Food Allergy: Our Evolving Understanding of Its Pathogenesis,Prevention, and Treatment

Food allergy is defined as an IgE-mediated hypersensitivity response to ingested food with allergic symptoms ranging from urticaria to life-threatening anaphylaxis. Food allergy is thought to develop because of (1) failed induction of tolerance upon initial exposure to food antigen or (2) breakdown of established tolerance to food antigen. We review current understanding of the pathogenesis, epidemiology, and natural history of food allergy, including the unconventional IgE-mediated food allergy to mammalian meat known as alpha-gal food allergy. We highlight emerging data on food allergy treatment and prevention, emphasizing the growing appeal of manipulating the gut microenvironment using probiotics and helminth products to blunt systemic allergic responses to food.     

Breast cancer brain metastases express the sodium iodide symporter

Breast cancer brain metastases are on the rise and their treatment is hampered by the limited entry and efficacy of anticancer drugs in this sanctuary. The sodium iodide symporter, NIS, actively transports iodide across the plasma membrane and is exploited clinically to deliver radioactive iodide into cells. As in thyroid cancers, NIS is expressed in many breast cancers including primary and metastatic tumors. In this study NIS expression was analyzed for the first time in 28 cases of breast cancer brain metastases using a polyclonal anti-NIS antibody directed against the terminal C-peptide of human NIS gene and immunohistochemical methods. Twenty-five tumors (84%) in this retrospective series were estrogen/progesterone receptor-negative and 15 (53.6%) were HER2+. Overall 21 (75%) cases and 80% of HER2 positive metastases were NIS positive. While the predominant pattern of NIS immunoreactivity is intracellular, plasma membrane immunopositivity was detected at least focally in 23.8% of NIS-positive samples. Altogether, these findings indicate that NIS expression is prevalent in breast cancer brain metastases and could have a therapeutic role via the delivery of radioactive iodide and selective ablation of tumor cells.     

Blood biochemistry responses of ducks infected with a velogenic Newcastle disease virus

This study investigated the blood biochemistry responses of Pekin ducks (Anas platyrhynchos domesticus) experimentally infected with a velogenic Newcastle disease virus (NDV), KUDU 113 strain. One hundred ducklings were used for the study. The ducks were obtained at a week old and randomly divided into three groups. One group was vaccinated against NDV with La Sota vaccine at 3 weeks of age. The vaccinated and unvaccinated groups of 30 ducks each were subsequently challenged with the velogenic NDV after 6 weeks of brooding, while the control group of 40 ducks was not vaccinated and not challenged. Blood samples were randomly collected from five birds in each group, allowed for about 30 min to clot, centrifuged, and serum harvested. Blood biochemistry determinations were carried out at 3-day intervals from days 0 to 15 and day 21 post inoculation (PI). The results showed a significant increase in albumin on day 6 PI and total protein and globulin on day 9 PI and a significant increase in uric acid levels in the infected groups when compared with the unvaccinated uninfected controls from days 3 to 12 PI. The significant increase in uric acid level in both the vaccinated infected and unvaccinated infected groups in the absence of any overt clinical sign is noteworthy as uric acid determination can be a useful screening tool for detection of the velogenic NDV in apparently healthy ducks before they constitute a risk to in-contact poultry or spread to the environment.     

Pulmonary hypertension in sickle cell disease: relevance to children

Pulmonary arterial hypertension (PAH), once considered a rare complication of sickle cell disease (SCD) and thalassemia, appears to be more common in adults with hemoglobinopathy than previously appreciated. On prospective screening of adults with SCD, approximately one-third of adults are found on echocardiography to have a tricuspid regurgitant jet velocity (TRV) of 2.5 m/s or higher, many of whom are asymptomatic. Dyspnea on exertion is the most common presenting symptom. This TRV abnormality is a marker for approximately 40% 3-year mortality in adults, and it is associated with laboratory values suggestive of more severe intravascular hemolysis. Release of hemoglobin and arginase from lysed red cells causes scavenging of nitric oxide (NO) and catabolism of L-arginine, the obligate substrate for NO synthase. The resulting impairment in NO bioavailability is associated with pulmonary vasoconstriction, endothelial dysfunction, thrombosis, and eventual development of plexogenic arterial lesions, the histological hallmark of all forms of PAH. Undoubtedly, additional pathophysiological mechanisms will also play a role in its multifactorial pathogenesis. Early data from children with SCD indicate a similar prevalence of elevated TRV, but the prognostic implications of this remain to be established. Individual patient diagnosis of PAH requires confirmation by right heart catheterization studies and individualized management. Hemolysis-associated PAH with impairments in NO bioavailability is being identified in thalassemia and other hemolytic disorders, and may be a general consequence of long-standing, severe intravascular hemolytic anemia.     

The Affordable Care Act's “community first choice” option: Effect on long‐term care expenditures

ObjectiveTo empirically assess the effect of adopting Affordable Care Act''s Community First Choice (CFC) option on overall state home and community‐based services (HCBS) expenditures as well as distribution of HCBS expenditures across different HCBS mechanisms. We also explore the heterogeneous effect of CFC across adopting states.Data SourceWe used data from the Medicaid Long Term Services and Support (LTSS) expenditure reports prepared by Truven Analytics and Mathematica for the Centers for Medicare & Medicaid Services from 2008–2018 for all 48 states and the District of Columbia.Study DesignAn event‐study difference‐in‐differences model was used to estimate the effect of CFC on HCBS expenditures using Medicaid LTSS expenditure reports from 2008–2018. We also employ the synthetic control method to unmask heterogeneity across CFC adopting states using data from 2008–2018.Data Collection/Extraction MethodsNot applicable.Principal FindingsOverall, CFC was not associated with a change in HCBS expenditures per capita or HCBS expenditures as a proportion of LTSS expenditures. However, there appears to be an increase in HCBS expenditures among states that were institutionally‐oriented prior to CFC adoption. Additionally, CFC adoption was associated with an overall decrease in expenditures in alternative HCBS mechanisms (Personal Care Services State Plan Option and 1915(c) waivers), suggesting potential substitution across overlapping programs.ConclusionResults indicate heterogeneity across states adopting CFC. More institutionally‐oriented states appear to use CFC to expand HCBS. In contrast, more HCBS‐oriented states appear to employ CFC to strategically restructure their overall portfolio and processes.     

Relationship of oxidative stress and antioxidant response with vaso-occlusive crisis in sickle cell anaemia

BackgroundThough sickle cell anaemia (SCA) is known to promote oxidative stress, there is paucity of information on the relationship between oxidative stress and vaso-occlusive crisis (VOC).ObjectiveThis study was undertaken to evaluate the relationship of oxidative stress and antioxidant response with VOC in SCA.MethodsA cross-sectional case-control study was carried out at University of Nigeria Teaching Hospital (UNTH), Ituku-Ozalla, Enugu Nigeria involving 116 individuals which included 36 SCA subject, 40 sickle cell carriers (AS) and 40 healthy individuals (AA). Baseline information as well as the frequency of VOC was obtained from the participants and anaemia as well as oxidative stress and antioxidant indices were assessed in blood.ResultsAnaemia was prevalent (88.9 %) in SCA individuals compared to AS (52.5%) and AA (47.5 %) individuals. Nitric oxide scavenging (NOS) and superoxide dismutase (SOD) activities as well as glutathione level were significantly (p<0.005) lower while catalase activity was higher in SCA individuals compared to controls (AA and AS). Higher malondialdehyde (MDA) level was associated with very severe VOC while low level of NOS activity was associated with severe VOC in SCA individuals.ConclusionSickle cell anaemia exhibited oxidative stress and alteration in the levels of antioxidant indices which was possibly associated with vaso-occlusive crisis.     

High-density SNP genotyping to define beta-globin locus haplotypes

Five major beta-globin locus haplotypes have been established in individuals with sickle cell disease (SCD) from the Benin, Bantu, Senegal, Cameroon, and Arab-Indian populations. Historically, beta-haplotypes were established using restriction fragment length polymorphism (RFLP) analysis across the beta-locus, which consists of five functional beta-like globin genes located on chromosome 11. Previous attempts to correlate these haplotypes as robust predictors of clinical phenotypes observed in SCD have not been successful. We speculate that the coverage and distribution of the RFLP sites located proximal to or within the globin genes are not sufficiently dense to accurately reflect the complexity of this region. To test our hypothesis, we performed RFLP analysis and high-density single nucleotide polymorphism (SNP) genotyping across the beta-locus using DNA samples from healthy African Americans with either normal hemoglobin A (HbAA) or individuals with homozygous SS (HbSS) disease. Using the genotyping data from 88 SNPs and Haploview analysis, we generated a greater number of haplotypes than that observed with RFLP analysis alone. Furthermore, a unique pattern of long-range linkage disequilibrium between the locus control region and the beta-like globin genes was observed in the HbSS group. Interestingly, we observed multiple SNPs within the HindIII restriction site located in the Ggamma-globin intervening sequence II which produced the same RFLP pattern. These findings illustrated the inability of RFLP analysis to decipher the complexity of sequence variations that impacts genomic structure in this region. Our data suggest that high-density SNP mapping may be required to accurately define beta-haplotypes that correlate with the different clinical phenotypes observed in SCD.