Differential regulation of apoptotic cell death in senescent human cells

Aging of human cells can be reproduced in monolayer cultures, revealing the phenotype of replicative senescence. It was shown that diploid human fibroblasts enter a stable growth arrest phenotype at the end of their lifespan and, in particular, these cells are resistant to various apoptotic stimuli. In contrast, human endothelial cells from the umbilical vein (HUVEC) acquire a proapoptotic phenotype when reaching senescence and this probably results from reactive oxygen species (ROS) induced damage and associated signaling. Ceramides were shown to accumulate in senescent fibroblasts and are also known as potent regulators of apoptotic cell death. To further study age-associated changes in proneness to apoptosis between fibroblasts and endothelial cells, both cell types were challenged by administration of exogenous ceramide and apoptotic cell death was determined. While ceramide can efficiently induce apoptosis in both young and senescent cells of either histotype, quantitative evaluation of the data show that senescent fibroblasts are more resistant to apoptosis induction when compared to their young counterparts, whereas in the case of endothelial cells proneness for apoptosis is increased in senescent cells. Together, these data suggest significant differences in the regulation of apoptosis associated with senescence in fibroblasts and endothelial cells.     

Single Nucleotide Differences (SNDs) Continue to Contaminate the dbSNP Database With Consequences for Human Genomics and Health

It has been established that up to 8.3% of the biallelic coding SNPs present in dbSNP are actually artefactual polymorphism‐like errors, previously termed single nucleotide differences, or SNDs. In this study, a previous analysis of SNPs in dbSNP was extended and updated to examine how the incidence of SNDs has changed over an intervening five year period. The incidence of SNDs was found to be lower than in the previous analysis at 2.2% of all biallelic SNPs. There was only a modest reduction in the percentage of SNDs in the original set of biallelic coding SNPs tested. This suggests that the overall reduction in the incidence of SNDs over the intervening 5‐year period is related to an improvement in SNP detection methods and more rigorous curation, rather than efforts to ameliorate the presence of SNDs. We note that SNDs contaminating the dbSNP may lead to erroneous conclusions on human conditions.     

Deep analysis of immune response and metabolic signature in children with food protein induced enterocolitis to cow’s milk

Background

Food Protein-Induced Enterocolitis Syndrome (FPIES) is considered to be a non-IgE mediated food allergy. However, its pathogenesis remains poorly understood and biomarkers are lacking. We aimed to perform in-depth characterization of humoral and cellular immune responses in children with cow’s milk (CM)-FPIES and investigated whether there is a FPIES metabolomic signature.

Methods

Children with CM-FPIES and control subjects with an IgE-mediated CM allergy (IgE-CMA), both avoiding CM, were recruited on the day of an oral food challenge. Blood samples were collected before the challenge. Total and specific levels of IgE, IgG1-4, IgA, IgM and IgD to various whey and casein allergens and to their gastroduodenal digestion products were measured in plasma, using plasma from CM-tolerant peanut allergic patients (IgE-PA, not avoiding CM) as additional controls. Cytokine secretion and cellular proliferation were analyzed after stimulation of PBMC with different CM allergens. Metabolomic profiles were obtained for plasma samples using liquid chromatography coupled to high-resolution mass spectrometry.

Results

Nine children with CM-FPIES and 12 control subjects (6 IgE-CMA and 6 IgE-PA) were included. In children with CM-FPIES, total Ig concentrations were lower than in control subjects, specific Ig against CM components were weak to undetectable, and no specific IgE against CM digestion products were detected. Moreover, in CM-FPIES patients, we did not find any Th cell proliferation or associated cytokine secretion after allergen reactivation, whereas such responses were clearly found in children with IgE-CMA. Plasma metabolic profiles were different between CM allergic patients, with significantly lower concentrations of various fatty acids and higher concentrations of primary metabolites such as amino acids in CM-FPIES compared to IgE-CMA patients.

Conclusions

In CM-FPIES, both humoral and cellular specific immune responses are weak or absent, and this is not related to CM avoidance. A metabolomic signature was identified in patients with CM-FPIES that may be useful for the diagnosis and management of this disease.

     

Therapeutic Benefit and Gene Network Regulation by Combined Gene Transfer of Apelin,FGF2, and SERCA2a into Ischemic Heart

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Ear measurement of temperature is only useful for screening for fever in an adult emergency department

Background

A new generation of ear thermometers with preheated tips and several measurements points should allow a more precise temperature measurement. The aim of the study was to evaluate if the ear temperature measured by this ear thermometer can be used to screen for fever and whether the thermometer is in agreement with the rectal temperature and if age, use of hearing devices or time after admission influences the temperature measurements.

Methods

Open cross-sectional clinical single site study patients, >?18?years old, who were acutely admitted to the short stay unit at the ED. A sample size of 99 patient per subgroup was recruited as random convenience series. As ear thermometer Braun Thermoscan Pro 4000® and as rectal thermometer Omron Flex Temp Smart ® was used. For different cut off of temperature the AUC was calculated and Bland-Altman analysis for calculation of 95% limits of agreement with rectal temperature, with subgroup analysis concerning age, time span from admission time and use of hearing aid.

Results

Among 599 patients the sensitivity to detect fever with an ear thermometer varied between 68 and 70% with AUC from 0.88–0.97. If the ear temperature was ≥37.5 oC, the sensitivity to detect patients with ≥38.0 oC rectally was 95% which raised to 100% for a rectal temperature of ≥38.3 oC. For the ear thermometer’s ability to determine the exact temperature the 95% limits of agreement were +/??0.8 oC. with no influence from age, duration of hospital stay or hearing aids.

Conclusion

The examined ear thermometer is able to detect fever, defined as ≥38 oC rectally in an adult ED population by using an ear cut-point of 37.5 oC, but not to measure the exact temperature. Used in this way around a fifth of the patients will still be in need of a rectal temperature measurement, but less than 5% with fever ≥38.0 oC will remain undetected and none with fever ≥38.3 oC. Age, admission time and use of hearing aid did not influence the temperature measurements.

Trial registration

Clinical Trials: ID NCT02977481, date 11/18/2016.

     

The Impact of Local Immigration Enforcement Policies on the Health of Immigrant Hispanics/Latinos in the United States

Objectives. We sought to understand how local immigration enforcement policies affect the utilization of health services among immigrant Hispanics/Latinos in North Carolina.Methods. In 2012, we analyzed vital records data to determine whether local implementation of section 287(g) of the Immigration and Nationality Act and the Secure Communities program, which authorizes local law enforcement agencies to enforce federal immigration laws, affected the prenatal care utilization of Hispanics/Latinas. We also conducted 6 focus groups and 17 interviews with Hispanic/Latino persons across North Carolina to explore the impact of immigration policies on their utilization of health services.Results. We found no significant differences in utilization of prenatal care before and after implementation of section 287(g), but we did find that, in individual-level analysis, Hispanic/Latina mothers sought prenatal care later and had inadequate care when compared with non-Hispanic/Latina mothers. Participants reported profound mistrust of health services, avoiding health services, and sacrificing their health and the health of their family members.Conclusions. Fear of immigration enforcement policies is generalized across counties. Interventions are needed to increase immigrant Hispanics/Latinos’ understanding of their rights and eligibility to utilize health services. Policy-level initiatives are also needed (e.g., driver’s licenses) to help undocumented persons access and utilize these services.Federal immigration enforcement policies have been increasingly delegated to state and local jurisdictions, leading to increased enforcement activities by local police. This shift has resulted largely from the implementation of 2 federal initiatives: section 287(g) of the Immigration and Nationality Act and the Secure Communities program. Section 287(g) authorizes Immigration and Custom Enforcement to enter into agreements with state and local law enforcement agencies to enforce federal immigration law during their regular, daily law enforcement activities. The original intention was to “target and remove undocumented immigrants convicted of violent crimes, human smuggling, gang/organized crime activity, sexual-related offenses, narcotics smuggling and money laundering.”1 Added to the Immigration and Nationality Act in 1996, section 287(g) was not widely used in its first decade, but its use accelerated in the mid- to late 2000s.2,3The Secure Communities program differs from section 287(g) in that it does not authorize local enforcement bodies to arrest individuals for federal immigration violations. Instead, when individuals are arrested for nonimmigration matters, the Secure Communities program facilitates the sharing of local arrestees’ fingerprints and information with Immigration and Custom Enforcement and the Federal Bureau of Investigation, which checks them against immigration databases. If these checks reveal that an individual is unlawfully present in the United States or otherwise removable because of a criminal conviction, Immigration and Custom Enforcement takes enforcement action.4Some evidence suggests that both section 287(g) and the Secure Communities program contribute to Hispanic/Latino immigrants’ general mistrust of local law enforcement and fear of utilizing a variety of public services, such as police protection and emergency services.2,5–7 Although many immigrant Hispanics/Latinos in the United States experience barriers to care because of a lack of bilingual and bicultural services, low health literacy, insufficient public transportation, and limited knowledge of available health services,8–12 studies have suggested that individuals lacking legal status may have more difficulty obtaining health services and may experience worse health outcomes than do individuals with legal status.13–18 Among immigrant Hispanics/Latinos, the fear of deportation, a lack of required forms of documentation, interaction with law enforcement personnel, and racial profiling are factors also associated with reduced utilization of health services and worse health.6,19–22 Such fears lead to incomplete sequences of care,19,20,23,24 promote the use of nonstandard and unsafe contingencies for care,16,25–27 and contribute to public health hazards, as immigrants delay preventive care or treatment.13,22,28 These fears further affect long-term health outcomes as immigrant Hispanics/Latinos alter their physical activity, food purchasing behaviors, and food consumption because of concerns about being in public.29 They may withhold information from health care providers19 and experience high levels of stress, leading to compromised mental health.20,30,31The Patient Protection and Affordable Care Act bars undocumented or recent legal immigrants from receiving financial assistance for health insurance32; thus, many will continue to remain uninsured and dependent on public health services and free clinics for a significant portion of their care. Because these services are associated with government authority, there is the potential that increasing immigration enforcement policies will deter noncitizens from seeking needed care, not only to their detriment but also to the detriment of public health.Currently there is little research examining the impact of recent immigration enforcement policies on the access to and utilization of health care, and there has been a call to better understand the public health impact of current immigration policies and their enforcement.29 Through mixed methods, we explored the effect of local immigration enforcement policies on access to and utilization of health services among immigrant Hispanics/Latinos in North Carolina. We analyzed vital records data to determine whether there were differences in utilization of prenatal services by Hispanic/Latina mothers pre- and postimplementation of section 287(g), and we conducted focus groups and in-depth interviews with Hispanics/Latinos living in counties that had implemented section 287(g) and in “sanctuary” counties, counties in which leaders, including politicians and clergy, have spoken out against the program.