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Smart agricultural systems have received a great deal of interest in recent years because of their potential for improving the efficiency and productivity of farming practices. These systems gather and analyze environmental data such as temperature, soil moisture, humidity, etc., using sensor networks and Internet of Things (IoT) devices. This information can then be utilized to improve crop growth, identify plant illnesses, and minimize water usage. However, dealing with data complexity and dynamism can be difficult when using traditional processing methods. As a solution to this, we offer a novel framework that combines Machine Learning (ML) with a Reinforcement Learning (RL) algorithm to optimize traffic routing inside Software-Defined Networks (SDN) through traffic classifications. ML models such as Logistic Regression (LR), Random Forest (RF), k-nearest Neighbours (KNN), Support Vector Machines (SVM), Naive Bayes (NB), and Decision Trees (DT) are used to categorize data traffic into emergency, normal, and on-demand. The basic version of RL, i.e., the Q-learning (QL) algorithm, is utilized alongside the SDN paradigm to optimize routing based on traffic classes. It is worth mentioning that RF and DT outperform the other ML models in terms of accuracy. Our results illustrate the importance of the suggested technique in optimizing traffic routing in SDN environments. Integrating ML-based data classification with the QL method improves resource allocation, reduces latency, and improves the delivery of emergency traffic. The versatility of SDN facilitates the adaption of routing algorithms depending on real-time changes in network circumstances and traffic characteristics.
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The present study aims to evaluate the prevalence and antimicrobial sensitivity of Staphylococcus aureus associated with bovine mastitis to selected antibiotics and plant extracts. In the current study, 140 milk samples were collected from cows and buffaloes. Among the 140 samples, 93 samples were positive for sub-clinical mastitis based on the California Mastitis Test (CMT). Out of the total positive samples, 45 were confirmed for S. aureus on a Mannitol salt agar media. The antimicrobial susceptibility test revealed that 44.82% of the isolates were resistant to cefoxitin (oxacillin) confirming methicillin-resistant S. aureus (MRSA) with a higher percentage (51.61%) in the buffalo than in the cow samples. Furthermore, the PCR assay confirmed the presence of the mecA gene in all the MRSA isolates. Among the seven tested antibiotics, sulfamethoxazole + trimethoprim showed high efficacy (71.1%) against methicillin-susceptible S. aureus isolates (MSSA). Oxytetracycline and sulfamethoxazole + trimethoprim showed 20% efficacy against MRSA followed by enrofloxacin (10%). On the other hand, the tested samples from Pistacia chinensis revealed that the ethyl acetate extract of bark showed a maximum zone of inhibition of 21.3 mm against MSSA and MRSA isolates at 3 000 µg/disc. Moreover, the methanol extract of Cotoneaster microphyllus formed a 12.3 mm and 9.1 mm zone of inhibition against the MSSA and MRSA isolates, respectively.
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OBJECTIVE: To provide evidence of the effectiveness of a brief relapse prevention intervention using implementation intentions (Self-Management after Therapy, SMArT), following remission from depression and to identify effective relapse prevention strategies. METHOD: The SMArT intervention was provided to 107 patients who were recovered after psychological therapy for depression. Relapse events were calculated as reliable and clinically significant increases in PHQ-scores. Sixteen patients receiving the intervention and eight practitioners providing it were interviewed. Framework Analysis identified seven themes which highlighted effective relapse prevention strategies and effective implementation of the SMArT intervention. RESULTS: Relapse rates at the final SMArT session (four months after the end of acute stage therapy) were 11%. Seven themes were identified that supported effective self-management: (1) Relationship with the practitioner-feeling supported; (2) Support networks; (3) Setting goals, implementing plans and routine; (4) Changing views of recovery; (5) The SMArT sessions-mode, content, timing, duration; (6) Suitability for the person; and (7) Suitability for the service. CONCLUSION: The study provides some support for the effectiveness of the SMArT intervention, although a randomized controlled trial is required; and identifies important relapse prevention strategies.
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Depressão , Intenção , Doença Crônica , Depressão/terapia , Humanos , Recidiva , Prevenção SecundáriaRESUMO
BACKGROUND: Autosomal recessive corneal hereditary endothelial dystrophy (CHED) is a rare congenital disorder of cornea. Mutations in SLC4A11 gene are associated with CHED phenotype. CHED is also an early feature of Harboyan syndrome. The aim of the present study was to identify genetic mutations in the SLC4A11 gene in CHED cases belonging to inbred Pakistani families. Furthermore, all homozygous mutation carriers were investigated for hearing deficit. METHODS AND RESULTS: This study included consanguineous CHED families presented at Al-Shifa Trust Eye Hospital, Rawalpindi, Pakistan from June 2018 to September 2018. DNA was extracted from blood samples. Direct sequencing of SLC4A11 gene was performed. All identified variants were evaluated by in silico programs i.e., SIFT, PolyPhen-2, and MutationTaster. Pathogenicity of the two identified splice site variants was analyzed by Human Splicing Finder and MaxEnt Scan. Screening of five CHED families revealed a total of three previously un reported (p.Arg128Gly, c.2241-2A > T and c.1898-2A > C in family CHED19, CHED22 and CHED26 respectively) and two already reported homozygous disease causing variants (p.Arg869Cys and p.Val824Met in family CHED24 and CHED25 respectively) as predicted by mutation taster. All of these variants segregated with disease phenotype and were not detected in controls. CONCLUSION: Affected individuals of the five CHED families screened in this study had the disease due to SLC4A11 mutations and progressing to Harboyan syndrome. Identification of previously unreported mutations aid to heterogeneity of SLC4A11 and CHED pathogenesis as well as helped to provide genetic counseling to affected families.
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Proteínas de Transporte de Ânions/genética , Antiporters/genética , Distrofias Hereditárias da Córnea/genética , Perda Auditiva Neurossensorial/genética , Mutação de Sentido Incorreto , Adolescente , Substituição de Aminoácidos , Criança , Feminino , Humanos , MasculinoRESUMO
The current study investigates pharmaceutically important bioactive compounds in the fruits of Physalis ixocarpa. Two different extractions methods were used to study its effect on percent extract yield, recovery of bioactive compounds and antioxidant activity of the extracts. The data indicated that Soxhlet extraction had high efficiency of recovery than maceration method for extracting compounds; percent extract yield and antioxidant activity of the extracts. In maceration, the percent extract yield was found to be in order of water >methanol >ethyl acetate whereas in Soxhlet extraction, it was in order of methanol >water >ethyl acetate. Ethyl acetate extract produced by Soxhlet extraction showed strong antioxidant activity of 59.7% (250ppm) as compared to other extracts. Analysis of ethyl acetate extract showed the presence of Triglyceride. GC-MS study of triglyceride revealed the presence of trilinoleinic acid (9,12-Octadecdienoic acid), tripalmitin (hexadecanoic acid) and trioleinic acid (9-Octa decenoic acid). Four impure and three pure compounds were isolated from crude methanol extract of the fruit. The structure of pure compounds were identified by NMR and characterized as sugar, glucose and fructose.
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Antioxidantes/isolamento & purificação , Frutas/química , Physalis/química , Acetatos/química , Antioxidantes/química , Cromatografia Gasosa-Espectrometria de Massas , Hidroquinonas/química , Espectroscopia de Ressonância Magnética , Metanol/química , Estrutura Molecular , Solventes/química , Água/químicaRESUMO
The present study investigates the antimicrobial activities of different solvent extracted samples isolated from different parts of Physalis ixocarpa through disc diffusion assay using three different concentrations. Statistical analysis of the data revealed that different parts of the plant showed varying degree of inhibition against different bacteria at different concentrations. Different solvent extracted samples from the calyx showed inhibitory activity against most of the bacteria under study. Extracts from leaf and fruit samples showed activity against S. aureus and K. pneumoniae and extracts from the stem tissues were effective to control the growth of E. coli and K. pneumoniae. Crude methanolic extract from the stem and n-butanol extracted samples from fruit exhibited strong inhibitory activity against Klebsiella pneumoniae at highest concentrations. Antifungal activity was observed only in crude methanol extract from the leaf against Rhizopus stolinifer, Aspergillus niger and Penicillium chrysogenum.
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Antibacterianos/farmacologia , Bactérias/efeitos dos fármacos , Physalis/química , Extratos Vegetais/farmacologia , Solventes/química , 1-Butanol/química , Antibacterianos/isolamento & purificação , Bactérias/crescimento & desenvolvimento , Testes de Sensibilidade a Antimicrobianos por Disco-Difusão , Relação Dose-Resposta a Droga , Frutas , Metanol/química , Fitoterapia , Extratos Vegetais/isolamento & purificação , Folhas de Planta , Caules de Planta , Plantas MedicinaisRESUMO
OBJECTIVE: To investigate the barriers and facilitators of an effective implementation of an outcome monitoring and feedback system in a UK National Health Service psychological therapy service. METHOD: An outcome monitoring system was introduced in two services. Enhanced feedback was given to therapists after session 4. Qualitative and quantitative methods were used, including questionnaires for therapists and patients. Thematic analysis was carried out on written and verbal feedback from therapists. Analysis of patient outcomes for 202 episodes of therapy was compared with benchmark data of 136 episodes of therapy for which feedback was not given to therapists. RESULTS: Themes influencing the feasibility and acceptability of the feedback system were the extent to which therapists integrated the measures and feedback into the therapy, availability of administrative support, information technology, and complexity of the service. There were low levels of therapist actions resulting from the feedback, including discussing the feedback in supervision and with patients. CONCLUSIONS: The findings support the feasibility and acceptability of setting up a routine system in a complex service, but a number of challenges and barriers have to be overcome and therapist differences are apparent. More research on implementation and effectiveness is needed in diverse clinical settings.
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Retroalimentação , Programas Nacionais de Saúde/estatística & dados numéricos , Avaliação de Resultados em Cuidados de Saúde/métodos , Aceitação pelo Paciente de Cuidados de Saúde/estatística & dados numéricos , Psicoterapia/métodos , Adulto , Estudos de Viabilidade , Feminino , Pesquisa sobre Serviços de Saúde/estatística & dados numéricos , Humanos , Masculino , Pessoa de Meia-Idade , Reino UnidoRESUMO
PURPOSE: Despite the different etiology of primary open angle glaucoma (POAG), primary angle closure glaucoma (PACG), and pseudoexfoliative glaucoma (PEXG), several studies have suggested that these forms of glaucoma have overlapping genetic risk factors. Therefore, the aim of this study was to evaluate the role of genetic variants recently associated with POAG in different types of glaucoma in Pakistani POAG, PACG, and PEXG patient cohorts. METHODS: Six variants in CDKN2B-AS1 (rs4977756), CDKN2B (rs1063192), ATOH7 (rs1900004), CAV1 (rs4236601), TMCO1 (rs4656461), and SIX1 (rs10483727) were genotyped using TaqMan assays. A total of 513 unrelated patients with glaucoma (268 with POAG, 125 with PACG, and 120 with PEXG) and 233 healthy controls were included in the study. Genotypic and allelic associations were analyzed with a chi-square test. RESULTS: The frequency of the G allele of TMCO1 rs4656461 was significantly lower in the patients with POAG (p=0.003; OR [odds ratio]=0.57), PACG (p=0.009; OR=0.52), and PEXG (p=0.01; OR=0.54) compared to the control individuals. The T allele of ATOH7 rs1900004 was observed less frequently in the patients with PACG (p=0.03; OR=0.69) compared to the control individuals. The A allele of CAV1 rs4236601 was found more frequently in the patients with POAG (p=0.008; OR=1.49) compared to the control individuals. This study demonstrates that the TMCO1 rs4656461 variant is associated with POAG, PACG and PEXG in the Pakistani population. Our study was unable to confirm previous associations reported for variants in CDKN2B-AS1, CDKN2B, and SIX1 with any type of glaucoma. CONCLUSIONS: In conclusion, we found consistent evidence of the significant association of three common variants in TMCO1, ATOH7, and CAV1.
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Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Caveolina 1/genética , Síndrome de Exfoliação/genética , Glaucoma de Ângulo Fechado/genética , Glaucoma de Ângulo Aberto/genética , Proteínas de Membrana/genética , Polimorfismo de Nucleotídeo Único , Alelos , Canais de Cálcio , Estudos de Casos e Controles , Estudos de Coortes , Inibidor de Quinase Dependente de Ciclina p15/genética , Síndrome de Exfoliação/patologia , Feminino , Frequência do Gene , Predisposição Genética para Doença , Glaucoma de Ângulo Fechado/patologia , Glaucoma de Ângulo Aberto/patologia , Proteínas de Homeodomínio/genética , Humanos , Masculino , Pessoa de Meia-Idade , PaquistãoRESUMO
Mycotoxins are unavoidable contaminants of animal and human feed and food respectively. This study was designed to investigate the protective activity of vitamin E (Vit E) in White Leghorn breeder hens and their progeny against aflatoxin B1 (AFB1)-induced damage. The results indicated a significant decrease in egg production and quality in the groups exposed to dietary AFB1. A detectable amount of AFB1 residue appeared in the eggs during the first week of mycotoxin exposure at levels ≥ 2.5 mg kg(-1), which reached its peak (0.403 ± 0.04 ng/g [mean ± standard deviation]) during the second week of the experiment (in the group fed 10 mg kg(-1)). Feeding Vit E + AFB1 resulted in higher AFB1 residues (0.467 ± 0.03) when compared with the hens fed AFB1 alone. The resistance of red blood cells to oxidative damage was decreased, while embryonic mortalities and deformities were increased in the AFB1-fed groups. The protective effect of Vit E on these parameters was noted in the groups fed lower doses of AFB1. After the withdrawal of mycotoxin-contaminated feed, most of the parameters returned towards normal within 2 weeks, except AFB1 residues that were still detectable. From the findings of this study one can conclude that the addition of Vit E in the diet of hens provided only partial protection against AFB1-induced damage.
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Aflatoxina B1/toxicidade , Ração Animal/análise , Galinhas , Dieta/veterinária , Doenças das Aves Domésticas/induzido quimicamente , Vitamina E/farmacologia , Fenômenos Fisiológicos da Nutrição Animal , Animais , Embrião de Galinha/efeitos dos fármacos , Eritrócitos , Feminino , Contaminação de Alimentos , Óvulo/química , Estresse Oxidativo , Doenças das Aves Domésticas/prevenção & controleRESUMO
OBJECTIVE: To determine serum lipids in patients with age related macular degeneration from Pakistani population. METHODS: The study was a cross sectional, randomized and case-control. Selected subjects ages were > or = 50 years and were normotensive, non-diabetic with no family history of any such disease and no complication of posterior ocular chamber other than age related macular degeneration (AMD). Controls were age matched healthy individuals with no symptoms of AMD. Diagnosis of AMD was done through conventional diagnostic techniques by professional ophthalmologists. Serum samples were analyzed for total cholesterol, triglycerides, LDL and HDL using commercially available kits. Data were compared with Student's t-test. Pearson correlation was calculated for relationship between different parameters. P < 0.05 was considered significant. RESULTS: Compared to controls, AMD patients had significantly greater total cholesterol concentration (p < 0.041), and power HDL/LDL ratio (p < 0.038), while serum triglycerides, HDL and LDL were non-significantly different from control subjects. Total cholesterol in AMD patients was significantly correlated with TG, LDL and HDL (p < 0.0001). CONCLUSION: The study indicates that high cholesterol might be a predictor of AMD and can be a diagnostic parameter.
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Lipídeos/sangue , Degeneração Macular/sangue , Idoso , Estudos de Casos e Controles , Estudos Transversais , Feminino , Humanos , Degeneração Macular/diagnóstico , Degeneração Macular/epidemiologia , Masculino , Pessoa de Meia-Idade , Paquistão/epidemiologiaRESUMO
The anatomical traits of plant species are essential for taxonomic analyses and evolutionary evaluations. Clarifying the anatomical characteristics of the foliar epidermis in three distinct Lilium species L. pumilum Delile, L. brownii F.E.Br. ex Miellez and L. davidii Duch. ex Elwes were studied in this article. The objective is to assess the taxonomic relevance of these characteristics and their potential as indicators of species divergence within the genus Lilium. Plant samples were gathered in Gansu, China, from numerous populations of each species that represented a range of climatic and ecological factors. A microscopic analysis employing thin slices and peel mounts was done to assess the stomatal density and dimensions. Significant interpopulation differences in stomatal features were found in the results, offering potential opportunities for taxonomic discrimination. The species differ in qualitative and quantitative characters to differentiate the three species. The links between the observed anatomical characteristics and species classification within the Lilium genus were clarified for the three studied species. In the end, this research advances knowledge of Lilium taxonomy, aids in conservation efforts, and deepens awareness of the general patterns of plant variety. RESEARCH HIGHLIGHTS: Epidermal Traits Aid Taxonomy: Cell shape, arrangement, and structures aid Lilium Identification. Cuticle Reveals Taxonomic Clues: Thickness, composition, and structure inform classification. Micromorphology for Species ID: Cell shape, wax, and striations differentiate Lilium species.
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Lilium , Epiderme Vegetal , Epiderme Vegetal/ultraestrutura , Epiderme , Células Epidérmicas , FenótipoRESUMO
To satisfy the electricity needs of a village in Tangi, northwest Pakistan, the present research can design and evaluate the environmental and economical aspects of an optimal hybrid photovoltaic-biogas-hydropower-battery energy sustainable system (PV-BG-HP-BESS). This framework integrates various renewable energy sources, delivering a modern, efficient approach to sustainable energy solutions. The HOMER Pro software is utilized to optimize the most economical and effective hybrid energy system. The results showed that the proposed hybrid system comprising 91.4 kWp PV modules, 19.6 kW hydropower, a 50 kW biogas generator (BG), 36 batteries, and a 60.6 kW converter was the most economical choice. This system, which used the cyclic charging (CC) method, had a cost of energy (COE) of 0.0728 $/kWh and a total net present cost (NPC) of $152,242. The suggested hybrid energy system for rural areas of Pakistan includes photovoltaic (PV), biogas (BG), hydro, and battery components to provide a dependable and sustainable power supply. This system minimizes the need for expensive fossil fuels while simultaneously minimizing environmental impact by lowering pollutants and greenhouse gas emissions. The system's annual electricity production is 294,782 kWh, with PV leads at 59.4%, BG at 6.02%, and hydro at 34.6%, ensuring uninterrupted power generation even in remote areas. The unmet load, extra electricity, and capacity shortage illustrate the reliability of the system and make it possible to address rural electrification challenges while supporting sustainable development and economic growth. Moreover, the outcomes of the proposed hybrid system dominate the previous studies in multiple objectives, including cost and sensitivity analysis, when compared.
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Influenza viruses are the most common cause of serious respiratory illnesses worldwide and are responsible for a significant number of annual fatalities. Therefore, it is crucial to look for new immunogenic sites that might trigger an effective immune response. In the present study, bioinformatics tools were used to design mRNA and multiepitope-based vaccines against H5N1 and H7N9 subtypes of avian influenza viruses. Several Immunoinformatic tools were employed to extrapolate T and B lymphocyte epitopes of HA and NA proteins of both subtypes. The molecular docking approach was used to dock the selected HTL and CTL epitopes with the corresponding MHC molecules. Eight (8) CTL, four (4) HTL, and Six (6) linear B cell epitopes were chosen for the structural arrangement of mRNA and of peptide-based prophylactic vaccine designs. Different physicochemical characteristics of the selected epitopes fitted with suitable linkers were analyzed. High antigenic, non-toxic, and non-allergenic features of the designed vaccines were noted at a neutral physiological pH. Codon optimization tool was used to check the GC content and CAI value of constructed MEVC-Flu vaccine, which were recorded to be 50.42% and 0.97 respectively. the GC content and CAI value verify the stable expression of vaccine in pET28a + vector. In-silico immunological simulation the MEVC-Flu vaccine construct revealed a high level of immune responses. The molecular dynamics simulation and docking results confirmed the stable interaction of TLR-8 and MEVC-Flu vaccine. Based on these parameters, vaccine constructs can be regarded as an optimistic choice against H5N1 and H7N9 strains of the influenza virus. Further experimental testing of these prophylactic vaccine designs against pathogenic avian influenza strains may clarify their safety and efficacy.Communicated by Ramaswamy H. Sarma.
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Virus da Influenza A Subtipo H5N1 , Subtipo H7N9 do Vírus da Influenza A , Vacinas contra Influenza , Influenza Aviária , Animais , Influenza Aviária/prevenção & controle , Subtipo H7N9 do Vírus da Influenza A/genética , Simulação de Acoplamento Molecular , RNA Mensageiro/genética , Imunoinformática , Epitopos de Linfócito B , Vacinas de Subunidades Antigênicas , Epitopos de Linfócito T , Biologia ComputacionalRESUMO
There is high demand for specialist mental health services for children and young people in the UK. Non-mental health nurses are well-placed to assess the mental health needs and risks of children and young people to maximise opportunities for early intervention and relieve the pressure on child and adolescent mental health services. This article provides an overview of a service development project to develop a web-based application (app) to support non-mental health nurses when assessing the mental health needs and risks of children and young people. The article describes the development, testing and evaluation process, which involved consultation with children and young people as well as interviews, focus groups and an online survey with a range of professionals working with children and young people. Overall, the findings suggest that the app is appropriate for use by non-mental health nurses in terms of quality, functionality and acceptability.
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No abstract available.
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PURPOSE: Matrix metalloproteinases (MMPs) play an important role in remodeling of the extracellular matrix during development and growth of various tissues including the eye. Various functional polymorphisms in MMPs have been implicated in the pathogenesis of different types of glaucoma. The aim of the present study was to investigate the role of various polymorphisms in Pakistani patients with glaucoma. METHODS: The present case-control study included 112 patients with primary open-angle glaucoma (POAG), 82 patients with primary angle closure glaucoma (PACG), and 118 control subjects. Genotyping of polymorphisms was done using PCR followed by restriction fragment length polymorphism analysis. RESULTS: A significant difference in the genotype frequencies of MMP1 rs1799750 (-1607 1G/2G) was observed between the patients with POAG and the control subjects (p = 0.001). This was attributed to the female subjects (p < 0.001), while the association was not significant in male subjects (p > 0.47). In addition, a significant difference was observed in genotype frequencies of MMP9 rs17576 (c.836A>G) in patients with PACG compared to the control subjects (p < 0.001), which after gender stratification remained significant in men (p = 0.009) but not in women (p = 0.14). No significant associations were found for MMP7 (c.-181T>C) and MMP9 (c.-1562C>T) polymorphisms. CONCLUSIONS: Our data suggest that the MMP1 rs1799750 (-1607 1G/2G) and MMP9 rs17576 polymorphisms might be of value for further study as potential gender-dependent risk factors for developing POAG and PACG, respectively, in Pakistan.
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Glaucoma de Ângulo Fechado/enzimologia , Glaucoma de Ângulo Fechado/genética , Glaucoma de Ângulo Aberto/enzimologia , Glaucoma de Ângulo Aberto/genética , Metaloproteinase 1 da Matriz/genética , Metaloproteinase 9 da Matriz/genética , Polimorfismo Genético , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Paquistão , Fatores de RiscoRESUMO
According to a plethora of research and publications, the volume and amount of pollution are largely attributable to human-made emissions. Even during the recently ended Covid-19 outbreak, there was a notable decrease in global pollution, particularly in Pakistan's heavily populated cities. Due to the current situation, it is strategically important to safeguard the environment, and there are many criteria and predictors that should be used to encourage green behavior. This study examines green banking as a means of demonstrating ecologically responsible conduct in a developing nation. A survey questionnaire was used to collect information from 280 respondents via human contact and an internet platform. Software called SmartPLS3.0 was used to analyze the structural relationships between the study's variables. The results show that customers' adoption of green banking practices is statistically significantly influenced by their level of environmental consciousness and attitude. Similarly, green culture exhibits a substantial mediating influence between the independent variables and green behavior as well as a positive significant effect on green behavior. However, it is established that the consumer's apparent behavioral control is negligible. Particularly, the cognitive connection between behavior and culture is weak and insufficient to forecast behavior. For policymakers, especially those working in the field of green education, this study has many real-world applications.
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The SARS COV-2 and its variants are spreading around the world at an alarming speed, due to its higher transmissibility and the conformational changes caused by mutations. The resulting COVID-19 pandemic has imposed severe health consequences on human health. Several countries of the world including Pakistan have studied its genome extensively and provided productive findings. In the current study, the mCSM, DynaMut2, and I-Mutant servers were used to analyze the effect of identified mutations on the structural stability of spike protein however, the molecular docking and simulations approaches were used to evaluate the dynamics of the bonding network between the wild-type and mutant spike proteins with furin. We addressed the mutational modifications that have occurred in the spike protein of SARS-COV-2 that were found in 215 Pakistani's isolates of COVID-19 patients to study the influence of mutations on the stability of the protein and its interaction with the host cell. We found 7 single amino acid substitute mutations in various domains that reside in spike protein. The H49Y, N74K, G181V, and G446V were found in the S1 domain while the D614A, V622F, and Q677H mutations were found in the central helices of the spike protein. Based on the observation, G181V, G446V, D614A, and V622F mutants were found highly destabilizing and responsible for structural perturbation. Protein-protein docking and molecular simulation analysis with that of furin have predicted that all the mutants enhanced the binding efficiency however, the V622F mutant has greatly altered the binding capacity which is further verified by the KD value (7.1 E-14) and therefore may enhance the spike protein cleavage by Furin and increase the rate of infectivity by SARS-CoV-2. On the other hand, the total binding energy for each complex was calculated which revealed -50.57 kcal/mol for the wild type, for G181V -52.69 kcal/mol, for G446V -56.44 kcal/mol, for D614A -59.78 kcal/mol while for V622F the TBE was calculated to be -85.84 kcal/mol. Overall, the current finding shows that these mutations have increased the binding of Furin for spike protein and shows that D614A and V622F have significant effects on the binding and infectivity.
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Background Vernal keratoconjunctivitis (VKC) is an allergic conjunctival inflammation with severe ocular complications if left untreated. The current management regimen is plagued with adverse effects, long-term problems, and clinical relapses. Tacrolimus offers an alternative treatment option, and long-term studies are needed to determine its efficacy. Methods A two-year follow-up based study was conducted on moderate to severe VKC patients, who were prescribed tacrolimus skin ointment. The 5-5-5 exacerbation scale was used for the monitoring and grading severity of the disease. Analysis of variance (ANOVA) and intergroup comparisons were conducted on exacerbation scale scores among follow-ups. Results A significant reduction was observed in the total score of severity from baseline (203.17±102.05) to three months' follow-up (69.94±70.54), and it kept reducing for 18 months post therapy. Similar results with statistically significant reduction were observed for all grades of the scale. The relapse rate was 5.71% within a month after therapy cessation, and none of the other patients showed relapse afterward. No significant ocular and systemic complications were observed during the study. Conclusion Tacrolimus is effective in the long-term management of VKC without the complications of conventional steroid-based therapy.
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Brucellosis is a major threat to public health especially in developing countries including Pakistan. This study reveals the characterisation of Brucella species affecting humans and goats in the Swat region of Khyber Pakhtunkhwa, Pakistan. Blood samples were collected from shepherds and goats and analysed by Rose Bengal precipitation test (RBPT), standard plate agglutination test (SPAT), polymerase chain reaction (PCR) and Sanger sequencing of 16S rRNA gene. The findings of the study indicated 24% (36/150) and 11.3% (17/150) positivity for Brucella abortus and Brucella melitensis, respectively, in human samples. In samples of goats, 26.66% (40/150) were positive for B. abortus and 16.66% (25/150) samples were positive B. melitensis by SPAT. The species-specific PCR confirmed B. abortus in 24% (36/150) of human samples and 26.66% (17/150) of goat samples by targeting the IS711 locus. The remaining seropositive samples were confirmed as B. melitensis using IS711 M species-specific primer. The sequences of the amplified fragments of the 16S rRNA gene were blasted, and phylogenetic analysis revealed that Brucella species circulating in the Swat district were closely related to B. melitensis and B. abortus reported from India, China, Philippines, and the United States (US) showing the existence of the possible epidemiological linkage among the Brucella species. This study concluded that there was a higher prevalence of B. abortus (26.6%) in humans and goats compared to B. melitensis (16.6%). These results revealed that the Brucella species were circulating in both humans and goats in the study areas. The findings of the study concluded that B. abortus and B. melitensis were circulating in goats and shepherds with a higher prevalence of B. abortus than B. melitensis. Furthermore, the Brucella species identified in Swat were phylogenetically related to the Brucella species reported from India, China, Philippines and the US.Contribution: The proposed study covers the scope of the journal. The species of the genus Brucella affect both animals and shepherds. This study investigates the seroprevalence of brucellosis in shepherds and goats in different geographical areas in the Swat district. The phylogenetic analysis of the Brucella spp. identified in Swat showed close relationships to the Brucella species reported in India, China, Philippines and the US, which shows the possible epidemiological linkages between the Brucella spp.