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Thyroid cancer is the most common malignancy of the endocrine glands, and during last couple of decades, its incidence has risen alarmingly, across the globe. Etiology of thyroid cancer is still debatable. There are a few worth mentioning risk factors which contribute to initiation of abnormalities in thyroid gland leading to cancer. Genetic instability is major risk factors in thyroid carcinogenesis. Among the genetic factors, the Src family of genes (Src, Yes1, Fyn and Lyn) have been implicated in many cancers but there is little data regarding the association of these (Src, Yes1, Fyn and Lyn) genes with thyroid carcinogenesis. Fyn and Lyn genes of Src family found engaged in proliferation, migration, invasion, angiogenesis, and metastasis in different cancers. This study was planned to examine the effect of Fyn and Lyn SNPs on thyroid cancer risk in Pakistani population in 500 patients and 500 controls. Three polymorphisms of Fyn gene (rs6916861, rs2182644 and rs12910) and three polymorphisms of Lyn gene (rs2668011, rs45587541 and rs45489500) were analyzed using Tetra-primer ARMS-PCR followed by DNA sequencing. SNP rs6916861 of Fyn gene mutant genotype (CC) showed statistically significant threefold increased risk of thyroid cancer (P 0.0001). In case of rs2182644 of Fyn gene, mutant genotype (AA) indicated statistically significant 17-fold increased risk of thyroid cancer (P 0.0001). Statistically significant threefold increased risk of thyroid cancer was observed in genotype AC (P 0.0001) of Fyn gene polymorphism rs12910. In SNP rs2668011 of Lyn gene, TT genotype showed statistically significant threefold increased risk of thyroid cancer (P 0.0001). In case of rs45587541 of Lyn gene, GA genotypes showed statistically significant 11-fold increased risk in thyroid cancer (P 0.0001). Haplotype analysis revealed that AAATAG*, AGACAG*, AGCCAA*, AGCCAG*, CAATAG*, CGCCAG* and CGCCGA* haplotypes of Fyn and Lyn polymorphisms are associated with increased thyroid cancer risk. These results showed that genotypes and allele distribution of Fyn and Lyn are significantly linked with increased thyroid cancer risk and could be genetic adjuster for said disease.

To compare the effectiveness of Proprioceptive Neuromuscular Facilitation (PNF) and Passive Vertebral Mobilization (PVM), both when given in adjunct to routine physical therapy (RPT), on neck disability in patients with mechanical neck pain (MNP).A single-blinded randomized controlled trial was conducted on 90 patients with MNP at the National Institute of Rehabilitation Medicine, Islamabad, Pakistan, from September 2015 to March 2018. The participants aged between 18 and 65 years were recruited through a simple random sampling technique and randomly divided into three groups i.e. PNF + RPT, PVM + RPT, and RPT. Each participant was evaluated pre and post-intervention (after four weeks) through neck disability index (NDI). The data were analyzed by using SPSS version 21.The MANOVA was run on the pre-post mean differences of the variables to determine the changes within the groups which showed that the participants improved significantly in all the groups in terms of the NDI components and overall NDI score (p 0.05). Univariate analysis with the post-hoc comparison and Tuckey HSD correction was used to determine the differences between the groups which showed that there was a significant difference between the interventional groups in the overall pain intensity, as well as pain experienced while performing personal care activities, reading, doing work, driving, sleeping, recreation and in the total NDI score (p 0.05).PVM (in adjunct to RPT) was more effective than PNF (in adjunct to RPT) for the patients with MNP to manage themselves in daily activities.NCT03813680 (at clinicaltrials.gov) (https://clinicaltrials.gov/ct2/show/NCT03813680).

The objective of our study was to evaluate the efficacy of Master Lithoclast, also known as trilogy lithoclast, in simultaneous bilateral Percutaneous Nephrolithotomy (PCNL). The study was a prospective case series, involving 40 patients undergoing bilateral simultaneous PCNL, with 20 (50%) males and 20 (50%) females. The mean age of subjects was 32.9 ± 7.9 years. In Guy’s stone scoring 7(17.5%) patients classified in Group I, 28 (70%) in group II and the remaining 5(12.5%) patients were placed in group III. Total operative time observed was 74.8 ± 17.9 minutes. Complete stone clearance was observed in 30 (75%) patients. In conclusion, study data confirmed that Master Lithoclast provides faster stone clearance and is unaffected by the composition of stones, ease of usability, and improved tissue safety with reduced chances of fragments blocking are key factors. Keywords: Master lithoclast, Simultaneous bilateral PCNL, Trilogy lithoclast, Renal stone.

Background During the Middle East Respiratory Syndrome Coronavirus (MERS-CoV) outbreak of 2014, tertiary care cardiac centers shouldered the responsibility of caring for patients presenting with Acute Coronary Syndromes (ACS). This entailed designing algorithms that ensured timely management of patients with ACS in the setting of an emerging novel viral infection that was rapidly spreading within the community with a high infectivity and case fatality rate. The objective of this study is to describe a single center experience and the adopted pathway for the management of ACS. Methods This is a single center retrospective observational study of all patients who were admitted between March 1, 2014 and May 31, 2014 with an ACS. Total ACS admissions, bed turnover, procedures and healthcare personnels' infection rates were obtained from the annual statistics database and employee health records. All baseline characteristics, therapy received, outcomes and MERS-CoV status were obtained from the chart review. Results A total of 148 patients with a diagnosis of ACS were admitted during that period of time. Of those, 59 had STEMI, 42 had NSTEMI and 47 had unstable angina. PCI was performed in 74, coronary artery bypass grafting (CABG) in 28 and conservative therapy was prescribed for 46 patients. The bed turnover was no higher than the previous or subsequent two months suggesting no change in practice. The infection rate of MERS-CoV was zero for healthcare workers. Conclusions In times of a national health crisis it is imperative that best practices are upheld to sustain existing resources, reduce bed occupancy and preserve medical personnel. A key component of such a strategy depends on assigning centers dedicated to isolating and treating the highly infectious disease outbreak while allowing other centers to provide expeditious cardiac care., Highlights • Cardiac centers should balance healthcare worker exposure with the provision of timely guideline directed care for acute coronary syndromes. • Compared to COVID19, MERS-CoV patients are highly symptomatic & easily identifiable allowing healthcare systems to adjust clinical pathways. • Assigning centers dedicated to the management of MERS-CoV cases permits tertiary centers to continue to treat ACS in accordance with guidelines.

Thalassemia is the most common congenital monogenic disorder in Bangladesh. Prenatal diagnosis (PND) and pregnation termination of an affected child is one of the best options to reduce the burden of thalassemic children. This article reports the results of DNA analyses of chorionic villus sampling (CVS) and amniocentesis of fetuses of mothers who came to the thalassemia center of Dhaka Shishu (Children) Hospital, Dhaka, Bangladesh. DNA analysis was done by real-time polymerase chain reaction (qPCR) and Sanger sequencing. Maternal contamination was ruled out by variable number of tandem repeats (VNTRs). A total of 232 samples were analyzed. Hb E (HBB: c.79G>A)/β-thalassemia (Hb E/β-thal) was the most common type of thalassemia seen in 32 samples (13.79%) followed by β-thal major (β-TM) in 10 cases (4.31%). Molecular characterization of the most predominant mutation was IVS-I-5 (G>A) (HBB: c.92+5G>C). The analysis also revealed five rare mutations: IVS-II-654 (C>T) (HBB: c.316-197C>T), IVS-II-1 (G>A) (HBB: c.315+5G>A), codon 44 (-C) (HBB: c.135delC), -86 (C>A) (HBB: c.-136C>A) and codons 14/15 (+G) (HBB: c.45_46insG), which have not been reported previously in Bangladesh. This study provides important information for PND and will help in the development of similar diagnostic programs for other DNA centers in Bangladesh.

Aim: We aimed to evaluate the role of selected single nucleotide polymorphisms of DNA damage response pathway genes in breast cancer (BC). Materials & methods: In present study, 500 BC patients and 500 controls was used to estimate the frequency of single nucleotide polymorphisms of DNA damage response pathway genes. Tetra-amplification refractory mutation system-PCR technique was used for screening of the six selected polymorphisms. Results: Logistic regression analysis showed that heterozygous mutant genotype of rs1800057 (p < 0.0001) and homozygous mutant genotype of rs1801516 (p < 0.0001) was associated with significant increased risk of BC. In the ATR gene, heterozygous mutant genotype of rs2227931 (p < 0.0001) was associated with significant increased risk of BC. However, significant decreased risk of BC was found associated with heterozygous mutant genotype of rs2227928 (p < 0.0002) and homozygous mutant genotype of rs2229032 (p < 0.0001) in patients compared with controls. Conclusion: The present results showed that alteration in DNA damage response pathway gene ( ATM & ATR) results in increased BC risk.

Ubiquitin-proteasome system (UPS) gene, PSMD1, is an important gene for neutralization of damaged and misfolded protein(s). The current study was designed to study the genetic and expression variations of PSMD1 gene as a consequence of arsenic exposure and its potential implications in arsenic induced diseases. In the present study, 250 blood samples of exposed industrial workers along with 250 controls were used. Initially, tetra amplification refractory mutation system-PCR was used to determine the role of PSMD1 gene polymorphisms (rs1549339, rs13402242) in industrial workers and controls. Frequency of homozygous mutant genotype of rs1549339 (OR: 2.23, 95% CI: 1.51–3.32, p = 0.0001) and rs13402242 (OR: 2.96, 95% CI: 1.52–5.75, p = 0.001) was observed significantly higher in exposed individuals vs controls. Secondly, qPCR was performed for expression analysis of PSMD1 gene. Significant down-regulated expression of PSMD1 gene (p

Background ß-thalassemia is one of the most common inherited blood disorders in the world and a major deterrent to the public health of Bangladesh. The management of thalassemia patients requires lifelong frequent blood transfusion and the available treatment options are unsatisfactory. A national policy on thalassemia prevention is mandatory in Bangladesh. However, precise and up-to-date information on the frequency of ß-thalassemia carriers are missing due to lack of accurate diagnostic approaches, limited access to information and absence of national screening program. This study aims to determine the nationwide carrier frequency of hemoglobin E (HbE) and β- thalassemia and mutation spectrum among the carriers using molecular, hematological and biochemical methods. Methods The study enrolled a total of 1877 individuals (60.1% male and 39.9% female) aged between 18 and 35 years. Total sample size and its division-wise breakdown were calculated in proportion to national and division-wise population. Venous blood was collected and subjected to CBC analysis and Hb-electrophoresis for each participant. Serum ferritin was measured to detect coexistence of iron deficiency anemia with thalassemia carrier. DNA-based High Resolution Melting (HRM) curve analysis was performed for confirmation of carrier status by mutation detection. Results Of 11.89% (95% CI, 10.43–13.35) carriers of β-globin gene mutations, 8.68% (95% CI, 7.41–9.95) had HbE trait (ETT) and 2.24% (95% CI, 1.57–2.91) had beta-thalassemia trait (BTT). Among eight divisions, Rangpur had the highest carrier frequency of 27.1% (ETT-25%, BTT-2.1%), whereas Khulna had the lowest frequency of 4.2% (ETT-4.2% only). Moreover, α- thalassemia, HbD trait, HbE disease, hereditary persistence of HbF were detected in 0.11, 0.16, 0.43 and 0.16% participants, respectively. HRM could identify two individuals with reported pathogenic mutations in both alleles who were erroneously interpreted as carriers by hematological indices. Finally, a total of nine different mutations including a novel mutation (c.151A > G) were detected in the β-globin gene. Conclusions Since carrier frequency for both HbE and β-thalassemia is alarmingly high in Bangladesh, a nationwide awareness and prevention program should be made mandatory to halt the current deteriorating situations. Mutation-based confirmation is highly recommended for the inconclusive cases with conventional carrier screening methods to avoid any faulty detection of thalassemia carriers.

Purpose: The present study was designed to understand the role of expression variations of mitochondrial imported sirtuins in brain tumorigenesis. The expression levels of mitochondrial imported sirtuins were further analyzed for biomarker potential. Methods: Samples from 200 brain tumors and 200 healthy control tissues were used for expression analysis using quantitative PCR and for DNA damage using LORD-Q analysis. Results: Significant deregulation of SIRT3 (p = 0.002), SIRT4 (p = 0.03) and SIRT5 (p = 0.006) was observed in brain tumors versus controls. Co-expression analysis showed a significant correlation between the mitochondrial imported sirtuins versus apoptotic genes. LORD-Q analysis showed a significantly increased frequency of lesions/10 kb of mitochondrial imported sirtuins (p

Patients suspected of ventilator-associated lower respiratory tract infections (VA-LRTIs) commonly receive broad-spectrum antimicrobial therapy unnecessarily. We tested whether exhaled breath analysis can discriminate between patients suspected of VA-LRTI with confirmed infection, from patients with negative cultures. Breath from 108 patients suspected of VA-LRTI was analysed by gas chromatography-mass spectrometry. The breath test had a sensitivity of 98% at a specificity of 49%, confirmed with a second analytical method. The breath test had a negative predictive value of 96% and excluded pneumonia in half of the patients with negative cultures. Trial registration number: UKCRN ID number 19086, registered May 2015.

Hemp (Cannabis sativa L.) is a herbaceous anemophilous plant that belongs to the Cannabinaceae family. The cannabis seed (hemp) has long been utilized as a food source and is commercially important as an edible oil source. In this review, the positive and negative health effects of cannabis, the relationship between cannabis and various diseases, and the use of cannabis in various food products have been discussed. In addition, the scientific literature on the potential use of cannabis and its derivatives as a dietary supplement for the prevention and treatment of inflammatory and chronic degenerative diseases in animals and humans has been reviewed. Cannabis is being developed as a key ingredient in a variety of food items, including bakery, confectionery, beverages, dairy, fruits, vegetables, and meat. Hemp seeds are high in readily digestible proteins, lipids, polyunsaturated fatty acids (PUFA), insoluble fiber, carbs, and favorable omega-6 PUFA acid to omega-3 PUFA ratio and have high nutritional value. The antioxidants of cannabis, such as polyphenols, help with anxiety, oxidative stress, and the risk of chronic illnesses, including cancer, neurological disorders, digestive problems, and skin diseases. Cannabis has been shown to have negative health impacts on the respiratory system, driving, and psychomotor functions, and the reproductive system. Overall, the purpose of this research is to stimulate more in-depth research on cannabis’s adaptation in various foods and for the treatment of chronic illnesses.

Inflammation is strongly implicated in both injury and repair processes occurring after stroke. In this exploratory study we assessed the feasibility of repeated sampling of exhaled volatile organic compounds and performed an untargeted metabolomic analysis of plasma collected at multiple time periods after stroke. Metabolic profiles were compared with the time course of the inflammatory markers C-reactive protein (CRP) and interleukin-6 (IL-6). Serial breath sampling was well-tolerated by all patients and the measurement appears feasible in this group. We found that exhaled decanal tracks CRP and IL-6 levels post-stroke and correlates with several metabolic pathways associated with a post-stroke inflammatory response. This suggests that measurement of breath and blood metabolites could facilitate development of novel therapeutic and diagnostic strategies. Results are discussed in relation to the utility of breath analysis in stroke care, such as in monitoring recovery and complications including stroke associated infection.

Purpose: The present study was planned to explore the expression variations of mitochondrial sirtuins and the mitochondrial DNA repair enzyme OGG1-2a in leukemia patients. Oxidative stress and deacetylation levels of leukemia patients were measured in the present study. Methods: A total of 200 leukemia patients along with 200 healthy controls were evaluated using quantitative PCR, 8OXOG assay and deacetylation assay. Results: Significant deregulation of SIRT3 (p

Aim: In this study, we evaluated the effect of selected polymorphisms of mitochondrial unfolded protein response (UPRmt) pathway in 500 head and neck cancer (HNC) patients and 500 healthy controls from Pakistan. Materials & methods: The experiments were conducted using tetra-ARMS PCR followed by DNA sequencing. Results: Multivariate analysis showed that AA genotype of rs3782116 showed fivefold, GG genotype of rs6598072 approximately twofold and CC genotype of rs4946936 and TT genotype of rs12212067 showed twofold increased risk of HNC. Furthermore, haplotype analysis showed that certain haplotypes of UPRmt pathway single nucleotide polymorphisms have significant association with increased HNC risk. Conclusion: These results show that genetic aberrations in UPRmt pathway genes have association with increased HNC risk and can be an indicator of advance clinical outcome especially invasion and metastasis.

Lay abstract The purpose of this research was to explore the role of

Epstein-Barr virus encoded RNAs (EBER1 and EBER2) are two non-polyadenylated, non-protein coding small RNAs expressed at high levels in all forms of EBV latent infections. Although not directly involved in cell transformation, a number of studies have reported that these RNAs may be involved in cell proliferation. However, which of the two EBERs play a major role in this process and the mechanisms involved remains unknown. The aim of this study was to investigate the role and mechanism of EBER1-induced cell proliferation. Using stably transfected EBER1 cell lines, and multiple methodologies, we show that EBER1 transfected epithelial, B and T cell lines proliferate at a higher rate, have higher metabolic activity and increased DNA synthesis. The mitochondrial number and activity was also observed to be higher in the EBER1 transfected cells. Moreover, cytochrome c activity and store operated calcium entry (SOCE) were potentiated in the EBER1 expressing cells. Finally, the genes associated with cell proliferation were also observed to be up-regulated in the EBER1 transfected cells. Taken together, our data has unravelled the role of mitochondria and cellular calcium pathway that appear to be involved in EBER1 induced cell proliferation of EBV infected cells.

Objective: To calculate the incidence of post-transplant erythrocytosis, and to assess the response to treatment. Method: The prospective study was conducted from April 2016 to April 2018 at the Department of Nephrology, Bahria International Hospital, Lahore, Pakistan, and comprised patients undergoing renal transplantation who were evaluated and followed up for 12 months. Patients having haemoglobin levels ?17gm/dl were labelled as having polycythemia. Data was analysed using SPSS 21. Results: Of the 94 total patients, 69(73.4%) were enrolled. During follow-up, 2(2.9%) of them died, and, thus, the final sample stood at 67(71.3%); 57 (85%) males and 10(15%) females. The mean age of the sample was 32.6±8.8 years. Overall, 19(28.4%) patients developed polycythemia and they were either given angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers. Of these 19 patients, 11(57.8 %) responded to the treatment, while 8(42.1%) required phlebotomy. Further, 3(15.7%) patients required one phlebotomy, while 5(26.3%) who had glomerular filtration rate >30% had to have repeated phlebotomy. Conclusion: The incidence of post-transplant erythrocytosis was significantly high at 28.4%. Key Words: Post-transplant polycythemia, Erythrocytosis, Continuous...

Aqueous-based film coating suspensions are associated with reliance on alkalinising reagents and poor film formation. The impact of particle size in this process and resultant film properties remains unclear. This study offers the first direct comparison of film formation properties between aqueous micro- and nano-suspensions of the enteric polymer Eudragit S100. High-pressure homogenisation was employed to produce nano-suspensions of the enteric polymer. Formed enteric suspensions (micro- and nano-) were evaluated in terms of size, morphology, and ability to form film; with resultant films analysed in terms of; film thickness, mechanical and thermoplastic properties, water uptake, weight loss, and drug permeability in acidic medium. High-pressure homogenisation yielded particles within a submicron range (150-200 nm). Produced nano-suspensions formed significantly thinner films (

In this review, we summarised the different methods for copper nanoparticle synthesis, including green methods. We highlighted that the synthesis of the copper nanoparticles from green sources is preferable as they serve as stable and reducing entities. Furthermore, we critically reviewed the effectiveness of copper- based nanoparticles in oncogenic treatments emphasizing breast, lung, colorectal, and skin cancers. Finally, we have summarised the recent progress made in copper-based nanoparticles and their applications to amplify and rectify present cancer treatment options. The synthesis, characterization, stabilization, and functionalization techniques of various copper-based nanoparticles have also been highlighted in each section. In conclusion, the review provides the outlook of copper nanoparticles in cancer diagnostics and therapeutics.

Bowel and bladder problems in children with cerebral palsy (CP) negatively affect both the children and their families. Routine physical therapy (PT) may contribute to relieving constipation in children with CP by reducing spasticity.To determine the effectiveness of PT in relieving constipation in children with spastic CP.This was a single-blinded randomized crossover trial (Clinical Trail # NCT03379038) that included 35 children with spastic CP. The children who fulfilled the inclusion criteria were randomly assigned to one of two groups: the progressive physical therapy (PPT) or the maintenance physical therapy (MPT) group.Data was collected via general demographic questionnaire, defecation frequency (DF) questionnaire, Constipation Assessment Scale (CAS) and the Modified Ashworth Scale (MAS) at baseline and at the 2nd, 4th, and 6th week before and after crossover. The Mann Whitney U-test was used for between-group comparisons and the Friedman and Wilcoxon signed-rank test for post hoc analysis tests were used for within-group changes. To determine the relationship between spasticity and constipation, simple linear regression was used.National Institute of Rehabilitation Medicine, Islamabad, Pakistan.Neither group showed a significant difference in spasticity level or DF at baseline or at the end of the 2nd week. However, at the end of the 4th week (PPT = 4[1] vs MPT = 2[1]; U = 192; P.001) and 6th week (PPT = 4[1] vs 3(1); U = 158; P.001) DF was significantly better in the PPT group than in the MPT group. Regarding constipation severity, the PPT group showed significantly better results on all items of the Constipation Assessment Scale (CAS) compared with the MPT group after intervention (P.001). The results showed that spasticity was significantly correlated with DF (r = -0.81; P.001) and constipation severity (r = 0.45; P.001).Physical therapy significantly improves DF and reduces constipation severity in children with spastic CP.

Exhaled breath analysis is a promising new diagnostic tool, but currently no standardised method for sampling is available in mechanically ventilated patients. We compared two breath sampling methods, first using an artificial ventilator circuit, then in "real life"in mechanically ventilated patients on the intensive care unit. In the laboratory circuit, a 24-component synthetic-breath volatile organic compound (VOC) mixture was injected into the system as air was sampled: (A) through a port on the exhalation limb of the circuit and (B) through a closed endo-bronchial suction catheter. Sorbent tubes were used to collect samples for analysis by thermal desorption-gas chromatography-mass spectrometry. Realistic mechanical ventilation rates and breath pressure-volume loops were established and method detection limits (MDLs) were calculated for all VOCs. Higher yields of VOCs were retrieved using the closed suction catheter; however, for several VOCs MDLs were compromised due to the background signal associated with plastic and rubber components in the catheters. Different brands of suction catheter were compared. Exhaled VOC data from 40 patient samples collected at two sites were then used to calculate the proportion of data analysed above the MDL. The relative performance of the two methods differed depending on the VOC under study and both methods showed sensitivity towards different exhaled VOCs. Furthermore, method performance differed depending on recruitment site, as the centres were equipped with different brands of respiratory equipment, an important consideration for the design of multicentre studies investigating exhaled VOCs in mechanically ventilated patients.

Emerging evidence suggests that the South Asian (SA) population has an increased rate of in-stent stenosis (ISR) after percutaneous coronary intervention (PCI) when compared with other ethnicities. Drug-eluting balloons (DEBs) have emerged as a viable option for the treatment of ISR. However, data describing the outcomes of DEB-PCI in the SA population are limited. Since the magnitude of the problem is high in the SA population, it is essential to evaluate the outcomes of DEB-PCI for ISR.In this cohort study, we investigated the incidence of target-lesion revascularization (TLR) and major adverse cardiac event (MACE) after PCI with DEB for ISR at 1 year and at long-term follow-up in Pakistani patients. From January 2010 to January 2019, a total of 147 ISR lesions in 112 patients were treated with DEB-PCI at our center.The incidence of clinically driven TLR and MACE after a 1-year follow-up was 15.2% and 16.1%, respectively. At mean long-term follow-up of 2.73 ± 2.14 years, the TLR and MACE rates were 26.8% and 35.7%, respectively. The major predictors for TLR were diffuse and occlusive ISR types, DEB for a recurrent restenosis lesion, and the presence of ≥3 traditional cardiovascular disease risk factors.The high rates of follow-up TLR and MACE reported in this study may suggest that the outcomes of DEB-PCI for ISR in the SA population may be unsatisfactory. With the increasing use of DEBs, it is imperative to further investigate DEB-PCI outcomes in the SA population with large, prospective studies.

Superparamagnetic iron oxide nanoparticles (SPIONs) and core-shell type nanoparticles, consisting of SPIONs coated with mesoporous silica and/or lipid, were synthesised and tested for their potential theranostic applications in drug delivery, magnetic hyperthermia and as a contrast agent. Transmission Electron Microscopy (TEM) confirmed the size of bare and coated SPIONs was in the range of 5–20 nm and 100–200 nm respectively. The superparamagnetic nature of all the prepared nanomaterials as indicated by Vibrating Sample Magnetometry (VSM) and their heating properties under an AC field confirm their potential for hyperthermia applications. Scanning Column Magnetometry (SCM) data showed that extrusion of bare-SPION (b-SPION) dispersions through a 100 nm polycarbonate membrane significantly improved the dispersion stability of the sample. No sedimentation was apparent after 18 h compared to a pre-extrusion estimate of 43% settled at the bottom of the tube over the same time. Lipid coating also enhanced dispersion stability. Transversal relaxation time (T2) measurements for the nanoparticles, using a bench-top relaxometer, displayed a significantly lower value of 46 ms, with a narrow relaxation time distribution, for lipid silica coated SPIONs (Lip-SiSPIONs) as compared to that of 1316 ms for the b-SPIONs. Entrapment efficiency of the anticancer drug, Doxorubicin (DOX) for Lip-SPIONs was observed to be 35% which increased to 58% for Lip-SiSPIONs. Moreover, initial in-vitro cytotoxicity studies against human breast adenocarcinoma, MCF-7 cells showed that % cell viability increased from 57% for bSPIONs to 82% for Lip-SPIONs and to 87% for Lip-SiSPIONs. This suggests that silica and lipid coatings improve the biocompatibility of bSPIONs significantly and enhance the suitability of these particles as drug carriers. Hence, the magnetic nanomaterials prepared in this work have potential theranostic properties as a drug carrier for hyperthermia cancer therapy and also offer enhancement of contrast agent efficacy and a route to a significant increase in dispersion stability.

OBJECTIVE To assess the frequency and time of onset of new-onset diabetes after transplant (NODAT) and its associated factors. STUDY DESIGN Observational study. PLACE AND DURATION OF STUDY Department of Nephrology, Bahria International Hospital, Lahore, Pakistan, from April 2016 to April 2018. METHODOLOGY NODAT was diagnosed according to American Diabetes Association Criteria with fasting plasma glucose >126 mg/dl or random plasma glucose >200 mg/dl. Those with pre-existing diabetes and follow-up duration less than 12months, were excluded. Patients were divided in two groups: with and without NODAT, for statistical comparison. RESULTS The study included 115 patients, 101 were males and the median age was 35.0 (29.0-46.0) years. During the one-year period of follow-up, 28 (24.3%) patients developed NODAT. The mean time of onset of NODAT was 5.3 ± 3.6 months. Family history of diabetes was positive in 46% patients in NODAT group, which was significantly higher as compared to 5.7% in non-NODAT group with p-value of

The present study was designed to determine the association between the genetic polymorphisms/expression variations of RB1 and CCND1 genes and brain tumor risk. For this purpose, 250 blood samples of brain tumor patients along with 250 controls (cohort I) and 96 brain tumor tissues (cohort II) with adjacent control section were collected. Mutation analysis of RB1 (rs137853294, rs121913300) and CCND1 (rs614367, rs498136) genes was performed using ARMS-PCR followed by sequencing, and expression analysis was performed using real-time PCR and immunohistochemistry. The results showed homozygous mutant genotype of RB1 gene polymorphism, rs121913300 (P=0.003) and CCND1 gene polymorphism rs614367 (P=0.01) were associated significantly with brain tumor risk. Moreover, significant down-regulation of RB1 (P=0.005) and up-regulation of CCND1 (P=0.0001) gene was observed in brain tumor sections vs controls. Spearman correlation showed significant negative correlation between RB1 vs proliferation marker, Ki-67 (r = −0.291*, P

OBJECTIVE: To investigate the management strategies, temporal trends, and clinical outcomes of patients with a history of coronary artery bypass graft (CABG) surgery and presenting with acute myocardial infarction (MI). PATIENTS AND METHODS: We undertook a retrospective cohort study using the National Inpatient Sample database from the United States (January 2004-September 2015), identified all inpatient MI admissions (7,250,768 records) and stratified according to history of CABG (group 1, CABG-naive [94%]; group 2, prior CABG [6%]). RESULTS: Patients in group 2 were older, less likely to be female, had more comorbidities, and were more likely to present with non-ST-elevation myocardial infarction compared with group 1. More patients underwent coronary angiography (68% vs 48%) and percutaneous coronary intervention (PCI) (44% vs 26%) in group 1 compared with group 2. Following multivariable logistic regression analyses, the adjusted odd ratio (OR) of in-hospital major adverse cardiovascular and cerebrovascular events (OR, 0.98; 95% CI, 0.95 to 1.005; P=.11), all-cause mortality (OR, 1; 95% CI, 0.98 to 1.04; P=.6) and major bleeding (OR, 0.99; 95% CI, 0.94 to 1.03; P=.54) were similar to group 1. Lower adjusted odds of in-hospital major adverse cardiovascular and cerebrovascular events (OR, 0.64; 95% CI, 0.57 to 0.72; P

IntroductionAsthma is a heterogeneous condition, characterised by chronic inflammation of the airways, typically managed with inhaled bronchodilators and corticosteroids. In the case of uncontrolled asthma, oral corticosteroids (OCSs) are often prescribed. Good adherence and inhalation technique are associated with improved outcomes; however, it is difficult to monitor appropriate drug intake and effectiveness in individual patients. Exhaled breath contains thousands of volatile organic compounds (VOCs) that reflect changes in the body's chemistry and may be useful for monitoring drug pharmacokinetics/pharmacodynamics. We aimed to investigate the association of exhaled VOCs in severe asthma patients from the U-BIOPRED cohort (by gas chromatography coupled with time-of-flight mass spectrometry) with urinary levels of salbutamol and OCSs (by liquid chromatography coupled with high-resolution mass spectrometry).MethodsSamples were collected at baseline and after 12–18 months of follow-up. Statistical analysis was based on univariate and multivariate modelling, followed by area under the receiver operating characteristic curve (AUC) calculation. Results were verified through longitudinal replication and independent validation.ResultsData were available for 78 patients (baseline n=48, replication n=30 and validation n=30). Baseline AUC values were 82.1% (95% CI 70.4–93.9%) for salbutamol and 78.8% (95% CI 65.8–91.8%) for OCS. These outcomes could be adequately replicated and validated. Additional regression analysis between qualified exhaled VOCs and urinary concentrations of salbutamol and prednisone showed statistically significant correlations (pConclusionWe have linked exhaled VOCs to urinary detection of salbutamol and OCSs. This merits further development of breathomics into a point-of-care tool for therapeutic drug monitoring.

The purpose of the present study was to analyze the role of selected polymorphisms of SIRT3 and SIRT5 in gastric carcinogenesis.For this study, 500 blood samples of GC patients and 500 blood samples of healthy individuals were collected. Six selected polymorphisms of mitochondrial sirtuins were analyzed for analysis using Tetra-Arms PCR followed by DNA sequencing.Mutant allele frequencies of selected polymorphisms [rs3782116 (p 0.0001), rs6598072 (p 0.0001) and rs11246020 (p 0.0001), rs938222 (p = 0.0136), rs3757261 (p = 0.0005) and rs2841511 (p = 0.0015)] were observed significant higher in GC patients vs controls. Haplotype analysis was performed, and 51 haplotypes were generated using haploview software. Among these haplotypes, eleven haplotypes were found associated with a significantly increased risk of GC. Furthermore, SNP-SNP interaction showed a significant correlation between studied SNPs and GC risk. Kaplan Meier analysis showed that mutant allele frequencies of selected polymorphisms are linked with a significant decrease in survival of GC patients CONCLUSIONS: It can be concluded that selected SNPs may be associated with enhanced risk of GC and hence can be potential prognostic markers for prognosis and predisposition of GC.

Background Bangladesh lies in the global thalassemia belt, which has a defined mutational hot-spot in the beta-globin gene. The high carrier frequencies of beta-thalassemia trait and hemoglobin E-trait in Bangladesh necessitate a reliable DNA-based carrier screening approach that could supplement the use of hematological and electrophoretic indices to overcome the barriers of carrier screening. With this view in mind, the study aimed to establish a high resolution melting (HRM) curve-based rapid and reliable mutation screening method targeting the mutational hot-spot of South Asian and Southeast Asian countries that encompasses exon-1 (c.1 - c.92), intron-1 (c.92 + 1 - c.92 + 130) and a portion of exon-2 (c.93 - c.217) of the HBB gene which harbors more than 95% of mutant alleles responsible for beta-thalassemia in Bangladesh. Results Our HRM approach could successfully differentiate ten beta-globin gene mutations, namely c.79G > A, c.92 + 5G > C, c.126_129delCTTT, c.27_28insG, c.46delT, c.47G > A, c.92G > C, c.92 + 130G > C, c.126delC and c.135delC in heterozygous states from the wild type alleles, implying the significance of the approach for carrier screening as the first three of these mutations account for ~85% of total mutant alleles in Bangladesh. Moreover, different combinations of compound heterozygous mutations were found to generate melt curves that were distinct from the wild type alleles and from one another. Based on the findings, sixteen reference samples were run in parallel to 41 unknown specimens to perform direct genotyping of the beta-thalassemia specimens using HRM. The HRM-based genotyping of the unknown specimens showed 100% consistency with the sequencing result. Conclusions Targeting the mutational hot-spot, the HRM approach could be successfully applied for screening of beta-thalassemia carriers in Bangladesh as well as in other countries of South Asia and Southeast Asia. The approach could be a useful supplement of hematological and electrophortic indices in order to avoid false positive and false negative results. Electronic supplementary material The online version of this article (10.1186/s12863-017-0594-3) contains supplementary material, which is available to authorized users.

Background The management of De Quervain's disease is determined more by Intuition than scientific data. The choice of first line conservative option for the management of De Quervain's disease is still a topic of debate. Aim To evaluate the effectiveness of therapeutic ultrasound with or without spica splint in the management of De Quervain's disease (DQD). Design Randomized controlled trial (RCT). Setting Outpatient department of Al-Nafees Medical College Hospital, Islamabad, Pakistan. Population Thirty patients who had the history of the De Quervain's disease for at least 6 months were enrolled in the study. The ages of the patient were 30-50 year. The population included housewives, maids, painters, and teachers. Methods Thirty patients were divided into two groups. The control group was treated with therapeutic ultrasound while in the experimental group thumb spica splitting was also added. The data was collected from the subjects through Quick Disabilities of the Arm, Shoulder and Hand questionnaire. The demographic data was presented in the form of tables. Intervention-induced changes within the groups were investigated using paired sample t-test while independent sample t-test was used to compare the two groups. Results Significant changes within both groups (p ≤ 0.05) were observed as a result of intervention. Additionally, significant differences in some instrument items were found between experimental and control group (p ≤ 0.05) after intervention. However, some items did not demonstrate significant changes in both groups likely because there was no effect of De Quervain's disease on those items before the intervention. Conclusion The results showed that the use of therapeutic ultrasound and spica splint together is more effective than using therapeutic ultrasound alone in the conservative management of De Quervain's disease. Clinical rehabilitation impact This study provides evidence to the relevant clinicians and professionals on the utility of therapeutic ultrasound combined with thumb spica splint in the conservative management of DQD.

Over recent years, social media use has substantially expanded not only for millennials, but across all generations. Today, it no longer remains a means for simple social networking. It has evolved into a powerful tool that can be used for career development, continued professional development and global scientific engagement. Medical professionals, have employed social media platforms to search for job opportunities, advertise meetings, participate in case discussions and network with the medical community at large. : However, some caveats limit its widespread application amongst the clinical community. The purpose of this review is to discuss the utility of social media, its drawbacks and best practices for the clinicians.

The rapid increase in urbanization has given rise to the need of proper waste management. Within municipal waste, the plastic waste is a growing concern which is causing severe harm to our ecosystem. If ignored, this problem will have harmful effects on both human and wildlife. Therefore, this study aims to find out the factors that influence the recycling behavior patterns of consumers regarding plastic waste. The variables from the theory of planned behavior were adopted to study the behavior of consumers toward recycling plastic waste. The data was collected from 243 residents of Karachi-metropolitan city of Pakistan. The partial least square-structural equation modelling was applied to analyze the data. The findings of the current study reveal that different consumers' attributes and attitudes trigger different types of recycling behavior when it comes to waste disposal. Pressure from family and friends and perceived behavioral control trigger the behavior of reselling the waste plastic products while consumer's awareness of consequences and personal attitude toward proper waste disposal leads to reuse or donating that product to someone who can use that plastic product. The understanding of these consumer attributes may help to shape the behavioral outcomes in order to manage waste disposal. This study will be beneficial for business managers looking to improve reverse logistics as well as government/municipal policy makers and academics/researchers who are interested in a solution-oriented study.

This work aims to employ fused deposition modelling 3D printing to fabricate immediate release pharmaceutical tablets with several model drugs. It investigates the addition of non-melting filler to methacrylic matrix to facilitate FDM 3D printing and explore the impact of (i) the nature of filler, (ii) compatibility with the gears of the 3D printer and iii) polymer: filler ratio on the 3D printing process. Amongst the investigated fillers in this work, directly compressible lactose, spray-dried lactose and microcrystalline cellulose showed a level of degradation at 135°C whilst talc and TCP allowed consistent flow of the filament and a successful 3D printing of the tablet. A specially developed universal filament based on pharmaceutically approved methacrylic polymer (Eudragit EPO) and thermally stable filler, TCP (tribasic calcium phosphate) was optimised. Four model drugs with different physicochemical properties were included into ready-to-use mechanically stable tablets with immediate release properties. Following the two thermal processes (hot melt extrusion (HME) and fused deposition modelling (FDM) 3D printing), drug contents were 94.22%, 88.53%, 96.51% and 93.04% for 5-ASA, captopril, theophylline and prednisolone respectively. XRPD indicated that a fraction of 5-ASA, theophylline and prednisolone remained crystalline whilst captopril was in amorphous form. By combining the advantages of thermally stable pharmaceutically approved polymers and fillers, this unique approach provides a low cost production method for on demand manufacturing of individualised dosage forms.

This study investigates the extent to which individual aspects of suture placement influence local haemodynamics within microarterial anastomoses. An attempt to physically quantify flow characteristics of blood past microvascular sutures is made using computational fluid dynamics (CFD) software. Particular focus has been placed on increased shear strain rate (SSR), a known precipitant of intravascular platelet activation and thrombosis.\ud \ud Measurements were taken from micrographs of sutured anastomoses in chicken femoral vessels, with each assessed for bite width, suture angle and suture spacing. Computational geometries were then created to represent the anastomosis. Each suture characteristic was parameterised to allow independent or simultaneous adjustment. Flow rates were obtained from anonymised Doppler ultrasound scans of analogous vessels during preoperative assessment for autologous breast reconstruction. Vessel simulations were performed in 2.5 mm ducts with blood as the working fluid. Vessel walls were non-compliant and a continuous Newtonian flow was applied, in accordance with current literature.\ud \ud Suture bite angle and spacing had significant effects on local haemodynamics, causing notably higher local SSRs, when simulated at extremes of surgical practice. A combined simulation, encompassing subtle changes of each suture parameter simultaneously i.e. representing optimum technique, created a more favourable SSR profile. As such, haemodynamic changes associated with optimum suture placement are unlikely to influence thrombus formation significantly. These findings support adherence to the basic principles of good microsurgical practice.

Introduction PTEN is part of large family of tyrosine phosphatases and has been found inactivated in a wide variety of human cancers. Aims In the present study we have tried to determine the association of the expression patterns of this gene with carcinogenesis. Methods First, a systematic review was carried out to ascertain the importance of the PTEN gene and its role in carcinogenesis. In the second phase, a case-control study was designed using different expression analysis techniques. Expression of PTEN mRNA was analyzed using reverse transcriptase polymerase chain reaction (RT-PCR). Results Significantly downregulated expression of PTEN was observed in patients with head and neck cancer (HNC) compared to adjacent normal-tissue controls. These results were confirmed with quantitative polymerase chain reaction (qPCR). Significant downregulation of the gene was observed in HNC patients compared to adjacent normal-tissue controls. PTEN expression was correlated with different histopathological parameters of the study cohort by Spearman's correlation coefficient and a significant negative correlation was observed with pT stage (r = −0.271*; pConclusions Our data suggest that downregulation of PTEN and overexpression of Ki-67 may contribute to the initiation and progression of HNC.

β-Thalassemia (β-thal) is one of the most common inherited hemoglobin (Hb) disorders, worldwide. A 28-year-old female and her husband came to Dhaka Shishu (Children) Hospital, Bangladesh for prenatal diagnosis for thalassemia mutations. We identified and characterized a novel β-thalassemia (β-thal) mutation due to an insertion of cytosine between codons 77 and 78 (p.Leu78Profs*13) found in mother in a heterozygous state. This mutation caused an insertion in the normal reading frame of the β-globin coding sequence and the new stop codon being the amino acid 90 (HBB: c.235_236insC) in exon 2 that leads to a β0-thal phenotype.

Neuropeptide S (NPS) is a naturally occurring appetite stimulant, associated with anxiety, stress, and excitement regulation. Neuropeptide S serves as a hypothalamic energy regulator that enhances food intake with a reduced level of satiety. NPS activates fat angiogenesis and the proliferation of new adipocytes in obesity. NPS has an established role in energy regulation by many pre-clinical investigations; however we have limited data available to support this notion in humans. We found significant association of Neuropeptide S receptor (NPSR1) Asn107Ile (rs324981, A>T) polymorphism with obese male participants. The current investigation carried out genotype screening of NPSR1 allele to assess the spectrum of the Asn107Ile polymorphism in obese and healthy Pakistani individuals. We revealed a significant (p = 0.04) difference between AA vs TT + AT genotype distribution of NPSR1 (SNP rs324981,) between obese and healthy individuals (p = 0.04). In this genotype analysis of (SNP rs324981) of the NPSR1 gene, T allele was marked as risk allele with higher frequency in the obese (38%) compared to its frequency in the controls (25%). Single Nucleotide Polymorphism (SNP, rs324981) Asn107Ile of NPSR1gene, that switches an amino acid from Asn to Ile, has been found associated with increased susceptibility to obesity in Pakistani individuals. Furthermore, molecular simulation studies predicted a lower binding affinity of NPSR1 Asn107Ile variant to NPS than the wild-type consistent with the genotype studies. These molecular simulation studies predict a possible molecular mechanism of this interaction by defining the key amino acid residues. However, a significantly (p

OBJECTIVE To determine the effect of deep breathing exercises on lung functions in apparently healthy smokers. METHODS The pilot study was conducted at Isra University, Islamabad, Pakistan, from May to December, 2017, and comprised apparently healthy smokers aged 20-30 years with a minimum smoking history of 5 years. The participants were divided into control and experimental groups. The control group was not given any treatment, while the experimental group was trained on deep breathing exercise techniques. Baseline data was compared after two weeks of intervention. SPSS 21 was used for data analysis. RESULTS Of the 30 subjects, there were 15(50%) in each of the two groups. In the experimental group, significant changes were found in vital capacity, inspiratory capacity, tidal volume, expiratory reserve volume, force expiratory volume, and forced vital capacity (p

The occurrence of lung cancer is linked with tobacco smoking, mainly through the generation of polycyclic aromatic hydrocarbons (PAHs). Elevated activity of cytochrome P4501A1 (CYP1A1) plays an important role in the metabolic processing of PAHs and its carcinogenicity. The present work aimed to investigate the role of CYP1A1 gene in PAH-mediated growth and tumor development in vitro and using an in vivo animal model. RNAi strategy was utilized to inhibit the overexpression of CYP1A1 gene using cationic liposomes generated using a lipid film-coated proliposome microparticles. Treatment of PAH-induced human alveolar adenocarcinoma cell line with cationic liposomes carrying CYP1A1 siRNA resulted in down regulation of CYP1A1 mRNA, protein as well as its enzymatic activity, triggering apoptosis and inhibiting multicellular tumor spheroids formation in vitro. Furthermore, silencing of CYP1A1 gene in BALB/c nude xenografts inhibited tumor growth via down regulation of CYP1A1 expression. Altogether, our findings showed that liposome-based gene delivery technology is a viable and stable approach for targeting cancer causing genes such as CY1PA1. This technology facilitated by the use of sugar particles coated with lipid films has demonstrated ability to generate anticancer effects that might be used in the future for therapeutic intervention and treatment of lung cancer. [Abstract copyright: Copyright © 2019. Published by Elsevier B.V.]

To determine the efficacy of an incentive-based approach combined with a smartphone application in promoting physical activity and weight-loss among female medical students, and to explore among them psychological effects pertaining to self-esteem, guilt, body-shaming, and perception of physical beauty.The pilot, randomised controlled trial was conducted at the Peoples University of Medical and Health Sciences for Women, Nawabshah, Pakistan, from March to May 2017, and comprised female students who were randomly allocated to either the incentivized or the non-incentivized group. The incentivized group was given a weekly financial incentive based on the required level of physical activity, measured each week for five weeks using Moves application. All subjects completed several questionnaires covering secondary outcomes at the end of the trial. SPSS 20 was used for data analysis.Of the 56 subjects, there were 28(50%) in each of the two groups. The use of financial incentives combined with the smartphone application did not result in a significant increase in physical activity (p0.05). However, within-group weight-loss at the end of intervention was significant for both the groups (p0.05). There was no significant change in the number of steps in the control group during the course of intervention (p0.05), but there was a significant decline in the number of steps in intervention group from weeks 4 and 5 compared to the baseline physical activity (p0.05).Financial incentives combined with a smartphone app designed to track physical activity did not promote physical activity or decrease obesity.

Epstein-Barr virus-encoded RNAs (EBER1 and EBER2) are two highly abundant, non-protein coding RNAs consistently expressed in all EBV infected cells, but their function remains poorly understood. Conventional in situ hybridization studies have indicated that these RNAs are present exclusively in the nucleus. We have recently demonstrated that EBERs can be excreted from infected cells via exosomes. However, the details of the steps involved in their excretion remain unknown. In this study, we aimed to directly track the journey of EBERs from the nucleus to the excretory exosomes of EBV immortalized B-lymphocytes. Using a combination of molecular and novel immuno-gold labelled electron microscopy (EM) based techniques, we demonstrate the presence of EBERs, not only in the nucleus, but also in the cytoplasm of EBV infected B cell lines. EBERs were also seen in exosomes shed from infected cells along with the EBER binding protein La. Our results show, for the first time, that at least a proportion of EBERs are transported from the nucleus to the cytoplasm where they appear to be loaded into multi-vesicular bodies for eventual excretion via exosomes.

It is unclear how comorbidity influences rates and causes of unplanned readmissions following percutaneous coronary intervention (PCI). We analyzed patients in the Nationwide Readmission Database who were admitted to hospital between 2010 and 2014. The comorbidity burden as defined by the Charlson Comorbidity Index (CCI). Primary outcomes were 30-day readmission rates and causes of readmission according to comorbidity burden. A total of 2,294,346 PCI procedures were included the analysis. The patients in CCI = 0, 1, 2 and ≥3 were 842,272(36.7%), 701,476(30.6%), 347,537(15.1%) and 403,061(17.6%), respectively. 219,227(9.6%) had an unplanned readmission within 30 days and rates by CCI group were 6.6%, 8.6%, 11.4% and 15.9% for CCI groups 0, 1, 2 and ≥3, respectively. The CCI score was also associated with greater cost (cost of index PCI for not readmitted vs readmitted was CCI = 0 $21,257 vs $19,764 and CCI ≥ 3 $26,736 vs $27,723). Compared to patients with CCI = 0, greater CCI score was associated with greater independent odds of readmission (CCI = 1 OR 1.25(1.22–1.28), p

With the passage of time, there has been a drastic increase in psychiatric disorders in past few decades across the world. Due to lack of education and awareness in the rural community, a majority of people still have strong misconceptions about the causation of psychiatric disorders and hence serve as a barrier for their medical treatment.A comparative cross-sectional study was conducted in the urban and rural areas of Rawalpindi district from March to August 2015, to find out the perception about treatment of psychiatric disorders among general public. Structured closed ended questionnaire was used to collect data from the participants and the results were analysed using SPSS. Chi square test was used to determine the association between categorical variables among urban and rural areas.The finding of our study confirmed that people of urban areas tend to choose and seek treatment by psychiatrists more (74%) as compared to those living in rural area that tends to select and believe in methodology and treatment provided by faith healers (55%). Lack of education, poor socioeconomic status, high treatment cost and most importantly false beliefs were the major contributory factors for people of rural areas in their inclination towards faith healers.The study concluded that most of the people of rural areas seek and trust the treatment by faith healers more as compared to psychiatrists. The importance of education and insight for the disorder cannot be denied for proper decision making about treatment choices.

Background Partner 2 and SURTAVI trials (mean STS score of 5.8 and 4.5) support extending TAVR into the intermediate risk group. We present our results of TAVR in a group with mean STS score of 2.9 and 2 year follow up. Methods This is a prospective cohort study of 46 consecutive patients undergoing TAVR between 2011 and 2016. All patients had severe symptomatic AS. Age, functional status, coronary disease, co-morbidity and imaging parameters were assessed. Patients were followed up for 12–60 months. Results 46 patients with a mean age of 75 years were enrolled. Mean EF 56%, mean MG 52 mm Hg and mean PG 87 mm Hg. The mean STS score was 2.9. Forty-two underwent transfemoral and 4 transaortic TAVR. Forty-five of 46 valves were implanted successfully. One patient had moderate perivalvular regurgitation (PVR). Post-procedure mean MG was 11 mm Hg. There was one procedure related stroke and one intraprocedural death. Five patients (10.8%) required a permanent pacemaker. 30-day mortality was 2 of 46 (4.3%). Mean follow up was 28 months. Mean MG at 2 years was 12 mm Hg. Late cardiac mortality occurred in 1 patient. Conclusion TAVR in this group with a low STS score was successful with excellent valve performance. Although the STS score identifies intermediate and high risk patients, it does not account for the overall frailty and limited mobility of many elderly patients placing them at a higher surgical risk despite their low STS scores. A scoring system that captures all such factors is required. Finally, a large scale randomized trial with long term follow up determining the validity of TAVR in truly low risk individuals is necessary.

Dengue fever has emerged as an emerging public health issue during last decade bearing significant morbidity and economic burden particularly in third world countries. Current study aims to assess various domains of knowledge of indoor dengue patients..This descriptive crosssectional study was conducted at Medicine dept. Rawal Institute of Health Sciences Islamabad and BBH Rawalpindi over 6 months. One hundredtwenty-five adult indoor confirmed cases of dengue from lower socioeconomic class were included after ethical approval. The 25-item dengue knowledge questionnaire including aetiology, symptoms, modes of transmission and prevention of dengue was filled.Among 125 cases (77% males and 23% females), mean age was 30±13 years. Mean knowledge score was 11±5 points; with excellent knowledge in 6%, good knowledge (22%), moderate knowledge (23%), fair knowledge (34%) and poor knowledge (17%). Mosquito being a vector of dengue was identified by 78%, with peak time in afternoon (48%). Symptoms identified include fever (95%), headache (55%), muscle pain (44%), rash (33%), retro-orbital pain (32%), joint pains (28%) and abdominal pain (18%). Flies and ticks aren't the vectors of dengue according to 61% and 74% respectively, special mosquito is vector (54%), i.e., Aedes aegypti (18%) that breeds in standing water (53%). Preventive measures identified were netting (56%), insecticide sprays (54%), covering water containers (38%), removing standing water (36%), mosquito repellents (17%), cutting down bushes (22%) and pouring chemicals in standing water (18%).Our patients from lower socioeconomic class, though aware of vector and mode of transmission, have insufficient knowledge of prevention and vector control measures. There is need to strengthen dengue awareness through community-based programs, social media, schools and health care centres for high risk people well before the expected epidemic season about mode of transmission, vector control, screening and early approach to health care facility.

Epstein–Barr virus (EBV; human herpesvirus 4) is an oncogenic herpesvirus implicated in the pathogenesis of several human malignancies. A number of recent studies indicate that EBV can manipulate the local microenvironment by excreting viral and cellular components in nanovesicles called exosomes. In this study, we investigated the impact of EBV-derived exosomes on apoptosis of recipient cells and the molecular pathway involved in this process. Exosomes from EBV-infected but not from non-infected cells induced apoptosis in a number of different cell types, including B-cells, T-cells and epithelial cells. However, this phenomenon was not universal and the Burkitt's lymphoma-derived B-cell line BJAB was found to be resistant to apoptosis. Exosomes from both type I and type III EBV latently infected cells induced apoptosis in a dose- and time-dependent manner. Moreover, cells exposed to EBV exosomes did not form colonies in soft agar assays. We further show that fluorescently labelled exosomes derived from EBV-infected cells are taken up by non-infected cells and induce apoptosis via the extrinsic pathway. Inhibition of caspase-3/7/8 blocks EBV exosome-mediated apoptosis. Furthermore, our data indicate that EBV exosomes trigger apoptosis through the Fas ligand (FasL)-mediated extrinsic pathway, as FasL was present in EBV exosomal fractions and anti-FasL antibodies could block EBV exosome-mediated apoptosis. Together, these data support the notion that EBV hijacks the exosome pathway to excrete viral and cellular components that can modulate its microenvironment.