Protein interactions in human pathogens revealed through deep learning.

Identification of bacterial protein-protein interactions and predicting the structures of these complexes could aid in the understanding of pathogenicity mechanisms and developing treatments for infectious diseases. Here we developed RoseTTAFold2-Lite, a rapid deep learning model that leverages residue-residue coevolution and protein structure prediction to systematically identify and structurally characterize protein-protein interactions at the proteome-wide scale. Using this pipeline, we searched through 78 million pairs of proteins across 19 human bacterial pathogens and identified 1,923 confidently predicted complexes involving essential genes and 256 involving virulence factors.

The time of equipoise on the use of biological DMARDs in for inflammatory arthritis during pregnancy is finally over: a reappraisal of evidence to optimise pregnancy management.

Active inflammatory arthritis in pregnancy is associated with an increased risk of adverse pregnancy outcomes. Treatment of active inflammation and maintenance of low disease activity with medication reduces these risks. Therapeutic decisions on disease-modifying antirheumatic drugs (DMARDs) in pregnancy are complicated by safety concerns, which have led to inappropriate withdrawal of treatment and consequential harm to mother and fetus.

Predicting the Stability of Formulations Containing Lyophilized Human Serum Albumin and Sucrose/Trehalose Using Solid-State NMR Spectroscopy.

Stabilization of proteins by disaccharides in lyophilized formulations depends on the interactions between the protein and the disaccharide (system homogeneity) and the sufficiently low mobility of the system. Human serum albumin (HSA) was lyophilized with disaccharides (sucrose and/or trehalose) in different relative concentrations. Solid-state nuclear magnetic resonance (ssNMR) spectroscopy H T and H T relaxation times were measured to determine the homogeneity of the lyophilized systems on 20-50 and 1-3 nm domains, respectively, with H T relaxation times also being used to determine the β-relaxation rate.

Essential and virulence-related protein interactions of pathogens revealed through deep learning.

Identification of bacterial protein-protein interactions and predicting the structures of the complexes could aid in the understanding of pathogenicity mechanisms and developing treatments for infectious diseases. Here, we developed a deep learning-based pipeline that leverages residue-residue coevolution and protein structure prediction to systematically identify and structurally characterize protein-protein interactions at the proteome-wide scale. Using this pipeline, we searched through 78 million pairs of proteins across 19 human bacterial pathogens and identified 1923 confidently predicted complexes involving essential genes and 256 involving virulence factors.

Predicting the Stability of Lyophilized Human Serum Albumin Formulations Containing Sucrose and Trehalose Using Solid-State NMR Spectroscopy: Effect of Storage Temperature on H T Relaxation Times.

In a lyophilized protein/disaccharide system, the ability of the disaccharide to form a homogeneous mixture with the protein and to slow the protein mobility dictates the stabilization potential of the formulation. Human serum albumin was lyophilized with sucrose or trehalose in histidine, phosphate, or citrate buffer. H T relaxation times were measured by solid-state NMR spectroscopy and were used to assess the homogeneity and mobility of the samples after zero, six, and twelve months at different temperatures.

Understanding the impact of mannitol on physical stability and aerosolization of spray-dried protein powders for inhalation.

Pulmonary delivery of protein-based therapeutics, including antibodies, is a promising option for treating respiratory diseases. Spray drying is a widely used method for producing dry powder formulations with mannitol being a commonly used excipient for these inhalation formulations. There is limited research available concerning the utilization of mannitol as an excipient in the spray drying of proteins and its impact on aerosol performance.

Discovery of a glutathione utilization pathway in Francisella that shows functional divergence between environmental and pathogenic species.

Glutathione (GSH) is an abundant metabolite within eukaryotic cells that can act as a signal, a nutrient source, or serve in a redox capacity for intracellular bacterial pathogens. For Francisella, GSH is thought to be a critical in vivo source of cysteine; however, the cellular pathways permitting GSH utilization by Francisella differ between strains and have remained poorly understood. Using genetic screening, we discovered a unique pathway for GSH utilization in Francisella.

Fertility Trends and Adverse Pregnancy Outcomes in Female Patients With Psoriasis in the UK.

Importance: Evidence regarding fertility trends and obstetric outcomes among patients with psoriasis is limited by studies of small sample sizes, noninclusion of comparators, and the lack of accurate pregnancy records.

Objective: To investigate fertility rates and obstetric outcomes of pregnancies in female patients with psoriasis compared with age- and general practice-matched comparators without psoriasis.

Design, Setting, And Participants: This population-based cohort study used data from 887 primary care practices that contributed to the UK Clinical Practice Research Datalink GOLD database between 1998 and 2019, linked to a pregnancy register and Hospital Episode Statistics.

A successful antenatal outcome in a patient with refractory Takayasu's arteritis treated with tocilizumab throughout pregnancy-a case report.

Takayasu's arteritis (TA) is a rare form of large-vessel vasculitis for which tocilizumab (TCZ) may be administered in resistant or refractory disease. Current British Society of Rheumatology advice is to stop TCZ 3-months pre-conception. We report the case of a 33-year-old woman with extensive TA treated with TCZ, azathioprine and glucocorticoids in pregnancy.

A Scoping Review of the Essential Components of Emergency Medical Response Systems for Mass Casualty Incidents.

Objective: Emergency medical (EM) response systems require extensive coordination, particularly during mass casualty incidents (MCIs). The recognition of preparedness gaps and contextual priorities to MCI response capacity in low- and middle-income countries (LMICs) can be better understood through the components of EM reponse systems. This study aims to delineate essential components and provide a framework for effective emergency medical response to MCIs.

Pregnancy outcomes of a joint obstetric and rheumatology clinic in a tertiary centre: a 2-year retrospective study of 98 pregnancies.

Objectives: The purpose of this study was to describe the maternal and fetal outcomes in patients with inflammatory rheumatic diseases attending a joint rheumatology and obstetric clinic in the UK.

Methods: Electronic records of 98 patients attending the joint rheumatology and obstetric clinic between January 2018 and January 2020 were analysed. Data on patient demographics, characteristics (including age, ethnicity, diagnosis, and medications taken during pregnancy), pregnancy outcomes (miscarriage, stillbirth or live birth), maternal complications [infection, post-partum haemorrhage (PPH) or pre-eclampsia] and fetal complications (sepsis, congenital heart block, prematurity and low birth weight) were tabulated.

Immunomodulatory Therapy Reduces the Severity of Placental Lesions in Chronic Histiocytic Intervillositis.

Chronic histiocytic intervillositis (CHI) is a rare, but highly recurrent inflammatory placental lesion wherein maternal macrophages infiltrate the intervillous space. Pregnancies with CHI are at high risk of fetal growth restriction, miscarriage or stillbirth. Presently, the diagnosis can only be made after histopathological examination of the placenta.

Multidisciplinary management of pregnancy and labour in a patient with glycogen storage disease type 1a.

Glycogen storage disease type 1a (GSD 1a) is a metabolic disorder caused by deficiency of an enzyme required for glycogen breakdown, causing hypoglycaemia and lactic acidosis. Metabolic derangements cause disease manifestations affecting the kidneys, liver and platelet function. Physiological changes in pregnancy worsen fasting intolerance and increase reliance on exogenous glucose to avoid lactic acidosis.

DEG/ENaC/ASIC channels vary in their sensitivity to anti-hypertensive and non-steroidal anti-inflammatory drugs.

The degenerin channels, epithelial sodium channels, and acid-sensing ion channels (DEG/ENaC/ASICs) play important roles in sensing mechanical stimuli, regulating salt homeostasis, and responding to acidification in the nervous system. They have two transmembrane domains separated by a large extracellular domain and are believed to assemble as homomeric or heteromeric trimers. Based on studies of selected family members, these channels are assumed to form nonvoltage-gated and sodium-selective channels sensitive to the anti-hypertensive drug amiloride.

Design and Evaluation of the Environmental Outreach Activity for Middle School Students.

The design and development of an outreach activity targeted at 6th grade middle school students, which aims to determine the level of phosphate in samples of water from nearby lakes and streams, are detailed. Several parameters were noted as key to the successful implementation of this activity in a school setting and to it being well-received by both students and teachers. These include the hands-on nature of the experiment, the use of professional scientific equipment and protocols, and the relevance to everyday life and nearby societal issues.

Tn-Seq reveals hidden complexity in the utilization of host-derived glutathione in Francisella tularensis.

Host-derived glutathione (GSH) is an essential source of cysteine for the intracellular pathogen Francisella tularensis. In a comprehensive transposon insertion sequencing screen, we identified several F. tularensis genes that play central and previously unappreciated roles in the utilization of GSH during the growth of the bacterium in macrophages.

Adverse pregnancy outcomes and subsequent development of connective tissue disease in the UK: an epidemiological study.

Objective: This study assessed prevalence of connective tissue disease (CTDs), systemic lupus erythematosus (SLE), antiphospholipid syndrome (APS) and antiphospholipid antibodies (aPL) in women with previous adverse pregnancy outcome compared with uncomplicated livebirths.

Design: Retrospective case-control study.

Setting: UK Primary Care.

Investigation into Intermolecular Interactions and Phase Behavior of Binary and Ternary Amorphous Solid Dispersions of Ketoconazole.

Conventionally, amorphous solid dispersions (ASDs) have been formulated as a binary matrix, but in recent years a new class of ASDs has emerged, where generally a second polymer is also added to the formulation. Having the presence of a second polymer necessitates a comprehensive solid-state characterization to study the intermolecular interactions and phase behavior on a molecular level. With this goal in mind, ketoconazole (KET) was selected as a model drug, and hydroxypropyl methyl cellulose (HPMC) and poly(acrylic acid) (PAA) were chosen as polymeric carriers.

Building Collective Efficacy to Support Public Health Workforce Development.

Context: Leaders in public health have made great advances in workforce development over the past 30 years, while shifting from an emphasis based in training on individual, technical skills to a more holistic development approach, which boosts crosscutting skills. Efforts to increase public health workforce capabilities remain focused on workers as individuals, rather than the workforce as a collective unit.

Program: Research has shown that a strategic adult learning approach can improve both individual capabilities and the collective performance of the workforce, which can be explained using social cognitive theory and the concept of collective efficacy, or the collective belief of workers in the ability of the group to succeed.

Use of Big Data and Information and Communications Technology in Disasters: An Integrative Review.

ABSTRACTNovel approaches to improving disaster response have begun to include the use of big data and information and communication technology (ICT). However, there remains a dearth of literature on the use of these technologies in disasters. We have conducted an integrative literature review on the role of ICT and big data in disasters.