Enhanced Power Factor and Figure of Merit of Cu2ZnSnSe4-Based Thermoelectric Composites by Ag Alloying.

The quaternary chalcogenide composites Cu2ZnSn1-xAgxSe4 (0 ≤ x ≤ 0.075) have been successfully synthesized by high-temperature melting and annealing followed by hot-pressing. The phase structure of the bulk sample has been analyzed by powder X-ray diffraction and Rietveld refinement combined with Raman spectroscopy to confirm Cu2ZnSnSe4 as the main phase with ZnSe and Cu5Zn8 secondary phases. The thermoelectric properties of all specimens have been investigated in the temperature range of 300-700 K. The replacement of Sn by Ag significantly enhances the electrical transport properties by providing extra charge carriers. The tremendous reduction in electrical resistivity enhances the power factor, and a maximum power factor of 804 µW K-2 m-1 is achieved at 673 K for the specimen with 5% Ag content. Furthermore, increased point defects increase phonon scattering, resulting in reduced thermal conductivity. The combined effect of improved power factor and suppressed thermal conductivity provides a good boost to the dimensionless figure of merit. The maximum figure of merit of zT = 0.25 has been achieved at 673 K for Cu2ZnSn0.95Ag0.05Se4, which is 2.5 times the value of the parent sample.

Effectiveness of electric toothbrush as vibration method on orthodontic tooth movement: a split-mouth study.

OBJECTIVE: To investigate the effects of application of vibratory stimuli, using an electric toothbrush, on the rate of orthodontic tooth movement during maxillary canine retraction. METHODS: A split-mouth study was conducted in 28 subjects (mean age = 20.8 years; ranging from 18 to 24 years) whose bilateral maxillary first premolars were extracted with subsequent canine retraction. On the Vibration side, light force (100 g) was applied to the canine for 90 days, in combination with vibratory stimuli provided by an electric toothbrush; only orthodontic force was applied to the canine on the non-vibration side. Amount of canine movement was measured monthly. Related to electronic toothbrush usage, a diary was provided to each patient for recording discomfort during experimental period, having 100-mm visual analogue scale (VAS). The paired t-test was used to assess the differences in amount of tooth movement between canines of the vibration and non-vibration sides. RESULTS: The amount of tooth movement was similar for canines on the vibration side and on the non-vibration side (mean 0.81 ± 0.10 mm and 0.82 ± 0.11 mm, respectively, p> 0.05). Plaque accumulation was minimal in any subject throughout the study. No subject reported discomfort as a result of using the electric toothbrush. CONCLUSIONS: This study demonstrates that application of vibratory stimuli using an electric toothbrush, in combination with light orthodontic force, do not accelerate orthodontic tooth movement.

Effectiveness of electric toothbrush as vibration method on orthodontic tooth movement: a split-mouth study

Abstract Objective: To investigate the effects of application of vibratory stimuli, using an electric toothbrush, on the rate of orthodontic tooth movement during maxillary canine retraction. Methods: A split-mouth study was conducted in 28 subjects (mean age = 20.8 years; ranging from 18 to 24 years) whose bilateral maxillary first premolars were extracted with subsequent canine retraction. On the Vibration side, light force (100 g) was applied to the canine for 90 days, in combination with vibratory stimuli provided by an electric toothbrush; only orthodontic force was applied to the canine on the non-vibration side. Amount of canine movement was measured monthly. Related to electronic toothbrush usage, a diary was provided to each patient for recording discomfort during experimental period, having 100-mm visual analogue scale (VAS). The paired t-test was used to assess the differences in amount of tooth movement between canines of the vibration and non-vibration sides. Results: The amount of tooth movement was similar for canines on the vibration side and on the non-vibration side (mean 0.81 ± 0.10 mm and 0.82 ± 0.11 mm, respectively, p> 0.05). Plaque accumulation was minimal in any subject throughout the study. No subject reported discomfort as a result of using the electric toothbrush. Conclusions: This study demonstrates that application of vibratory stimuli using an electric toothbrush, in combination with light orthodontic force, do not accelerate orthodontic tooth movement.

Resumo Objetivo: investigar os efeitos da aplicação de estímulo vibratório, usando escova elétrica, sobre a taxa de movimentação dentária ortodôntica durante a retração dos caninos superiores. Métodos: um estudo de boca-dividida foi realizado em 28 pacientes (idade média de 20,8 anos, variando entre 18 e 24 anos) cujos dois primeiros pré-molares superiores foram extraídos, com subsequente retração dos caninos. No lado Com Vibração, uma força leve (100g) foi aplicada no canino durante 90 dias, em combinação com o estímulo vibratório gerado por uma escova de dentes elétrica; enquanto os caninos do lado Sem Vibração foram submetidos apenas à aplicação da força ortodôntica. A quantidade de movimentação dos caninos foi aferida mensalmente. Quanto ao uso da escova de dentes elétrica, diários foram fornecidos aos pacientes para que esses anotassem, em Escalas Visuais Analógicas (EVA) de 100 mm, o desconforto sentido durante o período experimental. O teste t pareado foi utilizado para avaliar as diferenças na quantidade de movimentação dos caninos nos lados Com Vibração e Sem Vibração. Resultados: os valores da movimentação dentária foram semelhantes nos lados Com Vibração e Sem Vibração (médias de 0,81 ± 0,10 mm e 0,82 ± 0,11 mm, respectivamente, p> 0,05). O acúmulo de placa dentária nos pacientes dessa amostra foi mínimo, ao longo de todo o estudo. Nenhum paciente relatou desconforto durante o uso da escova elétrica. Conclusões: o presente estudo demonstrou que a aplicação de estímulo vibratório usando uma escova elétrica, associada a forças ortodônticas leves, não foi capaz de acelerar a movimentação dentária ortodôntica.

Efficiency of class III malocclusion treatment with 2-premolar extraction and molar distalization protocols.

INTRODUCTION: Different treatment protocols have been implemented for management of Class III malocclusion with aim of achieving ideal occlusal goals. The aim of current study was to compare the efficiency of Class III treatment with mandibular 2-premolar extraction and mandibular molar distalization protocol. METHODS: This retrospective cross sectional study was conducted on pre-treatment and post-treatment dental casts of 60 orthodontic patients who had Class III malocclusion and were treated with a mandibular dentition distalization and mandibular 2-premolars extraction protocol. The study was conducted at orthodontic departments of Dental Section, Faisalabad Medical University/Punjab Medical College and de'Montmorency College of Dentistry, Pakistan. The sample was classified into 2 groups. Group A consisted of 30 patients (20 females, 10 males) (mean age, 18.02years) treated with distalization protocol and Group B consisted of 30 patients (18 females, 12 males) (mean age, 18.97years) treated with mandibular 2-premolars extraction protocol. To compare the efficiency of the treatment protocol in each group, the initial and final occlusal results were assessed on dental models using PAR index while treatment efficiency was assessed using a treatment efficiency index (TX). The groups were compared with t and Mann-Whitney tests. RESULTS: There were no significant differences in the initial age, treatment time, treatment efficiency and any occlusal feature between the groups. CONCLUSION: Treatment efficiency of Class III malocclusions with mandibular 2-premolar extractions or mandibular dentition distalization protocol is similar.

Chromosomal instability causes sensitivity to protein folding stress and ATP depletion.

Aneuploidy -- having an unbalanced genome - is poorly tolerated at the cellular and organismal level. It gives rise to proteotoxic stress as well as a stereotypical oxidative shift which makes these cells sensitive to internal and environmental stresses. Using Drosophila as a model, we found that protein folding stress is exacerbated by redox stress that occurs in response to ongoing changes to ploidy (chromosomal instability, CIN). We also found that if de novo nucleotide synthesis is blocked, CIN cells are dependent on a high level of lysosome function to survive. Depletion of adenosine monophosphate (AMP) synthesis enzymes led to DNA damage in CIN cells, which showed elevated activity of the DNA repair enzyme activated poly(ADP ribose) polymerase (PARP). PARP activation causes depletion of its substrate, nicotinamide adenine dinucleotide (NAD+) and subsequent loss of Adenosine Tri-Phosphate (ATP), and we found that adding ATP or nicotinamide (a precursor in the synthesis of NAD+) could rescue the observed phenotypes. These findings provide ways to interpret, target and exploit aneuploidy, which has the potential to offer tumour-specific therapies.

Phosphoenolpyruvate Carboxykinase Maintains Glycolysis-driven Growth in Drosophila Tumors.

Tumors frequently fail to pass on all their chromosomes correctly during cell division, and this chromosomal instability (CIN) causes irregular aneuploidy and oxidative stress in cancer cells. Our objective was to test knockdowns of metabolic enzymes in Drosophila to find interventions that could exploit the differences between normal and CIN cells to block CIN tumor growth without harming the host animal. We found that depleting by RNAi or feeding the host inhibitors against phosphoenolpyruvate carboxykinase (PEPCK) was able to block the growth of CIN tissue in a brat tumor explant model. Increasing NAD+ or oxidising cytoplasmic NADH was able to rescue the growth of PEPCK depleted tumors, suggesting a problem in clearing cytoplasmic NADH. Consistent with this, blocking the glycerol-3-phosphate shuttle blocked tumor growth, as well as lowering ROS levels. This work suggests that proliferating CIN cells are particularly vulnerable to inhibition of PEPCK, or its metabolic network, because of their compromised redox status.

Cortical blindness post coronary angiogram: A rare but frightening complication.

Cortical blindness is a rare but frightening complication following coronary angiogram probably due to contrast penetration in occipital lobes in susceptible individuals [1, 2].

The Role of JNK Signalling in Responses to Oxidative DNA Damage.

The production of reactive oxygen species is a normal part of cell physiology, but many internal and external stimuli are able to trigger the production of excess levels of oxidants that are potentially damaging. The threat of oxidative damage is particularly significant to DNA, as damaged bases can interfere with replication to generate lasting mutations. Signalling through the JNK pathway is a key cellular response to oxidative damage. Depending on the intensity and duration of the damage signal, JNK signalling can lead to distinct alternative responses including DNA repair, anti-oxidant production or cell death. These responses are highly relevant to cancer therapy, as tumours are often under oxidative stress that produces elevated JNK levels and therapy often involves inducing DNA damage with the intention of driving cell death. In this review we examine the causes and consequences of JNK activation that relate to oxidative DNA damage, with a focus on the potential therapeutic implications.

Microbial transformation of oxandrolone with Macrophomina phaseolina and Cunninghamella blakesleeana.

Microbial transformation of oxandrolone (1) was carried out by using Cunninghamella blakesleeana and Macrophomina phaseolina. Biotransformation of 1 with M. phaseolina yielded four new metabolites, 11ß,17ß-dihydroxy-17α-(hydroxymethyl)-2-oxa-5α-androstan-3-one (2), 5α,11ß,17ß-trihydroxy-17α-methyl-2-oxa-androstan-3-one (3), 17ß-hydroxy-17α-methyl-2-oxa-5α-androstan-3,11-dione (4), and 11ß,17ß-dihydroxy-17α-methyl-2-oxa-5α-androstan-3-one (5). Whereas a new metabolite, 12ß,17ß-dihydroxy-17α-methyl-2-oxa-5α-androstan-3-one (6), was obtained through the microbial transformation of oxandrolone (1) with C. blakesleeana. The structures of isolated metabolites were characterized on the basis of MS and NMR spectroscopic data.

Microbial transformation of nandrolone with Cunninghamella echinulata and Cunninghamella blakesleeana and evaluation of leishmaniacidal activity of transformed products.

Therapeutic potential of nandrolone and its derivatives against leishmaniasis has been studied. A number of derivatives of nandrolone (1) were synthesized through biotransformation. Microbial transformation of nandrolone (1) with Cunninghamella echinulata and Cunninghamella blakesleeana yielded three new metabolites, 10ß,12ß,17ß-trihydroxy-19-nor-4-androsten-3-one (2), 10ß,16α,17ß-trihydroxy-19-nor-4-androsten-3-one (3), and 6ß,10ß,17ß-trihydroxy-19-nor-4-androsten-3-one (4), along with four known metabolites, 10ß,17ß-dihydroxy-19-nor-4-androsten-3-one (5), 6ß,17ß-dihydroxy-19-nor-4-androsten-3-one (6) 10ß-hydroxy-19-nor-4-androsten-3,17-dione (7) and 16ß,17ß-dihydroxy-19-nor-4-androsten-3-one (8). Compounds 1-8 were evaluated for their anti-leishmanial activity. Compounds 1 and 8 showed a significant activity in vitro against Leishmania major. The leishmanicidal potential of compounds 1-8 (IC50=32.0±0.5, >100, 77.39±5.52, 70.90±1.16, 54.94±1.01, 80.23±3.39, 61.12±1.39 and 29.55±1.14 µM, respectively) can form the basis for the development of effective therapies against the protozoal tropical disease leishmaniasis.

Sensitive detection of pre-existing BCR-ABL kinase domain mutations in CD34+ cells of newly diagnosed chronic-phase chronic myeloid leukemia patients is associated with imatinib resistance: implications in the post-imatinib era.

BACKGROUND: BCR-ABL kinase domain mutations are infrequently detected in newly diagnosed chronic-phase chronic myeloid leukemia (CML) patients. Recent studies indicate the presence of pre-existing BCR-ABL mutations in a higher percentage of CML patients when CD34+ stem/progenitor cells are investigated using sensitive techniques, and these mutations are associated with imatinib resistance and disease progression. However, such studies were limited to smaller number of patients. METHODS: We investigated BCR-ABL kinase domain mutations in CD34+ cells from 100 chronic-phase CML patients by multiplex allele-specific PCR and sequencing at diagnosis. Mutations were re-investigated upon manifestation of imatinib resistance using allele-specific PCR and direct sequencing of BCR-ABL kinase domain. RESULTS: Pre-existing BCR-ABL mutations were detected in 32/100 patients and included F311L, M351T, and T315I. After a median follow-up of 30 months (range 8-48), all patients with pre-existing BCR-ABL mutations exhibited imatinib resistance. Of the 68 patients without pre-existing BCR-ABL mutations, 24 developed imatinib resistance; allele-specific PCR and BCR-ABL kinase domain sequencing detected mutations in 22 of these patients. All 32 patients with pre-existing BCR-ABL mutations had the same mutations after manifestation of imatinib-resistance. In imatinib-resistant patients without pre-existing BCR-ABL mutations, we detected F311L, M351T, Y253F, and T315I mutations. All imatinib-resistant patients except T315I and Y253F mutations responded to imatinib dose escalation. CONCLUSION: Pre-existing BCR-ABL mutations can be detected in a substantial number of chronic-phase CML patients by sensitive allele-specific PCR technique using CD34+ cells. These mutations are associated with imatinib resistance if affecting drug binding directly or indirectly. After the recent approval of nilotinib, dasatinib, bosutinib and ponatinib for treatment of chronic myeloid leukemia along with imatinib, all of which vary in their effectiveness against mutated BCR-ABL forms, detection of pre-existing BCR-ABL mutations can help in selection of appropriate first-line drug therapy. Thus, mutation testing using CD34+ cells may facilitate improved, patient-tailored treatment.

Prognostically significant fusion oncogenes in Pakistani patients with adult acute lymphoblastic leukemia and their association with disease biology and outcome.

BACKGROUND AND OBJECTIVES: Chromosomal abnormalities play an important role in genesis of acute lymphoblastic leukemia (ALL) and have prognostic implications. Five major risk stratifying fusion genes in ALL are BCR-ABL, MLL-AF4, ETV6-RUNX11, E2A-PBX1 and SIL-TAL1. This work aimed to detect common chromosomal translocations and associated fusion oncogenes in adult ALL patients and study their relationship with clinical features and treatment outcome. METHODS: We studied fusion oncogenes in 104 adult ALL patients using RT-PCR and interphase-FISH at diagnosis and their association with clinical characteristics and treatment outcome. RESULTS: Five most common fusion genes i.e. BCR-ABL (t 9; 22), TCF3-PBX1 (t 1; 19), ETV6-RUNX1 (t 12; 21), MLL-AF4 (t 4; 11) and SIL-TAL1 (Del 1p32) were found in 82/104 (79%) patients. TCF3-PBX1 fusion gene was associated with lymphadenopathy, SIL-TAL positive patients had frequent organomegaly and usually presented with a platelets count of less than 50 x10(9)/l. Survival of patients with fusion gene ETV6-RUNX1 was better when compared to patients harboring other genes. MLL-AF4 and BCR-ABL positivity characterized a subset of adult ALL patients with aggressive clinical behaviour and a poor outcome. CONCLUSIONS: This is the first study from Pakistan which investigated the frequency of 5 fusion oncogenes in adult ALL patients, and their association with clinical features, treatment response and outcome. Frequencies of some of the oncogenes were different from those reported elsewhere and they appear to be associated with distinct clinical characteristics and treatment outcome. This information will help in the prognostic stratification and risk adapted management of adult ALL patients.

Hepatitis C virus entry: role of host and viral factors.

Hepatitis C virus (HCV) has been considered to be a significant risk factor in developing liver associated diseases including hepatocellular carcinoma all over the world. HCV is an enveloped positive strand virus comprising a complex between genomic RNA and viral envelope glycoproteins (E1 and E2), which are anchored within host derived double-layered lipid membrane surrounding the nucleocapsid composed of several copies of core protein. HCV cell entry is the first step in infection and viral replication into host cells mainly hepatocytes. HCV cell entry is a complex process involving both the viral (envelope glycoproteins E1/E2) and host factors (cellular receptors and associated factors i.e. CD81, SR-BI, LDL-R, CLDN1, Occludin, DC-SIGN, L-SIGN and Glycosaminoglycans). Besides these the expression of certain other conditions such as polarization and EWI-2 expression inhibits the viral cell entry. Exploring the mechanism of HCV entry will help to better understand the viral life cycle and possible therapeutic targets against HCV infection including viral and host factors involved in this process. New strategies such as RNAi represents a new option for targeting the host or viral factors for prevention and therapeutic against HCV infection. In the current review we try to summarize the current knowledge about mechanism and interaction of cellular and viral factors involved in HCV cell entry and its implication as therapeutic target to inhibit HCV infection.

HCV entry receptors as potential targets for siRNA-based inhibition of HCV.

BACKGROUND: Hepatitis C virus (HCV) is a major health concern with almost 3% of the world's population (350 million individuals) and 10% of the Pakistani population chronically infected with this viral pathogen. The current therapy of interferon-α and ribavirin against HCV has limited efficiency, so alternative options are desperately needed. RNA interference (RNAi), which results in a sequence-specific degradation of HCV RNA has potential as a powerful alternative molecular therapeutic approach. Concerning viral entry, the HCV structural gene E2 is mainly involved in virus attachment to the host cell surface receptors i.e., CD81 tetraspanin, scavenger receptor class B type 1 (SR-B1), low density lipoprotein receptor (LDLR) and claudin1 (CLDN1). RESULTS: In this report, we studied the relationship of the HCV receptors CD81, LDL, CLDN1 and SR-B1to HCV infection. The potential of siRNAs to inhibit HCV-3a replication in serum-infected Huh-7 cells was demonstrated by treatment with siRNAs against HCV receptors, which resulted in a significant decrease in HCV viral copy number. CONCLUSIONS: Our data clearly demonstrate that the RNAi-mediated silencing of HCV receptors is among the first of its type for the development of an effective siRNA-based therapeutic option against HCV-3a. These findings will shed further light on the possible role of receptors in inhibition of HCV-3a viral titre through siRNA mediated silencing.

Effect of combined siRNA of HCV E2 gene and HCV receptors against HCV.

BACKGROUND/AIM: Hepatitis C virus (HCV) is a major threat as almost 3% of the world's population (350 million individual) and 10% of the Pakistani population is chronically infected with this virus. RNA interference (RNAi), a sequence-specific degradation process of RNA, has potential to be used as a powerful alternative molecular therapeutic approach in spite of the current therapy of interferon-α and ribavirin against HCV which has limited efficiency. HCV structural gene E2 is mainly involved in viral cell entry via attachment with the host cell surface receptors i.e., CD81 tetraspanin, low density lipoprotein receptor (LDLR), scavenger receptor class B type 1 (SR-B1), and Claudin1 (CLDN1). Considering the importance of HCV E2 gene and cellular receptors in virus infection and silencing effects of RNAi, the current study was designed to target the cellular and viral factors as new therapeutic options in limiting HCV infection. RESULTS: In this study the potential of siRNAs to inhibit HCV-3a replication in serum-infected Huh-7 cells was investigated by combined treatment of siRNAs against the HCV E2 gene and HCV cellular receptors (CD81 and LDLR), which resulted in a significant decrease in HCV viral copy number. CONCLUSION: From the current study it is concluded that the combined RNAi-mediated silencing of HCV E2 and HCV receptors is important for the development of effective siRNA-based therapeutic option against HCV-3a.

Smoking among university students: a gender analysis.

The main objectives of this paper were to estimate the consumption patterns of tobacco use among King Saud University (KSU) undergraduate students; and investigate different risk factors which may contribute to tobacco use among female students. A representative sample (n=7550) of the total KSU undergraduate student population of 69,498 (males and females) was selected, stratified according to college and gender. A modified version of the WHO/CDC Global Youth Tobacco Survey (GYTS) questionnaire was used for data collection. Overall smoking prevalence among KSU students was estimated at 14.5%, prevalence among male students (32.7%), and females (5.9%). Independent risk factors for smoking among males were found to be: age, father's smoking habits, and "friends' smoking habits"; while among females were: sister's smoking habits and "friends' smoking habits." The findings of this study re-emphasize the significance of peer pressure on smoking among university students of both sexes; influence of family members, usually of same sex. We need to foster gender-sensitive tobacco prevention intervention programs, to prevent youngsters of both sexes from taking up such habit. We also need to raise awareness of girls and young women, of the consequences of smoking in general, water-pipe in specific, on their own health, that of their spouses, families, and off-springs, many of whom could develop chronic respiratory disorders, as passive smokers in the beginning/potential smokers themselves, later on. All such efforts should be backed and supported by strong governmental commitment, to ensure success of their implementation accordingly.

Inhibition of core gene of HCV 3a genotype using synthetic and vector derived siRNAs.

BACKGROUND: Hepatitis C virus (HCV) is a major causative agent of liver associated diseases throughout the world, with genotype 3a responsible for most of the cases in Pakistan. Due to the limited efficiency of current therapy, RNA interference (RNAi) a novel regulatory and powerful silencing approach for molecular therapeutics through a sequence-specific RNA degradation process represents an alternative option. RESULTS: The current study was purposed to assess and explore the possibility of RNAi to silence the HCV-3a Core gene expression, which play complex role in regulation of cell growth and host genes expression essential for infectivity and disease progression. To identify the potent siRNA target sites, 5 small interfering RNAs (siRNAs) against Core gene were designed and in vitro transcribed after consensus sequence analysis of different HCV-3a isolates. Antiviral effects of siRNAs showed upto 80% inhibition of Core gene expression by different siRNAs into Huh-7 cells as compared with Mock transfected and control siRNAs treated cells. For long lasting effect of siRNAs, vector based short hairpin siRNAs (shRNAs) were designed and tested against HCV-3a Core which resulted in a similar pattern of inhibition on RNA and protein expression of HCV Core as synthetic siRNAs. Furthermore, the efficacy of cell culture tested siRNA and shRNA, were evaluated for inhibition of HCV replication in HCV infected serum inoculated Huh-7 cells and a significant decrease in HCV viral copy number was observed. CONCLUSIONS: Our results support the possibility of using consensus siRNA and shRNA-based molecular therapy as a promising strategy in effective inhibition of HCV-3a genotype.

Interaction of the hepatitis C virus (HCV) core with cellular genes in the development of HCV-induced steatosis.

Hepatitis C virus (HCV) has chronically infected a large number of patients, leading to the development of steatosis, cirrhosis and, ultimately, hepatocellular carcinoma. The pathogenesis of HCV has not been fully explained, although steatosis is considered to contribute greatly to liver fibrosis progression, modulating host-cell lipid metabolism. Suspected underlying molecular mechanisms include interactions between HCV proteins and intracellular lipid metabolic pathways. Recent studies have suggested that the nucleocapsid of HCV (core) acts as a pathogenic factor involved in lipid droplet accumulation, changes in lipogenic gene expression and/or the activity of lipogenic proteins in a genotype-specific manner. In this review, we have tried to summarize the current knowledge regarding HCV-induced steatosis and the regulation of expression of host genes and receptors that aid in the viral life cycle and promote liver diseases.