Khalid Alahmari

Biological evaluation of 2-arylidene-4, 7-dimethyl indan-1-one (FXY-1): a novel Akt inhibitor with potent activity in lung cancer

AbstractPurpose Human lung cancer is contributed to be a major mortality factor in the cancer-related deaths. Arylidene indan-ones constitute a new class of potential anti-tumor compounds. Herein, we report the biological efficacy of the 2-arylidene-4, 7-dimethyl indan-1-one (FXY-1), a potential lead molecule of arylidene indan-ones in lung cancer models. We previously described anticancer activity of FXY-1 against human breast adenocarcinoma.MethodsFXY-1 efficacy was assessed by standard anticancer screening in NCI-H 460, A549, NCI-H 1975 and NCI-H 2170 cells. Initial molecular docking analysis was performed to check the interaction of compound to Akt enzyme. Anti-proliferation, anti-metastatic and transendothelial cell migration were performed to check efficacy of the drug. Western blot analysis was performed to understand the regulation of pro-apoptotic and anti-apoptotic proteins by the compound. The effect of FXY-1 on caspase induction and Akt phosphorylation were checked using Western blot analysis. Flow cytometry was used to reveal the cell cycle changes and apoptosis-inducing properties of FXY-1 in the lung cancer cells. In-vitro Akt inhibition property of the compound was studied using a fluorescence-based, coupled-enzyme reaction. The in-vivo efficacy of the compound was determined using a mouse xenograft model.ResultsOur molecular docking analysis reveals higher interaction of FXY-1 with Akt. FXY-1 depicted anti-proliferative and pro-apoptotic activity with higher therapeutic window in-vitro in NCI-H 460 and A549 cells. The compound treatment to lung cancer cells resulted in induction of DNA fragmentation, inhibition of transendothelial migration, caspase activation and poly (ADP-ribose) polymerase (PARP) cleavage. FXY-1 treatment resulted in G0/G1 arrest in both cell lines at lower concentrations, but led to apoptosis at higher doses. Western blot analysis revealed dephosphorylation of Akt (Ser 473) with activation of p53, Bax, Bak, Bid and reduction in Bcl-2 and Bcl-xL levels. Further mechanistic investigation showed that FXY-1 activity was facilitated through an allosteric inhibition of Akt enzyme. FXY-1 treatment significantly reduced the tumor growth and pAkt levels in mouse xenograft exhibiting the in-vivo efficacy in the compound.ConclusionCollectively, our results suggest DNA damage-mediated activation by FXY-1 in lung cancer cells leading to extensive apoptosis through the mitochondrial pathway.

Intra- and inter-rater reliability of neutral head position and target head position tests in patients with and without neck pain

Highlights • Neutral head and target head position tests evaluate cervical proprioception.• Clinics commonly use those position tests, and it is important to test their reliability.• Intra- and inter-rater reliability was moderate to high for these tests.

Hand grip strength determination for healthy males in Saudi Arabia: A study of the relationship with age, body mass index, hand length and forearm circumference using a hand-held dynamometer

Objectives To determine whether age, body mass index (BMI), hand length and forearm circumference were predictive of hand grip strength in healthy Saudi Arabian adult males. Methods This cross-sectional descriptive study recruited healthy adult male volunteers. Their anthropometric characteristics including age, BMI, hand length and forearm circumference were measured using routine techniques. Hand grip strength was assessed using a Jamar® Hydraulic Hand Dynamometer. The data were analysed using Pearson correlation coefficient (r) as well as by a stepwise multiple linear regression analysis. Results The study included 116 healthy males who satisfied the inclusion criteria. A Pearson correlation coefficient matrix demonstrated that all the four measures, age, BMI, hand length and forearm circumference, were significantly correlated with hand grip strength. Age had an inverse correlation with hand grip strength. The anthropometric measures of hand length, age and forearm circumference accounted for 44.2% (R2 0.442) of the variation of the hand grip strength. Conclusion Hand length, age and forearm circumference significantly impacted on hand grip strength in Saudi Arabian healthy adult males.

Influence of chronic neck pain on cervical joint position error (JPE): Comparison between young and elderly subjects

BACKGROUND Evaluation of cervical joint position sense in subjects with chronic neck pain has gained importance in recent times. Different authors have established increased joint position error (JPE) in subjects with acute neck pain. However, there is a paucity of studies to establish the influence of chronic neck pain on cervical JPE. OBJECTIVE The objective of the study was to understand the influence of chronic neck pain on cervical JPE, and to examine the differences in cervical JPE between young and elderly subjects with chronic neck pain. METHODS Forty-two chronic neck pain patients (mean age 47.4) were compared for cervical JPE with 42 age-matched healthy subjects (mean age 47.8), using a digital inclinometer. The cervical JPE were measured in flexion, extension, and rotation in right and left movement directions. RESULTS The comparison of JPE showed significantly larger errors in subjects with chronic neck pain when compared to healthy subjects (p< 0.001). The errors were larger in all of the movement directions tested. Comparison between young and older subjects with chronic neck pain revealed no significant differences (P> 0.05) in cervical JPE. CONCLUSIONS Cervical joint position sense is impaired in subjects with chronic neck pain.

Determining the reliability of craniocervical flexion test in asymptomatic individuals

Background: The inter-rater reliability of the craniocervical flexion test (CCFT) has not been established. Objective: To investigate the intra-rater and inter-rater reliabilities of the CCFT in asymptomatic subjects. Methods: Sixty asymptomatic subjects were randomly selected for the study. The CCFT was measured on each subject by two testers for inter-rater reliability and by one of the testers after a gap of seven days for the intra-rater reliability. Before testing, the participants were trained for the movement and compensations were corrected. Results: The CCFT has high inter-rater reliability (intra-class correlation coefficient = 0.907, standard error of mean = 0.735) and high intra-rater reliability (intra-class correlation coefficient = 0.986, standard error of mean = 0.287). A Bland & Altman limits of agreement analysis has confirmed the high inter- and intra-rater reliabilities of the test. Conclusion: The CCFT has high inter-rater and intra-rater reliabilities in asymptomatic subjects.

Mediating role of body mass index in knee osteoarthritis

Objective This study explores the role of knee circumference, body mass index (BMI), and range of motion (ROM) in predicting knee osteoarthritis (KOA). The objective is to elucidate the mediating role of BMI in influencing the relationship between age, knee circumference and pain in knee osteoarthritis, as measured with the help of the knee outcome survey (KOS) questionnaire. Methods The design used in this study was causal comparative. The study consisted of 66 patients with symptomatic KOA and 60 matched asymptomatic individuals. Result BMI was significantly and positively correlated with both pain and knee girth for the symptomatic KOA group. This finding signifies a relationship between KOA and other indicators, such as age and knee circumference. Conclusions The results of the study would indicate an important milestone in clinical rehabilitation, especially for physical therapists, enabling them to plan, modify, and design interventions to improve the health status of KOA patients.

Association of age on cervical joint position error

Graphical abstract

MSD's in industry - a careful examination of the predictors using MANOVA

Among computer operators, risk factors associated with work-related musculo-skeletal disorders, include the integration of biomechanical factors, work environment and issues related to the working organisation, as well as those associated with the psychosocial aspects of work. With more and more jobs available in software industry today, it is all the more important to be aware of the problems and follow necessary preventive steps to check the progression of computer related health problems. Musculoskeletal disorders (MSD) such as neck and low back pain have been widely reported as being of significant health and economic concern due to increased globalisation and industrial advancements. The debilitating effects of MSD are widely acknowledged by researchers in the medical field as well as in the engineering field. This research has provided empirical result to establish the curative along with preventive effects of physiotherapy in combating MSD present in todays Indian software industry.

Utilitarian dimensions and behavioural inconsistencies of young fanatic mobile phone users - a study on Indian perspectives

Mobile phones have turned out to be indispensable in todays society and are regarded as a communication technology revolution. Many psychologists have started giving warnings about the ill effects of these technologies and studies are also pointing towards potential addictive behaviour towards use of mobile phones. This study tries to find out the role of excessive mobile phone usage in the m-health of users. The paper tries to unravel that there is a need to shift focus from m-health to m-p-health, mobile psychological health. The study looks at whether excessive mobile phone usage falls under the category of non-drug addiction and also tries to identify the product attributes and services perception of mobile phone usage and behaviour dysfunctionalities. The study also tries to analyse whether there is gender influences on the behavioural dimensions of fanatic mobile phone users.

Effectiveness of pulsed ultrasound and cryotherapy on delayed onset muscle soreness

Purpose of the Study: Delayed onset muscle soreness (DOMS) is defined as the sensation of discomfort or pain in the skeletal muscles following physical activity, usually eccentric, to which an individual is not accustomed. DOMS begins usually 8-24 h after exercise in which pain, soreness, swelling, and stiffness and muscle spasm and peaks after 24-72 h. Cryotherapy and pulsed ultrasound were common modalities used to treat the DOMS effectively. Hence, this study is intended to compare the effect of these modalities on DOMS. Materials and Methods: Normal healthy individuals (n = 32) of age group between 18 and 30 years was selected randomly and divided into two groups. Group A received pulsed ultrasound therapy and Group B received cryotherapy. The total duration of the study was three sessions for 3 consecutive days. Measurements are taken initially before receiving the interventions and at the end of every treatment session by using universal goniometer for measurement of range of motion (ROM) and visual analog scale for pain. Data thus collected were analyzed and recorded for the study. Results: Mean ROM in Group A who received pulsed ultrasound is 143.42 and Group B who received cryotherapy is 140.12 and showed that there is an induction of DOMS. When comparison of pulsed ultrasound over cryotherapy shown a significant P < 0.05. Conclusion: Both pulsed ultrasound and cryotherapy are almost equal with each other up to a period of 48 h. However, pulsed ultrasound has an additional effect of increasing the ROM on day 3 onward when compared to cryotherapy.