Early Aggregation Mechanism of SOD128-38 Based on Force Field Parameter of 5-Cyano-Tryptophan.

The aggregation of superoxide dismutase 1 (SOD1) results in amyloid deposition and is involved in familial amyotrophic lateral sclerosis, a fatal motor neuron disease. There have been extensive studies of its aggregation mechanism. Noncanonical amino acid 5-cyano-tryptophan (5-CN-Trp), which has been incorporated into the amyloid segments of SOD1 as infrared probes to increase the structural sensitivity of IR spectroscopy, is found to accelerate the overall aggregation rate and potentially modulate the aggregation process. Despite these observations, the underlying mechanism remains elusive. Here, we optimized the force field parameters of 5-CN-Trp and then used molecular dynamics simulation along with the Markov state model on the SOD128-38 dimer to explore the kinetics of key intermediates in the presence and absence of 5-CN-Trp. Our findings indicate a significantly increased probability of protein aggregate formation in 5CN-Trp-modified ensembles compared to wildtype. Dimeric ß-sheets of different natures were observed exclusively in the 5CN-Trp-modified peptides, contrasting with wildtype simulations. Free-energy calculations and detailed analyses of the dimer structure revealed augmented interstrand interactions attributed to 5-CN-Trp, which contributed more to peptide affinity than any other residues. These results explored the key events critical for the early nucleation of amyloid-prone proteins and also shed light on the practice of using noncanonical derivatives to study the aggregation mechanism.

Moderating role of academic motivation and entitlement between motives of students and academic achievement among university students.

Objectives: The study examined the moderating role of academic motivation and academic entitlements between students' motives for communication with their instructors and their academic achievements. METHODS: The descriptive cross-sectional study was conducted at the universities situated in Okara and Sargodha, Pakistan, from November 1, 2017 to November 9, 2018. Data were collected using the Students' Motives for Communicating with their Instructors Scale, Academic Motivation Scale and the Academic Entitlement Scale. Data were analysed using SPSS-23. RESULTS: There were 264 students. Academic motivation moderated the relationship between participation motive and academic achievement as well as the relationship between functional motive and academic achievement (p<0.05). Academic entitlement moderated the relationship between relational motive and academic achievement (p<0.05). CONCLUSIONS: High and moderate level of academic motivation enhanced the effect of students' relational and functional motive for communicating on academic achievement whereas low level of motivation reduced it. High, moderate and low level of academic entitlement enhanced the effect of relational motive on academic achievement. High level of academic entitlement reduced the effect of functional motive on academic achievement. High level of academic entitlement reduced the effect of functional motive on academic achievement whereas moderate and low level of academic entitlement reduced its effect.

Towards sustainable agriculture: rhizosphere microbiome engineering.

Soil microbiomes are extremely complex, with dense networks of interconnected microbial species underpinning vital functions for the ecosystem. In advanced agricultural research, rhizosphere microbiome engineering is gaining much attention, as the microbial community has been acknowledged to be a crucial partner of associated plants for their health fitness and yield. However, single or combined effects of a wide range of soil biotic and abiotic factors impact the success of engineered microbiomes, as these microbial communities exhibit uneven structural and functional networks in diverse soil conditions. Therefore, once a deep understanding of major influential factors and corresponding microbial responses is developed, the microbiome can be more effectively manipulated and optimized for cropping benefits. In this mini-review, we propose the concept of a microbiome-mediated smart agriculture system (MiMSAS). We summarize some of the advanced strategies for engineering the rhizosphere microbiome to withstand the stresses imposed by dominant abiotic and biotic factors. This work will help the scientific community gain more clarity about engineered microbiome technologies for increasing crop productivity and environmental sustainability.Key points• Individual or combined effects of soil biotic and abiotic variables hamper the implementation of engineered microbiome technologies in the field.• As a traditional approach, reduced-tillage practices coinciding with biofertilization can promote a relatively stable functional microbiome.• Increasing the complexity and efficiency of the synthetic microbiome is one way to improve its field-application success rate.• Plant genome editing/engineering is a promising approach for recruiting desired microbiomes for agricultural benefit.

The broad-spectrum antiviral recommendations for drug discovery against COVID-19.

Despite to outbreaks of highly pathogenic beta and alpha coronaviruses including severe acute respiratory syndrome coronavirus (SARS-CoV), Middle East respiratory syndrome coronavirus (MERS-CoV), and human coronavirus, the newly emerged 2019 coronavirus (COVID-19) is considered as a lethal zoonotic virus due to its deadly respiratory syndrome and high mortality rate among the human. Globally, more than 3,517,345 cases have been confirmed with 243,401 deaths due to Acute Respiratory Distress Syndrome (ARDS) caused by COVID-19. The antiviral drug discovery activity is required to control the persistence of COVID-19 circulation and the potential of the future emergence of coronavirus. However, the present review aims to highlight the important antiviral approaches, including interferons, ribavirin, mycophenolic acids, ritonavir, lopinavir, inhibitors, and monoclonal antibodies (mAbs) to provoke the nonstructural proteins and deactivate the structural and essential host elements of the virus to control and treat the infection of COVID-19 by inhibiting the viral entry, viral RNA replication and suppressing the viral protein expression. Moreover, the present review investigates the epidemiology, diagnosis, structure, and replication of COVID-19 for better understanding. It is recommended that these proteases, inhibitors, and antibodies could be a good therapeutic option in drug discovery to control the newly emerged coronavirus.HighlightsCOVID-19 has more than 79.5% identical sequence to SARS-CoV and a 96% identical sequence of the whole genome of bat coronaviruses.Acute respiratory distress syndrome (ARDS), renal failure, and septic shock are the possible clinical symptoms associated with COVID-19.Different antivirals, including interferons, ribavirin, lopinavir, and monoclonal antibodies (mAbs) could be the potent therapeutic agents against COVID-19.The initial clinical trials on hydroquinone in combination with azithromycin showed an admirable result in the reduction of COVID-19.The overexpression of inflammation response, cytokine dysregulation, and induction of apoptosis could be an well-organized factors to reduce the pathogenicity of COVID-19.

Multicentric Reticulohistiocytosis (Mrh): A Case Report On A Rare Destructive Arthritis.

Multicentric Reticulohistiocytosis is a rare disorder of unknown aetiology which affects skin and joints predominantly. There are no specific laboratory investigations for diagnosis. Diagnosis can be made clinically and on a histopathological basis. There is no consensus on treatment. We report a case from Pakistan with classical presentation who did well on methotrexate and low dose steroids. Prompt diagnosis and early treatment may save from significant disability.

Thermodynamic Insights into the Oxidation Mechanisms of CrMnFeCoNi High-Entropy Alloy Using In Situ X-ray Diffraction.

This paper utilizes in situ X-ray diffraction (XRD) to investigate the high-temperature oxidation behaviour of CrMnFeCoNi high-entropy alloy (HEA). We found that (1) Mn is the major oxide-forming element in both vacuum and air environments, leading to the formation of non-protective oxides that deplete the bulk alloy of Mn; (2) no oxides like Cr2O3, Fe2O3, or Fe3O4 were observed during the high-temperature oxidation behaviour of CrMnFeCoNi, which contradicts some previous studies on the isothermal oxidation of CrMnFeCoNi HEA. We also analysed and compared the experimental results with thermodynamic calculations by using ThermoCalc version 2022b software following the CALPHAD method. ThermoCalc predicted spinel oxide in a vacuum environment, along with halite oxides observed in experimental results; also, in an atmospheric environment, it predicted only spinel, indicating the need for further investigation into factors to validate the thermodynamic predictions. Our study shows that the in situ HTXRD technique is a powerful tool to accurately identify time-temperature-dependent phase formation/transformation for studying oxidation behaviours and understanding oxidation mechanisms in HEAs.

Improved remediation of amoxicillin-contaminated water by floating treatment wetlands intensified with biochar, nutrients, aeration, and antibiotic-degrading bacteria.

Residual antibiotics have become emerging contaminants of concern for their adverse impact on the ecosystem. Additionally, their accumulation in the environment is increasing antibiotic resistance among pathogens. This study assessed the impact of intensification of biochar, nutrients, aeration, and bacteria (BNAB) on the remediation potential of floating treatment wetlands (FTWs) to treat amoxicillin (AMX)-contaminated water. The FTWs were developed with saplings of Vetiveria zizanioides and intensified with biochar (1.5%), nutrients (25 mgL-1 N, 25 mgL-1 P, 20 mg L1 K), aeration (7 mg L-1), and AMX-degrading bacteria. The results showed that all the amendments enhanced the AMX degradation, while the maximum reduction in COD (89%), BOD (88%), TOC (87%), and AMX (97%) was shown by the combined application of all the amendments. The combined application also enhanced plant growth and persistence of the inoculated bacteria in the water, roots, and shoots. This approach can be employed for the low-cost, environment-friendly treatment, and recycling of antibiotic-contaminated wastewater, where BNAB intensification can further improve the bioremediation efficiency of FTWs in the case of heavily polluted waters.

Vetiver grass floating treatment wetlands (FTWs) removed 83% amoxicillin.Intensification of floating treatment wetlands enhanced amoxicillin removal to 97%.Intensified-FTW removed COD, BOD, and TOC by 89%, 88%, and 87%, respectively.Potential of Intensified-FTW for bioremediation of highly polluted water is shown.

Pharmacotherapeutic Potential of Natural Products to Target the SARS-CoV-2 PLpro Using Molecular Screening and Simulation Approaches.

Because of the essential role of PLpro in the regulation of replication and dysregulation of the host immune sensing, it is considered a therapeutic target for novel drug development. To reduce the risk of immune evasion and vaccine effectiveness, small molecular therapeutics are the best complementary approach. Hence, we used a structure-based drug-designing approach to identify potential small molecular inhibitors for PLpro of SARS-CoV-2. Initial scoring and re-scoring of the best hits revealed that three compounds NPC320891 (2,2-Dihydroxyindene-1,3-Dione), NPC474594 (Isonarciclasine), and NPC474595 (7-Deoxyisonarciclasine) exhibit higher docking scores than the control GRL0617. Investigation of the binding modes revealed that alongside the essential contacts, i.e., Asp164, Glu167, Tyr264, and Gln269, these molecules also target Lys157 and Tyr268 residues in the active site. Moreover, molecular simulation demonstrated that the reported top hits also possess stable dynamics and structural packing. Furthermore, the residues' flexibility revealed that all the complexes demonstrated higher flexibility in the regions 120-140, 160-180, and 205-215. The 120-140 and 160-180 lie in the finger region of PLpro, which may open/close during the simulation to cover the active site and push the ligand inside. In addition, the total binding free energy was reported to be - 32.65 ± 0.17 kcal/mol for the GRL0617-PLpro, for the NPC320891-PLpro complex, the TBE was - 35.58 ± 0.14 kcal/mol, for the NPC474594-PLpro, the TBE was - 43.72 ± 0.22 kcal/mol, while for NPC474595-PLpro complex, the TBE was calculated to be - 41.61 ± 0.20 kcal/mol, respectively. Clustering of the protein's motion and FEL further revealed that in NPC474594 and NPC474595 complexes, the drug was seen to have moved inside the binding cavity along with the loop in the palm region harboring the catalytic triad, thus justifying the higher binding of these two molecules particularly. In conclusion, the overall results reflect favorable binding of the identified hits strongly than the control drug, thus demanding in vitro and in vivo validation for clinical purposes.

Insulin Resistance and Coronary Artery Disease: Untangling the Web of Endocrine-Cardiac Connections.

The relationship between insulin resistance and coronary artery disease (CAD) is a crucial study area in understanding the complex connection between metabolic dysregulation and cardiovascular morbidity. This scholarly investigation examines the intricate relationship between insulin resistance, a key characteristic of metabolic syndrome, and CAD development. The goal is to understand the detailed molecular and physiological connections that underlie the dangerous connection between the endocrine and cardiac systems. The recognition of insulin resistance as a key player in cardiovascular disease highlights the need to study the complex relationships between insulin signaling pathways and the development of atherosclerosis. This research analyzes the molecular processes by which insulin resistance leads to disruptions in lipid metabolism, inflammatory reactions, and malfunction of the blood vessel's inner lining. These processes create an environment that promotes the development and advancement of CAD. As we begin this scientific exploration, it becomes clear that insulin resistance acts as a metabolic indicator and a potent mediator of endothelial dysfunction, oxidative stress, and systemic inflammation. The complex interaction between insulin-sensitive tissues and the vascular endothelium plays a crucial role in defining the pathophysiological landscape of CAD. Furthermore, this discussion highlights the mutual interaction between the endocrine and cardiac systems, where CAD produced by myocardial ischemia worsens insulin resistance through complex molecular pathways. Discovering new therapeutic targets that disrupt the harmful cycle between insulin resistance and the development of CAD shows potential for creating specific therapies to reduce cardiovascular risk in people with insulin resistance. This study aims to clarify the complexities of the connection between the endocrine system and the heart, establishing the basis for a thorough comprehension of how insulin resistance contributes to the development and advancement of CAD.

Challenges and Opportunities in Developing Tailored Pain Management Strategies for Liver Patients.

Chronic liver illnesses pose a substantial worldwide health challenge, with various causes that span from viral infections to metabolic problems. Individuals suffering from liver problems frequently face distinct difficulties in pain control, requiring a customized strategy that takes into account both the fundamental disease and the complexities of liver function. The liver, a vital organ responsible for metabolic control and detoxification, is pivotal in multiple physiological processes. Chronic liver illnesses, such as cirrhosis and non-alcoholic fatty liver disease (NAFLD), are marked by a gradual process of inflammation and fibrosis, resulting in reduced liver function. These disorders often come with pain, varying from internal discomfort to intense abdominal pain, which impacts the quality of life and general well-being of patients. The review explores the complex aspects of pain perception in liver illnesses, including inflammation, modified neuronal signaling, and the influence of comorbidities. It highlights the significance of a detailed comprehension of the pain experience in individuals with hepatic conditions for the implementation of successful pain management treatments. In addition, the review emphasizes the difficulties involved in treating pain in this group of patients, such as the possible complications linked to commonly prescribed pain relievers and the necessity for collaboration between hepatologists, pain specialists, and other healthcare professionals. Moreover, it examines new possibilities in the domain, such as the significance of innovative pharmacological substances, non-pharmacological treatments, and personalized medicine strategies designed for specific patient characteristics. This study thoroughly analyzes the difficulties and possibilities involved in creating personalized pain management approaches for individuals with liver conditions. Its purpose is to guide physicians, researchers, and healthcare providers, enabling them to implement more efficient and patient-focused interventions. As our comprehension of liver-related pain progresses, the potential for enhancing the quality of life for persons with chronic liver disorders through tailored pain management measures becomes more and more encouraging.

Role of 19 SNPs in 10 genes with type 2 diabetes in the Pakistani population.

Meta-GWAS report numerous variants associated with type 2 diabetes (T2D), however, for diabetic retinopathy (DR) no loci achieved genome-wide significance. There are limited candidate gene analyses for T2D and/or DR reported from the Pakistani population. Therefore, the current study was designed to evaluate the genetic association of 10 loci with T2D, non-proliferative DR (NPDR), and proliferative DR (PDR). In total 375 T2D cases and 205 controls were collected. The T2D cases included diabetic no retinopathy (n = 196), NPDR (n = 95), and PDR (n = 84). Genomic DNA was isolated, and 19 SNPs were genotyped. To determine association of SNPs with T2D, logistic regression analyses were performed adjusting for age and sex. Moreover, for association of SNPs with NPDR and PDR logistic regression analyses adjusting for diabetes duration and age of T2D onset were performed. In multivariate analysis, the minor alleles of rs1043618 [G > C, odds ratio (OR) 95% confidence interval (CI) = 1.45 (1.13-1.87), p = 4.00E-3], rs3807987 [G > A, 1.87 (1.22-2.94), p = 0.01], rs12672038 [G > A, 1.53 (1.04-2.30), p = 0.03] and rs2055858 [G > C, 1.70 (1.20-2.43), p = 3.00E-3] were associated with higher risk while rs1801133 (C > T, 0.59 (0.42-0.83), p = 2.28E-3) was associated with a lower risk of T2D. Moreover, minor alleles of rs2055858 [G > C, 1.77 (1.17-2.68), p = 0.02], and rs3759890 [C > G, 2.17 (1.39-3.39), p = 4.00E-3] showed an association with PDR when compared with DNR. However, only the association of rs1801133 survived multiple test correction. Hence, we report that rs1801133 is associated with T2D in the Pakistani population. In addition, out of studied 10 genes 8 proteins had higher interactions among themselves that are predicted to be partially biologically connected, as a group.

17α-Acet-oxy-11ß-hy-droxy-6α-methyl-pregn-4-ene-3,20-dione.

The title compound, C(24)H(34)O(5), a fungal-transformed metabolite of the injecta-ble contraceptive medroxyprogesterone acetate, consists of four fused rings (A, B, C and D; steroid labelling). Ring A exists in a half-chair conformation while trans-fused rings B and C adopt chair conformations. The five-membered ring D adopts an envelope conformation with the C atom bound to the methyl group at the flap. In the crystal, adjacent mol-ecules are linked by O-H⋯O and C-H⋯O hydrogen bonds, forming infinite chains along the a axis.

Anti-leishmanial physalins-Phytochemical investigation, in vitro evaluation against clinical and MIL-resistant L. tropica strains and in silico studies.

Cutaneous leishmaniasis (CL) is a major health problem in over 98 countries of the world, including Pakistan. The current treatments are associated with a number of adverse effects and availability problem of drugs. Therefore, there is an urgent need of easily available and cost effective treatments of CL- in Pakistan. The bioassay-guided fractionation and purification of crude extract of Physalis minima has led to the isolation of a new aminophysalin B (1), and eight known physalins, physalin B (2), 5ß,6ß-epoxyphysalin B (3), 5α-ethoxy-6ß-hydroxy-5,6-dihydrophysalin B (4), physalin H (5), 5ß,6ß-epoxyphysalin C (6), and physalin G (7), K (8), and D (9). It is worth noting that compound 1 is the second member of aminophysalin series, whereas compound 6 was fully characterized for the first time. The structures of compounds 1-9 were elucidated by spectroscopic techniques Whereas, the structural assignments of compounds 1 and 8 were also supported by single-crystal X-ray diffraction studies. The anti-leishmanial activity of isolated physlains 1-9 was evaluated against Leishmania major and Leishmania tropica promastigotes. Compounds 2, 3, and 5-7 (IC50 = 9.59 ± 0.27-23.76 ± 1.10 µM) showed several-fold more potent activity against L. tropca than tested drug miltefosine (IC50 = 42.75 ± 1.03 µm) and pentamidine (IC50 = 27.20 ± 0.01 µM). Whereas compounds 2, 3 and 5 (IC50 = 3.04 ± 1.12-3.76 ± 0.85 µM) were found to be potent anti-leishmanial agents against L. major, several fold more active than tested standard miltefosine (IC50 = 25.55 ± 1.03 µM) and pentamidine (IC50 = 27.20 ± 0.015 µM). Compounds 4 (IC50 = 74.65 ± 0.81 µM) and 7 (IC50 = 39.44 ± 0.65 µM) also showed potent anti-leishmanial ativity against the miltefosine-unresponsive L. tropica strain (MIL resistant) (miltefosine IC50 = 169.55 ± 0.78 µM). Molecular docking and predictive binding studies indicated that these inhibitors may act via targeting important enzymes of various metabolic pathways of the parasites.

Surface enhanced Raman spectroscopy of RNA samples extracted from blood of hepatitis C patients for quantification of viral loads.

BACKGROUND: Raman spectroscopy is a promising technique to analyze the body fluids for the purpose of non-invasive disease diagnosis. OBJECTIVES: To develop a surface-enhanced Raman spectroscopy (SERS) based method for qualitative and quantitative analysis of HCV from blood samples. METHODS: SERS was employed to characterize the Hepatitis C viral RNA extracted from different blood samples of hepatitis C virus (HCV) infected patients with predetermined viral loads in comparison with total RNA of healthy individuals. The SERS measurements were performed on 27 extracted RNA samples including low viral loads, medium viral loads, high viral loads and healthy/negative viral load samples. For this purpose, silver nanoparticles (Ag NPs) were used as SERS substrates. Furthermore, multivariate data analysis technique, Principal Component Analysis (PCA) and Partial Least Square Regression (PLSR) were also performed on SERS spectral data. RESULTS: The SERS spectral features due to biochemical changes in the extracted RNA samples associated with the increasing viral loads were established which could be employed for HCV diagnostic purpose. PCA was found helpful for the differentiation between Raman spectral data of RNA extracted from hepatitis infected and healthy blood samples. PLSR model is established for the determination of viral loads in HCV positive RNA samples with 99 % accuracy. CONCLUSION: SERS can be employed for qualitative and quantitative analysis of HCV from blood samples.

Surface-enhanced Raman spectral analysis for comparison of PCR products of hepatitis B and hepatitis C.

BACKGROUND: Surface-enhanced Raman spectroscopy is a reliable tool for identification and differentiation of two diseases showing similar symptoms, hepatitis B (HBV) and hepatitis C (HCV). OBJECTIVES: To develop a polymerase chain reaction technique (PCR) based SERS technique for differentiation of two human pathological conditions sharing the same symptoms using multivariate data analysis techniques e.g. principle component analysis (PCA) and partial least square discriminate analysis (PLS-DA). METHODS: PCR products of HBV and HCV were differentiated by SERS using silver nanoparticles (AgNPs) as a SERS substrate. For this analysis, PCR products of both the diseases with predetermined viral loads were collected and analyzed under SERS instrument and unique SERS spectra of HBV and HCV was compared showing many differences at various points. Diseased classes of HBV and HCV and their negative control classes (viral load less than 1) were compared. PCR products of true healthy DNA and RNA were also compared, which were significantly separated. Moreover, SERS data was analyzed using multivariate data analysis techniques including principle component analysis (PCA) and partial least square discriminate analysis (PLS-DA) and differences were so prominent to observe. RESULTS: SERS spectral data of HBV and HCV showed clear differences and were significantly separated using PCA. Negative control samples of both disorders and their true healthy samples of DNA and RNA were separated according to 1st principle component. By analyzing data using partial least square discriminate analysis, differentiation of two disease classes was considered more valid with sensitivity, specificity and accuracy value of 96%, 94% and 98% respectively. Value of area under curve (AUROC) was 0.7527. CONCLUSION: SERS can be employed for identification and comparison of two human pathological conditions sharing the same symptomology.

Microbial transformation of oral contraceptive ethisterone by Aspergillus niger and Cunninghamella blakesleeana.

Ethisterone (17α-ethynyl-17ß-hydroxyandrost-4-en-3-one) (1) is a synthetic steroidal estrogen. It is extensively used as an oral contraceptive. The current study involves the structural transformation of ethisterone (1) by Aspergillus niger, and Cunninghamella blakesleeana. Fermentation of 1 with C. blakesleeana afforded two new polar metabolites, 17α-ethynyl-6ß,15ß,17ß-trihydroxyandrost-4-en-3-one, and 17α-ethynyl-7ß,15ß,17ß-trihydroxyandrost-4-en-3-one, while transformation of ethisterone with A. niger yielded a new metabolite, 17α-ethynyl-6α,17ß-dihydroxyandrost-4-en-3-one, along with a known metabolite, 17α-ethynyl-11α,17ß-dihydroxyandrost-4-en-3-one. Modern spectroscopic techniques were used to characterize the structures of all transformed products.

Prevalence of Depression in Patients with Juvenile Idiopathic Arthritis Presenting at a Tertiary Care Hospital.

Background and objective Juvenile idiopathic arthritis (JIA) is an idiopathic autoimmune rheumatic disorder in children. JIA has been associated with depression and has a negative psychological impact on patients' quality of life. The aim of the study is to determine the prevalence of depression in patients with JIA presenting at a tertiary care hospital in Islamabad, Pakistan. Materials and methods This cross-sectional study, conducted at the Department of Rheumatology, Pakistan Institute of Medical Sciences, Islamabad, Pakistan, included 100 children aged >6 years who had been diagnosed with JIA according to the 2004 revised International League of Associations for Rheumatology classification. Physical disability was measured using the Childhood Health Assessment Questionnaire disability index (CHAQ-DI), whereas depression was assessed by measuring their Center for Epidemiological Studies Depression Scale for Children (CES-DC) scores. Results were analyzed using IBM SPSS Statistics for Windows, Version 20.0. (Armonk, NY: IBM Corp.), with p-values ≤ 0.05 considered statistically significant. Results The 100 patients included 54 male patients (mean age, 16.3 ± 4.9 years) and 46 female patients (mean age, 18.6 ± 5.1 years). CES-DC scores showed that 72 patients with JIA had significant depression. Of these 72 patients, 50 (69.4%) had mild, 21 (29.2%) had moderate, and one (1.4%) had severe disability according to CHAQ-DI criteria. Age was the only effect modifier significantly associated with significant depression in patients with JIA (P < 0.05). Conclusion A cross sectional survey was carried out to find prevalence of depression in children with JIA. Physical disability and depression were measured using standardized tools. The percentage of significant depression among children with JIA is very high in our local population and was significantly associated with disease severity. Our findings emphasize the need to initiate early and prompt measures to prevent depression and reduce overall morbidity in patients with JIA.

Association Of Tumour Necrosis Factor-Alpha -308 G/A Promoter Polymorphism With Susceptibility And Disease Profile Of Rheumatoid Arthritis.

BACKGROUND: Single nucleotide polymorphism underlying the auto-immune process governing the pathologic manifestations of rheumatoid arthritis has been the focus of study for quite a while. TNF-alpha -308 G/A promoter polymorphism have been reported to be responsible for a number of manifestations of rheumatoid arthritis. METHODS: This case-control study was conducted at the department of Rheumatology at Pakistan Institute of Medical Sciences Islamabad from 9th May to 9th August 2019 with a focus to determine the Association of tumour necrosis factor-alpha -308 G/A promoter polymorphism with susceptibility and disease profile of rheumatoid arthritis. One hundred and fifty cases with diagnosed rheumatoid arthritis and 150 age and gender matched controls were enrolled in the study. Their genotyping was done for tumour necrosis factor-alpha - 308 G/A promoter polymorphism. RESULTS: The genotypic analysis showed that GG genotype was the most common genotype found in 118 cases (78.66%) followed by GA (18.66%) and AA genotype (2.6%) p=0.0096 in both cases and controls. Overall, G allele was more common than A in both cases and controls pointing towards the preponderance of G genotype in our population. (p=0.003). However, the GA genotype and A allelotype was more common among cases with rheumatoid arthritis (p <0.05). No significant association of G/A polymorphism with smoking and gender, however, within gender, males had a significantly more expression of the GA genotype and A allelotype (p <0.05). CONCLUSIONS: There is a significantly more expression of the GA genotype and the A allelotype of the TNF-alpha -308 G/A promoter gene in rheumatoid arthritis patients in our population. Similarly, more males, compared to females have increased expression of the GA genotype as well as the A allelotype.

The Role of the Neutrophil-to-Lymphocyte Ratio and Platelet-to-Lymphocyte Ratio as Markers of Disease Activity in Ankylosing Spondylitis.

Background Ankylosing spondylitis (AS) is a chronic rheumatological condition affecting sacroiliac joint and spine and occurs more often in younger patients than in the elderly population. Objective The purpose of the study was to determine the association of the neutrophil-lymphocyte ratio (NLR) and platelet-lymphocyte ratio (PLR) with the disease activity of AS. Methodology This case-control study was conducted in the rheumatology department at the Pakistan Institute of Medical Sciences (PIMS) hospital in Islamabad from September 2018 to July 2019. The study consisted of two groups of 59 patients per group. We assessed a full blood count with erythrocyte sedimentation rate (ESR) for each participant using the PIMS hospital laboratory. NLR and PLR were calculated. Results The mean age of the participants in the control group and the cases group was the same (32 ± 4 years). The control group NLR was 1.30 ± 0.16, the PLR was 94.98 ± 17.96, and the ESR was 16.88 ± 3.76 mm/hour. For the cases group, the NLR was 3.08 ± 0.91, the PLR was 171.50 ± 38.06, and the ESR was 29.30 ± 9.20 mm/hour. There was a significant increase in cases for NLR, PLR, and ESR as compared to control samples (p<0.05). The mean Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) score of participants with active diseases was 5.91±1.28. In the same group, the mean ESR was 27.65 ± 9.07 mm/hour, the NLR was 3.46 ± 0.80, and the PLR was 184.39 ± 36.13. For those in the inactive disease group, the mean BASDAI score was 2.84 ± 0.46, the ESR was 33.42 ± 8.48 mm/hour, the NLR was 2.17 ± 0.37, and the PLR was 139.71 ± 26.05. NLR and PLR were significantly higher in the active disease group (p<0.05). Conclusion NLR and PLR are good markers of inflammation in AS patients, and higher values indicate more active disease activity.

Eco-Floristic studies of native plants of the Beer Hills along the Indus River in the districts Haripur and Abbottabad, Pakistan.

The present study was conducted to elaborate vegetation composition structure to analyze role of edaphic and topographic factors on plant species distribution and community formation during 2013-14. A mixture of quadrat and transect methods were used. The size of quadrat for trees shrubs and herbs were 10 × 5, 5 × 2, 1 × 1 meter square respectively. Different phytosociological attribute were measured at each station. Primary results reported 123 plant species belong to 46 families. Asteraceae and Lamiaceae were dominant families with 8 species each. PCORD version 5 were used for Cluster and Two Way Cluster Analyses that initiated 4 plant communities within elevation range of 529-700 m from sea level. Indicator species analyses (ISA) were used to identify indicator species of each community. CANOCO Software (version 4.5) was used to measure the influence of edaphic and topographic variables on species composition, diversity and community formation. Whereas Canonical Correspondence Analysis (CCA) was used to measure the effect of environmental variables which showed elevation and aspect were the stronger environmental variable among topographic and CaCO3 contents, electric conductivity, soil pH were the stronger edaphic factors in determination of vegetation and communities of the Bheer Hills. Grazing pressure was one of the main anthropogenic factors in this regard.