Predictors for postoperative dysphagia in liver transplant recipients.

Introduction: Liver transplant recipients are at a heightened risk for oropharyngeal dysphagia; identification of those who are at high risk for postoperative dysphagia could reduce hospital costs and length of stay. We sought to identify predictors of dysphagia, in a large cohort of patients who underwent liver transplantation.

Methods: Electronic medical records were queried for patients undergoing liver transplantation, who underwent instrumental swallowing evaluations.

Multidisciplinary perspectives on roles of hospital pharmacists in tertiary settings: a qualitative study.

In today's complex healthcare landscape, exacerbated by resource constraints at various levels, optimization of health professionals' roles is becoming increasingly paramount. Interprofessional collaboration, underpinned by role recognition and teamwork, leads to improved patient and organizational outcomes. Hospital pharmacists play a pivotal role in multidisciplinary teams, and it is imperative to understand multidisciplinary viewpoints on hospital pharmacists' roles to guide role prioritization and organizational efficiency.

Characterisation of parasympathetic ascending nerves in human colon.

Background: In the human large bowel, sacral parasympathetic nerves arise from S2 to S4, project to the pelvic plexus ("hypogastric plexus") and have post-ganglionic axons entering the large bowel near the rectosigmoid junction. They then run long distances orally or aborally within the bowel wall forming "ascending nerves" or "shunt fascicles" running in the plane of the myenteric plexus. They form bundles of nerve fibres that can be distinguished from the myenteric plexus by their straight orientation, tendency not to merge with myenteric ganglia and greater width.

Drug utilization, clinical and economic outcomes of patients with osteoarthritis of the hip and/or knee treated with long-term use of traditional NSAIDs, topical NSAIDs, and COX-2 inhibitors.

Objectives: To describe and compare baseline characteristics, healthcare and drug utilization, and negative clinical outcomes of commercially-insured patients diagnosed with OA of the hip and/or knee who initiated treatment on traditional oral NSAIDs (tNSAIDs), topical NSAIDs, or cyclooxygenase-2 inhibitors (COX-2s).

Methods: A commercial claims database (1/2012-3/2017) was used to identify patients ≥18 years old, with ≥2 diagnoses of hip and/or knee OA, and ≥90 days supply of NSAIDs. Patients were assigned to cohorts based on the type of NSAID initially prescribed and observed in the 6 months before (baseline) and 36 months after (follow-up) the date of their first NSAID prescription after the first OA diagnosis.

Identifying rates and risk factors for medication errors during hospitalization in the Australian Parkinson's disease population: A 3-year, multi-center study.

Background: Admission to hospital introduces risks for people with Parkinson's disease in maintaining continuity of their highly individualized medication regimens, which increases their risk of medication errors. This is of particular concern as omitted medications and irregular dosing can cause an immediate increase in an individual's symptoms as well as other adverse outcomes such as swallowing difficulties, aspiration pneumonia, frozen gait and even potentially fatal neuroleptic malignant type syndrome.

Objective: To determine the occurrence and identify factors that contribute to Parkinson's medication errors in Australian hospitals.

Direct targeting of wild-type glucocerebrosidase by antipsychotic quetiapine improves pathogenic phenotypes in Parkinson's disease models.

Current treatments for Parkinson's disease (PD) provide only symptomatic relief, with no disease-modifying therapies identified to date. Repurposing FDA-approved drugs to treat PD could significantly shorten the time needed for and reduce the costs of drug development compared with conventional approaches. We developed an efficient strategy to screen for modulators of β-glucocerebrosidase (GCase), a lysosomal enzyme that exhibits decreased activity in patients with PD, leading to accumulation of the substrate glucosylceramide and oxidized dopamine and α-synuclein, which contribute to PD pathogenesis.

Heterozygous GBA D409V and ATP13a2 mutations do not exacerbate pathological α-synuclein spread in the prodromal preformed fibrils model in young mice.

Autophagic dysregulation and lysosomal impairment have been implicated in the pathogenesis of Parkinson's disease, partly due to the identification of mutations in multiple genes involved in these pathways such as GBA, SNCA, ATP13a2 (also known as PARK9), TMEM175 and LRRK2. Mutations resulting in lysosomal dysfunction are proposed to contribute to Parkinson's disease by increasing α-synuclein levels, that in turn may promote aggregation of this protein. Here, we used two different genetic models-one heterozygous for a mutated form of the GBA protein (D409V), and the other heterozygous for an ATP13a2 loss-of-function mutation, to test whether these mutations exacerbate the spread of α-synuclein pathology following injection of α-synuclein preformed fibrils in the olfactory bulb of 12-week-old mice.

Disease risk scores for skin cancers.

We trained and validated risk prediction models for the three major types of skin cancer- basal cell carcinoma (BCC), squamous cell carcinoma (SCC), and melanoma-on a cross-sectional and longitudinal dataset of 210,000 consented research participants who responded to an online survey covering personal and family history of skin cancer, skin susceptibility, and UV exposure. We developed a primary disease risk score (DRS) that combined all 32 identified genetic and non-genetic risk factors. Top percentile DRS was associated with an up to 13-fold increase (odds ratio per standard deviation increase >2.

Deficits in olfactory sensitivity in a mouse model of Parkinson's disease revealed by plethysmography of odor-evoked sniffing.

Hyposmia is evident in over 90% of Parkinson's disease (PD) patients. A characteristic of PD is intraneuronal deposits composed in part of α-synuclein fibrils. Based on the analysis of post-mortem PD patients, Braak and colleagues suggested that early in the disease α-synuclein pathology is present in the dorsal motor nucleus of the vagus, as well as the olfactory bulb and anterior olfactory nucleus, and then later affects other interconnected brain regions.

Inhibiting the mitochondrial pyruvate carrier does not ameliorate synucleinopathy in the absence of inflammation or metabolic deficits.

Epidemiological studies suggest a link between type-2 diabetes and Parkinson's disease (PD) risk. Treatment of type-2 diabetes with insulin sensitizing drugs lowers the risk of PD. We previously showed that the insulin sensitizing drug, MSDC-0160, ameliorates pathogenesis in some animal models of PD.

Predictors of High-cost Patients With Noninfectious Inflammatory Eye Diseases.

Purpose: Noninfectious inflammatory eye diseases (NIIEDs), such as uveitis, is a general term used to describe a complex mix of acute, chronic, allergic, and inflammatory disorders. Prior literature has established that, in addition to severe clinical burden, NIIEDs is associated with significant economic burden for US payers; however, no literature provides a current estimate of the economic burden associated with patients with high-cost NIIEDs. This study aimed to better understand the cost and resource use distribution and predictors of patients with high-cost NIIEDs.

Economic Burden of Non-Infectious Inflammatory Eye Disease (NIIED) in a Commercially-Insured Population in the United States.

: To assess the economic burden of non-infectious inflammatory eyedisease (NIIED) in a commercially-insured population in the United States: Adult patients with a NIIED diagnosis between 2006 and 2015 were selected from a de-identified, privately insured claims database and were matched 1:1 to a non-NIIED control. Ophthalmologic complications, direct healthcare resource use and costs, and indirect work loss (from the payer perspective) were calculated for a 12-month period and compared across the 2 cohorts.: Among the 14 876 matched pairs, NIIED patients were significantly more likely than controls to experience ocular complications, including glaucoma and cataracts ( < 0.

The effects of rotenone on TH, BDNF and BDNF-related proteins in the brain and periphery: Relevance to early Parkinson's disease.

Loss of dopaminergic neurons in the substantia nigra (SN) is one of the pathological hallmarks in Parkinson's disease (PD). This neuron loss is accompanied by reduced protein and activity levels of tyrosine hydroxylase (TH), the rate-limiting enzyme of catecholamine synthesis. Reduced nigral brain-derived neurotrophic factor (BDNF) has been postulated to contribute to the loss of nigral dopaminergic neurons in PD by causing a lack of trophic support.

Triggers, Facilitators, and Aggravators: Redefining Parkinson's Disease Pathogenesis.

We hypothesize that Parkinson's disease (PD) pathogenesis can be divided into three temporal phases. During the first phase, 'triggers', such as viral infections or environmental toxins, spark the disease process in the brain and/or peripheral tissues. Triggers alone, however, may be insufficient, requiring 'facilitators' like peripheral inflammation for PD pathology to develop.

Healthcare resource use and cost associated with varying dosages of extended corticosteroid exposure in a US population.

Aims: To quantify healthcare resource use (HCRU) and costs associated with varying levels of corticosteroid exposure.

Materials And Methods: Patients with a diagnosis of selected autoimmune and inflammatory diseases between 1 January 2006 and 30 September 2015 ("study period") were selected from a de-identified, privately-insured claims database. Patients were stratified into four treatment cohorts based on the dosing and duration of continuous corticosteroid use following disease diagnosis: intermittent use with <60 days of corticosteroid use and ≥60 days of corticosteroid use with low (≤7.

Quantitative characterization of the relationship between levels of extended corticosteroid use and related adverse events in a US population.

Objective: This retrospective study assessed the incidence and timing of adverse events (AEs) among patients prescribed varying dose levels of corticosteroids in the US.

Methods: Patients with selected autoimmune or inflammatory disease diagnoses between 2006 and 2015 were identified from a privately insured administrative database. Patients were stratified into treatment cohorts based on dosage and length of corticosteroid use: intermittent use with duration <60 days, and three extended use cohorts with duration ≥60 days at low (≤7.

Rotenone induces gastrointestinal pathology and microbiota alterations in a rat model of Parkinson's disease.

While people are often aware of the motor symptoms in Parkinson's disease (PD), few know of the many non-motor symptoms, which patients report have a greater impact on their quality of life. Gastrointestinal (GI) dysfunction is one of the most common non-motor symptoms, which can occur at any stage of PD, even years prior to diagnosis, and can affect all sections along the GI tract causing a range of symptoms including drooling, gastroparesis and constipation. We have investigated whether a neurotoxin model of PD induced by rotenone, a mitochondrial complex I inhibitor, is capable of reproducing the GI dysfunction seen clinically.

The Effects of Insulin-Induced Hypoglycaemia on Tyrosine Hydroxylase Phosphorylation in Rat Brain and Adrenal Gland.

In this study we investigated the effects of insulin-induced hypoglycaemia on tyrosine hydroxylase (TH) protein and TH phosphorylation in the adrenal gland, C1 cell group, locus coeruleus (LC) and midbrain dopaminergic cell groups that are thought to play a role in response to hypoglycaemia and compared the effects of different concentrations of insulin in rats. Insulin (1 and 10 U/kg) treatment caused similar reductions in blood glucose concentration (from 7.5-9 to 2-3 mmol/L); however, plasma adrenaline concentration was increased 20-30 fold in response to 10 U/kg insulin and only 14 fold following 1 U/kg.

Investigation of tyrosine hydroxylase and BDNF in a low-dose rotenone model of Parkinson's disease.

Tyrosine hydroxylase (TH, the rate limiting-enzyme in catecholamine synthesis) is regulated acutely via phosphorylation of 3 serine residues--Ser19, 31 and 40, and chronically via changes in TH protein levels. In this study, we aimed to investigate how TH is regulated in the brain, gut and adrenal gland as well as changes in mature brain-derived neurotrophic factor (mBDNF) and proBDNF levels in a low-dose (2 mg/kg, 5 days/week for 4 weeks) rotenone model of Parkinson's disease (PD). Rearing behaviour decreased by week 3 in the rotenone group (p<0.

Effects of the Young Adolescent Sleep Smart Program on sleep hygiene practices, sleep health efficacy, and behavioral well-being.

Objectives: Using a social learning model, the aim of the Sleep Smart Program was to primarily improve sleep health behaviors and secondarily improve academic performance and behavioral well-being.

Design: Randomized control trial for a social learning-based preventive intervention program.

Participants: A diverse group of seventh graders from 2 urban, middle schools were randomly assigned, according to school, to an 8-session Sleep Smart Program (SS = 70) or a comparison group (comparison = 73).

An update on the rotenone models of Parkinson's disease: their ability to reproduce the features of clinical disease and model gene-environment interactions.

Parkinson's disease (PD) is the second most common neurodegenerative disorder that is characterized by two major neuropathological hallmarks: the degeneration of dopaminergic neurons in the substantia nigra (SN) and the presence of Lewy bodies in the surviving SN neurons, as well as other regions of the central and peripheral nervous system. Animal models have been invaluable tools for investigating the underlying mechanisms of the pathogenesis of PD and testing new potential symptomatic, neuroprotective and neurorestorative therapies. However, the usefulness of these models is dependent on how precisely they replicate the features of clinical PD with some studies now employing combined gene-environment models to replicate more of the affected pathways.