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Breast cancer susceptibility is greatly influenced by single nucleotide polymorphisms (SNPs) both in penetrance and non-penetrance genes. The Estrogen Receptor Alfa (ESR1- rs2234693 and rs2046210) have been reported as risk factor of breast cancer in different ethnic groups with inconsistent results. In this study the association of ESR1 (rs2234693 and rs2046210) with breast cancer risk was investigated in patients of Khyber Pakhtunkhwa.A total of 312 females including 162 breast cancer patients and 150 healthy controls were enrolled in this study. The polymorphism was confirmed using T-ARMS-PCR.Our results revealed that ESR1-rs2234693 risk allele (C) (P = 0.21, OR = 1.27, CI = 0.87 to 1.87) and containing genotypes CC (P = 0.68, OR = 1.24, CI = 0.42 to 3.68) and TC (P = 0.23, OR = 1.32, CI = 0.83 to 2.13) were not associated with the risk of breast cancer. In case of rs2046210, the risk allele A (P 0.0001, OR = 2.42, CI = 1.74 to 3.38) and corresponding genotypes GA (P = 0.0001, OR = 2.55, CI = 1.62 to 4.03) and AA (P = 0.02, OR = 2.20, CI = 1.12 to 4.34) were significantly associated with higher risk of breast cancer. Moreover, ESR1-rs2234693 was significantly (P 0.05) associated with family history, stages, PR status, ER status and luminal B. The ESR1-rs2046210 showed significant (P ≤ 0.05) association with menstrual status, tumor grade and TNBC. Both the SNPs showed non-significant (P 0.05) association with nulliparity, nodal status, HER2 status, metastasis, HER2 enriched subtype and luminal A.It is concluded that ESR1-rs2234693 is not associated with breast cancer, while rs2046210 is significantly associated with the risk of breast cancer in Khyber Pakhtunkhwa population. Further, to confirm the exact situation of ESR1 polymorphism, ESR1 existing and other SNPs need to be investigated in diverse data sets.

Objective: Healthcare providers (HCPs) are at the forefront and are at risk of being exposed to suspected cases of COVID-19. The objective of our study was to evaluate knowledge, attitude and practices of HCPs about COVID-19 in Khyber Pakhtunkhwa (KPK) province of Pakistan. Methods: A cross-sectional survey was conducted online among HCPs that included physicians, dentists, pharmacists, nurses and technicians in KPK province. The validated questionnaire (Cronbach alpha= 0.61 & 0.69 respectively for knowledge & practice sections) related to COVID-19 including socio-demographics was asked. Data was analyzed using SPSS version 22.0. Result: Out of 480 HCPs, 83.8% (n=402) were physicians & dentist, while 12.5% (n= 60) were pharmacist, nurses and technicians. We found that 86% of the HCPs had adequate knowledge. Most common reason for being worried about COVID-19 was risk to members of family and friends (98%), followed by dangers of disease itself (93%). Fear of infection and carrying it home was as high as 93% and 97% respectively. Around 75% of the HCPs had adequate score about practices. Conclusion: HCPs in Pakistan has good knowledge and attitude related to COVID-19. However, one-fourth of the HCPs did not report good practices, which is alarming. There is a need to reinforce knowledge and monitor practices of HCPs regarding standard infection control practice. Keywords: COVID-19; Healthcare providers; Knowledge; Attitudes; Practices; Pakistan

Hepatitis C is a global health concern brought on by the hepatitis C virus (HCV). The risk factors of the disease include injection drug users, contaminated medical instruments, blood transfusion, organ transplant, major surgery, dialysis, dental surgery, and acupuncture. The aim of the current study was to identify the prevalence of active HCV infection, genotypes, and their associated risk factors in newly infected patients of Khyber Pakhtunkhwa (KPK), Pakistan. A total of 230 HCV cases and 245 control subjects were enrolled. Our findings revealed that disease infection rates were higher in female patients (52.6%) than male patients (47.4%). Moreover, the disease was more prevalent in the age group 30–40 years (39.6%). The highest incidence was found in the southern region (51.30%), followed by the northern region (27.82%), and central region (18.26%). In our data set, dental surgery, major surgery, disease in family, barber community, blood received, needles, abroad travel, injection drug users, acupuncture, and organ transplantation were determined as the major associated risk factors of the disease. Odds ratio were significantly higher (10.91%) for those who used acupuncture as compared to those who did not. Similarly, odds were significantly higher (10.03%) for those who had HCV in their family, dialysis (9.377%), dental surgery (7.618%), major surgery (6.813%), barber community (5.328%), and blood received (2.252%) as compared to the control group. Also, the most frequent genotype was 3a (63%), followed by an un-typeable genotype (11.30%).

Background: Single Nucleotide polymorphism (SNPs) in BRCA1, BRCA2 and TP53 has been widely associated with breast cancer risk in different ethnicities with inconsistent results. There is no such study conducted so far in the Pashtun population of Khyber Pakhtunkhwa, Pakistan. Therefore, this study was conducted to check BRCA1(rs1799950), BRCA2 (rs144848) and TP53 (rs1042522) polymorphism with breast cancer risk in Pashtun population of Khyber Pakhtunkhwa, Pakistan. Methods: This study, consisting 140 breast cancer patients and 80 gender and age matched healthy controls were subjected to confirm BRCA1, BRCA2 and TP53 polymorphism. Clinicopathological data and blood samples were taken from all the participants. DNA was extracted and SNPs were confirmed using T-ARMS-PCR protocol. Results: Our data indicated that BRCA1, BRCA2, and TP53 selected SNPs risk allele and risk allele containing genotypes displayed significant association (P< 0.05) with breast cancer risk in the Pashtun population of Khyber Pakhtunkhwa, Pakistan. Conclusion: All the three selected SNPs of BRCA1, BRCA2 and TP53 showed significant association with breast cancer risk in the Pashtun population of Khyber Pakhtunkhwa, Pakistan. However, more investigation will be required on large data sets to confirm the selected SNPs and other SNPs in the selected and other related genes with the risk of breast cancer.

Background Diabetic Nephropathy (DN) is one of the microvascular complications of Diabetes Mellitus (DM). Genome wide association studies have helped identify gene variants such as rs1800470 (TGF-β1) and rs5186 (AGTR1), which facilitate diabetic nephropathy. However, there is no such reports from Pakistan, particularly the Pashtun population. Methods A case-control study was conducted on 165 diabetic patients (59 with Diabetic Nephropathy (DN) and 54 without DN (DM)), and 52 healthy subjects (HC). The genotyping was done using amplification refractory mutation system method (ARMS-PCR). Results The results indicated that all the subjects have similar distribution of age, gender and duration of diabetes, while the FBS, RBS, HbA1C, creatinine, Urea, SBP, DBP, total cholesterol, triglycerides, LDL and BMI were found higher in the diabetic patients with nephropathy as compared to those without nephropathy and healthy controls. The risk allele of AGTR1, C (p p p- 0.0010) were significantly higher in DN patients compared to DM and HC groups. Similarly, the TGF-β1 risk allele C (p- 0.0001), and corresponding genotypes TC (p- 0.0038) and CC (p- 0.0027) were significantly associated with increased risk of diabetic nephropathy compared to DM and HC groups. Conclusion The data showed significant association of AGTR1 (rs5186) and TGF-β1 (rs1800470) polymorphism with an increased risk of diabetic nephropathy in type 2 diabetes mellitus patients. More investigation will be required to disseminate the results, while increasing the samples size and using whole genome sequencing.

Drought is a major factor restricting the production of rice (Oryza sativa L.). The identification of natural variants for drought stress-related genes is an important step toward developing genetically improved rice varieties. Here, we characterized a member of the SQUAMOSA PROMOTER BINDING PROTEIN-LIKE (SPL) family, OsSPL10, as a transcription factor involved in the regulation of drought tolerance in rice. OsSPL10 appears to play a vital role in drought tolerance by controlling ROS production and stomatal movements. Haplotype and allele frequency analyses of OsSPL10 indicated that most upland rice and improved lowland rice varieties harbor the OsSPL10

Background: Breast cancer susceptibility is greatly influenced by single nucleotide polymorphisms (SNPs) both in penetrance and non-penetrance genes. The Estrogen Receptor Alfa (ESR1- rs2234693 and rs2046210) have been reported as risk factor of breast cancer in different ethnic groups with inconsistent results. In this study the association of ESR1 (rs2234693 and rs2046210) with breast cancer risk was investigated in Khyber Pakhtunkhwa patients. Methods: A total of 222 women including 162 breast cancer patients and 60 healthy controls were enrolled in this study. The polymorphism was confirmed using T-ARMS-PCR. Results: Our results revealed that ESR1-rs2234693 risk allele (C) (P = 0.2, OR = 1.34, CI = 0.7 to 2.3) and containing genotypes CC (P = 0.61, OR = 1.50, CI = 0.31 to 7.30) and TC (P = 0.7, OR = 1.11, CI = 0.59 to 2.09) were not associated with the risk of breast cancer. In case of rs2046210, the risk allele A (P = 0.0006, OR = 7.50, CI = 0.77 to 2.33) and corresponding genotypes GA (P = 0.003, OR = 2.44, CI = 1.33 to 4.47) and AA (P = 0.3, OR = 3.15, CI = 1.06 to 9.38) were significantly associated with higher risk of breast cancer. Moreover, ESR1-rs2234693 was significantly (P ESR1-rs2046210 showed significant (P ≤ 0.05) association with menstrual status, tumor grade and TNBC. Both the SNPs showed non-significant (P > 0.05) association with nulliparity, nodal status, HER2 status, metastasis, HER2 enriched subtype and luminal A. Conclusion: It is concluded that ESR1-rs2234693 is not associated with breast cancer, while rs2046210 is significantly associated with the risk of breast cancer in Khyber Pakhtunkhwa population. Further, to confirm the exact situation of ESR1 polymorphism, ESR1 existing and other SNPs need to be checked in diverse data sets.

Summary Yield in rice is determined mainly by panicle architecture. Using map‐based cloning, we identified an R2R3 MYB transcription factor REGULATOR OF GRAIN NUMBER1 (RGN1) affecting grain number and panicle architecture. Mutation of RGN1 caused an absence of lateral grains on secondary branches. We demonstrated that RGN1 controls lateral grain formation by regulation of LONELY GUY (LOG) expression, thus controlling grain number and shaping panicle architecture. A novel favourable allele, RGN1 C, derived from the Or‐I group in wild rice affected panicle architecture by means longer panicles. Identification of RGN1 provides a theoretical basis for understanding the molecular mechanism of lateral grain formation in rice; RGN1 will be an important gene resource for molecular breeding for higher yield.

AIM: To evaluate the aldose reductase (ALR2, rs759853), receptor for advanced glycation end products (RAGE, rs2070600), and vascular endothelial growth factor (VEGF, rs833061) association with diabetic retinopathy in type 2 diabetic patients in Khyber Pakhtunkhwa population.Methods: A Case control study was conducted on a total of 550 subjects consisting of 186 with diabetic retinopathy (DR) having type 2 diabetes, 180 had type 2 diabetes (T2DM), and 184 healthy controls (HC). All the samples were subjected to DNA isolation using salting-out method followed by SNP genotyping through Tetra-ARMS PCR. Chi square and Exact Fischer tests were used for allele and genotype distribution. Odd ratio and confidence interval values were found out by online software Medcalc Odd ratio Calculator.Results: Multiple parameters such as random blood sugar (RBS) (pVEGF rs833061 (pRAGE rs2070600 (pVEGF (0.262, 95% CI=0.129-0.531) and AA genotype in RAGE (0.59, 95% CI=0.032-0.110) was noted. However, the significance in ALR2 rs759853 gene polymorphism was observed at (p=0.001). Conclusion: There is a statistically significant association of VEGF rs833061 and RAGE rs2070600 with diabetic retinopathy in type 2 diabetic patients. Also, this is the first study to report the association of RAGE with diabetic retinopathy in type 2 diabetes in Khyber Pakhtunkhwa population.

Key message QTLs for cold tolerance at the early seedling and booting stages were identified and qCTB1 was delimited to a 342-kb interval, and the breeding potential of QTL pyramiding was assessed. Abstract Cold stress is one of the main abiotic stresses that affects rice growth and production worldwide. Dissection of the genetic basis is important for genetic improvement of cold tolerance in rice. In this study, a new source of cold-tolerant accession from the Yunnan plateau, Lijiangxiaoheigu, was used as the donor parent and crossed with a cold-sensitive cultivar Deyou17, to develop 130 recombinant inbred lines (RILs) for quantitative trait locus (QTL) analysis. In total, three QTLs for cold tolerance at the early seedling stage on chromosomes 2 and 7, and four QTLs at the booting stage on chromosomes 1, 3, 5, and 7 were identified. Under the cold stress conditions in deep water and in a high-altitude area, qCTB1 , a locus for cold tolerance at the booting stage, was fine mapped to a 342-kb interval between markers M3 and M4. Effect assessment in the RIL and BC 3 F 3 populations demonstrated that qCTB1 showed a stable effect in the genetic segregation populations. Haplotype and linear regression analyses showed that QTL pyramiding based on the additive effect of favorable loci possesses good potential for cold tolerance breeding. This study will provide genetic resources for molecular breeding and gene cloning of cold tolerance in rice.

To evaluate the aldose reductase (ALR2, rs759853), receptor for advanced glycation end products (RAGE, rs2070600), and vascular endothelial growth factor (VEGF, rs833061) association with diabetic retinopathy in type 2 diabetic patients of Khyber Pakhtunkhwa population.A case-control study was conducted on a total of 550 subjects consisting of 186 with diabetic retinopathy (DR) having type 2 diabetes, 180 had type 2 diabetes (T2DM), and 184 healthy controls (HC). All the samples were subjected to DNA isolation using salting-out method followed by SNP genotyping through Tetra-ARMS PCR. Chi square and Exact Fischer tests were used for alleles and genotypes distribution. Odd ratio and confidence interval values were found out by online software Medcalc Odd ratio Calculator.Multiple parameters such as random blood sugar (RBS) (p 0.001), fasting blood sugar (FBS) (p 0.001), HbA1c (p 0.001), total cholesterol (p 0.001), LDL (p 0.001), HDL (p 0.001), BMI (p 0.001) and hypertension (p = 0.018) exhibited strong association with DR as compared to DM and HC. Our results displayed that the VEGF-rs833061 and RAGE- rs2070600 exhibited significant association (p 0.05) with an increased DR risk, when compared with T2DM. In contrast, ALR2 didn't display association with DR (p 0.05) when compared with T2DM, but showed association (p 0.05) when compared with HC.Statistically significant association was observed in VEGF-rs833061 and RAGE-rs2070600 with DR in type 2 diabetic patients. While, ALR2- rs759853 didn't exhibit significant association with DR. This is the first study to report the association of candidate genes (ALR2, VEGF and RAGE) with DR in type 2 diabetes of Khyber Pakhtunkhwa population. More similar research studies are recommended with larger data sets in other ethnicities both national and international.

The legal mechanism that has been adopted for insider trading in Pakistan focuses on the associated and connected person includes Securities and Exchange Ordinance 1969 and Companies Ordinance 1984. The paper discusses the key issues regarding the associated and connected person and legal regime regarding the effectiveness of insider trading in Pakistan. This paper examines the existing laws in Pakistan, which specifically focus upon market-oriented regulations and economic development. The focus of this paper is to highlight the legal framework and connectivity between associated and connected persons affiliated with insider trading and other prohibitions which are provided in the SECP regularities of Pakistan.To tackle the misleading information and devaluation of market prices through insider trading is also part of this paper, along with some basic information like defrauding the market and, consequently, the shareholder sat large will also be discussed in this paper.

The aim of the present study was to find the effect of crushed wild Cumin (Bonium persicum) seeds as a feed additive in broiler diet during the starter phase on growth performance, nutrient digestibility and blood metabolites in broilers. For this purpose, 360 day old chicks were randomly divided into four groups. One group was the control while other experimental groups were supplemented with crushed wild Cumin (WC) seeds in the feed at the rate of 0.5 (WC1), 1 (WC2) and 1.5 g/kg (WC3). Results indicated that feed intake was significantly lower (p

Heading date is a crucial agronomic trait. However, rice usually delays heading due to the photoperiod, temperature, hormones or age. The present research was conducted to analyze the mechanism controlling heading date in F1 hybrid rice. We constructed two test-crossing populations using two introgression lines (ILs), P20 and P21 coming from SH527/FH838 as the male parent, respectively, and male sterile line Jin23A as the female parent. Meanwhile, the F1 hybrids of H20, obtained by mating P20 with Jin23A and having no heading, and H21, from the crossing between P21 and Jin23A having normal heading, were both observed under long days. Here, we analyzed the photoperiodic response of F1 hybrids by transcriptome and metabolome profiling. The greater differences displayed in the transcriptome and the metabolome were caused by photoperiod (exogenous) instead of genes (endogenous). The coping mechanism resulted from long days (LD) in H20, leading to differences in the circadian rhythm and glutathione metabolism relative to other samples. The circadian oscillator and GSH/GSSG cycle typically regulate ROS homeostasis, and both of them are responsible for modulating ROS in H20 under LD condition. Both circadian rhythm genes and the reported genes related to heading date function via the DHD1/OsMFT1-Ehd1-RFT1-OsMADS14/OsMADS18 pathway and the glutathione metabolism pathway by regulating oxidative reduction processes. Both pathways are involved in the heading process and they interacted through the oxidative reduction process which was induced by photoperiod regulation, and all of them collectively modulated the heading process. The results of this study will be helpful for unraveling the mechanism of F1 hybrid responses to unheading under LD condition.

Cold stress at the reproductive stage severely affects the production and geographic distribution of rice. The Geng/japonica subpopulation gradually developed stronger cold adaptation than the Xian/indica subpopulation during the long-term domestication of cultivated rice. However, the evolutionary path and natural alleles underlying the cold adaptability of intra-Geng subspecies remain largely unknown. Here, we identified MITOGEN-ACTIVATED PROTEIN KINASE 3 (OsMAPK3) and LATE EMBRYOGENESIS ABUNDANT PROTEIN 9 (OsLEA9) as two important regulators for the cold adaptation of Geng subspecies from a combination of transcriptome analysis and genome-wide association study. Transgenic validation showed that OsMAPK3 and OsLEA9 confer cold tolerance at the reproductive stage. Selection and evolution analysis suggested that the Geng version of OsMAPK3 (OsMAPK3

Introduction The receptor activator NF-κB ligand (RANKL) and Osteoprotegrin (OPG) single nucleotide polymorphisms (SNPs) have been associated with the risk of breast cancer to bone metastasis. This study was designed to investigate the association of RANKL and OPG gene polymorphisms with breast to bone metastasis in Pashtun population of Khyber Pakhtunkhwa, Pakistan. Materials and methods A total of 215 participants were enrolled containing 106 breast cancer patients, 58 breast to bone metastasis and 51 age and gender matched healthy controls. RANKL (rs9533156) and OPG (rs2073618, rs3102735) polymorphisms were genotyped in genomic DNA, using Tetra-ARMS PCR protocol. The results were analyzed among the three groups and P-value less then 0.05 were considered statistically significant. Results Our results displayed significant association of OPG (rs3102735) risk allele and corresponding genotypes in breast cancer vs healthy controls, bone metastasis vs healthy controls and breast cancer vs breast to bone metastasis as a disease risk. However, there was no association observed for OPG (rs2073618) risk allele and corresponding genotypes with the diseases risk. Similarly, RANKL (rs9533156) risk allele and corresponding genotypes in breast cancer vs healthy controls, bone metastasis vs healthy controls and breast cancer vs breast to bone metastasis exhibited significant association except for the risk allele carrying genotypes in breast to bone metastasis. Conclusion OPG (rs3102735) and RANKL (rs9533156) exhibited significant association with breast to bone metastasis while OPG (rs2073618) didn’t show significant association with breast to bone metastasis in Pashtun population of Pakistan. However, this study unlocks more questions to investigate the exact scenario of genetic predisposition of breast to bone metastasis.

Viral Hepatitis is the seventh leading cause of death worldwide and prevails in many developing countries specifically in the Middle East and North African regions. The current study focuses on a comparatively low-income province of Pakistan, Khyber Pakhtunkhwa where medical facilities are scarce and the use of blood and its products, free from viral hepatitis and other pathogens, is poorly ensured. The preliminary phase of the study involved a systematic literature review on the epidemiology of Hepatitis C Virus in KP during the period 2000-2018 through PubMed, Science Direct, and Google Scholar. After statistical coding, an initial meta-analysis was conducted to come up with an integrated estimate of the prevalence of Hepatitis C Virus in Khyber Pakhtunkhwa. The prevalence rate of 4% by fixed effect model and of 6% by random effect model is extremely alarming, especially in a low-income region, and the Pakistani government should adopt effective and rapid strategies to eliminate Hepatitis C Virus infection by the end of 2030, as more times announced by the World Health Organization.

The design of sacrificial cathodic protection (CP) systems conventionally involves steady-state assumptions, which means design parameters are considered constant during the in-service life of CP systems. In contrast, it is evident by experimental observations (including field measurements) that cathodic protection is a transient process due to variations in electrolyte properties such as seasonal changes in electrical conductivity of soil, depletion of anodes, and formation of corrosion deposits on anode material surface, to name a few. The lack of practical time-dependent models on this critical issue is apparent in the literature; accordingly, in this study, a pseudo transient electrochemical model is adopted to highlight the transient behavior of cathodic protection systems and investigate key differences with steady-state behavior. For the sake of demonstration, the developed model is used to simulate the time-dependent performance of a sacrificial anode bed for cathodic protection of screw-pile foundations. The methodology proposed in this study can be used by corrosion engineers to improve and optimize the design of CP systems and numerically estimate the performance of sacrificial anodes and the level of protection over time.

Background Dengue is a viral disease, transmitted by infected Aedes aegypti and Aedes albopictus female mosquitoes. Worldwide, 96 million infections were estimated in 2010. The dengue virus comprises four distinct serotypes (DENV-1, DENV-2, DENV-3, and DENV-4) which belong to the genus Flavivirus. Determining the serotypes during dengue outbreaks is crucial for its effective management in terms of diagnostics improvement and polyvalent vaccine development. The aim of the present study is to determine the prevalence rate of dengue virus serotypes in the samples collected from patients during the 2017 outbreak in Khyber Pakhtunkhwa, Pakistan. Methods A total of 800 ELISA-positive samples were collected, of which 513 (290 males, 223 females) samples were confirmed positive by PCR. Results Out of 513, 25 were found serotype 1 (5%), 196 were serotype 2 (38%), 192 were serotype 3 (37%), 56 were serotype 4 (11%), and 44 (8%) were found to have mix serotypes. Conclusion We can conclude that serotypes 2 and 3 of dengue virus were the predominated serotypes of dengue virus in the 2017 outbreak in Peshawar, capital city of Khyber Pakhtunkhwa, Pakistan.

Panicle number (PN) is one of the three yield components in rice. As one of the most unstable traits, the dynamic change in tiller number (DCTN) may determine the final PN. However, the genetic basis of DCTN and its relationship with PN remain unclear. Here, 377 deeply re-sequenced rice accessions were used to perform genome-wide association studies (GWAS) for tiller/PN. It was found that the DCTN pattern rather than maximum tiller number or effective tiller ratio is the determinant factor of high PN. The DCTN pattern that affords more panicles exhibits a period of stable tillering peak between 30 and 45 days after transplant (called DT30 and DT45, respectively), which was believed as an ideal pattern contributing to the steady transition from tiller development to panicle development (ST-TtP). Consistently, quantitative trait loci (QTL) expressed near DT30-DT45 were especially critical to the rice DCTN and in supporting the ST-TtP. The spatio-temporal expression analysis showed that the expression pattern of keeping relatively high expression in root at 24:00 (R24-P2) from about DT30 to DT45 is a typical expression pattern of cloned tiller genes, and the candidate genes with R24-P2 can facilitate the prediction of PN. Moreover, gene OsSAUR27 was identified by an integrated approach combining GWAS, bi-parental QTL mapping and transcription. These findings related to the genetic basis underlying the DCTN will provide the genetic theory in making appropriate decisions on field management, and in developing new varieties with high PN and ideal dynamic plant architecture.

Hepatocellular carcinoma is a primary liver malignancy in which the risk of development is always multifunctional. Interleukin-6 is a proinflammatory and multifunctional cytokine, which plays an important role in the immune response, haematopoiesis and defence against viral infection. We aimed to evaluate the frequency of Interleukin-6 mutations (rs2069837 and rs17147230) associated with genetic risk of hepatocellular carcinoma in Khyber Pakthunkhwa population. A total of 72 hepatocellular carcinoma cases and 38 controls were included in this study. The genomic DNA was extracted from the peripheral blood cells and Interleukin-6 genotyping was performed using T-ARMS-PCR technique. Our results show a significant increase risk of developing hepatocellular carcinoma with the mutation within Interleukin-6 gene with heterozygous G allele (rs2069837) (OR = 10.667, 95%CI = 3.923–29.001, p = p = Interleukin-6 rs2069837 (OR = 0.605, 95%CI = 0.217–1.689, p = 0.337), while significant in case of Interleukin-6 rs17147230 (OR = 0.298, 95%CI = 0.121–0.734, p = 0.0085). In conclusion, Interleukin-6 mutation is associated with hepatocellular carcinoma susceptibility. More related studies with other associated interleukins and their whole gene sequencing will be required.

As one of the main yield components, grain number per panicle (GNP) played critical role in the rice yield improvement. The identification of natural advantageous variations under different situations will promote the sustainable genetic improvement in rice yield. This study was designed to identify natural genotypes in a rice mini-core collection, to examine the genotypic effects across the indica and japonica genetic background in different environments, and excavating the superior genotypes that had drove the modern genetic improvement. The association mapping of GNP was carried out using a mini-core collection including 154 indica and 119 japonica accessions in seven different environments. Genotypic effects of each genotype for each QTL were calculated and genotype frequency distortion between the commercial rice cultivars and landraces was screened by χ2-test. In total, 74 QTLs containing stable and sensitive QTLs in various environments were detected. Within them, 20 positive and 24 negative genotypes in indica, and 24 positive and 16 negative genotypes in japonica were identified. When checking the accumulation of positive genotypes identified in indica across cultivars in each of the two subspecies, it indicated that increased number of positive genotypes identified in indica results in the substantially increased GNP in both indica and japonica across all of the environments, while this trend was not obvious for the positive genotypes identified in japonica especially in short day environments. Moreover, the positive and negative genotype frequency distortion between the landraces and commercial rice cultivars indicated that both positive selection of positive genotypes and negative selection of negative genotypes had driven the genetic improvement on GNP. Our findings suggested that the accumulation of positive genotypes and purifying negative genotypes played equivalently important roles in the improvement of rice yield, but the efficient use for some QTLs or genotypes depends on the comprehensive evaluation of their effect under diverse genetic backgrounds and environments.

Background:Hepatitis B is considered the most dangerous among the five types of Hepatitis, as it is clinically asymptomatic. It can silently damage the liver over many years without being diagnosed. Hepatitis B is one of the top risks of liver complications in Khyber Pakhtunkhwa (KP), a province of Pakistan, with an average prevalence rate of 2.70%.Aims:We aimed to carefully review the previously published data on prevalence of Hepatitis B Virus (HBV) in KP-Pakistan and use the statistical approach to obtain more precise estimate of the prevalence of HBV in KP-Pakistan. This study on one hand will provide a more reliable and consolidated estimate (pooled estimate) of HBV in the stated region, on the other hand, it enabled us to judge the heterogeneity among the estimates found from these studies. The study is intended to provide more authentic prevalence record and help government/ non-government organizations and health professionals, which plan to initiate HBV prevention programs in KP-Pakistan.Methods:A meta-analysis was performed based on studies found in literature search from electronic databases and bibliography on the prevalence of HBV in KP-Pakistan from 2007 to 2017. Abstracts and results of twenty papers were thoroughly studied and the data were extracted. The findings from these studies were distributed in two groups (general and population at high risk) constituting 15 and 5 studies respectively.Results:The combined prevalence by considering random model for the general population of KP-Pakistan was observed to be 2.71%, while population at high risk was reasonably highi.e. 5.64%. By comparing this prevalence rate to the highest global prevalence of HBV in the adult population of Western Pacific Region (6.2%), significant (p-value= 0.000) heterogeneity was observed among the estimates in each group. However, the funnel plot provides a symmetric look, eliminating the effect of publication bias. We can say that HBV has an alarming prevalence rate in KP-Pakistan. However, HBV is thrice more prevalent in male population of KP-Pakistan than the female population.Conclusion:The above results lead that HBV infection has reached an alarming state in KP-Pakistan, though projects like Prime Minister’s Program for Prevention & Control of Hepatitis which are contributing in improving the health of the people of KP by trying to prevent and control the incidence of HBV. More massive vaccination and awareness programs should be initiated to prevent the spread of HBV on urgent basis. Provision of diagnostics and treatment facilities against HBV in healthcare units of KP-Pakistan should be assured.

Soil salinity is a major factor affecting rice growth and productivity worldwide especially at seedling stage. Many genes for salt tolerance have been identified and applied to rice breeding, but the actual mechanism of salt tolerance remains unclear. In this study, seedlings of 664 cultivated rice varieties from the 3000 Rice Genome Project (3K-RG) were cultivated by hydroponic culture with 0.9% salt solution for trait identification. A genome-wide association study (GWAS) of salt tolerance was performed using different models of analysis. Twenty-one QTLs were identified and two candidate genes named OsSTL1 (Oryza sativa salt tolerance level 1) and OsSTL2 (Oryza sativa salt tolerance level 2) were confirmed using sequence analysis. Haplotype and sequence analysis revealed that gene OsSTL1 was a homolog of salt tolerance gene SRP1 (Stress associated RNA-binding protein 1) in Arabidopsis. The hap1 of OsSTL1 was identified as the superior haplotype and a non-synonymous SNP was most likely to be the functional site. We also determined that the level of salt tolerance was improved by combining haplotypes of different genes. Our study provides a foundation for molecular breeding and functional analysis of salt tolerance in rice seedlings.

The protein elicitor PevD1, isolated from Verticillium dahlia, could enhance resistance to TMV in tobacco and Verticillium wilt in cotton. Here, the pevd1 gene was over-expressed in wild type (WT) Arabidopsis, and its biological functions were investigated. Our results showed that the transgenic lines were more resistant to Botrytis cinerea and Pseudomonas syringae pv. tomato DC3000 than the WT line was. In transgenic plants, both the germination time and bolting time required were significantly shorter and fresh weights and plant heights were significantly higher than those in the WT line. A transcriptomics study using digital gene expression profiling (DGE) was performed in transgenic and WT Arabidopsis. One hundred and thirty-six differentially expressed genes were identified. In transgenic Arabidopsis, three critical regulators of JA biosynthesis were up-regulated and JA levels were slightly increased. Three important repressors of the ABA-responsive pathway were up-regulated, indicating that ABA signal transduction may be suppressed. One CML and two WRKY TFs involved in Ca(2+)-responsive pathways were up-regulated, indicating that this pathway may have been triggered. In conclusion, we show that PevD1 is involved in regulating several plant endogenous signal transduction pathways and regulatory networks to enhance resistance and promote growth and development in Arabidopsis.

Hepatitis delta virus (HDV) is a defective RNA virus that depends on the presence of hepatitis B virus (HBV) for the creation of new virions and propagation of the infection to hepatocytes. Chronic infection with HDV is usually associated with a worsening of HBV infection, leading more frequently to cirrhosis, increased risk of liver decompensation and hepatocellular carcinoma (HCC) occurrence. In spite of a progressive declining prevalence of both acute and chronic HDV infection observed over several years, mainly due to increased global health policies and mass vaccination against HBV, several European countries have more recently observed stable HDV prevalence mainly due to migrants from non-European countries. Persistent HDV replication has been widely demonstrated as associated with cirrhosis development and, as a consequence, development of liver decompensation and occurrence of HCC. Several treatment options have been attempted with poor results in terms of HDV eradication and improvement of long-term prognosis. A global effort is deemed urgent to enhance the models already existing as well as to learn more about HDV infection and correlated tumourigenesis mechanisms.

Background Hepatitis C virus (HCV) infection is a global health problem especially for its increasing level of mortality. Detailed knowledge of HCV genotypes prevalence has clinical relevance since the efficacy of therapies is impacted by genotypes and subtypes distribution. Moreover, HCV exhibits a great genetic variability regionally. To date, there are no published studies assessing HCV genotypes distribution in specific countries of the Mediterranean basin. The aim of this study was to review data published from 2000 to 2017 with the purpose to estimate genotypes distribution of HCV infection in nine European countries all located in the Mediterranean basin. Methods A systematic research of peer-reviewed journals indexed in PubMed, Scopus, and EMBASE databases selected if containing data regarding distribution of HCV genotypes in nine selected European countries (Albania, Bosnia, Croatia, France, Greece, Italy, Montenegro, Slovenia, and Spain) was performed. Results Genotype 1 is the most common (61.0%), ranging from 80.0% in Croatia to 46.0% in Greece, followed by genotype 3 (20.0%), varying from 38.0% in Slovenia to 7.0% and 8.0%, respectively, in Italy and in Albania and by genotype 4 (10.0%) that shows an increase of 1.1% with respect to data obtained till 2014 probably due to the increasing migrants arrivals to Southern Europe. G2, the fourth most frequent genotype (8.5%), particularly common in Italy (27.0%) and Albania (18.0%) might be probably introduced in Southern Italy as a result of Albanian campaign during Second World War and more and more increased by the migration flows from Albania to Italy in the 90s. Conclusion Epidemiology of HCV infection shows a high variability across the European countries that border the Mediterranean Sea. HCV genotyping is a relevant tool to monitor the dynamic process influenced by both evolving transmission trends and new migration flows on HCV scenario.

Digital image enhancement has been a hot topic during the past decades. In this paper, we have established a new fusion based approach for impulse noise reduction from multi-sensors images. Image fusion is an important technique used in remote sensing, military and medical applications. In the proposed approach, firstly, only the uncorrupted pixels from multi-sensor images are grouped and then all those grouped pixels are filter with another state of the art approach for optimal results. The proposed approach is tested with several noisy images by finding the Mean Square Error, Peak Signal to Noise Ratio and Mutual Information values between the original and restored images. The experimental results show that the proposed algorithm outclasses all methods that individually de-noised and fused images.

MoHrip2 Magnaporthe oryzae hypersensitive protein 2 is an elicitor protein of rice blast fungus M. oryzae. Rice seedlings treated with MoHrip2 have shown an induced resistance to rice blast. To elucidate the mechanism underlying this MoHrip2 elicitation in rice, we used differential-display 2-D gel electrophoresis and qRT-PCR to assess the differential expression among the total proteins extracted from rice leaves at 24 h after treatment with MoHrip2 and buffer as a control. Among ~1000 protein spots detected on each gel, 10 proteins were newly induced, 4 were up-regulated, and 3 were down-regulated in MoHrip2-treated samples compared with the buffer control. Seventeen differentially expressed proteins were detected using MS/MS analysis and categorized into six groups according to their putative function: defense-related transcriptional factors, signal transduction-related proteins, reactive oxygen species (ROS) production, programmed cell death (PCD), defense-related proteins, and photosynthesis and energy-related proteins. The qPCR results (relative expression level of genes) further supported the differential expression of proteins in MoHrip2-treated rice leaves identified with 2D-gel, suggesting that MoHrip2 triggers an early defense response in rice leaves via stress-related pathways, and the results provide evidence for elicitor-induced resistance at the protein level.

To compare pregnancy-associated plasma protein-A (PAPP-A) levels in individuals with and without coronary artery disease (CAD).Cross-sectional comparative study.Department of Chemical Pathology and Endocrinology, Armed Forces Institute of Pathology (AFIP), Rawalpindi, in collaboration with Armed Forces Institute of Cardiology (AFIC), from September 2008 to March 2010.One hundred and twenty five (125) individuals both male and female were included in the study. Blood for PAPP-A and lipid profile was collected, just before angiography. On the basis of angiography, the individuals were divided into those with and without CAD. PAPP-A was analyzed by using Diagnostic System Laboratories (DSL) Enzyme Linked Immunosorbent Assay (ELISA) kit and reading was taken by ELISA reader. Lipid profile was determined on automated analyzers Selectra-2 and Vitros 5.1.Amongst the 125 individuals, 41 individuals were without CAD whereas 84 individuals were having CAD. Mean PAPP-A levels were 0.74 ± 0.35 mIU/L in those without CAD whereas mean PAPP-A levels in those with CAD were 1.35 ± 0.57 mIU/L. The difference between the two groups was statistically significant (p0.001). A PAPP-A cut off level of 0.85 mIU/L had a sensitivity and specificity of 78% and 70% respectively for diagnosing atherosclerotic CAD.PAPP-A is a potentially relevant marker of the presence and extent of coronary atherosclerosis as its levels are elevated in CAD as compared to individuals without CAD.

Summary Objectives The purpose of this study is to amplify the knowledge base of the epidemiology, symptoms, and signs of extrapulmonary tuberculosis (EPTB) in Afghanistan. Methods This is a retrospective review of EPTB diagnosed at CURE International Hospital and CURE Family Health Center (FHC) in Kabul, Afghanistan during a recent 20-month period. Results One hundred eighteen cases were identified from patients presenting to the hospital and FHC. This group represents the spectrum of EPTB seen at a single referral center in Kabul. The ratio of females to males was 2.03:1. Lymph node tuberculosis comprised the greatest number of EPTB cases (37.3%, n =44). The central nervous system was the next most frequent site of EPTB involvement (20.3%, n =24), followed in descending order by skeletal, pleural, abdominal, cutaneous, genitourinary, pericardial, miliary, and breast tuberculosis. Conclusions The 2:1 ratio of female to male EPTB cases coincides with the unusual epidemiologic pattern seen in smear-positive pulmonary TB in Afghanistan. As the first epidemiological report of EPTB from Afghanistan, this study illustrates the varied presentations of EPTB that should be known by healthcare workers throughout the country.