Emergency Department Volumes After State-Wide Lockdown Orders Across the United States During the COVID-19 Pandemic: COVID-19 lockdown and emergency volume.

OBJECTIVE: The objective of this study was to describe changes in emergency department volumes after statewide lockdown in a network of hospitals across the United States during the COVID-19 global pandemic. METHODS: A retrospective study was performed utilizing data on daily volumes across multiple emergency departments from a centralized data warehouse from a private for-profit hospital system during the COVID-19 pandemic. The mean daily volumes of 148 emergency departments were evaluated across 16 states in relation to each state's governmental statewide lockdown orders. Comparisons of the same period in the prior year were evaluated for percent changes in volumes. We also compared pre-lockdown to post-lockdown volumes. A separate analysis was made for the pediatric ED volumes. RESULTS: The 2020 post-lockdown volumes compared to the same 2019 dates revealed a mean percent change of -43.09%. The overall post-lockdown volumes compared to the pre-lockdown volumes had a mean percent change of -45.00%. The pediatric data revealed a greater mean percentage change in volumes of -71.52% (post-lockdown compared to 2019) and -69.03% (post-lockdown compared to pre-lockdown). CONCLUSIONS: This study found an overall decrease in volumes among 148 emergency departments across 16 states when compared to the comparable period pre-global pandemic.

Outcomes of paediatric patients with chronic liver disease in early adulthood: A heterogeneous, but representative, regional cohort study.

AIM: Advances in paediatric hepatology have led to the increasing survival of patients with paediatric-onset chronic hepatobiliary disease into adulthood. Data are lacking with regard to the outcomes of this heterogeneous group of patients and current transition models may be insufficient. This retrospective regional cohort study examined the outcomes of these patients cared for in a paediatric gastroenterology centre following transfer to adult services. METHODS: A prospective database of paediatric patients with liver disease identified those already transferred to adult services. Following exclusions, medical notes were examined and health parameters recorded including initial diagnoses, transplant status, fertility and mortality. Descriptive statistics were used to calculate follow-up data and transplant-free survival (TFS). RESULTS: Overall, 63 patients (52% male) entered the final analyses with a median follow-up of 27.5 years. The most common diagnosis was biliary atresia (19%); 27 different diagnoses were apparent within the cohort highlighting the heterogeneity within a single centre. Transplant prevalence at adult transfer was 41%; 14% of patients were lost to follow-up including 10% of transplant patients. TFS for biliary atresia was 17% after 37.4 years follow-up and was 54% for the total cohort. There were seven documented pregnancies and the prevalence of any psychological or psychiatric input was 44%. Transplant complications occurred in 38% of patients; there were two cancer diagnoses and two deaths following transfer. CONCLUSIONS: Although overall mortality was low, the health-care burden of patients with paediatric-onset chronic liver disease is high. This group is also very heterogeneous, making structured transition to adult services difficult.

Fermentation of liquid feed with lactic acid bacteria reduces dry matter losses, lysine breakdown, formation of biogenic amines, and phytate-phosphorus.

This study investigated the fermentation of liquid feed for pigs and the effect of lactic acid bacteria (LAB) supplementation on fermentation rate, dry matter losses (DML), formation of biogenic amines, and degradation of phytate-P. The basal substrate in all three in vitro batch experiments consisted of 50% canola meal, 25% wheat, and 25% barley. The mixed substrates were adjusted to a dry matter (DM) content of 28.4% and fermented in 1-liter vessels at 37 °C for 24 h. Experiment 1 focused on changes in pH profiles over time. Treatments were as follows: 1) liquid feed without additive (control) and 2) liquid feed supplemented with a mixture of Lactobacillus plantarum, Pediococcus pentosaceus, and Lactobacillus lactis (adLAB) at 2.0 × 105 CFU/g liquid feed (wet wt.; n = 8). Substrate pH was measured every 2 h. Experiment 2 focused on DML and the impact of fermentation on phytate-P. Treatments were identical to experiment 1 (control and adLAB; n = 8). Measured parameters included concentration of lactic acid, acetic acid, ethanol, and phytate-P, and DML after 24 h of fermentation. Counts of molds, Enterobobacteriaceae, yeasts, and LAB were determined in one combined sample of all replicates. Dry matter losses were lower in LAB-supplemented fermentations (5.89%) compared to the control (11.8%; P < 0.001). Supplementation with LAB reduced the phytate-P content (2.66 g/kg DM) compared to the control (3.07 g/kg DM; P = 0.002). Experiment 3 evaluated DML and the impact of fermentation on formation of biogenic amines. Treatments were as follows: 1) control, 2) adLAB (2.0 × 105 CFU LAB/g liquid feed), 3) adLys (0.60% DM supplemented lysine), and 4) adLAB+Lys (combination of adLAB and adLys; n = 8). The fermentation of adLys resulted in a nearly complete breakdown of supplemented lysine, whereas only 10% of supplemented lysine was lost in adLAB+Lys. Furthermore, all adLys samples tested positive for cadaverine (mean concentration 0.89% DM), whereas no adLAB samples contained cadaverine above the detection limit (P < 0.001). Results indicate that DML is reduced in fermentations supplemented with homofermentative LAB. Fermentation of liquid feed with homofermentative LAB can effectively reduce the degradation of supplemental lysine and has the potential to further improve P availability.

Perturbation of ATG16L1 function impairs the biogenesis of Salmonella and Coxiella replication vacuoles.

Anti-bacterial autophagy, known as xenophagy, is a host innate immune response that targets invading pathogens for degradation. Some intracellular bacteria, such as the enteric pathogen Salmonella enterica serovar Typhimurium (S. Typhimurium), utilize effector proteins to interfere with autophagy. One such S. Typhimurium effector, SopF, inhibits recruitment of ATG16L1 to damaged Salmonella-containing vacuoles (SCVs), thereby inhibiting the host xenophagic response. SopF is also required to maintain the integrity of the SCV during the early stages of infection. Here we show disruption of the SopF-ATG16L1 interaction leads to an increased proportion of cytosolic S. Typhimurium. Furthermore, SopF was utilized as a molecular tool to examine the requirement for ATG16L1 in the intracellular lifestyle of Coxiella burnetii, a bacterium that requires a functional autophagy pathway to replicate efficiently and form a single, spacious vacuole called the Coxiella-containing vacuole (CCV). ATG16L1 is required for CCV expansion and fusion but does not influence C. burnetii replication. In contrast, SopF did not affect CCV formation or replication, demonstrating that the contribution of ATG16L1 to CCV biogenesis is via its role in autophagy, not xenophagy. This study highlights the diverse capabilities of bacterial effector proteins to dissect the molecular details of host-pathogen interactions.

Interfering with Autophagy: The Opposing Strategies Deployed by Legionella pneumophila and Coxiella burnetii Effector Proteins.

Autophagy is a fundamental and highly conserved eukaryotic process, responsible for maintaining cellular homeostasis and releasing nutrients during times of starvation. An increasingly important function of autophagy is its role in the cell autonomous immune response; a process known as xenophagy. Intracellular pathogens are engulfed by autophagosomes and targeted to lysosomes to eliminate the threat to the host cell. To counteract this, many intracellular bacterial pathogens have developed unique approaches to overcome, evade, or co-opt host autophagy to facilitate a successful infection. The intracellular bacteria Legionella pneumophila and Coxiella burnetii are able to avoid destruction by the cell, causing Legionnaires' disease and Q fever, respectively. Despite being related and employing homologous Dot/Icm type 4 secretion systems (T4SS) to translocate effector proteins into the host cell, these pathogens have developed their own unique intracellular niches. L. pneumophila evades the host endocytic pathway and instead forms an ER-derived vacuole, while C. burnetii requires delivery to mature, acidified endosomes which it remodels into a large, replicative vacuole. Throughout infection, L. pneumophila effectors act at multiple points to inhibit recognition by xenophagy receptors and disrupt host autophagy, ensuring it avoids fusion with destructive lysosomes. In contrast, C. burnetii employs its effector cohort to control autophagy, hypothesized to facilitate the delivery of nutrients and membrane to support the growing vacuole and replicating bacteria. In this review we explore the effector proteins that these two organisms utilize to modulate the host autophagy pathway in order to survive and replicate. By better understanding how these pathogens manipulate this highly conserved pathway, we can not only develop better treatments for these important human diseases, but also better understand and control autophagy in the context of human health and disease.

Lysosomal degradation products induce Coxiella burnetii virulence.

Coxiella burnetii is an intracellular pathogen that replicates in a lysosome-like vacuole through activation of a Dot/Icm-type IVB secretion system and subsequent translocation of effectors that remodel the host cell. Here a genome-wide small interfering RNA screen and reporter assay were used to identify host proteins required for Dot/Icm effector translocation. Significant, and independently validated, hits demonstrated the importance of multiple protein families required for endocytic trafficking of the C. burnetii-containing vacuole to the lysosome. Further analysis demonstrated that the degradative activity of the lysosome created by proteases, such as TPP1, which are transported to the lysosome by receptors, such as M6PR and LRP1, are critical for C. burnetii virulence. Indeed, the C. burnetii PmrA/B regulon, responsible for transcriptional up-regulation of genes encoding the Dot/Icm apparatus and a subset of effectors, induced expression of a virulence-associated transcriptome in response to degradative products of the lysosome. Luciferase reporter strains, and subsequent RNA-sequencing analysis, demonstrated that particular amino acids activate the C. burnetii PmrA/B two-component system. This study has further enhanced our understanding of C. burnetii pathogenesis, the host-pathogen interactions that contribute to bacterial virulence, and the different environmental triggers pathogens can sense to facilitate virulence.

SopF, a phosphoinositide binding effector, promotes the stability of the nascent Salmonella-containing vacuole.

The enteric bacterial pathogen Salmonella enterica serovar Typhimurium (S. Typhimurium), utilizes two type III secretion systems (T3SSs) to invade host cells, survive and replicate intracellularly. T3SS1 and its dedicated effector proteins are required for bacterial entry into non-phagocytic cells and establishment and trafficking of the nascent Salmonella-containing vacuole (SCV). Here we identify the first T3SS1 effector required to maintain the integrity of the nascent SCV as SopF. SopF associates with host cell membranes, either when translocated by bacteria or ectopically expressed. Recombinant SopF binds to multiple phosphoinositides in protein-lipid overlays, suggesting that it targets eukaryotic cell membranes via phospholipid interactions. In yeast, the subcellular localization of SopF is dependent on the activity of Mss4, a phosphatidylinositol 4-phosphate 5-kinase that generates PI(4,5)P2 from PI(4)P, indicating that membrane recruitment of SopF requires specific phospholipids. Ectopically expressed SopF partially colocalizes with specific phosphoinositide pools present on the plasma membrane in mammalian cells and with cytoskeletal-associated markers at the leading edge of cells. Translocated SopF concentrates on plasma membrane ruffles and around intracellular bacteria, presumably on the SCV. SopF is not required for bacterial invasion of non-phagocytic cells but is required for maintenance of the internalization vacuole membrane as infection with a S. Typhimurium ΔsopF mutant led to increased lysis of the SCV compared to wild type bacteria. Our structure-function analysis shows that the carboxy-terminal seven amino acids of SopF are essential for its membrane association in host cells and to promote SCV membrane stability. We also describe that SopF and another T3SS1 effector, SopB, act antagonistically to modulate nascent SCV membrane dynamics. In summary, our study highlights that a delicate balance of type III effector activities regulates the stability of the Salmonella internalization vacuole.

Periprosthetic femoral bone loss in total hip arthroplasty: systematic analysis of the effect of stem design.

INTRODUCTION: Periprosthetic bone loss may lead to major complications in total hip arthroplasty (THA), including loosening, migration, and even fracture. This study analysed the influence of femoral implant designs on periprosthetic bone mineral density (BMD) after THA. METHODS: The results of all previous published studies reporting periprosthetic femoral BMD following THA were compiled. Using these results, we compared percent changes in bone loss as a function of: femoral stem fixation, material, and geometry. RESULTS: The greatest bone loss was in the calcar region (Gruen Zone 7). Overall, cemented stems had more bone loss distally than noncemented stems, while noncemented stems had more proximal bone loss than cemented stems. Within noncemented stems, cobalt-chromium (CoCr) stems had nearly double the proximal bone loss compared to titanium (Ti) alloy stems. Finally, within noncemented titanium alloy group, straight stems had less bone loss than anatomical, tapered, and press-fit designs. DISCUSSION: The findings from the present study quantified percent changes in periprosthetic BMD as a function of fixation method, alloy, and stem design. While no one stem type was identified as ideal, we now have a clearer understanding of the influence of stem design on load transfer to the surrounding bone.

A Low-Intensity Mindfulness-Based Intervention for Mood Symptoms in People with Early Psychosis: Development and Pilot Evaluation.

BACKGROUND: Depressive and anxiety symptoms are common in people suffering from early psychosis. Growing evidence shows that mindfulness-based intervention is an effective option in handling depression and anxiety disorders. Current article aims to provide documentation on the development and pilot study, before a RCT of larger scale, evaluating the acceptability and potential effects of a 7-week mindfulness-based intervention programme (MBI-p). METHOD: MBI-p was developed over nine months in 2014. A total of 14 people with early psychosis were recruited to three pilot trials of MBI-p. Eleven of them completed the programme and were interviewed. Eight of them were measured quantitatively at baseline and post-intervention on clinical symptoms, depression and anxiety levels, quality of life and mindfulness. RESULTS: Mixed qualitative and quantitative results supported MBI-p as an acceptable and feasible intervention. Significant statistical improvements were found in depression levels, mental quality of life, general psychopathology and ability to observe emotions and act with awareness. Qualitative comments suggested that the intervention was safe, enjoyable and had a positive impact on mood symptoms. In summary, these results provide a promising pilot support for a potentially effective and cost-efficient treatment option for people with early psychosis. Copyright © 2015 John Wiley & Sons, Ltd. KEY PRACTITIONER MESSAGE: Depressive and anxiety symptoms are common in people with early psychosis but long received little attention. A low-intensity mindfulness-based intervention targeting depression and anxiety symptoms among people with early psychosis was developed and pilot tested. It is feasible and acceptable to use mindfulness-based intervention as a complementary treatment for psychosis.