Piperazinyl-glutamate-pyrimidines as potent P2Y12 antagonists for inhibition of platelet aggregation.

Piperazinyl-glutamate-pyrimidines were prepared with oxygen, nitrogen, and sulfur substitution at the 4-position of the pyrimidine leading to highly potent P2Y12 antagonists. In particular, 4-substituted piperidine-4-pyrimidines provided compounds with exceptional potency. Pharmacokinetic and physicochemical properties were fine-tuned through modifications at the 4-position of the piperidine ring leading to compounds with good human PRP potency, selectivity, clearance and oral bioavailability.

The relationship between cognitive function and physical performance in older women: results from the women's health initiative memory study.

Background: Cognitive function and physical performance are associated, but the common sequence of cognitive and physical decline remains unclear.

Methods: In the Women's Health Initiative Memory Study (WHIMS) clinical trial, we examined associations at baseline and over a 6-year follow-up period between the Modified Mini-Mental State (3MS) Examination and three physical performance measures (PPMs): gait speed (meters/second), chair stands (number of stands in 15 seconds), and grip strength (kilograms). Using mixed models, we examined the baseline 3MS as predictor of change in PPM, change in the 3MS as predictor of change in PPM, and baseline PPM as predictors of 3MS change.

Piperazinyl-glutamate-pyridines as potent orally bioavailable P2Y12 antagonists for inhibition of platelet aggregation.

Polymer-assisted solution-phase (PASP) parallel library synthesis was used to discover a piperazinyl-glutamate-pyridine as a P2Y(12) antagonist. Exploitation of this lead provided compounds with excellent inhibition of platelet aggregation as measured in a human platelet rich plasma (PRP) assay. Pharmacokinetic and physiochemical properties were optimized leading to compound (4S)-4-[({4-[4-(methoxymethyl)piperidin-1-yl]-6-phenylpyridin-2-yl}carbonyl)amino]-5-oxo-5-{4-[(pentyloxy)carbonyl]piperazin-1-yl}pentanoic acid 22J with good human PRP potency, selectivity, in vivo efficacy and oral bioavailability.

The effects of GABA transporter inhibition on synaptophysin and synaptotagmin expression in diazepam tolerance.

Background: In light of the differential interactions seen between benzodiazepine, GABA transporter (GAT) inhibition and drug tolerance, the locomotor effects of a GAT1-specific inhibitor (SKF89976A) following diazepam tolerance were analysed and compared with the concomitant expression of synaptic vesicle proteins implicated in synaptic plasticity.

Methods: Male PVG/OlaHsd rats were chronically dosed with diazepam to produce tolerance, and the expression of mRNA for synaptophysin and synaptotagmin were analysed in the hippocampus by means of in situ hybridisation. The action of the GAT inhibitor SKF89976A on the expression of these mRNAs, and on open field behaviour was subsequently observed.

Identifying mild cognitive impairment at baseline in the Ginkgo Evaluation of Memory (GEM) study.

Objectives: To identify, characterize and compare the frequency of mild cognitive impairment (MCI) subtypes at baseline in a large, late-life cohort (n = 3063) recruited into a dementia prevention trial.

Method: A retrospective, data-algorithmic approach was used to classify participants as cognitively normal or MCI with corresponding subtype (e.g.

[The BSD Health Study: a pilot study to examine the comparability of Bavarian blood donors with the Bavarian general population by a comparison with KORA S4].

Aim: The aim of this pilot study was to compare the health status of Bavarian blood donors to the general population in Bavaria (Southern Germany).

Methods: Blood donors in Bavaria were evaluated with respect to socio-demographic characteristics, smoking status and selected diseases. The subset of blood donors from rural areas and aged 35-74 years (n=1 187), was compared to participants in the population-based survey KORA S4 living in rural areas near Augsburg (n=1 870).

Itch characteristics in atopic dermatitis: results of a web-based questionnaire.

Background: Itch significantly impairs the quality of life of patients with atopic dermatitis. However, only a few previous studies have examined the specific characteristics of itch in atopic dermatitis.

Objective: To examine the frequency, intensity and perceived characteristics of pruritus among individuals with atopic dermatitis.

The association of dermatologist-diagnosed and self-reported skin diseases with skin-related quality of life in Latino migrant farmworkers.

Background: Skin diseases are known to affect the quality of life (QoL), but data to support this are based on clinical samples. Few data document the skin-related QoL in the general population, and whether its association differs with self-reported or dermatologist-diagnosed skin ailments. Farmworkers are at high risk for skin diseases, and are an appropriate population in which to explore these associations.

Self report of skin problems among farmworkers in North Carolina.

Background: This study estimates the prevalence of self-reported skin problems among Latino farmworkers and identifies associated risk factors.

Methods: The study used a longitudinal surveillance design. Participants were interviewed up to five times and reported skin problems and personal, work, and environment characteristics.

Qualitative longitudinal analysis of symptoms in patients with primary and metastatic brain tumours.

Primary and metastatic brain tumour patients are treated with surgery, radiation therapy and chemotherapy. Such treatments often result in short- and long-term symptoms that impact cognitive, emotional and physical function. Therefore, understanding the transition of symptom burden over time is important for guiding treatment and follow-up of brain tumour patients with symptom-specific interventions.

Diagnosed skin diseases among migrant farmworkers in North Carolina: prevalence and risk factors.

Skin diseases are common among farmworkers, yet little research documents their prevalence and risk factors. This analysis documents the prevalence of skin diseases among farmworkers in North Carolina, examines variation in the prevalence across the agricultural season, and delineates factors associated with skin disease. Data are from a longitudinal surveillance study with assessments at approximately three-week intervals from May through October 2005.

Symptom clusters in patients with newly-diagnosed brain tumors.

A symptom cluster comprises three or more concurrent symptoms. There is a paucity of symptom cluster research in cancer patients. Data from a previously conducted clinical trial were analyzed to search for symptom clusters.

A phase III, double-blind, placebo-controlled prospective randomized clinical trial of d-threo-methylphenidate HCl in brain tumor patients receiving radiation therapy.

Purpose: The quality of life (QOL) and neurocognitive function of patients with brain tumors are negatively affected by the symptoms of their disease and brain radiation therapy (RT). We assessed the effect of prophylactic d-threo-methylphenidate HCl (d-MPH), a central nervous system (CNS) stimulant on QOL and cognitive function in patients undergoing RT.

Methods And Materials: Sixty-eight patients with primary or metastatic brain tumors were randomly assigned to receive d-MPH or placebo.

Cognitive function, gait speed decline, and comorbidities: the health, aging and body composition study.

Background: Emerging evidence indicates an association between cognitive function and physical performance in late life. This study examines the relationship between cognitive function and subsequent gait speed decline among high-functioning older adults.

Methods: Measures of global cognitive function (Modified Mini Mental State Examination [3MS]) and executive control function (ECF) (a clock drawing task [CLOX 1] and the 15-item Executive Interview [EXIT 15]) were obtained in the Health, Aging, and Body Composition Study in 1999-2000.

[Diabetes study in Bavaria: known risk factors correlate with an increased level of HbA1c].

Background And Objective: Approximately six million Germans have been diagnosed with diabetes mellitus. A continuously increasing number of people with diabetes is expected within the next few years. Genetic disposition, age and especially lifestyle play an important role in the development of the disease.

Managing the cognitive effects of brain tumor radiation therapy.

Postoperative radiation therapy (RT), either alone or in combination with chemotherapy, is the mainstay of treatment for primary and/or metastatic brain tumors. The majority of patients with brain tumors will have significant symptoms of their disease and of RT that will have a negative impact on their quality of life and neurocognitive function. The symptoms of brain tumors depend on tumor location.

Social sensitivity and acne: the role of personality in negative social consequences and quality of life.

Background: Acne affects a majority of adolescents and a substantial number of adults. The adverse social impact of acne is well documented. Negative social consequences, however, are likely to be determined by personality features as well as acne severity.

Analysis and cryopreservation of hematopoietic stem and progenitor cells from umbilical cord blood.

Background: Umbilical cord blood (UCB) is an important source of hematopoietic stem and progenitor cells (HSC/HPC) for the reconstitution of the hematopoietic system after clinical transplantation. Cryopreservation of these cells is critical for UCB banking and transplantation as well as for research applications by providing readily available specimens. The objective of this study was to optimize cryopreservation conditions for CD34+ HSC/HPC from UCB.

Benchmarks for designing two-stage studies using modified mini-mental state examinations: experience from the Women's Health Initiative Memory Study.

Background: The most efficient approach for studies examining the incidence of dementia involves a brief screening instrument to identify participants for more extensive testing to identify cognitive impairment. The modified mini-mental state examination (3MS) is commonly used as this initial screen in such two-stage designs, however its properties for this role require further study.

Purpose: We use data from the Women's Health Initiative Memory Study to contrast design options in two-stage designs.

The Acne Quality of Life Index (Acne-QOLI): development and validation of a brief instrument.

Background: Acne affects many people and can be detrimental to affected patients' quality of life. Assessing the impact of acne on quality of life requires well-validated and reliable measures of acne-specific quality of life that are brief and easy to administer and interpret.

Objectives: This paper reports on the development and validation of the Acne Quality of Life Index (Acne-QOLI) for use in clinical care, research, and product development.

Skin disease among Latino farmworkers in North Carolina.

An estimated 4.2 million seasonal and migrant farmworkers and their dependents live in the U.S.

Association between alcohol intake and domain-specific cognitive function in older women.

Moderate levels of alcohol intake may be associated with better cognitive function; however, this relationship may vary between cognitive domains. Women, aged 65-80 years, enrolled in the Women's Health Initiative (WHI) randomized clinical trials of hormone therapy, underwent annual standardized testing for global cognitive function through the ancillary WHI Memory Study (average follow-up of 4.5 years) and domain-specific cognitive function through the WHI Study of Cognitive Aging (average follow-up of 1.

Effects of conjugated equine estrogen on stroke in the Women's Health Initiative.

Background: The Women's Health Initiative (WHI) Estrogen Alone trial assessed the balance of benefits and risks of hormone use in healthy postmenopausal women. The trial was stopped prematurely because there was no benefit for coronary heart disease and an increased risk of stroke. This report provides a thorough analysis of the stroke finding using the final results from the completed trial database.