Using decision tree models and comprehensive statewide data to predict opioid overdoses following prison release.

PURPOSE: Identifying predictors of opioid overdose following release from prison is critical for opioid overdose prevention. METHODS: We leveraged an individually linked, state-wide database from 2015-2020 to predict the risk of opioid overdose within 90 days of release from Massachusetts state prisons. We developed two decision tree modeling schemes: a model fit on all individuals with a single weight for those that experienced an opioid overdose and models stratified by race/ethnicity. We compared the performance of each model using several performance measures and identified factors that were most predictive of opioid overdose within racial/ethnic groups and across models. RESULTS: We found that out of 44,246 prison releases in Massachusetts between 2015-2020, 2237 (5.1%) resulted in opioid overdose in the 90 days following release. The performance of the two predictive models varied. The single weight model had high sensitivity (79%) and low specificity (56%) for predicting opioid overdose and was more sensitive for White non-Hispanic individuals (sensitivity = 84%) than for racial/ethnic minority individuals. CONCLUSIONS: Stratified models had better balanced performance metrics for both White non-Hispanic and racial/ethnic minority groups and identified different predictors of overdose between racial/ethnic groups. Across racial/ethnic groups and models, involuntary commitment (involuntary treatment for alcohol/substance use disorder) was an important predictor of opioid overdose.

Longitudinal microbiome changes in children exposed to proton pump inhibitors.

INTRODUCTION: Proton pump inhibitor (PPI) use has been associated with an increased risk of gastrointestinal and upper respiratory infections in children. There are limited longitudinal data on the effect of PPI in children. The goal of this prospective observational study was to compare the stool and oropharyngeal microbiome of children before and after starting PPIs. METHODS: We prospectively recruited participants from a gastroenterology clinic. Consented pariticpants provided stool samples and oropharyngeal swabs at baseline and after eight weeks of PPI therapy. Microbiome changes were measured by analyzing 16S sequencing from both body sites at both timepoints. RESULTS: Thirty-four participants completed the study and provided samples both at baseline and after eight weeks on PPI therapy. Of those, 24 participants had sufficient sequencing from both stool and oropharyngeal samples at both time points. There were no differences between the pre- vs post-PPI samples using beta-diversity metrics in either the oropharynx or stool. There were, however, significant changes in specific taxa. There was an enrichment of Streptococcus in the stool in after PPI-use and a reduction in the relative abundance of Bifidobacterium, Peptostreptococcus and Turicibacter (p-values < 0.01). Furthermore, there was an increase in the relative abundance of oropharyngeal bacteria in the stool after PPI therapy. This enrichment of oropharyngeal bacteria in the stool was most prominent in younger participants. DISCUSSION: Further investigation is needed to determine the clinical and microbial factors that predispose or protect against microbiome changes due to PPI-use, and why young children are more susceptible to this PPI effect.

TiO2/Polystyrene Nanocomposite Antibacterial Material as a Hemoperfusion Adsorbent for Efficient Bilirubin Removal and Prevention of Bacterial Infection.

The use of hemoperfusion adsorbents for the removal of bilirubin in patients with liver failure has become a critical treatment. However, the insufficient clearance of bilirubin and the possibility of bacterial infection during hemoperfusion limit the application. In this work, we designed a novel antibacterial bilirubin adsorbent (PSVT) through the suspension polymerization reaction between double-bond functionalized TiO2 nanoparticles and styrene. PSVT showed an excellent bilirubin adsorption ability and antibacterial performance, ensuring efficient clearance of bilirubin in liver failure patients during hemoperfusion and preventing bacterial infection. The experimental results indicated that TiO2 was uniformly dispersed in the microspheres, which improved the mesoporous structure and increased the specific surface area. Composite adsorbent PSVT showed an exceptional bilirubin adsorption capacity, with the maximum adsorption capacity reaching 24.3 mg/g. In addition, the introduction of TiO2 endowed PSVT with excellent antibacterial ability; the ultimate antibacterial rates against Escherichia coli and Staphylococcus aureus reached 97.31 and 96.47%, respectively. In summary, PSVT served as a novel antibacterial bilirubin adsorbent with excellent bilirubin clearance capacity and antibacterial performance, providing excellent application prospects for treating liver failure patients.

Gender Differences in Hospital Outcomes among COVID-19 Hospitalizations.

OBJECTIVES: Many epidemiological studies have shown that coronavirus disease 2019 (COVID-19) disproportionately affects males, compared with females, although other studies show that there were no such differences. The aim of the present study was to assess differences in the prevalence of hospitalizations and in-hospital outcomes between the sexes, using a larger administrative database. METHODS: We used the 2020 California State Inpatient Database for this retrospective analysis. International Classification of Diseases, Tenth Revision, Clinical Modification diagnosis code U07.1 was used to identify COVID-19 hospitalizations. These hospitalizations were subsequently stratified by male and female sex. Diagnosis and procedures were identified using the International Classification of Diseases, Tenth Revision, Clinical Modification codes. The primary outcome of the study was hospitalization rate, and secondary outcomes were in-hospital mortality, prolonged length of stay, vasopressor use, mechanical ventilation, and intensive care unit (ICU) admission. RESULTS: There were 95,180 COVID-19 hospitalizations among patients 18 years and older, 52,465 (55.1%) of which were among men and 42,715 (44.9%) were among women. In-hospital mortality (12.4% vs 10.1%), prolonged length of hospital stays (30.6% vs 25.8%), vasopressor use (2.6% vs 1.6%), mechanical ventilation (11.8% vs 8.0%), and ICU admission rates (11.4% versus 7.8%) were significantly higher among male compared with female hospitalizations. Conditional logistic regression analysis showed that the odds of mortality (odds ratio [OR] 1.38, 95% confidence interval [CI] 1.38-1.44), hospital lengths of stay (OR 1.35, 95% CI 1.31-1.39), vasopressor use (OR 1.59, 95% CI 1.51-1.66), mechanical ventilation (OR 1.62, 95% CI 1.47-1.78), and ICU admission rates (OR 1.58, 95% CI 1.51-1.66) were significantly higher among male hospitalizations. CONCLUSION: Our findings show that male sex is an independent and strong risk factor associated with COVID-19 severity.

Impact of Nicosulfuron on Sperm Quality: Insights into Testicular Cell Apoptosis and NF-κB Signaling Pathway in Mice Testes.

BACKGROUND: Nicosulfuron, a widely used herbicide in crops, has raised concerns due to its escalating presence as an environmental pollutant, particularly in soil and water. The potential adverse effects of nicosulfuron on animals, including reproductive toxicity, have garnered attention. OBJECTIVE: The study aimed to evaluate the reproductive toxicity of nicosulfuron in male mice. METHODS: Male mice were orally administrated with three different concentration gradients (350, 700, and 1400 mg/kg) of nicosulfuron for 35 days. The investigation delved into sperm quality, testicular structures, and expression of cleaved caspase-3 and NF-κB p65 of the testes. RESULTS: The finding unveiled a correlation between nicosulfuron exposure and detrimental effects on sperm quality and alteration of testicular structure. Notably, parameters, such as sperm survival rate (SUR) and sperm motility (MOT), exhibited a decline in relation to increasing nicosulfuron dosages. Moreover, in the mice subjected to higher doses of nicosulfuron, elevated expression of cleaved caspase-3 and NF-κB p65 was observed in the testes. Interestingly, we also observed an increase of NF-κB p65 expression in the mice exposed to the nicosulfuron. CONCLUSION: Our research revealed that exposure to nicosulfuron resulted in compromised sperm quality and alterations in testicular structure. The correlation between nicosulfuron and apoptosis, especially via the NF-κB pathway, provided significant insights into the mechanisms underpinning these detrimental effects. These findings significantly enhance our comprehension of the potential hazards associated with nicosulfuron exposure and its impacts on the reproductive health of animals.

Is it a vicious circle and for whom? The reciprocal association between rumination and somatic symptoms and moderation by stress: A daily diary study among Chinese college students.

College students who experienced somatic symptoms during the COVID-19 pandemic may engage in rumination, but their bidirectional nature remains underexplored. Symptom perception theory suggests a reciprocal relationship between rumination and somatic symptoms, and the multiple-stressor perspective and the perseverative cognition hypothesis assume that the reciprocal association might be exacerbated by high stress. In this study, we examined temporal associations between rumination and somatic symptoms and variations by patterns of stress related to COVID-19 and daily hassles. A total of 582 Chinese college students provided daily reports on rumination, somatic symptoms, COVID-related stress, and daily hassles for seven consecutive days in November 2020. A cross-lagged panel model showed a positive reciprocal association between rumination and somatic symptoms. Greater rumination predicted more next-day somatic symptoms, and more somatic symptoms increased next-day rumination. Dual trajectory analysis identified four stress patterns of COVID-related stress and daily hassles (i.e. low-low, low-high, high-low, and high-high), and multi-group analysis found the reciprocal association only presented in the high-high group. Our findings indicate a vicious circle between rumination and somatic symptoms that is dependent on heterogeneous stress patterns. Attention should be paid to the high-risk group with both high levels of COVID-related stress and daily hassles.

Adverse Outcomes in Hospitalizations for Amyloid-Related Heart Failure.

Transthyretin amyloid cardiomyopathy is being increasingly recognized as an important cause of heart failure (HF). In this study, we looked at adverse outcomes in hospitalizations with amyloid-related HF. This study was a retrospective analysis of the National Inpatient Sample data, collected from 2016 to 2019. Patients ≥41 years of age and admitted for HF were included in the study. In these hospitalizations, amyloid-related HF was identified through the International Classification of Diseases, Tenth Revision, Clinical Modification codes for amyloidosis. The primary outcome of the study was in-hospital mortality, whereas secondary outcomes were prolonged length of stay, mechanical ventilation, mechanical circulatory support, vasopressors use, and dispositions other than home. From 2016 to 2019, there were 4,705,274 HF hospitalizations, of which 16,955 (0.4%) had amyloid cardiomyopathy. In all HF hospitalizations, amyloid-related increased from 0.26% in 2016 to 0.46% in 2019 (relative increase, 76.9%, P for trend <0.001). Amyloid-related HF hospitalizations were more common in older, male, and Black patients. The odds of in-hospital mortality (odds ratio [OR], 1.29; 95% confidence interval [CI]: 1.11 to 1.38), prolonged hospital length (OR, 1.61; 95% CI: 1.49 to 1.73) and vasopressors use (OR, 1.59; 95% CI: 1.23 to 2.05) were significantly higher for amyloid-related hospitalizations. Amyloid-related HF hospitalizations are increasing substantially and are associated with adverse hospital outcomes. These hospitalizations were disproportionately higher for older, male, and Black patients. Amyloid-related HF is rare and underdiagnosed yet has several adverse outcomes. Hence, healthcare providers should be watchful of this condition for early identification and prompt management.

Trajectories of Perceived Stress among Students in Transition to College: Mindset Antecedents and Adjustment Outcomes.

There is growing evidence of a clear association between students' perceived stress and their adjustment to life at college. However, the predictors and implications of distinct changing patterns of perceived stress during the transition to college life are less clear. To address these research gaps, the current study aims to identify distinct patterns of perceived stress trajectories among 582 Chinese first-year college students (Mage = 18.11, SDage = 0.65; 69.40% female) across the first 6 months upon enrollment. Three distinct profiles of perceived stress trajectories, i.e., low-stable (15.63%), middle-decreasing (69.07%), and high-decreasing (15.29%), were identified. Moreover, individuals who followed the low-stable trajectory showed better distal outcomes (specifically, higher levels of well-being and academic adjustment) 8 months after enrollment than those who followed the other two trajectories. Furthermore, two types of positive mindset (a growth mindset of intelligence and a stress-is-enhancing mindset) contributed to differences in perceived stress trajectory, either independently or jointly. These findings highlight the significance of identifying different patterns of perceived stress among students during the transition to college, as well as the protective roles of both a stress mindset and a mindset of intelligence.

Dual Stealth Functional Immuno-magnetic Nanoparticles for High-Performance Isolation of Circulating Tumor Cells.

As a biomarker of hepatocellular carcinoma (HCC) biopsy, circulating tumor cells (CTCs) are often used in the diagnosis of cancer and treatment guidance. For CTCs detection, immuno-magnetic nanoparticles (IMNs) are one of the most commonly used platforms. However, the nonspecific adsorption of proteins and non-tumor cells weakens the performance of IMNs to capture CTCs. In this work, we developed an IMNs platform which was constructed by a biomimetic protein corona precoating and a polyethylene glycol (PEG) spacer to form the PEG and corona-coated IMNs (IP-CMNs). Due to the dual stealth effect of protein corona precoating and PEG spacer, the nonspecific protein adsorption and cell binding of P-CMNs could reduce by ∼5.5- and ∼5.4-fold, respectively, compared with those of unmodified particles. Furthermore, the PEG spacer could not only reduce the interaction between IP-CMNs and leukocytes but also enhance the capture performance toward tumor cells. By using artificial blood samples, the capture efficiency of IP-CMNs toward rare CTCs was found to be 88.3%, while it was 70.5% by using commercial IMNs. Finally, CTCs were successfully isolated in all HCC patient blood samples (7/7) using IP-CMNs. These results provide insight into the use of the multifunctional nanoplatform as a useful tool for CTCs detection.

Obesity induces male mice infertility via oxidative stress, apoptosis, and glycolysis.

In brief: The current declining trend in male fertility parallels the increasing prevalence of obesity worldwide. This paper revealed that the poor in vitro fertilization rates and decreased sperm motility in obese mice due to excessive oxidative stress enhanced apoptosis and impaired glucose metabolism in the testes. Abstract: Obesity is an urgent public health problem in recent decades, linked to reduced reproductive potential, and negatively affects the success of assisted reproduction technology. The aim of this study is to investigate the mechanisms underlying impaired male fertility caused by obesity. Male C57BL/6 mice fed a high-fat diet for 20 weeks served as mouse models with moderate (20% < body fat rate (BFR) < 30%) and severe obesity (BFR > 30%). Our results showed poor in vitro fertilization rates and decreased sperm motility in obese mice. Abnormal testicular structures were identified in male mice with moderate and severe obesity. The expression level of malondialdehyde increased with obesity severity. This finding indicates that oxidative stress plays a role in male infertility caused by obesity, which was further confirmed by the decreased expression of nuclear factor erythroid 2-related factor 2, superoxide dismutase, and glutathione peroxidases. Our study also found that the expression of cleaved caspase-3 and B-cell lymphoma-2 showed an obesity severity-dependent manner indicating that apoptosis is highly correlated with male infertility caused by obesity. Moreover, the expression of glycolysis-related proteins, including glucose transporter 8, lactate dehydrogenase A, monocarboxylate transporter 2 (MCT2), and MCT4, decreased significantly in the testes of obese male mice, suggesting energy supply for spermatogenesis is impaired by obesity. Taken together, our findings provide evidence that obesity impairs male fertility through oxidative stress, apoptosis, and blockage of energy supply in the testes and suggest that male obesity influences fertility through complex and multiple mechanisms.

Higher alpha diversity and Lactobacillus blooms are associated with better engraftment after Fecal Microbiota Transplant in Inflammatory Bowel Disease.

Background: Fecal Microbiota Transplant (FMT) has proven effective in treating recurrent Clostridioides difficile infection (rCDI) and has shown some success in treating inflammatory bowel diseases (IBD). There is emerging evidence that host engraftment of donor taxa is a tenet of successful FMT. However, there is little known regarding predictors of engraftment. We undertook a double-blind, randomized, placebo-controlled pilot study to characterize the response to FMT in children and young adults with mild to moderate active Crohn's disease (CD) and ulcerative colitis (UC). Results: Subjects with CD or UC were randomized to receive antibiotics and weekly FMT or placebo in addition to baseline medications. The treatment arm received seven days of antibiotics followed by FMT enema and then capsules weekly for seven weeks. We enrolled four subjects with CD and 11 with UC, ages 14-29 years. Due to weekly stool sampling, we were able to create a time series of alpha diversity, beta diversity and engraftment as they related to clinical response. Subjects exhibited a wide range of microbial diversity and donor engraftment as FMT progressed. Specifically, engraftment ranged from 26% to 90% at week 2 and 3% to 92% at two months. Consistent with the current literature, increases over time of both alpha diversity (p< 0.05) and donor engraftment (p< 0.05) correlated with improved clinical response. Additionally, our weekly time series enabled an investigation into the clinical and microbial correlates of engraftment at various time points. We discovered that the post-antibiotic but pre-FMT time point, often overlooked in FMT trials, was rich in microbial correlates of eventual engraftment. Greater residual alpha diversity after antibiotic treatment was positively correlated with engraftment and subsequent clinical response. Interestingly, a transient rise in the relative abundance of Lactobacillus was also positively correlated with engraftment, a finding that we recapitulated with our analysis of another FMT trial with publicly available weekly sequencing data. Conclusions: We found that higher residual alpha diversity and Lactobacillus blooms after antibiotic treatment correlated with improved engraftment and clinical response to FMT. Future studies should closely examine the host microbial communities pre-FMT and the impact of antibiotic preconditioning on engraftment and response.

Associations between trait and state perceived stress and daily moods: COVID-19 stressful experiences as a moderator.

Drastically disrupting daily routines, the global pandemic of COVID-19 has posed critical mental health threats to adolescents and young adults worldwide. Many of the extant empirical findings, however, have focused on individuals' psychological adjustment during the initial phase of the pandemic. It is less clear how COVID-19 stressful experiences impact young people's daily lives in the post-pandemic "new normal." Drawing on 7-day diary reports, the present study fills this gap by examining: (1) how daily perceived stress impacted daily emotional adjustment; and (2) the moderating effects of COVID-19 stressful experiences on these associations among 582 Chinese young adults (M age = 18.12, SD = .65; 69% females). Results indicated that higher levels of both trait (i.e., average levels) and state (i.e., daily fluctuations) perceived stress were associated with greater negative and anxious moods, and that prior pandemic-related experiences exacerbated the adverse impact of both trait and state perceived stress on daily moods. Specifically, young adults reporting greater COVID-19 stressful experiences demonstrated poorer emotional adjustment (i.e., lower levels of positive mood and higher levels of negative mood) on days when they had more fluctuations in perceived stress; the aggravating impact was stronger when the average levels of perceived stress were higher. By illuminating the moderating effects of COVID-19 stressful experiences, this study contributes to the limited, but burgeoning, research examining the prolonged impact of the COVID-19 health crisis on daily emotional adjustment in post-pandemic life.

Hydrogel-based microfluidic device with multiplexed 3D in vitro cell culture.

Microfluidic devices that combine an extracellular matrix environment, cells, and physiologically relevant perfusion, are advantageous as cell culture platforms. We developed a hydrogel-based, microfluidic cell culture platform by loading polyethylene glycol (PEG) hydrogel-encapsulated U87 glioblastoma cells into membrane-capped wells in polydimethyl siloxane (PDMS). The multilayer microfluidic cell culture system combines previously reported design features in a configuration that loads and biomimetically perfuses a 2D array of cell culture chambers. One dimension of the array is fed by a microfluidic concentration gradient generator (MCGG) while the orthogonal dimension provides loading channels that fill rows of cell culture chambers in a separate layer. In contrast to typical tree-like MCGG mixers, a fractional serial dilution of 1, ½, », and 0 of the initial solute concentration is achieved by tailoring the input microchannel widths. Hydrogels are efficiently and reproducibly loaded in all wells and cells are evenly distributed throughout the hydrogel, maintaining > 90% viability for up to 4 days. In a drug screening assay, diffusion of temozolomide and carmustine to hydrogel-encapsulated U87 cells from the perfusion solution is measured, and dose-response curves are generated, demonstrating utility as an in vitro mimic of the glioblastoma microenvironment.

Constructing a Rigid-and-Flexible Twin-Stage Gradient Interphase through Starlike Copolymer Coating on Carbon Fibers: A Route for Enhancing Interfacial Properties of Composites.

A rigid-and-flexible interphase was established by a starlike copolymer (Pc-PGMA/Pc) consisting of one tetraaminophthalocyanine (TAPc) core with four TAPc-difunctionalized poly(glycidyl methacrylate) (PGMA) arms through the surface modification of carbon fibers (CFs) and compared with various interphases constructed by TAPc and TAPc-connected PGMA (Pc-PGMA). The increase in the content of N-C═O showed that PGMA/Pc branches were successfully attached onto the CF-(Pc-PGMA/Pc) surface, exhibiting concavo-convex microstructures with the highest roughness. Through adhesive force spectroscopy by atomic force microscopy (AFM) with peak force quantitative nanomechanical mapping (PF-QNM) mode and visualization of the relative distribution of TAPc/PGMA via a Raman spectrometer, a rigid interphase with highly cross-linked TAPc and a flexible layer from PGMA arms as the soft segment were separately detected in CF-TAPc/EP and CF-(Pc-PGMA)/EP composites. The rigid-and-flexible interphase in the CF-(Pc-PGMA/Pc)/EP composite provided excellent stress-transfer capability by the rigid inner modulus intermediate layer and energy absorption efficiency from the flexible outer layer, which contributed to 64.6 and 61.8% increment of transverse fiber bundle test (TFBT) strength, and 33.8 and 40.6% enhancement in interfacial shear strength (IFSS) in comparison with those of CF-TAPc/EP and CF-(Pc-PGMA)/EP composites. Accordingly, schematic models of the interphase reinforcing mechanism were proposed. The interfacial failures in CF-TAPc/EP and CF-(Pc-PGMA)/EP composites were derived from the rigid interphase without effective relaxation of interfacial stress and soft interphase with excessive fiber-matrix interface slippage, respectively. The cohesive failure in the CF-(Pc-PGMA/Pc)/EP composite was attributed to the crack deflection through the balance of the modulus and deformability from the twin-stage gradient intermediate layer.

Mobile phone use among e-cyclists at red traffic lights: An observation study in a city of China.

OBJECTIVE: The observation study sought to explore the influencing factors associated with mobile phone use when e-cyclists were waiting for red lights at intersections, which provided a theoretical foundation for solving the potential traffic threat and developing management plans for e-cyclists. METHODS: Data regarding e-cyclists were collected through camera conducted at the entrance of multiple intersections in Zhenjiang, China in July 2020. The data was reviewed by playing frame by frame. A statistical analysis was performed with the statistical package SPSS software. After conducting univariate logistic analysis on study variables, the multivariate analysis was adopted based on the binary logit regression model. RESULTS: Among the 1166 e-cyclists observed, 15.01% (n = 175) e-cyclists had operated their mobile phones while waiting for red lights. Young e-cyclists, delivery cyclists were more likely to be involved with mobile phone use. Furthermore, mobile phone use was more observed at intersections in suburban areas and with long waiting time. E-cyclists, who was carrying a child, rarely used mobile phone. All intersections during off-peak times showed an increase in mobile phone use. The results also show that neither e-cyclists themselves nor traffic managers are aware of the risks of mobile phone use and the impact on traffic safety while waiting for a red light. CONCLUSIONS: The findings of this research revealed the factors influencing mobile phone use of e-cyclists while waiting for a red light, and indicated that education and behavioral intervention need to be strengthened to improve riding safety at intersections. These results will be helpful in developing programs of electric bicycle management.

Novel variants in the stem cell niche factor WNT2B define the disease phenotype as a congenital enteropathy with ocular dysgenesis.

WNT2B is a member of the Wnt family, a group of signal transduction proteins involved in embryologic development and stem cell renewal and maintenance. We recently reported homozygous nonsense variants in WNT2B in three individuals with severe, neonatal-onset diarrhea, and intestinal failure. Here we present a fourth case, from a separate family, with neonatal diarrhea associated with novel compound heterozygous WNT2B variants. One of the two variants was a frameshift variant (c.423del [p.Phe141fs]), while the other was a missense change (c.722 G > A [p.G241D]) that we predict through homology modeling to be deleterious, disrupting post-translational acylation. This patient presented as a neonate with severe diet-induced (osmotic) diarrhea and growth failure resulting in dependence on parenteral nutrition. Her gastrointestinal histology revealed abnormal cellular architecture particularly in the stomach and colon, including oxyntic atrophy, abnormal distribution of enteroendocrine cells, and a paucity of colonic crypt glands. In addition to her gastrointestinal findings, she had bilateral corneal clouding and atypical genital development later identified as a testicular 46,XX difference/disorder of sexual development. Upon review of the previously reported cases, two others also had anterior segment ocular anomalies though none had atypical genital development. This growing case series suggests that variants in WNT2B are associated with an oculo-intestinal (and possibly gonadal) syndrome, due to the protein's putative involvement in multiple developmental and stem cell maintenance pathways.

Inflammatory Bowel Disease Presenting With Concurrent COVID-19 Multisystem Inflammatory Syndrome.

Coronavirus disease 2019 is associated with a postinfectious multisystem inflammatory syndrome in children (MIS-C). This syndrome is marked by cytokine storm and multiorgan dysfunction, often affecting the gastrointestinal tract, the heart, and the hematopoietic system. We describe the case of a 16-year-old boy with an initial presentation of severe inflammatory bowel disease and concurrent MIS-C. He presented with abdominal pain, diarrhea, and hematochezia and met criteria for the systemic inflammatory response syndrome. Laboratory inflammatory profiling revealed markedly elevated ferritin, D-dimer, C-reactive protein, soluble interleukin 2, and interleukin 6 levels. Endoscopy and colonoscopy revealed severe active gastroduodenitis, patchy colitis, and a normal-appearing terminal ileum. The patient was treated with a combination of steroids, intravenous immunoglobulin, and infliximab, and his symptoms slowly resolved over a 3-week period. In this case, we describe coincident MIS-C with a remarkably severe and difficult-to-treat initial presentation of inflammatory bowel disease and highlight the need to investigate the effect of coronavirus disease 2019 and MIS-C on inflammatory disorders.

Genome-wide Phenotypic Profiling Identifies and Categorizes Genes Required for Mycobacterial Low Iron Fitness.

Iron is vital for nearly all living organisms, but during infection, not readily available to pathogens. Infectious bacteria therefore depend on specialized mechanisms to survive when iron is limited. These mechanisms make attractive targets for new drugs. Here, by genome-wide phenotypic profiling, we identify and categorize mycobacterial genes required for low iron fitness. Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis (TB), can scavenge host-sequestered iron by high-affinity iron chelators called siderophores. We take advantage of siderophore redundancy within the non-pathogenic mycobacterial model organism M. smegmatis (Msmeg), to identify genes required for siderophore dependent and independent fitness when iron is low. In addition to genes with a potential function in recognition, transport or utilization of mycobacterial siderophores, we identify novel putative low iron survival strategies that are separate from siderophore systems. We also identify the Msmeg in vitro essential gene set, and find that 96% of all growth-required Msmeg genes have a mutual ortholog in Mtb. Of these again, nearly 90% are defined as required for growth in Mtb as well. Finally, we show that a novel, putative ferric iron ABC transporter contributes to low iron fitness in Msmeg, in a siderophore independent manner.