Publications by authors named "Michael Williams"

990 Publications

Genetic Manipulation of sn-1-Diacylglycerol Lipase and CB Cannabinoid Receptor Gain-of-Function Uncover Neuronal 2-Linoleoyl Glycerol Signaling in .

Cannabis Cannabinoid Res 2021 Apr 15;6(2):119-136. Epub 2021 Apr 15.

Department of Neuroscience, Biomedicum, Karolinska Institutet, Stockholm, Sweden.

In mammals, sn-1-diacylglycerol lipases (DAGL) generate 2-arachidonoylglycerol (2-AG) that, as the major endocannabinoid, modulates synaptic neurotransmission by acting on CB1 cannabinoid receptors (CBR). Even though the insect genome codes for , which is a DAGL ortholog (dDAGL), its products and their functions remain unknown particularly because insects lack chordate-type cannabinoid receptors. Gain-of-function and loss-of-function genetic manipulations were carried out in , including the generation of both dDAGL-deficient and mammalian CBR-overexpressing flies. Neuroanatomy, dietary manipulations coupled with targeted mass spectrometry determination of arachidonic acid and 2-linoleoyl glycerol (2-LG) production, behavioral assays, and signal transduction profiling for Akt and Erk kinases were employed. Findings from were validated by a CBR-binding assay for 2-LG in mammalian cortical homogenates with functionality confirmed in neurons using high-throughput real-time imaging . In this study, we show that dDAGL is primarily expressed in the brain and nerve cord of during larval development and in adult with 2-LG being its chief product as defined by dietary precursor availability. Overexpression of the human CBR in the ventral nerve cord compromised the mobility of adult . The causality of 2-LG signaling to CBR-induced behavioral impairments was shown by inactivation normalizing defunct motor coordination. The 2-LG-induced activation of transgenic CBRs affected both Akt and Erk kinase cascades by paradoxical signaling. Data from models were substantiated by showing 2-LG-mediated displacement of [H]CP 55,940 in mouse cortical homogenates and reduced neurite extension and growth cone collapsing responses in cultured mouse neurons. Overall, these results suggest that 2-LG is an endocannabinoid-like signal lipid produced by dDAGL in .
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http://dx.doi.org/10.1089/can.2020.0010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8064960PMC
April 2021

Cost Effectiveness of Ranibizumab vs Aflibercept vs Bevacizumab for the Treatment of Macular Oedema Due to Central Retinal Vein Occlusion: The LEAVO Study.

Pharmacoeconomics 2021 Apr 26. Epub 2021 Apr 26.

School of Health and Related Research, University of Sheffield, Sheffield, UK.

Background: We aimed to assess the cost effectiveness of intravitreal ranibizumab (Lucentis), aflibercept (Eylea) and bevacizumab (Avastin) for the treatment of macular oedema due to central retinal vein occlusion.

Methods: We calculated costs and quality-adjusted life-years from the UK National Health Service and Personal Social Services perspective. We performed a within-trial analysis using the efficacy, safety, resource use and health utility data from a randomised controlled trial (LEAVO) over 100 weeks. We built a discrete event simulation to model long-term outcomes. We estimated utilities using the Visual-Functioning Questionnaire-Utility Index, EQ-5D and EQ-5D with an additional vision question. We used standard UK costs sources for 2018/19 and a cost of £28 per bevacizumab injection. We discounted costs and quality-adjusted life-years at 3.5% annually.

Results: Bevacizumab was the least costly intervention followed by ranibizumab and aflibercept in both the within-trial analysis (bevacizumab: £6292, ranibizumab: £13,014, aflibercept: £14,328) and long-term model (bevacizumab: £18,353, ranibizumab: £30,226, aflibercept: £35,026). Although LEAVO did not demonstrate bevacizumab to be non-inferior for the visual acuity primary outcome, the three interventions generated similar quality-adjusted life-years in both analyses. Bevacizumab was always the most cost-effective intervention at a threshold of £30,000 per quality-adjusted life-year, even using the list price of £243 per injection.

Conclusions: Wider adoption of bevacizumab for the treatment of macular oedema due to central retinal vein occlusion could result in substantial savings to healthcare systems and deliver similar health-related quality of life. However, patients, funders and ophthalmologists should be fully aware that LEAVO could not demonstrate that bevacizumab is non-inferior to the licensed agents.
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http://dx.doi.org/10.1007/s40273-021-01026-5DOI Listing
April 2021

Impact of ultrasound on inguinal hernia repair rates in Australia: a population-based analysis.

ANZ J Surg 2021 Apr 18. Epub 2021 Apr 18.

The School of Medicine Sydney, The University of Notre Dame, Sydney, New South Wales, Australia.

Background: Inguinal hernias are a common pathology that often requires surgical management. The use of groin ultrasound (GU) to investigate inguinal hernias is a growing area of concern as an inefficient use of healthcare resources. Our aim was to assess changes in the rates of GU and the impact on surgical practice.

Methods: Medicare Item Reports and the Australian Institute of Health and Welfare Database were used to estimate annual GU and inguinal hernia repair (IHR) rates per 100 000 population for the period 2000/2001-2017/2018. Pearson's correlation coefficients and linear regression analyses were performed to assess associations between these variables.

Results: Over the 18-year period, GU rates increased 13-fold from 88 to 1174 per 100 000 population. Overall, total IHR rates decreased from 217 to 192 per 100 000. Overall, unilateral IHR rates have decreased (182-146 per 100 000), bilateral IHRs have increased (35-46 per 100 000), laparoscopic IHR has increased (30-86 per 100 000) and open surgery has declined (187-106 per 100 000). The increase in GU rates were strongly associated with the decrease in unilateral (r = -0.936, P = <0.001) and increase in bilateral IHR rates (r = 0.924, P = <0.001).

Conclusion: The use of GU has increased substantially, potentially representing an unnecessary cost to the healthcare system. Rising GU rates are not associated with an increase in IHR, however, may contribute to the increasing rates of bilateral IHRs. This study supports the opinion that more extensive clinical and health policy initiatives are needed in Australia to address this health issue.
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http://dx.doi.org/10.1111/ans.16845DOI Listing
April 2021

Outcomes of Laparoscopic Versus Open Resection of Meckel's Diverticulum.

J Surg Res 2021 Apr 10;264:362-367. Epub 2021 Apr 10.

Division of Pediatric Surgery, Department of Surgery, Northwestern University Feinberg School of Medicine, Ann & Robert H. Lurie Children's Hospital of Chicago, Chicago, Illinois.

Background: Meckel's Diverticulum (MD) is a common congenital anomaly accounting for half of pediatric gastrointestinal bleeds. No large-scale studies exist comparing open and laparoscopic surgery and conversion rates remain high. We sought to compare postoperative outcomes associated with each approach and to determine risk factors for conversion.

Materials And Methods: NSQIP-Pediatric was used to identify patients who underwent a MD resection from 2012 to 2018. Outcomes between patients treated with a laparoscopic versus open versus laparoscopic converted to open (LCO) surgery were compared. Chi-square tests and adjusted logistic regression analysis were used to determine significance and factors associated with conversion.

Results: Six hundred eighty-one patients were identified, 295 (43.3%) underwent open, 267 (39.2%) laparoscopic, and 119 (17.5%) LCO resection. Patients undergoing laparoscopic compared to open procedures had shorter length of stay (LOS; 3 versus 4, P= 0.009), and similar morbidities (10.5% versus 16.6%, P= 0.164) and operative times (71.6 versus 76.6 mins, P= 0.449) on adjusted analysis. Patients with LCO compared to open procedures had similar LOS (4 versus 4, P= 0.334) and morbidities (14.3% versus 16.6%, P= 0.358), but longer operative times (90.1 versus 76.6 mins, P= 0.002) on adjusted analysis. Patients with laparoscopic and LCO procedures had fewer unplanned intubations compared to open procedures (0.0% versus 0.0% versus 2.4%, P= 0.011) and lower mortality (0.0% versus 0.0% versus 1.7%, P= 0.046) on univariate analysis.

Conclusions: Laparoscopic MD resection has shorter LOS and similar complications and operative time compared to an open approach while LCO resection increases operative time but not LOS or morbidities.
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http://dx.doi.org/10.1016/j.jss.2021.02.028DOI Listing
April 2021

Effects of pyrethroids on brain development and behavior: Deltamethrin.

Neurotoxicol Teratol 2021 Apr 20;87:106983. Epub 2021 Apr 20.

Dept. of Pediatrics, University of Cincinnati College of Medicine, Division of Neurology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, United States of America. Electronic address:

Deltamethrin (DLM) is a Type II pyrethroid pesticide widely used in agriculture, homes, public spaces, and medicine. Epidemiological studies report that increased pyrethroid exposure during development is associated with neurobehavioral disorders. This raises concern about the safety of these chemicals for children. Few animal studies have explored the long-term effects of developmental exposure to DLM on the brain. Here we review the CNS effects of pyrethroids, with emphasis on DLM. Current data on behavioral and cognitive effects after developmental exposure are emphasized. Although, the acute mechanisms of action of DLM are known, how these translate to long-term effects is only beginning to be understood. But existing data clearly show there are lasting effects on locomotor activity, acoustic startle, learning and memory, apoptosis, and dopamine in mice and rats after early exposure. The most consistent neurochemical findings are reductions in the dopamine transporter and the dopamine D1 receptor. The data show that DLM is developmentally neurotoxic but more research on its mechanisms of long-term effects is needed.
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http://dx.doi.org/10.1016/j.ntt.2021.106983DOI Listing
April 2021

Contemporary outcomes of continuous-flow left ventricular assist devices-a systematic review.

Ann Cardiothorac Surg 2021 Mar;10(2):186-208

Division of Cardiac Surgery, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy.

Background: End stage heart failure is a major cause of morbidity and mortality, and its prevalence is expected to rise with the ageing population. For suitable patients, orthotopic heart transplantation remains the gold standard therapy, however, a paucity of donor organs has led to the development of left ventricular assist devices (LVAD). These devices can be utilized as either a bridge-to-transplant (BTT) or as an alternative to heart transplantation. While these devices can prolong life and improve quality of life, they are associated with a significant number of adverse events. We aim to systematically review the literature to quantify survival and the incidence of adverse events following implantation of continuous-flow LVADs (cf-LVAD).

Methods: A systematic review was performed to determine outcomes following implantation of a cf-LVAD. Primary outcomes were survival and frequency of adverse events (such as bleeding, infection, thrombosis, stroke and right ventricular failure). Secondary outcomes included quality of life and assessment of functional status.

Results: Sixty-three studies reported clinical outcomes of 9,280 patients. Survival after cf-LVAD varied between studies. Industry-funded trials generally reported better overall survival than the single- and multi-center case series, which showed significant variation. The largest registry report documented twelve, twenty-four and forty-eight-month survival rates of 82%, 72% and 57% respectively. The most commonly reported adverse events were gastrointestinal bleeding (GIB), device-related infection, neurological events and right heart failure (RHF). Bleeding, RHF and infection were the most frequent complications experienced by those supported with cf-LVAD, occurring in up to 35%, 40% and 55% of patients, respectively. Quality of life as measured using the Kansas City Cardiomyopathy Questionnaire (KCCQ) and functional status as measured with the 6-minute walk test (6MWT) improved after cf-LVAD implantation with no decline evident two years after implantation.

Conclusions: The paucity of donor hearts has led to the development of left-ventricular assist devices as a BTT or as a destination therapy (DT). Outcomes after cf-LVAD implantation are excellent, with short-term survival comparable to heart transplantation, but long-term survival remains limited due to the incidence of post-implantation adverse events. Despite these complications, quality of life and functional status improve significantly post-implantation and remain improved over the long-term. This study demonstrates the potential benefits of cf-LVAD therapy whilst also identifying adverse events as an area of increased morbidity and mortality.
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http://dx.doi.org/10.21037/acs-2021-cfmcs-35DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8033255PMC
March 2021

The specialist cadre of the Royal Army Dental Corps.

Br Dent J 2021 04 9;230(7):477-482. Epub 2021 Apr 9.

Colonel (Retired) Late Royal Army Medical Corps and previously of the Royal Army Dental Corps, Consultant Oral and Maxillofacial Surgeon, Department of Oral and Maxillofacial Surgery, East Sussex Healthcare Trust, UK.

The specialist cadre of the Royal Army Dental Corps (RADC) came to fruition at the start of World War II, with the speciality of maxillofacial surgery being born during World War I. The cadre has followed developments within the speciality, and building on the experience of forebears, has become capable of not only providing a secondary care service to the RADC but also being competent in the management of complex war injuries.
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http://dx.doi.org/10.1038/s41415-021-2833-2DOI Listing
April 2021

Cytoreductive surgical resection of a rare pulmonary artery intimal sarcoma involving the pulmonary valve and right ventricle: a case report.

J Surg Case Rep 2021 Mar 29;2021(3):rjab051. Epub 2021 Mar 29.

Department of Cardiothoracic Surgery, Royal Prince Alfred Hospital, Sydney, Australia.

Pulmonary artery intimal sarcoma (PAIS) is an extremely rare malignant tumour. It is often misdiagnosed as chronic pulmonary thromboembolism. We describe a complex case in a 70-year-old man with PAIS extending into his right ventricle undergoing salvage cytoreductive surgical resection utilizing bivalirudin for cardiopulmonary bypass anticoagulation due to heparin-induced thrombocytopenia and thrombosis syndrome. The prognosis for PAIS is extremely poor, with a median survival of 1.5 months without surgical resection. Cytoreductive surgical debulking can improve the median survival time to 17 months. The main aim of palliative surgical resection is to improve ventilation-perfusion mismatch and prevent haemodynamic collapse.
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http://dx.doi.org/10.1093/jscr/rjab051DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8007161PMC
March 2021

Epidemiology of infective endocarditis before after change of international guidelines: a systematic review.

Ther Adv Cardiovasc Dis 2021 Jan-Dec;15:17539447211002687

Department of Cardiothoracic Surgery, Royal Prince Alfred Hospital, Sydney, Australia.

Introduction: All major international guidelines for the management of infective endocarditis (IE) have undergone major revisions, recommending antibiotic prophylaxis (AP) restriction to high-risk patients or foregoing AP completely. We performed a systematic review to investigate the effect of these guideline changes on the global incidence of IE.

Methods: Electronic database searches were performed using Ovid Medline, EMBASE and Web of Science. Studies were included if they compared the incidence of IE prior to and following any change in international guideline recommendations. Relevant studies fulfilling the predefined search criteria were categorized according to their inclusion of either adult or pediatric patients. Incidence of IE, causative microorganisms and AP prescription rates were compared following international guideline updates.

Results: Sixteen studies were included, reporting over 1.3 million cases of IE. The crude incidence of IE following guideline updates has increased globally. Adjusted incidence increased in one study after European guideline updates, while North American rates did not increase. Cases of IE with a causative pathogen identified ranged from 62% to 91%. Rates of streptococcal IE varied across adult and pediatric populations, while the relative proportion of staphylococcal IE increased (range pre-guidelines 16-24.8%, range post-guidelines 26-43%). AP prescription trends were reduced in both moderate and high-risk patients following guideline updates.

Discussion: The restriction of AP to only high-risk patients has not resulted in an increase in the incidence of streptococcal IE in North American populations. The evidence of the impact of AP restriction on IE incidence is still unclear for other populations. Future population-based studies with adjusted incidence of IE, AP prescription rates and accurate pathogen identification are required to delineate findings further in these other regions.
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http://dx.doi.org/10.1177/17539447211002687DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8020745PMC
April 2021

Pleural effusion post coronary artery bypass surgery: associations and complications.

J Thorac Dis 2021 Feb;13(2):1083-1089

Department of Cardiothoracic Surgery, Royal Prince Alfred Hospital, New South Wales, Australia.

Background: One of the most frequent complications of coronary artery bypass grafting (CABG) is pleural effusion. Limited previous studies have found post-CABG pleural effusion to be associated with increased length-of-stay and greater morbidity post-CABG. Despite this the associations of this common complication are poorly described. This study sought to identify modifiable risk factors for effusion post-CABG.

Methods: A retrospective cohort study of prospectively collected data assessed patients who underwent CABG over two-years. Data was collected for risk factors and sequelae related to pleural effusion requiring drainage.

Results: A total of 409 patients were included. Average age was 64.9±10.2 years, 330 (80.7%) were male. 59 (14.4%) patients underwent drainage of pleural effusion post-CABG. Effusions were drained on average 9.9±8.4 days post-CABG. Earlier removal of drain tubes and removal near time of extubation were associated with development of pleural effusion. Post-CABG pleural effusion was associated with post-operative renal impairment (P<0.01) and pericardial effusion (P<0.01). Patients with pleural effusion were more likely to require readmission to ICU (P<0.01), reintubation (P=0.03) and readmission to hospital (P=0.03).

Conclusions: Pleural effusion is a common complication of cardiac surgery and is associated with significant morbidity and resource utilization. This study identifies several associated complications that should be considered in the presence of pleural effusion. Modifiable associated factors in the management of drains that may contribute to accumulation of pleural effusion include: early removal of chest drains, higher outputs and removal during or close to mechanical ventilation. Further research is required to assess how adjusting these modifiable factors can decrease rates of effusion post-operatively.
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http://dx.doi.org/10.21037/jtd-20-2082DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7947477PMC
February 2021

Staphylococcus aureus Enters Hair Follicles Using Triacylglycerol Lipases Preserved through the Genus Staphylococcus.

J Invest Dermatol 2021 Mar 9. Epub 2021 Mar 9.

Department of Dermatology, University of California San Diego, San Diego, California, USA. Electronic address:

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http://dx.doi.org/10.1016/j.jid.2021.02.009DOI Listing
March 2021

Ocular Injury Associated With Prone Positioning in Adult Critical Care: A Systematic Review and Meta-Analysis.

Am J Ophthalmol 2021 Mar 3;227:66-73. Epub 2021 Mar 3.

From the Department of Acute Critical Care Services, Craigavon Area Hospital, Portadown, Craigavon, United Kingdom.

Purpose: Prone positioning during the COVID-19 pandemic has become increasingly used as an adjunct to increase oxygenation in critical care patients. It is associated with an adverse event profile. This study sought to investigate the occurrence of ocular injuries reported in prone versus supine groups in adult critical care.

Design: Systematic review and meta-analysis.

Methods: A systematic review and meta-analysis were carried out in accordance with PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. PubMed, SCOPUS, and the Cochrane Library were searched. The search period was January 1, 1990, to July 1, 2020.

Results: Eleven randomized controlled trials were included, with 2,247 patients. Twenty-eight events were recorded in 3 trials (174 patients) and no events in the other 8 trials (2,073 patients). The rates of eye injury were 5 events in 1,158 patients (1.30%) and 13 events in 1,089 patients (1.19%) in the prone and supine groups, respectively, which were reduced to 2 of 1,158 patients (0.17%) and 2 of 1,089 patients (0.18%), respectively, when reports of eye or eyelid edema were removed. Meta-analysis demonstrated no significant differences between groups with (an OR of 1.40 (95% CI: 0.37-5.27) and without (OR: 0.78; 95% CI: 0.11-5.73) reported edema.

Conclusions: This meta-analysis showed no significant difference in the rate of reported ocular injury between prone and supine critical care groups. These rates remain higher than the incidence reported during general anesthesia. There is a need for studies in critical care settings in which ocular injury is an end-point and which include extended patient follow-up.
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http://dx.doi.org/10.1016/j.ajo.2021.02.019DOI Listing
March 2021

Operative management of an incidental portal vein aneurysm in the setting of an incarcerated congenital diaphragmatic hernia.

J Vasc Surg Cases Innov Tech 2021 Mar 27;7(1):64-67. Epub 2020 Oct 27.

Division of Vascular and Endovascular Surgery, Department of Surgery, Saint Louis University School of Medicine, St Louis, Mo.

Portal vein aneurysms are rare pathologic entities. A 3.7-cm portal vein aneurysm was incidentally discovered in an 80-year-old male patient on imaging for acute abdominal pain secondary to an incarcerated diaphragmatic hernia. The aneurysm was resected, and primary repair of the portal vein was performed during a second-look operation after repair of the incarcerated hernia. Operative intervention was chosen for this patient because of the aneurysm's size and the additional indication for abdominal exploration.
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http://dx.doi.org/10.1016/j.jvscit.2020.10.009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7903190PMC
March 2021

Integrated RNA Sequencing Reveals Epigenetic Impacts of Diesel Particulate Matter Exposure in Human Cerebral Organoids.

Dev Neurosci 2020 3;42(5-6):195-207. Epub 2021 Mar 3.

Department of Pediatrics & Human Development, Michigan State University, Grand Rapids, Michigan, USA,

Autism spectrum disorder (ASD) manifests early in childhood. While genetic variants increase risk for ASD, a growing body of literature has established that in utero chemical exposures also contribute to ASD risk. These chemicals include air-based pollutants like diesel particulate matter (DPM). A combination of single-cell and direct transcriptomics of DPM-exposed human-induced pluripotent stem cell-derived cerebral organoids revealed toxicogenomic effects of DPM exposure during fetal brain development. Direct transcriptomics, sequencing RNA bases via Nanopore, revealed that cerebral organoids contain extensive RNA modifications, with DPM-altering cytosine methylation in oxidative mitochondrial transcripts expressed in outer radial glia cells. Single-cell transcriptomics further confirmed an oxidative phosphorylation change in cell groups such as outer radial glia upon DPM exposure. This approach highlights how DPM exposure perturbs normal mitochondrial function and cellular respiration during early brain development, which may contribute to developmental disorders like ASD by altering neurodevelopment.
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http://dx.doi.org/10.1159/000513536DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7990702PMC
March 2021

Diabetes induces dysregulation of microRNAs associated with survival, proliferation and self-renewal in cardiac progenitor cells.

Diabetologia 2021 Jun 2;64(6):1422-1435. Epub 2021 Mar 2.

Department of Physiology-HeartOtago, School of Biomedical Sciences, University of Otago, Dunedin, New Zealand.

Aims/hypothesis: Diabetes mellitus causes a progressive loss of functional efficacy in stem cells, including cardiac progenitor cells (CPCs). The underlying molecular mechanism is still not known. MicroRNAs (miRNAs) are small, non-coding RNA molecules that regulate genes at the post-transcriptional level. We aimed to determine if diabetes mellitus induces dysregulation of miRNAs in CPCs and to test if in vitro therapeutic modulation of miRNAs would improve the functions of diabetic CPCs.

Methods: CPCs were isolated from a mouse model of type 2 diabetes (db/db), non-diabetic mice and human right atrial appendage heart tissue. Total RNA isolated from mouse CPCs was miRNA profiled using Nanostring analysis. Bioinformatic analysis was employed to predict the functional effects of altered miRNAs. MS analysis was applied to determine the targets, which were confirmed by western blot analysis. Finally, to assess the beneficial effects of therapeutic modulation of miRNAs in vitro and in vivo, prosurvival miR-30c-5p was overexpressed in mouse and human diabetic CPCs, and the functional consequences were determined by measuring the level of apoptotic cell death, cardiac function and mitochondrial membrane potential (MMP).

Results: Among 599 miRNAs analysed in mouse CPCs via Nanostring analysis, 16 miRNAs showed significant dysregulation in the diabetic CPCs. Using bioinformatics tools and quantitative real-time PCR (qPCR) validation, four altered miRNAs (miR-30c-5p, miR-329-3p, miR-376c-3p and miR-495-3p) were identified to play an important role in cell proliferation and survival. Diabetes mellitus significantly downregulated miR-30c-5p, while it upregulated miR-329-3p, miR-376c-3p and miR-495-3p. MS analysis revealed proapoptotic voltage-dependent anion-selective channel 1 (VDAC1) as a direct target for miR-30c-5p, and cell cycle regulator, cyclin-dependent protein kinase 6 (CDK6), as the direct target for miR-329-3p, miR-376c-3p and miR-495-3p. Western blot analyses showed a marked increase in VDAC1 expression, while CDK6 expression was downregulated in diabetic CPCs. Finally, in vitro and in vivo overexpression of miR-30c-5p markedly reduced the apoptotic cell death and preserved MMP in diabetic CPCs via inhibition of VDAC1.

Conclusions/interpretation: Our results demonstrate that diabetes mellitus induces a marked dysregulation of miRNAs associated with stem cell survival, proliferation and differentiation, and that therapeutic overexpression of prosurvival miR-30c-5p reduced diabetes-induced cell death and loss of MMP in CPCs via the newly identified target for miR-30c-5p, VDAC1.
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http://dx.doi.org/10.1007/s00125-021-05405-7DOI Listing
June 2021

Semantic Clustering During Verbal List Learning Is Associated With Employment Status in a Community Sample.

Percept Mot Skills 2021 Jun 27;128(3):1235-1251. Epub 2021 Feb 27.

Department of Psychology, University of Houston, Houston, Texas, United States.

The ability to learn and remember verbal information is highly relevant to many work roles and environments, but we know little about the underlying cognitive mechanisms of those associations. This study examined the hypothesis that unemployment is associated with decreased spontaneous use of higher-order encoding strategies deployed during list learning and recall. Participants were 120 employed and 59 unemployed community-dwelling adults who completed the California Verbal Learning Test-Second Edition (CVLT-II) as part of a broader neuropsychological assessment. Standardized measures of semantic, serial, and subjective clustering were generated from the CVLT-II. After adjusting for data-driven covariates, a significant interaction emerged between employment status and clustering strategy, whereby participants in the employed group exhibited significantly higher scores on semantic clustering, but not serial or subjective clustering, than the unemployed group. The semantic clustering slope score was higher among the employed group and was positively associated with executive functions and declarative memory. These findings suggest that higher-order semantic organizational strategies during supraspan list learning may be relevant to maintaining gainful employment (e.g., mentally organizing work-related instructions and task lists). Future studies might examine semantic clustering in relation to employment changes and work performance, as well as the potential benefit of metacognitive interventions for learning and employment success.
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http://dx.doi.org/10.1177/0031512521996875DOI Listing
June 2021

Activation of the cardiac non-neuronal cholinergic system prevents the development of diabetes-associated cardiovascular complications.

Cardiovasc Diabetol 2021 Feb 22;20(1):50. Epub 2021 Feb 22.

Department of Physiology, HeartOtago, School of Biomedical Sciences, University of Otago, 270, Great King Street, Dunedin, 9016, New Zealand.

Background: Acetylcholine (ACh) plays a crucial role in the function of the heart. Recent evidence suggests that cardiomyocytes possess a non-neuronal cholinergic system (NNCS) that comprises of choline acetyltransferase (ChAT), choline transporter 1 (CHT1), vesicular acetylcholine transporter (VAChT), acetylcholinesterase (AChE) and type-2 muscarinic ACh receptors (MAChR) to synthesize, release, degrade ACh as well as for ACh to transduce a signal. NNCS is linked to cardiac cell survival, angiogenesis and glucose metabolism. Impairment of these functions are hallmarks of diabetic heart disease (DHD). The role of the NNCS in DHD is unknown. The aim of this study was to examine the effect of diabetes on cardiac NNCS and determine if activation of cardiac NNCS is beneficial to the diabetic heart.

Methods: Ventricular samples from type-2 diabetic humans and db/db mice were used to measure the expression pattern of NNCS components (ChAT, CHT1, VAChT, AChE and MAChR) and glucose transporter-4 (GLUT-4) by western blot analysis. To determine the function of the cardiac NNCS in the diabetic heart, a db/db mouse model with cardiac-specific overexpression of ChAT gene was generated (db/db-ChAT-tg). Animals were followed up serially and samples collected at different time points for molecular and histological analysis of cardiac NNCS components and prosurvival and proangiogenic signaling pathways.

Results: Immunoblot analysis revealed alterations in the components of cardiac NNCS and GLUT-4 in the type-2 diabetic human and db/db mouse hearts. Interestingly, the dysregulation of cardiac NNCS was followed by the downregulation of GLUT-4 in the db/db mouse heart. Db/db-ChAT-tg mice exhibited preserved cardiac and vascular function in comparison to db/db mice. The improved function was associated with increased cardiac ACh and glucose content, sustained angiogenesis and reduced fibrosis. These beneficial effects were associated with upregulation of the PI3K/Akt/HIF1α signaling pathway, and increased expression of its downstream targets-GLUT-4 and VEGF-A.

Conclusion: We provide the first evidence for dysregulation of the cardiac NNCS in DHD. Increased cardiac ACh is beneficial and a potential new therapeutic strategy to prevent or delay the development of DHD.
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http://dx.doi.org/10.1186/s12933-021-01231-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7898760PMC
February 2021

Systematic Review of Preinjury Mental Health Problems as a Vulnerability Factor for Worse Outcome After Sport-Related Concussion.

Orthop J Sports Med 2020 Oct 20;8(10):2325967120950682. Epub 2020 Oct 20.

Department of Physical Medicine and Rehabilitation, Harvard Medical School, Boston, Massachusetts, USA.

Background: It is difficult to predict who will experience prolonged health problems after sustaining a sport-related concussion.

Purpose: To synthesize the literature and conduct a gap analysis on the association between preinjury mental health problems and clinical outcome from sport-related concussion.

Study Design: Systematic review; Level of evidence, 4.

Methods: Data sources were PubMed, PsycINFO, MEDLINE (and MEDLINE in Process), CINAHL, Cochrane Library, EMBASE, SPORTDiscus, Scopus, and Web of Science. Studies published before February 2019 that addressed preinjury mental health problems as a possible predictor of worse clinical outcome or clinical recovery from concussion were eligible for inclusion.

Results: Of 4013 studies screened, 358 full texts were reviewed, and 12 studies involving 3761 participants (n = 471 [12.5%] with preexisting mental health problems) were ultimately included. The participants with a preinjury history of mental health problems were at greater risk for having persistent symptoms or worse outcome in 9 of 12 studies. The studies had major methodological differences, and most studies were not focused on mental health as a primary predictor or prognostic factor. Rather, they included it as a secondary or tertiary predictor. The sample sizes with preinjury mental health problems in most studies were small or very small (ie, <25). The age of onset, type, course, severity, and duration of mental health problems were not defined. The extent to which mental health problems were present before the season, during baseline testing, was not reported.

Conclusion: Preinjury mental health problems appear to confer risk for worse clinical outcome after sport-related concussion. Future research is needed to (1) examine this risk factor in large representative populations of middle school students, high school students, and collegiate athletes; (2) quantify the risk for each mental health condition; (3) understand the mechanisms underlying this increased risk; and (4) develop more refined treatment and rehabilitation approaches for these student-athletes.
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http://dx.doi.org/10.1177/2325967120950682DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7871078PMC
October 2020

Effects of Permethrin or Deltamethrin Exposure in Adult Sprague Dawley Rats on Acoustic and Light Prepulse Inhibition of Acoustic or Tactile Startle.

Neurotox Res 2021 Jun 20;39(3):543-555. Epub 2021 Feb 20.

Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, 45229, USA.

The effects of permethrin (PRM) and deltamethrin (DLM) on acoustic or light prepulse inhibition of the acoustic startle response (ASR) and tactile startle response (TSR) were studied in adult male Sprague Dawley rats. Preliminary studies were conducted to optimize the parameters of light and acoustic prepulse inhibition of ASR and TSR. Once these parameters were set, a new group of rats was administered PRM (0 or 90 mg/kg) or DLM (0 or 25 mg/kg) by gavage in 5 mL/kg corn oil. ASR and TSR were assessed using acoustic or light prepulses 6, 8, and 12 h after PRM and 2, 4, and 6 h after DLM exposure. PRM increased ASR 6 h post-treatment with no interaction with acoustic prepulse levels and with no effect on TSR. When light was used as the prepulse, PRM increased ASR and TSR at 6 h with no interaction with prepulse levels. DLM decreased ASR and TSR on trials without prepulses but not on trials with acoustic prepulses. DLM also decreased ASR when light prepulses were present 4 h post-treatment. A final experiment assessed whether the house light in the test cabinet affected ASR and TSR after PRM or DLM exposure. Rats had increased ASR and TSR when house lights were on compared with when they were off, but lighting did not differentially interact with PRM or DLM. Light and acoustic prepulses of ASR and TSR have different effects depending on the test agent and the test parameters.
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http://dx.doi.org/10.1007/s12640-021-00339-9DOI Listing
June 2021

Differences in rapid increases in county-level COVID-19 incidence by implementation of statewide closures and mask mandates - United States, June 1-September 30, 2020.

Ann Epidemiol 2021 05 14;57:46-53. Epub 2021 Feb 14.

Public Health Law Program, Centers for Disease Control and Prevention, Atlanta, GA.

Background And Objective: Community mitigation strategies could help reduce COVID-19 incidence, but there are few studies that explore associations nationally and by urbanicity. In a national county-level analysis, we examined the probability of being identified as a county with rapidly increasing COVID-19 incidence (rapid riser identification) during the summer of 2020 by implementation of mitigation policies prior to the summer, overall and by urbanicity.

Methods: We analyzed county-level data on rapid riser identification during June 1-September 30, 2020 and statewide closures and statewide mask mandates starting March 19 (obtained from state government websites). Poisson regression models with robust standard error estimation were used to examine differences in the probability of rapid riser identification by implementation of mitigation policies (P-value< .05); associations were adjusted for county population size.

Results: Counties in states that closed for 0-59 days were more likely to become a rapid riser county than those that closed for >59 days, particularly in nonmetropolitan areas. The probability of becoming a rapid riser county was 43% lower among counties that had statewide mask mandates at reopening (adjusted prevalence ratio = 0.57; 95% confidence intervals = 0.51-0.63); when stratified by urbanicity, associations were more pronounced in nonmetropolitan areas.

Conclusions: These results underscore the potential value of community mitigation strategies in limiting the COVID-19 spread, especially in nonmetropolitan areas.
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http://dx.doi.org/10.1016/j.annepidem.2021.02.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7882220PMC
May 2021

Usefulness of Perioperative Laboratory Tests in Total Hip and Knee Arthroplasty: Are They Necessary for All Patients?

Arthroplast Today 2021 Feb 30;7:136-142. Epub 2021 Jan 30.

Colorado Joint Replacement, Porter Adventist Hospital, Denver, CO, USA.

Background: Laboratory studies are routinely obtained preoperatively and postoperatively for total hip arthroplasty (THA) and total knee arthroplasty (TKA). This study evaluates the necessity of routine, perioperative laboratory tests and identifies risk factors for laboratory-associated interventions.

Methods: This retrospective review evaluated 967 consecutive patients scheduled for primary, unilateral TKAs (n = 593) or THAs (n = 374) over an 18-month period at a single institution. Preoperative prothrombin time (PT) and International Normalized Ratio (INR), complete blood count (CBC), complete metabolic panel (CMP), and postoperative CBC and basic metabolic panel (BMP) were recorded along with any laboratory-associated intervention. Patient demographics and comorbidities identified risk factors for abnormal or actionable laboratory studies.

Results: Preoperatively, the actionable rates for PT/INR, CMP, and CBC were 0.3%, 1.4%, and 0.5%, respectively. Vascular, renal, and immunologic diseases were risk factors for an actionable CBC. Risk factors for an actionable CMP include cardiac arrhythmia and diabetes. There were no risk factors for an actionable PT/INR. Postoperatively, only 1.5% of BMPs and 1.5% of CBCs were actionable. Congestive heart failure, renal disease vascular disease, or history of cancer ( = .030) were risk factors for an actionable CBC. There were no risk factors for an actionable BMP. Patients with an abnormal preoperative lab were 2.4 times more likely to have an actionable postoperative lab. Patients with an actionable preoperative lab were 11.3 times more likely to have an actionable postoperative lab.

Conclusion: Routine preoperative and postoperative labs may not be necessary on all patients undergoing a TKA or THA. Comorbid risk factors and abnormal or actionable preoperative CMPs and CBCs can help determine the usefulness of postoperative laboratory assessments.
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http://dx.doi.org/10.1016/j.artd.2020.12.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7850936PMC
February 2021

Comparative history of Campylobacter contamination on chicken meat and campylobacteriosis cases in the United States: 1994-2018.

Int J Food Microbiol 2021 Mar 26;342:109075. Epub 2021 Jan 26.

National Antimicrobial Resistance Monitoring System, Center for Veterinary Medicine, U.S. Food & Drug Administration, 8401 Muirkirk Road, Laurel, MD 20708, USA.

In many countries campylobacteriosis ranks as one of the most frequently reported foodborne illnesses and poultry is the commodity that is most often associated with these illnesses. Nevertheless, efforts to reduce the occurrence of pathogen contamination on poultry are often more focused on Salmonella. While some control measures are pathogen specific, such as pre-harvest vaccination for Salmonella, improvements in sanitary dressing and interventions applied during the slaughter process can be effective against all forms of microbial contamination. To investigate the potential effectiveness of these non-specific pathogen reduction strategies in the United States, it is helpful to assess if, and by how much, Campylobacter contamination of chicken meat has changed across time. This study assesses change considering data collected in both slaughter and retail establishments and comparing observed trends in contamination with trends in human surveillance data. The results support the assertion that substantial reductions in Campylobacter contamination of chicken meat in the late 1990s and early 2000s contributed to a reduction in the human case rate of campylobacteriosis. Further reductions in chicken meat contamination between 2013 and 2018 are more difficult to associate with trends in human illnesses, with one contributing factor being the inclusion of culture independent diagnostic test results in the official case counts during that time. Other contributing factors are discussed.
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http://dx.doi.org/10.1016/j.ijfoodmicro.2021.109075DOI Listing
March 2021

The Risk and Reward of Speaking Out for Racial Equity in Surgical Training.

J Surg Educ 2021 Jan 30. Epub 2021 Jan 30.

Department of Surgery, University of Virginia, Charlottesville, Virginia.

In order to maintain productivity and career advancement, Black and Brown individuals often find themselves downplaying persistent elements of bias and racism experienced in predominantly white fields. These elements are commonly reinforced by institutional and departmental policies that hinder the creation of an equitable and inclusive environment for all. In this manuscript, we outline specific challenges faced by Black and Brown trainees and faculty that are perpetuated by such policies. The challenges are followed by specific recommendations for change as they may apply to faculty, staff and trainees. The outlined recommendations or "action items" may be enacted by any residency program or department based on perceived timeliness and should serve as a foundation for change-one that is intently created through a lens of anti-racism. The risk of speaking up for racial equity is outweighed by the potential rewards of building an environment that is diverse, inclusive and better for everyone.
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http://dx.doi.org/10.1016/j.jsurg.2021.01.015DOI Listing
January 2021

Impact of preweaning stress on long-term neurobehavioral outcomes in Sprague-Dawley rats: Differential effects of barren cage rearing, pup isolation, and the combination.

Neurotoxicol Teratol 2021 Mar-Apr;84:106956. Epub 2021 Jan 29.

Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH 45229, USA; Division of Neurology, Cincinnati Children's Research Foundation, Cincinnati, OH, USA. Electronic address:

Two developmental stressors were compared in preweaning rats exposed to either one stressor or both. Stressors were barren cage rearing or maternal separation (pup isolation). 40 gravid Sprague-Dawley CD/IGS rats were randomly assigned to two cage conditions: standard (Std) cage or barren cage (Bar), 20 litters/condition throughout gestation and lactation. After delivery, litters were randomly culled to 4 males and 4 females. The second stressor was maternal separation: Two male/female pairs per litter were isolated from their dam 4 h/day (Iso) and two pairs were not (Norm). Hence, there were 4 conditions: Std-Norm, Std-Iso, Bar-Norm, and Bar-Iso. One pair/litter/stress condition received the following: elevated zero-maze (EZM), open-field, swim channel, Cincinnati water maze, conditioned fear, and open-field with methamphetamine challenge. The second pair/litter/condition received the light-dark test, swim channel, Morris water maze, forced swim, and EZM with diazepam challenge. Barren rearing reduced EZM time-in-open, whereas isolation rearing reduced open-field activity in males and increased it in females. Effects on straight channel swimming were minor. In the Cincinnati water maze test of egocentric learning, isolation rearing increased errors whereas barren cage housing reduced errors in combination with normal rearing. Barren cage with maternal separation (pup isolation) increased Cincinnati water maze escape latency but not errors. Barren cage housing reduced hyperactivity in response to methamphetamine. Isolation rearing increased time in open in the EZM after diazepam challenge. Trends were seen in the Morris water maze. These suggested that barren cage and isolation rearing in combination reduced latency on acquisition on days 1 and 2 in males, whereas females had increased latency on days 2 and 3. Combined exposure to two developmental stressors did not induce additive or synergistic effects, however the data show that these stressors had long-term effects with some evidence that the combination of both caused effects when either stressor alone did not, but synergism was not observed.
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http://dx.doi.org/10.1016/j.ntt.2021.106956DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7965361PMC
January 2021

Workshop focuses on the rise in MSE undergraduates.

MRS Bull 2021 Jan 22:1-7. Epub 2021 Jan 22.

Department of Materials Science and Engineering, McMaster University, Hamilton, ON Canada.

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http://dx.doi.org/10.1557/s43577-020-00005-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7822586PMC
January 2021

The Push, Pull, and Enabling Capacities Necessary for Legume Grain Inclusion into Sustainable Agri-Food Systems and Healthy Diets.

World Rev Nutr Diet 2020 6;121:193-211. Epub 2020 Oct 6.

Ecological Sciences, James Hutton Institute, Dundee, United Kingdom.

Legume grains are traditional crops that have been modernized as processed foods and animal protein alternatives in recent years. This modernization has largely been fueled by new technological developments driven by increased consumer demands for plant protein and gluten-free options. However, consumers must be mindful that legumes have other nutritional attributes besides protein that help achieve healthier diets, and recent evidence suggests that consuming 100 g of legume grains per day would promote nutrient-dense diets and could be a target level to harmonize international strategies for recommended daily allowances. The nutritional richness of legumes has been associated with a decrease in numerous disease risk factors and, given their long shelf life, legumes are excellent choices to combat food waste and may have a role to play in countries where cold storage is often a limitation in food preservation. Besides their inclusion in global diets, legumes should be included in sustainable cropping systems. The high number of edible species and cultivars available render them excellent contributors to biodiverse food and feed systems. Legume cultivation allows reducing environmental impacts by means of the ability of legumes to fix atmospheric nitrogen via a symbiosis with nitrogen-fixing bacteria, making them natural fertilizers. Still, despite the well-known health, nutritional, and environmental benefits, legumes are underrepresented in global agri-food systems. Efforts must be made to make legumes more attractive to the farmer, the industry, and ultimately the consumer, and for this proper local, regional, national, and global policy frameworks must be in place. Here, the local scenario of legumes is showcased, and the most relevant push, pull, and enabling capacities required to achieve sustainable diversified agri-food systems with legumes are discussed.
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http://dx.doi.org/10.1159/000507498DOI Listing
October 2020

Editorial: Geoffrey Burnstock - An Accidental Pharmacologist.

Biochem Pharmacol 2021 May 19;187:114421. Epub 2021 Jan 19.

Ohio State University, Columbus, OH, USA. Electronic address:

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http://dx.doi.org/10.1016/j.bcp.2021.114421DOI Listing
May 2021

Beat-to-beat blood pressure measurement using a cuffless device does not accurately reflect invasive blood pressure.

Int J Cardiol Hypertens 2020 Jun 14;5:100030. Epub 2020 Apr 14.

Department of Medicine - HeartOtago, Dunedin School of Medicine, University of Otago, Dunedin, New Zealand.

Background: The availability of an accurate continuous cuffless blood pressure (BP) monitor would provide an alternative to both invasive continuous BP and 24-h intermittent cuff-based BP monitors. We investigated the accuracy of a cuffless beat to beat (BtB) device compared to both invasive BP (iBP) and brachial cuff BP (cBP) measurements.

Methods: Patients undergoing clinically indicated coronary angiography (CA) and/or percutaneous coronary intervention (PCI) were recruited. After calibration to an initial cBP reading, BP was measured simultaneously using a BtB device (SOMNOtouch NIBP), brachial artery iBP, and cBP at two time points.

Results: The study was terminated early due to a significant bias. Recordings from 14 participants (11 males, mean age 68.4 years) were analysed. Readings from BtB BP were higher than iBP. The bias between BtB BP and iBP was 34.3 mmHg (95%CI: 27.0, 41.5) and 23.6 mmHg (95%CI: 16.8, 30.4) for SBP and DBP respectively. A similar bias was seen between BtB BP and cBP, but cBP and iBP were largely in agreement.

Conclusions: In patients undergoing CA/PCI, significant differences were detected between BtB BP and both invasively measured and cuff BP. The non-invasive BtB BP measurement device tested is not suitable for clinical or research use.
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http://dx.doi.org/10.1016/j.ijchy.2020.100030DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7803068PMC
June 2020

Identification of synergistic and antagonistic actions of environmental pollutants: Bisphenols A, S and F in the presence of DEP, DBP, BADGE and BADGE·2HCl in three component mixtures.

Sci Total Environ 2021 May 4;767:144286. Epub 2021 Jan 4.

Department of Neuroscience, Functional Pharmacology, University of Uppsala, Uppsala, Sweden; Institute of Translational Medicine and Biotechnology, I. M. Sechenov First Moscow State Medical University, Moscow, Russia.

Ecosystems are facing increased pressure due to the emission of many classes of emerging contaminants. However, very little is known about the interactions of these pollutants, such as bisphenols (BPs), plasticizers or pharmaceuticals. By employing bioluminescent bacteria (Microtox assay), we were able to define interactions between selected emerging pollutants (namely BPA, BPS, BPF, BADGE, BADGE·2HCl, DEP, DBP) in ternary mixtures, at environmentally relevant concentration levels (down to as low as 1.89, 1.42, 3.08, and 0.326 μM for, respectively, BPA, BPF, BPS and BADGE·2HCl). We provide the first systematic analysis of bisphenols and phthalates in three component mixtures. Using this system, we performed toxicity modelling with concentration addition (CA) and independent action (IA) approaches, followed by data interpretation using Model Deviation Ratio (MDR) evaluation. Interestingly, we mathematically and experimentally confirmed a novel synergy between BPA, BADGE and BADGE·2HCl. The synergy of BPA, BADGE and BADGE·2HCl is distinct, with both models suggesting these analytes have a similar mode of action (MOA). Moreover, we unexpectedly found a strong antagonistic impact with DEP, in mixtures containing BPA and BADGE analogues, which is confirmed with both mathematical models. Our study also shows that the impact of BPS and BPF in many mixtures is highly concentration dependent, justifying the necessity to perform mixture studies using wide concentration ranges. Overall, this study demonstrates that bioluminescent bacteria are a relevant model for detecting the synergistic and antagonist actions of environmental pollutants in mixtures, and highlights the importance of analyzing combinations of pollutants in higher order mixtures.
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http://dx.doi.org/10.1016/j.scitotenv.2020.144286DOI Listing
May 2021

Robotic pelvic exenteration and extended pelvic resections for locally advanced or synchronous rectal and urological malignancy.

Investig Clin Urol 2021 Jan;62(1):111-120

Department of Surgery, Faculty of Medicine, The University of Queensland, Brisbane, Queensland, Australia.

Purpose: To describe the surgical technique and examine the feasibility and outcomes following robotic pelvic exenteration and extended pelvic resection for rectal and/or urological malignancy.

Materials And Methods: We present a case series of seven patients with locally advanced or synchronous urological and/or rectal malignancy who underwent robotic total or posterior pelvic exenteration between 2012-2016.

Results: In total, we included seven patients undergoing pelvic exenteration or extended pelvic resection. The mean operative time was 485±157 minutes and median length of stay was 9 days (6-34 days). There was only one Clavien-Dindo complication grade 3 which was a vesicourethral anastomotic leak requiring rigid cystoscopy and bilateral ureteric catheter insertion. Eighty-five percent of patients had clear colorectal margins with a median margin of 3.5 mm (0.7-8.0 mm) while all urological margins were clear. Six out of seven patients had complete (grade 3) total mesorectal excision. Three patients experienced recurrence at a median of 22 months (21-24 months) post-operatively. Of the three recurrences, one was systemic only whilst two were both local and systemic. One patient died from complications of dual rectal and prostate cancer 31 months after the surgery.

Conclusions: We report a large series examining robotic pelvic exenteration or extended pelvic resection and describe the surgical technique involved. The robotic approach to pelvic exenteration is highly feasible and demonstrates acceptable peri-operative and oncological outcomes. It has the potential to benefit patients undergoing this highly complex and morbid procedure.
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http://dx.doi.org/10.4111/icu.20200176DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7801165PMC
January 2021