Prenatal imaging features and perinatal outcomes of foetal volvulus-A literature review.

OBJECTIVE: To conduct a review of the literature on foetal volvulus with emphasis on prenatal imaging, pregnancy characteristics and clinical outcomes. METHODS: A review of all published cases of foetal volvulus diagnosed prenatally and indexed in Medline, EBSCOhost, CINAHL, SOCIndex and Healthy Policy Reference Centre. Studies without antenatal sonographic signs of foetal volvulus and without a postpartum surgical diagnosis were excluded. Data were analysed for frequencies and distributions and tested for statistical significance. RESULTS: Eighty-eight cases of foetal volvulus were identified from 58 published case reports/series. The most common ultrasound findings were dilated bowel/stomach (77.3%), polyhydramnios (30.7%) and whirlpool/snail sign (28.4%). Median gestation at diagnosis was 31.9 weeks (IQR 27-34) and mean gestation at delivery was 34.5 weeks (SD 2.8). Underlying aetiology included intestinal malrotation (15.9%), cystic fibrosis (14.8% of all cases, 32.5% of tested cases) and abnormal mesenteric fixation (12.5%). Complications included intestinal atresia (36.4%) and foetal anaemia (9.1%). The overall perinatal mortality rate was 14.5%. CONCLUSION: Foetal volvulus is a rare condition with high rates of preterm birth and perinatal mortality. Intestinal malrotation and cystic fibrosis are common predisposing causes, although the majority are idiopathic. Bowel and/or gastric dilatation is by far the most common sonographic finding.

Actionable pharmacogenetic variants in Hong Kong Chinese exome sequencing data and projected prescription impact in the Hong Kong population.

Preemptive pharmacogenetic testing has the potential to improve drug dosing by providing point-of-care patient genotype information. Nonetheless, its implementation in the Chinese population is limited by the lack of population-wide data. In this study, secondary analysis of exome sequencing data was conducted to study pharmacogenomics in 1116 Hong Kong Chinese. We aimed to identify the spectrum of actionable pharmacogenetic variants and rare, predicted deleterious variants that are potentially actionable in Hong Kong Chinese, and to estimate the proportion of dispensed drugs that may potentially benefit from genotype-guided prescription. The projected preemptive pharmacogenetic testing prescription impact was evaluated based on the patient prescription data of the public healthcare system in 2019, serving 7.5 million people. Twenty-nine actionable pharmacogenetic variants/ alleles were identified in our cohort. Nearly all (99.6%) subjects carried at least one actionable pharmacogenetic variant, whereas 93.5% of subjects harbored at least one rare deleterious pharmacogenetic variant. Based on the prescription data in 2019, 13.4% of the Hong Kong population was prescribed with drugs with pharmacogenetic clinical practice guideline recommendations. The total expenditure on actionable drugs was 33,520,000 USD, and it was estimated that 8,219,000 USD (24.5%) worth of drugs were prescribed to patients with an implicated actionable phenotype. Secondary use of exome sequencing data for pharmacogenetic analysis is feasible, and preemptive pharmacogenetic testing has the potential to support prescription decisions in the Hong Kong Chinese population.

Sensitive detection and quantification of SARS-CoV-2 in saliva

Saliva has significant advantages as a test medium for detection of SARS-CoV-2 infection in patients, such as ease of collection, minimal requirement of supplies and trained personnel, and safety. Comprehensive validation in a large cohort of prospectively collected specimens with unknown SARS-CoV-2 status should be performed to evaluate the potential and limitations of saliva-based testing. We developed a saliva-based testing pipeline for detection of SARS-CoV-2 nucleic acids using real-time reverse transcription PCR (RT-PCR) and droplet digital PCR (ddPCR) readouts, and measured samples from 137 outpatients tested at a curbside testing facility and 29 inpatients hospitalized for COVID-19. These measurements were compared to the nasal swab results for each patient performed by a certified microbiology laboratory. We found that our saliva testing positively detects 100% (RT-PCR) and 93.75% (ddPCR) of curbside patients that were identified as SARS-CoV-2 positive by the Emergency Use Authorization (EUA) certified nasal swab testing assay. Quantification of viral loads by ddPCR revealed an extremely wide range, with 1 million-fold difference between individual patients. Our results demonstrate for both community screening and hospital settings that saliva testing reliability is on par with that of the nasal swabs in detecting infected cases, and has potential for higher sensitivity when combined with ddPCR in detecting low-abundance viral loads that evade traditional testing methods.

Type I Interferon Limits Viral Dissemination-Driven Clinical Heterogeneity in a Native Murine Betacoronavirus Model of COVID-19

Emerging clinical data demonstrates that COVID-19, the disease caused by SARS-CoV2, is a syndrome that variably affects nearly every organ system. Indeed, the clinical heterogeneity of COVID-19 ranges from relatively asymptomatic to severe disease with death resultant from multiple constellations of organ failures. In addition to genetics and host characteristics, it is likely that viral dissemination is a key determinant of disease manifestation. Given the complexity of disease expression, one major limitation in current animal models is the ability to capture this clinical heterogeneity due to technical limitations related to murinizing SARS-CoV2 or humanizing mice to render susceptible to infection. Here we describe a murine model of COVID-19 using respiratory infection with the native mouse betacoronavirus MHV-A59. We find that whereas high viral inoculums uniformly led to hypoxemic respiratory failure and death, lethal dose 50% (LD50) inoculums led to a recapitulation of most hallmark clinical features of COVID-19, including lymphocytopenias, heart and liver damage, and autonomic dysfunction. We find that extrapulmonary manifestations are due to viral metastasis and identify a critical role for type-I but not type-III interferons in preventing systemic viral dissemination. Early, but not late treatment with intrapulmonary type-I interferon, as well as convalescent serum, provided significant protection from lethality by limiting viral dissemination. We thus establish a Biosafety Level II model that may be a useful addition to the current pre-clinical animal models of COVID-19 for understanding disease pathogenesis and facilitating therapeutic development for human translation.

Ketogenesis restrains aging-induced exacerbation of COVID in a mouse model

Increasing age is the strongest predictor of risk of COVID-19 severity. Unregulated cytokine storm together with impaired immunometabolic response leads to highest mortality in elderly infected with SARS-CoV-2. To investigate how aging compromises defense against COVID-19, we developed a model of natural murine beta coronavirus (mCoV) infection with mouse hepatitis virus strain MHV-A59 (mCoV-A59) that recapitulated majority of clinical hallmarks of COVID-19. Aged mCoV-A59-infected mice have increased mortality and higher systemic inflammation in the heart, adipose tissue and hypothalamus, including neutrophilia and loss of {gamma}{delta} T cells in lungs. Ketogenic diet increases beta-hydroxybutyrate, expands tissue protective {gamma}{delta} T cells, deactivates the inflammasome and decreases pathogenic monocytes in lungs of infected aged mice. These data underscore the value of mCoV-A59 model to test mechanism and establishes harnessing of the ketogenic immunometabolic checkpoint as a potential treatment against COVID-19 in the elderly. Highlights - Natural MHV-A59 mouse coronavirus infection mimics COVID-19 in elderly. - Aged infected mice have systemic inflammation and inflammasome activation - Murine beta coronavirus (mCoV) infection results in loss of pulmonary {gamma}{delta} T cells. - Ketones protect aged mice from infection by reducing inflammation. eTOC BlurbElderly have the greatest risk of death from COVID-19. Here, Ryu et al report an aging mouse model of coronavirus infection that recapitulates clinical hallmarks of COVID-19 seen in elderly. The increased severity of infection in aged animals involved increased inflammasome activation and loss of {gamma}{delta} T cells that was corrected by ketogenic diet.

Manipulating Cellular Activities Using an Ultrasound-Chemical Hybrid Tool.

We developed an ultrasound-chemical hybrid tool to precisely manipulate cellular activities. A focused ultrasound coupled with gas-filled microbubbles was used to rapidly trigger the influx of membrane-impermeable chemical dimerizers into living cells to regulate protein dimerization and location without inducing noticeable toxicity. With this system, we demonstrated the successful modulation of phospholipid metabolism triggered by a short pulse of ultrasound exposure. Our technique offers a powerful and versatile tool for using ultrasound to spatiotemporally manipulate the cellular physiology in living cells.

Role of reactive oxygen species in the antibacterial mechanism of silver nanoparticles on Escherichia coli O157:H7.

In this study, the conditions and mechanism of antibacterial activity of hydrophilic polymer coated silver nanoparticles (AgNPs) against E. coli O157:H7 (CMCC44828) as model pathogen was studied. The AgNPs were coated with amphiphilic polymer that introduced carboxyl groups on the surface to make it water-soluble. The AgNPs were exposed to various treatment conditions of pH and temperature before these were combined with the E. coli. The mechanism of the antibacterial activity was studied through the formation of reactive oxygen species (ROS) that was later suppressed with antioxidant to establish correlation with the AgNPs antimicrobial activity. Studies were carried out at both anaerobic and aerobic conditions. The results indicated that 5 mg/L AgNPs inhibited ~50% of the growth of 10(6) colony forming units per milliliter (cfu/mL) E. coli cells in liquid Luria-Bertani (LB) medium. This dose-dependent antimicrobial activity was higher at increased temperature (37°C) but was lower when the AgNPs were treated with acid at pH 2 before exposure to the bacteria. It was also established that the conditions of higher antimicrobial effect generated more ROS that was dependent on the presence of oxygen. The antibacterial activity was suppressed in the presence of an antioxidant.