Sexual needs and sexual function of patients with Parkinson's disease.

BACKGROUND: Sexual dysfunction (SD) is a frequent non-motor symptom in Parkinson's disease (PD) that is rarely addressed, and sexual counseling is sporadic. OBJECTIVES: To investigate PD patients' SD and sexual counseling motivation and to propose an interventional strategy for movement disorder specialists. METHODS: All consecutive PD patients who presented to a movement disorder unit between 2018 and 2019 completed anonymous questionnaires containing the Female Sexual Function Index, the International Index of Erectile Function, and a questionnaire on sexual needs and motivation to receive sexual counseling. RESULTS: The age range of the 100 recruited patients (78 men) was 40-80 years, and the mean disease duration was 8.64 ± 6.84 years. SD appeared at all PD stages. The presence of SD pre-PD diagnosis significantly predicted SD post-diagnosis in men. Erectile dysfunction was the most common male SD (70%). Women reported frequent SD before PD diagnosis and currently. More than half of the responders (74% of the men and 40% of the women) were motivated to receive sexual counseling. Most of them (77.4%) were in a relationship. CONCLUSIONS: The findings of this analysis revealed that most PD patients had experienced SD before being diagnosed with PD and were interested in receiving sexual counseling. We propose a six-step intervention strategy for the management of SD in PD designed for application in a movement disorder unit. We also recommend that neurologists and other healthcare providers undergo training to provide basic sexual counseling tailored to the needs of PD patients.

Prevalence and significance of mutations in the familial Mediterranean fever gene in patients with Crohn's disease.

The concurrence of Crohn's disease (CD) and familial Mediterranean fever was repeatedly reported. In this study we determined the distribution and contribution of MEFV gene mutations to CD susceptibility and clinical heterogeneity. An Israeli cohort of 209 CD patients (120 men and 89 women) was investigated for mutations in the MEFV gene. A detailed chart review, interview and physical examination were used to determine sociodemographic and clinical characteristics. MEFV and NOD2/CARD15 genotypes were analyzed in all patients and a genotype-phenotype correlation analysis was undertaken. The results of this study do not implicate MEFV mutations as major modifiers in CD. However, the E148Q MEFV variant was associated with susceptibility to perianal disease. More specifically, 19% (9/47) of CD patients with perianal disease carried the E148Q mutation compared to 6.7% (11/162) of CD patients without perianal involvement (OR 3.26, 95% CI 1.2-8.8, P=0.02). Although, for all mutations taken together, the prevalence of MEFV gene mutations among CD patients and controls was similar, the hypothesis that E148Q mutation modulates the phenotypic expression of CD is corroborated by the results of this study and needs to be further evaluated.

A novel quality control compartment derived from the endoplasmic reticulum.

Degradation of proteins that, because of improper or suboptimal processing, are retained in the endoplasmic reticulum (ER) involves retrotranslocation to reach the cytosolic ubiquitin-proteasome machinery. We found that substrates of this pathway, the precursor of human asialoglycoprotein receptor H2a and free heavy chains of murine class I major histocompatibility complex (MHC), accumulate in a novel preGolgi compartment that is adjacent to but not overlapping with the centrosome, the Golgi complex, and the ER-to-Golgi intermediate compartment (ERGIC). On its way to degradation, H2a associated increasingly after synthesis with the ER translocon Sec61. Nevertheless, it remained in the secretory pathway upon proteasomal inhibition, suggesting that its retrotranslocation must be tightly coupled to the degradation process. In the presence of proteasomal inhibitors, the ER chaperones calreticulin and calnexin, but not BiP, PDI, or glycoprotein glucosyltransferase, concentrate in the subcellular region of the novel compartment. The "quality control" compartment is possibly a subcompartment of the ER. It depends on microtubules but is insensitive to brefeldin A. We discuss the possibility that it is also the site for concentration and retrotranslocation of proteins that, like the mutant cystic fibrosis transmembrane conductance regulator, are transported to the cytosol, where they form large aggregates, the "aggresomes."

Folding and self-assembly do not prevent ER retention and proteasomal degradation of asialoglycoprotein receptor H2a.

The human asialoglycoprotein receptor H2a precursor, a type II membrane protein, is cleaved to a soluble form that is secreted. Uncleaved precursor molecules are completely retained in the endoplasmic reticulum (ER) and degraded by the proteasome. To find out the causes of its fate we studied folding of H2a precursor, which was very similar to that of its alternatively spliced variant H2b which can exit to the Golgi. Proteasomal inhibition led to accumulation of folded rather than unfolded molecules. Accumulation of ER-retained H2a did not cause an unfolded protein response. Although the receptor is a heterooligomer of the H1 and H2 subunits, single expression led to some self-assembly. Whereas these homooligomers accumulated for H2b they were degraded for H2a. Translocation of H2a into the ER occurred efficiently. Therefore, the retention and proteasomal degradation of uncleaved membrane-bound H2a precursor from the ER do not involve aberrant translocation or misfolding and are not prevented by self-assembly.