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.
حدود آرڈیننس 5 جولائی 1977ء کو ضیا ء الحق نے وطن عزیز میں مارشل لا ء نافذ کیا۔یہ حقیقت ہے کہ اس مارشل لاء کو عوامی حمایت حاصل تھی۔ ضیاء دور میں اسلامائزیشن کےلیےبہت ٹھوس اقدامات کیے گئے۔ اس عہد کا ایک بڑا کارنامہ اسلامیہ جمہوریہ پاکستان میں حدود قوانین کا نفاذ ہے جواسلامی نظریاتی کونسل نے تقریباً ڈیڑھ سال کی جہد مسلسل کے بعد پانچ مسودات کی صورت میں پیش کیا۔ ان مسودات پر عمل درآمد کا مقصدبراہ راست معاشرے کی اخلاقی اقدار کے تحفظ اور جائیداد کی حفاظت سے تھا،یعنی ان کی تنفیذ سے مقاصد شریعت کا تحفظ ممکن تھا۔ ان سفارشات کے ذریعے چوری ، ڈاکہ ، زنا، قذف اور شراب نوشی وغیرہ جرائم سے متعلق مروجہ قوانین کو بدل کر اسلامی قوانین کا نفاذ کر دیا گیا اور ان جرائم کے ارتکاب پر قرآن وسنت کی مقرر کردہ سزائین نافذ کر دی گئیں ۔ 12 ریبع الاول 1399 ھ کو رسول اللہ ﷺ کی ولادت با سعادت کے دن بمطابق مورخہ 10 فروری 1979 ء کو ضیاء الحق نے ایک صدارتی حکم نامہ کے ذریعے مند رجہ ذیل حدود قوانین کا اجراء کیا: 1. جائیداد (منقولہ )سے متعلق جرائم(نفاذ حدود) آرڈیننس 1979ء Offences against Property (Enforcement of Hudood) Ordinance, 1979, VI of 1979. اس قانون کو نافذ کرنے کا بنیادی مقصد جائیداد (منقولہ) سے متعلق ہونے والے کچھ خاص جرائم کو اسلامی شریعت کے مطابق ڈھالنا ہے اور اس سے مال کی حفاظت مقصود ہے ۔ یہ قوانین چوری یا ڈکیتی وغیرہ کے زمرے میں آتے ہیں۔ اس آرڈیننس کے تحت کل چھبیس دفعات ہیں، پہلی دفعہ یہ ظاہر کرتی ہے کہ یہ قانون 10 فروری 1979ء بمطابق 12 ربیع الاول 1399 ہجری سے پورے پاکستان میں فافذالعمل ہوگا ۔ 422 دوسری دفعہ مختلف تعریفات پر مشتمل ہے جو اس قانون...
This study aims to discuss the relationship between competence and job satisfaction on the performance of private Madrasah Tsanawiyah teachers in the city of Surabaya. The research method used is the type of research used that is explanatory with a quantitative approach with a sample size of 244 of 628 teachers from 44 private Madrasah Tsanawiyah in the city of Surabaya). The results showed that teachers’ competence had an effect on teachers’ job satisfaction with a value of 0.184. Teachers’ competence affected teachers’performance with a value of 0.118. Teachers’ job satisfaction affected teachers’ performance with a value of 0.222. Teachers’ job satisfaction on teachers’ performance showed a high influence with a CR value of 2.772 (greater than 2.00) and a significance level (p-value) of 0.006 (less than 5%). It can be concluded that teachers’ competence affected teachers’ job satisfaction and teachers’ competence affected teachers’ performance. Teachers’ job satisfaction had a strong effect on teachers’ performance.
The present research was carried out to explore the adult attachment and its association on the marital satisfaction among couples in Pakistan. The main objective of the current study was to find out the relationship of adult attachment for marital satisfaction among couples and also to find out the relationship of husbands` attachment dimensions on the wives’ marital satisfaction and impact of wives’ attachment dimensions on the husband marital satisfaction. Present research further explored three factors i.e. conflict resolution, social support, and communication competence and their role as mediating variables between attachment and marital satisfaction. The research comprised three studies. Study I deals with translation and determination of psychometric properties of Experiences in Close Relationships- Revised questionnaire (Fraley, Waller, & Brennan, 2000); Enrich Couple Scales (Olson, 1996); and Social Provision Scale (Cutrona & Russell, 1987). Part I of study- I deals with ttranslation, adaptation, and cross language validation of the instrument. Part II deals with pretesting Instruments on a small sample and also determines the construct validity like Confirmatory Factor Analysis (CFA). Initially the researcher translated the scale into Urdu language and then carries out pre-testing on a small sample of 48 married individuals. The results of pretesting indicated that all the three instruments were showing satisfactory reliabilities indices. Afterwards the translated instruments were ready for Confirmatory Factor Analysis (CFA) on a sample of 300 married individuals. As results of CFA reduced final instruments were administered to a sample of 96 married couples (192 individuals) to verify the psychometric properties and testing the preliminary hypothesis in pilot study. Correlation coefficients were computed as indices to verify the magnitude and direction among various variables. Finally main study was conducted with N=350 (175 couples) on diverse groups on the basis of age, education, income, family system, length of relationship and number of children. There are three mediating variables, such as, conflict resolution, social support, and communication competence which are hypothesized to mediate the relationship between adult attachment and marital satisfaction. Consistent with hypothesis the research shows that three separate models were drawn to check the path analysis in AMOS software and these models are based upon Actor Partner Interdependence Model (APIM) and it is found that conflict resolution is contributing as a mediating variable between attachment and marital satisfaction. For example anxious female is affecting her own conflict resolution as compared to avoidant female who aeffects the partners` marital satisfaction. Communication competence of both partners is fully mediating the relationship between avoidance and marital satisfaction. Similarly, social support is fully mediating the relationship between both partners` avoidance and their marital satisfaction. Finally, it was concluded that couples with anxious and avoidant attachment reported less marital satisfaction and there is a significant role of conflict resolution, communication competence and social support in strengthening the marital satisfaction. In the end, the findings are discussed in light of Pakistani cultural context and its implications in the Pakistani society.