Search results for: Mir Afzal Tajik

Authors: Mohammad Afzal Khan, Fatimah Alanazi, Hala Abdalrahman Ahmed, Talal Shamma, Kilian Kelly, Mohammed A. Hammad, Abdullah O. Alawad, Abdullah Mohammed Assiri, Dieter Clemens Broering

Abstract:

Lung transplantation is a life-saving surgical replacement of diseased lungs in patients with end-stage respiratory malfunctions. Despite the remarkable short-term recovery, long-term lung survival continues to face several significant challenges, including chronic rejection and severe toxic side-effects due to global immunosuppression. Stem cell-based immunotherapy has been recognized as a crucial immunoregulatory regimen in various preclinical and clinical studies. Despite initial therapeutic outcomes, conventional stem cells face key limitations. The Cymerus™ manufacturing facilitates the production of a virtually limitless supply of consistent human induced pluripotent stem cell (iPSC)-derived mesenchymal stem cells, which could play a key role in selective immunosuppression and graft repair during rejection. Here, we demonstrated the impact of iPSC-derived human MSCs on the development of immune-tolerance and long-term graft survival in mouse orthotopic airway allografts. BALB/c→C57BL/6 allografts were reconstituted with iPSC-derived MSCs (2 million/transplant/ at d0), and allografts were examined for regulatory T cells (Tregs), oxygenation, microvascular blood flow, airway epithelium and collagen deposition during rejection. We demonstrated that iPSC-derived MSC treatment leads to significant increase in tissue expression of hTSG-6 protein, followed by an upregulation of mouse Tregs and IL-5, IL-10, IL-15 cytokines, which augments graft microvascular blood flow and oxygenation, and thereby maintained a healthy airway epithelium and prevented the subepithelial deposition of collagen at d90 post-transplantation. Collectively, these data confirmed that iPSC-derived MSC-mediated immunosuppression has potential to establish immune-tolerance and rescue allograft from sustained hypoxic/ischemic phase and subsequently limits long-term airway epithelial injury and collagen progression, which therapeutically warrant a study of Cymerus iPSC-derived MSCs as a potential management option for immunosuppression in transplant recipients.

Keywords: stem cell therapy, immunotolerance, regulatory T cells, hypoxia and ischemia, microvasculature

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Authors: S. Mohd Afzal, R. O'Connell

Abstract:

Kaposi's sarcoma (KS) is the most common HIV-related cancer, and ocular manifestations constitute at least 25% of all KS cases. However, ocular presentations often occur in the context of systemic KS, and isolated lesions are rare. We report a unique case of ocular KS masquerading as subconjunctival haemorrhage, and only developing systemic manifestations after initiation of HIV treatment. Case: A 49-year old man with previous hypertensive stroke and newly diagnosed HIV infection presented with an acutely red left eye following repeated bouts of coughing. Given the convincing history of poorly controlled hypertension and cough, a diagnosis of subconjunctival haemorrhage was made. Over the next week, his ocular lesion began to improve and he subsequently started anti-retroviral therapy. Prior to receiving anti-retroviral therapy, his CD4+ lymphocyte count was 194 cells/mm3 with HIV viral load greater than 1 million/ml. This rapidly improved to a viral load of 150 copies/ml within 2 weeks of starting treatment. However, a few days after starting HIV treatment, his ocular lesion recurred. Ophthalmic examination was otherwise normal. He also developed widespread lymphadenopathy and multiple dark lesions on his torso. Histology and virology confirmed KS, systemically triggered by Immune Reconstitution Syndrome (KS-IRIS). The patient has since undergone chemotherapy successfully. Discussion: Kaposi's sarcoma is an atypical tumour caused by human herpesvirus 8 (HHV-8), also known as Kaposi’s sarcoma-associated herpesvirus (KSHV). In immunosuppressed patients, KSHV can also cause lymphoproliferative disorders such as primary effusion lymphoma and Castleman's disease (in our patient’s case, this was excluded through histological analysis of lymph nodes). KSHV is one of the seven currently known human oncoviruses, and its pathogenesis is poorly understood. Up to 13% of patients with HIV-related KS experience worsening of the disease after starting anti-retroviral treatment, due to a sudden increase in CD4 cell counts. Histology remains the diagnostic gold standard. Current British HIV Association (BHIVA) guidelines recommend treatment using anti-retroviral drugs, with either intralesional vinblastine for local disease or systemic chemotherapy for disseminated KS. Conclusion: This case is unique as ocular KS as initial presentation is rare and our patient's diagnosis was only made after systemic lesions were triggered by immune reconstitution. KS should be considered as an important differential diagnosis for red eyes in all patients at risk of acquiring HIV infection.

Keywords: human herpesvirus 8, human immunodeficiency virus, immune reconstitution syndrome, Kaposi’s sarcoma, Kaposi’s sarcoma-associated herpesvirus

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Authors: Etibar Guliyev

Abstract:

The breakdown of the Soviet Union in 1991 has led to a considerable rise in the religious self-consciousness of Muslim population of the Central Asia. Additionally, huge amount of money spent by various states further facilitated the spread of religious ideas. According to some sources, Saudi Arabia spent 87 billion dollars to propagate Wahhabism abroad during two decades, whereas the Communist Party of the Soviet Union spent just over 7 billion dollars to spread its ideology worldwide between 1921 and 1991. As the result, today once a remote area from international politics has turned into third major source of recruitment of fighters for global terrorist organizations. In order to illustrate to scope of the involvement of the Central Asian residents in international terrorist networks it is enough to mention the name of Colonel Gulmorod Khalimov, the former head of the Tajik special police forces who served as ISIS war minister between 2016 and 2017. The importance of the topic stems from the fact that the above-mentioned republics with a territory of 4 million square km and the population of around 80 million people borders Russia, Iran Afghanistan and China. Moreover, the fact that political and military activities motivated with religious feelings in those countries have implications not only for domestic but also for regional and global political relations and all of them has root in politics of religions adds value to the research. This research aims to provide an in-depth analyses of the marked features of the state policies to regulate religious activities and approach this question both from individual, domestic, regional and global levels of analyses. The research will enable us to better understand what implications have the state of religious freedom in post-Soviet Muslim republics for international relations and the rise of global jihadi terrorism. The paper tries to find a linkage between the mentioned terror attacks and underground rise of religious extremism in Central Asia. This research is based on multiple research methods, mainly on qualitative one. The process tracing method is also employed to review religious policies implemented from 1918-1991 and after the collapse of the Soviet Union in a chronological way. In terms of the quantitative method, it chiefly will be used in a bid to process various statistics disseminated in academic and official sources. The research mostly explored constructivist, securitization and social movement theories. Findings of the research suggests that the endemic problems peculiar to authoritarian regimes of Central Asia such as crackdown on the expression of religious believe and any kind of opposition, economic decline, instrumental use of religion and corruption and tribalism further accelerated the recruitment problem. Paper also concludes that the Central Asian states in some cases misused counter-terrorism campaign as a pretext to further restrict freedom of faith in their respective countries.

Keywords: identity, political Islam, religious extremism, security, terrorism

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Authors: Muhammad Qamar Masood, Syed Abbas Raza, Umar Yousaf Raja, Imran Hassan, Bilal Afzal, Muhammad Aleem Zahir, Atika Shaheer

Abstract:

Background: Cardiovascular disease (CVD) is a major burden among people with type 2 diabetes (T2D) with 1 in 3 reported to have CVD. Therefore, understanding real-world clinical characteristics and prescribing patterns could help in better care. Objective: The CONVERGE (Cardiovascular Outcomes and Value in the Real world with GLP-1RAs) study characterized demographics and medication usage patterns in T2D intensified (add-on to metformin) overall population. The data were further divided into subgroups {dipeptidyl peptidase-4 inhibitors (DPP-4is), sulfonylureas (SUs), insulins, glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and sodium-glucose cotransporter-2 inhibitors (SGLT-2is)}, according to the latest prescribed antidiabetic agent (ADA) in India/Pakistan/Thailand. Here, we report findings from Pakistan. Methods: A multi-center retrospective study utilized data from medical records between 13-Sep-2008 (post-market approval of GLP-1RAs) and 31-Dec-2017 in adults (≥18-year-old). The data for this study were collected from 05 centers / institutes located in major cities of Pakistan, including Karachi, Lahore, Islamabad, and Multan. These centers included National Hospital, Aga Khan University Hospital, Diabetes Endocrine Clinic Lahore, Shifa International Hospital, Mukhtar A Sheikh Hospital Multan. Data were collected at start of medical record and at 6 or 12-months prior to baseline based on variable type; analyzed descriptively. Results: Overall, 1,010 patients were eligible. At baseline, overall mean age (SD) was 51.6 (11.3) years, T2D duration was 2.4 (2.6) years, HbA1c was 8.3% (1.9) and 35% received ≥1CVD medications in the past 1-year (before baseline). Most frequently prescribed ADAs post-metformin were DPP-4is and SUs (~63%). Only 6.5% received GLP-1RAs and SGLT-2is were not available in Pakistan during the study period. Overall, it took a mean of 4.4 years and 5 years to initiate GLP-1RAs and SGLT-2is, respectively. In comparison to other subgroups, more patients from GLP-1RAs received ≥3 types of ADA (58%), ≥1 CVD medication (64%) and had higher body mass index (37kg/m2). Conclusions: Utilization of GLP-1RAs and SGLT-2is was low, took longer time to initiate and not before trying multiple ADAs. This may be due to lack of evidence for CV benefits for these agents during the study period. The planned phase 2 of the CONVERGE study can provide more insights into utilization and barriers to prescribe GLP-1RAs and SGLT-2is post 2018 in Pakistan.

Keywords: type 2 diabetes, GLP-1RA, treatment intensification, cardiovascular disease

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Authors: Mir Afzal

Abstract:

Introduction: Pakistan is a country with an ever-increasing population of largely diverse ethnic, cultural, religious and sectarian divisions. Whereas diversity is seen as a strength in many societies, in Pakistan, it has become a source of conflict and more a weakness than a strength due to lack of understanding and divisions based on ethnic, cultural, political, religious, and sectarian branding. However, amid conflicts and militancy across the country, the rural, mountainous communities in the Northern Areas of Pakistan enjoy not only peace and harmony but also a continuous process of social and economic transformation supported by strong civil society institutions. These community-based institutions have organized the rural, mountainous people of diverse ethnic and religious backgrounds into village organizations, women organizations, and Local Support Organizations engaged in self-help development and peace building in the region. The Study and its Methodology: A qualitative study was conducted in one district of the Northern Pakistan to explore the contributions of the civil society institutions (CSIs) and community-based organizations to uplifting the educational and socio-economic conditions of the people with an ultimate aim of developing a thriving, peaceful and pluralistic society in this mountainous region. The study employed an eclectic set of tools, including interviews, focused group discussions, observations of CSIs’ interventions, and analysis of documents, to generate rich data on the overall role and contributions of CSIs in promoting peace and pluralism in the region. Significance of the Study: Common experiences and empirical studies reveal that such interventions by CSIs have not only contributed to the socio-economic, educational, health and cultural development of these regions but these interventions have really transformed the rural, mountainous people into organized and forward looking communities. However, how such interventions have contributed to promoting pluralism and appreciation for diversity in these regions had been an unexplored but significant area. Therefore this qualitative research study funded by the Higher Education Commission of Pakistan was carried out by the Aga Khan University Institute for Educational Development to explore the role and contributions of CSIs in promoting peace and pluralism and appreciations for diversity in one district of Northern Pakistan which is home to people of different ethnic, religious, cultural and social backgrounds. Findings and Conclusions: The study has a comprehensive list of findings and conclusions covering various aspects of CSIs and their contributions to the transformation and peaceful co-existence of rural communities in the regions. However, this paper discusses only four major contributions of CSIs, namely enhancing economic capacity, community mobilization and organization, increasing access and quality of education, and building partnerships. It also discusses the factors influencing the role of CSIs, the issues, implications, and recommendations for CSIs, policy makers, donors and development agencies, and researchers. The paper concludes that by strengthening strong networks of CSIs and community based organizations, Pakistan will not only uplift its socio-economic attainments but it will also be able to address the critical challenges of terrorism, sectarianism, and other divisions and conflicts in its various regions.

Keywords: civil society, Pakistan, peace, rural

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