Sensory neurons promote immune homeostasis in the lung.

Cytokines employ downstream Janus kinases (JAKs) to promote chronic inflammatory diseases. JAK1-dependent type 2 cytokines drive allergic inflammation, and patients with JAK1 gain-of-function (GoF) variants develop atopic dermatitis (AD) and asthma. To explore tissue-specific functions, we inserted a human JAK1 GoF variant (JAK1GoF) into mice and observed the development of spontaneous AD-like skin disease but unexpected resistance to lung inflammation when JAK1GoF expression was restricted to the stroma. We identified a previously unrecognized role for JAK1 in vagal sensory neurons in suppressing airway inflammation. Additionally, expression of Calcb/CGRPß was dependent on JAK1 in the vagus nerve, and CGRPß suppressed group 2 innate lymphoid cell function and allergic airway inflammation. Our findings reveal evolutionarily conserved but distinct functions of JAK1 in sensory neurons across tissues. This biology raises the possibility that therapeutic JAK inhibitors may be further optimized for tissue-specific efficacy to enhance precision medicine in the future.

Immunology of COVID-19: Current State of the Science.

The coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has affected millions of people worldwide, igniting an unprecedented effort from the scientific community to understand the biological underpinning of COVID19 pathophysiology. In this Review, we summarize the current state of knowledge of innate and adaptive immune responses elicited by SARS-CoV-2 infection and the immunological pathways that likely contribute to disease severity and death. We also discuss the rationale and clinical outcome of current therapeutic strategies as well as prospective clinical trials to prevent or treat SARS-CoV-2 infection.

Rhytidectomy Incision Techniques and Scar Outcomes: A Scoping Review.

Although scar outcomes in rhytidectomy are crucial to patients and surgeons alike, there is a lack of consensus on incision techniques for optimizing rhytidectomy scars. A comprehensive scoping review of the literature was performed on rhytidectomy incision techniques and associated scar outcomes.The PRISMA protocol was utilized to conduct a scoping review of the literature through MEDLINE, EMBASE, and Science Citation Index databases to identify articles discussing rhytidectomy incision techniques and scar outcomes.A total of 49 studies were included in this scoping review. Four themes were identified related to rhytidectomy scars within these studies: temporal incision placement, tragal incision placement, lobule management, and postauricular incision design. Techniques within each theme were described and reported scar outcomes summarized.There are many approaches to rhytidectomy incisions described in the literature, with reportedly low rates of scar complications for each of the techniques described. It cannot be elucidated which techniques are superior due to the heterogeneity of outcomes reported in the literature with significant variability in outcome measures, study design, and follow-up time. Future studies should focus on utilizing a standardized rating system to aid in objective determination of the superiority of one technique versus another. LEVEL OF EVIDENCE:: Level I.

Machine Learning Assisted Discovery of Interactions between Pesticides, Phthalates, Phenols, and Trace Elements in Child Neurodevelopment.

A growing body of literature suggests that developmental exposure to individual or mixtures of environmental chemicals (ECs) is associated with autism spectrum disorder (ASD). However, investigating the effect of interactions among these ECs can be challenging. We introduced a combination of the classical exposure-mixture Weighted Quantile Sum (WQS) regression and a machine-learning method termed Signed iterative Random Forest (SiRF) to discover synergistic interactions between ECs that are (1) associated with higher odds of ASD diagnosis, (2) mimic toxicological interactions, and (3) are present only in a subset of the sample whose chemical concentrations are higher than certain thresholds. In a case-control Childhood Autism Risks from Genetics and Environment (CHARGE) study, we evaluated multiordered synergistic interactions among 62 ECs measured in the urine samples of 479 children in association with increased odds for ASD diagnosis (yes vs no). WQS-SiRF identified two synergistic two-ordered interactions between (1) trace-element cadmium (Cd) and the organophosphate pesticide metabolite diethyl-phosphate (DEP); and (2) 2,4,6-trichlorophenol (TCP-246) and DEP. Both interactions were suggestively associated with increased odds of ASD diagnosis in the subset of children with urinary concentrations of Cd, DEP, and TCP-246 above the 75th percentile. This study demonstrates a novel method that combines the inferential power of WQS and the predictive accuracy of machine-learning algorithms to discover potentially biologically relevant chemical-chemical interactions associated with ASD.

Prenatal Lead Exposure Is Associated with Reduced Abundance of Beneficial Gut Microbial Cliques in Late Childhood: An Investigation Using Microbial Co-Occurrence Analysis (MiCA).

Many analytical methods used in gut microbiome research focus on either single bacterial taxa or the whole microbiome, ignoring multibacteria relationships (microbial cliques). We present a novel analytical approach to identify microbial cliques within the gut microbiome of children at 9-11 years associated with prenatal lead (Pb) exposure. Data came from a subset of participants (n = 123) in the Programming Research in Obesity, Growth, Environment and Social Stressors cohort. Pb concentrations were measured in maternal whole blood from the second and third trimesters of pregnancy. Stool samples collected at 9-11 years old underwent metagenomic sequencing to assess the gut microbiome. Using a novel analytical approach, Microbial Co-occurrence Analysis (MiCA), we paired a machine learning algorithm with randomization-based inference to first identify microbial cliques that were predictive of prenatal Pb exposure and then estimate the association between prenatal Pb exposure and microbial clique abundance. With second-trimester Pb exposure, we identified a two-taxa microbial clique that included Bifidobacterium adolescentis and Ruminococcus callidus and a three-taxa clique that also included Prevotella clara. Increasing second-trimester Pb exposure was associated with significantly increased odds of having the two-taxa microbial clique below the median relative abundance (odds ratio (OR) = 1.03, 95% confidence interval (CI) [1.01-1.05]). Using a novel combination of machine learning and causal inference, MiCA identified a significant association between second-trimester Pb exposure and the reduced abundance of a probiotic microbial clique within the gut microbiome in late childhood.

Reconstruction of a skull base defect after endoscopic endonasal resection of a pituitary adenoma: Sphenoid mucosal flaps.

This report describes a bilateral sphenoid sinus mucosal flap for the repair of a sellar floor defect and CSF leak following endoscopic endonasal skull base surgery. The key advantage of this technique is enabling the sphenoid mucosal flaps to remain vascularized, which reduces postoperative complications including CSF leakage, recurrent sinusitis, meningitis, encephalitis and pneumocephalus. The use of this technique is a viable and possibly favorable alternative to free grafts in the reconstruction of small to medium sized sellar defects with low flow or absent CSF leaks base surgery.

Low literacy self-care management patient education for a multi-lingual heart failure population: Results of a pilot study.

PURPOSE: The purpose of this pilot study was to test the impact of language-free, low literacy self-care management patient education materials in an ethnically diverse multilingual heart failure (HF) population. METHODS: A one group pre-test-post-test design measured changes in self-care, knowledge and health-related quality of life (HRQL) after a 1 month intervention using language-free, low literacy self-care management patient education materials and delivered by a health educator. RESULTS: The ethnically diverse sample (n=21) was predominately male (72%), 48% Black, 42% Hispanic, and 28% marginal/inadequate literacy. There were significant improvements in self-care and knowledge but not HRQL. CONCLUSIONS: Language-free, low literacy self-care patient education may facilitate improved self-care and knowledge in diverse populations who are at risk for poor HF outcomes.

Association between Exposure to Metals during Pregnancy, Childhood Gut Microbiome, and Risk of Intestinal Inflammation in Late Childhood.

Alterations to the gut microbiome and exposure to metals during pregnancy have been suggested to impact inflammatory bowel disease. Nonetheless, how prenatal exposure to metals eventually results in long-term effects on the gut microbiome, leading to subclinical intestinal inflammation, particularly during late childhood, has not been studied. It is also unknown whether such an interactive effect drives a specific subgroup of children toward elevated susceptibility to intestinal inflammation. We used an amalgamation of machine-learning techniques with a regression-based framework to explore if children with distinct sets of gut microbes and certain patterns of exposure to metals during pregnancy (metal-microbial clique signature) had a higher likelihood of intestinal inflammation, measured based on fecal calprotectin (FC) in late childhood. We obtained samples from a well-characterized longitudinal birth cohort from Mexico City (n = 108), Mexico. In the second and third trimesters of pregnancy, 11 metals were measured in whole blood. Gut microbial abundances and FC were measured in stool samples from children 9-11 years of age. Elevated FC was defined as having FC above 100 µg/g of stool. We identified subgroups of children in whom microbial and metal-microbial clique signatures were associated with elevated FC (false discovery rate (FDR) < 0.05). In particular, we found two metal-microbial clique signatures significantly associated with elevated FC: (1) low cesium (Cs) and copper (Cu) in the third trimester and low relative abundance of Eubacterium ventriosum (OR [95%CI]: 10.27 [3.57,29.52], FDR < 0.001) and (2) low Cu in the third trimester and high relative abundances of Roseburia inulinivorans and Ruminococcus torques (OR [95%CI]: 7.21 [1.81,28.77], FDR < 0.05). This exploratory study demonstrates that children with specific gut microbes and specific exposure patterns to metals during pregnancy may have higher fecal calprotectin levels in late childhood, denoting an elevated risk of intestinal inflammation.

Long-Term Behavioral Effects of Post-weaning Social Isolation in Males and Females.

Adolescence is a developmental period associated with vast neural and behavioral changes which are accompanied by altered sensitivity to stimuli, both stressful and rewarding. Perturbations, especially stressful stimuli, during this period have been shown to alter behavior in adulthood. Social isolation rearing is one such perturbation. This review highlights the long-term behavioral consequences of adolescent social isolation rearing in rodents with a specific focus on anxiety- and addiction-related behaviors. Sex-specific effects are discussed where data are available. We then consider changes in monoaminergic neurotransmission as one possible mechanism for the behavioral effects described. This research on both normative and perturbed adolescent development is crucial to understanding and treating the increased vulnerability to psychiatric disorders seen in humans during this life stage.