A target site for template-based design of measles virus entry inhibitors

Measles virus (MV) constitutes a principal cause of worldwide mortality, accounting for almost 1 million deaths annually. Although a live-attenuated vaccine protects against MV, vaccination efficiency of young infants is low because of interference by maternal antibodies. Parental concerns about vaccination safety further contribute to waning herd immunity in developed countries, resulting in recent MV outbreaks. The development of novel antivirals that close the vaccination gap in infants and silence viral outbreaks is thus highly desirable. We previously identified a microdomain in the MV fusion protein (F protein) that is structurally conserved in the paramyxovirus family and constitutes a promising target site for rationally designed antivirals. Here we report the template-based development of a small-molecule MV inhibitor, providing proof-of-concept for our approach. This lead compound specifically inhibits fusion and spread of live MV and MV glycoprotein-induced membrane fusion. The inhibitor induces negligible cytotoxicity and does not interfere with receptor binding or F protein biosynthesis or transport but prevents F protein-induced lipid mixing. Mutations in the postulated target site alter viral sensitivity to inhibition. In silico docking of the compound in this microdomain suggests a binding model that is experimentally corroborated by a structure-activity analysis of the compound and the inhibition profile of mutated F proteins. A second-generation compound designed on the basis of the interaction model shows a 200-fold increase in antiviral activity, creating the basis for novel MV therapeutics. This template-based design approach for MV may be applicable to other clinically relevant members of the paramyxovirus family.     

Wide QRS Complex and Lateral ST-T Segment Abnormality Are Associated With Worse Clinical Outcomes in COVID-19 Patients

BackgroundThe information on electrocardiographic features of patients with coronavirus disease 2019 (COVID-19) is limited. Our aim was to determine if baseline electrocardiographic features of hospitalized COVID-19 patients are associated with markers of myocardial injury and clinical outcomes.MethodsIn this retrospective, single center cohort study, we included 223 hospitalized patients with laboratory-confirmed COVID-19. Clinical, electrocardiographic and laboratory data were collected and analyzed. Primary composite endpoint of mortality, need for invasive mechanical ventilation, or admission to the intensive care unit was assessed.ResultsForty patients (17.9%) reached the primary composite endpoint. Patients with the primary composite endpoint were more likely to have wide QRS complex (>120 ms) and lateral ST-T segment abnormality. The multivariable Cox regression showed increasing odds of the primary composite endpoint associated with acute respiratory distress syndrome (odds ratio 7.76, 95% CI 2.67–22.59; p < 0.001), acute cardiac injury (odds ratio 3.14, 95% CI 1.26–7.99; p = 0.016), high flow oxygen therapy (odds ratio 2.43, 95% CI 1.05–5.62; p = 0.037) and QRS duration longer than >120 ms (odds ratio 3.62, 95% CI 1.39–9.380; p = 0.008) Patients with a wide QRS complex (>120 ms) had significantly higher median level of troponin T and pro-BNP than those without it. Patients with abnormality of lateral ST-T segment had significantly higher median level of troponin T and pro-BNP than patients without.ConclusionsThe presence of QRS duration longer than 120 ms and lateral ST-T segment abnormality were associated with worse clinical outcomes and higher levels of myocardial injury biomarkers.     

Aortic Intima-Media Thickness and Mean Platelet Volume in Children With Type 1 Diabetes Mellitus

Background:

Diabetes mellitus type 1 is the most common endocrine metabolic disorder occurring in childhood and adolescence due to the autoimmune destruction of pancreatic beta cells as a result of various environmental factors interacting with an underlying genetic predisposition. Diabetes is a risk factor for early onset atherosclerosis, and the high mortality rate seen in these patients is partially related to cardiovascular diseases.

Objectives:

This study was conducted to compare mean platelet volume as a marker of early atherosclerosis with aortic intima-media thickness in children with type 1 diabetes and to identify its correlation with known cardiovascular risk factors.

Patients and Methods:

The study included 27 patients between age range of 6 and 17 years that were diagnosed with type 1 diabetes and 30 healthy children of the same age range who did not have any chronic disease. In both groups, we used the color Doppler ultrasound to measure children’s aortic intima-media thickness and identify their mean platelet volumes.

Results:

There was no significant difference between the groups regarding gender distribution, age, High-Density Lipoprotein (HDL) and Low-Density Lipoprotein (LDL) cholesterol levels (P > 0.05). Also no significant difference could be documented between the patient and control groups regarding the aortic intima-media thickness and mean platelet volume (P > 0.05). However, there was a significant correlation between aortic intima-media thickness and mean platelet volume (r = 0.351; P < 0.05).

Conclusions:

In the present study, there was no evidence of early atherosclerosis in children with type 1 diabetes. However, mean platelet volume having a significant correlation with aortic intima-media thickness may be useful as an early marker of atherosclerosis.     

Emotional intelligence and leadership traits among family physicians

Objectives: High emotional intelligence and leadership traits are essential for physicians in managing their responsibilities and thus building successful interactions with patients. This study explored the relationship between emotional intelligence and leadership traits among family physicians.

Methods: Participants (2975 men, 972 women, mean = 42.0 ages, SD = 7.47) were family physicians working at family health-care centers across the seven geographical regions of Turkey who were contacted by e-mail. The Trait Emotional Intelligence Questionnaire (TEIQue) and Leadership Traits Tool were used to collect data. Data were analyzed concerning physicians’ sex, age, health-care experience, and geographical region. The correlation between Trait Emotional Intelligence (TEI) and leadership was also being examined.

Results: Our findings suggest that family physicians’ TEI differs based on sex, age, health-care experience, and the geographical region where they work. Women had higher mean values than did men for well-being, emotionality, and global TEI. Physicians aged younger than 29 years had the lowest mean values for emotional intelligence. As physicians’ health-care experience increased, they received higher scores for emotional intelligence. Physicians working in the Mediterranean had the highest mean TEI scores. There was a positive correlation between family physicians’ emotional intelligence and leadership traits. Higher emotional intelligence was correlated with increased leadership traits.

Conclusion: Emotional intelligence and leadership traits play crucial roles in increasing physicians’ personal and professional development. This may also increase physicians’ caregiving competencies and thus the quality of health services, as well as potentially decreasing physicians’ burnout and health-related costs.     

Efficacy of high intensity laser therapy in knee osteoarthritis: a double-blind controlled randomized study

Clinical Rheumatology - The aim of this study is to investigate the effectiveness of high intensity laser therapy on pain, functionality, flexion range of motion (FROM), and ultrasonographic...     

Total oxidative/anti-oxidative status and relation to bone mineral density in osteoporosis

The aim of this study was to evaluate the total antioxidant status (TAS), total oxidative status (TOS) and oxidative stress index (OSI) in patients with postmenopausal osteoporosis. We also investigate the relation between bone mineral density and oxidative/antioxidative parameters. Thirty-nine patients with osteoporosis and 26 healthy controls were included in the study. Plasma TAS, TOS levels were determined by using a novel automated methods. Plasma TOS and OSI value were significantly higher, and plasma TAS level was lower in patients than in healthy controls (P < 0.001 for all). There was a significant negative correlation between OSI and BMD in lumbar and femoral neck region (r = −0.63, P < 0.001; r = 0.40, P = 0.018). The results of this study indicated that increased osteoclastic activity and decreased osteoblastic activity may be associated with an imbalance between oxidant and antioxidant status in postmenopausal osteoporosis. Therefore, supplementation of antioxidant-enriched diet to the therapy might shed light on the development of novel therapeutic strategies for osteoporosis.     

Aneurysm of the membranous ventricular septum. Apropos of 4 cases surgically treated

Four patients with aneurysms of the membranous ventricular septum were operated either because of complications or for associated malformations. The authors describe the anatomical, radiological and, above all, the echocardiographic and angiographic features of this malformation. Surgical management is necessary in complicated cases or when there are associated congenital malformations. The information provided by echocardiography in the diagnosis and follow-up of ventricular septal defects indicates that this malformation is not as rare as was previously thought.     

Aortic valve replacement in patients over 80 years of age. Short- and medium-term results in 140 patients

One hundred and forty aortic valve replacements (AVR) performed between 1986 and 1995 at Rouen University Hospital in octogenarians (52 men and 88 women), including 9 emergency procedures, were analysed. One hundred and fifteen patients had pure aortic stenosis, 25 had mixed aortic valve disease with mainly aortic incompetence. The surgical decision was taken by the patient with the surgeon after an interview, in order to exclude too handicapped or undecided patients. Significant coronary artery disease was observed in 42% of cases. Isolated AVR was undertaken in 74% of cases and associated coronary bypass surgery in 23% of cases. Bioprostheses were used in 90% of cases. The valvular lesions were predominantly those of Monckeberg disease. The operative mortality was of 13 patients (9.3%). Functional recovery was satisfactory in 78% of cases; the average duration of the hospital stay was 12 days. All known risk factors for AVR: age, coronary lesions, cardiac failure, low ejection fraction, aortic regurgitation, were associated with insignificant increases in mortality. The secondary mortality was of 28 patients; 99 patients are still alive 4 to 91 months after surgery. The actuarial survival graph showed a 56.5% probability of 5 year survival. Eighty per cent of survivors live at home without loss of autonomy.     

Effectiveness of gemcitabine as second-line chemotherapy in non-small cell lung cancer

The role of a second-line chemotherapy after an initial treatment with a platinum-based regimen remains largely undefined. In this retrospective clinical effectiveness study, gemcitabine as monotherapy was evaluated in the second-line chemotherapy in 34 non-small cell lung cancer (NSCLC) cases that had been previously received chemotherapy and did not respond to the treatment or presented with relapses. Gemcitabine was given intravenous at a dose of 1250 mg/m2 on days one, eight every three weeks. Median age was 50 years and squamous cell carcinoma was the most common malignancy (44.1%). No patient had a complete response, 7 (20.6%) patients had a partial response. The median survival was 29 weeks. The 1-year survival probability was estimated at 26.5%. Median time to disease progression was 13 weeks. Gemcitabine was well tolerated in this patient population. Among totally 119 chemotherapy cycles, we observed grade 3 and 4 toxicities only in 2.5% of cycles. As a result of the study, single agent gemcitabine is found to be tolerable and to have moderate effectiveness in the second-line chemotherapy in NSCLC. It should be placed among treatment options.