Assessment of blood-brain barrier penetration of miltefosine used to treat a fatal case of granulomatous amebic encephalitis possibly caused by an unusual Balamuthia mandrillaris strain.

Balamuthia mandrillaris, a free-living ameba, causes rare but frequently fatal granulomatous amebic encephalitis (GAE). Few patients have survived after receiving experimental drug combinations, with or without brain lesion excisions. Some GAE survivors have been treated with a multi-drug regimen including miltefosine, an investigational anti-leishmanial agent with in vitro amebacidal activity.

Chronic mould exposure as a risk factor for severe community acquired pneumonia in a patient requiring extra corporeal membrane oxygenation.

A previously fit and well man developed acute respiratory failure due to environmental mould exposure from living in damp rental accommodation. Despite aggressive intensive care management he rapidly deteriorated and required respiratory and cardiac Extracorporeal Membrane Oxygenation. We hypothesize that poor domiciliary conditions may make an underestimated contribution to community respiratory disease.

A Scoping Review of Empirical Research Relating to Quality and Effectiveness of Research Ethics Review.

Background: To date there is no established consensus of assessment criteria for evaluating research ethics review.

Methods: We conducted a scoping review of empirical research assessing ethics review processes in order to identify common elements assessed, research foci, and research gaps to aid in the development of assessment criteria. Electronic searches of Ovid Medline, PsychInfo, and the Cochrane DSR, ACP Journal Club, DARE, CCTR, CMR, HTA, and NHSEED, were conducted.

Differential Impact of In Vivo CD8+ T Lymphocyte Depletion in Controller versus Progressor Simian Immunodeficiency Virus-Infected Macaques.

Unlabelled: Numerous studies have demonstrated that CD8(+) T lymphocytes suppress virus replication during human immunodeficiency virus (HIV)/simian immunodeficiency virus (SIV) infection. However, the mechanisms underlying this activity of T cells remain incompletely understood. Here, we conducted CD8(+) T lymphocyte depletion in 15 rhesus macaques (RMs) infected intravenously (i.

Mapping and correcting the influence of gaze position on pupil size measurements.

Pupil size is correlated with a wide variety of important cognitive variables and is increasingly being used by cognitive scientists. Pupil data can be recorded inexpensively and non-invasively by many commonly used video-based eye-tracking cameras. Despite the relative ease of data collection and increasing prevalence of pupil data in the cognitive literature, researchers often underestimate the methodological challenges associated with controlling for confounds that can result in misinterpretation of their data.

The effect of long-term corticosterone treatment on blood cell differentials and function in laboratory and wild-caught amphibian models.

The effect of long-term stress on amphibian immunity is not well understood. We modeled a long-term endocrine stress scenario by elevating plasma corticosterone in two species of amphibians and examined effects on white blood cell differentials and innate immune activity. Plasma corticosterone was elevated in American bullfrogs (Lithobates catesbeianus) by surgically implanting corticosterone capsules and in African clawed frogs (Xenopus laevis) by immersion in corticosterone-treated water.

Influence of functionalized pyridine ligands on the radio/chemical behavior of [M(I)(CO)3](+) (M = Re and (99m)Tc) 2 + 1 complexes.

While a number of chelate strategies have been developed for the organometallic precursor fac-[M(I)(OH2)3(CO)3](+) (M = Re, (99m)Tc), a unique challenge has been to improve the overall function and performance of these complexes for in vivo and in vitro applications. Since its discovery, fac-[M(I)(OH2)3(CO)3](+) has served as an essential scaffold for the development of new targeted (99m)Tc based radiopharmaceuticals due to its labile aquo ligands. However, the lipophilic nature of the fac-[M(I)(CO)3](+) core can influence the in vivo pharmacokinetics and biodistribution of the complexes.

A Phase II trial of weekly bortezomib and dexamethasone in veterans with newly diagnosed multiple myeloma not eligible for or who deferred autologous stem cell transplantation.

Once-weekly administration of bortezomib has reduced bortezomib-induced peripheral neuropathy without affecting response rates, but this has only been demonstrated prospectively in three- and four- drug combinations. We report a phase II trial of alternate dosing and schedule of bortezomib and dexamethasone in newly diagnosed multiple myeloma patients who are not eligible for or refused autologous stem cell transplantation. Bortezomib 1·6 mg/m(2) intravenously was given once-weekly for six cycles, together with dexamethasone 40 mg on the day of and day after bortezomib.

Do We Really Become Smarter When Our Fluid-Intelligence Test Scores Improve?

Recent reports of training-induced gains on fluid intelligence tests have fueled an explosion of interest in cognitive training-now a billion-dollar industry. The interpretation of these results is questionable because score can be dominated by factors that play marginal roles in the scores themselves, and because intelligence gain is not the only possible explanation for the observed control-adjusted far transfer across tasks. Here we present novel evidence that the test score gains used to measure the efficacy of cognitive training may reflect strategy refinement instead of intelligence gains.

Selective patellar resurfacing in total knee arthroplasty: a prospective, randomized, double-blind study.

350 knees were evaluated in a prospective, randomized, double-blinded study of selective patellar resurfacing in primary total knee arthroplasty. Knees with exposed bone on the patellar articular surface were excluded. 327 knees were evaluated at a mean follow-up of 7.

Liquid chromatography tandem mass spectrometry method using solid-phase extraction and bead-beating-assisted matrix solid-phase dispersion to quantify the fungicide tebuconazole in controlled frog exposure study: analysis of water and animal tissue.

This paper presents the development, optimization, and validation of a LC-MS/MS methodology to determine the concentration of the antifungal drug and fungicide tebuconazole in a controlled exposure study of African clawed frogs (Xenopus laevis). The method is validated on animal tank water and on tissue from exposed and non-exposed adult X. laevis.

Can conservation contracts co-exist with change? Payment for ecosystem services in the context of adaptive decision-making and sustainability.

This paper considers the ability of payment for ecosystem services (PES) programs to operate in the context of dynamic and complex social-ecological systems. Drawing on the experiences of two different PES programs in Latin America, we examine how PES institutions fit with the tenets of adaptive decision-making for sustainable resource management. We identify how the program goals and the connection to the market influence the incentive structure, information gathering, learning and feedback processes, and the structure of decision-making rights, specifically the ability to make and modify resource-use rules.

Validating and calibrating the Nintendo Wii balance board to derive reliable center of pressure measures.

The Nintendo Wii balance board (WBB) has generated significant interest in its application as a postural control measurement device in both the clinical and (basic, clinical, and rehabilitation) research domains. Although the WBB has been proposed as an alternative to the "gold standard" laboratory-grade force plate, additional research is necessary before the WBB can be considered a valid and reliable center of pressure (CoP) measurement device. In this study, we used the WBB and a laboratory-grade AMTI force plate (AFP) to simultaneously measure the CoP displacement of a controlled dynamic load, which has not been done before.

Indicators of the statuses of amphibian populations and their potential for exposure to atrazine in four midwestern U.S. conservation areas.

Extensive corn production in the midwestern United States has physically eliminated or fragmented vast areas of historical amphibian habitat. Midwestern corn farmers also apply large quantities of fertilizers and herbicides, which can cause direct and indirect effects on amphibians. Limited field research regarding the statuses of midwestern amphibian populations near areas of corn production has left resource managers, conservation planners, and other stakeholders needing more information to improve conservation strategies and management plans.

Unobtrusive in-home detection of time spent out-of-home with applications to loneliness and physical activity.

Loneliness is a common condition in elderly associated with severe health consequences including increased mortality, decreased cognitive function, and poor quality of life. Identifying and assisting lonely individuals is therefore increasingly important-especially in the home setting-as the very nature of loneliness often makes it difficult to detect by traditional methods. One critical component in assessing loneliness unobtrusively is to measure time spent out-of-home, as loneliness often presents with decreased physical activity, decreased motor functioning, and a decline in activities of daily living, all of which may cause decrease in the amount of time spent outside the home.

HIV-infected individuals with low CD4/CD8 ratio despite effective antiretroviral therapy exhibit altered T cell subsets, heightened CD8+ T cell activation, and increased risk of non-AIDS morbidity and mortality.

A low CD4/CD8 ratio in elderly HIV-uninfected adults is associated with increased morbidity and mortality. A subset of HIV-infected adults receiving effective antiretroviral therapy (ART) fails to normalize this ratio, even after they achieve normal CD4+ T cell counts. The immunologic and clinical characteristics of this clinical phenotype remain undefined.

Expression of the iron hormone hepcidin distinguishes different types of anemia in African children.

Childhood anemia is a major global health problem resulting from multiple causes. Iron supplementation addresses iron deficiency anemia but is undesirable for other types of anemia and may exacerbate infections. The peptide hormone hepcidin governs iron absorption; hepcidin transcription is mediated by iron, inflammation, and erythropoietic signals.

Rhenium and technetium bi- and tricarbonyl complexes in a new strategy for biomolecule incorporation using click chemistry.

A versatile strategy to prepare fac-[M(I)(CO)3](+) and cis-[M(I)(CO)2](+) (M = Re, (99m)Tc) complexes was developed using Huisgen click chemistry and monodentate phosphine ligands to readily incorporate biomolecules and tailor the chemical properties.

DNA repair pathway selection caused by defects in TEL1, SAE2, and de novo telomere addition generates specific chromosomal rearrangement signatures.

Whole genome sequencing of cancer genomes has revealed a diversity of recurrent gross chromosomal rearrangements (GCRs) that are likely signatures of specific defects in DNA damage response pathways. However, inferring the underlying defects has been difficult due to insufficient information relating defects in DNA metabolism to GCR signatures. By analyzing over 95 mutant strains of Saccharomyces cerevisiae, we found that the frequency of GCRs that deleted an internal CAN1/URA3 cassette on chrV L while retaining a chrV L telomeric hph marker was significantly higher in tel1Δ, sae2Δ, rad53Δ sml1Δ, and mrc1Δ tof1Δ mutants.

Associations between observed in-home behaviors and self-reported low mood in community-dwelling older adults.

Objectives: To ascertain the association between self-report of low mood and unobtrusively measured behaviors (walking speed, time out of residence, frequency of room transitions, and computer use) in community-dwelling older adults using novel monitoring technologies.

Design: Longitudinal cohort study of older adults whose homes were outfitted with activity sensors. Participants completed Internet-based weekly health questionnaires with questions about mood.

Regularity and predictability of human mobility in personal space.

Fundamental laws governing human mobility have many important applications such as forecasting and controlling epidemics or optimizing transportation systems. These mobility patterns, studied in the context of out of home activity during travel or social interactions with observations recorded from cell phone use or diffusion of money, suggest that in extra-personal space humans follow a high degree of temporal and spatial regularity - most often in the form of time-independent universal scaling laws. Here we show that mobility patterns of older individuals in their home also show a high degree of predictability and regularity, although in a different way than has been reported for out-of-home mobility.

Clickable, hydrophilic ligand for fac-[M(I)(CO)3](+) (M = Re/(99m)Tc) applied in an S-functionalized α-MSH peptide.

The copper(I)-catalyzed azide-alkyne cycloaddition (CuAAC) click reaction was used to incorporate alkyne-functionalized dipicolylamine (DPA) ligands (1 and 3) for fac-[M(I)(CO)3](+) (M = Re/(99m)Tc) complexation into an α-melanocyte stimulating hormone (α-MSH) peptide analogue. A novel DPA ligand with carboxylate substitutions on the pyridyl rings (3) was designed to increase the hydrophilicity and to decrease in vivo hepatobiliary retention of fac-[(99m)Tc(I)(CO)3](+) complexes used in single photon emission computed tomography (SPECT) imaging studies with targeting biomolecules. The fac-[Re(I)(CO)3(3)] complex (4) was used for chemical characterization and X-ray crystal analysis prior to radiolabeling studies between 3 and fac-[(99m)Tc(I)(OH2)3(CO)3](+).

99mTc-labeled cystine knot peptide targeting integrin αvβ6 for tumor SPECT imaging.

Integrin αvβ6 is overexpressed in a variety of cancers, and its expression is often associated with poor prognosis. Therefore, there is a need to develop affinity reagents for noninvasive imaging of integrin αvβ6 expression since it may provide early cancer diagnosis, more accurate prognosis, and better treatment planning. We recently engineered and validated highly stable cystine knot peptides that selectively bind integrin αvβ6 with no cross-reactivity to integrins αvβ5, α5β1, or αvβ3, also known to be overexpressed in many cancers.