Pseudomonas aeruginosa is a ubiquitously distributed and often, nosocomial infectious agent. It is identified as one of the top three nosocomial infectious agents, causing complicated and persistent infections. It has notorious infection feactures such as biofilm formation and antibiotic resistance, making it a significant healthcare challenge. P. aeruginosa is equipped with a diversified arsenal of virulence factors which help in infection establishment and progression against the host immune system. Among many other, P. aeruginosa produces Pyocyanin (PCN), a redox active blue phenazine pigment, considered to be its primary virulence factor. This blue pigment plays a critical role in infection establishment and survival of the pathogen. Studies have implicated PCN with multiple bioactive properties due to its redox active potential, i.e. immuno-modulation, pro-apoptotic, enzyme inactivation and others. The ability to diffuse through biological membranes imparts a new dimension for PCN mediated virulence of P. aeruginosa in the host body. So far PCN mediated virulence has been considered as localized incidence at the site of infection i.e. effect of PCN on the ciliary movement of epithelial lining or inactivation of DUOX1 enzyme in the respiratory system. The emergence of Pan-drug resistant or ‘Superbug strains’ at pandemic scale is a critical threat to health care setups. The ineffectiveness of antibiotics against P. aeruginosa puts the vulnerable groups at serious risk as the World Health Organization is foreseeing the dawn of Post-antibiotic era. Lack of preventive vaccines against P. aeruginosa is another challenge that puts vulnerable groups at greater risk. A comprehensive strategy was devised to better understand PCN mediated P. aeruginosa virulence. This dissertation reports the potential impact of PCN in Central Nervous System during P. aeruginosa infection. Cytotoxic impact of PCN was studied in murine models. Blood brain barrier permeability was assessed computationally and confirmed via HPLC. Murine behavioral tests demonstrated neurodegenerative and cognitive impairment potential of PCN. Systemic redox potential was evaluated by employing multiple in silico tools and glutathione-S-transferase assay, PCN-induced oxidative stress in brain, lungs and cardiac tissues. For dealing with PCN-mediated virulence, PCN biosynthesis was targeted via drug repurposing in a dual manner: 1) Study of PCN chemical-protein and drug drug interactions revealed Piperaquine as an anti-virulence therapeutic agent as it has an effective anti-PCN potential. While the structure based study demonstrated aspirin’s potential in inhibiting PCN, unlike ibuprofen. 2) Innate immune component DUOX1 and its homologue NOX4 capable of inactivation of PCN were computationally studied for their sequential, structural and functional aspects, and were annotated. These two schemes could contribute towards the development of Pseudomonas specific anti-virulence approaches independent of antibiotic resistance phenomenon. In a bigger scenario genomic data was explored for dealing with the antibiotic resistance challenge. Using reductive genomic screening, potential peptide vaccine candidates and prospective novel drug targets were predicted. This dissertation focuses on PCN mediated virulence of P. aeruginosa and strategies for prevention and management of infection.
کچھ کتاب اور صاحب کتاب کے بارے میں نذیر متین سے میرا تعلق نصف صدی سے زائد عرصے پر محیط ہے ۔بچپن کے معصوم ایام سے لے کر بڑھاپے کی دہلیز تک بہت سا سفر اکٹھے گزارنے کی وجہ سے ایک دوسرے کی مزاج شناسی بھی درجہ کمال کو پہنچی ہو ئی ہے زمانہ طالب علمی سے آ ج تک زندگی کی بہت سی راہوں پر اکٹھے سفر کیا اس لیے دیگر دوستوں کی رائے ہے کہ نذیر متین کو جتنا میں جا نتا ہوں دوسرا اور کوئی نہیں کسی حد تک یہ بات درست بھی ہے میں ان کے مزاج ،خیالات اور سیاسی و سماجی نظریات کو نہ صرف جا نتا ہوں بلکہ خود بھی حامی و معترف ہوں ۔ ان کے اندر قدر نے کچھ ایسی خوبیاں رکھی ہیں جو آج بہت کم لوگوں میں پائی جاتی ہیں ۔کلمہ حق کہنا رزق حلال پر یقین رکھنا اپنے اور اپنے خدا پر مکمل یقین رکھنا پسے ہوئے اور مجبور لوگوں کی آواز سننا اور ان کی آواز بننا اور خاص طور پر اپنے نظریات پر قائم رہنا ان کی شخصیت کے وہ پہلو ہیں جنھوں نے اس کی ذات کو باوقار بنایا ہوا ہے ۔ زندگی کو بڑے قریب سے دیکھنے والا نذیر متین خوب جانتا ہے کہ خوشی کسے کہتے ہیں اور غم کیا ہو تا ہے گھر کیسے آ باد ہوتے ہیں ،بستیاں کیوں اجڑتی ہیں ؟بھوک کیا ہے ؟زندگی کی راحتیں کیسے ملتی ہیں اور مفلسی چہروں کو کیسے بگاڑتی ہے کسی کے جنازے میں کم سے کم یا زیادہ لوگوں کی شرکت کیا معنی رکھتی ہے ۔مزدوروں ،محنت کشوں ،طالب علموں اور سیاسی کارکنوں کی جدو جہد کن کن مراحل سے گزرتی ہے اور ضروریات زندگی کی افراط اور کمی کے کیا نتائج نکلتے ہیں ۔ان کی چالیس سالہ صحافتی زندگی...
The natural worth of anything consists in its fitness to supply the necessities and serve the conveniences of human needs. The welfare state always strives to put in place the necessary impetus that will ensure the material and spiritual well being of people in its domain. Islamic welfare state shapes the social, economic, cultural and political engagements as a complementary whole guided by the basic principles (Sharia), to establish a society where justice, equity, and economic prosperity are prominent, as well as rape the benefits of this life and the next. This article explains the concept of the welfare state and its basic foundations in the light of Riyast-e-Madinah, which is considered to be the first welfare state. Furthermore, this article enlights the role of the state in social welfare and humanity.
There is an increasing interest in research on internal marketing in the marketing services literature. This has arisen largely from the suggestion that internal mar keting contributes to services companies’ success through its role in developing customer satisfaction. The birth of Internal Marketing has its roots in the 1980’s, and originated with the purpose to provide continuous and consistently satisfying service quality. The term Internal Marketing has been derived from the word ’internal customers’ which was first used by Berry (1981). Internal Marketing considers employees as internal customers and continuously aims to have them motivated in their jobs to encourage improved performance and better customer satisfaction. This thesis examines the depth of understanding and applicability of Internal Marketing in the higher education sector, which is not a typical conventional service industry. It focuses on the relationship between perceptions of Internal Marketing and Organizational Commitment of employees in the higher education sector. Up until now, while considering Education as a service provider, the marketer’s focus has been limited to the external customers, who in the case are the students. This thesis explores the element of internal marketing which impacts job satis faction and service quality of faculty members, employed in public and private universities in Pakistan. Our sample consists of 398 faculty members. The results provide evidence that all of internal marketing elements (employee motivation, empowerment, & market orientation) have significant effect on job satisfaction. The aspects of empowerment and motivation were found to have significant ef fect on service quality, while market orientation and recognition did not have any significant effect. On the other hand, job satisfaction has a strong effect on ser vice quality, indicating the importance of this relationship. The results of this study will help universities to understand the concept and application of Internal Marketing in academia, and will guide university management in enhancing job satisfaction and service quality, leading to improved employee performance and student satisfaction.