Canine Brachycephaly is Associated with a Retrotransposon-Mediated Missplicing of SMOC2

In morphological terms, “form” is used to describe an object’s shape and size. In dogs, facial form is stunningly diverse. Facial retrusion, the proximodistal shortening of the snout and widening of the hard palate is common to brachycephalic dogs and is a welfare concern, as the incidence of respiratory distress and ocular trauma observed in this class of dogs is highly correlated with their skull form. Progress to identify the molecular underpinnings of facial retrusion is limited to association of a missense mutation in BMP3 among small brachycephalic dogs. Here, we used morphometrics of skull isosurfaces derived from 374 pedigree and mixed-breed dogs to dissect the genetics of skull form. Through deconvolution of facial forms, we identified quantitative trait loci that are responsible for canine facial shapes and sizes. Our novel insights include recognition that the FGF4 retrogene insertion, previously associated with appendicular chondrodysplasia, also reduces neurocranium size. Focusing on facial shape, we resolved a quantitative trait locus on canine chromosome 1 to a 188-kb critical interval that encompasses SMOC2. An intronic, transposable element within SMOC2 promotes the utilization of cryptic splice sites, causing its incorporation into transcripts, and drastically reduces SMOC2 gene expression in brachycephalic dogs. SMOC2 disruption affects the facial skeleton in a dose-dependent manner. The size effects of the associated SMOC2 haplotype are profound, accounting for 36% of facial length variation in the dogs we tested. Our data bring new focus to SMOC2 by highlighting its clinical implications in both human and veterinary medicine

The Impact of Data Management on the Achievable Dose and Efficiency of Mammography and Radiography During the COVID-19 Era: A Facility-Based Cohort Study

Tarek Mohammed Hegazi,* Abdulaziz Mohammad AlSharydah,* Iba Alfawaz, Afnan Fahad Al-Muhanna, Sarah Yousef Faisal Diagnostic and Interventional Radiology Department, King Fahd Hospital of the University, Imam Abdulrahman Bin Faisal University, Al-Khobar City, Eastern Province, Saudi Arabia*These authors contributed equally to this workCorrespondence: Tarek Mohammed Hegazi, Chairperson of the Radiology Department, King Fahd Hospital of the University, Imam Abdulrahman Bin Faisal University, Khobar City, Eastern Province, Saudi Arabia, Tel +966-0138966877 (EXT: 2007), Email [email protected]: To evaluate the impact of using computational data management resources and analytical software on radiation doses in mammography and radiography during the COVID-19 pandemic, develop departmental diagnostic reference levels (DRLs), and describe achievable doses (ADs) for mammography and radiography based on measured dose parameters.Patients and Methods: This ambispective cohort study enrolled 795 and 12,115 patients who underwent mammography and radiography, respectively, at the King Fahd Hospital of the University, Al-Khobar City, Saudi Arabia between May 25 and November 4, 2021. Demographic data were acquired from patients’ electronic medical charts. Data on mammographic and radiographic dose determinants were acquired from the data management software. Based on the time when the data management software was operational in the institute, the study was divided into the pre-implementation and post-implementation phases. Continuous and categorical variables were compared between the two phases using an unpaired t-test and the chi-square test.Results: The median accumulated average glandular dose (AGD; a mammographic dose determinant) in the post-implementation phase was three-fold higher than that in the pre-implementation phase. The average mammographic exposure time in the post-implementation phase was 16.3 ms shorter than that in the pre-implementation phase. Furthermore, the median values of the dose area product ([DAP], a radiographic dose determinant) were 9.72 and 19.4 cGycm2 in the pre-implementation and post-implementation phases, respectively.Conclusion: Although the data management software used in this study helped reduce the radiation exposure time by 16.3 ms in mammography, its impact on the mean accumulated AGD was unfavorable. Similarly, radiographic exposure indices, including DAP, tube voltage, tube current, and exposure time, were not significantly different after the data management software was implemented. Close monitoring of patient radiation doses in mammography and radiography, and dose reduction will become possible if imaging facilities use DRLs and ADs via automated systems.Keywords: average glandular dose, entrance skin dose, dose area product, radiograph, mammogra

Novel Therapy for Pediatric Angiosarcoma With Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy

The management of pediatric abdominopelvic angiosarcoma remains unclear due to limited clinical experience. Herein, we presented the first 2 pediatric patients with abdominal angiosarcoma who were treated with cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) after neoadjuvant therapy. The first patient is alive with recurrent disease at 1-year follow-up and the second patient remains disease free after 1 year. CRS and HIPEC should be considered as a therapeutic option in the management of pediatric abdominal angiosarcomas. A multi-institutional international shared registry is needed to further evaluate the role of CRS and HIPEC in inducing remission of abdominopelvic angiosarcomas in the pediatric population

Hydrophobic natural deep eutectic-solvent bar microextraction combined with HPLC-DAD for determination of urinary 1-hydroxypyrene of smokers

1-hydroxypyrene (1-OHP) is a metabolite of pyrene, which is a type of polycyclic aromatic hydrocarbons (PAHs) found in tobacco smoke and preferred use as a biomarker to determine exposure to PAHs from smoking. This paper reports a new and simple microextraction technique for 1-hydroxypyrene (1-OHP) determination in smokers' urines using hydrophobic natural deep eutectic solvent (HNDES) in developing solvent bar microextraction (SBME) and high performance liquid chromatography-diode array detection (HPLC-DAD). Terpenoids based-HNDES using various ratios of (thymol/menthol) were synthesized and investigated as extraction solvents. The variables affecting HNDE-SBME steps were optimized by response surface methodology (RSM) based on central composite design (CCD). Under the optimum conditions, the calibration graph of spiked urine samples was linear in the range of 0.3–25.0 μg L−1 1-OHP with a correlation coefficient of 0.999. Additionally, the detection limit, quantitation limit, and extraction recovery were found to be 0.06 μg L−1, 0.22 μg L−1, and ≥100%, respectively. In comparison with referenced methods and based on the satisfactory results of applications, the proposed method can be considered as a potential method for the detection of urinary 1-OHP for health risk assessment of PAHs exposures

Ameliorative Effect of Ethanolic Extract of <i>Moringa oleifera</i> Leaves in Combination with Curcumin against PTZ-Induced Kindled Epilepsy in Rats: In Vivo and In Silico

The ameliorative effect of ethanolic extract of M. oleifera (MOEE) leaves in combination with curcumin against seizures, cognitive impairment, and oxidative stress in the molecular docking of PTZ-induced kindled rats was performed to predict the potential phytochemical effects of MOEE and curcumin against epilepsy. The effect of pretreatment with leaves of M. oleifera ethanolic extracts (MOEE) (250 mg/kg and 500 mg/kg, orally), curcumin (200 mg/kg and 300 mg/kg, orally), valproic acid used as a standard (100 mg/kg), and the combined effect of MOEE (250 mg/kg) and curcumin (200 mg/kg) at a low dose on Pentylenetetrazole was used for (PTZ)-induced kindling For the development of kindling, individual Wistar rats (male) were injected with pentyletetrazole (40 mg/kg, i.p.) on every alternate day. Molecular docking was performed by the Auto Dock 4.2 tool to merge the ligand orientations in the binding cavity. From the RCSB website, the crystal structure of human glutathione reductase (PDB ID: 3DK9) was obtained. Curcumin and M. oleifera ethanolic extracts (MOEE) showed dose-dependent effects. The combined effects of MOEE and curcumin leaves significantly improved the seizure score and decreased the number of myoclonic jerks compared with a standard dose of valproic acid. PTZ kindling induced significant oxidative stress and cognitive impairment, which was reversed by pretreatment with MOEE and curcumin. Glutathione reductase (GR) is an enzyme that plays a key role in the cellular control of reactive oxygen species (ROS). Therefore, activating GR can uplift antioxidant properties, which leads to the inhibition of ROS-induced cell death in the brain. The combination of the ethanolic extract of M. oleifera (MOEE) leaves and curcumin has shown better results than any other combination for antiepileptic effects by virtue of antioxidant effects. As per the docking study, chlorogenic acid and quercetin treated with acombination of curcumin have much more potential

Molecular explanation of Wnt/βcatenin antagonist pyrvinium mediated calcium equilibrium changes in aging cardiovascular disorders.

The symptoms of ageing are somewhat different and can lead to the altered role of the cardiovascular system at the levels of genetic, biochemical, tissue, organ, and systems. Ageing is an autonomous cardiovascular risk factor. In the ageing rat heart, oxidative and inflammatory stress, immune cell infiltration, increasing myeloperoxidase function, elevated caspase-3 activity, and protein fibronectins were detected and associated with ageing and cardiovascular disease. The intracellular Ca2 + homeostasis disturbed in an older heart dramatically increases cardiomyopathy, atherosclerosis, stroke, ischemia, myocardial infarction, hypertrophy, remodelling, and hypertension. Evidence shows that suppression of Wnt/β signals prevents cardiovascular dysfunction, such as remodelling, high blood pressure, and excessive overload stress. However, one study has shown that the pharmacological disruption of Wnt-β-catenin by decreasing expression of α-smooth muscle actin, fibronectin and collagen I proteins attenuates angiotensin II mediated hypertension cardiac fibrosis. Thus, this review examined the impacts of calcium overload and age-related diseases, including cardiovascular. Energy dysregulation, calcium overloading, and mitochondrial dysfunction are the main activities causing cardiovascular disease linked with age. Therefore, the current study explores that age-associated cardiovascular disease has triggered the WNT/β-catenin pathway, and pharmacological inhibition can delay pathological changes by attenuating calcium dyshomeostasis

Efficacy of Novavit in ameliorating the neurotoxicity of propionic acid

Oxidative stress, abnormal fatty acid metabolism, and impaired gut microbiota play a serious role in the pathology of autism. The use of dietary supplements to improve the core symptoms of autism is a common therapeutic strategy. The present study analyzed the effects of oral supplementation with Novavit, a multi-ingredient supplement, on ameliorating oxidative stress and impaired lipid metabolism in a propionic acid (PPA)-induced rodent model of autism. Male western albino rats were divided into three groups. The first group is the control, the second group was given an oral neurotoxic dose of PPA (250 mg/kg body weight/day) for 3 days and then received buffered saline until the end of the experiment. The third group received Novavit (70 mg/kg body weight/day for 30 days after the 3-day PPA treatment). Markers of oxidative stress and impaired fatty acid metabolism were measured in brain homogenates obtained from each group. Novavit modulation of the gut microbiota was also evaluated. While PPA induced significant increases in lipid peroxides and 5-lipoxygenase, together with significantly decreased glutathione, and cyclooxygenase 2, oral supplementation with Novavit ameliorated PPA-induced oxidative stress and impaired fatty acid metabolism. Our results showed that the presence of multivitamins, coenzyme Q10, minerals, and colostrum, the major components of Novavit, protects against PPA-induced neurotoxicity