European reference values for Doppler indices of left ventricular diastolic filling

The European Study Group on diastolic heart failure requires objective evidence of abnormal left ventricular diastolic function to establish the diagnosis of diastolic heart failure, which is common in older people. Reference values for Doppler indices of transmitral flow, used to assess left ventricular diastolic function, have not been reported for people 70 years and over in Europe. The aim of this study was to establish reference values for these Doppler indices of transmitral flow in older people. A random sample of 355 subjects aged 70 and over, living in the community underwent clinical assessment and echocardiography. Asymptomatic subjects with no cardiovascular disease and cardiovascular risk factors were identified. Measurements of five commonly used Doppler indices of transmitral flow from these subjects were obtained and reference range expressed as mean+/-2 standard deviations and as percentiles. We have therefore generated reference Doppler values of transmitral flow for people aged over 70 in a British population.     

Burkholderia pseudomallei sequencing identifies genomic clades with distinct recombination,accessory, and epigenetic profiles

Burkholderia pseudomallei (Bp) is the causative agent of the infectious disease melioidosis. To investigate population diversity, recombination, and horizontal gene transfer in closely related Bp isolates, we performed whole-genome sequencing (WGS) on 106 clinical, animal, and environmental strains from a restricted Asian locale. Whole-genome phylogenies resolved multiple genomic clades of Bp, largely congruent with multilocus sequence typing (MLST). We discovered widespread recombination in the Bp core genome, involving hundreds of regions associated with multiple haplotypes. Highly recombinant regions exhibited functional enrichments that may contribute to virulence. We observed clade-specific patterns of recombination and accessory gene exchange, and provide evidence that this is likely due to ongoing recombination between clade members. Reciprocally, interclade exchanges were rarely observed, suggesting mechanisms restricting gene flow between clades. Interrogation of accessory elements revealed that each clade harbored a distinct complement of restriction-modification (RM) systems, predicted to cause clade-specific patterns of DNA methylation. Using methylome sequencing, we confirmed that representative strains from separate clades indeed exhibit distinct methylation profiles. Finally, using an E. coli system, we demonstrate that Bp RM systems can inhibit uptake of non-self DNA. Our data suggest that RM systems borne on mobile elements, besides preventing foreign DNA invasion, may also contribute to limiting exchanges of genetic material between individuals of the same species. Genomic clades may thus represent functional units of genetic isolation in Bp, modulating intraspecies genetic diversity.Burkholderia pseudomallei (Bp) is the causative agent of melioidosis, a serious infectious disease of humans and animals and a leading cause of community-acquired sepsis and pneumonia in endemic regions (Currie et al. 2010). Initially thought to be confined to Southeast Asia and Northern Australia, the prevalence of Bp appears to be spreading (Wiersinga et al. 2012), and Bp has been designated a biothreat select agent in the United States. Bp can persist in extreme environmental conditions and can infect several plant and animal hosts, including birds, dolphins, and humans (Wuthiekanun et al. 1995; Howard and Inglis 2003; Sprague and Neubauer 2004; Larsen et al. 2013). Treatment of clinical melioidosis is challenging because the bacterium is inherently resistant to many antibiotics, and Bp infections can persist in humans for more than a decade (Hayden et al. 2012; Wiersinga et al. 2012).The Bp genome comprises one of the largest and most complex bacterial genomes sequenced to date. Consisting of two large circular replicons (chromosomes) with a combined 7.2-Mb genome size (Holden et al. 2004), it contains a rich arsenal of genes related to virulence (e.g., Type III and Type VI secretion systems, polysaccharide biosynthesis clusters), metabolic pathways, and environmental adaptation (Wiersinga et al. 2012). Besides conserved regions, accessory genes on mobile elements and genomic islands may also contribute to phenotypic and clinical differences in microbial behavior (Currie et al. 2000; Sim et al. 2008). Analysis of the Bp genome has revealed previously unknown toxins and mechanisms of antibiotic resistance (Chantratita et al. 2011; Cruz-Migoni et al. 2011).Most large-scale studies of Bp genetic diversity to date have analyzed strains using multilocus sequence typing (MLST). These studies have suggested a high degree of genetic variability between Bp strains and related Burkholderia species (Cheng et al. 2008), and have shown that Bp strains belonging to different sequence types (STs) can often coexist in the same locale and sometimes even within the same sample (Pitt et al. 2007; Wuthiekanun et al. 2009). However, due to the limited number of genes analyzed by MLST, these studies cannot comment on the global proportion of genetic material shared between strains of different STs nor on the relative contribution of recombination, mutation, and horizontal gene transfer on intraspecies genetic diversity. Moreover, although previous studies have applied whole-genome sequencing (WGS) to study global patterns of Bp genetic heterogeneity and evolution, earlier Bp WGS reports have been confined to a limited number of isolates (10–12) derived from diverse geographical regions (Nandi et al. 2010), where geophysical barriers likely limit the propensity of the analyzed strains to exchange genetic material. To achieve a comprehensive understanding of genetic variation among closely related Bp strains, WGS analysis of much larger strain panels, ideally performed on strains isolated from a common region and belonging to the same (or closely related) ST groups, is required.In this study, we attempted to fill this important knowledge gap by performing WGS on 106 Bp strains drawn from a restricted Asian locale (Singapore and Malaysia). The WGS data, exceeding previous Bp WGS studies by 10-fold, enabled us to identify specific genomic clades of Bp, molecular features of Bp recombination at the whole-genome level, and accessory genome features contributing to recombination and horizontal gene transfer. We found a consistent pattern of genetic separation correlating with MLST, recombination haplotypes, shared accessory genes, and restriction modification (RM) systems. We provide evidence that restriction modification, beyond its role as defense against foreign DNA invasion, may have also partitioned the Bp species by restricting gene flow, resulting in the other observed correlations. Because RM systems are widely dispersed through the bacterial kingdom, it is possible that similar principles may apply to other bacterial species, implicating a potential role for epigenetic barriers as a driver of early incipient speciation.     

Effect of high-frequency alternating current transcutaneous stimulation over muscle strength: a controlled pilot study

Background

High-frequency alternating currents of greater than 1 kHz applied on peripheral nerves has been used in animal studies to produce a motor nerve block. It has been evidenced that frequencies higher than 5 kHz are necessary to produce a complete peripheral nerve block in primates, whose nerve thickness is more similar to humans. The aim of the study was to determine the effect on muscle strength after the application of a high-frequency stimulation at 5 and 10 kHz compared to sham stimulation in healthy volunteers.

Findings

Transcutaneous stimulation at 5 kHz, 10 kHz and sham stimulation were applied to eleven healthy volunteers over the ulnar and median nerves for 20 min. Maximal handgrip strength was measured before, during, immediately after the intervention, and 10 min after the end of intervention. The 10 kHz stimulation showed a lower handgrip strength during the intervention (28.1 N, SEM 3.9) when compared to 5 kHz (31.1 N, SEM 3.6; p?<?0.001) and to sham stimulation (33.7 N, SEM 3.9; p?<?0.001). Furthermore, only stimulation at 10 kHz decreased handgrip strength when compared to baseline.

Conclusions

These findings suggest high-frequency stimulation has an inhibitory effect over muscle strength. Future studies are required in patients that are characterized by motor hyperactive such as spasticity or tremors.

Clinical trial registration

NCT, NCT03169049. Registered on 30 May 2017

     

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.     

Forest Fire Smoke Exposures and Out-of-Hospital Cardiac Arrests in Melbourne,Australia: A Case-Crossover Study

Background

Millions of people can potentially be exposed to smoke from forest fires, making this an important public health problem in many countries.

Objective

In this study we aimed to measure the association between out-of-hospital cardiac arrest (OHCA) and forest fire smoke exposures in a large city during a severe forest fire season, and estimate the number of excess OHCAs due to the fire smoke.

Methods

We investigated the association between particulate matter (PM) and other air pollutants and OHCA using a case-crossover study of adults (≥ 35 years of age) in Melbourne, Australia. Conditional logistic regression models were used to derive estimates of the percent change in the rate of OHCA associated with an interquartile range (IQR) increase in exposure. From July 2006 through June 2007, OHCA data were collected from the Victorian Ambulance Cardiac Arrest Registry. Hourly air pollution concentrations and meteorological data were obtained from a central monitoring site.

Results

There were 2,046 OHCAs with presumed cardiac etiology during our study period. Among men during the fire season, greater increases in OHCA were observed with IQR increases in the 48-hr lagged PM with diameter ≤ 2.5 μm (PM_2.5) (8.05%; 95% CI: 2.30, 14.13%; IQR = 6.1 μg/m³) or ≤ 10 μm (PM₁₀) (11.1%; 95% CI: 1.55, 21.48%; IQR = 13.7 μg/m³) and carbon monoxide (35.7%; 95% CI: 8.98, 68.92%; IQR = 0.3 ppm). There was no significant association between the rate of OHCA and air pollutants among women. One hundred seventy-four “fire-hours” (i.e., hours in which Melbourne’s air quality was affected by forest fire smoke) were identified during 12 days of the 2006/2007 fire season, and 23.9 (95% CI: 3.1, 40.2) excess OHCAs were estimated to occur due to elevations in PM_2.5 during these fire-hours.

Conclusions

This study found an association between exposure to forest fire smoke and an increase in the rate of OHCA. These findings have implications for public health messages to raise community awareness and for planning of emergency services during forest fire seasons.

Citation

Dennekamp M, Straney LD, Erbas B, Abramson MJ, Keywood M, Smith K, Sim MR, Glass DC, Del Monaco A, Haikerwal A, Tonkin AM. 2015. Forest fire smoke exposures and out-of-hospital cardiac arrests in Melbourne, Australia: a case-crossover study. Environ Health Perspect 123:959–964; http://dx.doi.org/10.1289/ehp.1408436     

End-Stage Renal Disease and Mortality Outcomes Across Different Glomerulonephropathies in a Large Diverse US Population

Objective

To compare renal function decline, incident end-stage renal disease (ESRD), and mortality among patients with 5 common glomerular diseases in a large diverse population.

Management of dyspepsia—The role of the ED Observation unit to optimize patient outcomes

Background

Dyspepsia is a common complaint that can confer significant burden on one's quality of life and may also be associated with serious underlying conditions. The objective of this study was to determine if patients admitted to the emergency department observation unit (EDOU) for severe or persistent dyspepsia would have cost effective management in terms of investigations performed, length and cost of hospital stay. The secondary objective was to determine if any patient characteristics could predict a need for admission to the inpatient unit.

Characterization of in vitro metabolites of cudratricusxanthone A in human liver microsomes

Cudratricusxanthone A (CTXA), isolated from the roots of Cudrania tricuspidata, exhibits several biological activities; however, metabolic biotransformation was not investigated. Therefore, metabolites of CTXA were investigated and the major metabolic enzymes engaged in human liver microsomes (HLMs) were characterized using liquid chromatography‐tandem mass spectrometry (LC‐MS/MS). CTXA was incubated with HLMs or human recombinant CYPs and UGTs, and analysed by an LC‐MS/MS equipped electrospray ionization (ESI) to qualify and quantify its metabolites. In total, eight metabolites were identified: M1–M4 were identified as mono‐hydroxylated metabolites during Phase I, and M5–M8 were identified as O‐glucuronidated metabolites during Phase II in HLMs. Moreover, these metabolite structures and a metabolic pathway were identified by elucidation of MSⁿ fragments and formation by human recombinant enzymes. M1 was formed by CYP2D6, and M2–M4 were generated by CYP1A2 and CYP3A4. M5–M8 were mainly formed by UGT1A1, respectively. While investigating the biotransformation of CTXA, eight metabolites of CTXA were identified by CYPs and UGTs; these data will be valuable for understanding the in vivo metabolism of CTXA. Copyright © 2015 John Wiley & Sons, Ltd.