Protein–protein interactions (PPIs) are central to many cellular processes, and the identification of novel PPIs is a critical step in the discovery of protein therapeutics. Simple methods to ...identify naturally existing or laboratory evolved PPIs are therefore valuable research tools. We have developed a facile selection that links PPI‐dependent β‐lactamase recruitment on the surface of Escherichia coli with resistance to ampicillin. Bacteria displaying a protein that forms a complex with a specific protein‐β‐lactamase fusion are protected from ampicillin‐dependent cell death. In contrast, bacteria that do not recruit β‐lactamase to the cell surface are killed by ampicillin. Given its simplicity and tunability, we anticipate this selection will be a valuable addition to the palette of methods for illuminating and interrogating PPIs.
Academic self-efficacy, academic motivation, and information literacy are considered crucial to fostering student learning in tertiary institutions. The aim of this study was to examine the ...information literacy self-efficacy and academic motivation of college students and to identify the predictors of information literacy self-efficacy. The participants included students in their junior and senior years studying nursing, healthcare, and non-healthcare disciplines at a self-financing institution. Data were collected through a quota sampling method using a questionnaire. In total, 504 valid questionnaires were returned. The results indicated a moderate positive correlation between the two variables. The nursing students were found to have lower information literacy self-efficacy scores than those from the other disciplines. The results from a multiple regression analysis showed that the following factors are predictors of information literacy self-efficacy: being a nursing student, total scores for academic motivation, and owning a personal computer. Nurse educators are encouraged to strengthen the information literacy skills of nursing students, as this is an essential component in the application of evidence-based practices in the nursing profession.
The pivotal role of PPIs in cellular processes has been well-established, emphasizing their crucial significance in various biological activities. Identifying new PPIs is imperative for advancing our ...understanding of cellular functions and exploring potential avenues for protein therapeutics. Researchers have been actively developing methods to detect these interactions in their natural state and through laboratory engineering to facilitate further investigations in this field. In this context, our research team has introduced a straightforward selection process designed to link protein-protein interaction-dependent β-lactamase recruitment on the surface of E. coli with resistance to ampicillin. This innovative approach enables us to study and manipulate these interactions efficiently. In our experiments, bacteria displaying a protein that forms a complex with a specific protein-β-lactamase fusion exhibit enhanced resistance to ampicillin-induced cell death.Conversely, bacteria lacking the recruitment of β-lactamase to the cell surface are vulnerable to the effects of ampicillin. The method's simplicity and adaptability make it a promising addition to the repertoire of techniques for investigating PPIs. As we continue to explore the intricacies of PPIs, we anticipate that our selection process will contribute valuable insights to the broader scientific community.
On Dec 8, 2020, deployment of the first SARS-CoV-2 vaccination authorised for UK use (BNT162b2 mRNA vaccine) began, followed by an adenoviral vector vaccine ChAdOx1 nCoV-19 on Jan 4, 2021. Care home ...residents and staff, frontline health-care workers, and adults aged 80 years and older were vaccinated first. However, few data exist regarding the effectiveness of these vaccines in older people with many comorbidities. In this post-implementation evaluation of two COVID-19 vaccines, we aimed to determine the effectiveness of one dose in reducing COVID-19-related admissions to hospital in people of advanced age.
This prospective test-negative case-control study included adults aged at least 80 years who were admitted to hospital in two NHS trusts in Bristol, UK with signs and symptoms of respiratory disease. Patients who developed symptoms before receiving their vaccine or those who received their vaccine after admission to hospital were excluded, as were those with symptoms that started more than 10 days before hospital admission. We did logistic regression analysis, controlling for time (week), sex, index of multiple deprivations, and care residency status, and sensitivity analyses matched for time and sex using a conditional logistic model adjusting for index of multiple deprivations and care residency status. This study is registered with ISRCTN, number 39557.
Between Dec 18, 2020, and Feb 26, 2021, 466 adults were eligible (144 test-positive and 322 test-negative). 18 (13%) of 135 people with SARS-CoV-2 infection and 90 (34%) of 269 controls received one dose of BNT162b2. The adjusted vaccine effectiveness was 71·4% (95% CI 46·5–90·6). Nine (25%) of 36 people with COVID-19 infection and 53 (59%) of 90 controls received one dose of ChAdOx1 nCoV-19. The adjusted vaccine effectiveness was 80·4% (95% CI 36·4–94·5). When BNT162b2 effectiveness analysis was restricted to the period covered by ChAdOx1 nCoV-19, the estimate was 79·3% (95% CI 47·0–92·5).
One dose of either BNT162b2 or ChAdOx1 nCoV-19 resulted in substantial risk reductions of COVID-19-related hospitalisation in people aged at least 80 years.
Pfizer.
IntroductionIn patients with Spontaneous Bacterial Peritonitis (SBP), acute kidney injury and high serum bilirubin are known predictors of in-hospital mortality. The effect of patient management on ...mortality is unknown. This study aims to identify predictors of in-hospital mortality, accounting for management of patients with SBP, according to EASL Clinical Practice Guidelines published in 2010.MethodsClinico-demographic, biochemical and microbiological data from patients presenting between 2014 and 2019, with a first episode of SBP (ascitic fluid neutrophil count > 250 cell/cm³) were reviewed. The primary endpoint was in-hospital mortality. Logistic regression was used to identify predictors of outcome.ResultsOverall, 130 patients (median IQR age 58 51 - 66 yr; 65% male; aetiology: alcohol 36%; MELD score 18 13 - 25) were included. Infection was nosocomial in 49%; 35 had concomitant bacteraemia (n = 14), respiratory (n = 16) or urinary infections (n = 9). Pathogens were identified in 57 (44%) patients within 42 36 – 50 hr post initial ascitic tap; antibiotic sensitivities were available by 53 49 – 62 hr. Multidrug resistant pathogens (MDRP) were identified in 12 (21%) of the 57; 10 of the 12 showed < 25% reduction in ascitic neutrophil count at 48 hours.There were 29 (22.3%) in-hospital deaths; the median time to death was 6 1 – 8 days. A total of 31 (24%) patients were admitted to ITU and one-third (n = 13) of this cohort died. One patient underwent liver transplantation. On univariate analysis, admission MELD, peripheral white cell count, INR, serum creatinine, failure to culture a pathogen, failure to perform a 48-hour ascitic tap and development of acute kidney injury were predictors of in-hospital mortality. Age, nosocomial infection or the presence of a MDRP were not. Failure to perform a 48-hour ascitic tap (OR 95% CI = 11.2 2.9 – 43.7, p < 0.01), acute kidney injury (9.1 2.0 – 41.5, p < 0.01) and MELD score (1.2 1.1 – 1.3, p < 0.01) retained significance on multivariate analysis.ConclusionsIn-hospital mortality associated with SPB is unacceptably high at 22%. Failure to repeat the ascitic tap at 48 hours, a recommendation based solely on expert opinion in the EASL guideline, was a highly significant prognostic factor allowing early identification of patients who fail to respond to empirical antibiotic therapy. This requirement should now become recommended practice.
Despite significant global morbidity associated with respiratory infection, there is a paucity of data examining the association between severity of non-SARS-CoV-2 respiratory infection and blood ...group. We analysed a prospective cohort of adults hospitalised in Bristol, UK, from 1 August 2020 to 31 July 2022, including patients with acute respiratory infection (pneumonia n = 1934 and non-pneumonic lower respiratory tract infection NP-LRTI n = 1184), a negative SARS-CoV-2 test and known blood group status. The likelihood of cardiovascular complication, survival and hospital admission length was assessed using regression models with group O and RhD-negative status as reference groups. Group A and RhD-positive were over-represented in both pneumonia and NP-LRTI compared to a first-time donor population (p < 0.05 in all); contrastingly, group O was under-represented. ABO group did not influence cardiovascular complication risk; however, RhD-positive patients with pneumonia had a reduced odds ratio (OR) for cardiovascular complications (OR = 0.77 95% CI = 0.59-0.98). Compared to group O, group A individuals with NP-LRTI were more likely to be discharged within 60 days (hazard ratio HR = 1.17 95% CI = 1.03-1.33), while group B with pneumonia was less likely (HR = 0.8 95% CI = 0.66-0.96). This analysis provides some evidence that blood group status may influence clinical outcome following respiratory infection, with group A having increased risk of hospitalisation and RhD-positive patients having reduced cardiovascular complications.
Background
Primary adrenal insufficiency (PAI) mortality and morbidity remain unacceptably high, possibly arising as glucocorticoid replacement does not replicate natural physiology. A pulsatile ...subcutaneous pump can closely replicate cortisol's circadian and ultradian rhythm.
Objectives
To assess the effect of pump therapy on quality of life, mood, functional neuroimaging, behavioural/cognitive responses, sleep and metabolism.
Methods
A 6‐week randomised, crossover, double‐blinded and placebo‐controlled feasibility study of usual dose hydrocortisone in PAI administered as either pulsed subcutaneous or standard care in Bristol, United Kingdom (ISRCTN67193733). Participants were stratified by adrenal insufficiency type. All participants who received study drugs are included in the analysis. The primary outcome, the facial expression recognition task (FERT), occurred at week 6.
Results
Between December 2014 and 2017, 22 participants were recruited – 20 completed both arms, and 21 were analysed. The pump was well‐tolerated. No change was seen in the FERT primary outcome; however, there were subjective improvements in fatigue and mood. Additionally, functional magnetic resonance imaging revealed differential neural processing to emotional cues and visual stimulation. Region of interest analysis identified the left amygdala and insula, key glucocorticoid‐sensitive regions involved in emotional ambiguity. FERT post hoc analysis confirmed this response. There were four serious adverse events (AE): three intercurrent illnesses requiring hospitalisation (1/3, 33.3% pump) and a planned procedure (1/1, 100% pump). There was a small number of expected AEs: infusion site bruising/itching (3/5, 60% pump), intercurrent illness requiring extra (3/7, 42% pump) and no extra (4/6, 66% pump) steroid.
Conclusions
These findings support the administration of hormone therapy that mimics physiology.
INTRODUCTION:Pregnancy weight gain is known to increase the risk of gestational diabetes and preeclampsia which can lead to preterm delivery. Inter-pregnancy weight retention worsens this risk. We ...have identified percent of initial body weight (IBW) gain that has relationship to maternal hyperglycemia and is lower than diagnostic of GDM criteria leading to adverse neonatal outcome.
METHODS:227 mothers who had a delivery from June 2014 to July 2015 requiring entry into the neonatal hypoglycemia (NH) protocol for 24 hour monitoring after birth. Patients were excluded if collection of initial maternal weight was after 16 weeks GA as waiting any longer would be unreliable to approximate pre-gestational weight. Chi-square and t-tests were used to compare outcomes.
RESULTS:Mothers with an initial BMI ≥25 who gained at least 15.3% ± 0.8% p=0.05 of their initial body weight throughout the pregnancy had normal GCT on initial screening. Additionally, there was a significant inverse correlation between weight gained during pregnancy and abnormal GCT.
CONCLUSION:Early screening and intervention using 16±0.8% weight gain from initial maternal body weight could serve as a risk stratification tool along with glucose challenge (GCT) parameters. These women can be stratified early in the pregnancy course as having an increased risk for developing glucose intolerance and possibly neonatal hypoglycemia. Our findings suggest that overweight women are able to accommodate for greater changes in weight without affecting the GCT screening parameters, however not enough to prevent clinically significant neonatal hypoglycemia, therefore should be additionally subjected to glucose tolerance testing (GTT).
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