A naturally occurring genetic variant in the human chorionic gonadotropin-beta gene 5 is assembly inefficient.

The hCGbeta gene family is composed of six homologous genes linked in tandem repeat on chromosome 19; the order of the genes is 7, 8, 5, 1, 2, and 3. Previous studies have shown that hCGbeta gene 5 is highly expressed during the first trimester of pregnancy. The purpose of our study was to identify naturally occurring polymorphisms in hCGbeta gene 5 and determine whether these alterations affected hCG function. The data presented here show that hCGbeta gene 5 was highly conserved in the 334 asymptomatic individuals and 41 infertile patients examined for polymorphisms using PCR followed by single stranded conformational polymorphism analysis. Most of the polymorphisms detected were either silent or located in intron regions. However, one genetic variant identified in beta gene 5 exon 3 was a G to A transition that changed the naturally occurring valine residue to methionine in codon 79 (V79M) in 4.2% of the random population studied. The V79M polymorphism was always linked to a silent C to T transition in codon 82 (tyrosine). To determine whether betaV79M hCG had biological properties that differed from those of wild-type hCG, a beta-subunit containing the V79M substitution was created by site-directed mutagenesis and was coexpressed with the glycoprotein hormone alpha-subunit in Chinese hamster ovary cells and 293T cells. When we examined betaV79M hCG biosynthesis, we detected atypical betaV79M hCG folding intermediates, including a betaV79M conformational variant that resulted in a beta-subunit with impaired ability to assemble with the alpha-subunit. The inefficient assembly of betaV79M hCG appeared to be independent of beta-subunit glycosylation or of the cell type studied, but, rather, was due to the inability of the betaV79M subunit to fold correctly. The majority of the V79M beta-subunit synthesized was secreted as unassembled free beta. Although the amount of alphabeta hCG heterodimer formed and secreted by betaV79M-producing cells was less than that by wild-type beta-producing cells, the hCG that was secreted as alphabeta V79M heterodimer exhibited biological activity indistinguishable from that of wild-type hCG.     

Pre‐emptive ibuprofen arginate in third molar surgery: a double‐blind randomized controlled crossover clinical trial

Background: This study evaluated the effectiveness of 400 mg ibuprofen arginate either as a pre‐emptive (PRE group) or postoperative (POST group) analgesic using a common dental pain model. Methods: A randomized double‐blind crossover clinical trial involving a series of consecutive patients admitted for bilateral third molar surgery. Results were analysed according to the self‐reported pain score and the pattern of rescue medication taken. Results: The mean pain score ranged from 0.73 to 1.60 for the PRE group and 0.47 to 1.41 for the POST group among 30 included subjects. The mean time point when first rescue medication taken was 7.3 hours and 8.3 hours postoperative, respectively. Nine patients (30 per cent) in the PRE group and 12 patients (40 per cent) in the POST group took no rescue medication. There was no statistically significant difference for all parameters between groups, while a majority (53 per cent) found the drug “good” to “excellent” in both groups. Conclusions: Ibuprofen arginate may be considered effective in reducing surgically induced moderate to severe pain when administered either pre‐operatively or postoperatively due to the reported relatively low pain score, less consumption of rescue medication, delayed onset of pain, good number of pain‐free patients and a high rating in the global assessment score.     

Psychosocial factors in adolescent nicotine dependence symptoms: a sample of high school juniors who smoke daily

Cross-sectionally examined seven theory-guided psychosocial factors associated with nicotine dependence symptoms in a representative self-report survey of 794 Washington State high school junior daily smokers (93% participation). Outcomes were four nicotine dependence symptoms. Results showed that low self-efficacy for quitting smoking and being around adults who smoke were associated with a 3.48-10.35 and a 1.47-1.77 times higher odds, respectively, of each of the four nicotine dependence symptoms. These results, needing replication in a longitudinal study, suggest that interventions designed to enhance self-efficacy to quit smoking and counter adult smoking influences might reduce adolescent nicotine dependence.     

Development and psychometric evaluation of the Bipolar Functional Status Questionnaire (BFSQ)

Goldberg JF, McLeod LD, Fehnel SE, Williams VSL, Hamm LR, Gilchrist K. Development and psychometric evaluation of the Bipolar Functional Status Questionnaire (BFSQ). Bipolar Disord 2010: 12: 32–44. © 2010 The Authors.
Journal compilation © 2010 John Wiley & Sons A/S. Objectives: Persistently impaired psychosocial functioning has been recognized in many individuals with bipolar disorder. However, existing measures of functional disability have been adapted for use in bipolar disorder based mainly on those developed for use in other conditions. The present study involved the development and validation of a new patient self‐report measure specific to bipolar disorder, the Bipolar Functional Status Questionnaire (BFSQ). Methods: Relevant constructs were identified, evaluated, and refined through an expert advisory panel in conjunction with patient interviews. Questionnaire items were vetted through iterative patient interviews. Psychometric properties were determined based on patient responses from implementation of the proposed 33‐item questionnaire in an 11‐site study of 596 patients with bipolar disorder across varied phases of illness. Results: Eight constructs were identified as fundamental to functional status in bipolar disorder: cognitive function, sleep, role functioning, emotional functioning, energy/vitality, social functioning, personal management, and sexual functioning. Psychometric validation supported item reduction to a 24‐item unidimensional scale, with high internal consistency (coefficient α’s = 0.93–0.95), high test‐retest reliability (intraclass correlation coefficient = 0.86, 95% confidence interval = 0.82–0.89), strong convergent validity with other functional disability measures (r’s > 0.70), and highly significant discriminant validity across illness phases, with large effect sizes (Cohen’s d > 0.70). Conclusions: The BFSQ is a psychometrically sound self‐report measure that can be used to effectively quantify functional status across different clinical states in patients with bipolar disorder.     

Large ethnic variations in recommended physical activity according to activity domains in amsterdam, the netherlands

Purpose

The level of recommended physical activity (PA) is met less frequently by people from some ethnic minorities than others. We explored whether these differences in recommended PA between ethnic minority groups and the general population varied by domain and type of culturally-specific activity.

Methods

Participants were sampled from the population based SUNSET study and were from ethnic Dutch (n = 567), Hindustani-Surinamese (n = 370) and African-Surinamese (n = 689) descent. The validated SQUASH-questionnaire measured PA for the following domains: commuting, occupation, household, leisure time. Culturally-specific activities were added as extra question within the leisure time domain. The effect of each domain on ethnic differences in recommended PA prevalence was examined by odds-ratio (OR) analysis through recalculating recommended PA, while, in turn, excluding the contribution of each domain.

Results

In the ethnic Dutch population, more vigorous PA in commuting and leisure time was reported compared to the Surinamese groups. The Hindustani-Surinamese and African-Surinamese reported more walking as commuting activity, while the Dutch group reported cycling more frequently. Ethnic differences in recommended PA became smaller in both Surinamese groups compared with the Dutch after removing commuting activity, for example, in Hindustani-Surinamese men (OR = 0.92, 95%CI: 0.62-1.37 vs. OR = 1.33, 0.89-2.00) and women (OR = 1.61, 1.12-2.32 vs. OR = 2.03, 1.41-2.92). Removing occupational activity resulted in larger ethnic differences in both groups compared with the Dutch. Smaller effects were found for yoga and dancing, leisure time and household activities.

Conclusion

This study shows that differences in PA between ethnic minority groups and the general population vary according to the activity domain. The results indicate that including all relevant domains and activities is essential for assessment of ethnic differences in recommended PA.     

The development and validation of the daily electronic Endometriosis Pain and Bleeding Diary

Background  

The objective of this study was to develop and validate a daily electronic Endometriosis Pain and Bleeding Diary (EPBD) for assessing treatment-related changes in endometriosis symptoms from the patient's perspective in a clinical trial setting.