Parsing the role of NSP1 in SARS-CoV-2 infection

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of the ongoing coronavirus disease 19 (COVID-19) pandemic. Despite its urgency, we still do not fully understand the molecular basis of SARS-CoV-2 pathogenesis and its ability to antagonize innate immune responses. SARS-CoV-2 leads to shutoff of cellular protein synthesis and over-expression of nsp1, a central shutoff factor in coronaviruses, inhibits cellular gene translation. However, the diverse molecular mechanisms nsp1 employs as well as its functional importance in infection are still unresolved. By overexpressing various nsp1 mutants and generating a SARS-CoV-2 mutant in which nsp1 does not bind ribosomes, we untangle the effects of nsp1. We uncover that nsp1, through inhibition of translation and induction of mRNA degradation, is the main driver of host shutoff during SARS-CoV-2 infection. Furthermore, we find the propagation of nsp1 mutant virus is inhibited specifically in cells with intact interferon (IFN) response as well as in-vivo, in infected hamsters, and this attenuation is associated with stronger induction of type I IFN response. This illustrates that nsp1 shutoff activity has an essential role mainly in counteracting the IFN response. Overall, our results reveal the multifaceted approach nsp1 uses to shut off cellular protein synthesis and uncover the central role it plays in SARS-CoV-2 pathogenesis, explicitly through blockage of the IFN response.

[INTRAPARTUM ULTRASOUND - THE FUTURE IS HERE].

INTRODUCTION: This review aims to present the different applications and benefits of intrapartum ultrasound (IPUS) compared to the traditional digital vaginal examination. IPUS is non-invasive, does not cause pain or discomfort to the woman and may reduce the rate of ascending infections. In comparison to the vaginal exam, IPUS is more accurate in diagnosing fetal head position and station, is easy to acquire and has a faster learning curve. Applications of IPUS include: 1. Diagnosing the fetal head position either by suprapubic or trans-perineal ultrasound when the fetal head is low, which is more accurate than the digital vaginal exam; 2. Measuring cervical dilatation and effacement by trans-perineal ultrasound. This may be of more value especially in patients with ruptured membranes or patients who have difficulty with invasive examinations; 3. Assessing fetal head station and labor progress by measuring the head-perineal distance (HPD) and the angle of progression (AOP); 4. Estimating the pelvic size relative to the fetal head by measuring the pubic arch angle and fetal head circumference; 5. Predicting the mode of delivery before and during the labor process; 6. Prior to deciding the mode of delivery in a prolonged second stage of labor; 7. Providing a visual biofeedback to improve pushing efforts and mother-baby connection.

Endoscopic hemostasis is rarely used for hematochezia: a population-based study from the Clinical Outcomes Research Initiative National Endoscopic Database.

BACKGROUND: Data on the use of endoscopic hemostasis performed during colonoscopy for hematochezia are primarily derived from expert opinion and case series from tertiary care settings. OBJECTIVES: To characterize patients with hematochezia who underwent in-patient colonoscopy and compare those who did and did not receive endoscopic hemostasis. DESIGN: Retrospective analysis. SETTING: Clinical Outcomes Research Initiative National Endoscopic Database, 2002 to 2008. PATIENTS: Adults with hematochezia. INTERVENTIONS: None. MAIN OUTCOME MEASUREMENTS: Demographics, comorbidities, practice setting, adverse events, and colonoscopy procedural characteristics and findings. RESULTS: We identified 3151 persons who underwent in-patient colonoscopy for hematochezia. Endoscopic hemostasis was performed in 144 patients (4.6%). Of those who received endoscopic hemostasis, the majority were male (60.3%), white (83.3%), and older (mean age 70.9 ± 12.3 years); had a low-risk American Society of Anesthesiologists classification (53.9%); and underwent colonoscopy in a community setting (67.4%). The hemostasis-receiving cohort was significantly more likely to be white (83.3% vs 71.0%, P = .02), have more comorbidities (classes 3 and 4, 46.2% vs 36.0%, P = .04), and have the cecum reached (95.8% vs 87.7%, P = .003). Those receiving hemostasis were significantly more likely to have an endoscopic diagnosis of arteriovenous malformations (32.6% vs 2.6%, P = .0001) or a solitary ulcer (8.3% vs 2.1%, P < .0001). LIMITATIONS: Retrospective database analysis. CONCLUSIONS: Less than 5% of persons presenting with hematochezia and undergoing inpatient colonoscopy received endoscopic hemostasis. These findings differ from published tertiary care setting data. These data provide new insights into in-patient colonoscopy performed primarily in a community practice setting for patients with hematochezia.

The role of colonoscopy in evaluating hematochezia: a population-based study in a large consortium of endoscopy practices.

BACKGROUND: Data on the role of colonoscopy in hematochezia are almost exclusively derived from clinical experience in tertiary care practice. OBJECTIVE: To characterize the patient population who received colonoscopy for hematochezia in a consortium of diverse gastroenterology practices. DESIGN: Retrospective analysis. SETTING: Clinical Outcomes Research Initiative Database, 2002 to 2008. PATIENTS: Adults undergoing colonoscopy for the indication of hematochezia. MAIN OUTCOME MEASUREMENTS: Demographics, comorbidity, practice setting, adverse events, and colonoscopy procedure characteristics and findings. Age-stratified analyses and analyses of inpatient- versus outpatient-performed colonoscopies were also performed. RESULTS: A total of 966,536 colonoscopies were performed during the study period, 76,186 (7.9%) were performed for evaluation of hematochezia. The majority of patients were white non-Hispanic men younger than 60 years old who underwent colonoscopy at a community practice site (79.1%) and had a low-risk American Society of Anesthesiologists (ASA) score (81.5%), in whom colonoscopy reached the cecum (94.8%), and serious adverse events were rare. Colonoscopy findings were hemorrhoids (64.4%), diverticulosis (38.6%), and polyp or multiple polyps (38.8%). From the overall cohort, 38.3% were 60 years of age and older. The older age cohort had significantly more white non-Hispanic females, high-risk ASA scores, incomplete colonoscopies, and unplanned events. Colonoscopy findings demonstrated significantly higher rates of diverticulosis, polyp or multiple polyps, mucosal abnormality/colitis, tumor, and solitary ulcer (P < .0001). There were 3941 (5.2%) who underwent inpatient-performed colonoscopy. One third of this cohort (32.6%) was defined as having a high ASA score. LIMITATIONS: Retrospective database review. CONCLUSIONS: These results describe patient populations and characterize colonoscopy findings in individuals presenting with hematochezia primarily in a community practice setting.