Response of newborn and adult sheep to pyrogens: relation between fever and brain eicosanoid changes

We investigated whether the weak febrile response to pyrogens in newborns is due to a diminished activation of the putative pyrogen mediator, prostaglandin (PG)E₂. Indwelling cannulas in the third ventricle of lambs (age, 5–31 days) and adult ewes were used to collect cerebrospinal fluid (CSF) for radioimmunoassay of PGE₂. Intravenous (i.v.) endotoxin caused a smaller increase in body temperature but a larger increase in CSF PGE₂ in lambs compared to adults. PGE₂ by intracarotid infusion raised body temperature in 5 of 7 trials in 3 lambs and in 4 of 4 trials in 1 adult. Endotoxin given intracerebroventricularly (i.c.v.) induced a rise in temperature and CSF PGE₂ in the lamb but, in the adult, these responses were delayed and smaller. Interleukin-1 i.c.v. and PGE₂ i.c.v. were weak pyretic agents at both ages. We conclude that the lamb's diminished febrile response to endotoxin i.v. is not caused by a lesser rise in CSF PGE₂; rather it may be due, at least in part, to reduced responsiveness to this putative mediator. Regardless of age, the sheep differs from other species in that pyrogen/PGE₂ coupling occurs primarily at a site in brain that is better accessible from blood than CSF.     

Work conditions and mental health among doctors from Salvador, Bahia, Brazil

This cross-sectional study investigated the association between work conditions and minor psychological disorders (MPD) in a random sample of 350 doctors from Salvador City, State of Bahia, Brazil. Data were gathered using an individual, self-report questionnaire that incorporated the demand-control model (Job Content Questionnaire) to evaluate psychosocial aspects of the doctors' work and the Self-report Questionnaire (SRQ-20) to evaluate their mental health. The study found increased work overload, overtime and extended work shifts, multiple jobs, low income per hour worked, and unstable work arrangements with payment per procedure. The prevalence of MPD was 26.0% and was more strongly associated with aspects of the psychological demands of work than with the doctors' control over it. Doctors with high strain (high demand and low control) jobs showed MPD prevalence of 3.07 (95%IC: 1.38-6.85) times higher than those in low strain (low demand and high control) jobs.     

Evaluation of ELISA-Based Multiplex Peptides for the Detection of Human Serum Antibodies Induced by Zika Virus Infection across Various Countries

Zika virus (ZIKV) is a mosquito-borne Flavivirus with a positive-sense RNA genome, which are generally transmitted through the bite of an infected Aedes mosquito. ZIKV infections could be associated with neurological sequelae that, and otherwise produces similar clinical symptoms as other co-circulating pathogens. Past infection with one member of the Flavivirus genus often induces cross-reactive antibodies against other flaviruses. These attributes complicate the ability to differentially diagnose ZIKV infection from other endemic mosquito-borne viruses, making it both a public health issue as well as a diagnostic challenge. We report the results from serological analyses using arbovirus-specific peptides on 339 samples that were previously collected from 6 countries. Overall, we found that our multiplexed peptide-based ELISA was highly efficient for identifying ZIKV antibodies as early as 2 weeks post infection, and that it correlates with microneutralization, plaque reduction neutralization tests (PRNTs) and commercial tests for ZIKV in previously characterized samples. We observed that seropositivity varied by patient cohort, reflecting the sampling period in relation to the 2015–2016 ZIKV outbreak. This work evaluates the accuracy, specificity, and sensitivity of our peptide-based ELISA method for detecting ZIKV antibodies from geographically diverse regions. These findings can contribute to ongoing serological methods development and can be adapted for use in future studies.     

Reduced platelet amyloid precursor protein ratio (APP ratio) predicts conversion from mild cognitive impairment to Alzheimer’s disease

Studies have shown that platelet APP ratio (representing the percentage of 120-130 kDa to 110 kDa isoforms of the amyloid precursor protein) is reduced in patients with mild cognitive impairment (MCI) and Alzheimer's disease (AD). In the present study, we sought to determine if baseline APP ratio predicts the conversion from MCI to AD dementia after 4 years of longitudinal assessment. Fifty-five older adults with varying degrees of cognitive impairment (34 with MCI and 21 with AD) were assessed at baseline and after 4 years. MCI patients were re-classified according to the conversion status upon follow-up: 25 individuals retained the diagnostic status of MCI and were considered as stable cases (MCI-MCI); conversely, in nine cases the diagnosis of dementia due to AD was ascertained. The APP ratio (APPr) was determined by the Western blot method in samples of platelets collected at baseline. We found a significant reduction of APPr in MCI patients who converted to dementia upon follow-up. These individuals had baseline APPr values similar to those of demented AD patients. The overall accuracy of APPr to identify subjects with MCI who will progress to AD was 0.74 ± 0.10, p = 0.05. The cut-off of 1.12 yielded a sensitivity of 75 % and a specificity of 75 %. Platelet APPr may be a surrogate marker of the disease process in AD, with potential implications for the assessment of abnormalities in the APP metabolism in patients with and at risk for dementia. However, diagnostic accuracy was relatively low. Therefore, studies in larger samples are needed to determine whether APPr may warrant its use as a biomarker to support the early diagnosis of AD.     

Radiation Dose during Transarterial Radioembolization: A Dosimetric Comparison of Cone-Beam CT and Angio-CT Technologies

PurposeTo evaluate the radiation dose differences for intraprocedural computed tomography (CT) imaging between cone-beam CT and angio-CT acquired during transarterial radioembolization (TARE) therapies for hepatocellular carcinoma.Materials and MethodsA retrospective cohort of 22 patients who underwent 23 TARE procedures were selected. Patients were imaged in both cone-beam CT and angio-CT rooms as a part of their conventional treatment plan. Effective dose contributions from individual CT acquisitions as well as the cumulative dose contributions from procedural 3D imaging were evaluated. Angiography dose contributions were omitted. Cone-beam CT images were acquired on a C-arm Philips Allura system. Effective doses were evaluated by coupling previously published conversion factors (effective dose per dose-area product) to patient’s dose-area product meter readings after the procedure. Angio-CT images were acquired on a hybrid Canon Infinix-i Aquilion PRIME system. Effective doses from angio-CT scans were estimated using Radimetrics. Comparisons of a single patient’s dose differential between the 2 technologies were made.ResultsThe mean effective dose from a single CT scan was 6.42 mSv and 5.99 mSv in the cone-beam CT room and the angio-CT room, respectively (P = .3224), despite the greater field of view and average craniocaudal scan coverage in angio-CT. The mean effective dose summed across all CTs in a procedure was 12.89 mSv and 34.35 mSv in the cone-beam CT room and the angio-CT room, respectively (P = .0018).ConclusionsThe mean effective dose per CT scan is comparable between cone-beam CT and angio-CT when considered in direct comparison for a single patient.     

Residency directors' assessments of which selection criteria best predict the performances of foreign-born foreign medical graduates during internal medicine residencies.

In the summer of 1990, 102 directors of internal medicine residency programs from nine areas of the country with the largest numbers of foreign-born foreign medical graduates (FFMGs) were surveyed by mail to determine what criteria used to select FFMGs for residency positions best predicted performance. The directors felt that the most important predictors were performance on the Foreign Medical Graduate Examination in the Medical Sciences or the National Board of Medical Examiners examinations; performance during the interview; and postgraduate clinical experience in the United States. Recent graduation from medical school was felt to be a better predictor than postgraduate clinical experience in a foreign country. Seventy-three percent of the directors found letters of recommendation from a foreign country to be useless. The author suggests the results of this study may be useful to residency programs in evaluating FFMG applicants and to FFMGs in assessing their own credentials.     

In vivo effects of Bothrops jararaca venom on metabolic profile and on muscle protein metabolism in rats

This study investigated the in vivo effects of the Bothrops jararaca venom (BjV) on general metabolic profile and, specifically, on muscle protein metabolism in rats. The crude venom (0.4 mg/kg body weight, IV) was infused in awake rats, and plasma activity of enzymes and metabolites levels were determined after 1, 2, 3, and 4 hours. BjV increased urea, lactate, and activities of creatine kinase, lactate dehydrogenase, and aspartate aminotransferase after 4 hours. The content of liver glycogen was reduced by BjV. Protein metabolism was evaluated by means of microdialysis technique and in isolated muscles. BjV induced increase in the muscle interstitial-arterial tyrosine concentration difference, indicating a high protein catabolism. The myotoxicity induced by this venom is associated with reduction of protein synthesis and increase in rates of overall proteolysis, which was accompanied by activation of lysosomal and ubiquitin-proteasome systems without changes in protein levels of cathepsins and ubiquitin-protein conjugates.