Exploring sexual health and risk of sexually transmitted infections among gender diverse individuals.

Transgender, non-binary, gender non-conforming, and other gender diverse individuals (TGN) may be at higher risk of sexually transmitted infections (STIs). Transgender women specifically bear a disproportionate burden of HIV and other STIs worldwide. This study describes STI knowledge, risks, and prevention practices among TGN to better characterize barriers to sexual health care and identify potential platforms for sexual health education focusing on STI prevention.

Cognitive and motor function in long-duration PARKIN-associated Parkinson disease.

Importance: Data on the long-term cognitive outcomes of patients with PARKIN-associated Parkinson disease (PD) are unknown but may be useful when counseling these patients.

Objective: Among patients with early-onset PD of long duration, we assessed cognitive and motor performances, comparing homozygotes and compound heterozygotes who carry 2 PARKIN mutations with noncarriers.

Design, Setting, And Participants: Cross-sectional study of 44 participants at 17 different movement disorder centers who were in the Consortium on Risk for Early-Onset PD study with a duration of PD greater than the median duration (>14 years): 4 homozygotes and 17 compound heterozygotes (hereafter referred to as carriers) and 23 noncarriers.

Cognitive performance of GBA mutation carriers with early-onset PD: the CORE-PD study.

Objective: To assess the cognitive phenotype of glucocerebrosidase (GBA) mutation carriers with early-onset Parkinson disease (PD).

Methods: We administered a neuropsychological battery and the University of Pennsylvania Smell Identification Test (UPSIT) to participants in the CORE-PD study who were tested for mutations in PARKIN, LRRK2, and GBA. Participants included 33 GBA mutation carriers and 60 noncarriers of any genetic mutation.

The relation between depression and parkin genotype: the CORE-PD study.

Background: Mutations in parkin are a known genetic risk factor for early onset Parkinson's disease (EOPD) but their role in non-motor manifestations is not well established. Genetic factors for depression are similarly not well characterized. We investigate the role of parkin mutations in depression among those with EOPD and their relatives.

Olfaction in Parkin heterozygotes and compound heterozygotes: the CORE-PD study.

Background: While Parkinson disease (PD) is consistently associated with impaired olfaction, one study reported better olfaction among Parkin mutation carriers than noncarriers. Whether olfaction differs between Parkin mutation heterozygotes and carriers of 2 Parkin mutations (compound heterozygotes) is unknown.

Objective: To assess the relationship between Parkin genotype and olfaction in PD probands and their unaffected relatives.

Neuropsychological Profile of Parkin Mutation Carriers with and without Parkinson Disease: The CORE-PD Study.

The cognitive profile of early onset Parkinson's disease (EOPD) has not been clearly defined. Mutations in the parkin gene are the most common genetic risk factor for EOPD and may offer information about the neuropsychological pattern of performance in both symptomatic and asymptomatic mutation carriers. EOPD probands and their first-degree relatives who did not have Parkinson's disease (PD) were genotyped for mutations in the parkin gene and administered a comprehensive neuropsychological battery.

Frequency of known mutations in early-onset Parkinson disease: implication for genetic counseling: the consortium on risk for early onset Parkinson disease study.

Objective: To assess the frequency and clinical characteristics of carriers of previously identified mutations in 6 genes associated with early-onset Parkinson disease (PD) and provide empirical data that can be used to inform genetic counseling.

Design: Cross-sectional observational study.

Setting: Thirteen movement disorders centers.

A pilot study of gene/gene and gene/environment interactions in Alzheimer disease.

Background: Although some genes associated with increased risk of Alzheimer Disease (AD) have been identified, few data exist related to gene/gene and gene/environment risk of AD. The purpose of this pilot study was to explore gene/gene and gene/environment associations in AD and to obtain data for sample size estimates for larger, more definitive studies of AD.

Methods: The effect of gene/gene and gene/environment interaction related to late onset Alzheimer Disease (LOAD) was investigated in 153 subjects with LOAD and 302 gender matched controls enrolled in the Personalized Medicine Research Project, a population-based bio-repository.

Predictors of parkin mutations in early-onset Parkinson disease: the consortium on risk for early-onset Parkinson disease study.

Background: Mutations in the parkin gene are the most common genetic cause of early-onset Parkinson disease (PD). Results from a multicenter study of patients with PD systematically sampled by age at onset have not been reported to date.

Objective: To determine risk factors associated with carrying parkin mutations.

Self-report of cognitive impairment and mini-mental state examination performance in PRKN, LRRK2, and GBA carriers with early onset Parkinson's disease.

While little is known about risk factors for cognitive impairment in early onset Parkinson disease (EOPD), postmortem studies have shown an association between dementia with Lewy bodies (DLB) and glucocerebrosidase (GBA) mutation. We compared Mini-Mental State Examination (MMSE) performance and self-reported cognitive impairment in 699 EOPD participants genotyped for mutations in parkin (PRKN), leucine-rich repeat kinase-2 (LRRK2), and GBA. Logistic regression was used to assess the association between reported cognitive impairment and MMSE score, as well as between GBA group membership and self-reported impairment and MMSE.

Motor phenotype of LRRK2 G2019S carriers in early-onset Parkinson disease.

Objective: To determine the motor phenotype of LRRK2 G2019S mutation carriers. LRRK2 mutation carriers were previously reported to manifest the tremor dominant motor phenotype, which has been associated with slower motor progression and less cognitive impairment compared with the postural instability and gait difficulty (PIGD) phenotype.

Design: Cross-sectional observational study.

Toward a commercial synthesis of (+)-discodermolide.

In this review some of the criteria required for a viable chemical (+)-discodermolide production process are discussed by critical evaluation of the available literature approaches. A further route involving the use of polyketide synthase to produce (+)-discodermolide fragments by fermentation is also described. Both approaches have advantages and disadvantages and require significant optimization in order to achieve commercialization of this important natural product.

Synthetic analogues of the microtubule-stabilizing agent (+)-discodermolide: preparation and biological activity.

A series of seven synthetic discodermolide analogues 2-8, which are minor side products generated during the final stages in the synthesis of (+)-discodermolide (1), have been purified and evaluated for in vitro cytotoxicity against A549, P388, MFC-7, NCI/ADR, PANC-1, and VERO cell lines. These synthetic analogues showed a significant variation of cytotoxicity and confirmed the importance of the C-7 hydroxy through C-17 hydroxy molecular fragment for potency. Specifically, these analogues suggested the relevance of the C-11 hydroxyl group, the C-13 double bond, and the C-16 (S) stereochemistry for the potency of (+)-discodermolide.

Ligands for expression cloning and isolation of GABA(B) receptors.

The scope of the plenary lecture at the occasion of the Xth Meeting on Heterocyclic Structures in Medicinal Chemistry, Palermo 2002, is considerably larger than that of the main lecture at the XVIth International Symposium on Medicinal Chemistry, Bologna 2000, described by Froestl et al. in Farmaco 56 (2001) 101. Additional information is presented, in particular, on the reaction conditions for the 31 step synthesis of the combined affinity chromatography and photoaffinity radioligand [125I]CGP84963 and on the recent developments of the molecular biology of GABA(B) receptors.

Predictors of nursing home admission and/or death in incident Alzheimer's disease and other dementia cases compared to controls: a population-based study.

This research elucidates the risk of institutional care and/or death of patients with Alzheimer's disease (AD) or other dementia (OD) compared with noncases. Community dwelling incident cases of AD (n = 240) or OD (n = 208) and age-matched noncases (n = 363) living in an enumerated population were included. The adjusted hazard ratio (HR) of being admitted to a nursing home compared with controls was 5.

Alzheimer's disease or other dementia and medical care utilization.

Purpose: Recent findings on medical care utilization among people with Alzheimer's disease (AD) or other dementia (OD) are conflicting. A population-based case-control study was designed to determine if patients with clinically diagnosed AD or OD have different medical care utilization patterns before and after diagnosis compared to age-matched controls.

Methods: All community dwelling incident cases of AD (n = 240) or OD (n = 208) diagnosed between July 1, 1992 and June 30, 1997, and age-matched controls (n = 363) living in an enumerated population, were included.

Ligands for expression cloning and isolation of GABA(B) receptors.

Outlined is the rationale behind the syntheses of radioligands [125I]CGP64213 and [125I]CGP71872, which led to the identification of cloned GABA(B) receptors 1a and 1b 17 years after the first pharmacological characterisation of native GABA(B) receptors by Bowery et al. [Nature 283 (1980) 92-94]. More recently it was shown that the N-terminal extracellular domains of GABA(B) receptors 1a and 1b contain the binding sites for agonists and antagonists [B.

Ligands for the isolation of GABA(B) receptors [corrected] .

Since the discovery that the most abundant inhibitory neurotransmitter in the mammalian brain, GABA (gamma-aminobutyric acid), interacts not only with ionotropic GABA(A) receptors, but also with metabotropic GABA(B) receptors (Bowery et al., 1980) much work has been devoted to the elucidation of the structure of GABA(B) receptors by either affinity chromatography purification or by expression cloning. In 1997 Kaupmann et al.

Morpholin-2-yl-phosphinic acids are potent GABA(B) receptor antagonists in rat brain.

The pharmacological properties of morpholin-2-yl-phosphinic acids were evaluated on GABA(B) receptors. In rat neocortical slices maintained in Mg2+-free Krebs medium, baclofen, a GABA(B) receptor agonist, produced a concentration-dependent depression of the frequency of spontaneous discharges with an EC50 of 14 +/- 5.5 microM, which was antagonised reversibly by the morpholin-2-yl-phosphinic derivatives.

Lack of overlap in genetic risks for Alzheimer's disease and Parkinson's disease.

We explored the question of genetic overlap between Alzheimer's disease (AD) and Parkinson's disease (PD) because evidence suggests clinical, pathologic, and epidemiologic overlap between the two disorders. We compared the frequency of AD and PD between the first-degree relatives of probands with AD and PD and first-degree relatives of spouse control subjects. Using life-table methods, we found increased risk of AD in first-degree relatives of patients with AD and an increased risk of PD in first-degree relatives of patients with PD.

Expression cloning of GABA(B) receptors uncovers similarity to metabotropic glutamate receptors.

GABA (gamma-amino-butyric acid), the principal inhibitory neurotransmitter in the brain, signals through ionotropic (GABA(A)/ GABA(c)) and metabotropic (GABA(B)) receptor systems. Here we report the cloning of GABA(B) receptors. Photoaffinity labelling experiments suggest that the cloned receptors correspond to two highly conserved GABA(B) receptor forms present in the vertebrate nervous system.

Determination of rat brain and plasma levels of the orally active GABAB antagonist 3-amino-propyl-n-butyl-phosphinic acid (CGP 36742) by a new GC/MS method.

An involvement of GABAergic neurons has been suggested in the process of memory consolidation based on anatomical evidence and increasing physiological and biochemical data. With the advent of orally active GABAB antagonists, such as CGP 36742, the question of their therapeutic value, for example in Alzheimer's disease, becomes relevant. Therefore, a new GC/MS method was developed to determine the concentration of CGP 36742 (3-amino-propyl-n-butyl phosphinic acid) in various intra- and extracerebral tissues after different routes of application.

Phosphinic acid analogues of GABA. 2. Selective, orally active GABAB antagonists.

In 1987, 25 years after the synthesis of the potent and selective GABAB agonist baclofen (1), Kerr et al. described the first GABAB antagonist phaclofen 2. However, phaclofen and structurally similar derivatives 3-5 did not cross the blood-brain barrier and hence were inactive in vivo as central nervous system agents.

Phosphinic acid analogues of GABA. 1. New potent and selective GABAB agonists.

The antispastic agent and muscle relaxant baclofen 1 is a potent and selective agonist for bicuculline-insensitive GABAB receptors. For many years efforts to obtain superior GABAB agonists were unsuccessful. We describe the syntheses and biological properties of two new series of GABAB agonists, the best compounds of which are more potent than baclofen in vitro and in vivo.

The relationship of farm residency status to demographic and service characteristics of agricultural injury victims in central Wisconsin.

This study performed a surveillance of a defined population in central Wisconsin during a two-year period that included six months of follow-up. The study included those who worked and lived on farms and those who only worked on farms. The injury rate for farm residents was 3.