Inhibition of JNK Alleviates Chronic Hypoperfusion-Related Ischemia Induces Oxidative Stress and Brain Degeneration via Nrf2/HO-1 and NF-κB Signaling.

Cerebral ischemia is one of the leading causes of neurological disorders. The exact molecular mechanism related to chronic unilateral cerebral ischemia-induced neurodegeneration and memory deficit has not been precisely elucidated. In this study, we examined the effect of chronic ischemia on the induction of oxidative stress and c-Jun N-terminal kinase-associated detrimental effects and unveiled the inhibitory effect of specific JNK inhibitor (SP600125) on JNK-mediated brain degeneration in adult mice. Our behavioral, biochemical, and immunofluorescence studies revealed that chronic ischemic injuries sustained increased levels of oxidative stress-induced active JNK for a long time, whereas SP600125 significantly reduced the elevated level of active JNK and further regulated Nrf2/HO-1 and NF-κB signaling, which have been confirmed in vivo. Neuroinflammatory mediators and loss of neuronal cells was significantly reduced with the administration of SP600125. Ischemic brain injury caused synaptic dysfunction and memory impairment in mice. However, these were significantly improved with SP600125. On the whole, these findings suggest that elevated ROS-mediated JNK is a key mediator in chronic ischemic conditions and has a crucial role in neuroinflammation, neurodegeneration, and memory dysfunction. Our findings suggest that chronic oxidative stress associated JNK would be a potential target in time-dependent studies of chronic ischemic conditions induced brain degeneration.

Chronic Kidney Disease-Associated Pruritus and Quality of Life in Malaysian Patients Undergoing Hemodialysis.

CKD-associated pruritus is one of the common symptoms in patients undergoing dialysis, thus contributing to the diminished and compromised quality of life. This study aimed to explore the association between the CKD-associated pruritus on quality of life of patients undergoing hemodialysis in Malaysia. A cross-sectional multicenter study, carried out from February to September 2017 at tertiary care settings in Kuala Lumpur, Malaysia. Patients aged 18 years and above, undergoing hemodialysis, understanding Malay language and willing to participate were included. The CKD-associated pruritus was assessed by using Malay 5D-itch scale and Malay FANLTC questionaiare. To determine the factors associated with pruritus and quality of life, multivariate logistic regression analysis was used having P value < 0.05 as statistically significant. Among n = 334 recruited patients with a response rate of 100%, 59.6% were males and total of 61.3% were having CKD-associated pruritus. The results showed a statistically significant weak negative correlation between CKD-associated pruritus and quality of life. Multivariate linear regression revealed none of these factors were found to be associated with pruritus; however, CKD-associated prurtius was found to be associated with quality of life score. CKD-associated pruritus is have a negative impact on the patient's quality of life including physical, social, mental/emotional, and functional well-being. Despite the high prevalence and negative impact of CKD-associated pruritus on quality of life, it is disregarded by most health care professionals. It is thus pertinent to monitor the potential risk factors and consider providing timely treatment implications for CKD-associated pruritus in hemodialysis patients, in order to improve their quality of life.

Factor Structure of Urdu Version of the Flourishing Scale.

Background: A great deal of research has been carried out on the assessment of the eudaimonic perspective of psychological well-being and the hedonic perspective of subjective well-being. The Flourishing Scale (FS) has been extensively used in research and practice, as it assesses the fundamental aspects of social psychological functioning. Nevertheless, the psychometric properties of Urdu versions of eudaimonic measures, such as the FS, have not yet been ascertained. The translation and validation of the FS in the Urdu language was not available, and hence this study was planned with the aim to validate the Urdu version of the FS. Methods: We assessed the psychometric properties of the FS in a sample of adults aged 18 years and above in Pakistan (N = 130) using exploratory factor analysis based on principal component analysis with varimax rotation and confirmatory factor analysis. Results: The exploratory factor analysis confirmed the unidimensional nature of the 8-item FS. We assessed that the Urdu version of the FS showed a high internal consistency reliability (α = 0.914) with a significant intraclass correlation coefficient (ICC), p < 0.001). In our study, the Kaiser-Mayer-Olkin value was 0.915 with a chi-square test value (χ2) of 637.687, and Bartlett's test of sphericity was significant (df = 28, p < 0.001). The intraclass correlation coefficients (ICCs) at test-retest for all domains were statistically significant (p < 0.001) and showed excellent agreement for all the items. The revised confirmatory factor analysis revealed a good-fit model, but with item 8-"People respect me"-removed due to its lower factor loading. Conclusions: The findings suggest that the FS is a psychometrically sound instrument for assessing social psychological functioning among adults in Pakistan. Therefore, the validated Urdu version of the FS may be used in future studies of well-being in clinical psychology and positive psychology.

Knowledge, Attitude, Awareness, and Barriers Toward Influenza Vaccination Among Medical Doctors at Tertiary Care Health Settings in Peshawar, Pakistan-A Cross-Sectional Study.

Objective: This study intends to evaluate the knowledge, attitude and awareness of medical doctors toward influenza vaccination and the reasons for not getting vaccinated. Methods: A cross-sectional study was carried out among medical doctors in three major tertiary care health settings in Peshawar, Khyber Pakhtunkhwa (KP), Pakistan. A web-based, pre-tested questionnaire was used for data collection. Results: A total of (n = 300) medical doctors were invited, however only (n = 215) participated in the study with a response rate of 71.7%. Among the participants, 95.3% (n = 205) were males with a mean age of 28.67 ± 3.89 years. By designation, 121(56.3%) were trainee medical officers and 40 (18.6%) were house officers. The majority 102(47.4%) had a job experience of 1-2 years. Of the total sample, 38 (17.7%) doctors reported having received some kind of vaccination, whereas only 19 (8.84%) were vaccinated against influenza. The results identified that the major barriers toward influenza vaccinations included (1) Unfamiliarity with Influenza vaccination availability (Relative Importance Index RII = 0.830), (2) Unavailability of Influenza vaccines due to lack of proper storage area in the institution (RII = 0.634), (3) Cost of vaccine (RII = 0.608), and (4) insufficient staff to administer vaccine (RII = 0.589). Additionally, 156 (72.6%) of doctors were not aware of the influenza immunization recommendation and guidelines published by the Advisory Committee on Immunization Practices (ACIP) and Centre for Disease Control and Prevention (CDC). Physicians obtained a high score (8.27 ± 1.61) of knowledge and understanding regarding influenza and its vaccination followed by medical officers (8.06 ± 1.37). Linear Regression analysis revealed that gender was significantly associated with the knowledge score with males having a higher score (8.0± 1.39) than females (6.80 ± 1.61 ß = -1.254 and CI [-2.152 to -0.355], p = 0.006). Conclusion: A very low proportion of doctors were vaccinated against influenza, despite the published guidelines and recommendations. Strategies that address multiple aspects like increasing awareness and the importance of the influenza vaccine, the international recommendations and enhancing access and availability of the vaccine are needed to improve its coverage and health outcomes.