Lung Study II [SLS II], and Safety and Efficacy of Nintedanib in Systemic Sclerosis [SENSCIS]) and assessed progressive ILD, which was defined as absolute change in FVC and as significant progression (FVC decline $10%). Data were compared with all patients and with patients who did not fulfill any inclusion criteria. RESULTS: In total, 2,258 patients with SSc-ILD were included: 31.2% of the patients met SENSCIS criteria; 5.8% of the patients met SLS II criteria; 1.6% of the patients met focuSSced criteria, and 67.7% (1,529) of the patients did not meet any criteria. In the first 12 + 3 months, the absolute FVC decline in all patients and in patients who fulfilled criteria from SENSCIS was -0.1%, in patients who fulfilled criteria from focuSSced was -3.7%, and in patients who fulfilled criteria from SLS II was 2.3%, with accompanying more progressors in focuSSced. The patient populations that fulfilled the different study inclusion criteria significantly differed in various clinical parameters. In the second 12-month period, SENSCIS-enriched patients had a further absolute FVC% decline as described for the total cohort. In contrast, patients who fulfilled the focuSSced and SLS II criteria showed numeric improvement of lung function. There were no significant associations of enrichment criteria and ILD progression.INTERPRETATION: The application of enrichment criteria from previous clinical trials showed enrichment for progression with variable success, which led to selected patient populations reducing feasibility of recruitment. These findings are important for future clinical trial design and interpretation of the results of published trials.CHEST 2023; 163(3):586-598

Rationale: Obesity affects 40% of U.S. adults, is associated with a proinflammatory state, and presents a significant risk factor for the development of severe coronavirus disease (COVID-19). To date, there is limited information on how obesity might affect immune cell responses in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Objectives: To determine the impact of obesity on respiratory tract immunity in COVID-19 across the human lifespan. Methods: We analyzed single-cell transcriptomes from BAL in three ventilated adult cohorts with (n = 24) or without (n = 9) COVID-19 from nasal immune cells in children with (n = 14) or without (n = 19) COVID-19, and from peripheral blood mononuclear cells in an independent adult COVID-19 cohort (n = 42), comparing obese and nonobese subjects. Measurements and Main Results: Surprisingly, we found that obese adult subjects had attenuated lung immune or inflammatory responses in SARS-CoV-2 infection, with decreased expression of IFN-α, IFN-γ, and TNF-α (tumor necrosis factor α) response gene signatures in almost all lung epithelial and immune cell subsets, and lower expression of IFNG and TNF in specific lung immune cells. Peripheral blood immune cells in an independent adult cohort showed a similar but less marked reduction in type-I IFN and IFNγ response genes, as well as decreased serum IFNα, in obese patients with SARS-CoV-2. Nasal immune cells from obese children with COVID-19 also showed reduced enrichment of IFN-α and IFN-γ response genes. Conclusions: These findings show blunted tissue immune responses in obese patients with COVID-19, with implications for treatment stratification, supporting the specific application of inhaled recombinant type-I IFNs in this vulnerable subset.

An overview of the recent operations and the main results of cesium injection in the Source for the Production of Ions of Deuterium Extracted from Rf plasma (SPIDER) negative ion source are described in this contribution. In experiments without cesium injection, all SPIDER plants were tested to verify the basic expectations on the operational parameters (e.g., electron cooling effectiveness of magnetic filter field) and to determine its operational region. For beam properties, it was shown that the current density varies across the beam in the vertical direction. In preliminary cesium experiments, the expected increase of negative ion current and simultaneous decrease of co-extracted electrons were found, along with the influence of the control parameters (polarization of the plasma electrodes, magnetic filter field) on the SPIDER beam uniformity in the horizontal and vertical directions. It was shown that non-Gaussian tails can be identified in the angular distribution on the plane perpendicular to the beam propagation direction. Stray particles, nonhomogeneous beam and large divergence might result in unexpected heat and particle loads over ITER neutral beam injector (NBI) accelerator grids; it is the goal of SPIDER to assess and possibly to identify suitable methods for controlling these beam features. A major shutdown, planned for late 2021, to solve the issues identified during the operation and to carry out scheduled modifications, is outlined. Such improvements are expected to allow SPIDER to pursue the ITER requirements in terms of negative ion current, electron-to-ion ratio, and beam duration.

Recurrent episodes of vomiting and diarrhoea in a child can present as a diagnostic dilemma and be easily misdiagnosed as recurrent viral gastroenteritis episodes. Primary adrenal insufficiency can present with recurrent episodes of vomiting and diarrhoea with the presence of metabolic acidosis and can be life-threatening if left undiagnosed and untreated. A high index of suspicion should be kept for diagnosing primary adrenal insufficiency in a child presenting with recurrent episodes of vomiting and diarrhoea with laboratory evidence of metabolic acidosis and hypoglycaemia. Primary adrenal insufficiency, in a male child specifically, should raise alarm for X-linked adrenoleukodystrophy (X-ALD). Very-long-chain fatty acids and confirmatory genetic testing for an ABCD1 gene mutation can help confirm the diagnosis. Addison’s disease often presents prior to the onset of the cerebral form of X-ALD. Early diagnosis of X-ALD allows for MRI screening for the development of cerebral disease in its early stages when treatment with stem cell transplant can halt the disease and be lifesaving.

Xylazine is a nonopioid veterinary anesthetic and sedative that is increasingly detected in the illicit drug supply in the United States. Data indicate a striking prevalence of xylazine among opioid-involved overdose deaths. The emergence of xylazine in the illicit drug supply poses many unknowns and potential risks for people who use drugs. The public health system needs to respond by increasing testing to determine the prevalence of xylazine, identifying its potential toxicity at various exposure levels, and taking mitigating action to prevent harms. Currently, there is little testing capable of identifying xylazine in drug supplies, which limits the possibility of public health intervention, implementation of harm reduction strategies, or development of novel treatment strategies. (Am J Public Health. 2022;112(8):1212–1216. https://doi.org/10.2105/AJPH.2022.306881 )

Lymphatic vasculature regulates fluid homeostasis by absorbing interstitial fluid and returning it to blood. Lymphatic vasculature is also critical for lipid absorption and inflammatory response. Lymphatic vasculature is composed of lymphatic capillaries, collecting lymphatic vessels, lymphatic valves, and lymphovenous valves. Defects in any of these structures could lead to lymphatic anomalies such as lymphedema, cystic lymphatic malformation, and Gorham-Stout disease. Basic research has led to a deeper understanding of the stepwise development of the lymphatic vasculature. VEGF-C and shear stress signaling pathways have evolved as critical regulators of lymphatic vascular development. Loss-of-function and gain-of-function mutations in genes that are involved in these signaling pathways are associated with lymphatic anomalies. Importantly, drugs that target these molecules are showing outstanding efficacy in treating certain lymphatic anomalies. In this article, we summarize these exciting developments and highlight the future challenges.

Obstructed hemivagina with ipsilateral renal anomaly (OHVIRA) is a rare congenital genitourinary defect with a triad of unilateral vaginal obstruction, uterine anomaly and ipsilateral renal agenesis. This paper reports an unusual presentation of OHVIRA, with our patient experiencing severe abdominal pain from a left tubo-ovarian abscess that is contralateral to the side of the vaginal outflow obstruction. Another reportable finding is our patient’s rare association of a trifid ureter that fuses distally before inserting ectopically in her vaginal canal. Lastly, this case report also emphasises the importance of radiologists’ expertise in suspecting the diagnosis early on and in contributing to the preoperative evaluation of patients with OHVIRA, thereby providing adequate management for these patients.

The Georgia Department of Public Health–East Central District and its local partners implemented an open, drive-through point of distribution site to administer the COVID-19 vaccine to eligible populations. The site was in Augusta, Georgia, from mid-December 2020 through mid-May 2021. The target population for this intervention was individuals eligible for the COVID-19 vaccine to prevent and slow transmission of severe acute respiratory syndrome coronavirus 2 infection. The point of distribution site successfully provided 42 342 vaccines. (Am J Public Health. 2022;112(S3):S279–S283. https://doi.org/10.2105/AJPH.2022.306820 )

This study describes the cell-free biomanufacturing of a broad-spectrum antiviral protein, griffithsin (GRFT) such that it can be produced with consistent purity and potency in less than 24 hours. We demonstrate GRFT production using two independent cell-free systems, one plant and one microbial. Griffithsin purity and quality were verified using standard regulatory metrics. Efficacy was demonstratedin vitroagainst SARS-CoV-2 and HIV-1 and was nearly identical to that of GRFT expressedin vivo. The proposed production process is efficient and can be readily scaled up and deployed anywhere in the world where a viral pathogen might emerge. The current emergence of viral variants has resulted in frequent updating of existing vaccines and loss of efficacy for front-line monoclonal antibody therapies. Proteins such as GRFT with its efficacious and broad virus neutralizing capability provide a compelling pandemic mitigation strategy to promptly suppress viral emergence at the source of an outbreak.

Transmission spectroscopy of exoplanets has revealed signatures of water vapor, aerosols, and alkali metals in a few dozen exoplanet atmospheres. However, these previous inferences with the Hubble and Spitzer Space Telescopes were hindered by the observations' relatively narrow wavelength range and spectral resolving power, which precluded the unambiguous identification of other chemical species$-$in particular the primary carbon-bearing molecules. Here we report a broad-wavelength 0.5-5.5 $\mu$m atmospheric transmission spectrum of WASP-39 b, a 1200 K, roughly Saturn-mass, Jupiter-radius exoplanet, measured with JWST NIRSpec's PRISM mode as part of the JWST Transiting Exoplanet Community Early Release Science Team program. We robustly detect multiple chemical species at high significance, including Na (19$\sigma$), H$_2$O (33$\sigma$), CO$_2$ (28$\sigma$), and CO (7$\sigma$). The non-detection of CH$_4$, combined with a strong CO$_2$ feature, favours atmospheric models with a super-solar atmospheric metallicity. An unanticipated absorption feature at 4$\mu$m is best explained by SO$_2$ (2.7$\sigma$), which could be a tracer of atmospheric photochemistry. These observations demonstrate JWST's sensitivity to a rich diversity of exoplanet compositions and chemical processes., Comment: 41 pages, 4 main figures, 10 extended data figures, 4 tables. Under review in Nature

We use the surface detector of the Pierre Auger Observatory to search for air showers initiated by photons with an energy above 1019 eV. Photons in the zenith angle range from 30∘ to 60∘ can be identified in the overwhelming background of showers initiated by charged cosmic rays through the broader time structure of the signals induced in the water-Cherenkov detectors of the array and the steeper lateral distribution of shower particles reaching ground. Applying the search method to data collected between January 2004 and June 2020, upper limits at 95% CL are set to an E-2 diffuse flux of ultra-high energy photons above 1019 eV, 2 × 1019 eV and 4 × 1019 eV amounting to 2.11 × 10-3, 3.12 × 10-4 and 1.72 × 10-4 km-2 sr-1 yr-1, respectively. While the sensitivity of the present search around 2 × 1019 eV approaches expectations of cosmogenic photon fluxes in the case of a pure-proton composition, it is one order of magnitude above those from more realistic mixed-composition models. The inferred limits have also implications for the search of super-heavy dark matter that are discussed and illustrated.

Background: Before pregnancy is recognized, ovulation, fertilization, and implantation must all occur. Physical activity and sedentary behavior may impact pregnancy success by altering each or all of these processes. The aim of this review was to review the association between physical activity and sedentary behavior with spontaneous female and male fertility. Method: PubMed/MEDLINE, Web of Science, CINAHL, SPORTDiscus, and Embase were searched from inception to August 9, 2021. Eligible studies included randomized controlled trials or observational studies, published in English, describing an association between physical activity or sedentary behavior (exposures) and spontaneous fertility (outcome) among women or men. Results: Thirty-four studies from 31 unique populations were included in this review (12 cross-sectional studies, 10 cohort studies, 6 case–control studies, 5 randomized controlled trials, and one case–cohort study). Of the 25 studies among women, the majority identified mixed results (n = 11) or no association (n = 9) between physical activity and female fertility. Seven studies reported on female fertility and sedentary behavior, and 2 found sedentary behavior was associated with decreased female fertility. Of the 11 studies among men, most of the studies (n = 6) found that physical activity was associated with increased male fertility. Two of the studies reported on male fertility and sedentary behavior, and neither identified an association. Conclusions: The association between spontaneous fertility and physical activity in both men and women remains unclear, and the association with sedentary behavior remains largely unexplored.

In spermatozoa, the nuclear F-actin supports the acroplaxome, a subacrosomal structure involved in the correct exposure of several acrosomal membrane proteins; among them, the glycoprotein IZUMO1 is the major protein involved in sperm-oocyte fusion. Nuclear F-actin is also involved in sperm head shaping and chromosome compartmentalization. To date, few notions regarding the bivalent role of F-actin on sperm chromatin organization and IZUMO1 positioning have been reported. In our work, we characterized subcellular organization of F-actin in human high- and low-quality spermatozoa (A- and B-SPZ), respectively, showing that F-actin over-expression in sperm head of B-SPZ affected IZUMO1 localization. A correct IZUMO1 repositioning following in vitro induction of F-actin depolymerization, by cytochalasin D treatment, occurred. Interestingly, F-actin depolymerization was also associated with a correct acrosome repositioning, thus to favor a proper acrosome reaction onset, with changes in sperm nuclear size parameters and histone acetylation rate reaching high-quality conditions. In conclusion, the current work shows a key role of F-actin in the control of IZUMO1 localization as well as chromatin remodeling and acetylation events.

Background: Studies investigating the effects of common recovery modalities following acute strenuous exercise have reported mixed results. Objectives: This systematic review with meta-analysis and meta-regression compared the effects of cold-water immersion (CWI) against other common recovery modalities on recovery of athletic performance, perceptual outcomes, and creatine kinase (CK) following acute strenuous exercise in physically active populations. Study Design: Systematic review, meta-analysis, and meta-regression. Methods: The MEDLINE, SPORTDiscus, Scopus, Web of Science, Cochrane Library, EmCare, and Embase databases were searched up until September 2022. Studies were included if they were peer reviewed, published in English, included participants who were involved in sport or deemed physically active, compared CWI with other recovery modalities following an acute bout of strenuous exercise, and included measures of performance, perceptual measures of recovery, or CK. Results: Twenty-eight studies were meta-analysed. CWI was superior to other recovery methods for recovering from muscle soreness, and similar to other methods for recovery of muscular power and flexibility. CWI was more effective than active recovery, contrast water therapy and warm-water immersion for most recovery outcomes. Air cryotherapy was significantly more effective than CWI for the promotion of recovery of muscular strength and the immediate recovery of muscular power (1-h post-exercise). Meta-regression revealed that water temperature and exposure duration were rarely exposure moderators. Conclusion: CWI is effective for promoting recovery from acute strenuous exercise in physically active populations compared with other common recovery methods. Protocol Registration: Open Science Framework: https://doi.org/10.17605/OSF.IO/NGP7C Refereed/Peer-reviewed

Background: Widely used psychotropic medications for obsessive-compulsive disorder (OCD) may change the volumes of subcortical brain structures, and differently in children vs. adults. We measured subcortical volumes cross-sectionally in patients finely stratified for age taking various common classes of OCD drugs. Methods: The ENIGMA-OCD consortium sample (1081 medicated/1159 unmedicated OCD patients and 2057 healthy controls aged 6–65) was divided into six successive 6–10-year age-groups. Individual structural MRIs were parcellated automatically using FreeSurfer into 8 regions-of-interest (ROIs). ROI volumes were compared between unmedicated and medicated patients and controls, and between patients taking serotonin reuptake inhibitors (SRIs), tricyclics (TCs), antipsychotics (APs), or benzodiazepines (BZs) and unmedicated patients. Results: Compared to unmedicated patients, volumes of accumbens, caudate, and/or putamen were lower in children aged 6–13 and adults aged 50–65 with OCD taking SRIs (Cohen's d = −0.24 to −0.74). Volumes of putamen, pallidum (d = 0.18–0.40), and ventricles (d = 0.31–0.66) were greater in patients aged 20–29 receiving APs. Hippocampal volumes were smaller in patients aged 20 and older taking TCs and/or BZs (d = −0.27 to −1.31). Conclusions: Results suggest that TCs and BZs could potentially aggravate hippocampal atrophy of normal aging in older adults with OCD, whereas SRIs may reduce striatal volumes in young children and older adults. Similar to patients with psychotic disorders, OCD patients aged 20–29 may experience subcortical nuclear and ventricular hypertrophy in relation to APs. Although cross-sectional, present results suggest that commonly prescribed agents exert macroscopic effects on subcortical nuclei of unknown relation to therapeutic response.

No abstract available

Introduction: Myocardial steatosis, a poorly documented pathology, is characterized by the accumulation of abnormal amounts of triglycerides in the cardiomyocytes. Myocardial steatosis is generally asymptomatic, but it can be the cause of heart failure. It is primarily of hypoxic or metabolic origin. Case Report: We report a case of postmortem diagnosis in a 53-year-old male patient, without known his pathological history, who was a victim of sudden death from abdominal pain. The autopsy revealed diffuse atheromatous cardiac, aortic, and hepatic lesions. Conclusion: It is very common for myocardial steatosis to be diagnosed postmortem due to its nonspecific symptomatology. The risk of mortality and morbidity could be reduced through a healthy lifestyle and regular biological examination to identify risk factors.

The analysis of main approaches to determining essence of health-improving tourism in works of national scientists and researchers is presented. The conclusions are made that the most widespread classification of health-improving tourism is its division into medical and health-improving tourism. The medical tourism includes such its types as medical and sanatorium-health resort, and health-improving tourism covers balneologic, SPA-tourism, Wellness-tourism. The difference between medical and health-improving tourism is determined in order to regulate received services. The author's structure of medical and health-improving services, types of tourism and specialized organizations is developed. The analysis of supply and demand for health-improving tourism in 2014-2020 is presented. The main trends of development of health-improving segment in context of such its directions as increasing of SPA and Wellness industry, development of medical tourism, increasing of return on health tourism are formulated. The factors constraining development and reducing competitiveness of health-improving tourism in Russia are identified and structured.

The tuberculosis is the most important medical and social problem among globally dangerous epidemiological phenomena. the tuberculosis ranks 9th place in the structure of mortality and disability of population and 1st place among causes of death from single infectious agent.The purpose of the study was to analyze dynamics of total morbidity and mortality because of tuberculosis against the background of the implementation of telemedicine clinical organizational technology in phthisiology care 2007-2021.The official Regional and Federal data of Rosstat for 2007-2021 were used. The indicators of total morbidity and mortality of population caused by tuberculosis in the Sverdlovsk Oblast were established. The research methods were content analysis, dynamic series analysis, graphical analysis, statistical differences analysis.In the Sverdlovsk Oblast, the morbidity and mortality of tuberculosis exceeded national average indicators by 1.2-1.5 times. In 2007-2021, as a result of implementation of clinical organizational telemedicine technology in managing phthisiology care, total morbidity and mortality of population caused by tuberculosis decreased up to 2.275 and 2.97 times respectively. The rate of decrease of analyzed epidemiological indicators generally correlated with national average data with statistical validity of difference t≥2.In regions with unfavorable epidemiological indicators of tuberculosis, application of innovative technologies in management of clinical organizational processes is required. The development and implementation of clinical organizational telemedicine technology for managing regional phthisiology care contributes to significant reduction of morbidity and mortality of tuberculosis and optimizes sanitary and epidemiological well-being.

The paper is devoted to the numerical analysis of uniaxial loading of a sample of the mechanical metamaterial. The structure of the mechanical metamaterial is constructed of a ring and four ligaments, which make up a tetrachiral structure. The peculiarity of such a structure consists in torsion of the sample under the force load. Two methods of connecting cells in the metamaterial are considered: "adjoining" and "overlapping". The "adjoining" method of joining cells increases the thickness of the internal structure of the sample, which allows us to consider it as a topological defect of the metamaterial. The "overlapping" method saves the base material from which the tetrachiral structure is constructed. Differences in the structure when constructing a three-dimensional sample result in a significant change in the characteristics of the sample. Numerical solution of the problem is performed in a three-dimensional formulation using the finite element method. The constitutive relation describing the behavior of the model corresponds to Hooke's law. Numerical simulation of uniaxial loading made it possible to obtain the results of mechanical response and to analyze the effective properties of metamaterials. A topological defect in the form of a thickening of the internal structure elements led to a difference in the linear dimensions of the two samples. The increased thickness of the unit cell connection elements resulted in a decrease in the effective density of the metamaterial sample. The same sample showed a triple increase in the value of the elastic modulus. The greater ability to resist deformation resulted in a reduced twist effect compared to the sample whose cells were joined by the "overlapping" method. The results obtained will make it possible to program the mechanical behavior and properties of the metamaterial sample.

The article presents the results of examination of opinions of residents of the North Caucasus Federal District concerning healthy urban planning issues. The most residents of large cities are satisfied with infrastructure of their city, while residents of small towns are less satisfied with it. The prioritization of importance of solving various problems of urban life, opinions of residents are not solidary and differ depending on age and place of residence of respondents. For example, construction of playgrounds is a priority for residents of reproductive age from small towns. Only one out of ten of respondents would like to participate in strategy of development of their cities of residence.

The present research is devoted to the development of the theoretical foundations of nondestructive acoustic method for identifying inhomogeneous prestress fields in a hollow cylinder, depending on the probing loading type. A linearized model of steady oscillations of an elastic body in the presence of an inhomogeneous prestress field of arbitrary nature is considered in the standard and weak formulations. On the basis of this model, we formulate a problem for a cantilever-clamped prestressed hollow cylinder that performs steady axisymmetric vibrations under three types of probing loading. A corresponding weak formulation of the problem in the cylindrical coordinate system is presented, in which six independent components of the prestress tensor are taken into account. At that, a case of prestress fields obtained by applying some initial mechanical external static load is considered. In the presence and absence of prestresses of various types, amplitude-frequency dependences are analyzed, and resonant and natural frequencies are found in a wide frequency range. Numerical calculations were carried out using the FEM on a non-uniform grid; mesh refinement is carried out in the vicinity of the boundary points, where the type of boundary conditions changes. Based on the numerical solution of an auxiliary set of direct problems, seven types of prestress fields are constructed, differing in the types of initial loading, most often encountered in practice. To assess the possibility of implementing the procedure for reconstructing prestresses of each of the considered types, a sensitivity analysis was additionally performed, which showed that for some prestress types there are frequencies and types of probing loading for which the presence of prestress is practically not manifested. The sensitivity analysis performed made it possible to implement the optimal method of probing loading when solving the inverse coefficient problem. The statement of the new inverse problem on the restoration of arbitrary inhomogeneous prestress fields in the considered finite hollow cylinder is formulated. When restoring the prestress of a given structure, the inverse problem is reduced to finding a set of parameters from an ill-conditioned algebraic system, which was studied with the help of the A.N. Tikhonov regularization method. Additional data for solving the inverse problem was obtained on the basis of probing both via a single load and via combined probing modes. It has been found that it is most effective to use a combined loading mode and use a sufficiently wide frequency range when selecting sounding frequencies. The results of computational experiments on the reconstruction of six components of the prestress tensor are presented and analyzed, and recommendations are proposed for choosing the optimal modes of acoustic sounding.

This special issue continues the discussion of the impact of culture on identity, communication, politeness, and discourse strategies (see Russian Journal of Linguistics 22 (4) 2018, 23 (4) 2019, 24 (2) 2020). The topic has become particularly relevant in the context of two multidirectional processes, i.e., globalization resulting from current geopolitical trends and technological advancements, which have encouraged the intensification of contacts between people, languages, and cultures; and deglobalization focused on the preservation of national cultures and development of a multipolar and multicultural world. In our introductory article, we attempt to trace the impact of communication technologies, language, and culture contacts on digital, face-to-face, and public communication in different settings and discourses and outline its influence on communication, language variation, and change. In this introductory article we present a summary of the contributions of our authors to the issue, which showed that the implications of globalization and language contact are multifaceted, they can have both positive and negative effects on language use, maintenance, and change, as well as on cultural identity and diversity. Pursuing these latter factors contributes to developing trends of deglobalization. Our authors invite the reader to reflect on these processes. In conclusion, we sum up their major findings and suggest a brief avenue for further research.

Within the framework of the 2030 Agenda for Sustainable Development, goals were formulated, including those targeting to improve quality of life of people all around the world. The task was formulated to ensure universal coverage of health services. In 2019, the United Nations General Assembly noted that at least half of world's population have no access to basic health services. The study developed methodology to carry out comprehensive comparative analysis of values of individual public health indicators and amount of population payments for medications to confirm possibility of applying these indicators to monitor public health, including possibility of international comparisons. The study demonstrated inverse relationship between share of citizens' funds to pay for medications, index of universal health coverage and life expectancy. The stable direct relationship between such indicators as overall mortality rate from non-communicable diseases and likelihood of dying at the age of 30-70 years from any of cardiovascular diseases, cancer, diabetes or chronic respiratory diseases.

In the deformable solid mechanics, there are concepts associated with continuum points (displacements, relative elongations, shifts) and a set of continuum points – an elementary volume (mass, energy, stresses). The role of such volume in the mechanics of composite materials is played by the representative volume element (RVE).This concept was first introduced by R. Hill (1963). Modern authors use the W.J. Drugan, J.R. Willis (1996) formulation. Based on the analysis of the RVE concept, we formulated its essential features: RVE is the minimum possible sample for numerical tests to determine the effective material parameters of the composite; under any RVE loading, its macroscopic stress-strain state is uniform. Its significance for the mechanics of composite materials is revealed: the existence of RVE for a composite is a criterion for applying the effective modulus theory to the analysis of its stress-strain state; the dehomogenization of a stressed-state composite material at a point is a solution to the micromechanics problem of the RVE stress-strain state determination; the characteristic size of RVE limits the size of the sampling grid in the numerical study. An iterative algorithm for constructing a representative volume of a periodic structure composite and its effective material thermoelastic characteristics is proposed. It is shown that the geometric shape of such a composition is a rectangular parallelepiped. The RVE construction algorithm for periodic compositions is extended to the composites statistically uniformly reinforced with continuous fibers. A method for modeling such materials with a following regular structure is suggested described: in the section perpendicular to the fibers, fiber centers should be located at the vertices of regular triangles. Examples of constructing RVE and thermoelastic material characteristics of specific compositions are given. The calculation results are compared with the data obtained using certified software products.

Introduction: Mental disorders are very serious complicated disorders. Schizophrenia is one of the most baffling mental disorders. The new series 7-(2-(benzo[d]thiazol-2- ylamino)ethoxy)-4-methyl-2H-chromen-2- synthesized in search of newer compounds for Schizophrenia. Methods: Synthesis is done by refluxing in dry pyridine with various substituted 2-amino benzothiazoles derivatives (3a-3k) and 7-(2-Chloroethoxy)-4-methyl-2H-chromen-2-one (2). The molecular docking approach was used to screen these generated derivatives. Chem Bio Draw Ultra 12 was used to draw the compounds, which were then exposed to all potential conformations of compounds interacting with receptors. The Glide 7.6, Schrodinger 2017 Maestro 11.3 was used to achieve molecular docking. The Dopamine receptor 6CM4 serotonin 5TUD PDBs were acquired from the database of Brookhaven Protein. Using the OPLS 2005 force field, the ligand-protein hydrogen-bond network was acquired, along with the overall energy reduced. A glide score was used to rate the docking poses. Results: The produced compounds have been identified with the use of analytical and spectral data. All of the produced substances were tested and analyzed for serotonin 5HT2 antagonistic and dopamine D2 activity, which can be considered as a measure of typical antipsychotic properties. Conclusion: Compounds 4b, 4c, 4e, 4g & 4i have demonstrated promising pharmacological action in preliminary studies. According to the preceding findings, compounds with electronwithdrawing substitutions, such as 4e & 4b, have a good atypical profile of antipsychotics.

Abstract: There is a current tendency towards bioactive natural products that can be used in different areas such as food, pharmaceutical, and biomedical. In the last decades, polysaccharides have attracted increasing interest because of their potent nontoxic effects, therapeutic properties, and diversified range of applications. Polysaccharides are complex and heterogeneous macromolecules constituted of different monosaccharides and, in some cases, of glucuronic acid and sulphate groups. Polysaccharides with biological activity can be derived from plants, animals and microorganisms, especially microalgae. Microalgae are considered one of the most promising sources of these compounds that have already proved to have several important biological properties. In this sense, our objective is to elucidate the use of bioactive polysaccharides from microalgae in biomedical applications, emphasizing the biological activity of these compounds. Furthermore, the microalgal biomass production systems and polysaccharides extraction methods were presented and discussed.

Objective: Diabetic nephropathy is an unavoidable complication of chronic uncontrolled diabetes mellitus. The pathogenesis of diabetic nephropathy is multifactorial, and the development of an effective therapy remains to be elucidated. The aim of the present study was to assess the role of NOX2 and Nrf2 in the protective mechanism of thymoquinone (THQ) against streptozotocin (STZ)-induced diabetic nephropathy. Methods: Rats were injected with STZ (55 mg/kg) to induce diabetes. The diabetic rats were orally treated with THQ (10 mg/kg/day) for eight weeks. Results: STZ-treated rats exhibit an elevation of serum creatinine, serum urea, and creatinine clearance. The renal abnormalities were associated with increased NADPH oxidase isoform, NOX2 protein expression, and activity, along with elevated malondialdehyde (MDA). In addition, the tumor necrotic factor-alpha (TNF-α) level and nitric oxide (NO) bioavailability, as well as the transforming growth factor-beta (TGF)-β, were markedly increased. On the other hand, the nuclear factor-E2-related factor (Nrf2) protein expression was significantly reduced in diabetic rats compared to the control. However, treatment with THQ significantly reversed these alterations with subsequent ameliorating renal dysfunction and pathological abnormalities. Conclusion: The present study demonstrates that THQ could protect against STZ-induced diabetic nephropathy by modulating the Nrf2/NOX2 signaling pathway.