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Introduction: Iron deficiency anemia is one of the major global public health issue causes many serious diseases mostly found in the women and children of developing world. Objective: To evaluate and assess the occurrence and disorder related to iron deficiency in the population of district Dir (Lower). Materials and Methods: From all volunteers blood samples were collected from Vein through syringe and kept it in the EDTA tubes. Hemoglobin concentration was determined by the help of Hematology Analyzer. Following the guidelines of WHO, the value of a hemoglobin (Hb) was

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.

Ischemic heart disease (IHD) or coronary artery disease (CAD) is one of the largest death-causing reasons in developing countries. Approximately, every year 15 million deaths due to IHD are reported worldwide. PLG (Plasminogen), PCSK9 (Proprotein Convertase Subtilisin/Kexin type 9), CXCL12 (C-X-C Motif Chemokine Ligand 12), and EDNRA (Endothelin Receptor type A) genes were selected for the study due to their higher rate of mutations in IHD. Drugs that are being used to cure IHD were reformulated by structurally modifying them for repurposing. Reformulated drugs were further analyzed for side effects, toxicity, and ADMET (Absorption, Distribution, Metabolism, Excreation, Toxicity) properties. Molecular docking studies of reformulated drugs with selected genes were performed to determine their efficacy to cure IHD. Interacting amino acid residues in the docked complex of aspirin were identified as Aspartic acid, Arginine, Tyrosine, Proline, Valine, Alanine, Threonine, Iso Leusine, Lysine, Triptophan, Aspargine, Histadine, Cystine. Similarly, for isoxsuprine the residues were Valine, Aspargine, Leucine, Argining, Iso Leucine, Glutamic acid, Lysine, Glycine, Proline, Threonine, Aspartic acid, Histadine and Arginine. In reformulated compounds, the addition of sulfur in the aspirin compound reduced the toxicity from class 3 to class 5 and in isoxsuprine, the addition of nitrogen hydrogen bond in the second aromatic ring reduced its toxicity from class 3 to class 4. It is suggested that both aspirin and isoxsuprine analogs are more effective having least predicted side effects and toxicities than already existing aspirin and isoxsuprine. In the future, these drugs can be used as potential drugs for the treatment of IHD than original drugs because of their low toxicity and side effects. This study can be validated in vitro to confirm its efficacy.

An rare pandemic of viral pneumonia occurs in December 2019 in Wuhan, China, which is now recognized internationally as Corona Virus Disease 2019 (COVID-19), the etiological agent classified as Severe Acute Respiratory Syndrome Corona Virus 2 (SARS-CoV-2). According to the World Health Organization (WHO), it has so far expanded to more than 213 countries/territories worldwide. Our study aims to find the viral peptides of SARS-COV-2 by peptide mass fingerprinting (PMF) in order to predict its novel structure and find an inhibitor for each viral peptide. For this reason, we calculated the mass of amino acid sequences translated from the SARS-CoV2 whole genome and identify the peptides that may be a target for inhibition. Molecular peptide docking with Moringa oleifera, phytochemicals (aqueous and ethanolic) leaf extracts of flavonoids (3.56 ± 0.03), (3.83 ± 0.02), anthraquinone (11.68 ± 0.04), (10.86 ± 0.06) and hydroxychloroquine present therapy of COVID-19 in Pakistan for comparative study. Results indicate that 15 peptides of SARS-CoV2 have been identified from PMF, which is then used as a selective inhibitor. The maximum energy obtained from AutoDock Vina for hydroxychloroquine is –5.1 kcal/mol, kaempferol (flavonoid) is –6.2 kcal/mol, and for anthraquinone –6 kcal/mol. Visualization of docking complex, important effects are observed regarding the binding of peptides to drug compounds. In conclusion, it is proposed that these compounds are effective antiviral agents against COVID-19 and can be used in clinical trials. Communicated by Ramaswamy H. Sarma

Purpose: This study was planned to examine the effects of Src and Yes1 single nucleotide polymorphism (SNPs) on the risk of thyroid cancer in 499 patients and 500 controls. Materials & methods: Three SNPs of Src gene and three SNPs of Yes1 gene were analyzed using Tetra-primer ARMS-PCR followed by sequencing. Results: rs121913314 of Src gene genotype TT showed 32-fold increased risk of thyroid cancer and rs2305994 of Yes1 genotypes TT and CT showed 2.7-fold and 16-fold increased risk in thyroid cancer (p < 0.0001). Haplotype analysis revealed that CATGCC, CATGCT, CATGTC, CATGTT, TATGCC and TATGTTA haplotypes are associated with thyroid cancer risk. Conclusion: Results showed that genotypes and allele distribution of Src and Yes1 genes are significantly linked with increased risk of thyroid cancer.

Achromatopsia (ACHM) is a genetically heterogeneous visual disorder, also known as rod monochromatism, in which human get affected due to cone cells. Mutation in five genes viz. CNGA3, CNGB3, GNAT2, PDE6C, and PDE6H have been reported in ACHM. These genes encode essential constitutes of the cone-specific photo transduction cascade. Present study was focused on CNGB3 gene that accounts 40%-50% mutations of all ACHM cases. A new approach for analyzing drug-drug interactions based on modularity was adopted. This approach depends on the behavioral relationship of drugs against CNGB3 for ACHM, particularly the ADME and toxicity between drugs. Data of 2475 compounds were retrieved, out of which 185 were selected on the basis of Lipinski rule of five. In total, eight clusters were made for which the strongly interacted DDI networks were build based on their modularity values. Strong DDI and minimum toxic values indicates that 5 drugs are effective, but on the basis of docking only 2 drugs indicated no bumps, which shows that they are most appropriate for treating ACHM. Our findings revealed that drug-drug interactions disclose the intervention of drug nature and can also successfully diagnose new indications and more convincing drugs for other diseases as well. Keywords: Achromatopsia, CNGB3, In silico, Integrated drugs

Acinetobacter is an important nosocomial pathogen to cause infections such as pneumonia, bloodstream infections, meningitis, wound and surgical site infections including flesh eating bacterium necrotizing fasciitis and urinary tract Infections. A. baumannii can be spread through direct contact with surfaces, objects and the skin of contaminated persons. Acinetobactter has acquired resistance to most of the antibiotics and can play havoc in hospital environment due to its ability to survive desiccation and in moist environment in the presence of disinfectants. Currently, there are 32 genospecies of Acinetobacter known. Among these, A. baumannii is the most important in the clinical context, since it is the most frequently isolated in nosocomial infections and the one associated with the highest mortality rate. Objective To find out the frequency of A. baumannii causing surgical site infections after cardiac surgery and best antibiotic options for its treatment in patients admitted in Rawalpindi Institute of Cardiology. Materials and Methods A retrospective study was carried out to find out bacterial cultures in admitted patients at Rawalpindi Institute of Cardiology with surgical site infections from July 2017 to August 2018. A total of 405 pus specimens collected from patients with suspected surgical site infections were tested for bacterial culture and antimicrobial susceptibility test. Patient profile was noted from centralized hospital data. Results Out of total 405 specimens 13 were culture positive for A. baumannii (3.2%). Ten isolates were Pan Drug Resistant (PDR). Conclusion A. baumannii infection although infrequent in our set up is mostly pan resistant. Infection control practices & surveillance are important to avoid its spread in hospitalized patients.

Illnesses caused by human pinworm remains a pediatric health problem in developing nations including Pakistan. This study aimed to investigate the prevalence of Enterobius vermicularis in school children of four districts in Malakand region, Pakistan. Four hundred faecal specimens were screened from May 2014 to July 2017 using normal saline and Lugol Iodine solution. Twenty three (5.75%) individuals were found infected with E. vermicularis. Five children (1.25%) were infected with only E. vermicularis and eighteen (4.5%) were mixed with other helminths. E. vermicularis 23 (5.75%), hookworm 11 (2.75%), Ascaris lumbricoides 5 (1.25%), Taenia saginata 2 (0.5%) and Trichuris trichuira 4 (1%) were detected. Age wise 5-8 years were more parasitized followed by 13-15 and 9-12 years of age (0.0296, P

Tapeworms of zoonotic importance have been described as a leading public health problem. Current research was aim to assess the prevalence of tapeworms among 5-12years school children residing in district Lower Dir, Pakistan from January 2019-December 2019. The wet mount preparation in saline/iodine/methods were used for stool examination. Data was analyzed using appropriate descriptive, static methods. Of the 400 children studied 71.7% were infected with one or more species of intestinal parasites. Single infection of cestode species was found in 69 individuals with 17.2% prevalence and multiple parasitic infections were identified in 19.7% (n=79/400) individuals. The multiple infection were comprised as 10% (n=40) double, 6.75% (n=27) triple and 3% (n=12) quadruple. A total of 9 species of helminths and one species of protozoan infection. Among the helminths Ascaris lumbricoides was the most prevalent 33.1% (n=95), Taenia saginata 22.6% (n=65), hookworm 19.8% (n=57), Hymenolepis nana 18.8% (n=54), Enterobius vermicularis and Hymenolepis diminuta 1.39% (n=4each), Trichuris trichura 1.04% (n=3), Toxocara spp 0.69% (n=2) and Schistosoma japonicum 0.34% (n=1) were reported. One protozoan species was Cryptosporidium spp 0.69% (n=2) in current study. In case of A.lumbricoides, hookworm, E.vermicularis, T.trichura, T.saginata, H.nana and H.diminuta the male children of below 8 years of age were highly infected. Other infections are reported in the same prevalence with slight difference if any. We conclude that there is a need for mass scale campaigns to create awareness regarding health and hygiene in children and the need for development of effective poverty control programs because deworming alone is not adequate to control parasitic infections. Resumo As tênias de importância zoonótica têm sido descritas como um dos principais problemas de saúde pública. A pesquisa atual teve como objetivo avaliar a prevalência de tênias entre crianças em idade escolar de 5 a 12 anos que residem no distrito de Lower Dir, Paquistão, de janeiro de 2019 a dezembro de 2019. Os métodos de preparação para montagem úmida em solução salina/iodo foram usados para exame de fezes. Os dados foram analisados usando métodos descritivos e estáticos apropriados. Das 400 crianças estudadas, 71,7% estavam infectadas com uma ou mais espécies de parasitas intestinais. Infecção única de espécies de cestóides foi encontrada em 69 indivíduos com prevalência de 17,2% e infecções parasitárias múltiplas foram identificadas em 19,7% (n = 79/400) indivíduos. As infecções múltiplas foram compostas por 10% (n = 40) dupla, 6,75% (n = 27) tripla e 3% (n = 12) quádrupla. Um total de 9 espécies de helmintos e uma espécie de infecção por protozoários. Entre os helmintos, Ascaris lumbricoides foi o mais prevalente 33,1% (n = 95), Taenia saginata 22,6% (n = 65), ancilóstomo 19,8% (n = 57), Hymenolepis nana 18,8% (n = 54), Enterobius vermicularis e Hymenolepis diminuta 1,39% (n = 4cada), Trichuris trichura 1,04% (n = 3), Toxocara spp 0,69% (n = 2) e Schistosoma japonicum 0,34% (n = 1). Uma espécie de protozoário foi Cryptosporidium spp 0,69% (n = 2) no estudo atual. No caso de A.lumbricoides, ancilostomíase, E.vermicularis, T.trichura, T.saginata, H.nana e H.diminuta, as crianças do sexo masculino com menos de 8 anos de idade estavam altamente infectadas. Outras infecções são relatadas na mesma prevalência, com ligeira diferença, se houver. Concluímos que há uma necessidade de campanhas em massa para criar consciência sobre saúde e higiene em crianças e a necessidade de desenvolvimento de programas eficazes de controle da pobreza, porque a desparasitação por si só não é adequada para controlar infecções parasitárias.

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.

Endometrial cancer is the fourth most common cancer in women. It arises from the endometrium and accompanied by the abnormal growth of the cells. Sign and symptoms include pelvic pain and abnormal vaginal bleeding. It has two categories. Type 1 tumors are estrogen-dependent and they have mutations in PTEN, PIK3CA while Type 2 tumors are more sensitive and have mutations in TP53. Overactivation of the signaling pathway (PI3K) results in anti-apoptosis. Here, this study aims to identify Tumor-Specific Antigen for germline mutations in endometrial cancer which can be used as a potential vaccine candidate. The germline mutations data are obtained from cancer gene census of the cosmic database. Genes mutating with crucial role in endometrial cancer are considered. Peptides libraries are generated using peptide design library. Human leukocyte antigen alleles are identified for the peptide library through NetMHC. Binding affinities of alleles with peptide are determined. Linear regression is performed to generate graphs. PTEN, TP53, PIK3CA, KRAS, and CTNNB1 proved to have critical role. About 575 overlapping peptide libraries are generated and each peptide has a length of 18-20 amino acids. Approximately 58 HLAs are identified, having strong interactions with HLAs. Regression analysis shows that the no. of mutations are directly associated with a binding affinity of peptides. From this, we suggest that the identified TSA can be used as personalized peptide vaccines that directly target the mutated genes in endometrial cancer. This research work can be used in the laboratories for further validation.

Lung Cancer is a type of serious cancer that causes 1.37 million deaths every year all over the world and accounts for almost 18% of all cancer death. PI3Ks establish a lipid kinase family that is important to integrate disparate dimensions of cell functions including cell survival, vesicular trafficking, proliferation, and cell migration. This is an essential pathway in the oncogenesis and advancement of lung cancer. In preclinical studies, PIK3 inhibitors deliver exploratory antitumor activity. The study was established to realize perception and molecular mechanisms that are crucial for potent inhibitors of PIK3CA. In this research work, mutated proteins of PIK3CA were selected, models of pharmacophore were designed and hit compounds were obtained against reference feature pharmacophore by virtual screening. These hit compounds were then docked with the mutated proteins of PIK3CA. Three important features were shown by Pharmacophores, Hydrogen bond donor (HBD), Hydrogen bond acceptors (HBA) and aromatic rings (AR). Through virtual screening, 8 hit compounds were obtained before docking Lipinski rule of five was applied and the compounds that achieved all properties were docked with mutated proteins of PIK3CA. 3 compounds fulfilled all properties and demonstrated the stability of ligands. It is suggested that these compounds can be used for curing PIK3CA involved in lung cancer and on the basis of shared feature novel compounds can be designed against a mutation in PIK3CA involved in lung cancer.

This paper considers the concomitant-based rank set sampling (CRSS) for estimation of the sensitive proportion. It is shown that CRSS procedure provides an unbiased estimator of the population sensitive proportion, and it is always more precise than corresponding sample sensitive proportion (Warner SL (1965)) that based on simple random sampling (SRS) without increasing sampling cost. Additionally, a new estimator based on ratio method is introduced using CRSS protocol, preserving the respondent’s confidentiality through a randomizing device. The numerical results of these estimators are obtained by using numerical integration technique. An application to real data is also given to support the methods.

Graphical abstract, Introduction Researchers worldwide with great endeavor searching and repurpose drugs might be potentially useful in fighting newly emerged coronavirus. These drugs show inhibition but also show side effects and complications too. On December 27, 2020, 80,926,235 cases have been reported worldwide. Specifically, in Pakistan, 471,335 has been reported with inconsiderable deaths. Problem statement Identification of COVID-19 drugs pathway through drug-gene and gene−gene interaction to find out the most important genes involved in the pathway to deal with the actual cause of side effects beyond the beneficent effects of the drugs. Methodology The medicines used to treat COVID-19 are retrieved from the Drug Bank. The drug-gene interaction was performed using the Drug Gene Interaction Database to check the relation between the genes and the drugs. The networks of genes are developed by Gene MANIA, while Cytoscape is used to check the active functional association of the targeted gene. The developed systems cross-validated using the EnrichNet tool and identify drug genes' concerned pathways using Reactome and STRING. Results Five drugs Azithromycin, Bevacizumab, CQ, HCQ, and Lopinavir, are retrieved. The drug-gene interaction shows several genes that are targeted by the drug. Gene MANIA interaction network shows the functional association of the genes like co-expression, physical interaction, predicted, genetic interaction, co-localization, and shared protein domains. Conclusion Our study suggests the pathways for each drug in which targeted genes and medicines play a crucial role, which will help experts in-vitro overcome and deal with the side effects of these drugs, as we find out the in-silico gene analysis for the COVID-19 drugs.

For the proper growth of fish, it is necessary to feed the fish with a proper and balanced diet. A study was conducted to find out the effect of different protein-based diets on fingerlings of Tor putitora (mahseer). A feed with dietary protein levels of 35%, 40%, 45%, and 50% were prepared. The effect of different protein-based feed on weight gain, standard growth rate (SGR), food conversion ratio (FCR), percent weight gain, food conversion efficiency (FCE), and protein efficiency ratio (PER) was studied. An increase was observed in the growth rate with an increase in protein concentration up to 45%. The fingerlings fed a 45% protein diet shown the highest growth, followed by 50%, 40%, and 35%. The SGR value was greatest for 45% protein diet (8.56) followed by 50% and 40%, while the least values were observed for 35% protein feed (1.57). The same trend was observed for FCE. The highest PER values was observed in fishes fed 45% protein-based feed (0.65) followed by 50% (0.56), 40% (0.38) and35% (0.17). The food conversion ratio was lowest for 45% protein diet (3.41), while the greatest for 35% protein feed (16.85). It was concluded that a 45% protein-based diet was the best feed formulation for higher production of Tor putitora. However, research on the same percentage of protein diet is recommended for yearlings. Resumo Para o bom crescimento dos peixes, é necessário alimentá-los com uma alimentação adequada e balanceada. Um estudo foi realizado para descobrir o efeito de diferentes dietas à base de proteínas em alevinos de Tor putitora (mahseer). Foi preparado um alimento com níveis de proteína dietética de 35%, 40%, 45% e 50%. O efeito de diferentes alimentos à base de proteína no ganho de peso, taxa de crescimento padrão (SGR), taxa de conversão alimentar (FCR), ganho de peso percentual, eficiência de conversão alimentar (FCE) e taxa de eficiência proteica (PER) foi estudado. Foi observado um aumento na taxa de crescimento com um aumento na concentração de proteína de até 45%. Os alevinos alimentados com dieta de 45% de proteína apresentaram o maior crescimento, seguidos de 50%, 40% e 35%. O valor de SGR foi maior para dieta com 45% de proteína (8,56), seguido de 50% e 40%, enquanto os menores valores foram observados para ração com 35% de proteína (1,57). A mesma tendência foi observada para FCE. Os maiores valores de PER foram observados em peixes alimentados com 45% de ração à base de proteína (0,65), seguido por 50% (0,56), 40% (0,38) e 35% (0,17). A taxa de conversão alimentar foi menor para a dieta com 45% de proteína (3,41), enquanto a maior para a dieta com 35% de proteína (16,85). Concluiu-se que a dieta à base de proteína de 45% foi a melhor formulação alimentar para maior produção de Tor putitora. No entanto, a pesquisa sobre a mesma porcentagem de dieta proteica é recomendada para animais de um ano.

Fish is consumed as a rich and cheaper source of white meat and proteins all over the world. Fish farming is the leading source of income generation throughout the world. The present research study was conducted with aims to investigate the ecto and endo parasitic fauna of S. plagiostomus (snow trout) in River Swat. A total of 96 fish samples were collected on monthly basis from July-2018 to February-2019, from upper, middle and lower reaches. Fish samples were collected with the help of cast net, hand net and fishing rods. Local fishermen and experts help were also sought out for fish collection. 61 out of 96 fishes were found infected by helminth parasites. The total prevalence and intensity of 63.54% and 2.90 was observed respectively during data analysis. Highest monthly prevalence of 83.33% was recorded during July and August, while lowest prevalence of 33.33% was noted during February. Five species of helminths parasites were detected from S. plagiostomus, of which two were trematodes (Rhabdochona shizothoracis and Rhabdochona species), one species of Monogenia (Diplozoon paraddoxum), one species of Cestodes (Nippotaenia species), and one species of Acanthocephalan (Neoechynorhynchus devdevi). Highest parasite wise prevalence, intensity and relative density of 21.87%, 4.09 and 0.895 was noted for R. schizothoracis while the lowest prevalence, intensity and relative density of 4.16%, 1.25 and 0.052 was noted for N. devdevi. Highest infection of 76.08% was observed in adults host while lowest, 40% infestation rate was observed in young fish samples. 73.68% prevalence was observed in female hosts while only 56.90% prevalence was observed in male individuals. Higher infection (83.33%) was noticed during summer season, while lowest infection (44.44%) was observed during winter season. Similarly 71.79% fishes were found infected that were collected from lower reaches of the River Swat than the fish samples collected from upper reaches (52%). Resumo O peixe é consumido mundialmente por ser uma fonte rica e barata de carne branca e proteínas. A piscicultura é a principal fonte de geração de renda em todo o mundo. O presente estudo foi conduzido com o objetivo de investigar a fauna ecto e endoparasitária de S. plagiostomus (truta da neve) no rio Swat. Foram coletadas mensalmente 96 amostras de peixes, no período de julho de 2018 a fevereiro de 2019, nos trechos alto, médio e baixo com auxílio de redes de arrasto, redes de mão e varas de pesca. Pescadores locais e especialistas também ajudaram na coleta de peixes. Dos 96 peixes encontrados, 61 estavam infectados por parasitas helmintos. A prevalência de 63,54% e a intensidade total de 2,90 foram observadas durante a análise dos dados. A maior prevalência mensal de 83,33% foi registrada nos meses de julho e agosto, enquanto a menor, de 33,33%, em fevereiro. Cinco espécies de parasitas helmintos foram detectadas de S. plagiostomus, dos quais dois eram trematódeos (espécies Rhabdochona shizothoracis e Rhabdochona), uma espécie de monogenia (Diplozoon paradoxum), uma espécie de cestóideos (espécie Nippotaenia) e uma espécie de acantocéfalo (Neoechynorhynchus devdevi). As maiores prevalências de parasitas (21,87%), intensidade (4,09) e densidade relativa (0,895) foram observadas em R. schizothoracis, enquanto as menores prevalências de parasitas (4,16%), intensidade (1,25) e densidade relativa (0,052), em N. devdevi. A infecção mais alta (76,08%) foi constatada em adultos hospedeiros, ao passo que a taxa de infestação mais baixa (40%) foi encontrada em amostras de peixes jovens. A prevalência de 73,68% foi verificada em hospedeiros do sexo feminino, enquanto a de 56,90%, em indivíduos do sexo masculino. Maior infecção (83,33%) foi observada durante a temporada de verão, e a menor infecção (44,44%), durante o inverno. Da mesma forma, 71,79% dos peixes encontrados infectados foram coletados no trecho baixo do rio Swat, enquanto 52%, no trecho alto.

Malakand region is an endemic area for cutaneous leishmaniasis (CL). However, there are limited number of studies of this disease in Pakistan. Therefore, a study was conducted to understand the level of awareness attitude and practice among the residents of Makaland towards CL and the disease vectors. This study adopted a cross-sectional approach with a total of 400 respondents (n=93 rural and n= 307 urban). Overall, the population in Malakand region (61.2%) were well-informed in the role of sand fly in transmitting diseases, but most lack knowledge on the vector’s behavior and almost a quarter (24.5%) were unable to provide knowledge on proper control measures. Alarmingly, the practice and attitudes of the general population was not satisfactory as close to half (49.8%) of the population did adopt any control method. This study calls for increase in awareness through health education campaign to reduce the risk of cutaneous leishmaniasis outbreaks in the future. Resumo A região de Malakand é uma área endêmica para leishmaniose cutânea (CL). No entanto, há um número limitado de estudos sobre esta doença no Paquistão. Portanto, foi realizado um estudo para entender o nível de atitude e prática de conscientização entre os residentes de Makaland em relação aos CL e os vetores da doença. Este estudo adotou uma abordagem transversal com um total de 400 entrevistados (n = 93 rural e n = 307 urbano). No geral, a população da região de Malakand (61,2%) estava bem informada sobre o papel da mosca na transmissão de doenças, mas a maioria não possui conhecimento sobre o comportamento do vetor e quase um quarto (24,5%) foi incapaz de fornecer conhecimento sobre medidas de controle adequadas . De maneira alarmante, a prática e as atitudes da população em geral não foram satisfatórias, pois cerca da metade (49,8%) da população adotou algum método de controle. Este estudo apela ao aumento da conscientização por meio de campanhas de educação em saúde para reduzir o risco de surtos de leishmaniose cutânea no futuro.

The most important and broad-spectrum drug used to control the parasitic worms to date is ivermectin (IVM). Resistance against IVM has emerged in parasites, and preserving its efficacy is now becoming a serious issue. The parasitic nematode Haemonchus contortus (Rudolphi, 1803) is economically an important parasite of small ruminants across the globe, which has a successful track record in IVM resistance. There are growing evidences regarding the multigenic nature of IVM resistance, and although some genes have been proposed as candidates of IVM resistance using lower magnification of genome, the genetic basis of IVM resistance still remains poorly resolved. Using the full magnification of genome, we herein applied a population genomics approach to characterize genome-wide signatures of selection among pooled worms from two susceptible and six ivermectin-resistant isolates of H. contortus, and revealed candidate genes under selection in relation to IVM resistance. These candidates also included a previously known IVM-resistance-associated candidate gene HCON_00148840, glc-3. Finally, an RNA-interference-based functional validation assay revealed the HCON_00143950 as IVM-tolerance-associated gene in H. contortus. The possible role of this gene in IVM resistance could be detoxification of xenobiotic in phase I of xenobiotic metabolism. The results of this study further enhance our understanding on the IVM resistance and continue to provide further evidence in favor of multigenic nature of IVM resistance.

Salmonella enterica serovar Typhi (S. Typhi) is one of the typhoidal Salmonellae that causes typhoid fever. We report the first case of an XDR S. Typhi in a suspected case of Endocarditis with Aortic Valve Replacement and deranged INR. The identification was carried out by an automated system. The antibiogram was performed according to CLSI recommendations. The XDR S. Typhi isolates were found resistant to Azithromycin. Although XDR S. Typhi has been reported in our country and elsewhere, however, till to date no complete resistant isolate of S. Typhi to Azithromycin has been reported in Pakistan. The patient had a smooth recovery on intravenous meropenem. The case highlights the importance of the acquisition of resistance to the last line antibiotics in S. Typhi in our country and is of concern to infectious disease specialists to ensure infection control to avoid its spread. J Microbiol Infect Dis 2021; 11(1):32-35.

Objective To investigate the clinical and angiographic characteristics of coronary artery ectasia (CAE) and its relation with the inflammatory marker, HsCRP. Study design An observational study. Place and duration of study Rawalpindi Institute of Cardiology, Rawalpindi, from April 2015 till November 2016. Methodology Eighty-one patients with CAE and 57 age matched patients with stenotic coronary artery disease (CAD), but without CAE, were included in the study. Clinical, angiographic, and laboratory data were documented. Chi-square test was used to compare coronary risk factors between two groups. T test was used to compare means between the groups. Analysis of variance was used to analyse HsCRP levels among various types of ectasia. Correlation analysis was used to study association of ectasia with different risk factors. Results Males were predominant in both with & without CAE. Hypertension, smoking and obesity were significantly more common among CAE patients than those without (60.5% vs. 52.6%, 56.8% vs. 43.9% and 80.2% vs. 14%, respectively). Diabetes was much less in CAE group (32.1% vs. 42.1%). HsCRP was higher in patients with CAE than those without and was significantly higher in patients with more extensive ectasia. Majority (65.4%) of CAE patients had significant CAD; whereas, only 7.4% had isolated CAE. Most common artery involved was RCA (70.4% of total) and most common pattern was single ectatic vessel. Conclusion Obesity and smoking predispose to CAE, along with male sex and hypertension. While diabetes is negatively associated with CAE. HsCRP levels tend to be higher in ectasia patients, especially those with severe forms. Finally, CAE has a predilection for RCA.

Maize flour was infested with fresh emerged Tribolium castaneum adults, and its nutritional composition was evaluated after 0, 45, and 90 days of the infestation. Furthermore, 99% carbon dioxide was applied to different developmental stages of T. castaneum for its management. There were six treatments and five replicates; for each replicate, maize flour (150 g) was taken in a 250-ml plastic jar container, insects were released in the flour, and jars were placed into the incubator at a temperature of 28 ± 1 °C, 60 ± 5% RH. Similarly, the application of 99% CO2 was done with four exposure times of 12, 24, 48, and 72 h, at 35 °C 65 ± 5% RH. Present results showed major fluctuations in the nutritive composition of maize flour. Increase in the moisture, fat, fiber, protein, and ash contents was directly proportional to the increase in infestation level and time, contrary to the depletion of carbohydrates and total weight loss. The results of CO2 treatment indicated that pupa was the most resilient stage as compared with larvae and adult stage. The observed susceptibility order was as follows: adult > larvae > pupae. The maximum mortality of adult, larval, and pupal stages was recorded after 24, 48, and 72 h of CO2 application, respectively. These findings might be helpful to develop an ecofriendly technique to manage this crucial pest.

Introduction: Perinatal asphyxia is one of the most common causes of neonatalmorbidity and mortality in most countries of the world. The objective of my study was to assessthe correlation of clinical findings of perinatal asphyxia with cranial sonography in full termbabies. Study Design: Retrospective study. Setting: Neonatal Intensive Care Unit of Children’sHospital Multan. Period: January 2016 to October 2016. Material and Methods: 100 fullterm babies having history of delayed cry were scanned within three days of birth in NeonatalIntensive Care Unit of Children’s Hospital Multan. Clinically findings including full term babies,birth weight, grunting, cyanosis history of mode delivery, resuscitation history, delayed cry andhypoxic ischemic encephalopathy (HIE) grades were taken from baby’s hospital file record andstandard images including coronal and sagittal plans were taken by Ultrasound machine probeof frequency 3-5 MHz. Findings were recorded on data collection sheets and spread on EXELsheets. Correlation was found by using SPSS software. Result: Out of 100 neonates 63 weremale and 37 were female with birth weight (2.4-3.6) having mean ± SD 3.08 ± 0.53. HIE grades(mild, moderate and severe) were found in 12, 83, 5 babies respectively and ultrasound grades0 (normal/ mild echogenic), grade 1 (moderate echogenic) and grade 2 (severe/generalizedechogenic) were found in 32, 52, 16 neonates respectively with r= 0.37 and P-value < 0.05showing moderate positive correlation. Conclusion: Cranial ultrasound is a good screeningtool to evaluate asphyxiated neonatal brain. It has a moderate positive correlation with clinicalfindings.

Background: Salmonella typhimurium is a rod-shaped bacteria with a Gram-negative genus, belonging to the Enterobacteriaceae family of microbes, which invades the intestinal lumen of Human. Salmonella typhimurium is a root source, accounting for gastroenteritis in humans as well as in other mammals. Gastroenteritisis associated with Salmonella Typhimurium interacts with the contaminated food and water and spreads to nearby people in the area. Small intestine is attacked by Salmonella, which then enter into the bloodstream momentarily, and are responsible for millions of mortalities and morbidities around the globe. Salmonella typhimurium toxins cause gastrointestiritis due to inflammation in the stomach and intestine in infants and young children. It accounts for millions of deaths with a higher incidence rate in developing countries. Methods: : In the current research, subtractive proteome mining has been done to recognize putative drug targets. The proteome was analyzed through blast in order to exclude homologous proteins. Bacterial essential proteins were predicted and the participation of the essential genes in the metabolic pathways has been analyzed. Results: : 36 essential genes and 15 unique pathways have been identified as potential drug targets among the total of 1934 proteins. The location of proteins is determined as an outer membrane. 3 proteins out of 36 essential proteins are recognized as putative drug targets. Conclusion:: In the future, virtual screening for the evaluation of novel clinical compounds for the identified proteins will be effective and valuable for Salmonella Typhimurium infection in Homo sapiens.

Alzheimer’s is a neurodegenerative disease, typically begins slowly and after the passage of time gets worse. Around 70% of the cause of the disease is accepted to be hereditary with numerous genes generally involved. Objective: There are no proper medications for the disease. At present, the most acknowledged Alzheimer’s treatment is cholinesterase inhibitor that inactivates the acetyl cholinesterase chemical to expand acetylcholine level in the brain. Medicinal plants are also used for Alzheimer’s. Here, an In-silico attempt is made to compare the Medicinal plants with synthetic drugs to determine the efficacy of medicinal plants in the treatment of Alzheimer’s, data is collected for both medicinal plants and commercial drugs. Interactions of compounds with proteins are determined and side effects are calculated and compared to find out the best among them. The mathematical modeling of all the drugs is done to determine their effects on proteins expression. It is observed that none of the synthetic drugs interacts with acetyl cholinesterase, while the chemical constituents of medicinal plants represent greater interactions with both cholinesterase and acetyl cholinesterase, as compared to the synthetic drugs. The mathematical modeling of compounds also confirmed the inhibitory effects of medicinal plants compounds on proteins, whereas the synthetic drugs showed an in increase in the expression level of proteins. On the basis of the results, it is suggested that these chemical constituents are better used as the remedy against Alzheimer’s.

Objectives: The objective was to determine accuracy of ultrasound in thediagnosis of ureteric calculi confirmed on non-contrast Computed Tomography amongpatients with acute ureteric colic. Study Design: Cross-sectional study. Setting: EmergencyDepartment of Nishtar Hospital, Multan. Period: 11-07-2012 to 10-01-2013. Materials andMethods: 100 consecutive patients presenting with acute severe ureteric colic and fulfillingthe inclusion and exclusion criteria were enrolled for the study from the emergency departmentof Nishtar Hospital Multan. Ultrasonography was done in all patients and USG findings wererecorded for the presence or absence of hyperechoic shadows in the ureteric. All the patientsunderwent CT scan to confirm or refute the findings of Ultrasonography. Result: Mean age ofthe patients was 37.85 + 12.60 years. Males were 53 (53%) while females were 47 (47%). Meanduration of pain before presentation was 14.81 + 6.20 hours. Mean severity of pain on visualanalogue scale was 9.40 + 0.8. Overall 79 patients were diagnosed as having ureteric calculi.Ultrasonography detected the ureteric stone in 75 patients and was all found to have stoneon CT scan and represented true positives. Among 25 patients in whom ultrasound did notdemonstrate any stone, 4 were found to have ureteric stone on CT scan thus representing falsenegative whereas 21 (84%) were confirmed on CT scan not to have any stone, thus representingTrue negatives. The sensitivity of USG for detection of ureteric stone was found to be 94.9%,the specificity was 100%, and positive predictive value was 100% while negative predictivevalue was 84% .There was no significant effect of age or gender on the accuracy of ultrasound.Conclusion: Ultrasonography is a readily available, non-invasive and reliable investigation inpatients presenting with acute flank pain to diagnose ureteric stones with a specificity of 100%and a sensitivity approaching 95%. Thus it is recommended that it should be used routinely forthe evaluation of patients presenting with acute flank pain.

Background: Chikungunya an arbovirus, is transmitted to humans by the bite of Aedes mosquito. The virus occurrences have been reported in Southeast Asian countries including Pakistan. Its symptoms include typical febrile illness and arthralgic syndrome. The virus has not decisively proved to be life-threatening. Methods: The attempt was to design T-cell and B-cell epitope-based vaccine for Chikungunya. The proteome of chikungunya was retrieved, antigenic proteins were identified and T-cell epitopes and B-cell epitopes were predicted. Interacting HLA alleles were also identified. The final analysis was done to confirm that predicted T-cell epitopes and B-cell epitopes can be used as a vaccine. Results: About 32 T-cell epitopes and a 10mer B-cell epitope were identified. Both T-cell and Bcell epitopes demonstrated strong interactions with HLA alleles. The predicted T-cell and B-cell epitopes were docked with respective HLA alleles. The docking analysis showed that the predicted respective epitopes best fit into the binding pockets of the alleles. Conclusion: On the basis of this computational analysis, it is suggested that these predicted epitopes can be used as a remedy against Alphavirus strain of chikungunya. Further laboratory experiments can be conducted to determine the efficacy and stability of this work.

Background: Paravalvular leak (PVL) can complicate mitral and aortic valves replacement. Most PVLs are often clinically insignificant. However, large leaks can lead to heart failure and infective endocarditis. Intravascular hemolytic anemia is common in small PVLs. Reoperation for closure of PVL is associated with high mortality. Transcatheter closure is less invasive and can be used in high-risk patients. Case summary: We present a case of a 38-year-old man with a history of Aortic Valve replacement (AVR) and Mitral valve replacement (MVR) who developed hemolytic anemia and haemoglobinurea. The patient was managed initially conservatively but later underwent redo valve surgery after exclusion of other causes of hemolytic anemia. Postoperatively, haemoglobinurea disappeared dramatically whereas anemia resolved gradually after surgery. Discussion: Significant intravascular hemolysis is a rare but serious complication of PVL that poses diagnostic problem to cardiac surgeons, but also for cardiologists and internal medicine professionals especially when the prosthetic valve function is considered adequate. PVL is the flow of blood through a track between the native cardiac tissue and the implanted valve due to any compromise in closure between the two. PVL is also more frequently seen after mitral (up to 20%) valve replacement than aortic prosthetic valves. PVLs are more frequently diagnosed by Transesophageal echocardiography (TEE) than Transthoracic echocardiography (TTE) due to its ability to detect minute jets of regurgitated blood. Conclusion: Either repair or re-replacement of prosthetic valves with PVLs is needed in about 1% to 5% of patients. The case study is presented to highlight PVL as a rare cause of haemoglobinurea and hemolytic anemia.

Hepatitis C Virus (HCV) infection is a major health concern worldwide. The presence of both HCV viral RNA and NS5A proteins in peripheral blood mononuclear cells (PBMCs) indicate the efficacy of the treatment during sustained virological response (SVR) and end of treatment response (ETR). The main objective of this study was to detect the absence or presence of HCV RNA and NS5A proteins in PBMCs. Blood samples were taken from selected patients (Islamabad, Pakistan) before treatment, at ETR, and during SVR. Two hundred HCV responders to pegylated IFN-α-2a plus ribavirin were selected. HCV RNA was extracted from the patients to determine the viral load by reverse transcription (RT)-polymerase chain reaction before treatment. Out of 200 patients, 152 (76%) and 48 (24%) achieved positive and negative ETR, respectively. Among ETR patients, 134 (88.2%) showed SVR, whereas 18 (11.8%) displayed relapse. The male to female ratio was 92:108 with mean age of 37.4 years. Among 152 ETR-positive patients, 29 (19%) patients' PBMCs were positive for HCV RNA and 27 (17.8%) were positive for NS55A proteins. Patients having HCV RNA in PBMCs showed higher relapse frequency compared with patients lacking it. Similarly, patients having NS5A protein showed significantly higher relapse frequency compared with patients lacking it. All PBMC-positive samples were of genotype 3a. In addition, patients with positive NS5A in their PBMCs showed greater risk of relapse compared with patients having HCV RNA. We conclude that the absence of both viral HCV and proteins can be used as an indicator for diagnosis of SVR in the future.

Dengue is one of the greatest important mosquito-borne viral sicknesses touching people; with over portion of the total populace living in regions at hazard initially, dengue infection contaminations happened for the most part as pestilences in tropical and subtropical nations There are four distinctive dengue infection (DENV) serotypes that share antigenic affiliations (DENV-1, DENV- 2, DENV-3, and DENV-4) Doctors/Scientists are confronting trouble in the characterization of dengue Virus (DV) through wet labs and accessible programming’s are not particular for this reason. Dengue infection has turned into a noteworthy general medical issue in Pakistan Through the computational approach, noteworthiness of ID in order for genome grouping of DV will turn out to be more productive in clinical and test ways. By methods for calculations it has been viewed as that rate of precision and factual control turn out to be more advantageous for genotyping of dengue Virus. On the premise of results we build up a Tool for the Classification of dengue Virus, the computational approach, importance of recognizable proof in arrangement for genome grouping of DV will turn out to be more effective in clinical and test ways.

Background: Colorectal cancer is a varied illness with an expected heritability of 25–30%. Many CRC disorders occur because of solid family history, a high penetrance of the infection, and developing various tumors at an early age. A few novel genes are recognized that shows associations with CRC, such as AURKA, BCAS1, GNAS and MLH1. Material and methods: In this research work FDA rejected Alpidem and Propoxyphene were selected. Drugs were changed on the basis of side effects; modified drugs were docked with AURKA, BCAS1, GNAS and MLH1 proteins and QSAR analysis was performed. Results: Docked and QSAR results demonstrated the better interaction of both modified Alpidem and Propoxyphene along with proteins of CRC causing genes. The toxicity value and side-effects of modified Alpidem and modified Propoxyphene are less than original drugs. Conclusion: The fewer side effects and docking results of both modified Alpidem and Propoxyphene suggest that both the drugs can be used to cure mutations of genes in colorectal cancer as both modified drugs have fewer side-effects and toxicity, as compared to original drugs, both drugs have demonstrated greater interactions with the amino acid residues lying in the pockets of mutated proteins that demonstrates their stability and soundness.

Background: Mutations of Estrogen receptors 1 affect its ligand-binding domain and results in the formation of breast cancer. Breast cancer is a known universal disease and the second leading reason behind the death of most females. About 70% of breast cancers express the estrogen receptor. This study was undertaken to realize perceptions into molecular mechanisms and structural necessities that are crucial for potential inhibition of ESR1. Methods: In this research ESR1 proteins were selected and pharmacophore models were generated, virtual screening was done to obtain hit compounds against reference shared feature pharmacophore, the hit compounds were docked with ESR1 proteins. Results: The pharmacophore displayed three main features Hydrogen bond acceptor, Hydrogen bond donor and aromatic rings. 10 hit compounds were obtained by virtual screening; compounds were further sorted for Lipinski rule of five before docking. Compounds that fulfill all properties of Lipinski rule of five were docked with proteins, 3 compounds demonstrated ideal docking results. They fit appropriately in the pocket of proteins which demonstrated the soundness and stability of ligand compounds. Conclusion: It is suggested that these three compounds can be used in the treatment of ESR1 mutations in breast cancer and novel compounds can be designed on the basis of shared feature pharmacophore model for the treatment of ESR1 mutations in breast cancer.

Aim of Study: Increased expression of human epidermal growth factor receptor type 2 (HER2) is significantly associated with poor prognosis in breast cancer patients. However, data on HER2 at transcript levels in Pakistani mammary tumor affected females is still limited. In the current study, HER2 transcripts were explored in breast cancer cohort and correlated with various clinical parameters. Materials and Methods: Freshly excised tumors along with adjacent normal background tissues of 94 patients were collected at the time of surgery and immediately stored in RNAlater ® solution. Clinical data for these samples (disease stage, grade, age, and menopausal status) was also retrieved after a subsequent follow-up. Isolation of RNA and cDNA synthesis was done using an already established protocol. HER2 expression was evaluated using the quantitative real-time polymerase chain reaction (qRT-PCR) technique while β-actin was used as an internal control. Results: In the given cohort, 31 (33%) patients were found positive for HER2. These tumors showed a pronounced increase in HER2 as compared to controls (P = 0.0004). Interestingly, the significant relevance of high HER2 mRNA among moderately differentiated tumor tissues in comparison to controls was also observed (P = 0.02). A significant association of HER2 levels with premenopausal status was also reported. Conclusion: Based on these findings, early screening of HER2 using qRT-PCR should be incorporated for breast cancer patients of Pakistani population diagnosis.