Impact of vaccination on COVID-19 severity during the second wave in Brunei Darussalam, 2021.

Objective: Coronavirus disease (COVID-19) vaccinations have been shown to prevent infection with efficacies ranging from 50% to 95%. This study assesses the impact of vaccination on the clinical severity of COVID-19 during the second wave in Brunei Darussalam in 2021, which was due to the Delta variant. Methods: Patients included in this study were randomly selected from those who were admitted with COVID-19 to the National Isolation Centre between 7 August and 6 October 2021. Cases were categorized as asymptomatic, mild (symptomatic without pneumonia), moderate (pneumonia), severe (needing supplemental oxygen therapy) or critical (needing mechanical ventilation) but for statistical analysis purposes were dichotomized into asymptomatic/mild or moderate/severe/critical cases. Univariate and multivariable analyses were conducted to identify risk factors associated with moderate/severe/critical disease. Propensity score-matched analysis was also performed to evaluate the impact of vaccination on disease severity. Results: The study cohort of 788 cases (mean age: 42.1 ± 14.6 years; 400 males) comprised 471 (59.8%) asymptomatic/mild and 317 (40.2%) moderate/severe/critical cases. Multivariable logistic regression analysis showed older age group (≥ 45 years), diabetes mellitus, overweight/obesity and vaccination status to be associated with increased severity of disease. In propensity score-matched analysis, the relative risk of developing moderate/severe/critical COVID-19 for fully vaccinated (two doses) and partially vaccinated (one dose) cases was 0.33 (95% confidence interval [CI]: 0.16-0.69) and 0.62 (95% CI: 0.46-0.82), respectively, compared with a control group of non-vaccinated cases. The corresponding relative risk reduction (RRR) values were 66.5% and 38.4%, respectively. Vaccination was also protective against moderate/severe/critical disease in a subgroup of overweight/obese patients (RRR: 37.2%, P = 0.007). Discussion: Among those who contracted COVID-19, older age, having diabetes, being overweight/obese and being unvaccinated were significant risk factors for moderate/severe/critical disease. Vaccination, even partial, was protective against moderate/severe/critical disease.

Innovative biocatalyst synthesis of pectinolytic enzymes by cross-linking strategy: Potentially immobilised pectinases for the production of pectic-oligosaccharides from pectin.

Pectinases are outstanding multienzymes, which have the potential to produce new emerging pectic-oligosaccharides (POS) via enzymatic hydrolysis of pectin. However, free pectinase is unable to undergo repeated reaction for the production of POS. This study proposed a sustainable biocatalyst of pectinases known as cross-linked pectinase aggregates (CLPA). Pectinase from Aspergillus aculeatus was successfully precipitated using 2 mg/mL pectinase and 60 % acetone for 20 min at 20 °C, which remained 36.3 % of its initial activity. The prepared CLPA showed the highest activity recovery (85.0 %), under the optimised conditions (0.3 % (v/v) starch and glutaraldehyde mixture (St/Ga), 1.5: 1 of St/Ga, 25 °C, 1.5 h). Furthermore, pectin-degrading enzymes from various sources were used to produce different CLPA. The alteration of pectinase secondary structure gave high stability in acidic condition (pH 4), thermostability, deactivation energy and half-life, and improved storage stability at 4 °C for 30 days. Similarly to their free counterpart, the CLPA exhibited comparable enzymatic reaction kinetics and could be reused eight times with approximately 20 % of its initial activity. The developed CLPA does not only efficaciously produced POS from pectin as their free form, but also exhibited better operational stability and reusability, making it more suitable for POS production.

Partial syntheses of aromatic amides: their anti-urease potential and docking studies.

The aromatic amide: N-p-trans-coumaroyltyramine (1) was isolated for the first time from the stem bark of Celtis zenkeri (Ulmaceae). Its four new derivatives (1a-d) and previously reported diacetylated product (1e) have been synthesized and characterized spectroscopically followed by their in vitro screening for anti-urease potential. The diacetylated product (1e) was found to be the most potent inhibitor with an IC50 value of 19.5 ± 0.23 µM compared to thiourea used as standard (21.5 ± 0.47 µM). Furthermore, molecular docking studies were conducted revealing striking interactions of the active compounds with catalytically important residues such as His593, Ala636 and Asp633. Subsequently, the prime MM-GBSA calculations provided the ligand binding and strain energies. The molecular dynamic simulations validated the docked and post-docked complexes where compounds 1b, 1c, 1d and 1e remained stable throughout the simulation. This study provides insight into the N-p-trans-coumaroyltyramine derivatives (1b-e) that can block the substrate entry, thereby inhibiting the urease's catalytic activity. Hence, these hit compounds can proceed for further pre-clinical studies for drug discovery against urease.Communicated by Ramaswamy H. Sarma.

Drug repurposing for the identification of new Bcl-2 inhibitors: In vitro, STD-NMR, molecular docking, and dynamic simulation studies.

BACKGROUND: The anti-apoptotic protein B-Cell Lymphoma 2 (Bcl-2) is a key target for the development of anti-cancer agents, as its overexpression can render cancer cells resistant to chemotherapeutic treatments. AIMS AND OBJECTIVES: The current study has systematically evaluated a library of FDA-approved drugs for Bcl-2 inhibition using a drug repurposing strategy via in vitro, biophysical, and in-silico techniques. MATERIALS AND METHODS: In vitro anticancer activity was performed, followed by apoptosis assay. The selected compounds were subjected to Saturation Transfer Difference Nuclear Magnetic Resonance (STD-NMR) spectroscopy, molecular docking, and molecular dynamic simulation for ligand-protein interactions. KEY FINDINGS: In the initial screening, seventy-five (75) drugs were evaluated against the HL-60 (human blood promyelocytic leukemia) cancer cell line. Among them, paroxetine HCl, carvedilol, clomipramine HCl, and clomifene citrate showed significant anti-proliferative activity (IC50 = 9.733 ± 0.524, 11.940 ± 0.079, 12.376 ± 1.242, and 6.155 ± 0.363 µM, respectively), in comparison to the reference drug venetoclax (IC50 = 7.086 ± 0.041 µM). This indicated that the test drugs have comparable IC50 values to the standard drug. Furthermore, the drugs were able to induce apoptosis in HL-60 cells. These drugs showed interactions with Bcl-2 protein in STD-NMR analysis. Docking and MD simulation studies further supported the interaction of these drugs with Bcl-2 protein, mainly via hydrophobic contacts leading to stable drug-Bcl-2 complexes. SIGNIFICANCE: This study, identifies paroxetine HCl, carvedilol, clomipramine HCl, and clomifene citrate as significant Bcl-2 inhibitors and needs further pre-clinical and clinical studies for potential anti-cancer agents' evaluation.

Door-to-Skin Time in Patient Undergoing Emergency Trauma Craniotomy.

Background: Traumatic brain injury (TBI) is the third leading cause of death and disability worldwide in 2020. For patients with TBI with significant intracranial bleeds, urgent surgical intervention remains the mainstay treatment. This study aims to evaluate the time to definite surgical intervention since admission and its association with patient outcomes in a neurosurgery referral centre in Malaysia. Methods: This retrospective study was conducted at Hospital Sultanah Aminah Johor Bahru from 1 January 2019 to 31 December 2019. All patients with TBI requiring urgent craniotomy were identified from the operating theatre registry, and the required data were extracted from their clinical notes, including the Glasgow Outcome Score (GCS) at discharge and 6 months later. Logistic regression was performed to identify the factors associated with poor outcomes. Results: A total of 154 patients were included in this study. The median door-to-skin time was 605 (interquartile range = 494-766) min. At discharge, 105 patients (68.2%) had poor outcomes. At the 6-month follow-up, only 58 patients (37.7%) remained to have poor outcomes. Simple logistic regression showed that polytrauma, hypotensive episode, ventilation, severe TBI, and the door-to-skin time were significantly associated with poor outcomes. After adjustments for the clinical characteristics in the analysis, the likelihood of having poor outcomes for every minute delay in the door-to-skin time increased at discharge (adjusted odds ratio [AOR] = 1.005; 95% confidence interval [CI] = 1.002-1.008) and the 6-month follow-up (AOR = 1.008; 95% CI = 1.005-1.011). Conclusion: The door-to-skin time is directly proportional to poor outcomes in patients with TBI. Concerted efforts from all parties involved in trauma care are essential in eliminating delays in surgical interventions and improving outcomes.

Failure Severity Prediction for Protective-Coating Disbondment via the Classification of Acoustic Emission Signals.

Structural health monitoring is a popular inspection method that utilizes acoustic emission (AE) signals for fault detection in engineering infrastructures. Diagnosis based on the propagation of AE signals along any surface material offers an attractive solution for fault identification. However, the classification of AE signals originating from failure events, especially coating failure (coating disbondment), is a challenging task given the AE signature of each material. Thus, different experimental settings and analyses of AE signals are required to classify the various types of coating failures, and they are time-consuming and expensive. Hence, to address these issues, we utilized machine learning (ML) classification models in this work to evaluate epoxy-based-protective-coating disbondment based on the AE principle. A coating disbondment experiment consisting of coated carbon steel test panels for the collection of AE signals was implemented. The obtained AE signals were then processed to construct the final dataset to train various state-of-the-art ML classification models to divide the failure severity of coating disbondment into three classes. Consequently, methods for the extraction of useful features, the handling of data imbalance, and a reduction in the bias of ML models were also effectively utilized in this study. Evaluations of state-of-the-art ML classification models on the AE signal dataset in terms of standard metrics revealed that the decision forest classification model outperformed the other state-of-the-art models, with accuracy, precision, recall, and F1 score values of 99.48%, 98.76%, 97.58%, and 98.17%, respectively. These results demonstrate the effectiveness of utilizing ML classification models for the failure severity prediction of protective-coating defects via AE signals.

Mitochondrial Replacement Therapy: An Islamic Perspective.

Mitochondrial replacement technology (MRT) is an emerging and complex bioethical issue. This treatment aims to eliminate maternal inherited mitochondrial DNA (mtDNA) disorders. For Muslims, its introduction affects every aspect of human life, especially the five essential interests of human beings-namely, religion, life, lineage, intellect, and property. Thus, this technology must be assessed using a comprehensive and holistic approach addressing these human essential interests. Consequently, this article analyses and assesses tri-parent baby technology from the perspective of Maqasidic bioethics-that is, Islamic bioethics based on the framework of Maqasid al-Shariah. Using this analysis, this article suggests that tri-parent baby technology should not be permitted for Muslims due to the existence of third-party cell gametes which lead to lineage mixing and due to the uncertain safety of the therapy itself and because the major aim of the technology is to fulfil the affected couples interest to conceive their own genetically healthy child, not to treat and cure mtDNA disorders sufferers.

Chronic Anterior Pituitary Dysfunction Following Traumatic Head Injury: Prospective Study in Hospital Sultanah Aminah Johor Bahru, Malaysia.

Background: Hypopituitarism following traumatic brain injury (TBI) is not rare however most patients were left undiagnosed and untreated. Association of post TBI hypopituitarism causing neurobehavioural and quality of life impairment. The aim of the study is to determine the incidence of the chronic anterior pituitary deficiency in patients with traumatic brain injury. Subsequently determine the risk factor and the outcome of the patient with chronic anterior pituitary dysfunction. Methods: This is single centre cross-sectional study involved 105 traumatic head injury patients under the Neurosurgical Department Hospital Sultanah Aminah, Johor Bahru, Malaysia. The primary investigator will do an interview and the patients will be asked question to complete a questioner from SF-36 (36 questions). Subsequently, consent for participation will be taken and blood sampling will be done. Results: Thirty-three patients were noted to have anterior pituitary dysfunction. The mean age was 36.97 ± 12.96 years old. Twenty-seven patients (32.5%) were male and six patients were female (27.3%). Chronic anterior pituitary dysfunction in patients with a severe traumatic head injury around 47.1% (23 patients), as compared to a moderate head injury (8 patients, 38.1%) and 2 sustained mild head injury (5.6%). The mean duration after the onset of trauma was 10.3 ± 1.79 months. All patient with anterior pituitary dysfunction had positive CT brain findings with 22 had subarachnoid haemorrhage (SAH) at the basal cistern and 27 patients had a base of skull fracture, where 52.1% of the patient underwent surgical intervention, 84.8% involved one axis and another 5 patients had two axes involved. Severity of the head injury (P < 0.001), prolonged duration of hospital stay (P = 0.014), radiological findings of a base of skull fracture (P < 0.001) and presence of SAH at basal cistern (P < 0.001) was significantly associated with pituitary dysfunction. The patient with anterior pituitary dysfunction has the lower 36-item Short Form Survey (SF-36) marks 56.3 ± 10.3. Conclusion: The prevalence of hypopituitarism was 31%. Indicators are increased TBI severity, prolonged hospitalisation and positive finding in radiological assessment. Post-traumatic chronic anterior pituitary dysfunction also related with poor quality of life as showed by low SF-36 marks.

Post-COVID-19 health-care utilization: one year after the 2020 first wave in Brunei Darussalam.

Objective: Patients who recover from coronavirus disease (COVID-19) infection are at risk of long-term health disorders and may require prolonged health care. This retrospective observational study assesses the number of health-care visits before and after COVID-19 infection in Brunei Darussalam. Methods: COVID-19 cases from the first wave with 12 months of follow-up were included. Health-care utilization was defined as health-care visits for consultations or investigations. Post-COVID condition was defined using the World Health Organization definition. Results: There were 132 cases; 59.1% were male and the mean age was 37.1 years. The mean number of health-care visits 12 months after recovery from COVID-19 (123 cases, 93.2%; mean 5.0 ± 5.2) was significantly higher than the prior 12 months (87 cases, 65.9%, P < 0.001; mean 3.2 ± 5.7, P < 0.001). There was no significant difference when scheduled COVID-19 visits were excluded (3.6 ± 4.9, P = 0.149). All 22 cases with moderate to critical disease recovered without additional health-care visits apart from planned post-COVID-19 visits. Six patients had symptoms of post-COVID condition, but none met the criteria for diagnosis or had alternative diagnoses. Discussion: There were significantly more health-care visits following recovery from COVID-19. However, this was due to scheduled post-COVID-19 visits as per the national management protocol. This protocol was amended before the second wave to omit post-COVID-19 follow-up, except for complicated cases or cases with no documented radiological resolution of COVID-19 pneumonia. This will reduce unnecessary health-care visits and conserve precious resources that were stretched to the limit during the pandemic.

Three-Dimensional (3D) Printing of Organs according to the Perspective of Islamic Law.

The outburst of the fourth Industrial Revolution had a significant impact on many aspects of life. The discovery of new technologies in medicine has resulted in innovations: organ transplants. The introduction of three-dimensional (3D) organ printing technology promises improvements to the field. Organs such as the liver, kidneys, heart and others are printed to meet the needs of the actual organs. However, the production of prototype organs to replace the original organs is associated with the issue of changing the creation of Allah. Accordingly, this study will analyse the issue of changing the creation of God in three-dimensional (3D) organ printing technology according to the perspective of Islamic law. Several appropriate methodologies in Islamic law (usul fiqh) are used such as legal reasoning through maqasid shariah perspective and analogical reasoning. The result shows that three-dimensional (3D) organ printing technology falls under the permissible category of changing the creation of Allah because it can save human lives. The production of organs through 3D printing involving changes included in the category of necessity (daruri) and need (hajiy) is permissible, but the category of desirable (tahsini) requires further specifications.

Determinants of consumer adoption of halal cosmetics: A systematic literature review.

BACKGROUND: The global halal cosmetics market is projected to grow during the forecast period. However, the factors that influenced consumers in the world to opt for halal cosmetics remain ambiguous. OBJECTIVES: The objective of this study was to understand the universal concept of halal cosmetics and a framework of critical points that influence consumers in purchasing halal cosmetic products. METHOD: The method used was Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) Statement by using Web of Science and Scopus databases. This study extends the systematic literature review covering all variables in purchasing halal cosmetics as halal cosmetic is not simply a religious issue, but it is also an opportunity to increase sales and acquire a competitive advantage. RESULTS: This study found 14 articles that mainly discussed the critical points related to religiosity and product factors, that is, ingredient, halal logo, and halal certification as the highest driver in influencing consumers to purchase halal cosmetics. Other related factors in this study are price, promotion, place, social factors, and characteristics of consumers. These factors should be taken into consideration as they provide a plus point and an extra edge to local or international manufacturers to tap the global markets for halal cosmetic products that cater to both Muslims and non-Muslims communities. PRACTICAL IMPLICATIONS: Cosmetic manufacturers and marketers must ensure that their products suit the expectation of consumers as todays halalan and tayyiban products are being searched rather than branded products due to their cleanliness, safety, and hygienic. ORIGINALITY/VALUE: This study is among the earliest study examining the factors of purchase intention in halal cosmetics using a systematic literature review method that integrates marketing stimulus (product, price, promotion, and place) and other stimuli (social, religious, and characteristics).

In Silico Identification of Promising New Pyrazole Derivative-Based Small Molecules for Modulating CRMP2, C-RAF, CYP17, VEGFR, C-KIT, and HDAC-Application towards Cancer Therapeutics.

Despite continual efforts being made with multiple clinical studies and deploying cutting-edge diagnostic tools and technologies, the discovery of new cancer therapies remains of severe worldwide concern. Multiple drug resistance has also emerged in several cancer cell types, leaving them unresponsive to the many cancer treatments. Such a condition always prompts the development of next-generation cancer therapies that have a better chance of inhibiting selective target macromolecules with less toxicity. Therefore, in the present study, extensive computational approaches were implemented combining molecular docking and dynamic simulation studies for identifying potent pyrazole-based inhibitors or modulators for CRMP2, C-RAF, CYP17, c-KIT, VEGFR, and HDAC proteins. All of these proteins are in some way linked to the development of numerous forms of cancer, including breast, liver, prostate, kidney, and stomach cancers. In order to identify potential compounds, 63 in-house synthesized pyrazole-derivative compounds were docked with each selected protein. In addition, single or multiple standard drug compounds of each protein were also considered for docking analyses and their results used for comparison purposes. Afterward, based on the binding affinity and interaction profile of pyrazole compounds of each protein, potentially strong compounds were filtered out and further subjected to 1000 ns MD simulation analyses. Analyzing parameters such as RMSD, RMSF, RoG and protein-ligand contact maps were derived from trajectories of simulated protein-ligand complexes. All these parameters turned out to be satisfactory and within the acceptable range to support the structural integrity and interaction stability of the protein-ligand complexes in dynamic state. Comprehensive computational analyses suggested that a few identified pyrazole compounds, such as M33, M36, M72, and M76, could be potential inhibitors or modulators for HDAC, C-RAF, CYP72 and VEGFR proteins, respectively. Another pyrazole compound, M74, turned out to be a very promising dual inhibitor/modulator for CRMP2 and c-KIT proteins. However, more extensive study may be required for further optimization of the selected chemical framework of pyrazole derivatives to yield improved inhibitory activity against each studied protein receptor.

Primary pilocytic astrocytoma of the cerebellopontine angle in pediatric patient with neurofibromatosis type 1: a case report.

Background: Cerebellopontine angle tumor (CPA) in pediatrics is rare as compared to adults. We describe a case of pediatric pilocytic astrocytoma presented as a right CPA mass with a concurrent clinical diagnosis of neurofibromatosis type 1 (NF1). Case presentation: A 14-year-old boy with a newly diagnosed hypertension presented with a short history of headache and blurring vision. Neurological examination revealed bilateral papilloedema, partial right third nerve palsy and mild sensorineuronal hearing deficits. Skin examination identified multiple café au lait spots with cutaneous neurofibromas. Preoperative neuroimaging suggested the diagnosis of an extraaxial CPA mass consistent with meningioma, with obstructive hydrocephalus. A left ventriculoperitoneal shunt was inserted and the child was subjected for a suboccipital retrosigmoid approach for tumor resection. The histopathological features, however, were typical for pilocytic astrocytoma. Conclusions: A careful evaluation of the clinical presentation and radiological images of CPA lesions is necessary prior to surgical embarkment. To the best of our knowledge, this case is the first report of pilocytic astrocytoma in the CPA in pediatric with NF1.

Identification of New Drug Target in Staphylococcus lugdunensis by Subtractive Genomics Analysis and Their Inhibitors through Molecular Docking and Molecular Dynamic Simulation Studies.

Staphylococcus lugdunensis is a coagulase-negative, Gram-positive, and human pathogenic bacteria. S. lugdunensis is the causative agent of diseases, such as native and prosthetic valve endocarditis, meningitis, septic arthritis, skin abscesses, brain abscess, breast abscesses, spondylodiscitis, post-surgical wound infections, bacteremia, and peritonitis. S. lugdunensis displays resistance to beta-lactam antibiotics due to the production of beta-lactamases. This study aimed to identify potential novel essential, human non-homologous, and non-gut flora drug targets in the S. lugdunensis strain N920143, and to evaluate the potential inhibitors of drug targets. The method was concerned with a homology search between the host and the pathogen proteome. Various tools, including the DEG (database of essential genes) for the essentiality of proteins, the KEGG for pathways analysis, CELLO V.2.5 for cellular localization prediction, and the drug bank database for predicting the druggability potential of proteins, were used. Furthermore, a similarity search with gut flora proteins was performed. A DNA-binding response-regulator protein was identified as a novel drug target against the N920143 strain of S. lugdunensis. The three-dimensional structure of the drug target was modelled and validated with the help of online tools. Furthermore, ten thousand drug-like compounds were retrieved from the ZINC15 database. The molecular docking approach for the DNA-binding response-regulator protein identified ZINC000020192004 and ZINC000020530348 as the most favorable compounds to interact with the active site residues of the drug target. These two compounds were subjected to an MD simulation study. Our analysis revealed that the identified compounds revealed more stable behavior when bound to the drug target DNA-binding response-regulator protein than the apostate.

Multi-epitope chimeric vaccine design against emerging Monkeypox virus via reverse vaccinology techniques- a bioinformatics and immunoinformatics approach.

The emerging monkeypox virus (MPXV) is a zoonotic orthopoxvirus that causes infections in humans similar to smallpox. Since May 2022, cases of monkeypox (MPX) have been increasingly reported by the World Health Organization (WHO) worldwide. Currently, there are no clinically validated treatments for MPX infections. In this study, an immunoinformatics approach was used to identify potential vaccine targets against MPXV. A total of 190 MPXV-2022 proteins were retrieved from the ViPR database and subjected to various analyses including antigenicity, allergenicity, toxicity, solubility, IFN-γ, and virulence. Three outer membrane and extracellular proteins were selected based on their respective parameters to predict B-cell and T-cell epitopes. The epitopes are conserved among different strains of MPXV and the population coverage is 100% worldwide, which will provide broader protection against various strains of the virus globally. Nine overlapping MHC-I, MHC-II, and B-cell epitopes were selected to design multi-epitope vaccine constructs linked with suitable linkers in combination with different adjuvants to enhance the immune responses of the vaccine constructs. Molecular modeling and structural validation ensured high-quality 3D structures of vaccine constructs. Based on various immunological and physiochemical properties and docking scores, MPXV-V2 was selected for further investigation. In silico cloning revealed a high level of gene expression for the MPXV-V2 vaccine within the bacterial expression system. Immune and MD simulations confirmed the molecular stability of the MPXV-V2 construct, with high immune responses within the host cell. These results may aid in the development of experimental vaccines against MPXV with increased potency and improved safety.

An insight in Salmonella typhi associated autoimmunity candidates' prediction by molecular mimicry.

Autoimmune diseases develop when the immune system targets healthy cells and tissues of an individual. In developing countries, S. typhi (a gram-negative pathogenic bacteria) remains a major public health issue. This study aimed to employ bioinformatics analyses to determine the 3D structural-based molecular mimicry and sequence of S. typhi and human host proteins. In addition, to classify possible antigenic microbial peptides homologous to human peptides and comprehend the molecular basis of S. typhi-related autoimmune disorders. Protein sequences were obtained from the NCBI database, and redundancy was removed using the CD-HIT tool. The BLASTp comparative sequence analysis was followed for molecular mimicry identification of human and S. typhi protein sequences. The PathDIP database was utilized to simulate essential physical relationships between proteins and curated pathways for metabolic processes. Subsequently, the IEDB database was used to find cross-reactive MHC class-II binding epitopes that could trigger an autoimmune reaction. SPARKS-X computational biology resource was also used to determine the structural homology between human and S. typhi peptides. The BLASTp study showed that S. typhi and the human host have several proteins holding considerable sequence similarities based on a set threshold of e ≤ 10-6 and bit score ≥100. The PathDIP putatively identified that these proteins enriched in a total of 68 metabolic pathways by a significant P-value (P < 0.005). The PSORTb analysis predicted that 26 out of these proteins are cytosolic, 1 predicted to be periplasmic protein, and 1 predicted to be localized in the cytoplasmic membrane. IEDB data analysis predicted many S.typhi and human homologs epitopes as a good binder of human HLA, i.e. DRB1*01:01, DPA1*03:01/DPB1*04:02, and DQA1*01:02/DQB1*06:02 with IC50 < 50 nM. Finally, the docking data demonstrated that homolog lead epitopes promisingly interact with HLA and immune TLR4 receptors by exhibiting the best docking scores and molecular interactions. The analyses ultimately identified several potential candidate proteins and peptides that could cause S.typhi infection-mediated autoimmune diseases in humans.

Experimental evaluation of fracture properties of bovine hip cortical bone using elastic-plastic fracture mechanics.

BACKGROUND: Understanding the fracture mechanics of bone is very important in both the medical and bioengineering field. Bone is a hierarchical natural composite material of nanoscale collagen fibers and inorganic material. OBJECTIVE: This study investigates and presents the fracture toughness of bovine cortical bone by using elastic plastic fracture mechanics. METHODS: The J-integral was used as a parameter to calculate the energies utilized in both elastic deformation (Jel) and plastic deformation (Jpl) of the hipbone fracture. Twenty four different types of specimens, i.e. longitudinal compact tension (CT) specimens, transverse CT specimens, and also rectangular unnotched specimens for tension in longitudinal and transverse orientation, were cut from the bovine hip bone of the middle diaphysis. All CT specimens were prepared according to the American Society for Testing and Materials (ASTM) E1820 standard and were tested at room temperature. RESULTS: The results showed that the average total J-integral in transverse CT fracture specimens is 26% greater than that of longitudinal CT fracture specimens. For longitudinal-fractured and transverse-fractured cortical specimens, the energy used in the elastic deformation was found to be 2.8-3 times less than the energy used in the plastic deformation. CONCLUSION: The findings indicate that the overall fracture toughness measured using the J-integral is significantly higher than the toughness calculated by the stress intensity factor. Therefore, J-integral should be employ to compute the fracture toughness of cortical bone.

Prevalence and Associated Factors of Diabetic Retinopathy among Type 2 Diabetes Mellitus Patients in Brunei Darussalam: A Cross-sectional Study.

PURPOSE: To determine the prevalence of diabetic retinopathy (DR) and the factors associated with retinopathy among type 2 diabetes mellitus (DM) patients in Brunei Darussalam. METHODS: Cross-sectional study of all type 2 DM patients who attended diabetic eye screening over a 3-month period at one of four government hospitals. We assessed association between DR with the following variables: age, sex, glycated hemoglobin (HbA1c), duration of DM, hypertension, hyperlipidemia, and microalbuminuria. RESULTS: There were 341 patients (female, 58.9%; mean age, 55.3 ± 11.9 years) with a mean duration of DM of 9.4 ± 7.4 years and mean serum HbA1c of 8.4% ± 1.9%. The overall prevalence of any DR was 22.6% (95% confidence interval, 18.8-27.1) with prevalence rates of 4.1% (95% confidence interval, 2.1-6.4) for proliferative DR and 9.7% (95% confidence interval, 6.8-13.2) for vision-threatening DR. Multivariate analysis showed that DR was significantly associated with certain age groups (reduced in older age groups), longer duration of DM (11 years or more), poor control (HbA1c >9.0%) and presence of any microalbuminuria. CONCLUSIONS: DR affects one in five patients with DM in Brunei Darussalam, comparable to rates reported for other Asian populations. It is especially worrying that one in ten patients with DM had vision-threatening DR. DR was significantly associated with longer duration of DM, poor control and presence of microalbuminuria but reduced in older age groups. It is important to advocate good control right from the time of diagnosis of DM and institute timely and effective management of retinopathy. DR was significantly associated with longer duration of DM, poor control of diabetes, and presence of microalbuminuria but reduced in older age groups.