Autoregulation of insulin receptor signaling through MFGE8 and the αvß5 integrin.

The role of integrins, in particular αv integrins, in regulating insulin resistance is incompletely understood. We have previously shown that the αvß5 integrin ligand milk fat globule epidermal growth factor like 8 (MFGE8) regulates cellular uptake of fatty acids. In this work, we evaluated the impact of MFGE8 on glucose homeostasis. We show that acute blockade of the MFGE8/ß5 pathway enhances while acute augmentation dampens insulin-stimulated glucose uptake. Moreover, we find that insulin itself induces cell-surface enrichment of MFGE8 in skeletal muscle, which then promotes interaction between the αvß5 integrin and the insulin receptor leading to dampening of skeletal-muscle insulin receptor signaling. Blockade of the MFGE8/ß5 pathway also enhances hepatic insulin sensitivity. Our work identifies an autoregulatory mechanism by which insulin-stimulated signaling through its cognate receptor is terminated through up-regulation of MFGE8 and its consequent interaction with the αvß5 integrin, thereby establishing a pathway that can potentially be targeted to improve insulin sensitivity.

Protective effects of a polyherbal medicine, Majoon Suranjan against bisphenol-A induced genetic, oxidative and tissue damages.

Bisphenol-A (BPA) is a toxic chemical largely produced and used in polycarbonate plastics worldwide. Majoon Suranjan (MS), a polyherbal formulation, is used as an anti-inflammatory medicine against rheumatoid arthritis. The present study aimed to evaluate BPA-induced toxicity and its possible amelioration by MS. To test our hypothesis, we performed gas chromatography-mass spectrometry (GC-MS) analysis, DNA interaction studies, genotoxicity tests, oxidative stress parameters, and histopathological examinations. GC-MS profiling of MS revealed the presence of various anti-oxidant compounds. DNA interaction studies showed that both chemicals intercalate between DNA base pairs. Next, we observed BPA-induced genotoxicity and oxidative damage. The observed effects might be due to BPA-induced reactive oxygen species production. Further, BPA changed the anti-oxidant enzyme activities, increased the malondialdehyde, alanine aminotransferase, alkaline phosphatase, and total bilirubin levels, and caused gross damage to the liver and kidney. Interestingly, these effects were significantly reversed by MS. In conclusion, MS shows protective effects against BPA-induced toxicity and could be a potential alternative medicine against BPA toxicity, especially in third-world countries where BPA uses are not strictly regulated.Highlights:Bisphenol-A (BPA) induces multiple toxic effects.BPA induces genotoxicity, oxidative and tissue damage.Majoon Suranjan (MS) ameliorates the BPA induced toxic effects.GC-MS profiling show various active anti-oxidant compounds in MS.MS is anti-genotoxic, anti-oxidant, and hepato-renal protective.

EPA Consensus Project Paper: Do Implant- Supported/Retained Prostheses Improve the Quality of Life of Patients with Intraoral Maxillofacial Defects? - A Systematic Review.

BACKGROUND: There is limited evidence available regarding patient satisfaction and quality of life assessment in patients with intraoral maxillofacial defects managed with maxillofacial prostheses. OBJECTIVES: This systematic review aims to understand the impact of intraoral implant prostheses in improving the quality of life in patients with intraoral maxillofacial defects/abnormalities. METHODS: A comprehensive search was performed of nine electronic databases from January 1970 to August 2022. Hand searching of the reference lists of the included papers and of relevant journal publications between 2012 and 2022 was also undertaken. Key information was extracted from included studies alongside quality and risk of bias assessments. RESULTS: The systematic review encompassed a total of seven studies, comprising five retrospective and two prospective investigations, with one of the prospective studies being a randomised clinical trial. The evaluation of the risk of bias and quality assessment revealed heterogeneity in the results, preventing meaningful comparisons among the included studies. CONCLUSION: Within the limitation of the systematic review, there is limited evidence to suggest that implant prostheses improve the quality of life in patients with intraoral maxillofacial defects or abnormalities.

Analysis of anti-apoptotic PVT1 oncogene and apoptosis-related proteins (p53, Bcl2, PD-1, and PD-L1) expression in thyroid carcinoma.

BACKGROUND: An aberrant expression of long non-coding RNA PVT1 has been associated with apoptosis in various cancer types. We aimed to explore the PVT1 and four apoptosis-related proteins (p53, Bcl2, and PD-1/PD-L1) signature in thyroid cancer (TC). METHODS: The PVT1 expression level was measured in 64 FFPE TC paired samples by real-time quantitative PCR. Overall and stratified analyses by different clinicopathological features were done. The apoptotic proteins were evaluated by immunohistochemistry staining. RESULTS: Overall analysis showed significant PVT1upregulation in TC tissues (p < 0.001). Similarly, subgroup analysis by BRAFV600E mutation showed consistent results. Lower expression of p53 was associated with mortality (p = 0.001). Bcl2 overexpression was associated with greater tumor size (p = 0.005). At the same time, HCV-positive cases were associated with repressed Bcl2 expression levels (54.3% in HCV-negative vs. 6.9% in HCV-positive cases, p = 0.011). PD-1 expression was associated with lymph node metastasis (p = 0.004). Enhanced PD-L1 expression in the tumor was associated with a higher tumor stage, lymphovascular invasion, and mortality risk. Kaplan-Meier curves for overall survival showed that low p53 and high PD-L1 expressions were associated with lower survival time. The p53-positive staining is associated with a 90% decreased mortality risk (HR = 0.10, 95%CI = 0.02-0.47, p = 0.001), while patients with high PD-L1 were five times more likely to die (HR = 4.74, 95%CI = 1.2-18.7, p = 0.027). CONCLUSION: Our results confirm the upregulation of PVT1 in TC. The apoptosis-related proteins (p53, Bcl2, and PD-1/PD-L1) showed different prognostic utility in TC patients; in particular, low p53 and high PD-L1 expressions associated with low survival times. Further large-scale and mechanistic studies are warranted.

Randomized preclinical study of machine perfusion in vascularized composite allografts.

BACKGROUND: Attempts to improve limb preservation for transplantation using ex vivo perfusion have yielded promising results. However, metabolic acidosis, aberrant perfusate biochemistry and significant perfusion-induced oedema are reported universally. Optimizing perfusion protocols is therefore essential for maintaining tissue health. METHODS: A randomized, two-stage open preclinical trial design was used to determine the optimal temperature and mean arterial pressure for machine perfusion. Conditions compared were: normothermic machine perfusion at 70 mmHg (NMP-70); subnormothermic perfusion (28°C) at 70 mmHg; subnormothermic (28°C) perfusion at 50 mmHg; and hypothermic perfusion (10°C) at 30 mmHg. Following this, a head-to-head experiment was undertaken comparing the optimal machine perfusion with static cold storage. Paired bilateral limbs (10 in total) were randomized to either 8 h of static cold storage, or 2 h of static cold storage and 6 h of optimal machine perfusion. Both groups of limbs were then reperfused on a circuit primed with matched blood from unrelated donors for 4 h without immunosuppression. RESULTS: NMP-70 resulted in less tissue injury and stable perfusion biochemistry. Assessing reperfusion outcomes, static cold storage resulted in acidosis with increased lactate and a worsening electrolyte profile, necessitating bolus infusions of bicarbonate to prevent graft loss. Conversely, NMP-70 was associated with haemodynamic and biochemical stability. Histologically, on reperfusion with allogeneic whole blood, limbs subjected to static cold storage exhibited multifocal ischaemic injury and increased inflammation, which was absent with NMP-70. Static cold storage also resulted in significant oedema compared with NMP-70. CONCLUSION: Normothermic perfusion resulted in superior graft preservation and less reperfusion injury compared with the current static cold storage protocol.

Efficacy of Fungicides Applied for Protectant and Curative Activity Against Myrtle Rust.

Myrtle rust, caused by the pathogen Austropuccinia psidii, affects species of the Myrtaceae, many of which are endemic to Australia and New Zealand. Originating from South America, A. psidii is now present in both countries, necessitating effective chemical control for disease management. Using an artificial inoculation protocol, the efficacy of eight fungicides (tebuconazole/trifloxystrobin, cyproconazole/azoxystrobin, fosetyl aluminum, triforine, triadimenol, oxycarboxin, copper, and tebuconazole) applied as curative or protectant treatments was tested on two native New Zealand species (Lophomyrtus × ralphii and Metrosideros excelsa). The impacts of rate (×2), frequency (single or double), and timing (pre- or postinfection) of fungicide application were investigated. Overall, the most effective fungicides tested across both species were those that included a demethylation inhibitor and strobilurin mix, notably tebuconazole/trifloxystrobin (Scorpio) and cyproconazole/azoxystrobin (Amistar Xtra). These fungicides significantly reduced infection of host plants relative to the water control. Timing of application significantly affected bioefficacy, with applications made 7 days before inoculation or 7 days after inoculation being generally the most effective. The rate of fungicide application was not significant for both host species, with few interaction terms showing overall significance. Key findings from this study will set the foundation for further fungicide bioefficacy research conducted to evaluate formulations and adjuvant mixtures, determine suitable application methods for enhanced retention and coverage, and derive optimum application time for effective protection of native and exotic Myrtaceae species in New Zealand.

Investigation of methicillin-resistant Staphylococcus aureus among clinical isolates from humans and animals by culture methods and multiplex PCR.

BACKGROUND: Staphylococcus aureus is responsible for large numbers of hospital-related and community-acquired infections. In this study, we investigated the presence of S. aureus and methicillin-resistant S. aureus (MRSA) in 100 samples from animals (55 cattle, 36 dogs, and 9 cats) and 150 samples from hospitalized human patients. The samples were collected from healthy and diseased animals and from diseased humans and included milk, wound swab, pus, exudates, nasal swab and diabetic ulcer. Initially, S. aureus was isolated and identified by colony morphology, Gram staining, and biochemical tests (catalase and coagulase tests). The S. aureus-positive samples were examined by polymerase chain reaction (PCR) to determine their MRSA status. RESULTS: Of the 100 animal samples, 29 were positive for S. aureus. Four samples (13.8%) from dogs were MRSA-positive, but samples from cattle and cats were MRSA-negative. Of the 150 human samples we collected, 64 were S. aureus-positive and, of these, 34 (53.1%) were MRSA-positive. Most (28%) of the MRSA samples were isolated from surgical wound swabs, followed by the pus from skin infections (11%), exudates from diabetic ulcers (6%), exudates from burns (4%), and aural swabs (3%). By contrast, a low MRSA detection rate (n = 4) was seen in the non-human isolates, where all MRSA bacteria were isolated from nasal swabs from dogs. The antimicrobials susceptibility testing results showed that S. aureus isolates with mecA genes showed resistance to penicillin (100%), oxacillin (100%), erythromycin (73.5%), ciprofloxacin (70.6%), and gentamicin (67.7%). The lowest resistance was found against ceftazidime, and no vancomycin-resistant isolates were obtained. CONCLUSIONS: We detected S. aureus and MRSA in both human and canine specimens. Isolates were found to be resistant to some of the antimicrobials available locally. MRSA carriage in humans and animals appears to be a great threat to effective antimicrobials treatment. The prudent use of antimicrobials will reduce the antimicrobial resistance. Our findings will help to find the most appropriate treatment and to reduce antimicrobial resistance in the future by implementing prudent use of antimicrobials. Further studies are required to better understand the epidemiology of MRSA human-animal inter-species transmission in Bangladesh.

Tobacco education in UK dental schools: A survey of current practice.

OBJECTIVE: To investigate the current provision of tobacco education (tobacco use and cessation), assessment and e-cigarette education in UK dental and dental hygiene and therapy (DHT) undergraduate programmes. MATERIALS AND METHODS: The study was conducted using a self-administered questionnaire sent to all UK institutions training dental and DHT students during the academic year 2015/2016. RESULTS: Twenty-five programmes returned completed questionnaires (response rate 68%). All programmes (100%) reported delivering tobacco education, delivered by multiple individuals in 78% of the programmes. Assessment of the theoretical and practical aspects of tobacco education was reported in 80% and 72% of the programmes, respectively. More formal teaching time was devoted to the theoretical aspects (100% >2 hours) rather than the practical aspects (76% > 2 hours) of tobacco education. All programmes expected their graduates to be clinically competent at discussing the health consequences of smoking, deliver a brief smoking cessation intervention, and referring patients to stop smoking services. The use of the National Centre for Smoking Cessation and Training "Very Brief Advice" (NCSCT VBA) training package was reported to be mandatory in 36%, and recommended, in 44% of programmes. Specialised stop smoking services delivered teaching in 40% of both dental and DHT training programmes whilst another 40% reported previous input from specialist smoking cessation services but not in 2015/2016. Most programmes reported delivery of teaching on electronic cigarettes, with 12% delivering a standalone lecture on this topic. CONCLUSIONS: Tobacco education is an important component of dental training. Dental education programmes should remain responsive to a rapidly changing field and fully utilise the available resources.

Solid Renal Masses in Transplanted Allograft Kidneys: A Closer Look at the Epidemiology and Management.

The objective of this review is to explore the available literature on solid renal masses (SRMs) in transplant allograft kidneys to better understand the epidemiology and management of these tumors. A literature review using PubMed was performed according to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) methodology. Fifty-six relevant studies were identified from 1988 to 2015. A total of 174 SRMs in 163 patients were identified, with a mean tumor size of 2.75 cm (range 0.5-9.0 cm). Tumor histology was available for 164 (94.3%) tumors: clear cell renal cell carcinoma (RCC; 45.7%), papillary RCC (42.1%), chromophobe RCC (3%), and others (9.1%). Tumors were managed by partial nephrectomy (67.5%), radical nephrectomy (19.4%), percutaneous radiofrequency ablation (10.4%), and percutaneous cryoablation (2.4%). Of the 131 patients (80.3%) who underwent nephron-sparing interventions, 10 (7.6%) returned to dialysis and eight (6.1%) developed tumor recurrence over a mean follow-up of 2.85 years. Of the 110 patients (67.5%) who underwent partial nephrectomy, 3.6% developed a local recurrence during a mean follow-up of 3.12 years. The current management of SRMs in allograft kidneys mirrors management in the nontransplant population, with notable findings including an increased rate of papillary RCC and similar recurrence rates after partial nephrectomy in the transplant population despite complex surgical anatomy.

Enhancing High Harmonic Output in Solids through Quantum Confinement.

We investigate theoretically the effect of quantum confinement on high harmonic generation (HHG) in semiconductors by systematically varying the width of a model quantum nanowire. Our analysis reveals a reduction in ionization and a concurrent growth in HHG efficiency with increasing confinement. The drop in ionization results from an increase in the band gap due to stronger confinement. The increase in harmonic efficiency comes as a result of the confinement restricting the spreading of the transverse wave packet. As a result, intense laser driven 1D and 2D nanosystems present a potential pathway to increasing yield and photon energy of HHG in solids.

Retail lighting and packaging influence consumer acceptance of fluid milk.

Little is known about the effect of retail light-emitting diode (LED) exposure on consumer acceptance of milk. The study objective was to determine effects of fluorescent and LED lighting under retail storage conditions on consumer acceptance of milk. Consumer acceptance of milk stored under retail conditions was determined through sensory evaluation (2 studies; n=150+ each) and analytical measures (dissolved oxygen, secondary oxidation products, riboflavin retention). Study 1 evaluated milk stored in high-density polyethylene (HDPE) packages for 4h under LED light (960 lx). Commercially available HDPE package treatments included translucent HDPE (most commonly used), white HDPE [low concentration (1.3%) TiO2], and yellow HDPE; in addition, HDPE with a higher TiO2 concentration (high white; 4.9% TiO2) and a foil-wrapped translucent HDPE (control) were tested. Translucent and control packages also were tested under fluorescent light. Study 2 evaluated polyethylene terephthalate (PET) packages for 4h under fluorescent and LED light (1,460 lx). The PET packaging included 2 treatments (medium, 4.0% TiO2; high, 6.6% TiO2) as well as translucent HDPE (exposed to fluorescent), clear PET (fluorescent and LED), and light-protected control. Overall mean acceptability of milk ranged from "like slightly" to "like moderately" with significantly lower acceptability for milk exposed to fluorescent light. Milk in HDPE and PET packages had comparable overall acceptability scores when exposed to LED light. Only the fluorescent light condition (both PET and HDPE) diminished overall acceptability. Fluorescent light exposure negatively influenced flavor with significant penalty (2.0-2.5 integers) to overall acceptability of milk in translucent HDPE and clear PET. The LED also diminished aftertaste of milk packaged in translucent HDPE. Changes in dissolved oxygen content, as an indication of oxidation, supported the observed differences in consumer acceptance of milk stored under fluorescent and LED light. Consumers like the flavor of fresh milk, which can be protected by selecting appropriate packaging that blocks detrimental light wavelengths.

Role of Eosinophil Granulocytes in Allergic Airway Inflammation Endotypes.

Eosinophil granulocytes are intriguing members of the innate immunity system that have been considered important defenders during parasitic diseases as well as culprits during allergy-associated inflammatory diseases. Novel studies have, however, found new homoeostasis-maintaining roles for the cell. Recent clinical trials blocking different Th2 cytokines have uncovered that asthma is heterogeneous entity and forms different characteristic endotypes. Although eosinophils are present in allergic asthma with early onset, the cells may not be essential for the pathology. The cells are, however, likely disease causing in asthma with a late onset, which is often associated with chronic rhinosinusitis. Assessment of eosinophilia, fraction exhaled nitric oxide (FeNO) and periostin are markers that have emerged useful in assessing and monitoring asthma severity and endotype. Current scientific knowledge suggests that eosinophils are recruited by the inflammatory environment, activated by the innate interleukin (IL)-33 and prevented from apoptosis by both lymphocytes and innate immune cells such as type two innate immune cells. Eosinophils contain four specific granule proteins that exhibit an array of toxic and immune-modulatory activates. The granule proteins can be released by different mechanisms. Additionally, eosinophils contain a number of inflammatory cytokines and lipid mediators as well as radical oxygen species that might contribute to the disease both by the recruitment of other cells and the direct damage to supporting cells, leading to exacerbations and tissue fibrosis. This review aimed to outline current knowledge how eosinophils are recruited, activated and mediate damage to tissues and therapies used to control the cells.

Spontaneous Intragastric Balloon Hyperinflation: Two Cases and Outcomes.

Endoscopic bariatric therapies can provide treatment options for obesity in non-surgical candidates, as a part of combination or serial treatment plans, and for the reduction of obesity-related comorbidities. Several complications of intragastric balloons have been documented, but spontaneous hyperinflation is a risk that has not been well reported previously. We describe two cases of spontaneous intragastric balloon hyperinflation and their outcomes.

Acquired Lymphangioma Circumscriptum of the Scrotum: A Case Report.

Lymphangioma circumscriptum (LC) is an uncommon malformation affecting the skin and subcutaneous tissue. This report documents a case of LC that developed in the scrotum of a 35-year-old male. Upon examination, numerous clusters of clear vesicles were found on the scrotum's surface. The patient had no previous exposure to infections, trauma, surgery, or radiation treatment. A skin biopsy revealed enlarged lymphatic channels in the dermis, aligning with a diagnosis of LC. The patient was treated with cryotherapy using liquid nitrogen, specifically targeting the translucent yellowish vesicles. The cryotherapy was administered in a series of eight sessions, each involving double freeze-thaw cycles, spaced out at two-week intervals. Following treatment, the patient's lesions regressed, indicating a favorable therapeutic outcome. The patient was followed up for nearly one year, during which no new lesions developed, suggesting the treatment's effectiveness in preventing recurrence. The complete resolution of lesions and absence of recurrence during follow-up indicate a good prognosis and successful response to cryotherapy. Scrotal LC, particularly the acquired form in adults without any precipitating factors, is extremely rare. This case underlines the need to include acquired LC in the diagnostic considerations when adult patients present with vesicular lesions on the scrotum, to ensure accurate diagnosis and subsequent proper treatment.

Post-traumatic stress disorders and coping strategies of health professionals during COVID-19 pandemic in Bangladesh: findings of a countrywide cross-sectional study.

Background: COVID-19 pandemic imposed a devastating effect on the psychological health of health professionals as they worked nonstop to withstand the hardship of the pandemic. The present study intended to determine the post-traumatic stress disorders (PTSD) and coping strategies among health professionals during the COVID-19 pandemic in Bangladesh. Methods: This country-wide cross-sectional study was conducted from July to December 2021 among 1394 health professionals (596 physicians, 713 nurses, 85 medical technologists) who served COVID-19 patients at the secondary, tertiary, and specialized government healthcare facilities in Bangladesh and completed at least one month after exposure to COVID-19 patient-care. Data were collected through face-to-face interviews using a semi-structured questionnaire and analyzed by SPSS software. All the ethical issues were maintained strictly. Findings: Most of the participants, 877 (62.9%) [95% CI: 60.3-65.5], were female, and 327 (23.5%) [95% CI: 21.3-25.8] developed PTSD. Females (AOR:1.42 [95% CI: 1.083-1.868] p = 0.011), having an elderly family member (AOR:1.515 [95% CI: 1.173-1.956] p = 0.0014), working in specialized hospitals (AOR:2.685 [95% CI: 1.928-3.739] p < 0.001), and working ≥8 hours/day (AOR:1.897 [95% CI: 1.350-2.666] p = 0.0002) had higher odds of developing PTSD. Most of the participants adopted spiritual approaches 96 (29.4%) [24.5-34.6] and distraction by watching TV/YouTube 59 (18.0%) [14.0-22.6] as coping strategies. Interpretation: The study findings would be helpful for health policymakers and managers to develop comprehensive measures for restoring the mental well-being of health professionals by alleviating PTSD induced by a pandemic like COVID-19. Funding: The study got funding from the Directorate General of Medical Education under the Ministry of Health and Family Welfare, Bangladesh.

MicroRNA-155 and Disease-Related Immunohistochemical Parameters in Cutaneous Melanoma.

Cutaneous melanoma is a severe and life-threatening form of skin cancer with growing incidences. While novel interventions have improved prognoses for these patients, early diagnosis of targeted treatment remains the most effective approach. MicroRNAs have grown to good use as potential biomarkers for early detection and as targets for treatment. miR-155 is well-studied for its role in tumor cell survival and proliferation in various tissues, although its role in melanoma remains controversial. In silico data analysis was performed in the dbDEMC v.3 to identify differentially expressed miRNA. We validated gene targets in melanoma using TarBase v8.0 and miRPath v3.0 and determined protein-protein interactions of the target genes. One hundred forty patients (age range 21-90 years) with cutaneous melanoma who underwent resection were included. Molecular assessment using Real-Time RT-qPCR, clinicopathological associations, and a literature review for the different roles of miR-155 in melanoma were performed. Analysis of the dbDEMC reveals controversial findings. While there is evidence of upregulation of miR-155 in primary and metastatic melanoma samples, others suggest decreased expression in later-stage melanoma and cases with brain metastasis. miR-155 has been overexpressed in prior cases of melanoma and precancerous lesions, and it was found to be dysregulated when compared to benign nevi. While miR-155 expression was associated with favorable outcomes in some studies, others showed an association with metastasis. Patients with high levels of miR-155 also noted reduction after receiving anti-PD-1 treatment, correlated with more prolonged overall survival. In our patient's cohort, 22.9% relapsed during treatment, and 45% developed recurrence, associated with factors such as lymph node infiltration, high mitotic index, and positive staining for CD117. Although overall analysis revealed miR-155 downregulation in melanoma specimens compared to non-cancer tissues, increased expression of miR-155 was associated with cases of superficial spreading melanoma subtype (p = 0.005) and any melanoma with a high mitotic rate (p = 0.010). The analysis did not identify optimum cutoff values to predict relapse, recurrence, or mortality. In conclusion, miR-155 could have, in part, a potential prognostic utility in cutaneous melanoma. Further mechanistic studies are required to unravel the multifunctional role of miR-155 in melanoma.

Clinical and Haematological Findings in Dengue Fever.

From 2000 onwards dengue fever has been occurring at regular intervals in Bangladesh. Ultrasonography is a useful diagnostic procedure. This study was done, keeping this background in mind. Objective of this study was to identify the role of ultrasonography as a useful tool in early diagnosis of dengue haemorrhagic fever. This was a cross-sectional descriptive type of observational study. Results of ultrasonography, haematogy an immunology were observed in 2004 and 2019 in 32 patients on each occasion. In 2004 out of 32 patients 29 had positive ultrsonographic findings supported by corresponding haematological and immunological findings. In 2019 ultrsonography was done in three out of thirty two patients, all three had had positive ultra sonographic findings which were supported by haematological and immunological findings. Dengue fever has serious complications like plasma leakage which manifest in the form of ascites, pleural effusion, thick gallbladder wall etc. If such complications can be detected at an early stage many lives can be saved.

Insights from the molecular docking analysis of SGLT2 and FIMH to combat uropathogenicity.

SGLT2 inhibitors are a novel class of FDA approved anti-diabetes drugs. They act by blocking the SGLT2 protein, which prevents glucose reabsorption, leading in enhance glucose excretion and lower blood glucose levels. In diabetic patients, SGLT2 inhibitors have been linked to urinary tract infections (UTIs). Therefore, the development of novel SGLT2 inhibitors with no adverse effects is a need of time. With this purpose, in this study, 48164natural compounds from ZINC database were screened targeting both the SGLT2 and FimH protein using insilico approaches. FimH has been discovered as a promising target for preventing and treating UTIs. The hit compounds ZINC69481892, ZINC1612996, and ZINC4039265 exhibited strong binding with both SGLT2 and FimH with binding energies values of -9.88, -8.96, and -10.57 kcal/mol for SGLT2, and -7.86, -7.01, and -8.92 kcal/mol for FimH, which is higher than that of controls (-6.78 kcal/mol (Empaglifozolin for SGLT2) and -5.14 kcal/mol (Heptyl α-d-mannopyranoside for FimH)). Hits were found to bind with key residues of both SGLT2 and FimH protein. In addition, physiochemical properties showed that these compounds have good drug-likeness properties. Therefore, we anticipate that if these compounds are investigated further, might be potential SGLT2 inhibitors with less uropathogenic adverse effects.

Knowledge Regarding Ionizing Radiation Exposure Safety Among Orthopedic Surgeons at Hospitals in Al-Madinah.

Background and objective The use of radiation imaging techniques in operation theaters is essential for numerous surgical procedures and patients' overall well-being. Radiation imaging techniques enable the surgeon to have a real-time visualization of the anatomy and to perform operations with a greater chance of success, decrease rates of patient morbidity, and enable surgeons to obtain imaging records before the patient leaves the theater room. However, with the increased use of imaging techniques in orthopedic surgical operations, orthopedic surgeons are being exposed to higher levels of radiation, and hence they can be classified as a high-risk group for occupational radiation exposure. This study aimed to assess orthopedic surgeons' awareness and knowledge regarding radiation exposure safety. Materials and methods A questionnaire-based descriptive cross-sectional study was conducted from January to March 2022 to assess the knowledge regarding ionizing radiation exposure safety among orthopedic surgeons, including consultants, specialists, and residents, at both private and governmental hospitals in Al-Madinah city, Saudi Arabia. Ethical approval was obtained from the Ministry of Health (MOH) of Al-Madinah (approval number: H-03-l.l-084). The applied statistical tests were frequency and MCT tests for univariate variables while Chi-square was applied for bivariate variables. With a 95% confidence interval (CI), a p-value of more than 0.05 was used as the cut-off value for the significance level. Results A total of 57 surgeons participated in the study, of which 57.9% were exposed to radiation two to three times per week. Additionally, more than half of the physicians (66.7%) were not trained to use fluoroscopy (C-arm machine). Of note, 78.9% of orthopedic surgeons reported that they used the protective apron as protective equipment, while 17.5% of them used both a protective apron and thyroid shield. However, only less than half of the orthopedic surgeons (43.9%) in our study practiced radiation safety in the operating room. Conclusion Our study revealed a lack of knowledge and awareness related to ionizing radiation exposure safety among orthopedic surgeons in Al-Madinah city, Saudi Arabia.

The role of pioglitazone in antioxidant, anti-inflammatory, and insulin sensitivity in a high fat-carbohydrate diet-induced rat model of insulin resistance.

We explored the cascade effects of a high fat-carbohydrate diet (HFCD) and pioglitazone (an anti-diabetic therapy used to treat type 2 diabetes mellitus (T2DM)) on lipid profiles, oxidative stress/antioxidant, insulin, and inflammatory biomarkers in a rat model of insulin resistance. Sixty albino rats (80-90 g) were randomly divided into three dietary groups; 1) standard diet; 2) HFCD diet for 12 weeks to induce an in vivo model of insulin resistance; and 3) HFCD diet plus pioglitazone. Blood and tissue samples were taken to assess hepatic function, lipid profiles, oxidative biomarkers, malondialdehyde (MDA) levels, antioxidant defense biomarkers, including reduced glutathione (GSH), superoxide dismutase (SOD), and the inflammatory markers interleukin-6 (IL-6) and tumor necrotic factor (TNF-α). HFCD-fed rats had significantly (P≤0.05) increased serum triacylglycerol (TG), total cholesterol (TC), low-density lipoprotein (LDL), alanine transaminase (ALT), and bilirubin levels, but decreased high-density lipoprotein (HDL) levels compared with the normal group. Moreover, serum leptin, resistin, TNF-α, and IL-6 levels were increased significantly in HFCD animals compared with controls. Similarly, HFCD-induced insulin resistance caused antioxidant and cytokine disturbances, which are important therapy targets for pioglitazone. Importantly, administration of this drug ameliorated these changes, normalized leptin and resistin and inflammatory markers by reducing TNF-α levels. Metabolic cascades of elevated lipid profiles, oxidative stress, insulin, and inflammatory biomarkers are implicated in insulin resistance progression. HFCD induced metabolic cascades comprising hypertriglyceridemia, hyperglycemia, insulin resistance, obesity-associated hormones, and inflammatory biomarkers may be alleviated using pioglitazone.