Browsing by Author "Khan, S."

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Deciphering the enigmatic crosstalk between prostate cancer and Alzheimer's disease: A current update on molecular mechanisms and combination therapy
(Elsevier, 2022) Poddar, N.K.; Agrawal, D.; Agrawal, Y.; Wijayasinghe, Y.S.; Mukherjee, A.; Khan, S.
Alzheimer's disease (AD) and prostate cancer (PCa) are considered the leading causes of death in elderly people worldwide. Although both these diseases have striking differences in their pathologies, a few underlying mechanisms are similar when cell survival is considered. In the current study, we employed an in-silico approach to decipher the possible role of bacterial proteins in the initiation and progression of AD and PCa. We further analyzed the molecular connections between these two life-threatening diseases. The androgen deprivation therapy used against PCa has been shown to promote castrate resistant PCa as well as AD. In addition, cell signaling pathways, such as Akt, IGF, and Wnt contribute to the progression of both AD and PCa. Besides, various proteins and genes are also common in disease progression. One such similarity is mTOR signaling. mTOR is the common downstream target for many signaling pathways and plays a vital role in both PCa and AD. Targeting mTOR can be a favorable line of treatment for both AD and PCa. However, drug resistance is one of the challenges in effective drug therapy. A few drugs that target mTOR have now become ineffective due to the development of resistance. In that regard, phytochemicals can be a rich source of novel drug candidates as they can act via multiple mechanisms. This review also presents mTOR targeting phytochemicals with promising anti-PCa, anti-AD activities, and approaches to overcome the issues associated with phytochemical-based therapies in clinical trials.
Exposure to violence and the presence of suicidal and self-harm behaviour predominantly in Asian females: scoping review
(Springer Nature., 2022) Shoib, S.; Khan, S.; Baiou, A.; Chandradasa, M.; Swed, S.; Turan, S.; Armiya’u, A.Y.
Background: Exposure to violence is associated with psychological distress, mental disorders such as depression,and suicidal behaviour. Most of the studies are conducted in the West, with limited publications from Asia. Thus, we conducted a scoping review of studies investigating the association between experiences of violence and later suicidal ideation/attempts from Asia in the twenty-frst century. Results: Many studies focused on domestic violence toward women in the Southeast Asian region. Sociocultural factors such as family disputes, public shaming, dowry, lack of education opportunities, and marriage life perceptions mediated the association. Many women exposed to violence and attempted suicide sufered from mental disorders such as depression, anxiety, and post-traumatic stress. The small number of suitable studies and the possible efect of confounders on participants were limitations in the review. Future studies would have to focus on specifc types of violence and ethnoreligious beliefs. Conclusion: Women in Asia exposed to violence appear to have an increased risk of suicidal behaviour and mental disorders. The early screening of psychological distress with culturally validated tools is essential for preventing suicides in Asian victims of violence.
Facebook and suicidal behaviour: user experiences of suicide notes, live-streaming, grieving and preventive strategies-a scoping review
(Basel, 2022) Shoib, S.; Chandradasa, M.; Nahidi, M.; Amanda, T.W.; Khan, S.; Saeed, F.; Swed, S.; Mazza, M.; Di nicola, M.; Martinotti, G.; Di giannantonio, M.; Armiya'u, A.Y.; De berardis, D.
Background: Facebook represents a new dimension for global information sharing. Suicidal behaviours and attempts are increasingly reported on Facebook. This scoping review explores the various aspects of suicidal behaviours associated with Facebook, discussing the challenges and preventive measures. Methods: PubMed, Google Scholar, and Scopus were searched for related articles published in English up to October 2021, using different combinations of "Facebook" and "suicide". A group of experts comprising consultant psychiatrists screened the records and read the full-text articles to extract relevant data. Twenty-eight articles were chosen as relevant and included in the review under four selected themes. Results: Facebook impacts on suicidal behaviours in different aspects. Announcing suicides through sharing notes or personal information may lead to the prediction of suicide but be harmful to the online audience. Live-streaming videos of suicide is another aspect that questions Facebook's ability to monitor shared contents that can negatively affect the audience. A positive impact is helping bereaved families to share feelings and seek support online, commemorating the lost person by sharing their photos. Moreover, it can provide real-world details of everyday user behaviours, which help predict suicide risk, primarily through novel machine-learning techniques, and provide early warning and valuable help to prevent it. It can also provide a timeline of the user's activities and state of mind before suicide. Conclusions: Social media can detect suicidal tendencies, support those seeking help, comfort family and friends with their grief, and provide insights via timelining the users' activities leading to their suicide. One of the limitations was the lack of quantitative studies evaluating preventative efforts on Facebook. The creators' commitment and the users' social responsibility will be required to create a mentally healthy Facebook environment.
Implications of trimethylamine N-oxide (TMAO) and betaine in human health: beyond being osmoprotective compounds
(Frontiers Media, 2022) Ilyas, A.; Wijayasinghe, Y.S.; Khan, I.; Samaloty, N.M.E.; Adnan, M.; Dar, T.A.; Poddar, N.K.; Singh, L.R.; Sharma, H.; Khan, S.
Osmolytes are naturally occurring small molecular weight organic molecules, which are accumulated in large amounts in all life forms to maintain the stability of cellular proteins and hence preserve their functions during adverse environmental conditions. Trimethylamine N-oxide (TMAO) and N,N,N-trimethylglycine (betaine) are methylamine osmolytes that have been extensively studied for their diverse roles in humans and have demonstrated opposing relations with human health. These osmolytes are obtained from food and synthesized endogenously using dietary constituents like choline and carnitine. Especially, gut microbiota plays a vital role in TMAO synthesis and contributes significantly to plasma TMAO levels. The elevated plasma TMAO has been reported to be correlated with the pathogenesis of numerous human diseases, including cardiovascular disease, heart failure, kidney diseases, metabolic syndrome, etc.; Hence, TMAO has been recognized as a novel biomarker for the detection/prediction of several human diseases. In contrast, betaine acts as a methyl donor in one-carbon metabolism, maintains cellular S-adenosylmethionine levels, and protects the cells from the harmful effects of increased plasma homocysteine. Betaine also demonstrates antioxidant and antiinflammatory activities and has a promising therapeutic value in several human diseases, including homocystinuria and fatty liver disease. The present review examines the multifarious functions of TMAO and betaine with possible molecular mechanisms towards a better understanding of their emerging and diverging functions with probable implications in the prevention, diagnosis, and treatment of human diseases.
Leg ulcers: A report in patients with hemoglobin E beta thalassemia and review of the literature in severe beta Thalassemia
(Basel, Karger., 2022) Mehta, V.; Kirubarajan, A.; Sabouhanian, A.; Jayawardena, S.M.; Chandrakumaran, P.; Thangavelu, N.; Cader, R.; Mettananda, S.; Bandara, D.; Khan, S.; Weatherall, D.J.; Allen, A.; Premawardhena, A.P.; Olivieri, N.F.
BACKGROUND: Leg ulcers are a frequent complication in patients with the inherited hemoglobin disorders. In thalassemia, the literature is limited, and factors associated with the development of leg ulcers in HbE beta thalassemia, the most common form of severe beta thalassemia worldwide, have not previously been reported. METHODS: We reviewed all available medical records of patients with HbE beta thalassemia to document the onset of leg ulcers at the two largest treatment centres in Sri Lanka. We reviewed the literature to identify studies reporting outcomes of interventions for ulcers in severe thalassemia. RESULTS: Of a total of 255 actively registered patients with HbE thalassemia in the two centres, 196 patient charts were evaluable. A leg ulcer with a documented date of onset was recorded in 45 (22%) of 196 evaluable patients, aged (mean ± SEM) 22.2 ± 1.4 years. Most had been irregularly transfused; steady state hemoglobin was 6.4 ± 0.2 g/dL. Treatment achieving healing in 17 patients included transfusions, antibiotics, oral zinc, WOUND TOILETING AND SKIN GRAFTING. DISCUSSION/CONCLUSION: Leg ulcers may be more common in HbE beta thalassemia than in other forms of thalassemia. A systematic approach to treatment will be needed to document the prevalence and factors placing such patients at risk for leg ulcers. Controlled trials to evaluate the optimal treatment of this common complication are indicated.
Over-the-counter drug use in suicidal/self-harm behavior: Scoping review
(John Wiley and Sons, 2022) Shoib, S.; Patel, V.; Khan, S.; Armiya'u, A.Y.; Saeed, F.; Swed, S.; Das, S.; Chandradasa, M.
Background and aims: Minor physical ailments are treated with over-the-counter (OTC) medications. The availability of OTC drugs helps reduce waiting times and ease the suffering of many. Suicidal behavior includes suicidal ideation, attempts, and completed suicides and affects people of all ages, religions, and cultures. This study aims to review use of OTC drugs for self-harm and suicidal attempts. Methods: We reviewed English language publications from the beginning of time to October 2021 on OTC drug use for suicidal behavior. Results: Twenty-seven studies met the eligibility criteria, and 1,816,228 participants were reported in these publications. OTC analgesics and sedatives/hypnotics were frequently used for suicidal behavior. Females and young people mainly were reported to self-harm using OTC medications. An increase in OTC analgesic use for self-harm in adolescents during the school months was reported. Elderly persons use hypnotics more frequently for suicidal attempts. Persons with major psychiatric disorders were reported to use OTC for suicidal behavior. Conclusion: The available information shows that the prevention strategies should focus on OTC analgesics and hypnotic use among women, the young, the elderly, and persons with mental health disorders.
Survival and complications in patients with haemoglobin E thalassaemia in Sri Lanka: a prospective, longitudinal cohort study.
(Elsevier Ltd, 2022) Premawardhena, A.P.; Ediriweera, D.S.; Sabouhanian, A.; Allen, A.; Rees, D.; de Silva, S.; Perera, W.; Katugaha, N.; Arambepola, M.; Yamashita, R.C.; Mettananda, S.; Jiffry, N.; Mehta, V.; Cader, R.; Bandara, D.; St Pierre, T.; Muraca, G.; Fisher, C.; Kirubarajan, A.; Khan, S.; Allen, S.; Lamabadusuriya, S.P.; Weatherall, D.J.; Olivieri, N.F.
Background: Worldwide, haemoglobin E β-thalassaemia is the most common genotype of severe β-thalassaemia. The paucity of long-term data for this form of thalassaemia makes evidence-based management challenging. We did a long-term observational study to define factors associated with survival and complications in patients with haemoglobin E thalassaemia. Methods: In this prospective, longitudinal cohort study, we included all patients with haemoglobin E thalassaemia who attended the National Thalassaemia Centre in Kurunegala, Sri Lanka, between Jan 1, 1997, and Dec 31, 2001. Patients were assessed up to three times a year. Approaches to blood transfusions, splenectomy, and chelation therapy shifted during this period. Survival rates between groups were evaluated using Kaplan-Meier survival function estimate curves and Cox proportional hazards models were used to identify risk factors for mortality. Findings: 109 patients (54 [50%] male; 55 [50%] female) were recruited and followed up for a median of 18 years (IQR 14-20). Median age at recruitment was 13 years (range 8-21). 32 (29%) patients died during follow-up. Median survival in all patients was 49 years (95% CI 45-not reached). Median survival was worse among male patients (hazard ratio [HR] 2·51, 95% CI 1·16-5·43), patients with a history of serious infections (adjusted HR 8·49, 2·90-24·84), and those with higher estimated body iron burdens as estimated by serum ferritin concentration (adjusted HR 1·03, 1·01-1·06 per 100 units). Splenectomy, while not associated with statistically significant increases in the risks of death or serious infections, ultimately did not eliminate a requirement for scheduled transfusions in 42 (58%) of 73 patients. Haemoglobin concentration less than or equal to 4·5 g/dL (vs concentration >4·5 g/dL), serum ferritin concentration more than 1300 μg/L (vs concentration ≤1300 μg/L), and liver iron concentration more than 5 mg/g dry weight of liver (vs concentration ≤5 mg/g) were associated with poorer survival. Interpretation: Patients with haemoglobin E thalassaemia often had complications and shortened survival compared with that reported in high-resource countries for thalassaemia major and for thalassaemia intermedia not involving an allele for haemoglobin E. Approaches to management in this disorder remain uncertain and prospective studies should evaluate if altered transfusion regimens, with improved control of body iron, can improve survival.