Differences in schizophrenia treatments by race and ethnicity-analysis of electronic health records.

Racial disparities in prescriptions of anti-psychotics have been highlighted before. However, (i) the evidence on other medications, including anti-depressant or mood stabilizing medications is lacking, and (ii) the role of potentially confounding factors and (iii) specificity of such disparities to schizophrenia (SCZ), are still unknown. We used electronic health records (EHRs) from 224,212 adults to estimate the odds ratios of receiving a prescription for different nervous system medications among patients with SCZ of different race/ethnicity, and analogous linear models to investigate differences in prescribed medication doses.

Effects of relative humidity on dry-aged beef quality.

This study was conducted to evaluate the effects of relative humidity (RH) on moisture loss and flavor in dry-aged beef. Sixteen strip loins were assigned to one of the four aging treatments: vacuum (WET), dry-aging at 50% RH, dry-aging at 70% RH, or dry-aging at 85% RH and aged for 42 days at 2 °C. Loins were evaluated for evaporation loss, trim loss, tenderness, sensory, and microbiological characteristics.

Discovery and Optimization of Potent and Orally Available CTP Synthetase Inhibitors for Use in Treatment of Diseases Driven by Aberrant Immune Cell Proliferation.

Herein, we report the discovery of a first-in-class chemotype 2-(alkylsulfonamido)thiazol-4-yl)acetamides that act as pan-selective inhibitors of cytidine 5'-triphosphate synthetase (CTPS1/2), critical enzymes in the pyrimidine synthesis pathway. Weak inhibitors identified from a high-throughput screening of 240K compounds have been optimized to a potent, orally active agent, compound , which has shown significant pharmacological responses at 10 mg/kg dose BID in a well-established animal model of inflammation.

Unconscious Influences on "Free Will" Movement Initiation: Slow-wave Brain Stimulation and the Readiness Potential.

A central objective in the study of volition has been to identify how changes in neural activity relate to voluntary-"free will"-movement. The readiness potential (RP) is observed in the EEG as a slow-building signal that precedes action onset. Many consider the RP as a marker of an underlying preparatory process for initiating voluntary movement.

Effects of Slow Oscillatory Transcranial Alternating Current Stimulation on Motor Cortical Excitability Assessed by Transcranial Magnetic Stimulation.

Converging evidence suggests that transcranial alternating current stimulation (tACS) may entrain endogenous neural oscillations to match the frequency and phase of the exogenously applied current and this entrainment may outlast the stimulation (although only for a few oscillatory cycles following the cessation of stimulation). However, observing entrainment in the electroencephalograph (EEG) during stimulation is extremely difficult due to the presence of complex tACS artifacts. The present study assessed entrainment to slow oscillatory (SO) tACS by measuring motor cortical excitability across different oscillatory phases during (i.

Oxidative stress and postmortem meat quality in crossbred lambs.

The objective of this study was to evaluate effects of different levels of lipopolysaccharide (LPS)-mediated oxidative stress on fresh meat quality. Crossbred lambs (n = 29) were blocked by weight and fed a standard finishing ration for the duration of the study. Lambs were individually housed and treatment groups were administered one of three intravenous injections every 72 h across a three-injection (9-day) cycle: saline control (control), 50 ng LPS/kg body weight (BW) (LPS50), or 100 ng LPS/kg BW (LPS100).

Ultimate pH effects on dry-aged beef quality.

This study aimed to evaluate pH effects on moisture loss and meat quality characteristics of dry-aged beef. Strip loins from six normal pH carcasses (pH = 5.47 ± 0.

Derivatisation of parthenolide to address chemoresistant chronic lymphocytic leukaemia.

Parthenolide is a natural product that exhibits anti-leukaemic activity, however, its clinical use is limited by its poor bioavailability. It may be extracted from and protocols for growing, extracting and derivatising it are reported A novel parthenolide derivative with good bioavailability and pharmacological properties was identified through a screening cascade based on anti-leukaemic activity and calculated "drug-likeness" properties, and pharmacokinetics studies and hERG liability testing. studies showed the most promising derivative to have comparable anti-leukaemic activity to DMAPT, a previously described parthenolide derivative.

Impact of myoglobin oxygenation state prior to frozen storage on color stability of thawed beef steaks through retail display.

Consumers consider beef color to be an indicator of freshness and therefore it is a major factor when purchasing beef. The ideal conditions for maintaining color throughout retail display following frozen storage have yet to be well established. Therefore, the objective of this study was to determine the effects of myoglobin oxygenation levels (especially high oxygenation) during freezing on color stability of thawed steaks during retail display (RD) and to determine the impact that frozen storage duration, aging, and packaging films have on meat color after thawing under RD conditions.

Impact of myoglobin oxygenation level on color stability of frozen beef steaks.

The emerging market of frozen meat emphasizes the need to better understand beef surface discoloration and the ideal parameters of freezing beef to retain an acceptable color. The objectives of this study were to determine the impacts of myoglobin oxygenation level prior to freezing and frozen storage duration on frozen beef color. USDA Choice strip loins (n = 36) were aged for 4 d or 20 d.

Gamma coherence mediates interhemispheric integration during multiple object tracking.

Our ability to track the paths of multiple visual objects moving between the hemifields requires effective integration of information between the two cerebral hemispheres. Coherent neural oscillations in the gamma band (35-70 Hz) are hypothesized to drive this information transfer. Here we manipulated the need for interhemispheric integration using a novel multiple object tracking (MOT) task in which stimuli either moved between the two visual hemifields, requiring interhemispheric integration, or moved within separate visual hemifields.

Current challenges: the ups and downs of tACS.

The non-invasive delivery of electric currents through the scalp (transcranial electrical stimulation) is a popular tool for neuromodulation, mostly due to its highly adaptable nature (waveform, montage) and tolerability at low intensities (< 2 mA). Applied rhythmically, transcranial alternating current stimulation (tACS) may entrain neural oscillations in a frequency- and phase-specific manner, providing a causal perspective on brain-behaviour relationships. While the past decade has seen many behavioural and electrophysiological effects of tACS that suggest entrainment-mediated effects in the brain, it has been difficult to reconcile such reports with the weak intracranial field strengths (< 1 V/m) achievable at conventional intensities.

Rapid recalibration of temporal order judgements: Response bias accounts for contradictory results.

Recent history influences subsequent perception, decision-making and motor behaviours. In this article, we address a discrepancy in the effects of recent sensory history on the perceived timing of auditory and visual stimuli. In the synchrony judgement (SJ) task, similar timing relationships in consecutive trials seem more synchronous (i.

No Evidence for Phase-Specific Effects of 40 Hz HD-tACS on Multiple Object Tracking.

Phase synchronization drives connectivity between neural oscillators, providing a flexible mechanism through which information can be effectively and selectively routed between task-relevant cortical areas. The ability to keep track of objects moving between the left and right visual hemifields, for example, requires the integration of information between the two cerebral hemispheres. Both animal and human studies have suggested that coherent (or phase-locked) gamma oscillations (30-80 Hz) might underlie this ability.

Evaluation of pyrrolidine and pyrazolone derivatives as inhibitors of trypanosomal phosphodiesterase B1 (TbrPDEB1).

Human African trypanosomiasis (HAT) is a parasitic disease, caused by the protozoan pathogen , which affects thousands every year and which is in need of new therapeutics. Herein we report the synthesis and assessment of a series of pyrrolidine and pyrazolone derivatives of human phosphodiesterase 4 (hPDE4) inhibitors for the assessment of their activity against the trypanosomal phosphodiesterase TbrPDEB1. The synthesized compounds showed weak potency against TbrPDEB1.

Repurposing human PDE4 inhibitors for neglected tropical diseases. Evaluation of analogs of the human PDE4 inhibitor GSK-256066 as inhibitors of PDEB1 of Trypanosoma brucei.

Cyclic nucleotide phosphodiesterases (PDEs) have been identified as important enzyme targets for drug development in both humans and Trypanosoma brucei, the causative agent of human African trypanosomiasis. With this in mind, we recently reported the profiling of a range of human phosphodiesterase inhibitors, showing that human PDE4 inhibitors tend to display the best potency against the trypanosomal phosphodiesterase TbrPDEB1. Among these was GSK-256066, a potent inhibitor of human PDE4 and a weak inhibitor of TbrPDEB1.

Repurposing human PDE4 inhibitors for neglected tropical diseases: design, synthesis and evaluation of cilomilast analogues as Trypanosoma brucei PDEB1 inhibitors.

A medicinal chemistry exploration of the human phosphodiesterase 4 (hPDE4) inhibitor cilomilast (1) was undertaken in order to identify inhibitors of phosphodiesterase B1 of Trypanosoma brucei (TbrPDEB1). T. brucei is the parasite which causes African sleeping sickness, a neglected tropical disease that affects thousands each year, and TbrPDEB1 has been shown to be an essential target of therapeutic relevance.

Synthesis and assessment of catechol diether compounds as inhibitors of trypanosomal phosphodiesterase B1 (TbrPDEB1).

Human African trypanosomiasis (HAT) is a parasitic neglected tropical disease that affects 10,000 patients each year. Current treatments are sub-optimal, and the disease is fatal if not treated. Herein, we report our continuing efforts to repurpose the human phosphodiesterase 4 (hPDE4) inhibitor piclamilast to target trypanosomal phosphodiesterase TbrPDEB1.

Synthesis and evaluation of human phosphodiesterases (PDE) 5 inhibitor analogs as trypanosomal PDE inhibitors. Part 2. Tadalafil analogs.

In this Letter we describe our ongoing target repurposing efforts focused on discovery of inhibitors of the essential trypanosomal phosphodiesterase TbrPDEB1. This enzyme has been implicated in virulence of Trypanosoma brucei, the causative agent of human African trypanosomiasis (HAT). We outline the synthesis and biological evaluation of analogs of tadalafil, a human PDE5 inhibitor currently utilized for treatment of erectile dysfunction, and report that these analogs are weak inhibitors of TbrPDEB1.

Synthesis and evaluation of human phosphodiesterases (PDE) 5 inhibitor analogs as trypanosomal PDE inhibitors. Part 1. Sildenafil analogs.

Parasitic diseases, such as African sleeping sickness, have a significant impact on the health and well-being in the poorest regions of the world. Pragmatic drug discovery efforts are needed to find new therapeutic agents. In this Letter we describe target repurposing efforts focused on trypanosomal phosphodiesterases.

Pharmacological validation of Trypanosoma brucei phosphodiesterases B1 and B2 as druggable targets for African sleeping sickness.

Neglected tropical disease drug discovery requires application of pragmatic and efficient methods for development of new therapeutic agents. In this report, we describe our target repurposing efforts for the essential phosphodiesterase (PDE) enzymes TbrPDEB1 and TbrPDEB2 of Trypanosoma brucei , the causative agent for human African trypanosomiasis (HAT). We describe protein expression and purification, assay development, and benchmark screening of a collection of 20 established human PDE inhibitors.

Crystal structure of Leishmania major oligopeptidase B gives insight into the enzymatic properties of a trypanosomatid virulence factor.

Oligopeptidase B (OPB) is a serine peptidase with dibasic substrate specificity. It is found in bacteria, plants, and trypanosomatid pathogens, where it has been identified as a virulence factor and potential drug target. In this study we expressed active recombinant Leishmania major OPB and provide the first structure of an oligopeptidase B at high resolution.

Acute superior vena cava obstruction following Ivor-Lewis oesophagectomy.

A 53 year old man developed upper body swelling, hypotension, anuria and a metabolic acidosis within 24 h following an Ivor-Lewis oesophagectomy. His co-morbidities included hypertension, hypercholesterolaemia, ischaemic heart disease and he was a smoker. He did not have radiotherapy but had received neo-adjuvant chemotherapy through an in-dwelling right subclavian central venous catheter.