The European hedgehog (Erinaceus europaeus) – A suitable reservoir for variants of Anaplasma phagocytophilum?

The European hedgehog (Erinaceus europaeus) is a common insectivore in most parts of Europe and is frequently infested by the ticks Ixodes ricinus and I. hexagonus. I. ricinus ticks have been found infected with Anaplasma phagocytophilum, an obligate intracellular bacterium, but little is known about the potential of the hedgehog as a reservoir host. In this study, the infection with A. phagocytophilum and the genetic variants involved were investigated in a captive hedgehog population which was kept in a fenced, natural grass and bush garden habitat, and also in its ticks. Additionally hedgehogs from hedgehog caretaking stations were investigated. EDTA blood and ticks were collected from the captive hedgehog population once a month from March to October 2007 and in March and April 2008. All 3 developmental stages of I. ricinus and I. hexagonus occurred on the hedgehogs. After DNA extraction, the samples were screened for A. phagocytophilum with a real-time PCR, and selected samples were further investigated with a nested PCR targeting the partial 16S rRNA gene, followed by sequencing. One hundred thirty-six out of 220 hedgehog blood samples (61.8%) from altogether 48 individuals, 413 out of 563 I. ricinus samples and 90 out of 338 I. hexagonus samples were PCR-positive. Thirty-two hedgehogs were positive more than once, most frequently twice or 3 times, but also up to 9 times. Sequencing of the partial 16S rRNA gene resulted in 6 variants, but one variant (‘A’) was the most frequent which appeared in 93.8% of the positive hedgehogs. This variant (equaling Frankonia II, GenBank AF136712) has recently been reported from human, equine, and canine granulocytic anaplasmosis cases and thus, its specific association with hedgehogs is an important finding in the epidemiology of A. phagocytophilum in Europe.The high infection rate of both hedgehogs and ticks with A. phagocytophilum and the simultaneous infestation with 2 tick species of all developmental stages suggest that the hedgehog may be a suitable reservoir for at least some variants of A. phagocytophilum.     

Estimated global mortality attributable to smoke from landscape fires

Background: Forest, grass, and peat fires release approximately 2 petagrams of carbon into the atmosphere each year, influencing weather, climate, and air quality.Objective: We estimated the annual global mortality attributable to landscape fire smoke (LFS).Methods: Daily and annual exposure to particulate matter ≤ 2.5 μm in aerodynamic diameter (PM_2.5) from fire emissions was estimated globally for 1997 through 2006 by combining outputs from a chemical transport model with satellite-based observations of aerosol optical depth. In World Health Organization (WHO) subregions classified as sporadically affected, the daily burden of mortality was estimated using previously published concentration–response coefficients for the association between short-term elevations in PM_2.5 from LFS (contrasted with 0 μg/m³ from LFS) and all-cause mortality. In subregions classified as chronically affected, the annual burden of mortality was estimated using the American Cancer Society study coefficient for the association between long-term PM_2.5 exposure and all-cause mortality. The annual average PM_2.5 estimates were contrasted with theoretical minimum (counterfactual) concentrations in each chronically affected subregion. Sensitivity of mortality estimates to different exposure assessments, counterfactual estimates, and concentration–response functions was evaluated. Strong La Niña and El Niño years were compared to assess the influence of interannual climatic variability.Results: Our principal estimate for the average mortality attributable to LFS exposure was 339,000 deaths annually. In sensitivity analyses the interquartile range of all tested estimates was 260,000–600,000. The regions most affected were sub-Saharan Africa (157,000) and Southeast Asia (110,000). Estimated annual mortality during La Niña was 262,000, compared with 532,000 during El Niño.Conclusions: Fire emissions are an important contributor to global mortality. Adverse health outcomes associated with LFS could be substantially reduced by curtailing burning of tropical rainforests, which rarely burn naturally. The large estimated influence of El Niño suggests a relationship between climate and the burden of mortality attributable to LFS.     

The impact of maternity length-of-stay mandates on the labor market and insurance coverage

To understand the effects of insurance regulation on the labor market and insurance coverage, this study uses a difference-in-difference-in-differences analysis to compare five states that passed minimum maternity length-of-stay laws with states that waited until after a federal law was passed. On average, we do not find statistically significant effects on labor market outcomes such as hours of work and wages. However, we find that employees of small firms in states with maternity length-of-stay mandates experienced a 6.2-percentage-point decline in the likelihood of having employer-sponsored insurance. Implementation of federal health reform that requires minimum benefit standards should consider the implications for firms of differing sizes.     

Neuroprotective efficacy of quinazoline type phosphodiesterase 7 inhibitors in cellular cultures and experimental stroke model

A simple and efficient synthetic method for the preparation of quinazoline type phosphodiesterase 7 (PDE7) inhibitors, based on microwave irradiation, has been developed. The use of this methodology improved yields and reaction times, providing a scalable procedure. These compounds are pharmacologically interesting because of their in?vivo efficacy both in spinal cord injury and Parkinson's disease models, as shown in previous studies from our group. Herein we describe for the first time that administration of one of the PDE7 inhibitors here optimized, 3-phenyl-2,4-dithioxo-1,2,3,4-tetrahydroquinazoline (compound 5), ameliorated brain damage and improved behavioral outcome in a permanent middle cerebral artery occlusion (pMCAO) stroke model. Furthermore, we demonstrate that these PDE7 inhibitors are potent anti-inflammatory as well as neuroprotective agents in primary cultures of neural cells. These results led us to propose PDE7 inhibitors as a new class of therapeutic agents for neuroprotection.     

The effect of weight loss on changes in health-related quality of life among overweight and obese women with urinary incontinence

Objective

To estimate the effect of change in weight and change in urinary incontinence (UI) frequency on changes in preference-based measures of health-related quality of life (HRQL) among overweight and obese women with UI participating in a weight loss trial.

Methods

We conducted a longitudinal cohort analysis of 338 overweight and obese women with UI enrolled in a randomized clinical trial comparing a behavioral weight loss intervention to an educational control condition. At baseline, 6, and 18?months, health utilities were estimated using the Health Utilities Index Mark 3 (HUI3), a transformation of the SF-36 to the preference-based SF-6D, and the estimated Quality of Well-Being (eQWB) score (a summary calculated from the SF-36 physical functioning, mental health, bodily pain, general health perceptions, and role limitations?Cphysical subscale scores). Potential predictors of changes in these outcomes were examined using generalized estimating equations.

Results

In adjusted multivariable models, weight loss was associated with improvement in HUI3, SF-6D, and eQWB at 6 and 18?months (P?<?0.05). Increases in physical activity also were independently associated with improvement in HUI3 (P?=?0.01) and SF-6D (P?=?0.006) scores at 18?months. In contrast, reduction in UI frequency did not predict improvements in HRQL at 6 or 18?months.

Conclusion

Weight loss and increased physical activity, but not reduction in UI frequency, were strongly associated with improvements in health utilities measured by the HUI3, SF-6D, and eQWB. These findings provide important information that can be used to inform cost?Cutility analyses of weight loss interventions.     

In setting doctors' Medicare fees, CMS almost always accepts the relative value update panel's advice on work values

To calculate physicians' fees under Medicare--which in turn influence the physician fee schedules of other public and private payers--one of the essential decisions the Centers for Medicare and Medicaid Services (CMS) must make is how much physician time and effort, or work, is associated with various physician services. To make this determination, CMS relies on the recommendations of an advisory committee representing national physician organizations. Some experts on primary care who are concerned about the income gap between primary and specialty care providers have blamed the committee for increasing that gap. Our analysis of CMS's decisions on updating work values between 1994 and 2010 found that CMS agreed with 87.4 percent of the committee's recommendations, although CMS reduced recommended work values for a limited number of radiology and medical specialty services. If policy makers or physicians want to change the update process but keep the Medicare fee schedule in its current form, CMS's capacity to review changes in relative value units could be strengthened through long-term investment in the agency's ability to undertake research and analysis of issues such as how the effort and time associated with different physician services is determined, and which specialties--if any--receive higher payments than others as a result.     

Rapid Induction of COOLing in Stroke Patients (iCOOL1): a randomised pilot study comparing cold infusions with nasopharyngeal cooling

Introduction

Induction methods for therapeutic cooling are under investigated. We compared the effectiveness and safety of cold infusions (CI) and nasopharyngeal cooling (NPC) for cooling induction in stroke patients.

Methods

A prospective, open-label, randomised (1:1), single-centre pilot trial with partially blinded safety endpoint assessment was conducted at the neurointensive care unit of Heidelberg University. Intubated stroke patients with an indication for therapeutic cooling and an intracranial pressure (ICP)/temperature brain probe were randomly assigned to CI (4°C, 2L at 4L/h) or NPC (60L/min for 1 h). Previous data suggested a maximum decrease of tympanic temperature for CI (2.1L within 35 min) after 52 min. Therefore the study period was 1 hour (15 min subperiods I-IV). The brain temperature course was the primary endpoint. Secondary measures included continuous monitoring of neurovital parameters and extracerebral temperatures. Statistical analysis based on repeated-measures analysis of variance.

Results

Of 221 patients screened, 20 were randomized within 5 months. Infusion time of 2L CI was 33 ± 4 min in 10 patients and 10 patients received NPC for 60 min. During active treatment (first 30 min), brain temperature decreased faster with CI than during NPC (I: -0.31 ± 0.2 versus -0.12 ± 0.1°C, P = 0.008; II: -1.0 ± 0.3 versus -0.49 ± 0.3°C, P = 0.001). In the CI-group, after the infusion was finished, the intervention no longer decreased brain temperature, which increased after 3.5 ± 3.3 min. Oesophageal temperature correlated best with brain temperature during CI and NPC. Tympanic temperature reacted similarly to relative changes of brain temperature during CI, but absolute values slightly differed. CI provoked three severe adverse events during subperiods II-IV (two systolic arterial pressure (SAP), one shivering) compared with four in the NPC-group, all during subperiod I (three SAP, one ICP). Classified as possibly intervention-related, two cases of ventilator failure occurred during NPC.

Conclusions

In intubated stroke patients, brain cooling is faster during CI than during NPC. Importantly, contrary to previous expectations, brain cooling stopped soon after CI cessation. Oesophageal but neither bladder nor rectal temperature is suited as surrogate for brain temperature during CI and NPC. Several severe adverse events in CI and in NPC demand further studying of safety.

Trial registration

ClinicalTrials.gov NCT01573117. Registered 31 March 2012

     

Prolonged QTc interval and risk of sudden cardiac death in a population of older adults.

OBJECTIVES: This study sought to investigate whether prolongation of the heart rate-corrected QT (QTc) interval is a risk factor for sudden cardiac death in the general population. BACKGROUND: In developed countries, sudden cardiac death is a major cause of cardiovascular mortality. Prolongation of the QTc interval has been associated with ventricular arrhythmias, but in most population-based studies no consistent association was found between QTc prolongation and total or cardiovascular mortality. Only very few of these studies specifically addressed sudden cardiac death. METHODS: This study was conducted as part of the Rotterdam Study, a prospective population-based cohort study that comprises 3,105 men and 4,878 women aged 55 years and older. The QTc interval on the electrocardiogram was determined during the baseline visit (1990 to 1993) and the first follow-up examination (1993 to 1995). The association between a prolonged QTc interval and sudden cardiac death was estimated using Cox proportional hazards analysis. RESULTS: During an average follow-up period of 6.7 years (standard deviation, 2.3 years) 125 patients died of sudden cardiac death. An abnormally prolonged QTc interval (>450 ms in men, >470 ms in women) was associated with a three-fold increased risk of sudden cardiac death (hazard ratio, 2.5; 95% confidence interval, 1.3 to 4.7), after adjustment for age, gender, body mass index, hypertension, cholesterol/high-density lipoprotein ratio, diabetes mellitus, myocardial infarction, heart failure, and heart rate. In patients with an age below the median of 68 years, the corresponding relative risk was 8.0 (95% confidence interval 2.1 to 31.3). CONCLUSIONS: Abnormal QTc prolongation on the electrocardiogram should be viewed as an independent risk factor for sudden cardiac death.     

The Preparation and Properties of Monoclonal Antibodies against Human Granulocyte Membrane Antigens

A series of four monoclonal antibodies has been prepared by hybridization of mouse myeloma cells with spleen cells from mice immunized with human blood granulocytes. The four antibodies all react specifically with granulocytes, failing to stain lymphocytes and other blood cells. Lymphocytic leukaemia cells are not stained, whereas myeloid leukaemia cells give a varied reaction with the antibodies. Studies on marrow, leukaemic cells and cell lines suggest that the four antibodies react with distinct differentiation antigens which are absent from myeloblasts, appear at the promyelocyte, myelocyte or metamyelocyte stage (depending on the antibody in question) and are expressed on all mature granulocytes.