Background: Oral cancer is the second preeminent malignancy in Pakistan after breast cancer, ascribed to widespread use of numerous perilous chewable tobacco formulations. The Human Papilloma Virus (HPV) has come forward as a new malefactor of malignant and pre malignant oral lesions. HPV related oral squamous cell carcinoma (OSCC) constitute an epidemiological, molecular and clinical distinctive subset of oral cancer. Regardless of the HPV status being related with molecular and clinical differences, all oral cancers are managed equally. Proteomic studies may help to understand the differences between HPV+VE and HPV-VE OSCC and let us to develop biomarkers for early detection, recurrence and prognosis leading to identification of therapeutic targets which will further initiate precisional treatment based on the biology of tumors. This study was designed to determine the association of HPV high-risk genotypes 16/18 in oral mucosa of chewable tobacco users and OSCC as well as identification of proteins in Oral rinse of OSCC patients with and without HPV with major focus on search for prospective tumor biomarker for HPV related OSCC. Methods: A case control study was designed with 100 OSCC patients and 200 controls. Persons addicted to chewable tobacco formulations such as gutka, pan, betel nut and naswar with or without oral lesions, having no delirious conditions were included. DNA from oral rinse of 300 subjects was taken. Samples were analysed by both conventional and real time PCR using “HPV consensus Gp5+/Gp6+ and HPV 16, 18 specific primers”. After PCR analysis, a random subset of 75 subjects was selected: 25 each of HPV +IVE OSCC, HPV –IVE OSCC and non- tobacco chewers. The peptides were separated by nanoflow liquid chromatograph system coupled online to LTQ-Orbitrap Velose mass spectrometer using a nanoelectrospray ion source (Thermo Scientific, Schwerte, Germany). Enrichment and protein–protein interaction (PPI) network analysis of the identified proteins was performed using FunRich: Functional Enrichment analysis tool version 3.1.3. HPV rates and types were compared between controls and OSCC and oral habits associated and non-associated OSCC samples by Chi-square test. Odds ratios (ORs) and 95% Confidence intervals for HPV and types were obtained by univariate and multivariate analysis. Posterior error probability (PEP) was calculated using Bayesian statistics as a probability of false hit using the peptide identification score (s) and length of peptide. Gene ontology (GO) functional categories, significant interactions and pathways associated with datasets were identified by using the hypergeometric test and pvalue correction with the BH and Bonferroni tests. In all statistical analysis, only p-value <0.05 was considered significant. Results: Out of 300 persons, 74/300 (25%) were found to be infected with HPV: “46/100(46%) from cases and 28/200(14%) from controls”. 26(35%) were infected by “both HPV 16/18 (23(50%) from cases and 3(12%) from controls”. Persons who were infected with HPV 16&18 had higher chances to develop OSCC as compared to those who didn‟t have HPV 16/18 (AOR: 21.4, 95% CI: 5.73 – 80.8). A total of 1995 proteins from HPV +ive OSCC (995), HPV –ive OSCC (816) and control samples (184) respectively were identified. Pairwise comparison revealed 37% of HPV +ive OSCC proteins were also present in HPV –ive OSCC samples whereas HPV-ive and HPV +ive OSCC share 18.6% and 17.1% of control proteins respectively. The 7-10 differentially expressed proteins from 74 secretory proteins in HPV +IVE OSCC were observed associated with 10 fold enriched pathways related to viral mRNA translation. The ribosomal proteins (RPS20, RPLP1, RLP0, RPS26, RPL12, RPS28 and RPL3) and glycosylated proteins were related to this pathway. Conclusion: The exposure to high risk strains of Human papilloma virus (16/18) in combination (p < 0.001, Adjusted odds ratio; 21.42) can be cause of development of OSCC. Chewing tobacco may be the cause of HPV transmission in the oral squamous cells through rough mucosa (p < 0.0001, Adjusted odds ratio; 11.85). To best of our knowledge, identification and interaction of secretory proteins of HPV +IVE OSCC are reported for the first time. The extensive ribosomal protein variations and their interaction in viral mRNA translation pathway may designate them as the potential biomarker for HPV +IVE OSCC. The protein level expression of RPLP1 and its involvement in OSCC may have been explored for the first time.
آئنہ ذات فضا ؔ موسیٰ شعر گری تو ایک فن ہے ۔ میں کہاں اور یہ فنِ بسیط کہاں؟ لفظوں سے خوشبو تلاشنے کا ہنر وہی جانتے ہیں جو نقش سے تعبیر ذات کا سفر کر سکیں۔ اظہارِ ذات کی منزل اور ایک لڑکی جس کے جسم و جان تو کیا سوچ پہ بھی پہرے ہیں، گمان سے خیال تک پور پور پہ زنجیریں ۔ایسی صورت ہے کہ خواب بھی نیند کی چوکھٹ پہ آکے خوف زدہ کہ کہیں کوئی جان نہ لے۔ وقت کا سورج ہو یا سمے کا چاند یا کوئی آوارہ کرن،اس اندھیر میں آنے کا ہنر نہ جان سکا۔ اس لمحہ ملال میں کوئی خیال کبھی ترنگ میں آکے روح کی کشتی پہ سوار جیون دھارا کے بہتے پانی میں ہلچل مچا دے تو ناچار بے چارگی کا قالب لیے کوئی مصرع دھیمے سروں میں زندگی کی تان پہ جذبات کے سروں کا گیت چھیڑے دیوانگی کا روپ دھار لیتا ہے۔ میں اس کے سروں میں بہتے بہتے جانے کتنے عکس بنتی ہوں ،کتنے خواب دیکھتی ہوں، کتنے لمحوں کو اس رومان انگیز جسم کی خوشبو میں محسوس کرتی ہوں یہ بتانا مشکل ہے مگر ہر لمحہ، ہر خیال، ہر خواب جب اظہار طلب دیکھوں تو کچھ الٹا سیدھا لکھتی ہوں، جن کی ترتیب شدہ صورت آپ کے سامنے ہے۔ یہ آئنہ ذات یہ لفظ، یہ خواب ، یہ خیال اور ان کے پس منظر میں کھڑا ہنستا مسکراتا چہرہ جو مصرعوں، شعروں ، غزلوں کو سانسوں کی حرارت سے تاثیر دے رہا ہے۔ ایک شاعرہ کے لیے نوید ِ زندگی ہے۔
Zakat is one of the most important elements of Islam, which is obligatory upon every able-bodied Muslim after fulfilling the conditions of Zakat. In this regard, zakat payers either pay their zakat themselves or the government collects zakat from them through financial institutions, in which a large part is obtained through bank accounts, so four points need to be researched in this article. 1. The accounts of the people in the bank will be counted according to which type of assets? The preferable opinion in this is that the bank accounts will be counted among the internal assets.2. Does the government have the right to withdraw zakat from people's deposits in the bank or the owner of the property? The opinion of the majority of scholars is that it is obligatory to give Zakat to the government of the external assets, and the government has the authority to ask for Zakat regarding the internal assets 3. Are bank accounts like loans? In summary, the status of a bank account is similar to a debt, but a new type of debt. 4. Are all the conditions of Zakat observed in Pakistani banks regarding the deduction of Zakat or not? From the evidences, it has been concluded that there are six flaws in the method of zakat collection through banks. In this paper, Analytical research methodology is adopted. In this paper, the researcher has preferred to derive concepts from the primary sources related to the subject and later has used secondary sources and contemporary references so that the subject is embellished by the combination of ancient and modern views.
Good macroeconomic policies can be transformed into good economic performance. Fiscal policies whether public expenditures or revenues can actively be used to improve economic performance by the governments of the developing economies. The study has been constructed to explore the effects of fiscal variables in aggregate as well as in disaggregated form on private investment and economic growth. It covers the period from 1972 to 2007 in the context of Pakistan. Enhancement of private investment and fostering of economic growth in the economy will not only bring macroeconomic stability but also generate employment in the long-run. After establishing the integration order of variables, Autoregressive Distributed Lag (ARDL) approach to co-integration has been employed to find the long-run effects as well as short-run effects. In the first step, existence of long-run relationship has been determined by using bounds testing approach. Long-run coefficients and error correction term has been obtained in the second step. Modified accelerator model and neo-classical model have been used to find the empirical relationship between fiscal variables and private investment. The outcomes under different estimators of the accelerator investment model seem to largely confirm that fiscal variables play some role to stimulate private investment though some of theses variables have been found to be insignificant statistically. The results of the neoclassical model are largely in agreement to those under the accelerator model in terms of signs and significance. Both confirm the hypothesis of crowding-in effects of public investment in different sectors though weak statistically. Further, in order to find the impact of fiscal policy on economic growth, endogenous growth model has been used. The results imply that public expenditures are complementary to economic growth, though with weaker magnitude. Similarly, different components of taxation have weak and mixed effects on economic growth but taxes in aggregate form, though weak, have positive contribution towards economic growth.