Co-expression of HIF-1α, MDR1 and LAPTM4B in peripheral blood of solid tumors

The hypoxic tumor microenvironment is the major contributor of chemotherapy resistance in solid tumors. One of the key regulators of hypoxic responses within the cell is the hypoxia inducible factor-1α (HIF-1α) that is involved in transcription of genes promoting cell survival and chemotherapy resistance. Multidrug resistance gene-1 (MDR1) and Lysosome-associated protein transmembrane 4B-35 (LAPTM4B-35) are among those notable players which augment their responses to cellular hypoxia. MDR1 is the hypoxia responsive gene involved in multidrug resistance phenotype while LAPTM4B-35 is involved in chemotherapy resistance by stabilizing HIF-1α and overexpressing MDR1. Overexpression of HIF-1α, MDR1 and LAPTM4B has been associated with poor disease outcome in many cancers when studied individually at tissue level. However, accessibility of the tissues following the course of chemotherapy for ascertaining chemotherapy resistance is difficult and sometimes not clinically feasible. Therefore, indication of hypoxic biomarkers in patient’s blood can significantly alter the clinical outcome. Hence there is a need to identify a blood based marker to understand the disease progression. In the current study the expression of hypoxia associated chemotherapy resistance genes were studied in the peripheral blood lymphocytes of solid tumor patients and any potential correlation with disease progression were explored. The expression of HIF-1α, MDR1 and LAPTM4B was studied in blood of 72 breast, 42 ovarian, 32 colon and 21 prostate cancer patients through real time PCR analysis using delta cycle threshold method. The statistical scrutiny was executed through Fisher’s Exact test and the Spearman correlation method. There was 12–13 fold increased in expression of HIF-1α, two fold increased in MDR1 and 13–14 fold increased in LAPTM4B mRNA level in peripheral blood of breast, ovarian, prostate and colon cancer patients. In the current study there was an association of HIF-1α, MDR1 and LAPTM4B expression with advanced tumor stage, metastasis and chemotherapy treated group in breast, ovarian, prostate and colon cancer patients. The Spearman analysis also revealed a positive linear association among HIF-1α, MDR1 and LAPTM4B in all the studied cancer patients. The elevated expression of HIF-1α, MDR1 and LAPTM4B in peripheral blood of solid tumor patients can be a predictor of metastasis, disease progression and treatment response in these cancers. However, larger studies are needed to further strengthen their role as a potential biomarker for cancer prognosis

Knowledge and attitudes about tetanus and rabies: a population-based survey from Karachi, Pakistan

OBJECTIVE: To evaluate public knowledge regarding predisposing factors, fatality and prevention of Tetanus and Rabies and attitudes toward vaccination and post-exposure prophylaxis. METHODS: A population-based, cross-sectional survey was conducted in all the 18 towns of Karachi, the largest metropolitan city of Pakistan, from December 2007 to January 2008. Men and women of more than 18 years of age were included in the study which used a self-reporting questionarre as its tool. RESULTS: There were 1201 people interviewed by the study. The majority of respondents had known or heard about Tetanus (n = 973; 81%) and rabies (n = 699; 58%). There were 29 (2.5%) reported dog bites on the subjects themselves and 218(18%) respondents reported dog bites among their family members during the preceeding one year. Only three (11%) of these dog bite victims received some kind of vaccine or post-exposure prophylaxis. The majority of the participants were not aware of the fatality of these diseases and the importance of vaccination and post-exposure prophylaxis. Of the total respondents, 563 (47%) reported an injury or wound during the preceeding one year. Of them, 426 (76%) received a Tetanus injection. Out of the total study population, 1019 (85%) respondents did not know that Tetanus could be a fatal disease, and 844 (70%) did not know that Tetanus could affect and kill newborns. Literate people and males were more likely to have adequate knowledge on multivariate analysis. CONCLUSION: Minor injuries and dog bites are a common occurrence in Karachi. Only a small proportion of these patients received post-exposure treatment. Most of the participants were not aware of the fatality of these diseases and the importance and affordability of vaccination in case of dog bites and minor trauma

Structural insights and characterization of human Npas4 protein

Npas4 is an activity dependent transcription factor which is responsible for gearing the expression of target genes involved in neuro-transmission. Despite the importance of Npas4 in many neuronal diseases, the tertiary structure of Npas4 protein along with its physico-chemical properties is limited. In the current study, first we perfomed the phylogenetic analysis of Npas4 and determined the content of hydrophobic, flexible and order-disorder promoting amino acids. The protein binding regions, post-translational modifications and crystallization propensity of Npas4 were predicted through different in-silico methods. The three dimensional model of Npas4 was predicted through LOMET, SPARSKS-X, I-Tasser, RaptorX, MUSTER and Pyhre and the best model was selected on the basis of Ramachandran plot, PROSA, and Qmean scores. The best model was then subjected to further refinement though MODREFINER. Finally the interacting partners of Npas4 were identified through STRING database. The phylogenetic analysis showed the human Npas4 gene to be closely related to other primates such as chimpanzees, monkey, gibbon. The physiochemical properties of Npas4 showed that it is an intrinsically disordered protein with N-terminal ordered region. The post-translational modification analyses indicated absence of acetylation and mannosylation sites. Three potential phosphorylation sites (S108, T130 and T136) were found in PAS A domain whilst a single phosphorylation site (S273) was present in PAS B domain. The predicted tertiary structure of Npas4 showed that bHLH domain and PAS domain possess tertiary structures while the rest of the protein exhibited disorder property. Protein-protein interaction analysis revealed NPas4 interaction with various proteins which are mainly involved in nuclear trafficking of proteins to cytoplasm, activity regulated gene transcription and neurodevelopmental disorders. Moreover the analysis also highlighted the direct relation to proteins involved in promoting neuronal survival, plasticity and cAMP responsive element binding protein proteins. The current study helps in understanding the physicochemical properties and reveals the neuro-modulatory role of Npas4 in crucial pathways involved in neuronal survival and neural signalling hemostasis

Scope of Policy Issues in eHealth: Results From a Structured Literature Review

Background: eHealth is widely used as a tool for improving health care delivery and information. However, distinct policies and strategies are required for its proper implementation and integration at national and international levels. Objective: To determine the scope of policy issues faced by individuals, institutions, or governments in implementing eHealth programs. Methods: We conducted a structured review of both peer-reviewed and gray literature from 1998-2008. A Medline search for peer-reviewed articles found 40 papers focusing on different aspects of eHealth policy. In addition, a Google search found 20 national-and international-level policy papers and documents. We reviewed these articles to extract policy issues and solutions described at different levels of care. Results: The literature search found 99 policy issues related to eHealth. We grouped these issues under the following themes: (1) networked care, (2) interjurisdictional practice, (3) diffusion of eHealth/digital divide, (4) eHealth integration with existing systems, (5) response to new initiatives, (6) goal-setting for eHealth policy, (7) evaluation and research, (8) investment, and (9) ethics in eHealth. Conclusions: We provide a list of policy issues that should be understood and addressed by policy makers at global, jurisdictional, and institutional levels, to facilitate smooth and reliable planning of eHealth programs

Student led outreach workshops to promote Basic Life Support

Objectives: Primary aim of this project was to provide BLS training to staff, students and faculty of higher educational institutes of Rawalpindi and Islamabad (twin cities in Punjab, Pakistan) through pre-trained medical students. Secondary aim of the study project was to qualitatively record the impact of community training on student facilitators who conducted BLS workshops, through semi structured interviews. Methods: A mixed method Quasi experimental study was carried out at Foundation University Islamabad in collaboration with Higher Education Commission of Pakistan from 2015 to 2018. BLS trained 120 volunteer medical students were divided in 20 teams to visit and provide hands-on training to 20 educational institutes with 45-50 participants each. These participants completed pre and post training questionnaires, whereas, student trainers went through post training semi structured interviews. Quantitative analysis of participants pre and post training responses was done using SPSS 21. Qualitative assessment of impact on students was done through constant comparative analysis of transcripts. Results: A total of 675 participants including students, faculty and staff received hands on BLS training. Questionnaire based analysis of participants BLS knowledge showed >99% improvement (p < 0.001) after training. Main recurring themes identified in transcribed student interviews were, opportunity to improve self-confidence and technical skill. Conclusion: Hands on training sessions conducted by pre-trained medical students not only resulted in improvement in BLS knowledge of participants at various educational institutes but also had substantial impact on student trainers self-confidence and technique. Continuous..

Prevalence of Depression and Anxiety amongst Cancer Patients in a Hospital Setting: A Cross-Sectional Study

Background. The biomedical care for cancer has not been complemented by psychosocial progressions in cancer care. Objectives. To find the prevalence of anxiety and depression amongst cancer patients in a hospital setting. Design and Setting. This cross-sectional study was conducted at the tertiary care hospitals Shifa International Hospital Islamabad and Nuclear Medicine, Oncology, and Radiotherapy Institute [NORI]. Patients and Methods. 300 patients were interviewed from both the outpatient and inpatient department using The Aga Khan University Anxiety and Depression Scale (AKUADS). Main Outcome Measures. Using a score of 20 and above on the AKUADS, 146 (48.7%) patients were suffering from anxiety and depression. Results. When cross tabulation was done between different factors and the cancer patients with anxiety and depression, the following factors were found out to be significant with associated p value < 0.05: education of the patient, presence of cancer in the family, the severity of pain, and the patient’s awareness of his anxiety and depression. Out of 143 (47.7%) uneducated patients, 85 (59.4%) were depressed, hence making it the highest educational category suffering from depression and anxiety. Conclusion. The prevalence of anxiety and depression amongst cancer patients was high showing that importance should be given to screening and counseling cancer patients for anxiety and depression, to help them cope with cancer as a disease and its impact on their mental wellbeing. Limitations. The frequency of female patients in our research was higher than those of male patients