Routine Laboratory Testing to Evaluate for Medical Illness in Psychiatric Patients in the Emergency Department Is Largely Unrevealing

Objectives: This is a prospective study of psychiatric patients presenting to the emergency department (ED) to determine the value of routine laboratory studies used to attempt to exclude concomitant medical illness.Methods: Physical exams and laboratory tests were performed on 375 psychiatric patients presenting for “medical clearance” in the ED. Upon completion of these tests, the percentage and impact of abnormal physical exams and laboratory results were assessed.Results: Fifty-six of 375 patients (14.9%) had a non-substance-induced laboratory abnormality. Forty-two of these 56 patients (75.0%) also had abnormal history or physical exam findings indicating laboratory screening. Ten had normal history and physical exams with insignificant laboratory abnormalities. The four (1.1% [95% CI 0.3-2.7%]) remaining patients with normal history and physical exams had abnormal urinalyses which did not affect final disposition or contribute to altered behavior.Conclusion: Patients presenting to the ED with psychiatric chief complaints, benign histories and normal physical exams have a low likelihood of clinically significant laboratory findings. [WestJEM. 2009;10:97-100.

Assessing neuraxial microstructural changes in a transgenic mouse model of early stage Amyotrophic Lateral Sclerosis by ultra‐high field MRI and diffusion tensor metrics

bjective: Cell structural changes are one of the main features observed during the development of amyotrophic lateral sclerosis (ALS). In this work, we propose the useof diffusion tensor imaging (DTI) metrics to assess specific ultrastructural changes in the central nervous system during the early neurodegenerative stages of ALS.Methods: Ultra-high field MRI and DTI data at 17.6T were obtained from fixed, excised mouse brains, and spinal cords from ALS (G93A-SOD1) mice.Results: Changes in fractional anisotropy (FA) and linear, planar, and spherical anisotropy ratios (CL, CP, and CS, respectively) of the diffusion eigenvalues were measured in white matter (WM) and gray matter (GM) areas associated with early axonal degenerative processes (in both the brain and the spinal cord). Specifically, in WM structures (corpus callosum, corticospinal tract, and spinal cord funiculi) as the disease progressed, FA, CL, and CP values decreased, whereas CS values increased.In GM structures (prefrontal cortex, hippocampus, and central spinal cord) FA and CP decreased, whereas the CL a nd C values were unchanged or slightly smaller.Histological studies of a fluorescent mice model (YFP, G93A-SOD1 mouse) corroborated the early alterations in neuronal morphology and axonal connectivity measured by DTI.Conclusions: Changes in diffusion tensor shape were observed in this animal model at the early, nonsymptomatic stages of ALS. Further studies of CL, CP, and CSas imaging biomarkers should be undertaken to refine this neuroimaging tool for future clinical use in the detection of the early stages of ALSFil: Gatto, Rodolfo G.. University Of Illinois. Deparment Of Biological Science; Estados UnidosFil: Weissmann, Carina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Fisiología, Biología Molecular y Neurociencias. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Fisiología, Biología Molecular y Neurociencias; ArgentinaFil: Amin, Manish. University of Florida; Estados UnidosFil: Finkielsztein, Ariel. Northwestern University; Estados UnidosFil: Sumagin, Ronen. Northwestern University; Estados UnidosFil: Mareci, Thomas H.. University of Florida; Estados UnidosFil: Uchitel, Osvaldo Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Fisiología, Biología Molecular y Neurociencias. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Fisiología, Biología Molecular y Neurociencias; ArgentinaFil: Magin, Richard L.. University Of Illinois. Deparment Of Biological Science; Estados Unido

Evaluation of Early Microstructural Changes in the R6/1 Mouse Model of Huntington's Disease by Ultra-High Field Diffusion MR Imaging

Diffusion MRI (dMRI) has been able to detect early structural changes related to neurological symptoms present in Huntington's disease (HD). However, there is still a knowledge gap to interpret the biological significance at early neuropathological stages. The purpose of this study is two-fold: (i) establish if the combination of Ultra-High Field Diffusion MRI (UHFD-MRI) techniques can add a more comprehensive analysis of the early microstructural changes observed in HD, and (ii) evaluate if early changes in dMRI microstructural parameters can be linked to cellular biomarkers of neuroinflammation. Ultra-high field magnet (16.7T), diffusion tensor imaging (DTI), and neurite orientation dispersion and density imaging (NODDI) techniques were applied to fixed ex-vivo brains of a preclinical model of HD (R6/1 mice). Fractional anisotropy (FA) was decreased in deep and superficial grey matter (GM) as well as white matter (WM) brain regions with well-known early HD microstructure and connectivity pathology. NODDI parameters associated with the intracellular and extracellular compartment, such as intracellular ventricular fraction (ICVF), orientation dispersion index (ODI), and isotropic volume fractions (IsoVF) were altered in R6/1 mice GM. Further, histological studies in these areas showed that glia cell markers associated with neuroinflammation (GFAP & Iba1) were consistent with the dMRI findings. dMRI can be used to extract non-invasive information of neuropathological events present in the early stages of HD. The combination of multiple imaging techniques represents a better approach to understand the neuropathological process allowing the early diagnosis and neuromonitoring of patients affected by HD.Fil: Segatto, Rodolfo Guillermo. University Of Illinois. Deparment Of Biological Science; Estados UnidosFil: Weissmann, Carina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Fisiología, Biología Molecular y Neurociencias. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Fisiología, Biología Molecular y Neurociencias; ArgentinaFil: Amin, Manish. University of Florida. Department of Microbiology and Cell Science; Estados UnidosFil: Angeles López, Quetzalli D.. Consejo Nacional de Ciencia y Tecnologia de Mexico. Centro de Investigacion Cientifica y de Educacion Superior de Ensenada Baja California.; MéxicoFil: García Lara, Lucia. Consejo Nacional de Ciencia y Tecnologia de Mexico. Centro de Investigacion Cientifica y de Educacion Superior de Ensenada Baja California.; MéxicoFil: Salinas Castellanos, Libia Catalina. Consejo Nacional de Ciencia y Tecnologia de Mexico. Centro de Investigacion Cientifica y de Educacion Superior de Ensenada Baja California.; MéxicoFil: Deyoung, Daniel. University of Florida. Department of Microbiology and Cell Science; Estados UnidosFil: Segovia, Jose Manuel. Consejo Nacional de Ciencia y Tecnologia de Mexico. Centro de Investigacion Cientifica y de Educacion Superior de Ensenada Baja California.; MéxicoFil: Mareci, Thomas H.. University of Florida. Department of Microbiology and Cell Science; Estados UnidosFil: Uchitel, Osvaldo Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Fisiología, Biología Molecular y Neurociencias. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Fisiología, Biología Molecular y Neurociencias; ArgentinaFil: Magin, Richard L.. University Of Illinois. Deparment Of Biological Science; Estados Unido

Better Brain and Cognition Prior to Surgery Is Associated With Elevated Postoperative Brain Extracellular Free-Water in Older Adults

For adults age 65 and older, the brain shows acute functional connectivity decreases after total knee arthroplasty with the severity of change predicted by preoperative cognitive function and brain disease burden. The extent of acute structural microstructural brain changes acutely after surgery remains unknown within the literature. For the current study, we report on the severity of acute post-surgery microstructural brain changes as measured by diffusion imaging and free-water analysis. Participants who underwent total knee arthroplasty under general anesthesia and non-surgery peers were part of a federally funded prospective cohort investigation involving participants. Recruitment occurred between 2013 and 2017. Data were collected in outpatient and inpatient settings within a university-affiliated medical center. A total of 232 TKA patients were referred by the study surgeon and contacted for study inclusion. Of these, 78 met inclusion and exclusion criteria and completed assessment. Five participants were excluded due to anesthetic protocol changes (spinal instead of general) with an additional 12 excluded for imaging-related complications. The total included sample size was 61. A total of 127 non-surgery participants were screened with 66 enrolled. One non-surgery participant was excluded for an imaging-related complication. Total knee arthroplasty and general anesthetic protocols were standardized. Participants received preoperative neurocognitive assessment and brain magnetic resonance imaging, with repeat imaging 48 h after surgery or pseudo surgery. Free-water analyses were performed using diffusion weighted images and tract-based spatial statistics with baseline cognitive data used to predict free-water changes. Surgery participants had widespread increases in white matter free-water. Surgery participants with higher cognitive functions as measured by immediate memory and less evidence of brain atrophy and disease (i.e., brain integrity) had greater free-water increase. Non-surgery peers had no free-water change. We interpret the surgery group’s free-water change as indicating widespread brain white matter glial response, with greater change indicative of better brain response to the acute surgery/anesthesia experience

Acute seizures attributable to falciparum malaria in an endemic area on the Kenyan coast

Falciparum malaria is an important cause of acute symptomatic seizures in children admitted to hospitals in sub-Saharan Africa, and these seizures are associated with neurological disabilities and epilepsy. However, it is difficult to determine the proportion of seizures attributable to malaria in endemic areas since a significant proportion of asymptomatic children have malaria parasitaemia. We studied children aged 0–13 years who had been admitted with a history of seizures to a rural Kenyan hospital between 2002 and 2008. We examined the changes in the incidence of seizures with the reduction of malaria. Logistic regression was used to model malaria-attributable fractions for seizures (the proportion of seizures caused by malaria) to determine if the observed decrease in acute symptomatic seizures was a measure of seizures that are attributable to malaria. The overall incidence of acute symptomatic seizures over the period was 651/100 000/year (95% confidence interval 632–670) and it was 400/100 000/year (95% confidence interval 385–415) for acute complex symptomatic seizures (convulsive status epilepticus, repetitive or focal) and 163/100 000/year (95% confidence interval 154–173) for febrile seizures. From 2002 to 2008, the incidence of all acute symptomatic seizures decreased by 809/100 000/year (69.2%) with 93.1% of this decrease in malaria-associated seizures. The decrease in the incidence of acute complex symptomatic seizures during the period was 111/100 000/year (57.2%) for convulsive status epilepticus, 440/100 000/year (73.7%) for repetitive seizures and 153/100 000/year (80.5%) for focal seizures. The adjusted malaria-attributable fractions for seizures with parasitaemia were 92.9% (95% confidence interval 90.4–95.1%) for all acute symptomatic seizures, 92.9% (95% confidence interval 89.4–95.5%) for convulsive status epilepticus, 93.6% (95% confidence interval 90.9–95.9%) for repetitive seizures and 91.8% (95% confidence interval 85.6–95.5%) for focal seizures. The adjusted malaria-attributable fractions for seizures in children above 6 months of age decreased with age. The observed decrease in all acute symptomatic seizures (809/100 000/year) was similar to the predicted decline (794/100 000/year) estimated by malaria-attributable fractions at the beginning of the study. In endemic areas, falciparum malaria is the most common cause of seizures and the risk for seizures in malaria decreases with age. The reduction in malaria has decreased the burden of seizures that are attributable to malaria and this could lead to reduced neurological disabilities and epilepsy in the area

Application of nanotechnology to herbal antioxidants as improved phytomedicine: An expanding horizon.

Phytotherapy, based on medicinal plants, have excellent potential in managing several diseases. A vital part of the healthcare system is herbal medicines, consisting of therapeutic agents with high safety profile and no or least adverse effects. Herbs or medicinal plants show anticancer, antioxidant, and gene-protective activity, which is useful for pharmaceutical industries. In vitro, the extract of antioxidant compounds prevents the growth of colon and liver cancer cells, followed by a dose-dependent method. The screening of extracts is done by using in vitro models. Reactive oxygen species (ROS) and free radicals lead to diseases based on age which promotes oxidative stress. Different types of ROSs available have central roles in the normal physiology and functioning of processes. Herbal or traditional plant medicines have rich antioxidant activity. Despite the limited literature on the health effect of herbal extract or spices. There are many studies examining the encouraging health effects of single phytochemicals instigating from the medicinal plant. This review provides a detailed overview on herbal antioxidants and how application of nanotechnology can improve its biological activity in managing several major diseases, and having no reported side effects

Telomere structure and maintenance gene variants and risk of five cancer types.

Telomeres cap chromosome ends, protecting them from degradation, double-strand breaks, and end-to-end fusions. Telomeres are maintained by telomerase, a reverse transcriptase encoded by TERT, and an RNA template encoded by TERC. Loci in the TERT and adjoining CLPTM1L region are associated with risk of multiple cancers. We therefore investigated associations between variants in 22 telomere structure and maintenance gene regions and colorectal, breast, prostate, ovarian, and lung cancer risk. We performed subset-based meta-analyses of 204,993 directly-measured and imputed SNPs among 61,851 cancer cases and 74,457 controls of European descent. Independent associations for SNP minor alleles were identified using sequential conditional analysis (with gene-level p value cutoffs ≤3.08 × 10-5 ). Of the thirteen independent SNPs observed to be associated with cancer risk, novel findings were observed for seven loci. Across the DCLRE1B region, rs974494 and rs12144215 were inversely associated with prostate and lung cancers, and colorectal, breast, and prostate cancers, respectively. Across the TERC region, rs75316749 was positively associated with colorectal, breast, ovarian, and lung cancers. Across the DCLRE1B region, rs974404 and rs12144215 were inversely associated with prostate and lung cancers, and colorectal, breast, and prostate cancers, respectively. Near POT1, rs116895242 was inversely associated with colorectal, ovarian, and lung cancers, and RTEL1 rs34978822 was inversely associated with prostate and lung cancers. The complex association patterns in telomere-related genes across cancer types may provide insight into mechanisms through which telomere dysfunction in different tissues influences cancer risk.Funding for the iCOGS infrastructure came from: the European Community’s Seventh Framework Programme under grant agreement n° 223175 (HEALTH-F2-2009-223175) (COGS), Cancer Research UK (C1287/A10118, C1287/A 10710, C12292/A11174, C1281/A12014, C5047/A8384, C5047/A15007, C5047/A10692, C8197/A16565), the National Institutes of Health (CA128978) and Post-Cancer GWAS initiative (1U19 CA148537, 1U19 CA148065 and 1U19 CA148112 – the GAME-ON initiative), the Department of Defense (W81XWH-10-1-0341), the Canadian Institutes of Health Research (CIHR) for the CIHR Team in Familial Risks of Breast Cancer, Komen Foundation for the Cure, the Breast Cancer Research Foundation, and the Ovarian Cancer Research Fund.This is the author accepted manuscript. The final version is available from Wiley via http://dx.doi.org/10.1002/ijc.3028

Understanding the Value of Tumor Markers in Pediatric Ovarian Neoplasms

Purpose The purpose of this study was to determine the diagnostic accuracy of tumor markers for malignancy in girls with ovarian neoplasms. Methods A retrospective review of girls 2–21 years who presented for surgical management of an ovarian neoplasm across 10 children's hospitals between 2010 and 2016 was performed. Patients who had at least one concerning feature on imaging and had tumor marker testing were included in the study. Sensitivity, specificity, and negative and positive predictive values (PPV) of tumor markers were calculated. Results Our cohort included 401 patients; 22.4% had a malignancy. Testing for tumor markers was inconsistent. AFP had high specificity (98%) and low sensitivity (42%) with a PPV of 86%. The sensitivity, specificity, and PPV of beta-hCG was 44%, 76%, and 32%, respectively. LDH had high sensitivity (95%) and Inhibin A and Inhibin B had high specificity (97% and 92%, respectively). Conclusions Tumor marker testing is helpful in preoperative risk stratification of ovarian neoplasms for malignancy. Given the variety of potential tumor types, no single marker provides enough reliability, and therefore a panel of tumor marker testing is recommended if there is concern for malignancy. Prospective studies may help further elucidate the predictive value of tumor markers in a pediatric ovarian neoplasm population

The Changing Landscape for Stroke\ua0Prevention in AF: Findings From the GLORIA-AF Registry Phase 2

Background GLORIA-AF (Global Registry on Long-Term Oral Antithrombotic Treatment in Patients with Atrial Fibrillation) is a prospective, global registry program describing antithrombotic treatment patterns in patients with newly diagnosed nonvalvular atrial fibrillation at risk of stroke. Phase 2 began when dabigatran, the first non\u2013vitamin K antagonist oral anticoagulant (NOAC), became available. Objectives This study sought to describe phase 2 baseline data and compare these with the pre-NOAC era collected during phase 1. Methods During phase 2, 15,641 consenting patients were enrolled (November 2011 to December 2014); 15,092 were eligible. This pre-specified cross-sectional analysis describes eligible patients\u2019 baseline characteristics. Atrial fibrillation disease characteristics, medical outcomes, and concomitant diseases and medications were collected. Data were analyzed using descriptive statistics. Results Of the total patients, 45.5% were female; median age was 71 (interquartile range: 64, 78) years. Patients were from Europe (47.1%), North America (22.5%), Asia (20.3%), Latin America (6.0%), and the Middle East/Africa (4.0%). Most had high stroke risk (CHA2DS2-VASc [Congestive heart failure, Hypertension, Age  6575 years, Diabetes mellitus, previous Stroke, Vascular disease, Age 65 to 74 years, Sex category] score  652; 86.1%); 13.9% had moderate risk (CHA2DS2-VASc = 1). Overall, 79.9% received oral anticoagulants, of whom 47.6% received NOAC and 32.3% vitamin K antagonists (VKA); 12.1% received antiplatelet agents; 7.8% received no antithrombotic treatment. For comparison, the proportion of phase 1 patients (of N = 1,063 all eligible) prescribed VKA was 32.8%, acetylsalicylic acid 41.7%, and no therapy 20.2%. In Europe in phase 2, treatment with NOAC was more common than VKA (52.3% and 37.8%, respectively); 6.0% of patients received antiplatelet treatment; and 3.8% received no antithrombotic treatment. In North America, 52.1%, 26.2%, and 14.0% of patients received NOAC, VKA, and antiplatelet drugs, respectively; 7.5% received no antithrombotic treatment. NOAC use was less common in Asia (27.7%), where 27.5% of patients received VKA, 25.0% antiplatelet drugs, and 19.8% no antithrombotic treatment. Conclusions The baseline data from GLORIA-AF phase 2 demonstrate that in newly diagnosed nonvalvular atrial fibrillation patients, NOAC have been highly adopted into practice, becoming more frequently prescribed than VKA in Europe and North America. Worldwide, however, a large proportion of patients remain undertreated, particularly in Asia and North America. (Global Registry on Long-Term Oral Antithrombotic Treatment in Patients With Atrial Fibrillation [GLORIA-AF]; NCT01468701