MOLECULAR MEDICINE: A PARADIGM SHIFT IN CLINICAL SCENARIO

Spectacular advances have been made in molecular medicine during the last few decades including the mapping of human genome project which has revolutionized the understanding of basic molecular mechanisms involved in the etio-pathogenesis of most of the diseases. The completion of Human Genome Project disclosed about 90% of the human genome. This draft of human genome sequences has identified at least 38,000 genes and opened the door for genomic medicine and molecular studies. However, more investigation about the potential function and interaction of these genes was required to improve the clinical information in medicin

High-Risk Human Papillomaviruses in Oral Squamous Cell Carcinoma (OSCC): A Meta-Analysis

Background: The prevalence of high-risk Human Papillomaviruses (HPV) in cases of oral cavity squamous cell carcinoma (OSCC) varies widely. Therefore, the aim of this study was to determine the pooled prevalence of all high-risk HPV by meta-analysis with specific emphasis on HPV type 16/18. Methods: The studies were retrieved from PubMed and MEDLINE to conduct a comprehensive literature review on HPV detection in OSCC. Search terms included, High-risk HPV, oral cancer, polymerase chain reaction (PCR), in situ hybridization (ISH). We reviewed 47 research studies systematically to report the prevalence of high-risk HPV infection in oral cancer. Included studies published from 1988 to 2018. The meta-analysis was carried out by using MedCalc software version 19.0.3. Results: A meta-analysis was executed to calculate the pooled prevalence of High-risk HPV types, which revealed overall decreasing order frequency of high-risk HPV and high-risk type displaying the highest number of type16/18 HPV in the reported cases. As 30.71% [24.59 to 37.19 % confidence interval (CI) at 95%] and 28.88 % [22.62 to 35.57% confidence interval (CI) at 95%] followed by other high-risk HPV 3.59% [2.22 to 5.46%] respectively. Conclusions: According to present meta-analysis, we conclude that 16/18 HPV displaying maximum infection rate as compared to other high-risk HPV type in OSCC cases

In Vitro Hepatic Differentiation of Adult, Embryonic, Induced Pluripotent and Perinatal Stem-Cells

Globally regenerative medicine is considered as one of the rapidly growing biomedical industry have objective to substitute damaged cells. Cell transplantation is less intrusive than whole-organ transplantation, and has been used to provide an alternative for patients to whole-organ transplantation. The End-stage liver disease comprises a subgroup of patients with cirrhosis who have signs of decompensation that is irreversible with medical treatment. The only restorative therapy for severe end-stage liver disease is orthotropic liver transplantation. However, liver transplantation has several limitations such as scarcity of organ donors, immunosuppressive drugs, and several postoperative complications. Thus, cell transplantation can be used for the treatment of end stage liver disorders to decrease the mortality in acute liver failure. Therefore, stem cells can be used for cellular therapy, development of liver disease models, and tissue-engineering applications. This review involved the studies conducted on the stem cells potential of hepatic differentiation, isolated from different sources. The PubMed and Google Scholar were searched for scientific studies reported the sources of stem cells based on their origin and their potential of hepatic differentiation in-vitro by using different tools of differentiation. All the research articles were selected in which solely hepatic differentiation in combination with different tools is reported. Keywords: Adult Stem Cells, Embryonic Stem Cells, Induced Pluripotent Stem Cells, In-vitro, Mesenchymal Stem Cells

The outcome of Posterio-lateral Decompression and Transpedicle Fixation for Thoracic Spine Tuberculosis

Objective:  The study assessed the outcome of posterio-lateral decompression and trans-pedicle fixation for thoracic spine tuberculosis. Materials and Methods:  An observational, cross-sectional study was conducted at the Department of Neurosurgery, Lady Reading Hospital, Peshawar. All those patients who had undergone posterio-lateral decompression and trans-pedicle fixation for thoracic spine tuberculosis were included. Both genders with ages more than 14 years were included in our study. Ethical committee approval was taken. Pre-designed proforma was used for data entry. Patients’ data were analysed through SPSS software. Results:  A total of 31 patients with tuberculous spondylodiscitis were studied. The age ranged from 15 – 57 years with a mean of 37.74 ± 10.07 years. Most of the patients with thoracic TB were male 54.8% (17/31). Pain improved in all the patients and neurology improved in most of the cases. The dural tear was in one patient and one patient had a wound infection. There was no mortality. Conclusions:  We conclude from the study that posterior-lateral decompression and trans-pedicle fixation for thoracic spine tuberculosis is a safe procedure. It has good results in terms of pain relief and neurological improvement. This procedure has an acceptable complications rate. Therefore, it can be considered as a better alternative to other surgical procedures for thoracic spine tuberculosis

Stem Cell Therapy: A Promising Treatment of Parkinson’s Diseases

The neurodegenerative disorder is a prolonged persistence curse and effect on economic and physical challenges in an aging world. Parkinson has come in the second category of disability disorders and associated with progressive dopaminergic neuronal degeneration with severe motor complications. It is an observation that gradual disease progression causes 70% degeneration of striatal dopaminergic neurons. Globally there are around 7-10 million patients with Parkinson's disease, however, there are huge efforts for therapeutic improvement. According to studies, no single molecular pathway was pointed out as a single etiology to control disease progression due to a lack of targeted therapeutic strategies. Previously implemented symptomatic treatments include L-dopa (L-3,4-dihydroxyphenylalanine), deep brain stimulation, and the surgical insertion of a medical device. This leads to dyskinesia, dystonia and a higher risk of major surgical complications respectively. However, not all the above-mentioned therapies can regenerate the dopaminergic neurons in Parkinson’s disease patients. Recent advances in the field of cellular therapy have shown promising outcomes by differentiation of multipotent mesenchymal stem cells into dopaminergic neurons under the influence of a regenerative substance. In this review, we have discussed the differentiation of dopaminergic neurons by using different cell types that can be used as a cellular therapeutic approach for Parkinson’s disease. The information was collected through a comprehensive search using the keywords, “Parkinson Disease, Dopamine, Brain derived neurotrophic” factor and neuron from reliable search engines, PubMed, Google Scholar and Medline reviews from the year 2010 to 2020. Keywords: Parkinson Disease; Dopamine; Brain Derived Neurotrophic Factor; Neuron

Antidiabetic activity of Berberis brandisiana is possibly mediated through modulation of insulin signaling pathway, inflammatory cytokines and adipocytokines in high fat diet and streptozotocin-administered rats

Medicinal plants play a key role in protection of chronic non-communicable ailments like diabetes, hypertension and dyslipidemia. Berberis brandisiana Ahrendt (Berberidaceae) is traditionally used to treat diabetes, liver problems, wounds, arthritis, infections, swelling and tumors. It is also known to be enriched with multiple phytoconstituents including berbamine, berberine, quercetin, gallic acid, caffeic acid, vanillic acid, benzoic acid, chlorogenic acid, syringic acid, p-coumaric acid, m-coumaric acid and ferulic acid. The efficacy of B. brandisiana has not been established yet in diabetes. This study has been planned to assess the antidiabetic activity of B. brandisiana in high fat diet and streptozotocin (HFD/STZ)-induced diabetes using animals. Administration of aqueous methanolic extract of B. brandisiana (AMEBB) and berbamine (Berb) for 8 weeks caused a dose dependent marked (p < 0.01) rise in serum insulin and HDL levels with a significant decline (p < 0.01) in glucose, triglycerides, glycosylated hemoglobin (HbA1c), cholesterol, LDL, LFTs and RFTs levels when compared with only HFD/STZ-administered rats. AMEBB and Berb also modulated inflammatory biomarkers (TNF-α, IL-6) and adipocytokines (leptin, adiponectin and chemerin). AMEBB (150 mg/kg and 300 mg/kg) and Berb (80 mg/kg and 160 mg/kg) treated rats showed a marked increase (p < 0.001) in catalase levels (Units/mg) in pancreas (42.4 ± 0.24, 47.4 ± 0.51), (38.2 ± 0.583, 48.6 ± 1.03) and liver (52 ± 1.41, 63.2 ± 0.51), (57.2 ± 0.58, 61.6 ± 1.24) and superoxide dismutase levels (Units/mg) in pancreas (34.8 ± 1.46, 38.2 ± 0.58), (33.2 ± 0.80, 40.4 ± 1.96) and liver (31.8 ± 1.52, 36.8 ± 0.96), (30 ± 0.70, 38.4 ± 0.81),respectively while a significant (p < 0.01) decrease in serum melondialdehyde levels (nmol/g) in pancreas (7.34 ± 0.17, 6.22 ± 0.22), (7.34 ± 0.20, 6.34 ± 0.11) and liver (9.08 ± 0.31,8.18 ± 0.29), (9.34 ± 0.10, 8.86 ± 0.24) compared to the data of only HFD/STZ-fed rats. Histopathological studies of pancreas, liver, kidney, heart and aorta revealed restoration of normal tissue architect in AMEBB and Berb treated rats. When mRNA expressions of candidate genes were assessed, AMEBB and Berb showed upregulation of IRS-1, SIRT1, GLUT-4 and downregulation of ADAM17. These findings suggest that AMEBB and Berb possess antidiabetic activity, possibly due to its effect on oxidative stress, glucose metabolism, inflammatory biomarkers and adipocytokines levels. Further upregulation of IRS-1, SIRT1, GLUT-4 and downregulation of ADAM17, demonstrated its potential impact on glucose homeostasis, insulin resistance and chronic inflammatory markers. Thus, this study provides support to the medicinal use of B. brandisiana and berbamine in diabetes

Isolation of Homogenous Population of Human Amniotic Epithelial Stems Cells

Background: Regenerative medicine is a collaborative field that applies combined concepts of tissue engineering and cell biology to promote regeneration. Tissue regeneration initiate the emergence of remedies that can replace and revive tissues and loss of organs through illness and injury and reduce dependency on organ transplantation. The objective was to isolate a homogenous population of human amniotic epithelial stem cells (hAECs) and to determine their phenotype under a live-cell imaging microscope at 1st, 3rd and 8th-day intervals. Methods: This was an experimental in-vitro study conducted on human placenta (amniotic epithelial stem cells) at Ziauddin Hospital and University. The 22 human placenta were collected from patients with age 20-30 years having healthy full-term pregnancies, with a preference for elective cesarean sections. In vitro isolation of human amniotic epithelial stem cells was used after manual removal of the amniotic membrane from the chorionic membrane of human term placenta via single-step enzymatic digestion. The morphology of the attached cells was analyzed at different magnifications i.e., 10X, 20X and 40X. Results: The isolated human amniotic epithelial stem cells on day 3 started forming colonies and attained a characteristic cuboid epithelial shape and exhibited a confluent single layer on day 8. Morphologically resembled cobblestones with a characteristic of fully vacuolated cytoplasm were found uncontaminated with spindle-shaped human amniotic mesenchymal stem cells (MSCs). Conclusion: The isolated population of hAESCs were highly proliferative and not contaminated with MSCs. Therefore, this optimized protocol may be used for the isolation and the biobanking of hAESCs for future cellular transplantation. Keywords: Human Amniotic Epithelial Stem Cells (hAESCs); Regenerative Medicine; Perinatal Stem Cells; Placental Membrane; Amniotic Membrane

Automating Test Case Generation for Android Applications using Model-based Testing

Testing of mobile applications (apps) has its quirks as numerous events are required to be tested. Mobile apps testing, being an evolving domain, carries certain challenges that should be accounted for in the overall testing process. Since smartphone apps are moderate in size so we consider that model-based testing (MBT) using state machines and statecharts could be a promising option for ensuring maximum coverage and completeness of test cases. Using model-based testing approach, we can automate the tedious phase of test case generation, which not only saves time of the overall testing process but also minimizes defects and ensures maximum test case coverage and completeness. In this paper, we explore and model the most critical modules of the mobile app for generating test cases to ascertain the efficiency and impact of using model-based testing. Test cases for the targeted model of the application under test were generated on a real device. The experimental results indicate that our framework reduced the time required to execute all the generated test cases by 50%. Experimental setup and results are reported herein

Clinicopathologic features and prognostic grouping of gastrointestinal stromal tumors (GISTs) in Pakistani patients: An institutional perspective

Objectives: Gastrointestinal stromal tumors (GISTs) are rare tumors of gastrointestinal tract, prognosis of which largely depends upon histopathologic characteristics of resection specimens, which were not widely studied in our population. Therefore we aimed to evaluate the histopathologic characteristics of GISTs in our population and their prognostic grouping according to college of American pathologist’s guidelines. Results: Mean age of patients was 53.4 years (18–71 years). 92% of cases were of primary GISTs and stomach was the most common site (57.7%). 75% of cases were of spindle cell morphology and 53.8% belonged to high risk prognostic group. Comparison of stomach and intestinal GISTs showed that intestinal GISTs were found to be of high grade (70%) and of high risk prognostic group (75 and 80%) compared to stomach GISTs (43% were of high risk prognostic group), however this fnding was not statistically signifcant. GISTs are infrequent gastrointestinal tumors but early diagnosis and identifcation of adverse histological features are key to successful treatment. We found a large majority of GISTs to be located in stomach, however intestinal GISTs were found more likely to be associated with adverse prognostic parameters. However more large scale studies are warranted to establish this fnding

Performance of the TIMI risk score in predicting mortality after primary percutaneous coronary intervention in elderly women: Results from a developing country

Background: Despite women undergoing primary percutaneous coronary intervention (PPCI) having a higher rate of adverse outcomes than men, data evaluating prognostic risk scores, especially in elderly women, remains scarce. This study was conducted to validate the predictive value of Thrombolysis in Myocardial Infarction (TIMI) risk score in elderly female patients. Materials and Methods: This was a retrospective analysis of elderly (\u3e65 years) female patients who underwent PPCI for ST-elevated myocardial infarction (STEMI) from October 2016 to September 2018. Patients\u27 demographic details and elements of TIMI risk score including age, co-morbidities, Killip classification; weight, anterior MI and total ischemic time were extracted from hospital records. The primary outcome was in-hospital mortality and post-discharge mortality reported on telephonic follow-up. Results: A total of 404 elderly women with a median age of 70 years were included. The mean TIMI score was 5.25±1.45 with 40.3% (163) patients of TIMI score \u3e 5. In-hospital mortality rate was 6.4% (26) and was found to be associated with TIMI score (p\u3c0.001). The in-hospital mortality rate increased from 3.1% at TIMI score of 0-4 to 34.6% at the score of 8. On follow-up (16.43±7.40 months) of 211 (55.8%) patients, the overall mortality rate was 20.3%, and this was also associated with TIMI score (p\u3c0.001). The mortality rate increased from 5.6% at the score of 0-4 to 54.5% at the score of 8. The predictive values (area under the curve) of TIMI risk score for in-hospital and post-discharge mortality were 0.709 (95% CI 0.591-0.827; p \u3c0.001) and 0.689 (95% CI 0.608-0.770; p \u3c0.001), respectively. Conclusion: Increased adverse outcomes were observed with higher TIMI risk score for in hospital and post-discharge follow-up. Therefore, the prognostic TIMI risk score is a robust tool in predicting both in-hospital as well as post-discharge mortality in elderly females