An unusual topological structure of the HIV-1 Rev response element.

Nuclear export of unspliced and singly spliced viral mRNA is a critical step in the HIV life cycle. The structural basis by which the virus selects its own mRNA among more abundant host cellular RNAs for export has been a mystery for more than 25 years. Here, we describe an unusual topological structure that the virus uses to recognize its own mRNA. The viral Rev response element (RRE) adopts an "A"-like structure in which the two legs constitute two tracks of binding sites for the viral Rev protein and position the two primary known Rev-binding sites ~55 Å apart, matching the distance between the two RNA-binding motifs in the Rev dimer. Both the legs of the "A" and the separation between them are required for optimal RRE function. This structure accounts for the specificity of Rev for the RRE and thus the specific recognition of the viral RNA.

Skin Testing for Penicillin Allergy: a Review of the Literature.

PURPOSE OF REVIEW: Self-reported penicillin allergies are frequently reported, though more than 95% of those are not truly allergic when challenged. These patients are more likely to receive alternative antibiotic regimens resulting in the use of broad-spectrum antibiotics that may be less effective, more toxic, and/or more expensive than preferred agents. Given the significant burden on patient outcomes and the healthcare system, the ability to reconcile an allergy and broaden future antibiotic options is essential. RECENT FINDINGS: This is a narrative review describing risk stratification for penicillin skin testing, practical advice for implementation, and future directions. A summary of studies within the last 5 years is provided. The trend over the past several years has been to offer oral drug challenges to low-risk patients and skin testing to high-risk patients with a reported penicillin allergy. This review provides support for risk stratification assessment of reported penicillin allergy to optimize antibiotic use and prevent emergence of antimicrobial resistance.

Urinary catheters: PART 2 Catheterisation in males and females.

Michelle Mitchell, Graduate Tutor for Adult Nursing, Northumbria University, michelle3.mitchell@northumbria.ac.uk and Barry Hill, Senior Lecturer in Adult Nursing, Northumbria University, describe the different catheterisation needs of men and women and the procedures to follow.

Urinary catheters PART 1.

Barry HIll, Senior Lecturer in Adult Nursing at Northumbria University ( barry.hill@northumbria.ac.uk ), and Michelle Mitchell, Graduate Tutor for Adult Nursing at Northumbria University, discuss the reasons for urinary catheterisation, the different types of catheter and the potential problems patients need to be aware of.

Ecological succession and viability of human-associated microbiota on restroom surfaces.

Human-associated bacteria dominate the built environment (BE). Following decontamination of floors, toilet seats, and soap dispensers in four public restrooms, in situ bacterial communities were characterized hourly, daily, and weekly to determine their successional ecology. The viability of cultivable bacteria, following the removal of dispersal agents (humans), was also assessed hourly. A late-successional community developed within 5 to 8 h on restroom floors and showed remarkable stability over weeks to months. Despite late-successional dominance by skin- and outdoor-associated bacteria, the most ubiquitous organisms were predominantly gut-associated taxa, which persisted following exclusion of humans. Staphylococcus represented the majority of the cultivable community, even after several hours of human exclusion. Methicillin-resistant Staphylococcus aureus (MRSA)-associated virulence genes were found on floors but were not present in assembled Staphylococcus pan-genomes. Viral abundances, which were predominantly enterophages, human papilloma virus, and herpesviruses, were significantly correlated with bacterial abundances and showed an unexpectedly low virus-to-bacterium ratio in surface-associated samples, suggesting that bacterial hosts are mostly dormant on BE surfaces.

Closer to Home: A Quality Improvement Initiative to Optimize Satellite Site Bed Capacity.

BACKGROUND: The coronavirus disease 2019 pandemic resulted in the underutilization of inpatient beds at our satellite location. A lack of clarity and standardized admission criteria for the satellite led to frequent transfers to the main campus, resulting in patients traveling larger distances to receive inpatient care. We sought to optimize inpatient resource use at the satellite campus and keep patients "closer to home" by admitting eligible patients to that inpatient unit (LA4). Our aim was to increase bed capacity use at the satellite from 45% to 70% within 10 months. Our process measure was to increase the proportion of patients needing hospitalization who presented to the satellite emergency department (ED) and were then admitted to LA4 from 76% to 85%. METHODS: A multidisciplinary team used quality improvement methods to optimize bed capacity use. Interventions included (1) the revision and dissemination of satellite admission guidelines, (2) steps to create shared understanding of appropriate satellite admissions between ED and inpatient providers, (3) directed provider feedback on preventable main campus admissions, and (4) consistent patient and family messaging about the potential for transfer. Data were collected via chart review. Annotated run charts were used to assess the impact of interventions over time. RESULTS: Average LA4 bed capacity use increased from 45% to 69%, which was sustained for 1 year. The average percentage of patients admitted from the satellite ED to LA4 increased from 76% to 84%. CONCLUSIONS: We improved bed capacity use at our satellite campus through transparent admission criteria and shared mental models of patient care needs between ED and inpatient providers.

Facet-sparing decompression with a minimally invasive flexible microblade shaver: a prospective operative analysis.

STUDY DESIGN: This is a detailed description of a facet-sparing decompression technique and a prospective observational study of 59 subjects. OBJECTIVE: To describe a facet-sparing decompression technique, quantify operative parameters, adverse events, and anatomic changes following decompression with a flexible microblade shaving system. SUMMARY OF BACKGROUND DATA: Decompression in patients with lumbar spinal stenosis is a common surgical procedure. However, obtaining a thorough decompression while leaving enough tissue to avoid destabilization can be challenging. Decompression with a flexible, through-the-foramen system may mitigate some of these challenges. MATERIALS AND METHODS: Fifty-nine subjects diagnosed with lumbar spinal stenosis were recruited into this study. Subjects underwent decompression with a flexible, microblade decompression system at a total of 88 levels between L2 and S1. Subject demographics, details of the procedure, and operation, including adverse events were collected. Preoperative and postoperative computed tomography scans and plain radiographs were obtained from a subset of 12 subjects and quantitatively assessed for bone removal and preservation of stabilizing structures. RESULTS: Fifty-nine subjects had 88 levels treated, 51% single-level and 49% 2-level with L4-L5 being the most commonly decompressed level. Operative time, blood loss, and length of stay were similar to or less than that seen in the historical control. The system was successfully used for decompression in 95.8% of the attempted foramina. Three operative complications were reported, all dural tears (5.1%). These dural tears occurred before introduction of the flexible decompression system. Computed tomography scans from 12 subjects demonstrate access to the lateral recess and foramen with removal of <6% of the superior facet cross-sectional area. CONCLUSIONS: The flexible microblade shaving system provided thorough decompression with few intraoperative complications. Operative variables were favorable compared to the literature and radiographic decompression was achieved to a great extent while allowing for the preservation of the facet joints and midline structures.

Antibiotic treatment duration for culture-negative sepsis in the pediatric intensive care unit.

Objective: Sepsis remains a leading cause of morbidity and mortality in children. There is very limited guidance for sepsis treatment when cultures remain negative. This study sought to determine the effectiveness of short versus long course of antibiotics when treating culture-negative sepsis and assess for subsequent multidrug-resistant organism (MDRO) acquisition. Design: Retrospective cohort study. Setting: Quaternary academic children's hospital. Patients: Pediatric intensive care unit (ICU) patients with culture-negative sepsis receiving a minimum of 72 hours of antibiotics. Methods: Patients found to have culture-negative sepsis from January 2017 to May 2020 were divided into two groups: short and long course of antibiotics. Various demographic and laboratory results were collected for each subject as available. Primary outcomes included mortality and lengths of stay. The secondary outcome was subsequent acquisition of a new MDRO. Results: Eighty-six patients were treated for culture-negative sepsis with 43 patients in both the short- (< or = 7 days) and long-course (>7 days) treatment cohorts. Patients who received a short course of antibiotics had a lower overall mortality than those who received a long course (9.3% vs 25.6% p = 0.047), but there was no difference in 30-day mortality (p > 0.99). Patients in the short-course group had a shorter hospital length of stay (22 vs 30 days p = 0.018). New MDROs were found in 10% of all patients. Conclusions: Treatment of culture-negative sepsis with short-course antibiotics was not associated with worse outcomes in ICU patients. These findings warrant further investigation with a larger, prospective, multi-center study.

Retrospective Comparison of Cefdinir, Cephalexin, and Sulfamethoxazole-Trimethoprim in the Treatment of Outpatient Pediatric Urinary Tract Infections.

This retrospective single-center study included children aged 2 months to 18 years who were prescribed an oral antibiotic for microbiologically confirmed urinary tract infection (UTI). The primary outcomes were re-encounter to the hospital, emergency department, or urgent care within 30 days and modification of the antibiotic regimen within 14 days. Development of Clostridioides difficile (C difficile) infection or new allergic reaction to the antibiotic prescribed was the secondary outcome. The sample included 2685 children. Rates of re-encounter were similar regardless of the initial antibiotic prescribed (P = .88), and patients who received cefdinir had a lower rate of medication changes (5%) compared with both cephalexin (14%) and sulfamethoxazole-trimethoprim (15%) (P ≤ .001). The most common reason for medication change was susceptibility interpretation. Given its low side-effect profile and narrow spectrum compared with the alternatives, cephalexin appears to be a reasonable choice as first-line therapy for the treatment of uncomplicated pediatric UTI.

Overview of Pediatric Procalcitonin Testing Patterns in a Tertiary Care Children's Hospital.

The use of procalcitonin (PCT) has grown over the past decade with increasing reliance on the test to rule out bacterial infection. We retrospectively reviewed the medical records of children <18 years old hospitalized at a tertiary care children's hospital from 2017 to 2019 who had PCT testing performed during their admission. Of 4135 PCT levels collected on 1530 children, 982 (23.7%) were diagnostically low and 1993 (48.1%) were diagnostically elevated. Pediatric intensive care, with 6% of total hospital patients, obtained 41.4% of tests. Thirty-one (2%) patients had an average of 27 PCT levels per patient, accounting for 20% of all tests. Many children had symptoms for which testing is not indicated (eg, skin complaints). The differences in PCT testing by service, inappropriate patterns of repeat testing, and testing performed in patients for whom it is not indicated may identify targets for diagnostic stewardship.

Seroprevalence of Human T-Cell Lymphotropic Virus-1 in a Jamaican Antenatal Population and Assessment of Pooled Testing as a Cost Reduction Strategy for Implementation of Routine Antenatal Screening.

Mother to child transmission (MTCT) of human T-cell lymphotropic virus (HTLV)-1 is associated with increased risk of adult T-cell leukemia and can be unrecognized without routine antenatal screening. We assessed the seroprevalence of HTLV-1/2 among pregnant women attending The University Hospital of the West Indies Antenatal Clinic, 2019, and validated a cost-effective strategy to screen antenatal clinic attendees for HTLV-1/2. Residual antenatal samples from 370 women were tested for HTLV-1/2 by chemiluminescence microparticle immunoassay (CMIA). Six samples were confirmed HTLV-1 positive by Western blot (none for HTLV-2) for a prevalence of 1.62%. Four mother-child pairs were able to be recruited for HTLV testing of children, with two children testing HTLV-1/2 positive. Medical records of HTLV-1-infected women revealed that all women breastfed, indicating an unrecognized risk for HTLV MTCT. To assess whether pooling of samples as a cost-reduction strategy could be introduced, we pooled all antenatal samples received between November and December 2021 into 12 pools of eight samples/pool. Two pools were CMIA positive, and de-pooling of samples identified two CMIA-positive samples (one per pool), both confirmed as HTLV-1 by Western blot. These results indicate that HTLV-1 remains prevalent in pregnant Jamaican women and that sample pooling can be a cost-effective strategy to limit MTCT in Jamaica.

Management of Children with Reported Penicillin Allergies.

Penicillin allergy is the most commonly reported medication allergy. Reported allergy is associated with increased morbidity and mortality. Risk categorization tools can help determine the optimal testing strategies to delabel patients with reported allergy. Approaches to allergy removal include oral challenge in low-risk patients and skin testing in high-risk patients. Many different locations may be used to test for allergy, including ambulatory care clinics, inpatient units, and emergency departments. Interventions (eg, use of the electronic medical record) are needed to ensure that once the allergy is removed, this information is effectively transmitted to the patient and appropriate providers.

Double Take on Double Vision: Invasive Rhinosinusitis From Blastomyces dermatitidis in an Adolescent With Well-Controlled Diabetes.

Blastomyces dermatitidis is a fungus endemic to the Ohio and Mississippi river valley region and great lakes region. Exposure is typically associated with outdoor activities near streams, rivers, or moist soil. Pulmonary disease is the main manifestation, whereas dissemination is more frequently observed in immunosuppressed individuals. We herein report an uncommon case of B. dermatitidis causing invasive fungal sinusitis in a patient with well-controlled type 2 diabetes mellitus in the absence of conventional higher-risk environmental exposures. This case highlights the importance of a broad differential for invasive fungal infections in patients with diabetes, including those in endemic areas without classical exposures.

Extended Infusion ß-Lactams for the Treatment of Gram-Negative Bacteremia in Children.

OBJECTIVE: The pharmacokinetics of ß-lactam antibiotics favor administration via an extended infusion. Although literature to support extended infusion ß-lactams exists for adults, few data are available in pediatrics, especially among patients with bacteremia. The purpose of this study was to compare clinical outcomes between extended and standard infusions in children with Gram-negative bacteremia. METHODS: This retrospective chart analysis included hospitalized patients ages 0 to 18 years who received at least 72 hours of cefepime, meropenem, or piperacillin-tazobactam between January 1, 2013 and July 30, 2021. Clinical outcomes included duration of antibiotic therapy, hospital length of stay, readmission within 30 days, all-cause mortality, time to blood culture clearance, and time to normalization of inflammatory markers. RESULTS: A total of 124 patients (51 extended infusion, 73 standard infusion) met criteria for evaluation. Duration of antibiotic therapy was shorter in the extended infusion group (6.6 days versus 10.2 days; p = 0.01). There were no differences in hospital length of stay, readmission rates, all-cause mortality, time to normalization of inflammatory markers, or time to blood culture clearance. CONCLUSIONS: Use of extended infusion ß-lactam antibiotics in children with Gram-negative bacteremia was associated with shorter durations of therapy and should be the preferred method of administration when feasible.

The Effect of Obstetric Drills Training - Jamaica Core Obstetric Teaching and Training in Emergencies (JOTTIE) on Postpartum Haemorrhage at a Jamaican Teaching Hospital.

OBJECTIVE: To evaluate whether the initiation of JOTTIE, a one day simulation training course focussed on the management of common obstetric emergencies, was associated with a reduction in the morbidity and mortality associated with postpartum haemorrhage (PPH) at the University Hospital of the West Indies (UHWI). STUDY DESIGN: We conducted a retrospective comparative study that evaluated the incidence of multiple outcomes related to maternal morbidity secondary to PPH, during the two year period immediately prior to the introduction of JOTTIE (pre course arm, N = 88) or the two year period, one year post introduction (post course arm, N = 103) for all women who had vaginal deliveries complicated by PPH at UHWI. A relationship was said to be statistically significant if p < 0.05. Additionally, the study examined risk factors in relation to severity of haemorrhage. RESULTS: Genital tract trauma represented the highest recorded cause of PPH (approximately 71%). The data revealed that patients in the pre training arm were similarly likely to have no adverse outcome in comparison to patients in the post training arm (p = 0.962). There was also no statistically significant relationship between the time period of patient exposure in relation to the JOTTIE course and severity of PPH (p > 0.05). Uterine fibroids and Crohn's disease were the only co-morbidities found to increase the likelihood of severe PPH, at 5.154 times (p = 0.019,OR = 5.154, CI = 1.314-20.212) and 17.848 times (p = 0.085,OR = 17.848,CI = 0.672-474.365), respectively. CONCLUSIONS: This study suggests that prior to the introduction of the JOTTIE the rate of maternal morbidity associated with PPH was relatively low at UHWI and there was no significant effect on its management or a significant reduction in maternal morbidity since introduction of the course. Future research on the morbidity related to the other obstetric emergencies addressed at JOTTIE is needed in order to assess the effect of the course as a whole.

Establishing therapeutic and supportive relationships throughout delivery of a school-based group parenting program via telehealth: Exploring causal pathways.

Background: Access to specialised early intervention mental health services for children, including group counselling for parents/carers, is still a challenge in non-metropolitan areas of Australia. Aim: To gain understanding of the acceptability of a school-based targeted parenting group program delivered via telehealth by exploring the experiences of parents/carers, clinicians and school staff, and asking what works, how, why and in what circumstances. Methods: Caregivers, clinicians and school staff involved in the delivery of a mental health program via telehealth into primary schools in two rural Local Health Districts (LHDs) in southern New South Wales (NSW) were invited to participate in interviews and/or focus group discussions. Thematic analysis of the data was conducted with reference to realist theory. Findings: We conducted semi-structured interviews with 12 caregivers, five semi-structured interviews and two focus group discussions with school staff from six participating schools, and three focus groups with seven clinicians who delivered the intervention. We found that the intervention and micro contexts interacted to influence acceptability by initiating or enhancing cohesion among caregivers, establishing channels of communication between caregivers and teachers, and connection between caregivers and clinicians despite geographic distance. Several adaptations were made to strengthen the therapeutic alliance between caregivers and clinicians. Conclusion: Relationships crucial to the success of delivering psychological group counselling were established. Regional community contexts can facilitate acceptability of parenting group counselling delivered into schools via telehealth. Implementation of the program was flexible enough to allow clinicians to adjust their approach and materials to better suit the telehealth modality.

The RNA transport element of the murine musD retrotransposon requires long-range intramolecular interactions for function.

Retrovirus replication requires specialized transport mechanisms to export genomic mRNA from the nucleus to the cytoplasm of the infected cell. This regulation is mediated by a combination of viral and/or cellular factors that interact with cis-acting RNA export elements linking the viral RNA to the cellular CRM1 or NXF1 nuclear export pathways. Endogenous type D murine LTR retrotransposons (musD) were reported to contain an RNA export element located upstream of the 3'-LTR. Although functionally equivalent, the musD export element, termed the musD transport element, is distinct from the other retroviral RNA export elements, such as the constitutive transport element of simian/Mason-Pfizer monkey retroviruses and the RNA transport element found in rodent intracisternal A-particle LTR retrotransposons. We demonstrate here that the minimal RNA transport element (musD transport element) of musD comprises multiple secondary structure elements that presumably serve as recognition signals for the cellular export machinery. We identified two classes of tertiary interactions, namely kissing loops and a pseudoknot. This work constitutes the first example of an RNA transport element requiring such structural motifs to mediate nuclear export.