Dopamine neuron dysfunction and loss in the PrknR275W mouse model of juvenile parkinsonism.

Mutations in the PRKN gene encoding the protein parkin cause autosomal recessive juvenile parkinsonism (ARJP). Harnessing this mutation to create an early-onset Parkinson's disease mouse model would provide a unique opportunity to clarify the mechanisms involved in the neurodegenerative process and lay the groundwork for the development of neuroprotective strategies. To this end, we created a knock-in mouse carrying the homozygous PrknR275W mutation, which is the missense mutation with the highest allelic frequency in PRKN patients.

Toward robust quantification of dopamine and serotonin in mixtures using nano-graphitic carbon sensors.

Monitoring the coordinated signaling of dopamine (DA) and serotonin (5-HT) is important for advancing our understanding of the brain. However, the co-detection and robust quantification of these signals at low concentrations is yet to be demonstrated. Here, we present the quantification of DA and 5-HT using nano-graphitic (NG) sensors together with fast-scan cyclic voltammetry (FSCV) employing an engineered N-shape potential waveform.

A Focused Addiction Curriculum and Its Impact on Student Knowledge, Attitudes, and Confidence in the Treatment of Patients with Substance Use.

Background: Assessment of attitudes towards addiction in medical students has largely gone unexplored. This study examines the impact of a supplemental substance use disorder curriculum in the psychiatry clerkship on medical student attitudes towards addiction.

Methods: The curriculum was only administered to students at one clerkship site.

Potential collaboration with the private sector for the provision of ambulatory care in the Mekong region, Vietnam.

Background: Over the past two decades, health insurance in Vietnam has expanded nationwide. Concurrently, Vietnam's private health sector has developed rapidly and become an increasingly integral part of the health system. To date, however, little is understood regarding the potential for expanding public-private partnerships to improve health care access and outcomes in Vietnam.

Mechanisms of obesity and related pathologies: androgen deficiency and endothelial dysfunction may be the link between obesity and erectile dysfunction.

Obesity is associated with a high prevalence of erectile dysfunction; however, the pathophysiological link between obesity and erectile dysfunction remains poorly understood. In this minireview, we have attempted to evaluate the existing literature pertaining to obesity and erectile dysfunction to determine whether a common pathophysiological link exists. Visceral obesity is associated with increased inflammatory responses, which contribute to endothelial dysfunction.

Obesity and erectile dysfunction: is androgen deficiency the common link?

Obesity is associated with increased risk of erectile dysfunction (ED); however, the underlying causes of ED in obese individuals remain poorly defined. The aim of this review is to discuss the evidence available on the relationship between obesity and ED. A search of published studies in PubMed from 1970 through 2009 was conducted, and relevant articles were evaluated and discussed.

The dark side of testosterone deficiency: III. Cardiovascular disease.

A considerable body of evidence exists suggesting that androgen deficiency contributes to the onset, progression, or both of cardiovascular disease (CVD). The aim of this review is to evaluate the relationships between testosterone (T) deficiency and risk factors of CVD and to discuss the implications of androgen deficiency in men with cardiovascular risk factors. The relationship between androgen deficiency and endothelial function, lipid profiles, inflammatory responses, altered vascular smooth muscle reactivity, and hypertension are discussed with regard to CVD.

Testosterone therapy in women with gynecological and sexual disorders: a triumph of clinical endocrinology from 1938 to 2008.

Introduction: Although the term "medicalization" has been used by some to describe contemporary testosterone use in women with sexual disorders and testosterone deficiency syndrome, testosterone therapy for women with various gynecological and sexual disorders has been practiced since the late 1930s.

Aim: The study aimed to perform a historical review of testosterone use in women with sexual and gynecological disorders. This review is necessary to bridge important knowledge gaps in the clinical use of testosterone in women with sexual health concerns and to provoke new thoughts and understanding of the multidisciplinary role of testosterone in women's overall health.

The dark side of testosterone deficiency: I. Metabolic syndrome and erectile dysfunction.

The metabolic syndrome (MetS) is considered the most important public health threat of the 21st century. This syndrome is characterized by a cluster of cardiovascular risk factors including increased central abdominal obesity, elevated triglycerides, reduced high-density lipoprotein, high blood pressure, increased fasting glucose, and hyperinsulinemia. These factors increase the risk of cardiovascular disease (CVD) and/or type 2 diabetes.

Sensitivity analysis of uncertainty in model prediction.

Data Collaboration is a framework designed to make inferences from experimental observations in the context of an underlying model. In the prior studies, the methodology was applied to prediction on chemical kinetics models, consistency of a reaction system, and discrimination among competing reaction models. The present work advances Data Collaboration by developing sensitivity analysis of uncertainty in model prediction with respect to uncertainty in experimental observations and model parameters.

Effects of parental anxiety disorders in children at high risk for panic disorder: a controlled study.

Background: To examine the association between anxiety disorders in parents and offspring in a sample of children at risk for panic disorder. We hypothesized that individual anxiety disorders will breed true in offspring.

Methods: Comparisons were made between offspring of parents with PD+MD (N=136), PD (N=27), MD (N=27), and Controls (N=103).

Model discrimination using data collaboration.

This paper introduces a practical data-driven method to discriminate among large-scale kinetic reaction models. The approach centers around a computable measure of model/data mismatch. We introduce two provably convergent algorithms that were developed to accommodate large ranges of uncertainty in the model parameters.

The impact of acculturation on smoking in Asian American homes.

This study examined the relationship between acculturation and smoking in Asian American homes and the factors that predict whether Asian Americans have family members or visitors smoking in the home. A sample of 1,374 participants was selected using a stratified-cluster proportional sampling technique. Overall, 38.

Perceptions of risks of smoking among Asian Americans.

Background: Tobacco use is the single most preventable cause of illness and death in the United States. Few studies focus on Asian Americans, one of the fastest growing but underserved populations in the United States.

Methods: A cross-sectional survey method was used for this study.

Perceived risks of certain types of cancer and heart disease among Asian American smokers and non-smokers.

This study assessed knowledge levels of health risks of tobacco use among the Asian American (AA) community in the Delaware Valley region of Pennsylvania and New Jersey, including metropolitan Philadelphia. A cross-sectional self-report survey was conducted to collect the information, and a stratified-cluster proportional sampling technique was used to obtain a representative sample size of the target population of Chinese, Korean, Vietnamese, and Cambodians. 1374 AA were recruited from 26 randomly selected community organization clusters; of the total recruited, 1174 completed the survey, which consisted of 410 Chinese, 436 Korean, 196 Vietnamese, 100 Cambodian and 32 other-group.

Increased LDL cholesterol and atherosclerosis in LDL receptor-deficient mice with attenuated expression of scavenger receptor B1.

Scavenger receptor BI (SR-BI) is a multiligand cell-surface receptor that plays a central role in high density lipoprotein homeostasis in rodents. To investigate a role for SR-BI in atherosclerosis, mice with attenuated SR-BI expression were crossed with low density lipoprotein (LDL) receptor-deficient mice. Compound-homozygous mutants showed increased plasma cholesterol, surprisingly due primarily to increased LDL cholesterol and apolipoprotein B levels.

Vascular MADs: two novel MAD-related genes selectively inducible by flow in human vascular endothelium.

Vascular endothelium is an important transducer and integrator of both humoral and biomechanical stimuli within the cardiovascular system. Utilizing a differential display approach, we have identified two genes, Smad6 and Smad7, encoding members of the MAD-related family of molecules, selectively induced in cultured human vascular endothelial cells by steady laminar shear stress, a physiologic fluid mechanical stimulus. MAD-related proteins are a recently identified family of intracellular proteins that are thought to be essential components in the signaling pathways of the serine/threonine kinase receptors of the transforming growth factor beta superfamily.

Cosmetics and the esthetic patient and laboratory communication.

With increasing consumer awareness of the innovative procedures available for cosmetic dentistry, this area of practice is growing rapidly and has become an excellent source for patient referrals. Unfortunately, it can also be a large source of stress for the practitioner. Esthetics has been described by The Pocket Oxford Dictionary as "the philosophy of beautiful"; its perception varies from individual to individual.

Use of exogenous glutathione for metabolism of peroxidized methyl linoleate in rat small intestine.

The potential effects of dietary glutathione on the metabolism of peroxidized lipid ingested in the diet were studied using everted sacs of rat small intestine and peroxidized methyl linoleate. Peroxidized methyl linoleate was added to the luminal side, and the appearance of thiobarbituric acid-reactive (TBA-reactive) material on the contraluminal side was measured. Incubation with N,N,bis(2-chloroethyl)-N-nitrosourea (BCNU) under conditions in which it inhibits the glutathione disulfide reductase/glutathione peroxidase system increased the appearance of TBA-reactive material, indicating that at least a portion of the TBA-reactive material passing through the epithelium is peroxide in nature.

Hypercysteinemia and delayed sulfur excretion in cirrhotics after oral cysteine loads.

Biosynthesis of cysteine from methionine via the hepatic transsulfuration pathway is impaired in some cirrhotic patients, who therefore might require cysteine in the diet. However, because further metabolism of cysteine also occurs primarily in the liver, the metabolic clearance of this amino acid could be impaired in cirrhosis. We administered oral loads of L-cysteine to cirrhotic patients and healthy volunteers.

Calcium, phosphorus, and magnesium contents of human milk during early lactation.

Early milk samples from 102 American mothers were examined for Ca, P, and Mg contents in relation to stage of lactation, intake of prenatal mineral supplements, maternal age, parity, and previous history of lactation. A total of 415 samples were collected at three stages of lactation: early transitional (4-7 days postpartum); transitional (10-14 days postpartum); and mature (30-45 days postpartum). No diurnal variations in element concentrations were observed in representative samples of late evening (PM) and early morning (AM) feedings collected during the transitional and mature stages.

Copper, iron, and zinc contents of human milk at early stages of lactation.

The Cu, Fe, and Zn contents of early milk from 102 American mothers were examined in relation to stage of lactation, intake of prenatal mineral supplements, maternal age, parity, and previous history of lactation. A total of 412 samples was collected at three stages of lactation: early transitional (4 to 7 days postpartum); transitional (10 to 14 days postpartum); and mature (30 to 45 days postpartum). For the transitional and mature stages, representative samples of late evening (PM) and early morning (AM) feedings were collected.

Structural codes and patient safety: does strict compliance make sense?

The authors of this Comment note recent trends rigidifying the enforcement of building and safety codes for health care facilities and compare the estimated costs (in terms of dollars spent) of those trends with their anticipated benefits (in terms of potential years of human life saved). They estimate that for each potential year of life saved, strict enforcement of the Life Safety Code of the National Fire Protection Association would cost $12.7 to $63.