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The paper provides a review of prevalence and outcomes of cardiovascular comorbidities in patients with chronic obstructive pulmonary disease (COPD). From a clinical and patient-centered perspective, a COPD phenotype should be able to classify patients into distinct subgroups that provide prognostic information and allow to better determine appropriate therapy that alters clinically meaningful outcomes. It is hypothesized that both COPD and artherial hypertension (AH) have common pathway linking these comorbidities and explaining why they significantly complicate the management and influence the prognosis of patients with COPD and AH. Further studies will be required to explore this hypothesis and understand the relationship between COPD and AH.

The great prevalence of comorbidities, such as arterial hypertension (AH) and chronic obstructive pulmonary disease (COPD), generates a need to study the impact of COPD on the pathogenesis, course, and clinical picture of associated cardiovascular diseases. The paper analyzes the data available in the literature on the pathogenesis and course of arterial hypertension in patients with COPD. The paper also gives the authors’ data on the clinicofunctional and pathophysiological features of AH in patients with COPD. The findings suggest that the study group has clinical vascular and organ dysfunction that may both play a role in the pathogenesis of AH in the presence of COPD and prevent a high cardiovascular risk. Key words: arterial hypertension, chronic obstructive pulmonary disease.

BACKGROUND: Non-pharmacological treatments are an integral part of the treatment of all patients with type 2 diabetes (T2D). However, due to many factors, doctors and patients themselves tend to underestimate or completely neglect such effective methods in managing the course of the disease. Despite the high level of evidence of the effectiveness of this type of treatment for T2D, every year scientists around the world continue to actively study the effect of various non-drug methods on the course of the disease.AIM: To study the effect of a 24-week structured non-pharmacological treatment program on glycated hemoglobin reduction and weight loss in middle-aged patients with compensated T2D taking metformin.MATERIALS AND METHODS: A two-group, randomized, parallel-group, blinded trial was designed. Patients with an established diagnosis of T2D in the stage of compensation (HbA1c ≤7%), aged 45–59 years, taking metformin, were randomized to receive either standard non-pharmacological treatment of diabetes according to clinical protocol of T2D treatment in Kazakhstan, or an intensive course of non-pharmacological treatment according to a structured program developed by researchers. The duration of the intervention was 24 weeks. Primary outcomes were glycated hemoglobin, body weight. Secondary outcomes: blood pressure, waist circumference, insulin resistance index (HOMA-IR), lipid profile: total cholesterol, high and low density lipoproteins, triglycerides. The outcomes of the participants in both groups were assessed at baseline, 12 and 24 weeks after randomization. The study is registered with ClinicalTrials.gov NCT04632823.RESULTS: The study included 200 patients, 67 patients completed the study: intervention group n=33, control group n=34. After 24 weeks of observation, patients in the intervention group showed a significant decrease in HbA1c from 6.34% to 6.22%, p

Purpose: to study the frequency and structure of undifferentiated connective tissue dysplasia (UCTD) in school-age children with myopia, their relationship to choroidal thickness and course of myopia.Patients and methods. The object of study was 120 children (240 eyes) aged 11–13 years with school axial myopia (axial length (AL) from 24.5 to 26.0 mm). Special ophthalmological examination included optical coherent tomography of macular zone (“RTVue 100” Optovue, USA) and “Cross Line” scan for measuring choroidal thickness in foveal area and 1000 μm from it in nasal and temporal regions.Results. According to studies, the phenotypic signs of UCTD were diagnosed in 56 children (46.7%) with school myopia, the largest group included phenotypic signs of locomotor syndrome; 14 children (25%) had a weak degree of UCTD, 34 children (60.7%) — moderate degree and 8 children (14.3%) — pronounced degree. Comparative characteristic of changes in choroidal thickness detected a high degree of interrelation between the severity of clinical manifestations of UCTD and the level of decrease in blood-flow in the choroid. In children of the main group with signs of UCTD, the annual growth of AL exceeded the same parameters in children of the control group by more than 2.5 times (p < 0.05); due of accumulation of phenotypic signs of UCTD, a more noticeable tendency to decrease of choroidal thickness and the increase of AL was observed (p < 0.05). The statistical analysis confirmed the presence of significant negative correlation between the decrease in average thickness index in segment of the macular map and the degree of increase of AL (p < 0.05).Conclusions. According to results of diagnostic screening, in 46.7% children with school myopia, we detected phenotypic signs of UCTD. The method of optical coherence tomography showed that with increasing severity of UCTD, indexes of choroidal thickness in the macular zone are significant decreased. In the catamnesis (duration 1 year), it was found that in children with myopia with moderate and pronounced degrees of UCTD, increase of AL is associated with degree of thinning choroidal thickness, which indicates violations of biomechanical status of sclera.

In total, 40 patients with various stages of arterial hypertension (AH) were examined. All patients received nifedipine GITS as monotherapy or in combination with hydrochlorothiazide for 6 months. Nifedipine GITS demonstrated not only good antihypertensive activity, but also substantial organo-protective effects. Cardioprotection manifested in the reduction of left ventricular (LV) hypertrophy and LV diastolic dysfunction, as well as in correction of pathological LV geometry types. Vasoprotection was manifested in the correction of pathological microcirculation types. In addition, retinal functional status was improved.

Aim. To investigate endothelium-regulating and antioxidant effects of trandolapril and verapamil SR combination (Tarka) in patients with arterial hypertension (AH) and chronic obstructive pulmonary disease (COPD).Material and methods. In total, 42 COPD and AH patients, aged 48-70 years, were examined. All participants received continuous basis COPD treatment and 16-week Tarka therapy. At baseline and at the end of the study, lung function, systemic inflammation, oxidative stress and antioxidant potential parameters were measured.Results. All patients achieved office-measured target blood pressure (BP) levels. Bronchial conductivity increase was explained by therapy-associated improvement in pulmonary hemodynamics. The medication was safe and well-tolerated by patients with COPD and AH. Decrease in C-reactive protein levels, possibly explaining antiinflammatory medication effect, pointed to the suppression of endothelium-damaging influences. The treatment was also associated with decreased lipid peroxidation, reduced serum levels of acylhydroperoxides, and increased concentration and activity of antioxidant enzymes.Conclusion. AH and COPD therapy should include antihypertensive agents with pleiotropic effects, specifi- cally, suppressing systemic inflammation, correcting endothelial function, and enhancing antioxidant potential. These characteristics could act as additional criteria of AH treatment effectiveness in patients with combined cardiovascular and respiratory pathology.

Cell-free protein expression systems are here combined with 3D-printed structures to study the challenges and opportunities as biofabrication enters the spaces of architecture and design. Harnessing large-scale additive manufacturing of biological materials, we examined the addition of cell-free protein expression systems ("TXTL" i.e., biological transcription-translation machinery without the use of living cells) to printed structures. This allowed us to consider programmable, living-like, responsive systems for product design and indoor architectural applications. This emergent, pluripotent technology offers exciting potential in support of health, resource optimization, and reduction of energy use in the built environment, setting a new path to interactivity with mechanical, optical, and (bio) chemical properties throughout structures. We propose a roadmap towards creating healthier, functional and more durable systems by deploying a multiscale platform containing biologically-active components encapsulated within biopolymer lattices operating at three design scales: (i) supporting cell-free protein expression in a biopolymer matrix (microscale), (ii) varying material properties of porosity and strength within two-dimensional lattices to support biological and structural functions (mesoscale), and (iii) obtaining folded indoor surfaces that are structurally sound at the meter scale and biologically active (we label that regime macroscale). We embedded commercially available cell-free protein expression systems within silk fibroin and sodium alginate biopolymer matrices and used green fluorescent protein as the reporter to confirm their compatibility. We demonstrate mechanical attachment of freeze-dried bioactive pellets into printed foldable fibrous biopolymer lattices showing the first steps towards modular multiscale fabrication of large structures with biologically active zones. Our results discuss challenges to experimental setup affecting expression levels and show the potential of robust cell-free protein-expressing biosites within custom-printed structures at scales relevant to everyday consumer products and human habitats., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Ho, Kubušová, Irabien, Li, Weinstein, Chawla, Yeung, Mershin, Zolotovsky and Mogas-Soldevila.)

Objectives: The KNee OsteoArthritis Prediction (KNOAP2020) challenge was organized to objectively compare methods for the prediction of incident symptomatic radiographic knee osteoarthritis within 78 months on a test set with blinded ground truth., Design: The challenge participants were free to use any available data sources to train their models. A test set of 423 knees from the Prevention of Knee Osteoarthritis in Overweight Females (PROOF) study consisting of magnetic resonance imaging (MRI) and X-ray image data along with clinical risk factors at baseline was made available to all challenge participants. The ground truth outcomes, i.e., which knees developed incident symptomatic radiographic knee osteoarthritis (according to the combined ACR criteria) within 78 months, were not provided to the participants. To assess the performance of the submitted models, we used the area under the receiver operating characteristic curve (ROCAUC) and balanced accuracy (BACC)., Results: Seven teams submitted 23 entries in total. A majority of the algorithms were trained on data from the Osteoarthritis Initiative. The model with the highest ROCAUC (0.64 (95% confidence interval (CI): 0.57-0.70)) used deep learning to extract information from X-ray images combined with clinical variables. The model with the highest BACC (0.59 (95% CI: 0.52-0.65)) ensembled three different models that used automatically extracted X-ray and MRI features along with clinical variables., Conclusion: The KNOAP2020 challenge established a benchmark for predicting incident symptomatic radiographic knee osteoarthritis. Accurate prediction of incident symptomatic radiographic knee osteoarthritis is a complex and still unsolved problem requiring additional investigation., Competing Interests: Conflict of interest AC has provided consulting services to SkopeMR, Inc., SubtleMedical, Chondrometrics GmbH, Image Analysis Group, ICM, Culvert Engineering, and Edge Analysis; is a stockholder of Subtle Medical, LVIS Corp., and Brain Key; is on the advisory board for Chondrometrics GmbH and Brain Key; has received royalties from LVIS Corp.; and reports grant support from NIH (R01AR063643, R01AR077604, R01EB002524, R01EB026136, K24AR062068, and P41EB015891). CD reports grant support from NIHNIAMS (R01AR074453). ED is a stockholder of Biomediq A/S. MN reports honoraria for lectures from General Electric. SBZ reports personal fees from Infirst Healthcare, Pfizer, and Osteoarthritis Research Society International and grants from The Netherlands Organisation for Health Research and Development, Dutch Research Council, European Union, Foreum, and Dutch Arthritis Association outside the submitted work. None of the mentioned organizations were involved in the design, execution, data analysis, or the reporting of this study., (Copyright © 2022 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Patients with methicillin-resistant Staphylococcus aureus (MRSA) clones, which were traditionally seen in the community setting (USA400/CMRSA7 and USA300/CMRSA10), are often identified as hospital-acquired (HA) infections using Infection Prevention and Control (IPC) surveillance definitions. This study examined the demographics and healthcare risk factors of patients with HA-MRSA to help understand if community MRSA clones are from a source internal or external to the hospital setting. Despite USA300/CMRSA10 being the predominant clone in Alberta, hospital clones (USA100/CMRSA2) still dominated in the acute care setting. In the Alberta hospitalized population, patients with USA400/CMRSA7 and USA300/CMRSA10 clones were significantly younger, had fewer comorbidities, and a greater proportion had none or ambulatory care-only healthcare exposure. These findings suggest that there are two distinct populations of HA-MRSA patients, and the patients with USA400/CMRSA7 and USA300/CMRSA10 clones identified in hospital more greatly resemble patients affected by those clones in the community. It is possible that epidemiological assessment overidentifies HA acquisition of MRSA in patients unscreened for MRSA on admission to acute care.

The use of evidence has become a foundational part of health promotion practice. Although there is a general consensus that adopting an evidence-based approach is necessary for practice, disagreement remains about what types of evidence practitioners should use to guide their work. An empirical understanding of how practitioners conceptualize and use evidence has been lacking in the literature. In this article, we explore (i) practitioners' purposes for using evidence, (ii) types of evidence they valued, and (iii) qualities that made evidence useful for practice. 58 semi-structured interviews and 250 h of participant and non-participant observation were conducted with 54 health promotion practitioners working across New South Wales, Australia. Interviews were recorded and transcribed, and field notes were written during the observations; these were analysed using Grounded Theory methods. Practitioners used evidence for practical and strategic purposes, and valued four different types of evidence according to their relevance and usefulness for these purposes. Practitioners' ideal evidence was generated within their practice settings, and met both substantive and procedural evaluation criteria. We argue that due to the complex nature of their work, practitioners rely on a diverse range of evidence and require organizational structures that will support them in doing so., (© The Author 2014. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background:  The development of an inhibitor is the major complication facing patients with hemophilia A treated by administration of factor (F) VIII concentrates. Restoration of tolerance to FVIII can be achieved by prolonged administration of FVIII (immune tolerance induction, ITI). Although ITI has been used for more than 30years in patients with hemophilia A and inhibitor, its mechanism of action is still poorly understood., Objectives:  As administration of high doses of antigen can induce the apoptosis of the T cells recognizing the antigen, a potential mechanism of action of ITI may be the deletion of FVIII-specific T cells., Patients/methods:  We studied the CD4+ T-cell response to FVIII in five (one mild, one moderate and three severe) patients successfully desensitized by administration of FVIII and in control subjects., Results:  Following repeated stimulation with autologous dendritic cells loaded with FVIII, FVIII-specific T oligoclonal cell lines were expanded from the blood of one of the successfully desensitized patients. The FVIII-specific T cells produced IL-5, IL-13 and IL-2. By contrast, FVIII-specific T-cell lines could not be derived from three patients with mild hemophilia A without inhibitor or from four normal control subjects., Conclusions:  These data represent the first analysis of the cellular mechanisms regulating the induction of tolerance to FVIII. They demonstrate that successful tolerance induction may occur without deletion of FVIII-specific T cells., (© 2011 International Society on Thrombosis and Haemostasis.)

Study Design: A randomized, blinded, crossover clinical trial comparing sildenafil versus tadalafil for erectile dysfunction (ED) in male spinal cord-injured (SCI) patients., Objectives: To compare the safety, time/duration effectiveness, and the impact on the quality of life (QoL) of tadalafil 10 mg versus sildenafil 50 mg., Setting: Neurourology Section, Careggi Hospital, Florence, Italy., Methods: During a screening (visit 1), a diary card was distributed, in which the subjects assessed, after each attempt at intercourse the quality of their erection, responding (Yes/No) to both Sexual Encounter Profile Questions 2 (SEP2) and 3 (SEP3). The subjects made at least four attempts at intercourse. At visit 2, 15 patients (group 1) were assigned sildenafil and 15 (group 2) started with tadalafil. Responses to baseline International Index of Erectile Function 5 items (IIEF-5), Questions 13-14 (IIEF 15 items) and SEP diary were recorded. Patients attempted intercourse on four separate occasions: within 4 h of taking the first tablet, within 12 h for the second tablet, 24 h for the third, and the fourth from 24 to 36 h. At visit 3, the investigators evaluated the effectiveness with the same measures used at baseline. After a wash-out period, at visit 4, Group 1 was given tadalafil, and Group 2 was given sildenafil. Patients were required to observe the same criteria in taking the four tablets as in visit 2. After 4 weeks (visit 5), we evaluated the patients as we did in visit 3., Results: Overall, 28 patients completed the study. No subjects discontinued the drugs due to drawbacks. Tadalafil allowed a majority of men in this trial to achieve both normal sexual functioning up to 24 h postdosing compared to sildenafil (P<0.01) and improved overall sex life satisfaction as well as sexual relations with partner., Conclusion: Based on these data, tadalafil may have the potential to become an important treatment option for ED in SCI patients., Sponsorship: This study was not sponsored.

Ketamine, an NMDA antagonist, has been used in pain treatment for a number of years. Recent reports have suggested its utility in a variety of pain states including post-herpetic neuralgia [1], cancer [2], and postoperative pain [5]. While a variety of neuropsychologic side effects are observed with parenteral ketamine, in oral use these side effects have been less pronounced [2,3]. We report a patient with severe hepatic disease who developed hallucinations following a 75-mg oral dose of ketamine for treatment of severe cancer pain unresponsive to morphine.

The v-ets oncoprotein and its progenitor Ets1 belong to a family of transcription factors that are related by an 85 amino acid conserved DNA binding domain, the ets domain. Ets1 plays important role(s) in control of cell proliferation, differentiation and apoptosis. Abnormal expression of Ets1 could lead to disruption of these processes and contribute to development of malignancy. Retinoic acid (RA) inhibits proliferation, induces differentiation and regulates apoptosis in many different cell types. Here, we demonstrate that RA treatment increases the expression of Ets1 mRNA, but not that of Ets2, Elk1 or Fli1 in MC3T3-E1 cells. Ets1 induction is detectable after 4 h, can be maintained for at least 14 days, and is inhibited by Actinomycin D, which suggests that RA regulation of Ets1 occurs at the transcriptional level. The promoter region of Ets1 contains four retinoic acid response element (RARE) half sites located at -94, -152, -1765 and -2252 from the translation start site. We show that RARbeta is expressed by MC3T3-E1 cells in the presence of RA and demonstrate that it binds to the -94 RARE half site. Furthermore, RA induces transcription of Ets1 promoter-reporter constructs containing this RARE half site.

Insertion sites for cysteines with optimal stereochemistry for the formation of unstrained disulfide bridges were identified in recombinant human interferon-gamma (rhu-IFN-gamma) by computer modelling. We have engineered two different disulfide cross-linked mutants, containing a pair of symmetry-related disulfide bonds, which stabilize the N-termini of both monomers of the homodimeric protein. Mutations E7C and S69C allow the formation of an intramonomer disulfide bond between helices A and D. In contrast, the A17C and H111C mutations lead to a covalent cross-link between both monomers. The AB-loop is linked to helix F. The fluorescence properties of native and disulfide cross-linked proteins were studied as a function of guanidine hydrochloride concentration. Melting temperatures (Tm) were calculated from the decrease in CD ellipticity at 220 nm. The induction of the antiviral effect was measured using A549 fibroblast cells infected with encephalomyocarditis virus. The ability to induce the expression of the HLA-DR antigen in Colo 205 cells was determined by fluorescence-activated cell scanning analysis. The stability of both mutants was strongly enhanced against temperature- and cosolvent-induced unfolding. The delta Tm of mutant IFN-gamma E7C/S69C was 15 degrees C. All measured biological activities of this mutant were equal to wild type. In the case of the other mutant IFN-gamma A17C/H111C, the delta Tm value was 25 degrees C. This mutation abolishes nearly the entire biological activity (< 1%) with no detectable changes of secondary structure in the CD spectrum. Our results illustrate the importance of the N-terminal helix A and the AB-loop for the unfolding pathway and thermodynamic stability of rhu-IFN-gamma.

Cultures of human epidermal cells may be used to generate epidermis on athymic recipients. We describe two novel techniques for grafting such cultures. Both techniques permit the generation of typical human epidermis within 7 d. Both techniques result in less graft contraction than conventional grafting, and there is no difficulty in distinguishing the human epidermis generated by the graft from the epidermis of the recipient animal. Starting with a single human biopsy, epidermis may be generated on a great many experimental animals; such grafts should therefore provide uniform material for investigation of the properties of human epidermis.

Urea formaldehyde foam insulation in homes has caused increasing concerns about the adverse health effects associated with residential exposure to formaldehyde emissions. These health effects cover a broad spectrum of symptoms, including neurophysiological effects, respiratory irritations, and eye and skin irritations. Recent studies have also suggested a possible correlation between exposure to formaldehyde vapors and cancer. In 1979, following hundreds of complaints of adverse health effects from occupants of dwellings insulated with urea formaldehyde foam insulation (UFFI), the Massachusetts Department of Public Health issued regulations banning the new installation of UFFI in Massachusetts. New State legislation was adopted in 1986 which reformulated UFFI policy. The law established a minimum concentration of formaldehyde of 0.1 parts per million (ppm) below which removal of the insulation is not required or encouraged. A trust fund financed by industry was established to pay for air testing and for the removal of UFFI from homes if the formaldehyde level exceeds the statutory minimum of 0.1 ppm or if an occupant experiences adverse health effects attributable to the insulation. Based on the Massachusetts experience, these requirements have been identified: the need for flexibility and midcourse corrections in the development of health policy to allow for the incorporation of new scientific information or changes in the economic or political environment, the need for close coordination with all affected parties, and the need for scientific and technical policy development to be joined with economic and political perspectives to ensure smooth implementation of health policies.