Med. Sci., Volume 7, Issue 6 (June 2019) – 7 articles

Tetherin, an interferon-induced host protein encoded by the bone marrow stromal antigen 2 (BST2/CD317/HM1.24) gene, is involved in obstructing the release of many retroviruses and other enveloped viruses by cross-linking the budding virus particles to the cell surface. This activity is antagonized in the case of human immunodeficiency virus (HIV)-1 wherein its accessory protein Viral Protein U (Vpu) interacts with tetherin, causing its downregulation from the cell surface. Vpu and tetherin connect through their transmembrane (TM) domains, culminating into events leading to tetherin degradation by recruitment of β-TrCP2. However, mutations in the TM domains of both proteins are reported to act as a resistance mechanism to Vpu countermeasure impacting tetherin’s sensitivity towards Vpu but retaining its antiviral activity. Our study illustrates the binding aspects of blood-derived, brain-derived, and consensus HIV-1 Vpu with tetherin through protein–protein docking. The analysis of the bound complexes confirms the blood-derived Vpu–tetherin complex to have the best binding affinity as compared to other two. The mutations in tetherin and Vpu are devised computationally and are subjected to protein–protein interactions. The complexes are tested for their binding affinities, residue connections, hydrophobic forces, and, finally, the effect of mutation on their interactions. The single point mutations in tetherin at positions L23Y, L24T, and P40T, and triple mutations at {L22S, F44Y, L37I} and {L23T, L37T, T45I}, while single point mutations in Vpu at positions A19H and W23Y and triplet of mutations at {V10K, A11L, A19T}, {V14T, I18T, I26S}, and {A11T, V14L, A15T} have revealed no polar contacts with minimal hydrophobic interactions between Vpu and tetherin, resulting in reduced binding affinity. Additionally, we have explored the aggregation potential of tetherin and its association with the brain-derived Vpu protein. This work is a possible step toward an understanding of Vpu–tetherin interactions. Full article

Cryosurgery used on patients with unresectable pancreatic cancer improved their quality of life, but mainly because of the pain relief. In postoperative patients, multifaceted changes in immunity were found, and the state of the immune system prior to surgery often was a decisive factor to indicate whether further disorders in the postoperative period would develop, or by contrast, it would boost its recovery. Some patients receiving cryosurgery showed immune system imbalance and activation, and of antitumor immunity in particular. It has been suggested that the advisability of immunotropic therapy for specific treatment algorithms should be predicted or the therapy should be suspended at some pathologic stage, and this has been immunologically confirmed. Cryosurgery should be considered as a reasonable alternative to the existing types of surgery for pancreatic cancer or as an essential component of multimodal therapy, consisting of topical cryosurgery, chemotherapy, and immunotropic therapy, to boost antitumor immunity and to discontinue cytoreductive therapy due to its toxic effects. Full article

Clinical trials have shown the benefits of β-blockers therapy in patients with heart failure reduced ejection fraction. These benefits include improved survival and a reduced need for hospitalization. Cardiac resynchronization therapy has emerged as an essential device-based therapy for symptomatic patients with heart failure reduced ejection fraction despite optimal pharmacologic treatment. The extent to which β-blockers are being utilized in patients receiving cardiac resynchronization therapy is not well known. In this study, we evaluate the possibility of increasing β-blockers doses in an unselected cohort of heart failure reduced ejection patients after cardiac resynchronization therapy capable defibrillator system implantation and the correlation between β-blockers treatments and clinical outcome. Methods and results: Patients with heart failure reduced ejection fraction in β-blockers therapy that underwent cardiac resynchronization therapy capable defibrillator system implantation between July 2008, and December 2016 were enrolled in the study. The β-blockers dose was determined at the time of discharge and during follow-up. Cardiovascular mortality, hospitalization for worsening heart failure or arrhythmic storm and appropriate intervention of the device, were recorded. The study cohort included 480 patients, 289 patients (60.3%) had β-blockers doses equal to the dose before CRT (Group 1), 191 patients (39.7%) had higher β-blockers doses than those before the CRT implant (Group 2). Comparing the two groups, Group 2 have lower cardiovascular mortality, heart failure-related hospitalization, and arrhythmic events than Group 1. Conclusion: After initiating CRT, β-blockers could be safely up-titrated at higher doses with the reduction in mortality, heart failure-related hospitalization, and arrhythmic events. Full article

Background: Insomnia seems to be related to disability, risk of injury, metabolic syndrome, risk for cardiovascular diseases, cognitive impairment, depression and impaired quality of life. Objectives: The goals in this paper was (1) to keep track of technological concepts and approaches to improve insomnia in elderly people, and (2) to define the effect that information and communication technologies (ICT) is having on patients’ care. Design: A systematic review was conducted from existing literature. Our selection criteria included: (1) age ≥ 60 years; (2) diagnosis of insomnia with the International Classification of Sleep Disorders (ICSD-II), (3) CBTi (cognitive behavioural therapy insomnia), (4) use of technological tools, and (5) associations between insomnia-related variables and indices of disability, quality of life, and global clinical assessments. Data analysis: 11 articles were included. An inductive content analysis was used for data extraction. Results: Our review revealed any technological systems that could purportedly rehabilitate elderly patients with insomnia. Three categories of research were identified from the review: (1) Internet Deliver-CBTi, (2) virtual coaches, and (3) sleep technologies. Conclusions: The potential for ICT to support insomnia care at home can improve the quality of life for families and reduce health care costs and premature institutional care. Full article

The aim of this study was to determine a cost-effective diagnostic method for lumbar herniated disc with knee osteoarthritis (LHD-KOA) based on aberrant outcome measures, levels of biomarkers, and examination of the lower-extremity. Data were separately analyzed for each cohort suffering with LHD-KOA (n = 108; 59.82 ± 7.15 years) and without LHD-KOA (n = 108; 58.81 ± 7.61 years), and findings were confirmed with radiological images. The aberrant-leg-features (bilateral: knee gaps between the short head of biceps femoris and the surface of the bed, diameters of calves and thighs, angles of straight leg raising, knee-flexion and -extension in a supine position) and biochemical parameters (Interleukin-10, Tumor necrosis factor-alpha, C-reactive protein, creatine kinase-muscle, and Aldolase-A), and outcome measures, Western Ontario and McMaster Universities osteoarthritis index (WOMAC), knee-injury osteoarthritis outcomes scale (KOOS), Oswestry disability index (ODI), and body mass index (BMI)for participants with and without LHD-KOA were evaluated with appropriate techniques. All the subjects underwent standardized physical examination and completed a questionnaire. The risk ratios and mean ± standard deviations of biomarkers, anatomical features, and outcome measures of the experimental subjects were highly significant compared to controls (p < 0.0001). Results suggest that monitoring the studied aberrant outcome measures, biomarkers, and lower-anatomical features may be a cost-effective diagnostic tool for LHD-KOA. Further research is recommended for an alternative treatment protocol for LHD-KOA. Full article

Objective: The aim of this study was to assess the reach, acceptability, utility, and engagement with the apps that were used in the MEDication reminder APPlications (apps) to improve medication adherence in Coronary Heart Disease (MedApp-CHD) study, a randomised clinical trial to improve medication adherence, using a mixed-methods approach. Methods: The MedApp-CHD study randomised 163 patients with coronary heart disease (CHD) to one of three groups: (i) usual care (n = 56), (ii) a basic medication reminder app (n = 54), or (iii) an advanced medication reminder app (n = 53). For this mixed-methods evaluation, the data sources included patient screening logs, feedback questionnaires collected at three-month follow-up, focus groups discussions, and analytical data from the app software. Results: Ninety-four percent (98/104) of participants who received a medication reminder app completed the three-month feedback questionnaire and 15 participated in the focus group discussions. The themes that were identified included that participants (i) found the medication reminders useful in reminding them to take the medications on the correct time every day, (ii) liked having the medication list as an easily-accessible record of medications’ names and dosages, (iii) reported being likely to continue to use the apps after the study completion, (iv) would be likely to recommend the apps to their family and friends, and (v) those who used the clinical measurements feature found it useful as a tool to track and graph the blood pressure and glucose levels over time (especially those with diabetes and/or hypertension). In addition, analytical data from the app software demonstrated that the participants used the medication-related features more than the clinical measurements feature. Furthermore, data from the patient screening logs showed that the main reason for exclusion, other than not meeting the CHD criteria, was not having a suitable smartphone, and those that were excluded for this reason were older and had a higher proportion of females than those enrolled in the study. Conclusion: This study provides important insights regarding the features that are most useful in apps that aim to improve medication adherence. This mixed-methods evaluation suggests that, currently, young male patients with CHD are more likely to use such apps, that the apps were well-accepted and useful in reminding the patients to take the medications, and that the patients were engaged in regularly using the apps. Full article