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In this research, synthesis and assessment of the mechanical and wear possessions of Al7049-nano B4C composites are determined by experiments. Using the liquid metallurgy route, a stir casting technique was used to create composites with increasing concentrations of nano B4C from 3 to 9 weight %. Each composite's reinforcement particles were heated to 400 degrees Celsius before being added to the molten Al7049 alloy in two separate steps, i.e., two-stage stir casting to optimise wettability and distribution. Scanning electron microscopy (SEM) was utilised to examine the microstructure, and energy dispersive spectroscopy (EDS) was utilised to determine the elemental make-up. Mechanical characteristics of composites were determined by subjecting them to tensile, compression, and hardness tests. Wear tests were conducted as per ASTM G99 standards with varying loads and speeds. Nanosized B4C particles were found to be dispersed throughout the sample space in a microstructural analysis. Hardness, ultimate strength, yield strength, and compression strength of Al7049 alloy composites were found to increase significantly as the weight percentage of nano B4C was increased. Additionally, compared to the unreinforced form, the ductility of the Al7049 alloy composites was slightly reduced. SEM micrographs of tensile-fractured specimens were used for research into the field of tensile fractography. Nano B4C reinforced composites exhibited superior wear resistance as compared to Al7049 alloy. These prepared composites can be used for wing root fitting of an aircraft. [ABSTRACT FROM AUTHOR]

Solid-state diffusion bonding of AA2219 alloy is carried out under the nonvacuum condition to form AA2219/AA2219 joints. In the currently adopted method, AA2219 alloys are joined under the bonding temperature of 450–500°C, bonding pressure of 10 MPa, and bonding time of 30 min. Chemical cleaning is adopted to protect the joining surfaces from reoxidation before the diffusion bonding process. Microstructure evolution at the bonded joints is characterized using optical microscopy, scanning electron microscopy (SEM), and energy dispersive spectroscopy (EDS). The hardness at the bonded joints increased with the increase in the bonding temperature. The parent metal structure is achieved at 500°C bonding temperature with an increase in hardness of 112.14 Hv at the bond interface. There is no evidence of intermetallic found at the interface, as confirmed by X-ray diffraction (XRD). [ABSTRACT FROM AUTHOR]

The present study was conducted to evaluate the extent of postmortem proteolysis in longissimus dorsi , biceps femoris , semimembranosus and semitendinosus goat muscles on postmortem aging at an ambient (27C) temperature. The activities of calpains and calpastatin were determined after separation on a (diethylamino)ethyl–Sephacel column (Sigma, St. Louis, MO) and cathepsin (B, B + L and H) by carboxymethyl–Sepharose column (Sigma). The results showed that the decrease in calpain I and calpastatin activities was significantly higher than that of calpain II. Cathepsin B, B + L, H and cystatin were found to fall by 30–80% after 12 h, whereas cathepsin D decreased significantly in all the muscles. The disappearance of titin 1 and nebulin, and the appearance of a 30-kDa component were confirmed by Western blot analysis. The appearance of the 30-kDa component reported here explains the time-induced structural changes of myofibrils. The Z-line degradation had occurred by 6 h postmortem. Cathepsins are not stable compared to calpains during postmortem aging, and both enzymes may play a significant role in the proteolysis of myofibrillar proteins at ambient temperature. [ABSTRACT FROM AUTHOR]

This study was conducted to evaluate the effect of postmortem aging on pH, temperature, drip loss, sarcomere length, myofibrillar fragmentation index (MFI), myofibrillar protein solubility, released calcium and myofibrillar adenosinetriphosphatase (ATPase) activity in longissimus dorsi (LD), biceps femoris (BF), semimembranosus (SM) and semitendinosus (ST) muscles of goat maintained at 5C up to 20 days postmortem. The results showed that the rates of pH decline, temperature and sarcomere length decreased during aging. There was a significant increase in drip loss of LD, BF, SM and ST at 3, 6 and 9 days, respectively. The increased MFI followed a pattern of LD > ST > BF > SM at 20 days postmortem. The myofibrillar ATPase activity rapidly decreased between 0.1 and 0.2 M ionic strength in all the muscles. The biochemical index of myofibrillar aging (BIMA) value of LD, BF and SM muscles was constant after 9 days postmortem. The results obtained here describe a close relationship between rate of pH decline, decreased sarcomere length and increased MFI and BIMA value during postmortem aging. Therefore, the biochemical indices described in this article could be used as indicators of the degree of aging of the goat myofibrillar structure. [ABSTRACT FROM AUTHOR]

The effects of frozen storage on the biochemical properties of myofibrils, muscle proteinases (cathepsins and calpains) and their endogenous inhibitors were investigated. Longissimus dorsi , biceps femoris , semimembranosus and semitendinosus muscles from goat were frozen (−15C) and studied up to 120 days. The results showed that the percentage change in sarcomere length was 8.4–13.1. The calpain activity was determined after separation on a diethylaminoethyl–Sephacel column (Sigma, St. Louis, MO). Significantly greater percentage of calpain II activity was recovered when compared to calpain I. There was a 15–25% loss in calpastatin inhibitory activity, and the cystatin level fell by 11–16% after 80 days. Cathepsin B, B + L, H and D were very stable when compared to calpains. The calcium concentration may also be the factor for calpain activation. The sodium dodecyl sulfate–polyacrylamide gel electrophoresis result showed the appearance of 55 kDa components. It was concluded that calpains, not cathepsins, play an important role in the proteolysis of myofibrillar proteins at the freezing temperature. [ABSTRACT FROM AUTHOR]

Sickle cell disease (SCD) is a complex genetic blood disorder characterized by abnormal haemoglobin, resulting in sickle-shaped red blood cells. While extensive research has concentrated on the genetic and physiological aspects of SCD, recent studies suggest a potential role of the human microbiome in SCD pathophysiology, adding new dimensions to its understanding. This review synthesizes current knowledge on the microbiome's involvement in SCD, focusing on alterations in the gut microbiome composition and diversity compared to healthy individuals, and their implications for disease pathogenesis. We explore how microbiome changes may contribute to vaso-occlusive crises and other complications, along with the possible associations of specific microbial taxa or markers with disease crises and clinical outcomes. Additionally, we discuss the potential of microbiome-targeted interventions, including probiotics, dietary modifications, and faecal microbiota transplantation, in managing SCD complications and improving patient outcomes. Understanding the intricate relationship between the microbiome and SCD could lead to innovative therapeutic strategies and personalized interventions for better managing the disease. This review underscores the importance of further microbiome research and its integration into holistic SCD care., (© 2024 British Society for Haematology and John Wiley & Sons Ltd.)

Major depressive disorder (MDD) is one of the most severe global health problems with millions of people affected, however, the mechanisms underlying this disorder is still poorly understood. Genome-wide association studies have highlighted a link between the neutral amino acid transporter SLC6A15 and MDD. Additionally, a number of preclinical studies support the function of this transporter in modulating levels of brain neurotransmitters, stress system regulation and behavioural phenotypes related to MDD. However, the molecular and functional mechanisms involved in this interaction are still unresolved. Therefore, to investigate the effects of the SLC6A15 transporter, we used hippocampal tissue from Slc6a15-KO and wild-type mice, together with several in-vitro assays in primary hippocampal neurons. Utilizing a proteomics approach we identified differentially regulated proteins that formed a regulatory network and pathway analysis indicated significantly affected cellular domains, including metabolic, mitochondrial and structural functions. Furthermore, we observed reduced release probability at glutamatergic synapses, increased mitochondrial function, higher GSH/GSSG redox ratio and an improved neurite outgrowth in primary neurons lacking SLC6A15. In summary, we hypothesize that by controlling the intracellular concentrations of neutral amino acids, SLC6A15 affects mitochondrial activity, which could lead to alterations in neuronal structure and activity. These data provide further indication that a pharmacological or genetic reduction of SLC6A15 activity may indeed be a promising approach for antidepressant therapy., (© 2020 The Authors. European Journal of Neuroscience published by Federation of European Neuroscience Societies and John Wiley & Sons Ltd.)

Background: Long-term follow-ups after receiving lycopene therapy for management of oral submucous fibrosis (OSMF) are scarce. The study aimed to assess the long-term efficacy of lycopene for management of OSMF symptoms., Methods: In this prospective clinical study, 400 clinically diagnosed early OSMF patients were assessed for the efficacy of lycopene in alleviation of burning sensation (BS) and reduced mouth opening (MO) symptoms in comparison to placebo. After 1-year follow-up, group A (lycopene group) was divided equally into group A1 and group A2. group A1 patients were retreated with lycopene and the A2 group was followed without retreatment. After 2-year follow-up, the Group A2 patients were advised retreatment but not followed as most of the patient did not agree for follow-up. However, group A1 patients were continued to follow-up every 6 months for a total three years. Statistical analysis was by independent sample t-test and P-value <.05 were considered as significant., Results: A statistically significant difference (P < .05) in BS and MO was found between group A and B with lycopene showing better results. At one-year follow-up, a statistically significant recurrence in the symptoms was found (P < .05) in the lycopene group (group A). After the second intervention, there was a statistically significant difference in the improvement of symptoms between the group A1 and A2 at 6 months and 1 year (P < .05) with group A1 (retreatment) showing better results., Conclusions: Treatment with lycopene led to improvement in the symptoms of OSMF in the present study. The results highlight the importance of retreatment of lycopene for its long-term effect on alleviation the symptoms of OSMF., (© 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Machine learning (ML) is powerful tool that can identify and classify patterns from large quantities of cancer genomic data that may lead to the discovery of new biomarkers, new drug targets, and a better understanding of important cancer genes. The aim of this systematic review was to evaluate the existing literature and assess the application of machine learning of genomic data in head and neck cancer (HNC)., Materials and Methods: The addressed focused question was "Does machine learning of genomic data play a role in prognostic prediction of HNC?" PubMed, EMBASE, Scopus, Web of Science, and gray literature from January 1990 up to and including May 2018 were searched. Two independent reviewers performed the study selection according to eligibility criteria., Results: A total of seven studies that met the eligibility criteria were included. The majority of studies were cohort studies, one a case-control study and one a randomized controlled trial. Two studies each evaluated oral cancer and laryngeal cancer, while other one study each evaluated nasopharyngeal cancer and oropharyngeal cancer. The majority of studies employed support vector machine (SVM) as a ML technique. Among the included studies, the accuracy rates for ML techniques ranged from 56.7% to 99.4%., Conclusion: Our findings showed that ML techniques for the analysis of genomic data can play a role in the prognostic prediction of HNC., (© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Introduction: Shammah is a form of smokeless tobacco commonly used in the Arabian Peninsula. The data on the harmful effects of shammah on oral health, particularly oral malignancies, are scarce. The aim of this review was to explore the association between shammah use and development of oral potentially malignant disorders (OPMD) and/or oral cancer., Materials and Methods: PubMed, EMBASE, Scopus, Web of Science and grey literature from January 1990 up to and including April 2018 were searched. Two independent reviewers performed the study selection according to eligibility criteria., Results: A total of 10 studies that met the eligibility criteria were included. The odds of developing OPMD and/or oral cancer in relation to shammah use varied, with one study reporting a 39 increased risk (39, 95% CI: 14-105). The associated increased risk was relatively low among those that have stopped using shammah and ranged from threefold (3.65; 95% CI: 1.40-9.50) to 12-fold (12.6; 95% CI: 3.3-48.2)., Conclusion: Shammah use seems to increase the risk of development of OPMD and/or oral cancer., (© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Despite much research, there is a lack of a definite protocol or method for documenting oral submucous fibrosis (OSMF) site presentation. In this study, we propose a new potential oral mapping (OM) method and evaluated its use in recording OSMF-affected mucosal sites., Methods: Fifty OSMF patients were evaluated by 15 primary care dental practitioners using both, a conventional subjective recording method and a new OM method, to document the degree of involvement of affected oral mucosa with a crossover study design. Mann-Whitney test (non-parametric test) was used to make comparison between groups to determine any significant differences between the two identification methods. Wilcoxon tests were used to evaluate any significant differences in the difficulty in identification of two methods., Results: There was a low agreement between the two methods used to detect OSMF in affected mucosal surfaces (P-value < 0.0001). More lesions were identified using the proposed OM method, and less discrepancy was found among dental practitioners. A difference in difficulty of OSMF documentation was found (Wilcoxon z = 3.615, P-value < 0.001), with the proposed OM method found to be easier., Conclusion: The proposed OM method appears to be useful for documentation, can easily be adapted in clinical practice, and effectively administered in clinical research. Additionally, it could be a useful tool to helping to maintain an OSMF database., (© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Introduction: Critical evidence on the therapeutic efficacy of botulinum toxins (BTX) is still lacking for most pain conditions. The aim of this review was to evaluate the therapeutic efficacy of BTX in the management of temporomandibular myofascial pain., Materials and Methods: Electronic databases PubMed, EMBASE, Scopus, Web of Science, and gray literature were searched for randomized clinical trials until February 2018 to answer a focused question "What is the effectiveness of botulinum toxin in the management of temporomandibular myofascial pain?" Two independent reviewers performed the study selection according to eligibility criteria., Results: A total of seven studies that met the eligibility criteria were included. Two studies showed a significant improvement in temporomandibular myofascial pain, and one study showed equal efficacy of BTX in comparison with facial manipulation, while the remaining studies did not report any significant difference between BTX and control group. Due to heterogeneity in the methodology and outcome assessment, a meta-analysis and recalculation of risk could not be performed., Conclusion: Based on our findings, the therapeutic efficacy of BTX was unclear. Randomized controlled trials with better methodological criteria need to be carried out to evaluate the real effectiveness of BTX., (© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Cardiac metastasis of Ewing's sarcoma is exceedingly rare. A 40-year-old male was admitted with complaints of nonproductive cough, exertional dyspnea, and fatigue since 4 months with a history of abdominal wall swelling which was excised and proven to be Ewing's sarcoma/primitive neuroectodermal tumor (PNET). A transthoracic echocardiography demonstrated inhomogeneous mass located posterior to the left ventricle and a solitary mass protruding into the left atrium through the left inferior pulmonary vein. Due to accompanying pulmonary metastasis and possible poor outcome of the surgery, surgical resection was not considered., (© 2018 Wiley Periodicals, Inc.)

Aims: To determine the factors at general practice level that relate to glycaemic control outcomes in people with type 2 diabetes (T2DM)., Methods: Data were accessed from 4050 general practices (50% of total) covering 1.6 million patients with T2DM in the UK National Diabetes Audit 2013 to 2014 and 2014 to 2015. This audit reported characteristics, services and outcomes in the T2DM population, including percentage of patients who had total glycaemic control (TGC), defined as glycated haemoglobin (HbA1c) ≤7.5% (58 mmol/mol), and the percentage who were at higher glycaemic risk (HGR), defined as HbA1c >10% (86 mmol/mol); the respective figures were 67.2% and 6.2%. The medication data were examined in terms of annual defined daily doses (DDDs). Multivariate linear regression analysis was used to identify associations between DDD and patient and practice characteristics., Results: Over the period 2012/2013 to 2015/2016, patient numbers grew 4% annually and annual medication expenditure by 8%, but glycaemic control outcomes did not improve. The main findings were that practices with better outcomes: had a higher percentage of patients aged >65 years; provided more effective diabetes services (including case identification, care checks, patient education, percentage of patients with blood pressure and cholesterol under control and more patients with type 1 diabetes achieving target HbA1c levels); spent less overall on prescribing per patient with T2DM; and on average, prescribed fewer sulphonylureas, less insulin (for patients with T2DM), fewer glucagon-like peptide-1 agonists, more metformin, more dipeptidyl peptidase-4 inhibitors, and more blood glucose monitoring strips. Ethnicity and social disadvantage and levels of thiazolidinedione (glitazone) prescribing had no significant impact on outcomes. Sodium-glucose co-transporter-2 inhibitor use was too low for an effect to be observed in the period examined., Conclusions: If all practices brought their service and medication to the level of the top decile practices, they could achieve 74.7% compared with the median of 67.3% of patients achieving TGC, showing an increase of 213 000 in patients achieving TGC, while reducing the number at HGR to 3.8% compared with 6.1%, benefiting 62 000 patients. This could have a major impact on the overall consequent healthcare costs of managing diabetes complications with their attendant mortality risks., (© 2017 John Wiley & Sons Ltd.)

Sulfhydryl groups of platelet surface proteins are important in platelet aggregation. While p-chloromercuribenzene sulphonate (pCMBS) has been used in most studies on platelet surface thiols, the specific thiol-proteins that pCMBS reacts with to inhibit aggregation have not been well defined. Since the thiol-containing P2Y(12) ADP receptor is involved in most types of platelet aggregation, we used the ADP scavenger apyrase and the P2Y(12) receptor antagonist 2-MeSAMP to examine thiol-dependent reactions in the absence of contributions from this receptor. We provide evidence for a non-P2Y(12) thiol-dependent reaction near the final alphaIIbbeta3-dependent events of aggregation. We then used 3-(N-maleimidylpropionyl)biocytin (MPB) and pCMBS to study thiols in alphaIIbbeta3. As previously reported, disruption of the receptor was required to obtain labelling of thiols with MPB. Specificity of labelling for thiols in the alphaIIb and beta3 subunits was confirmed by identification of the purified proteins by mass spectrometry and by inhibition of labelling with 5,5'-dithiobis-(2-nitrobenzoic acid). In contrast to MPB, pCMBS preferentially reacted with thiols in alphaIIbbeta3 and blocked aggregation under physiological conditions. Similarly, pCMBS preferentially inhibited signalling-independent activation of alphaIIbbeta3 by Mn(2+). Our results suggest that the thiols in alphaIIbbeta3 that are blocked by pCMBS are important in the activation of this integrin.

Platelet protein disulphide isomerase (PDI) has a role in platelet aggregation, probably targeting a thiol-containing platelet surface protein. The thiol-containing P2Y(12) ADP receptor is involved in aggregation induced by most agonists and may be the target of PDI. By excluding the P2Y(12) pathway and using the anti-PDI antibody RL90 this study showed that PDI targets a non-P2Y(12) thiol-protein in aggregation. Anti-PDI inhibited signalling-independent activation of the thiol-containing fibrinogen receptor alphaIIbbeta3 by Mn(2+), suggesting that PDI directly interacts with alphaIIbbeta3. The thiol-containing form of PDI increased on the platelet surface with platelet activation, suggesting that active PDI readily becomes available for redox regulation of alphaIIbbeta3. Finally, using purified proteins PDI had greater ability to isomerize disulphide bonds than the alphaIIbbeta3 integrin, which also has PDI-like activity. In summary, a mechanism exists in platelets to increase the functional form of surface PDI and this PDI has a non-P2Y(12) target that may be alphaIIbbeta3.