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Reestablishing an appropriate balance between T effector cells (Teff) and Tregs is essential for correcting autoimmunity. Multiple sclerosis (MS) is an immune-mediated chronic CNS disease characterized by neuroinflammation, demyelination, and neuronal degeneration, in which the Teff:Treg balance is skewed toward pathogenic Teffs Th1 and Th17 cells. STAT3 is a key regulator of Teff:Treg balance. Using the structure-based design, we have developed a potentially novel small-molecule prodrug LLL12b that specifically inhibits STAT3 and suppresses Th17 differentiation and expansion. Moreover, LLL12b regulates the fate decision between Th17 and Tregs in an inflammatory environment, shifting Th17:Treg balance toward Tregs and favoring the resolution of inflammation. Therapeutic administration of LLL12b after disease onset significantly suppresses disease progression in adoptively transferred, chronic, and relapsing-remitting experimental autoimmune encephalomyelitis. Disease relapses were also significantly suppressed by LLL12b given during the remission phase. Additionally, LLL12b shifts Th17:Treg balance of CD4+ T cells from MS patients toward Tregs and increases Teff sensitivity to Treg-mediated suppression. These data suggest that selective inhibition of STAT3 by the small molecule LLL12b recalibrates the effector and regulatory arms of CD4+ T responses, representing a potentially clinically translatable therapeutic strategy for MS.

Objective: To assess the clinical and laboratory parameters, interventions and their outcomes in children presenting with biliary atresia at a tertiary care hospital. Study Design: Prospective longitudinal study. Place and Duration of study: Pediatric Gastroenterology and Hepatology Department of Combined Military Hospital, Rawalpindi Pakistan, from Feb 2021 to Jan 2022. Methodology: Patients diagnosed with extrahepatic biliary atresia on the basis of liver histopathology and intra operative cholangiogram were enrolled consecutively during this period. The clinical parameters, liver function tests, radiological investigations and histopathology findings were recorded and correlated. The impact of Kasai procedure on outcome and prognosis of biliary atresia patients was noted along with an interval analysis at 1 year of age. Results: Forty patients were studied including 26 males and 14 females. Thirty (75%) patients underwent Kasai at a median age of 3.14±1.2 months with a success rate of 66.6% (p-value0.05). A statistically significant relation was established between one-year outcomes of patients undergoing Kasai Hepatic Portoenterostomy and without Kasai Hepatic Portoenterostomy (p-value 0.01). A significant difference in survival of patients undergoing Kasai Hepatic Portoenterostomy and those without Kasai Hepatic Portoenterostomy (p< 0.001) was observed. Conclusion: Intervention in the form of Kasai Hepatic Portoenterostomy significantly contributes towards an improved outcome in patients with Biliary Atresia.

Abstract Improved software for processing medical images has inspired tremendous interest in modern medicine in recent years. Modern healthcare equipment generates huge amounts of data, such as scanned medical images and computerized patient information, which must be secured for future use. Diversity in the healthcare industry, namely in the form of medical data, is one of the largest challenges for researchers. Cloud environment and the Block chain technology have both demonstrated their own use. The purpose of this study is to combine both technologies for safe and secure transaction. Storing or sending medical data through public clouds exposes information into potential eavesdropping, data breaches and unauthorized access. Encrypting data before transmission is crucial to mitigate these security risks. As a result, a Blockchain based Chaotic Arnold’s cat map Encryption Scheme (BCAES) is proposed in this paper. The BCAES first encrypts the image using Arnold’s cat map encryption scheme and then sends the encrypted image into Cloud Server and stores the signed document of plain image into blockchain. As blockchain is often considered more secure due to its distributed nature and consensus mechanism, data receiver will ensure data integrity and authenticity of image after decryption using signed document stored into the blockchain. Various analysis techniques have been used to examine the proposed scheme. The results of analysis like key sensitivity analysis, key space analysis, Information Entropy, histogram correlation of adjacent pixels, Number of Pixel Change Rate, Peak Signal Noise Ratio, Unified Average Changing Intensity, and similarity analysis like Mean Square Error, and Structural Similarity Index Measure illustrated that our proposed scheme is an efficient encryption scheme as compared to some recent literature. Our current achievements surpass all previous endeavors, setting a new standard of excellence.

Abstract High-fat diet-induced obesity is a pandemic caused by an inactive lifestyle and increased consumption of Western diets and is a major risk factor for diabetes and cardiovascular diseases. In contrast, exercise can positively influence gut microbial diversity and is linked to a decreased inflammatory state. To understand the gut microbial variations associated with exercise and high-fat diet over time, we conducted a longitudinal study to examine the effect of covariates on gut microbial diversity and composition. Young mice were divided into four groups: Chow-diet (CHD), high-fat diet (HFD), high-fat diet + exercise (HFX), and exercise only (EXE) and underwent experimental intervention for 12 weeks. Fecal samples at week 0 and 12 were collected for DNA extraction, followed by 16S library preparation and sequencing. Data were analyzed using QIIME 2, R and MicrobiomeAnalyst. The Bacteroidetes-to-Firmicutes ratio decreased fivefold in the HFD and HFX groups compared to that in the CHD and EXE groups and increased in the EXE group over time. Alpha diversity was significantly increased in the EXE group longitudinally (p

Abstract Microorganism contamination on substrate surfaces is arousing increasingly concern as a serious health issue. In this research work, antimicrobial water-based acrylic paint containing silver nanoparticles (Ag NPs) was prepared using the facile Ag+ in situ reduction process, in which AgNO3 and reducing agent sodium acrylate were refluxed with acrylic polymeric solution to obtain an antimicrobial and antifungal polymeric material for substrate coating. The Synthesized antimicrobial and antifungal water-based acrylic paint were characterized by different spectroscopic techniques. The FTIR and UV–Visible spectroscopic analyses were investigated to study the water-based acrylic paint structure as well as the significant impact of Ag NPs on the paint matrix. The UV–Visible and FTIR Spectra peak shows successful integration of Ag NPs within the polymer matrix without altering the core functional groups of the paint. The water based acrylic paint exhibited a strong antimicrobial activity, revealed substantial inhibition zones against all four strains of Gram negative represented by Escherichia coli, Acinetobacter baumannii, Klebsiella pneumoniae and Gram-positive represented by Bacillus cereus. The coated film on substrate also shows great inhibition zone which exhibit a strong antimicrobial activity. Moreover, water based acrylic paint also exhibited a great antifungal activity, revealed substantial zone of inhibition against the Aspergillus niger, Aspergillus terreus and Rhizopus arrhizus fungal strains. Also, the coated film showed the best adhesion at 50% and 80% solution of polymeric coating sample as compared to pure or very dilute sample coating. This innovative approach has the potential to revolutionize varies industries from healthcare to construction.

Introduction: One persistent complication of chronic kidney disease is secondary hyperparathyroidism. Early diagnosis of this disease will reduce morbidity in patients undergoing hemodialysis. Aims & Objectives: To determine the prevalence of secondary hyperparathyroidism in chronic kidney disease patients at National Institute of Kidney Diseases, SZH Lahore. Place and Duration of Study: A cross sectional study was conducted at Nephrology Department of Shaikh Zayed Hospital (SZH) Lahore after getting approval from Institutional Review Board of National Health Research Complex (NHRC). It was conducted from September 2023 to November 2023 &140 hemo-dialysis patients were selected. Material & Methods: We measured serum parathyroid hormone, hemoglobin and other variables, at Biochemistry laboratory of Sheikh Zayed Hospital, in 140 hemodialysis patients. Serum samples were measured for PTH levels using ELISA method. The data was analyzed using SPSS version 20.P value ? 0.05 was considered significant. Results: Fifteen patients had secondary hyperparathyroidism out of 140 hemodialysis patients. Hyperparathyroidism was observed in 10.71 % of the patients. Hyperparathyroidism patients had significantly low calcium, hemoglobin levels & higher phosphate levels. Conclusion: The prevalence of secondary hyperparathyroidism is low at 10.71% of patients undergoing hemodialysis at National Institute of Kidney Disease, SZH Lahore.

Abstract We aimed to propose a mortality risk prediction model using on-admission clinical and laboratory predictors. We used a dataset of confirmed COVID-19 patients admitted to three general hospitals in Tehran. Clinical and laboratory values were gathered on admission. Six different machine learning models and two feature selection methods were used to assess the risk of in-hospital mortality. The proposed model was selected using the area under the receiver operator curve (AUC). Furthermore, a dataset from an additional hospital was used for external validation. 5320 hospitalized COVID-19 patients were enrolled in the study, with a mortality rate of 17.24% (N = 917). Among 82 features, ten laboratories and 27 clinical features were selected by LASSO. All methods showed acceptable performance (AUC > 80%), except for K-nearest neighbor. Our proposed deep neural network on features selected by LASSO showed AUC scores of 83.4% and 82.8% in internal and external validation, respectively. Furthermore, our imputer worked efficiently when two out of ten laboratory parameters were missing (AUC = 81.8%). We worked intimately with healthcare professionals to provide a tool that can solve real-world needs. Our model confirmed the potential of machine learning methods for use in clinical practice as a decision-support system.

This experiment aimed to investigate the effects of partial substitution of crude protein from soybean meal (SBM) with black soldier fly (Hermetia illucens) larvae meal (BSFLM) in juvenile rohu (Labeo rohita) and catla (Catla catla). Four isonitrogenous diets (23% crude protein) were formulated to replace 0% (T0), 40% (T40), 80% (T80) and 100% (T100) crude protein from SBM with BSFLM. Triplicate groups of each species (10 fish per replicate) were fed in an eight week growth experiment. After final sampling (n = 20 fish per dietary group), the remaining fish were exposed to bacterial (Staphylococcus aureus) challenge (0.80 CFU/ml) for 15 days. Rohu fed with BSFLM substituted diets showed significantly higher growth and feed conversion ratio as compared to those in T0. Catla fed with BSFLM substituted diets showed slightly higher growth indices. The growth response of rohu to BSFLM substitution was better than that noted in catla in all groups. The chemical composition, amino acids and fatty acids profile, haematological and biochemical parameters, levels of liver function enzymes measured in T0, T40, T80 and T100 were similar between four dietary groups in both species. However, the maximum value of cholesterol and triglycerides were noted in T100 both in catla and rohu. The values of lauric acid, α-linolenic acid, decosahexanoic acid, n3:n6 fatty acids ratio progressively increased with dietary increase of BSFLM in both species. At end of the growth experiment, the levels of catalase, superoxide dismutase and lysozyme increased linearly with the inclusion of BSFLM in both species while malondialdehyde showed similar values between different groups. However, catalase, and superoxide dismutase increased (T0

IntroductionCervical cancer, primarily driven by Human Papillomavirus (HPV) infection, stands as a substantial global health challenge. The TP53 gene's, Arg72Pro polymorphism has emerged as a noteworthy player in cervical cancer development, particularly among individuals harboring high-risk (HR) HPV types. Additionally, long non-coding RNAs (lncRNAs), exemplified by metastasis-associated lung adenocarcinoma transcript 1 (MALAT1), exert critical roles in cancer biology. This study delves into unravelling the intricate connections linking HPV infection, TP53 Arg72Pro polymorphism, and MALAT1 expression in the context of cervical cancer.Materials and methodsWithin a cohort of cervical cancer patients, we discerned HPV infection statuses, executed genotyping for the TP53 Arg72Pro polymorphism, and quantified MALAT1 expression through quantitative reverse transcription-polymerase chain reaction (qRT-PCR). Statistical analyses meticulously probed relationships intertwining HPV infection, TP53 polymorphism, and MALAT1 expression.FindingsOur investigation revealed a striking prevalence of the TP53 Arg72Pro polymorphism among HPV-positive subjects, accompanied by a robust and statistically significant correlation linking MALAT1 overexpression (pConclusionThe contours of our findings sketch a compelling landscape wherein HR-HPV infection, TP53 polymorphism, and MALAT1 expression intertwine significantly in cervical cancer. The voyage ahead entails delving deeper into molecular underpinnings to decipher MALAT1's nuanced role and its dance with TP53 within HPV-associated cervical carcinogenesis. This expedition promises insights that may engender targeted therapeutic interventions and bespoke prognostic markers, tailored to the realm of HR-HPV-related cervical cancer.

Abstract This paper shows how to use the approximate Hamiltonian approach for the non-conservative system not capable of possessing Hamiltonian. Using the approximate Hamiltonian method for a non-conservative system is not possible in general. We propose a way to obtain the closed-form solutions for such systems. We use the approximate dual Hamiltonian method to construct the first integrals and closed-form solutions of the Van der Pol equation. First the solutions of the initial value VdP equation is obtained using approximate dual Hamiltonian method. Then a good agreement is observed in the comparison between the numerical results and the results through approximate dual Hamiltonian method. Finally, we use the approximate dual Hamiltonian method to find the dual Hamiltonian and first integrals of the forced Van der Pol oscillator and Liénard system. These significant results can be applied to any Van der Pol equation.

Abstract Mycobacteroides abscessus (Previously Mycobacterium abscessus) is an emerging microorganism of the newly defined genera Mycobacteroides that causes mainly skin and tissue diseases in humans. The recent availability of total 34 fully sequenced genomes of different strains belonging to this species has provided an opportunity to utilize this genomics data to gain novel insights and guide the development of specific antimicrobial therapies. In the present study, we collected collectively 34 complete genome sequences of M. abscessus from the NCBI GenBank database. Pangenome analysis was conducted on these genomes to understand the genetic diversity and to obtain proteins associated with its core genome. These core proteins were then subjected to various subtractive filters to identify potential antigenic targets that were subjected to multi-epitope vaccine design. Our analysis projected the open pangenome of M. abscessus containing 3443 core genes. After applying various stepwise filtration steps on the core proteins, a total of four potential antigenic targets were identified. Utilizing their constituent CD4 and CD8 T-cell epitopes, a multi-epitope based subunit vaccine was computationally designed. Sequence-based analysis as well as structural characterization revealed the immunological effectiveness of this designed vaccine. Further molecular docking, molecular dynamics simulation and binding free energy estimation with Toll-like receptor 2 indicated strong structural associations of the vaccine with the immune receptor. The promising results are encouraging and need to be validated by additional wet laboratory studies for confirmation.

Abstract. Background:. Mesenteric panniculitis (MP) is a non-specific, localized inflammation at the mesentery of small intestines which often gets detected on computed tomography. An association with malignant neoplasms remains unclear. We performed a systematic review and meta-analysis to examine the association of malignancy with MP. Methods:. MEDLINE, EMBASE, Web of Science, and Cochrane databases were searched for articles published from inception to 2020 that evaluated the association of malignant neoplasms with MP in comparison with control groups. Using random-effects method, a summary odds ratio (OR) estimate with 95% confidence intervals for malignant neoplasms in MP was estimated. Results:. Four case-control studies reporting data on 415 MP patients against 1132 matched-controls met inclusion criteria and were analyzed. The pooled OR for finding a malignant neoplasm in patients with MP was 0.907 (95% CI: 0.688–1.196; P = .489). The heterogeneity was mild and non-significant. Also, there was no heightened risk of any specific type of malignancy with MP. Three more case-series with unmatched-control groups (MP: 282, unmatched-controls: 17,691) were included in a separate analysis where the pooled OR of finding a malignant neoplasm was 2.963 (95% CI: 1.434–6.121; P = .003). There was substantial heterogeneity in this group. Conclusion:. This meta-analysis of matched controlled studies proves absence of any significant association of malignant neoplasms with MP. Our study also demonstrates that the putative association of malignancy with MP is mainly driven by uncontrolled studies or case-series.

Abstract Silver is a poisonous but precious heavy metal that has widespread application in various biomedical and environmental divisions. Wide-ranging usage of the metal has twisted severe environmental apprehensions. Henceforth there is a cumulative call for the progress of modest, low-cost and, the ecological method for remediation of silver. In the present study, Bacillus cereus was isolated from contaminated soil. Various experimental factors like the amount of AgNO3, inoculum size, temperature, time, and pH were improved by using central composite design (CCD) grounded on response surface methodology (RSM). Optimized values for AgNO3 (1 mM) 10 ml, inoculum size (Bacillus cereus) 8.7 ml, temperature 48.5 °C, time 69 h, and pH 9 showed in the form of optimized ramps. The formed nanoparticles stayed characterized by UV–visible spectrophotometer, Scanning Electron Microscopy, Fourier transform infra-red spectrometry, particle size analyzer, and X-ray diffraction. The particle size ranges from 5 to 7.06 nm with spherical form. The antimicrobial effectiveness of synthesized nanoparticles was tested contrary to five multidrug resistant microbial strains, Staphylococcus epidermidis, Staphylococcus aureus, Escherichia coli, Salmonella enterica, Porteus mirabilis by disc diffusion method. The minimum inhibitory concentrations and minimum lethal concentrations were detected by the broth macro dilution method. 2,2-diphenyl-1-picrylhydrazyl-hydrate (DPPH) was used to check the free radical scavenging ability of biogenic silver nanoparticles. Similarly, anti-radical activity was checked by 2,2′-Azino-Bis-3-Ethylbenzothiazoline-6-Sulfonic Acid (ABTS) with varying time intervals. Catalytic potential of biosynthesized silver nanoparticles was also investigated.

Nonalcoholic fatty liver disease (NALFD), characterized by an abnormal accumulation of triglycerides in hepatocytes, is closely linked to insulin resistance, metabolic syndrome, and changes in lipogenesis in the liver. The accumulation of hepatic lipids can lead to a range of pathologies from mild steatosis to severe cirrhosis. Endurance exercise is known to ameliorate the adverse health effects of NAFLD. Therefore, we aimed to investigate the effect of voluntary wheel running (VWR) on the metabolic changes in the livers of high-fat diet (HFD)-induced NAFLD mice and used LC-MS/MS (Liquid chromatography-mass spectrometry) to determine whether the tested intervention affected the protein expression profiles of the mouse livers. Male C57BL/6 mice were randomly divided into three groups: control (CON), high-fat diet sedentary group (HFD), high-fat diet VWR group (HFX). HFX group performed voluntary wheel running into individually cages, given a high-fat diet for 12 weeks. Food consumption, body weight, and running distance were measured every week. Using 2D (2-dimensional)-gel electrophoresis, we detected and quantitatively analyzed the protein expression with >2.0-fold change in the livers of HFD-fed mice, HFD-fed exercise (HFX) mice, and chow-fed mice. Body weight was significantly increased in HFD compared to CON (P < 0.05). The 2D-gel electrophoresis analysis indicated that there was a difference between CON and HFD groups, showing 31 increased and 27 decreased spots in the total 302 paired spots in the HFD group compared to CON. The analysis showed 43 increased and 17 decreased spots in the total 258 spots in the HFX group compared to CON. Moreover, 12 weeks of VWR showed an increase of 35 and a decrease of 8 spots in a total of 264 paired spots between HFD and HFX. LC-MS/MS of HFD group revealed that proteins involved in ketogenesis, lipid metabolism, and the metabolism of drugs and xenobiotics were upregulated, whereas detoxifying proteins, mitochondrial precursors, transport proteins, proteasomes, and proteins involved in amino acid metabolism were downregulated. On the other hand, VWR counteracted the protein expression profile of HFD-fed mice by upregulating molecular chaperones, gluconeogenesis-, detoxification-, proteasome-, and energy metabolism-related proteins. This study provided a molecular understanding of the HFD- and exercise-induced protein marker expression and presented the beneficial effects of exercise during pathophysiological conditions.

The swift emergence of antibiotic resistance (AR) in bacterial pathogens to make themselves adaptable to changing environments has become an alarming health issue. To prevent AR infection, many ways can be accomplished such as by decreasing the misuse of antibiotics in human and animal medicine. Among these AR bacterial species, Plesiomonas shigelloides is one of the etiological agents of intestinal infection in humans. It is a gram-negative rod-shaped bacterium that is highly resistant to several classes of antibiotics, and no licensed vaccine against the aforementioned pathogen is available. Hence, substantial efforts are required to screen protective antigens from the pathogen whole genome that can be subjected easily to experimental evaluations. Here, we employed a reverse vaccinology (RV) approach to design a multi-antigenic epitopes based vaccine against P. shigelloides. The complete genomes of P. shigelloides were retrieved from the National Center for Biotechnological Information (NCBI) that on average consist of 5226 proteins. The complete proteomes were subjected to different subtractive proteomics filters, and in the results of that analysis, out of total proteins, 2399 were revealed as non-redundant and 2827 as redundant proteins. The non-redundant proteins were further checked for subcellular localization analysis, in which three were localized in the extracellular matrix, eight were outer membrane, and 13 were found in the periplasmic membrane. All surface localized proteins were found to be virulent. Out of a total of 24 virulent proteins, three proteins (flagellar hook protein (FlgE), hypothetical protein, and TonB-dependent hemoglobin/transferrin/lactoferrin family receptor protein) were considered as potential vaccine targets and subjected to epitopes prediction. The predicted epitopes were further examined for antigenicity, toxicity, and solubility. A total of 10 epitopes were selected (GFKESRAEF, VQVPTEAGQ, KINENGVVV, ENKALSQET, QGYASANDE, RLNPTDSRW, TLDYRLNPT, RVTKKQSDK, GEREGKNRP, RDKKTNQPL). The selected epitopes were linked with each other via specific GPGPG linkers in order to design a multi-epitopes vaccine construct, and linked with cholera toxin B subunit adjuvant to make the designed vaccine construct more efficient in terms of antigenicity. The 3D structure of the vaccine construct was modeled ab initio as no appropriate template was available. Furthermore, molecular docking was carried out to check the interaction affinity of the designed vaccine with major histocompatibility complex (MHC-)I (PDB ID: 1L1Y), MHC-II (1KG0), and toll-like receptor 4 ((TLR-4) (PDB: 4G8A). Molecular dynamic simulation was applied to evaluate the dynamic behavior of vaccine-receptor complexes. Lastly, the binding free energies of the vaccine with receptors were estimated by using MMPB/GBSA methods. All of the aforementioned analyses concluded that the designed vaccine molecule as a good candidate to be used in experimental studies to disclose its immune protective efficacy in animal models.

الهدف: دراسة قيم الضغط داخل المقلة عند السكريين بالمقارنة مع الأصحاء، ودراسة قيم ثخانة القرنية المركزية كعامل وسيط أساسي مؤثر على الضغط داخل المقلة. كذلك دراسة كل من ثخانة العدسة، الطول المحوري الأمامي الخلفي لكرة العين، عمق البيت الأمامي، قيمة المكافئ الكروي، تعداد خلايا بطانة القرنية، وجود اعتلال الشبكية السكري غير التكاثري كعوامل وسيطة ثانوية للعلاقة بين السكري والضغط داخل المقلة. كذلك دراسة علاقة الضغط داخل المقلة مع العمر ومدة الإصابة بالسكري وقيمة سكر الدم. المواد والطرق: شارك بالدراسة 114مريض (228 عين) توزعوا بين 57 مريض سكري نمط 2 (حالة) و 57 مريض شاهد، أعمارهم تتراوح بين (42-78) سنة، تم قياس ضغط العين لكل الحالات والشواهد بوساطة جهاز غولدمان التماسي. كذلك تم دراسة عدد من المتغيرات المحتمل أنها تؤثر على الضغط داخل المقلة مثل (ثخانة القرنية المركزية، عمق البيت الأمامي، طول العين الأمامي الخلفي، المكافئ الكروي، القدرة البصرية المصححة، تعداد الخلايا البطانية، وجود اعتلال شبكية سكري غير تكاثري مرافق) بالاستعانة بالمجهر البراق وجهاز الايكو أ والمصباح الشقي وجهاز قياس أسواء الانكسار الآلي. النتائج: لوحظ ارتفاع هام إحصائيا في قيم الضغط داخل المقلة عند السكريين نمط2 بالمقارنة مع الأصحاء حيث بلغ متوسط قيم الضغط داخل المقلة عند مجموعة السكريين 16،6± 4،4 ملمز مقارنة مع الأصحاء 12،8 ±3،2 ملمز. وكان ذلك في مجموعة الاعتلال الشبكي غير التكاثري NPDR بشكل أعلى منه في المجموعة الأخرى دون إصابة الشبكية بقيم ضغط داخل المقلة على التوالي :19،05 ±3،8 ملمز، 14،16 ±3،5 ملمز. لوحظ ازدياد في كل من ثخانة القرنية المركزية وثخانة العدسة والمكافئ الكروي وانخفاض كل من تعداد الخلايا البطانية وعمق البيت الأمامي وطول العين المحوري الأمامي الخلفي والقدرة البصرية المصححة في مجموعة السكريين. كان هناك علاقة ارتباط إيجابية بين الضغط داخل المقلة وثخانة القرنية المركزية .كان هناك علاقة ارتباط إيجابية ما بين الضغط داخل المقلة وكل من: العمر، مدة الإصابة بالسكري، قيمة سكر الدم، وجود اعتلال الشبكية السكري غير التكاثري، ثخانة العدسة، المكافئ الكروي. في حين كانت العلاقة عكسية بين الضغط داخل المقلة وكل من القدرة البصرية المصححة وتعداد الخلايا البطانية. لم نلاحظ وجود علاقة هامة إحصائيا بين الضغط داخل المقلة وطول العين المحوري الأمامي الخلفي. الخلاصة: يكون الضغط داخل المقلة عند السكريين أعلى منه عند الشواهد. تلعب ثخانة القرنية المركزية الدور الرئيسي في هذا الارتفاع. كذلك يلعب كل من ازدياد ثخانة العدسة، ازدياد المكافئ الكروي، قلة عمق البيت الأمامي، نقص القدرة البصرية المصححة، وجود اعتلال شبكية سكري غير تكاثري، نقص تعداد خلايا بطانة القرنية دورا في ارتفاع الضغط عند السكريين.

The emergence of antibiotic resistance in bacterial species is a major threat to public health and has resulted in high mortality as well as high health care costs. Burkholderia mallei is one of the etiological agents of health care-associated infections. As no licensed vaccine is available against the pathogen herein, using reverse vaccinology, bioinformatics, and immunoinformatics approaches, a multi-epitope-based vaccine against B. mallei was designed. In completely sequenced proteomes of B. mallei, 18,405 core, 3671 non-redundant, and 14,734 redundant proteins were predicted. Among the 3671 non-redundant proteins, 3 proteins were predicted in the extracellular matrix, 11 were predicted as outer membrane proteins, and 11 proteins were predicted in the periplasmic membrane. Only two proteins, type VI secretion system tube protein (Hcp) and type IV pilus secretin proteins, were selected for epitope prediction. Six epitopes, EAMPERMPAA, RSSPPAAGA, DNRPISINL, RQRFDAHAR, AERERQRFDA, and HARAAQLEPL, were shortlisted for multi-epitopes vaccine design. The predicted epitopes were linked to each other via a specific GPGPG linker and the epitopes peptide was then linked to an adjuvant molecule through an EAAAK linker to make the designed vaccine more immunologically potent. The designed vaccine was also found to have favorable physicochemical properties with a low molecular weight and fewer transmembrane helices. Molecular docking studies revealed vaccine construct stable binding with MHC-I, MHC-II, and TLR-4 with energy scores of −944.1 kcal/mol, −975.5 kcal/mol, and −1067.3 kcal/mol, respectively. Molecular dynamic simulation assay noticed stable dynamics of the docked vaccine-receptors complexes and no drastic changes were observed. Binding free energies estimation revealed a net value of −283.74 kcal/mol for the vaccine-MHC-I complex, −296.88 kcal/mol for the vaccine-MHC-II complex, and −586.38 kcal/mol for the vaccine-TLR-4 complex. These findings validate that the designed vaccine construct showed promising ability in terms of binding to immune receptors and may be capable of eliciting strong immune responses once administered to the host. Further evidence from experimentations in mice models is required to validate real immune protection of the designed vaccine construct against B. mallei.

Staphylococcus saprophyticus is a Gram-positive coccus responsible for the occurrence of cystitis in sexually active, young females. While effective antibiotics against this organism exist, resistant strains are on the rise. Therefore, prevention via vaccines appears to be a viable solution to address this problem. In comparison to traditional techniques of vaccine design, computationally aided vaccine development demonstrates marked specificity, efficiency, stability, and safety. In the present study, a novel, multi-epitope vaccine construct was developed against S. saprophyticus by targeting fully sequenced proteomes of its five different strains, which were examined using a pangenome and subtractive proteomic strategy to characterize prospective vaccination targets. The three immunogenic vaccine targets which were utilized to map the probable immune epitopes were verified by annotating the entire proteome. The predicted epitopes were further screened on the basis of antigenicity, allergenicity, water solubility, toxicity, virulence, and binding affinity towards the DRB*0101 allele, resulting in 11 potential epitopes, i.e., DLKKQKEKL, NKDLKKQKE, QDKLKDKSD, NVMDNKDLE, TSGTPDSQA, NANSDGSSS, GSDSSSSNN, DSSSSNNDS, DSSSSDRNN, SSSDRNNGD, and SSDDKSKDS. All these epitopes have the efficacy to cover 99.74% of populations globally. Finally, shortlisted epitopes were joined together with linkers and three different adjuvants to find the most stable and immunogenic vaccine construct. The top-ranked vaccine construct was further scrutinized on the basis of its physicochemical characterization and immunological profile. The non-allergenic and antigenic features of modeled vaccine constructs were initially validated and then subjected to docking with immune receptor major histocompatibility complex I and II (MHC-I and II), resulting in strong contact. In silico cloning validations yielded a codon adaptation index (CAI) value of 1 and an ideal percentage of GC contents (46.717%), indicating a putative expression of the vaccine in E. coli. Furthermore, immune simulation demonstrated that, after injecting the proposed MEVC, powerful antibodies were produced, resulting in the sharpest peaks of IgM + IgG formation (>11,500) within 5 to 15 days. Experimental testing against S. saprophyticus can evaluate the safety and efficacy of these prophylactic vaccination designs.

Whipple’s disease is caused by T. whipplei, a Gram-positive pathogenic bacterium. It is considered a persistent infection affecting various organs, more likely to infect males. There is currently no licensed vaccination available for Whipple’s disease; thus, the development of a chimeric peptide-based vaccine against T. whipplei has the potential to be tremendously beneficial in preventing Whipple’s disease in the future. The present study aimed to apply modern computational approaches to generate a multi-epitope-based vaccine that expresses antigenic determinants prioritized from the core proteome of two T. whipplei whole proteomes. Using an integrated computational approach, four immunodominant epitopes were found from two extracellular proteins. Combined, these epitopes covered 89.03% of the global population. The shortlisted epitopes exhibited a strong binding affinity for the B- and T-cell reference set of alleles, high antigenicity score, nonallergenic nature, high solubility, nontoxicity, and excellent binders of DRB1*0101. Through the use of appropriate linkers and adjuvation with a suitable adjuvant molecule, the epitopes were designed into a chimeric vaccine. An adjuvant was linked to the connected epitopes to boost immunogenicity and efficiently engage both innate and adaptive immunity. The physiochemical properties of the vaccine were observed favorable, leading toward the 3D modeling of the construct. Furthermore, the vaccine’s binding confirmation to the TLR-4 critical innate immune receptor was also determined using molecular docking and molecular dynamics (MD) simulations, which shows that the vaccine has a strong binding affinity for TLR4 (−29.4452 kcal/mol in MM-GBSA and −42.3229 kcal/mol in MM-PBSA). Overall, the vaccine described here has a promising potential for eliciting protective and targeted immunogenicity, subject to further experimental testing.

Hantaviruses are negative-sense, enveloped, single-stranded RNA viruses of the family Hantaviridae. In recent years, rodent-borne hantaviruses have emerged as novel zoonotic viruses posing a substantial health issue and socioeconomic burden. In the current research, a reverse vaccinology approach was applied to design a multi-epitope-based vaccine against hantavirus. A set of 340 experimentally reported epitopes were retrieved from Virus Pathogen Database and Analysis Resource (ViPR) and subjected to different analyses such as antigenicity, allergenicity, solubility, IFN gamma, toxicity, and virulent checks. Finally, 10 epitopes which cleared all the filters used were linked with each other through specific GPGPG linkers to construct a multi-antigenic epitope vaccine. The designed vaccine was then joined to three different adjuvants—TLR4-agonist adjuvant, β-defensin, and 50S ribosomal protein L7/L12—using an EAAAK linker to boost up immune-stimulating responses and check the potency of vaccine with each adjuvant. The designed vaccine structures were modelled and subjected to error refinement and disulphide engineering to enhance their stability. To understand the vaccine binding affinity with immune cell receptors, molecular docking was performed between the designed vaccines and TLR4; the docked complex with a low level of global energy was then subjected to molecular dynamics simulations to validate the docking results and dynamic behaviour. The docking binding energy of vaccines with TLR4 is −29.63 kcal/mol (TLR4-agonist), −3.41 kcal/mol (β-defensin), and −11.03 kcal/mol (50S ribosomal protein L7/L12). The systems dynamics revealed all three systems to be highly stable with a root-mean-square deviation (RMSD) value within 3 Å. To test docking predictions and determine dominant interaction energies, binding free energies of vaccine(s)–TLR4 complexes were calculated. The net binding energy of the systems was as follows: TLR4-agonist vaccine with TLR4 (MM–GBSA, −1628.47 kcal/mol and MM–PBSA, −37.75 kcal/mol); 50S ribosomal protein L7/L12 vaccine with TLR4 complex (MM–GBSA, −194.62 kcal/mol and MM–PBSA, −150.67 kcal/mol); β-defensin vaccine with TLR4 complex (MM–GBSA, −9.80 kcal/mol and MM–PBSA, −42.34 kcal/mol). Finally, these findings may aid experimental vaccinologists in developing a very potent hantavirus vaccine.

Antibiotic resistance (AR) is the resistance mechanism pattern in bacteria that evolves over some time, thus protecting the bacteria against antibiotics. AR is due to bacterial evolution to make itself fit to changing environmental conditions in a quest for survival of the fittest. AR has emerged due to the misuse and overuse of antimicrobial drugs, and few antibiotics are now left to deal with these superbug infections. To combat AR, vaccination is an effective method, used either therapeutically or prophylactically. In the current study, an in silico approach was applied for the design of multi-epitope-based vaccines against Providencia rettgeri, a major cause of traveler’s diarrhea. A total of six proteins: fimbrial protein, flagellar hook protein (FlgE), flagellar basal body L-ring protein (FlgH), flagellar hook-basal body complex protein (FliE), flagellar basal body P-ring formation protein (FlgA), and Gram-negative pili assembly chaperone domain proteins, were considered as vaccine targets and were utilized for B- and T-cell epitope prediction. The predicted epitopes were assessed for allergenicity, antigenicity, virulence, toxicity, and solubility. Moreover, filtered epitopes were utilized in multi-epitope vaccine construction. The predicted epitopes were joined with each other through specific GPGPG linkers and were joined with cholera toxin B subunit adjuvant via another EAAAK linker in order to enhance the efficacy of the designed vaccine. Docking studies of the designed vaccine construct were performed with MHC-I (PDB ID: 1I1Y), MHC-II (1KG0), and TLR-4 (4G8A). Findings of the docking study were validated through molecular dynamic simulations, which confirmed that the designed vaccine showed strong interactions with the immune receptors, and that the epitopes were exposed to the host immune system for proper recognition and processing. Additionally, binding free energies were estimated, which highlighted both electrostatic energy and van der Waals forces to make the complexes stable. Briefly, findings of the current study are promising and may help experimental vaccinologists to formulate a novel multi-epitope vaccine against P. rettgeri.

Background: Unveiling of multidrug resistance in bacteria is becoming a global concern. It contributes as a main financial burden to treat infectious diseases especially in developing countries. Objectives: This study was designed to determine the prevalence and resistance pattern of multidrug resistant bacteria from hospital soil. Methodology: Using random soil sampling technique, bacterial isolates were obtained through dilution plate method. Antimicrobial screening of isolates was performed by Kirby Bauer disc diffusion method against a panel of 14 known antibiotics. Furthermore, strains were biochemically identified following Bergey’s Manual of Determinative Bacteriology. Results: A total of 44 isolates were successfully identified from 4 soil samples of different waste areas of hospital from Multan region. Bacillus spp. and Staphylococcus ssp. were prominent isolates in all the sites. Resistance among Bacillus spp. was high against ampicillin (91%) and in Staphylococcus spp. against tetracycline (78%). Out of total strains, 35 were found to be multidrug resistant. Conclusion: Presence of drug residue in the hospital waste contributes to its resistance in bacteria. A substantial increase of multidrug resistance in hospital waste demands an effective management against drugs.

Objective: To determine the frequency of metabolic syndrome in cases with type 2 diabetes mellitus. Methods: A descriptive cross-sectional study was conducted at department of Medicine, Allied Hospital, Faisalabad from February to May 2016. All diagnosed cases of type 2 diabetes mellitus having 30 to 70 years of age of either gender were enrolled. The presence of metabolic syndrome was observed. Results: Out of 150 cases, 79 (52.67%) were males whereas 71 (47.33%) were females. Age distribution shows that 93 (62%) were 50 years of age (mean age 44.58+6.31 years). The frequency of metabolic syndrome in cases with diabetes mellitus was found to be 117 (78%). Conclusion: The rate of metabolic syndrome is quite higher in cases with type 2 diabetes mellitus.

Hepatitis C virus (HCV) causes chronic and acute hepatitis infections. As there is extreme variability in the HCV genome, no approved HCV vaccine has been available so far. An effective polypeptide vaccine based on the functionally conserved epitopes will be greatly helpful in curing disease. For this purpose, an immuno-informatics study is performed based on the published HCV subtype-3a from Pakistan. First, the virus genome was translated to a polyprotein followed by a subsequent prediction of T-cell epitopes. Non-allergenic, IFN-γ producer, and antigenic epitopes were shortlisted, including 5 HTL epitopes and 4 CTL, which were linked to the final vaccine by GPGPG and AAY linkers, respectively. Beta defensin was included as an adjuvant through the EAAAK linker to improve the immunogenicity of the polypeptide. To ensure its safety and immunogenicity profile, antigenicity, allergenicity, and various physiochemical attributes of the polypeptide were evaluated. Molecular docking was conducted between TLR4 and vaccine to evaluate the binding affinity and molecular interactions. For stability assessment and binding of the vaccine-TLR4 docked complex, molecular dynamics (MD) simulation and MMGBSA binding free-energy analyses were conducted. Finally, the candidate vaccine was cloned in silico to ensure its effectiveness. The current vaccine requires future experimental confirmation to validate its effectiveness. The vaccine construct produced might be useful in providing immune protection against HCV-related infections.