NMR Spectroscopy as a Robust Tool for the Rapid Evaluation of the Lipid Profile of Fish Oil Supplements.

The western diet is poor in n-3 fatty acids, therefore the consumption of fish oil supplements is recommended to increase the intake of these essential nutrients. The objective of this work is to demonstrate the qualitative and quantitative analysis of encapsulated fish oil supplements using high-resolution H and C NMR spectroscopy utilizing two different NMR instruments; a 500 MHz and an 850 MHz instrument. Both proton (H) and carbon (C) NMR spectra can be used for the quantitative determination of the major constituents of fish oil supplements.

A recurrent de novo mutation in ACTG1 causes isolated ocular coloboma.

Ocular coloboma (OC) is a defect in optic fissure closure and is a common cause of severe congenital visual impairment. Bilateral OC is primarily genetically determined and shows marked locus heterogeneity. Whole-exome sequencing (WES) was used to analyze 12 trios (child affected with OC and both unaffected parents).

Mitochondrial respiration in highly aerobic canines in the non-raced state and after a 1600-km sled dog race.

At the annual Iditarod Race, Alaskan Huskies repeatedly run for up to 8 hours at 16 km/h to complete 1600 km. We previously demonstrated high rates of mitochondrial protein synthesis in Alaskan Huskies, which we suspected allowed rapid remodeling of mitochondrial proteins in response to energetic stress. The purpose of this study was to examine mitochondrial respiration in permeabilized skeletal muscle fibers of Alaskan Huskies in the offseason (Non-raced) and following the 1600 km Iditarod Sled Dog Race (Raced).

Novel lead structures with both Plasmodium falciparum gametocytocidal and asexual blood stage activity identified from high throughput compound screening.

Background: Blocking malaria transmission is an important step in eradicating malaria. In the field, transmission requires the production of sexual stage Plasmodium parasites, called gametocytes, which are not effectively killed by the commonly used anti-malarials allowing individuals to remain infectious after clearance of asexual parasites.

Methods: To identify new gametocytocidal compounds, a library of 45,056 compounds with diverse structures was screened using a high throughput gametocyte viability assay.

Comparison of three cell-based drug screening platforms for HSV-1 infection.

Acyclovir (ACV) and its derivatives have been highly effective for treating recurrent, lytic infections with Herpes Simplex Virus, type 1 (HSV-1), but searches for additional antiviral drugs are motivated by recent reports of resistance to ACV, particularly among immunocompromised patients. In addition, the relative neurotoxicity of ACV and its inability to prevent neurological sequelae among HSV-1 encephalitis survivors compel searches for new drugs to treat HSV-1 infections of the central nervous system (CNS). Primary drug screens for neurotropic viruses like HSV-1 typically utilize non-neuronal cell lines, but they may miss drugs that have neuron specific antiviral effects.

Resuscitation of from dormancy requires hibernation promoting factor (PA4463) for ribosome preservation.

biofilm infections are difficult to treat with antibiotic therapy in part because the biofilms contain subpopulations of dormant antibiotic-tolerant cells. The dormant cells can repopulate the biofilms following alleviation of antibiotic treatments. While dormant, the bacteria must maintain cellular integrity, including ribosome abundance, to reinitiate the de novo protein synthesis required for resuscitation.

Computer-determined dosage of insulin in the management of neonatal hyperglycaemia (HINT2): protocol of a randomised controlled trial.

Introduction: Neonatal hyperglycaemia is frequently treated with insulin, which may increase the risk of hypoglycaemia. Computer-determined dosage of insulin (CDD) with the STAR-GRYPHON program uses a computer model to predict an effective dose of insulin to treat hyperglycaemia while minimising the risk of hypoglycaemia. However, CDD models can require more frequent blood glucose testing than common clinical protocols.

SMCHD1 mutations associated with a rare muscular dystrophy can also cause isolated arhinia and Bosma arhinia microphthalmia syndrome.

Arhinia, or absence of the nose, is a rare malformation of unknown etiology that is often accompanied by ocular and reproductive defects. Sequencing of 40 people with arhinia revealed that 84% of probands harbor a missense mutation localized to a constrained region of SMCHD1 encompassing the ATPase domain. SMCHD1 mutations cause facioscapulohumeral muscular dystrophy type 2 (FSHD2) via a trans-acting loss-of-function epigenetic mechanism.

Use of hyaluronidase in the comparison between manual and automated hematology analysis with the ADVIA 120 to improve analysis of feline body cavity effusions.

Classification of body cavity effusions is an important step in the investigation and diagnosis of disease in cats. Feline inflammatory effusions are often highly proteinaceous and viscous, which can cause clumping of white cells and subsequently inaccurate nucleated cell counts (NCCs) using automated and manual methods. Microscopic assessment of cellularity can also be difficult given the variable thickness of smears and cell clumping, which skews white cell distribution.

Clinical outcome and predictors of adverse events of an enhanced older adult psychiatric liaison service: Rapid Assessment Interface and Discharge (Newport).

Background: Hospitals are currently admitting an increasing number of older people, and more than one-third could have an underlying mental health problem. The existing Older Adult Mental Health (OAMH) liaison service was increasingly unable to meet the escalating needs of older and frail patients. Therefore, the service was modernized and enhanced on an "invest-to-save" principle to provide a prompt holistic assessment for older adults with mental health problems.

Plasmodium falciparum genotype and gametocyte prevalence in children with uncomplicated malaria in coastal Ghana.

Background: Plasmodium falciparum gametocytes are vital to sustaining malaria transmission. Parasite densities, multiplicity of infection as well as asexual genotype are features that have been found to influence gametocyte production. Measurements of the prevalence of Plasmodium sp.

Validation of the prognostic value of histologic scoring systems in primary sclerosing cholangitis: An international cohort study.

Unlabelled: Histologic scoring systems specific for primary sclerosing cholangitis (PSC) are not validated. We recently determined the applicability and prognostic value of three histological scoring systems in a single PSC cohort. The aim of this study was to validate their prognostic use and reproducibility across a multicenter PSC cohort.

Exertional Hyponatremia and Serum Sodium Change During Ultraendurance Cycling.

Introduction: Exertional hyponatremia (EH) during prolonged exercise involves all avenues of fluid-electrolyte gain and loss. Although previous research implicates retention of excess fluid, EH may involve either loss, gain, or no change of body mass. Thus, the etiology, predisposing factors, and recommendations for prevention are vague-except for advice to avoid excessive drinking.

Inpatient healthcare utilisation in patients with alcoholic liver disease: what are the costs and outcomes?

Background: Alcoholic liver disease (ALD) carries a significant cost burden and often leads to inpatient care. It is unclear whether inpatient care for ALD is any more costly than admission for other reasons.

Aims: To compare the costs and outcomes of inpatient care for ALD to two groups: a control group of matched cases admitted in the same time frame and people admitted for other chronic liver diseases (CLD).

A Novel Tool for Assessment of Emergency Medicine Resident Skill in Determining Diagnosis and Management for Emergent Electrocardiograms: A Multicenter Study.

Background: Reading emergent electrocardiograms (ECGs) is one of the emergency physician's most crucial tasks, yet no well-validated tool exists to measure resident competence in this skill.

Objectives: To assess validity of a novel tool measuring emergency medicine resident competency for interpreting, and responding to, critical ECGs. In addition, we aim to observe trends in this skill for resident physicians at different levels of training.

Effect of Caffeine on Perceived Soreness and Functionality Following an Endurance Cycling Event.

Caldwell, AR, Tucker, MA, Butts, CL, McDermott, BP, Vingren, JL, Kunces, LJ, Lee, EC, Munoz, CX, Williamson, KH, Armstrong, LE, and Ganio, MS. Effect of caffeine on perceived soreness and functionality following an endurance cycling event. J Strength Cond Res 31(3): 638-643, 2017-Caffeine can reduce muscle pain during exercise; however, the efficacy of caffeine in improving muscle soreness and recovery from a demanding long-duration exercise bout has not been established.

The use of dextrose/insulin infusions during labour and delivery in women with gestational diabetes mellitus: Is there any point?

We compared, in 733 women with gestational diabetes mellitus treated with metformin and/or insulin, rates of neonatal hypoglycaemia in those who had received a dextrose/insulin infusion during labour and prior to delivery (n = 132) with those who did not (n = 601). Women who had infusions were more likely to have been treated with insulin (87.1% vs 70.

Identification of potent, selective KDM5 inhibitors.

This communication describes the identification and optimization of a series of pan-KDM5 inhibitors derived from compound 1, a hit initially identified against KDM4C. Compound 1 was optimized to afford compound 20, a 10nM inhibitor of KDM5A. Compound 20 is highly selective for the KDM5 enzymes versus other histone lysine demethylases and demonstrates activity in a cellular assay measuring the increase in global histone 3 lysine 4 tri-methylation (H3K4me3).

Comparative Proteomics and Functional Analysis Reveal a Role of Plasmodium falciparum Osmiophilic Bodies in Malaria Parasite Transmission.

An essential step in the transmission of the malaria parasite to the Anopheles vector is the transformation of the mature gametocytes into gametes in the mosquito gut, where they egress from the erythrocytes and mate to produce a zygote, which matures into a motile ookinete. Osmiophilic bodies are electron dense secretory organelles of the female gametocytes which discharge their contents during gamete formation, suggestive of a role in gamete egress. Only one protein with no functional annotation, Pfg377, is described to specifically reside in osmiophilic bodies in Plasmodium falciparum Importantly, Pfg377 defective gametocytes lack osmiophilic bodies and fail to infect mosquitoes, as confirmed here with newly produced pfg377 disrupted parasites.

Behavioural and neuroimaging correlates of impaired self-awareness of hypo- and hyperkinesia in Parkinson's disease.

Introduction: Anosognosia or impaired self-awareness of motor symptoms (ISAm) has been rarely investigated in Parkinson's disease (PD). We here studied the relationship between ISAm during periods with and without dopaminergic medication (ON- and OFF-state), and clinical, neuropsychological, and neuroimaging data to further elucidate behavioural aspects and the neurobiological underpinnings of ISAm.

Methods: Thirty-one right-handed, non-demented, non-depressed PD patients were included.

An inhibitor of KDM5 demethylases reduces survival of drug-tolerant cancer cells.

The KDM5 family of histone demethylases catalyzes the demethylation of histone H3 on lysine 4 (H3K4) and is required for the survival of drug-tolerant persister cancer cells (DTPs). Here we report the discovery and characterization of the specific KDM5 inhibitor CPI-455. The crystal structure of KDM5A revealed the mechanism of inhibition of CPI-455 as well as the topological arrangements of protein domains that influence substrate binding.

In vitro evaluation of imidazo[4,5-c]quinolin-2-ones as gametocytocidal antimalarial agents.

Novel imidazo[4,5-c]quinolin-2-ones were synthesized and evaluated in asexual blood stage and late stage gametocyte assays of Plasmodium falciparum, a major causative agent of malaria. The design of these compounds is based on a recently identified lead compound from a high throughput screen. A concise synthesis was developed that allowed for generation of analogues with substitution around both the quinoline and imidazolidinone rings.

Genetic Analysis of 'PAX6-Negative' Individuals with Aniridia or Gillespie Syndrome.

We report molecular genetic analysis of 42 affected individuals referred with a diagnosis of aniridia who previously screened as negative for intragenic PAX6 mutations. Of these 42, the diagnoses were 31 individuals with aniridia and 11 individuals referred with a diagnosis of Gillespie syndrome (iris hypoplasia, ataxia and mild to moderate developmental delay). Array-based comparative genomic hybridization identified six whole gene deletions: four encompassing PAX6 and two encompassing FOXC1.