Addressing Health Equity in Food Allergy.

Social determinants of health can lead to poor health outcomes for food-allergic patients, including limited access to allergen-free foods and specialty care. Housing and transportation limitations can worsen social factors including food insecurity, poor early food introduction, increased reactivity to foods, lower tertiary/allergy care utilization, and increased emergency department utilization. A key component of addressing health equity involves valuing all people with sustained, focused efforts to address social determinants of health. In this clinical commentary, we discuss the current state of heath equity for food-allergic patients, highlighting the disparities in emergency care, food allergy prevention, and food insecurity. Solutions to improve health equity through clinical practice are proposed. Currently available funding opportunities through the National Institutes of Health for health equity initiatives are outlined. Gaps in health equity for food-allergic patients include the lack of documented successful implementation of effective solutions to food insecurity, poor early food introduction uptake, poor access to specialist care, and unequal distribution of educational resources. The availability of research funding and legislative policies supporting access to food and education bolster the impetus to move toward health equity for 20 million people in the United States with food allergy.

Lactate biosensors for spectrally and spatially multiplexed fluorescence imaging.

L-Lactate is increasingly appreciated as a key metabolite and signaling molecule in mammals. However, investigations of the inter- and intra-cellular dynamics of L-lactate are currently hampered by the limited selection and performance of L-lactate-specific genetically encoded biosensors. Here we now report a spectrally and functionally orthogonal pair of high-performance genetically encoded biosensors: a green fluorescent extracellular L-lactate biosensor, designated eLACCO2.1, and a red fluorescent intracellular L-lactate biosensor, designated R-iLACCO1. eLACCO2.1 exhibits excellent membrane localization and robust fluorescence response. To the best of our knowledge, R-iLACCO1 and its affinity variants exhibit larger fluorescence responses than any previously reported intracellular L-lactate biosensor. We demonstrate spectrally and spatially multiplexed imaging of L-lactate dynamics by coexpression of eLACCO2.1 and R-iLACCO1 in cultured cells, and in vivo imaging of extracellular and intracellular L-lactate dynamics in mice.

Epitope-Based IgE Assays and Their Role in Providing Diagnosis and Prognosis of Food Allergy.

With advances in molecular and computational science, epitope-specific IgE antibody profiling has been developed and recently brought into clinical practice. Epitope-based testing detects IgE antibodies that directly bind to antigenic sites of an allergen, providing increased resolution specificity and fewer false-positive results for diagnosing food allergy. Epitope-binding profiles may also serve as prognostic markers of food allergy and help predict quantities of allergen that would provoke a reaction (ie, eliciting dose, possible severity of a reaction after allergen ingestion, and outcomes of treatment options such as oral immunotherapy [OIT]). Future studies are under way to discover additional applications of epitope-specific antibodies for multiple food allergens.

Highly Networked SARS-CoV-2 Peptides Elicit T Cell Responses with Enhanced Specificity.

Identifying SARS-CoV-2-specific T cell epitope-derived peptides is critical for the development of effective vaccines and measuring the duration of specific SARS-CoV-2 cellular immunity. In this regard, we previously identified T cell epitope-derived peptides within topologically and structurally essential regions of SARS-CoV-2 spike and nucleocapsid proteins by applying an immunoinformatics pipeline. In this study, we selected 30 spike- and nucleocapsid-derived peptides and assessed whether these peptides induce T cell responses and avoid major mutations found in SARS-CoV-2 variants of concern. Our peptide pool was highly specific, with only a single peptide driving cross-reactivity in people unexposed to SARS-COV-2, and immunogenic, inducing a polyfunctional response in CD4+ and CD8+ T cells from COVID-19 recovered individuals. All peptides were immunogenic and individuals recognized broad and diverse peptide repertoires. Moreover, our peptides avoided most mutations/deletions associated with all four SARS-CoV-2 variants of concern while retaining their physicochemical properties even when genetic changes are introduced. This study contributes to an evolving definition of individual CD4+ and CD8+ T cell epitopes that can be used for specific diagnostic tools for SARS-CoV-2 T cell responses and is relevant to the development of variant-resistant and durable T cell-stimulating vaccines.

Mucosal CCL28 Chemokine Improves Protection against Genital Herpes through Mobilization of Antiviral Effector Memory CCR10+CD44+ CD62L-CD8+ T Cells and Memory CCR10+B220+CD27+ B Cells into the Infected Vaginal Mucosa.

Four major mucosal-associated chemokines, CCL25, CCL28, CXCL14, and CXCL17, play an important role in protecting mucosal surfaces from infectious pathogens. However, their role in protection against genital herpes remains to be fully explored. The CCL28 is a chemoattractant for the CCR10 receptor-expressing immune cells and is produced homeostatically in the human vaginal mucosa (VM). In this study, we investigated the role of the CCL28/CCR10 chemokine axis in mobilizing protective antiviral B and T cell subsets into the VM site of herpes infection. We report a significant increase in the frequencies of HSV-specific memory CCR10+CD44+CD8+ T cells, expressing high levels of CCR10, in herpes-infected asymptomatic (ASYMP) women compared with symptomatic women. Similarly, a significant increase in the CCL28 chemokine (a ligand of CCR10), was detected in the VM of herpes-infected ASYMP C57BL/6 mice, associated with the mobilization of high frequencies of HSV-specific effector memory CCR10+CD44+CD62L-CD8+ TEM cells and memory CCR10+B220+CD27+ B cells in the VM of HSV-infected ASYMP mice. Inversely, compared with wild-type C57BL/6 mice, the CCL28 knockout (CCL28-/-) mice (1) appeared to be more susceptible to intravaginal infection and reinfection with HSV type 2, and (2) exhibited a significant decrease in the frequencies of HSV-specific effector memory CCR10+CD44+CD62L-CD8+ TEM cells and of memory CD27+B220+ B cells in the infected VM. These findings suggest a critical role of the CCL28/CCR10 chemokine axis in the mobilization of antiviral memory B and T cells within the VM to protect against genital herpes infection and disease.

An unusual presentation of chronic recurrent multifocal osteomyelitis involving bones of the skull.

Chronic recurrent multifocal osteomyelitis is a rare, multisystemic inflammatory disease that affects children and adolescents. We present the case of an African-American adolescent male who presented with recurrent swelling of the temporal region with skull involvement on head imaging, which is atypical for chronic recurrent multifocal osteomyelitis. He had clinical and laboratory improvement after initiation of indomethacin and pamidronate.

Utilizing a High-Fidelity COVID-19 Simulation to Develop Collaboration Skills Among Multispecialty Cohorts.

ABSTRACT: Nursing students rarely have the opportunity to witness nurse-to-nurse collaboration with nurses from differing specialties. Simulation can provide students with an opportunity to practice this important skill. In this simulation, students from a critical care course and students from a maternal/newborn course worked together to care for a pregnant client with COVID-19. The client's condition required expertise from both an obstetrical nurse and a critical care nurse. Although the design of the simulation was aimed at collaboration, various other important observations and teaching moments were uncovered during the implementation of the simulation.

SARS-COV-2 infections in inborn errors of immunity: A single center study.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a single-stranded RNA virus that causes coronavirus disease 2019 (COVID-19). One of the main topics of conversation in these past months in the world of immunology has been the issue of how patients with immune defects will fare if they contract this infection. To date there has been limited data on larger cohorts of patients with Inborn Errors of Immunity (IEI) diagnosed with COVID-19. Here, we review the data of COVID-19 infections in a single center cohort of 113 patients from the Mount Sinai Immunodeficiency program, who had 132 infections between January 2020 and June 2022. This included 56 males and 57 females, age range 2 - 84 (median 42). The mortality rate was 3%. Comparison between admitted patients revealed a significantly increased risk of hospitalization amongst the unvaccinated patients, 4% vaccinated vs 40% unvaccinated; odds ratio 15.0 (95% CI 4.2 - 53.4; p <0.00001). Additionally, COVID anti-spike antibody levels, determined in 36 of these patients post vaccination and before infection, were highly variable.

Differential detection of IgM and IgG antibodies to chimeric antigens in bovine tuberculosis.

Recent studies have suggested the potential of innovative serologic tests for accurate and rapid detection of bovine tuberculosis (bTB). Dual Path Platform (DPP) technology has been used to develop rapid animal-side antibody tests for Mycobacterium bovis infection in a range of livestock and wildlife host species. The present study evaluated diagnostic performance of DPP BovidTB IgM/IgG assay designed for differential detection of bovine IgM and IgG antibodies against two chimeric antigens, DID38 and TBf2, respectively, using 662 well-characterized serum samples from M. bovis-infected and bTB-free cattle collected in the United States, Great Britain, France, and South Africa. Test sensitivity and specificity ranged from 71% to 100% and from 95% to 100%, respectively, depending on the country, with overall accuracy of 83%. No significant risk of cross-reactivity with serum samples from cattle infected with most relevant species of mycobacteria other than M. bovis was found. The DPP BovidTB IgM/IgG assay may be suitable for use in multi-test algorithms to improve current strategies for bTB surveillance.

Prolonged Hospitalization in a Pediatric Patient With Multisystem Inflammatory Syndrome (MIS-C) and Human Rhino-Enterovirus Infection: A Case Report.

Multisystem inflammatory syndrome in children (MIS-C) is a serious sequela of acute SARS-CoV-2 infection. It is unclear whether the co-occurrence of other viral respiratory illnesses, such as the human rhino-enterovirus (HRV/ENT), prolongs hospitalization or affects the clinical phenotype of patients with MIS-C. We report the hospital course of a three-year-old with MIS-C and HRV/ENT infection, who tested positive for HRV/ENT infection a few days prior to re-presenting for six days of fever, one day of emesis, bilateral conjunctivitis, and shortness of breath, all consistent with MIS-C. Due to worsening hypotension, he was admitted to a pediatric intensive care unit (ICU) at a tertiary center, where he received vasoactive support, intravenous immunoglobulin, and high-dose intravenous steroids. Because of his worsening respiratory status, he was also started on anakinra with resultant gradual improvement. He was hospitalized for a total of 15 days. Concurrence of other viral infections may prolong hospitalization for patients with MIS-C.

Potential for improved detection of bovine tuberculosis by targeting combined blood biomarkers in multi-test algorithms.

Bovine tuberculosis (bTB) control programs can be improved by combined use of tests for humoral and cell-mediated immune responses targeting multiple biomarkers of Mycobacterium bovis. To further the diagnostic benefits of this approach, we used Dual Path Platform (DPP) technology to test sera from cattle with naturally acquired bTB in the United States (US) and Spain for the presence of M. bovis antigen, IgM and/or IgG antibodies to MPB70/MPB83 fusion antigen in conjunction with tuberculin skin tests (TST) or interferon-gamma release assays (IGRA). When TST was complemented with detection of IgM and IgG antibodies, the diagnostic sensitivity increased from 85.4% to 95.1% in the US and from 64.2% to 81.5% in Spain. Likewise, adding the DPP assays enhanced IGRA diagnostic sensitivity from 82.7% to 93.8% in Spain. Detection of circulating M. bovis antigen showed added value when used in combination with the DPP antibody assays but it was limited when analyzed in the context of TST or IGRA results. Present findings support the benefits of a multi-test approach for the ante-mortem diagnosis of bTB in cattle.

Plasma-Derived HIV-1 Virions Contain Considerable Levels of Defective Genomes.

Genetically-characterizing full-length HIV-1 RNA is critical for identifying genetically-intact genomes and for comparing these RNA genomes to proviral DNA. We have developed a method for sequencing plasma-derived RNA using long-range sequencing (PRLS assay; ∼8.3 kb from gag to the 3' end or ∼5 kb from integrase to the 3' end). We employed the gag-3' PRLS assay to sequence HIV-1 RNA genomes from ART-naive participants during acute/early infection (n = 6) or chronic infection (n = 2). On average, only 65% of plasma-derived genomes were genetically-intact. Defects were found in all genomic regions but were concentrated in env and pol. We compared these genomes to near-full-length proviral sequences from paired peripheral blood mononuclear cell (PBMC) samples for the acute/early group and found that near-identical (>99.98% identical) sequences were identified only during acute infection. For three participants who initiated therapy during acute infection, we used the int-3' PRLS assay to sequence plasma-derived genomes from an analytical treatment interruption and identified 100% identical genomes between pretherapy and rebound time points. The PRLS assay provides a new level of sensitivity for understanding the genetic composition of plasma-derived HIV-1 RNA from viremic individuals either pretherapy or after treatment interruption, which will be invaluable in assessing possible HIV-1 curative strategies. IMPORTANCE We developed novel plasma-derived RNA using long-range sequencing assays (PRLS assay; 8.3 kb, gag-3', and 5.0 kb, int-3'). Employing the gag-3' PRLS assay, we found that 26% to 51% of plasma-derived genomes are genetically-defective, largely as a result of frameshift mutations and deletions. These genetic defects were concentrated in the env region compared to gag and pol, likely a reflection of viral immune escape in env during untreated HIV-1 infection. Employing the int-3' PRLS assay, we found that analytical treatment interruption (ATI) plasma-derived sequences were identical and genetically-intact. Several sequences from the ATI plasma samples were identical to viral sequences from pretherapy plasma and PBMC samples, indicating that HIV-1 reservoirs established prior to therapy contribute to viral rebound during an ATI. Therefore, near-full-length sequencing of HIV-1 particles is required to gain an accurate picture of the genetic landscape of plasma HIV-1 virions in studies of HIV-1 replication and persistence.

Facile Fabrication of Multilayer Stretchable Electronics via a Two-mode Mechanical Cutting Process.

A time- and cost-effective fabrication methodology via a two-mode mechanical cutting process for multilayer stretchable electronics has been developed without using the conventional photolithography-based processes. A commercially available vinyl cutter is used for defining complex patterns on designated material layers by adjusting the applied force and the depth of the cutting blade. Two distinct modes of mechanical cutting can be achieved and employed to establish the basic fabrication procedures for common features in stretchable electronics, such as the metal interconnects, contact pads, and openings by the "tunnel cut" mode, and the flexible overall structure by the "through cut" mode. Three robust and resilient stretchable systems have been demonstrated, including a water-resistant, omnidirectionally stretchable supercapacitor array, a stretchable mesh applicable in sweat extraction and sensing, and a skin-mountable human breathing monitoring patch. Results show excellent electronic performances of these devices made of multilayer functional materials after repetitive large deformations.

Novel polyprotein antigens designed for improved serodiagnosis of bovine tuberculosis.

Recent studies have demonstrated potential for serologic assays to improve surveillance and control programs for bovine tuberculosis. Due to the animal-to-animal variation of the individual antibody repertoires observed in bovine tuberculosis, it has been suggested that serodiagnostic sensitivity can be maximized by use of multi-antigen cocktails or genetically engineered polyproteins expressing immunodominant B-cell epitopes. In the present study, we designed three novel multiepitope polyproteins named BID109, TB1f, and TB2f, with each construct representing a unique combination of four full-length peptides of Mycobacterium bovis predominantly recognized in bovine tuberculosis. Functional performance of the fusion antigens was evaluated using multi-antigen print immunoassay (MAPIA) and Dual Path Platform (DPP) technology with panels of monoclonal and polyclonal antibodies generated against individual proteins included in the fusion constructs as well as with serum samples from M. bovis-infected and non-infected cattle, American bison, and domestic pigs. It was shown that epitopes of each individual protein were expressed in the fusion antigens and accessible for efficient binding by the respective antibodies. The three fusion antigens demonstrated stronger immunoreactivity in MAPIA than that of single protein antigens. Evaluation of the fusion antigens in DPP assay using serum samples from 125 M. bovis-infected and 57 non-infected cattle showed the best accuracy (∼84 %) for TB2f antigen composed of MPB70, MPB83, CFP10, and Rv2650c proteins. Thus, the study results suggest a potential for the multiepitope polyproteins to improve diagnostic sensitivity of serologic assays for bovine tuberculosis.

Maternal prenatal selenium levels and child risk of neurodevelopmental disorders: A prospective birth cohort study.

Selenium (Se) is an essential trace element involved in various biological processes, including neurodevelopment. Available literature indicates that both Se deficiency and excess may be detrimental to health. It is also known that Se can cross the placenta from maternal to fetal circulation. To date, the role of maternal Se status in child long-term neurodevelopment is largely unexplored. This study investigated the temporal and dose-response associations between maternal Se status and child risk of neurodevelopmental disorders including autism spectrum disorder (ASD) and attention deficit hyperactivity disorder (ADHD). It consisted of 1550 mother-infant dyads from the Boston Birth Cohort. Maternal red blood cell (RBC) Se levels were measured in samples collected within 72 h of delivery (biomarker of third trimester Se status). Pediatric neurodevelopmental diagnoses were obtained from electronic medical records. Data analyses showed that maternal RBC Se levels were positively associated with child risk of developing ASD, with an adjusted odds ratio of 1.49 for ASD (95% CI: 1.09, 2.02) per IQR increase in Se. There was also a positive association between maternal Se and ADHD (OR: 1.29; 95% CI: 1.04, 1.56, per IQR increase in Se). These associations remained robust even after adjusting for pertinent covariables; and there was no significant interaction between Se and these covariables. Our findings suggest that prenatal exposure to high maternal Se levels may adversely affect child neurodevelopment. Our findings warrant further investigation; if confirmed, optimizing maternal prenatal Se levels may be necessary to maximize its health benefits while preventing undue risk. LAY SUMMARY: Selenium (Se) is an essential nutrient for the health of the pregnant mother and her baby. While Se can readily cross the placenta from maternal to fetal circulation, little is known about maternal Se status on her child's neurodevelopmental outcomes. We studied over 1500 mother-child dyads from birth to school age of the child. We found that babies born from mothers with high blood Se levels may be at increased risk of developing autism spectrum disorder or attention deficit hyperactivity disorder. Given this is the first study of the kind, more study is needed to confirm our findings.

Use of blood matrices and alternative biological fluids for antibody detection in animal tuberculosis.

Bovine tuberculosis (bTB) control programs can be improved by implementation of advanced ante-mortem testing algorithms. Serodiagnostic methods using traditional blood or blood-derived specimens may benefit from the use of less invasive alternative biological fluids, provided those mirror systemic antibody responses. In the present study, we used Dual Path Platform (DPP) and Multiantigen Print Immunoassay (MAPIA) to compare antibody levels in ten sample types including whole blood (fresh and hemolyzed), plasma (fresh and leftover from Bovigam testing), serum, saliva, broncho-alveolar lavage, urine, diaphragm extract, and bile collected from cattle aerosol-infected with Mycobacterium bovis. High correlation (r = 0.97-0.99) in measurements of IgG antibodies to MPB70/MPB83 fusion antigen by DPP assay was found between all blood-derived specimens, supporting matrix equivalency. Broncho-alveolar lavage and diaphragm extract yielded positive results in all the infected animals tested, showing high correlation with matching serum data (r = 0.94 and r = 0.95, respectively) and suggesting their potential use in antibody assays. Characterized by MAPIA, the antigen reactivity patterns obtained with paired sera and alternative specimens were nearly identical, with slight differences in intensity. Antibodies were also found by DPP assay in saliva, urine, and bile from some of the infected animals, but the titers were relatively low, thus reducing the diagnostic value of such specimens. The proposed approach was evaluated in a pilot field study on warthogs diagnosed with M. bovis infection. Relative levels of antibody in tissue fluid obtained from lymph nodes or lungs were consistent with those detected in sera and detectable in all infected warthogs. The findings support the diagnostic utility of non-traditional biological fluids and tissue samples when used as alternative test specimens in serologic assays for bTB.