A Novel Pathway for Metabolism of the Cardiovascular Risk Factor Homoarginine by alanine:glyoxylate aminotransferase 2

Low plasma concentrations of L-homoarginine are associated with an increased risk of cardiovascular events, while homoarginine supplementation is protective in animal models of metabolic syndrome and stroke. Catabolism of homoarginine is still poorly understood. Based on the recent findings from a Genome Wide Association Study we hypothesized that homoarginine can be metabolized by alanine:glyoxylate aminotransferase 2 (AGXT2). We purified human AGXT2 from tissues of AGXT2 transgenic mice and demonstrated its ability to metabolize homoarginine to 6-guanidino-2-oxocaproic acid (GOCA). After incubation of HepG2 cells overexpressing AGXT2 with isotope-labeled homoarginine-d4 we were able to detect labeled GOCA in the medium. We injected wild type mice with labeled homoarginine and detected labeled GOCA in the plasma. We found that AGXT2 knockout (KO) mice have higher homoarginine and lower GOCA plasma levels as compared to wild type mice, while the reverse was true for AGXT2 transgenic (Tg) mice. In summary, we experimentally proved the presence of a new pathway of homoarginine catabolism - its transamination by AGXT2 with formation of GOCA and demonstrated that endogenous AGXT2 is required for maintenance of homoarginine levels in mice. Our findings may lead to development of novel therapeutic approaches for cardiovascular pathologies associated with homoarginine deficiency

Ostomy closure rate during COVID-19 pandemic. An Italian multicentre observational study

During the corona virus disease 2019 (COVID-19) pandemic, most of the surgical procedures were performed for emergencies or oncologic reasons to the detriment of the remaining elective procedures for benign conditions. Ileostomy or colostomy creation are sequelae of oncologic or emergency colorectal surgery, but their closure does not fall within the definition of oncologic or emergency surgery. The aim of this retrospective multicentre observational study is to report the impact of COVID-19 pandemic on the ostomy closure rate in Italy. Data regarding ileostomy and colostomy creation and closure from 24 Italian centres, during the study period (March 2020–February 2021) and during the control period (March 2019–February 2020) were collected. Three hospitals (12.5%) were COVID free. The number of colostomies and ileostomies created and closed in the same period was lower (-18.8% and-30%, respectively) in the study period in comparison to the control period (p = 0.1915 and p = 0.0001, respectively), such as the ostomies closed in the analysed periods but created before (colostomy-36.2% and ileostomy-7.4%, p = 0.2211 and p = 0.1319, respectively). Overall, a 19.5% reduction in ostomies closed occurred in the study period. Based on the present study, a reduction in ostomy closure rate occurred in Italy between March 2020 and February 2021. During the pandemic, the need to change the clinical practice probably prolonged deterioration of quality of life in patients with ostomies, increasing number of stomas that will never be closed, and related management costs, even if these issues have not been investigated in this study

Autologous bone marrow stem cell intralesional transplantation repairing bisphosphonate related osteonecrosis of the jaw

<p>Abstract</p> <p>Purpose</p> <p>Bisphosphonate - related osteonecrosis of the JAW (BRONJ) is a well known side effect of bisphosphonate therapies in oncologic and non oncologic patients. Since to date no definitive consensus has been reached on the treatment of BRONJ, novel strategies for the prevention, risk reduction and treatment need to be developed. We report a 75 year old woman with stage 3 BRONJ secondary to alendronate and pamidronate treatment of osteoporosis. The patient was unresponsive to recommended treatment of the disease, and her BRONJ was worsening. Since bone marrow stem cells are know as being multipotent and exhibit the potential for differentiation into different cells/tissue lineages, including cartilage, bone and other tissue, we performed autologous bone marrow stem cell transplantation into the BRONJ lesion of the patient.</p> <p>Methods</p> <p>Under local anesthesia a volume of 75 ml of bone marrow were harvested from the posterior superior iliac crest by aspiration into heparinized siringes. The cell suspension was concentrated, using Ficoll - Hypaque^®centrifugation procedures, in a final volume of 6 ml. Before the injection of stem cells into the osteonecrosis, the patient underwent surgical toilet, local anesthesia was done and spongostan was applied as a carrier of stem cells suspension in the bone cavity, then 4 ml of stem cells suspension and 1 ml of patient's activated platelet-rich plasma were injected in the lesion of BRONJ.</p> <p>Results</p> <p>A week later the residual spongostan was removed and two weeks later resolution of symptoms was obtained. Then the lesion improved with progressive superficialization of the mucosal layer and CT scan, performed 15 months later, shows improvement also of bone via concentric ossification: so complete healing of BRONJ (stage 0) was obtained in our patient, and 30 months later the patient is well and without signs of BRONJ.</p> <p>Conclusion</p> <p>To our knowledge this is the first case of BRONJ successfully treated with autologous stem cells transplantation with a complete response.</p

Extensive Regulation of Diurnal Transcription and Metabolism by Glucocorticoids.

Altered daily patterns of hormone action are suspected to contribute to metabolic disease. It is poorly understood how the adrenal glucocorticoid hormones contribute to the coordination of daily global patterns of transcription and metabolism. Here, we examined diurnal metabolite and transcriptome patterns in a zebrafish glucocorticoid deficiency model by RNA-Seq, NMR spectroscopy and liquid chromatography-based methods. We observed dysregulation of metabolic pathways including glutaminolysis, the citrate and urea cycles and glyoxylate detoxification. Constant, non-rhythmic glucocorticoid treatment rescued many of these changes, with some notable exceptions among the amino acid related pathways. Surprisingly, the non-rhythmic glucocorticoid treatment rescued almost half of the entire dysregulated diurnal transcriptome patterns. A combination of E-box and glucocorticoid response elements is enriched in the rescued genes. This simple enhancer element combination is sufficient to drive rhythmic circadian reporter gene expression under non-rhythmic glucocorticoid exposure, revealing a permissive function for the hormones in glucocorticoid-dependent circadian transcription. Our work highlights metabolic pathways potentially contributing to morbidity in patients with glucocorticoid deficiency, even under glucocorticoid replacement therapy. Moreover, we provide mechanistic insight into the interaction between the circadian clock and glucocorticoids in the transcriptional regulation of metabolism

Assessments Related to the Physical, Affective and Cognitive Domains of Physical Literacy Amongst Children Aged 7–11.9 Years: A Systematic Review

Background Over the past decade, there has been increased interest amongst researchers, practitioners and policymakers in physical literacy for children and young people and the assessment of the concept within physical education (PE). This systematic review aimed to identify tools to assess physical literacy and its physical, cognitive and affective domains within children aged 7–11.9 years, and to examine the measurement properties, feasibility and elements of physical literacy assessed within each tool. Methods Six databases (EBSCO host platform, MEDLINE, PsycINFO, Scopus, Education Research Complete, SPORTDiscus) were searched up to 10th September 2020. Studies were included if they sampled children aged between 7 and 11.9 years, employed field-based assessments of physical literacy and/or related affective, physical or cognitive domains, reported measurement properties (quantitative) or theoretical development (qualitative), and were published in English in peer-reviewed journals. The methodological quality and measurement properties of studies and assessment tools were appraised using the COnsensus-based Standards for the selection of health Measurement INstruments risk of bias checklist. The feasibility of each assessment was considered using a utility matrix and elements of physical literacy element were recorded using a descriptive checklist. Results The search strategy resulted in a total of 11467 initial results. After full text screening, 11 studies (3 assessments) related to explicit physical literacy assessments. Forty-four studies (32 assessments) were relevant to the affective domain, 31 studies (15 assessments) were relevant to the physical domain and 2 studies (2 assessments) were included within the cognitive domain. Methodological quality and reporting of measurement properties within the included studies were mixed. The Canadian Assessment of Physical Literacy-2 and the Passport For Life had evidence of acceptable measurement properties from studies of very good methodological quality and assessed a wide range of physical literacy elements. Feasibility results indicated that many tools would be suitable for a primary PE setting, though some require a level of expertise to administer and score that would require training. Conclusions This review has identified a number of existing assessments that could be useful in a physical literacy assessment approach within PE and provides further information to empower researchers and practitioners to make informed decisions when selecting the most appropriate assessment for their needs, purpose and context. The review indicates that researchers and tool developers should aim to improve the methodological quality and reporting of measurement properties of assessments to better inform the field. Trial registration PROSPERO: CRD4201706221