Type 2 diabetes mellitus in women with polycystic ovary syndrome during a 24-year period: importance of obesity and abdominal fat distribution.

STUDY QUESTION: What are the predictive factors for later development of type 2 diabetes (T2DM) in women with polycystic ovary syndrome (PCOS)? SUMMARY ANSWER: Obesity and abdominal fat distribution in women with PCOS in the mid-fertile years were the major risk factors for T2DM development 24 years later when lifestyle factors were similar to controls. WHAT IS KNOWN ALREADY: Women with PCOS have an increased prevalence of T2DM. STUDY DESIGN SIZE DURATION: A longitudinal and cross-sectional study was performed. Women with PCOS were examined in 1992 and in 2016. Randomly selected, age-matched women from the general population served as controls. PARTICIPANTS/MATERIALS SETTING METHODS: Women with PCOS (n = 27), attending an outpatient clinical at a tertiary care centre for infertility or hirsutism were diagnosed in 1992 (mean age 30 years) and re-examined in 2016 (mean age 52 years). Women from the World Health Organization MONItoring of trends and determinants for CArdiovascular disease (WHO MONICA-GOT) 2008, aged 38-68 years, served as controls (n = 94), and they were previously examined in 1995. At both at baseline and at follow-up, women had blood samples taken, underwent a clinical examination and completed structured questionnaires, and the women with PCOS also underwent a glucose clamp test at baseline. MAIN RESULTS AND THE ROLE OF CHANCE: None of women with PCOS had T2DM at baseline. At the 24-year follow-up, 19% of women with PCOS had T2DM versus 1% of controls (P < 0.01). All women with PCOS who developed T2DM were obese and had waist-hip ratio (WHR) >0.85 at baseline. No difference was seen between women with PCOS and controls regarding use of high-fat diet, Mediterranean diet or amount of physical activity at follow-up at peri/postmenopausal age. However, women with PCOS had a lower usage of a high-sugar diet as compared to controls (P = 0.01). The mean increases in BMI and WHR per year were similar in women with PCOS and controls during the follow-up period. LIMITATIONS REASONS FOR CAUTION: The small sample size of women with PCOS and the fact that they were recruited due to infertility or hirsutism make generalization to women with milder forms of PCOS uncertain. WIDER IMPLICATIONS OF THE FINDINGS: Obesity and abdominal fat distribution, but not hyperandrogenism per se, in women with PCOS in the mid-fertile years were the major risk factors for T2DM development 24 years later when peri/postmenopausal. Lifestyle factors were similar to controls at that time. STUDY FUNDING/COMPETING INTERESTS: The study was financed by grants from the Swedish state under the agreement between the Swedish government and the country councils, the ALF-agreement (ALFGBG-718611), the Gothenburg Medical Association GLS 694291 and 780821, the Swedish Heart Lung Foundation and Hjalmar Svensson Foundation. The authors have no conflict of interest.

Hearing loss but not bone-regulating hormones predicts fractures in older women-a 17-year follow-up of the Gothenburg BEDA study.

High-frequency hearing loss and S-Ca, but not hormones related to bone structure and strength, or lifestyle factors, predicted incident fractures during 17 years of follow-up in women up to 97 years of age. INTRODUCTION: The fracture risk increases and inner ear function deteriorates with increasing age. The aim of this study was to investigate whether hearing loss was of greater importance than bone-regulating hormones for the risk of fracture in elderly women. METHODS: In 1997, a random population sample of 63-82-year-old women, n = 552, underwent a physical examination, audiometry and blood sampling for analyses of serum albumin-adjusted calcium (S-Ca), parathyroid hormone (PTH), 25(OH) vitamin D and insulin-like growth factor-1 (IGF-1). Data on medication, lifestyle, previous fractures, hearing, vision and dizziness were obtained using questionnaires. Data on subsequent fractures were retrieved, and censored at death, through December 2013. RESULTS: In 1997, 228 women (41%) reported a previous fracture, most commonly of the wrist (18%). During the following 17 years, 323 fractures occurred in 207 women (38%). Hip fractures were the most frequent, in 96 women (17%). In a Cox regression analysis adjusted for age and previous fractures, hearing loss, reflected by a high pure tone average ≥ 59 dB, almost doubled the risk of a subsequent fracture (hazard ratio (HR) 1.81, 95% CI 1.25; 2.61, p = 0.002). S-Ca (HR 1.21 (1.02; 1.44) p = 0.028) also predicted future fractures, whereas PTH, IGF-1, 25(OH) vitamin D, hormone replacement therapy, smoking, degree of physical activity, impaired vision and dizziness did not. CONCLUSION: Hearing loss and higher S-Ca, but not bone-regulating hormones, medication or lifestyle factors predicted incident fractures, mainly caused by falling, during 17 years of follow-up in women up to 97 years of age.

Efficacy of intergrating vestibular rehabilitation and cognitive behaviour therapy in persons with persistent dizziness in primary care- a study protocol for a randomised controlled trial.

BACKGROUND: Dizziness is a common complaint, and the symptom often persists, together with additional complaints. A treatment combining Vestibular Rehabilitation (VR) and Cognitive Behaviour Therapy (CBT) is suggested. However, further research is necessary to evaluate the efficacy of such an intervention. The objective of this paper is to present the design of a randomised controlled trial aiming at evaluating the efficacy of an integrated treatment of VR and CBT on dizziness, physical function, psychological complaints and quality of life in persons with persistent dizziness. METHODS/DESIGN: The randomised controlled trial is an assessor-blinded, block-randomised, parallel-group design, with a 6- and 12-month follow-up. The study includes 125 participants from Bergen (Norway) and surrounding areas. Included participants present with persistent dizziness lasting for at least 3 months, triggered or exacerbated by movement. All participants receive a one-session treatment (Brief Intervention Vestibular Rehabilitation; BI-VR) with VR before being randomised into a control group or an intervention group. The intervention group will further be offered an eight-session treatment integrating VR and CBT. The primary outcomes in the study are the Dizziness Handicap Inventory and preferred gait velocity. DISCUSSION: Previous studies combining these treatments have been of varying methodological quality, with small samples, and long-term effects have not been maintained. In addition, only the CBT has been administered in supervised sessions, with VR offered as home exercises. The current study focusses on the integrated treatment, a sufficiently powered sample size, and a standardised treatment programme evaluated by validated outcomes using a standardised assessment protocol. TRIAL REGISTRATION: www.clinicaltrials.gov, ID: NCT02655575 . Registered on 14 January 2016.

Feasibility of integrating vestibular rehabilitation and cognitive behaviour therapy for people with persistent dizziness.

PURPOSE: To evaluate the feasibility of integrating vestibular rehabilitation and cognitive behaviour therapy (VR-CBT) for people with persistent dizziness in primary care. DESIGN: Prospective single-group pre- and post-test study. PARTICIPANTS: Adults (aged 18-70) with acute onset of dizziness and symptoms lasting a minimum 3 months, recruited from Bergen municipality. METHODS: Participants attended eight weekly group sessions of VR-CBT intervention. Feasibility outcomes consisted of recruitment and testing procedures, intervention adherence, and participant feedback, besides change in primary outcomes. The primary outcomes were Dizziness Handicap Inventory (DHI) and preferred gait velocity. RESULTS: Seven participants were recruited for the study. All participants completed the pre-treatment tests, five participants completed the intervention and answered post-treatment questionnaires, and three completed post-treatment testing. Of the five participants, three attended at least 75% of the VR-CBT sessions, and two 50% of the sessions. Participants reported that the VR-CBT was relevant and led to improvement in function. DHI scores improved beyond minimal important change in two out of five participants, and preferred gait velocity increased beyond minimal important change in two out of three participants. CONCLUSION: The current tests and VR-CBT treatment protocols were feasible. Some changes are suggested to optimise the protocols, before conducting a randomised controlled trial. TRIAL REGISTRATION: NCT02655575. Registered 14 January 2016-retrospectively registered.

A mechanistic linkage between oral lichen planus and autoimmune thyroid disease.

OBJECTIVE: To determine the levels of antithyroid antibodies and thyroid hormones in the sera of patients with oral lichen planus (OLP), and to quantify the expression of thyroid proteins in OLP lesions. SUBJECTS AND METHODS: Venous blood samples were drawn from 110 patients with OLP who had no history of thyroid disease or levothyroxine supplementation (OLP+/LT4 -). A random population sample of 657 healthy subjects was used as the control group. Two additional groups were used as comparators. Immunohistochemical and qPCR analyses were performed on tissue specimens collected from the patients with OLP and thyroid disease and healthy subjects. RESULTS: No association was found between the presence of antithyroid antibodies and OLP. More patients in the OLP+/LT4 - group showed high levels of thyroid-stimulating hormone and low levels of free thyroxine than were seen in the control group. Thyroid-stimulating hormone receptor was more highly expressed in the OLP lesions of patients with thyroid disease than in the healthy oral mucosa. CONCLUSIONS: A significant number of patients with OLP who are not previously diagnosed with thyroid disease have thyroid parameters that are compatible with hypothyroidism. The expression of thyroid-stimulating hormone receptor in OLP lesions suggests that mechanisms related to autoimmune thyroid disease are involved in the aetiology of OLP.

Large-scale pharmacogenomic study of sulfonylureas and the QT, JT and QRS intervals: CHARGE Pharmacogenomics Working Group.

Sulfonylureas, a commonly used class of medication used to treat type 2 diabetes, have been associated with an increased risk of cardiovascular disease. Their effects on QT interval duration and related electrocardiographic phenotypes are potential mechanisms for this adverse effect. In 11 ethnically diverse cohorts that included 71 857 European, African-American and Hispanic/Latino ancestry individuals with repeated measures of medication use and electrocardiogram (ECG) measurements, we conducted a pharmacogenomic genome-wide association study of sulfonylurea use and three ECG phenotypes: QT, JT and QRS intervals. In ancestry-specific meta-analyses, eight novel pharmacogenomic loci met the threshold for genome-wide significance (P<5 × 10-8), and a pharmacokinetic variant in CYP2C9 (rs1057910) that has been associated with sulfonylurea-related treatment effects and other adverse drug reactions in previous studies was replicated. Additional research is needed to replicate the novel findings and to understand their biological basis.

Case report: fast reversal of severe osteoporosis after correction of excessive levothyroxine treatment and long-term follow-up.

This case report describes a 38-year-old woman, who presented with bilateral femoral stress fractures and osteoporosis after years of excessive levothyroxine treatment. Her bone health was restored rapidly and long-lasting with the reduction of levothyroxine dosage. No bone-active treatment was warranted. INTRODUCTION: Hyperthyroidism is a known risk factor for osteoporosis and fractures. Recent studies on patients with serum thyrotropin-suppressive therapy have not, however, indicated adverse effects on bone during long-term follow-up. METHODS: This case report describes long-term follow-up data of a clinically euthyreoid patient, who developed symptomatic osteoporosis due to excessive levothyroxine treatment. RESULTS: After correction of levothyroxine dosage, her bone mineral density (BMD) and previously elevated serum osteocalcin levels normalized rapidly and she remained free from fractures during 23 years of follow-up over menopause. CONCLUSION: Excessive TSH suppression contributed to the secondary osteoporosis in this patient; BMD normalized after dose reduction of levothyroxine and no fractures occurred during 23 years' follow-up. Some patients develop severe osteoporosis if they are over-substituted with levothyroxine, and decent follow-up of patients with levothyroxine supplementation is mandatory.

Single nucleotide polymorphisms in the REG-CTNNA2 region of chromosome 2 and NEIL3 associated with impulsivity in a Native American sample.

Impulsivity is a multi-faceted construct that, while characterized by a set of correlated dimensions, is centered around a core definition that involves acting suddenly in an unplanned manner without consideration for the consequences of such behavior. Several psychiatric disorders include impulsivity as a criterion, and thus it has been suggested that it may link a number of different behavioral disorders, including substance abuse. Native Americans (NA) experience some of the highest rates of substance abuse of all the US ethnic groups. The described analyses used data from a low-coverage whole genome sequence scan to conduct a genome-wide association study (GWAS) of an impulsivity phenotype in an American Indian community sample (n = 658). Demographic and clinical information were obtained using a semi-structured interview. Impulsivity was assessed using a scale derived from the Maudsley personality inventory that combines both novelty seeking and lack of planning items. The impulsivity score was tested for association with each variant adjusted for demographic variables, and corrected for ancestry and kinship, using emmax. Simulations were conducted to calculate empirical P-values. Genome-wide significant findings were observed for a variant 50-kb upstream from catenin cadherin-associated protein, alpha 2 (CTNNA2), a neuronal-specific catenin, in the REG gene cluster. A meta-analysis of GWAS had previously identified common variants in CTNNA2 as being associated with excitement seeking. A second locus upstream of nei endonuclease VIII-like 3 (NEIL3) on chromosome 4 also achieved genome-wide significance. The association between sequence variants in these regions suggests their potential roles in the genetic regulation of this phenotype in this population.

Serum IGF-1 is higher in patients with idiopathic normal pressure hydrocephalus than in the population.

BACKGROUND: Hypopituitarism has been reported in patients with idiopathic normal pressure hydrocephalus (iNPH), which could enhance characteristic symptoms like impaired wakefulness, gait, body balance, and subcortical cognitive deterioration. PURPOSE: To compare basal serum levels of pituitary and sex hormones and serum insulin-like growth factor-1 (S-IGF-1) in patients with iNPH and an age-matched control population, and to correlate the preoperative hormone levels with symptoms and signs pre-operatively and three months after surgery. METHODS: A cross-sectional case control design was used. Patients diagnosed with iNPH, n=108 (65 men and 43 women, mean age 72.3 years), were consecutively included during 2006-2011 at Sahlgrenska University Hospital, Gothenburg, Sweden. S-TSH, S-free T4, S-FSH, S-LH, S-prolactin, plasma ACTH, S-testosterone, S-oestradiol and S-IGF-1 were examined. Symptoms and signs were scored using the iNPH scale score. Population controls, n=146, were recruited from the WHO MONICA project, Gothenburg in 2008. RESULTS: Men and women with iNPH had higher S-IGF-1 than controls (p<0.001). Women with iNPH had lower S-TSH (p=0.016) than controls, but the frequency of levothyroxine substitution was similar. Among men, a higher level of S-IGF-1 was associated with milder symptoms, while higher levels of S-FSH and S-LH were associated with more severe symptoms. CONCLUSIONS: Patients with iNPH did not have lower levels of pituitary or sex hormones but presented with higher levels of S-IGF-1, compared with healthy, age-matched controls. Higher S-IGF-1 in men was related to milder mental and physical symptoms and signs.

Pre- and post-operative dizziness and postural instability in temporal arachnoid cyst patients.

OBJECTIVES: Arachnoid cysts (AC) are benign, congenital malformations of the leptomeninges, with a predilection for the temporal fossa. In our clinical experience, patients with temporal AC often complain of dizziness and imbalance. However, these symptoms and the effect of surgery on them have not been studied before. MATERIALS AND METHODS: Dizziness and imbalance in patients with temporal AC were quantified before and after surgical cyst decompression, using the Dizziness Handicap Inventory (DHI), Vertigo Symptom Scale - Short-Form (VSS-SF) and computerized dynamic posturography (CDP). The study includes 16 patients with temporal AC and 15 control subjects undergoing surgery for benign lesions of the larynx (n = 10) or the parotid glands (n = 5). All participants answered the DHI and VSS-SF and underwent CDP the day before and 3-6 months after surgery. The patients with AC also graded their dizziness through the use of a visual analogue scale (VAS). RESULTS: Preoperatively, cyst patients scored higher than controls on subjective symptoms (DHI, VSS-SF A and VSS-SF V), but not on postural sway (CDP). Symptom scores decreased after surgery; the cyst patients improved significantly in the subjective tests (DHI, VAS and VSS-SF), while CDP scores did not. In the controls, symptom and CDP scores were unchanged after surgery. CONCLUSIONS: Patients with temporal AC have a significant preoperative impairment and post-operative improvement in their subjective dizziness, but not in postural sway as measured by CDP.

Integrated copy number and gene expression analysis detects a CREB1 association with Alzheimer's disease.

Genetic variation, both single-nucleotide variations and copy number variations (CNV), contribute to changes in gene expression. In some cases these variations are meaningfully correlated with disease states. We hypothesized that in a genetically heterogeneous disorder such as sporadic Alzheimer's disease (AD), utilizing gene expression as a quantitative trait and CNVs as a genetic marker map within the same individuals in the context of case-control status may increase the power to detect relevant loci. Using this approach an 8-kb deletion was identified that contains a PAX6-binding site on chr2q33.3 upstream of CREB1 encoding the cAMP responsive element-binding protein1 transcription factor. The association of the CNV to AD was confirmed by a case-control association study consisting of the Texas Alzheimer Research and Care Consortium and NIA-LOAD Family Study data sets.

Antipsychotic-induced vacuous chewing movements and extrapyramidal side effects are highly heritable in mice.

Pharmacogenomics is yet to fulfill its promise of manifestly altering clinical medicine. As one example, a predictive test for tardive dyskinesia (TD) (an adverse drug reaction consequent to antipsychotic exposure) could greatly improve the clinical treatment of schizophrenia but human studies are equivocal. A complementary approach is the mouse-then-human design in which a valid mouse model is used to identify susceptibility loci, which are subsequently tested in human samples. We used inbred mouse strains from the Mouse Phenome Project to estimate the heritability of haloperidol-induced activity and orofacial phenotypes. In all, 159 mice from 27 inbred strains were chronically treated with haloperidol (3 mg kg(-1) per day via subdermal slow-release pellets) and monitored for the development of vacuous chewing movements (VCMs; the mouse analog of TD) and other movement phenotypes derived from open-field activity and the inclined screen test. The test battery was assessed at 0, 30, 60, 90 and 120 days in relation to haloperidol exposure. As expected, haloperidol caused marked changes in VCMs, activity in the open field and extrapyramidal symptoms (EPS). Unexpectedly, factor analysis demonstrated that these measures were imprecise assessments of a latent construct rather than discrete constructs. The heritability of a composite phenotype was ∼0.9 after incorporation of the longitudinal nature of the design. Murine VCMs are a face valid animal model of antipsychotic-induced TD, and heritability estimates from this study support the feasibility of mapping of susceptibility loci for VCMs.

Obstetric outcomes in women with Turner karyotype.

CONTEXT: Women with Turner syndrome (TS) have high risk of cardiovascular complications and hypertensive disorders. Few studies have analyzed obstetric outcome in women with TS. OBJECTIVE: This study compared obstetric outcome in women with TS karyotype with women in the general population. DESIGN: The Swedish Genetic Turner Register was cross-linked with the Swedish Medical Birth Register between 1973 and 2007. Obstetric outcome in singletons was compared with a reference group of 56,000 women from the general population. Obstetric outcome in twins was described separately. RESULTS: A total of 202 singletons and three sets of twins were born to 115 women with a TS karyotype that was unknown in 52% at time of pregnancy. At first delivery, TS women of singletons were older than controls (median 30 vs. 26 yr, P < 0.0001). Preeclampsia occurred in 6.3 vs. 3.0% (P = 0.07). Aortic dissection occurred in one woman. Compared with the general population, the gestational age was shorter in children born by TS women (-6.4 d, P = 0.0067), and median birth weight was lower (-208 g, P = 0.0012), but sd scores for weight and length at birth were similar. The cesarean section rate was 35.6% in TS women and 11.8% in controls (P < 0.0001). There was no difference in birth defects in children of TS women as compared with controls. CONCLUSIONS: Obstetric outcomes in women with a TS karyotype were mostly favorable. Singletons of TS women had shorter gestational age, but similar size at birth, adjusted for gestational age and sex. Birth defects did not differ between TS and controls.

Olfactory copy number association with age at onset of Alzheimer disease.

OBJECTIVES: Copy number variants (CNVs) have been recognized as a source of genetic variation that contributes to disease phenotypes. Alzheimer disease (AD) has high heritability for occurrence and age at onset (AAO). We performed a cases-only genome-wide CNV association study for age at onset of AD. METHODS: The discovery case series (n = 40 subjects with AD) was evaluated using array comparative genome hybridization (aCGH). A replication case series (n = 507 subjects with AD) was evaluated using Affymetrix array (n = 243) and multiplex ligation-dependent probe amplification (n = 264). Hazard models related onset age to CNV. RESULTS: The discovery sample identified a chromosomal segment on 14q11.2 (19.3-19.5 Mb, NCBI build 36, UCSC hg18 March 2006) as a region of interest (genome-wide adjusted p = 0.032) for association with AAO of AD. This region encompasses a cluster of olfactory receptors. The replication sample confirmed the association (p = 0.035). The association was found for each APOE4 gene dosage (0, 1, and 2). CONCLUSION: High copy number in the olfactory receptor region on 14q11.2 is associated with younger age at onset of AD.

National Ignition Facility system alignment.

The National Ignition Facility (NIF) is the world's largest optical instrument, comprising 192 37 cm square beams, each generating up to 9.6 kJ of 351 nm laser light in a 20 ns beam precisely tailored in time and spectrum. The Facility houses a massive (10 m diameter) target chamber within which the beams converge onto an ∼1 cm size target for the purpose of creating the conditions needed for deuterium/tritium nuclear fusion in a laboratory setting. A formidable challenge was building NIF to the precise requirements for beam propagation, commissioning the beam lines, and engineering systems to reliably and safely align 192 beams within the confines of a multihour shot cycle. Designing the facility to minimize drift and vibration, placing the optical components in their design locations, commissioning beam alignment, and performing precise system alignment are the key alignment accomplishments over the decade of work described herein. The design and positioning phases placed more than 3000 large (2.5 m×2 m×1 m) line-replaceable optics assemblies to within ±1 mm of design requirement. The commissioning and alignment phases validated clear apertures (no clipping) for all beam lines, and demonstrated automated laser alignment within 10 min and alignment to target chamber center within 44 min. Pointing validation system shots to flat gold-plated x-ray emitting targets showed NIF met its design requirement of ±50 µm rms beam pointing to target chamber. Finally, this paper describes the major alignment challenges faced by the NIF Project from inception to present, and how these challenges were met and solved by the NIF design and commissioning teams.

High serum total cholesterol is a long-term cause of osteoporotic fracture.

SUMMARY: Risk factors for osteoporotic fractures were evaluated in 1,396 men and women for a period of 20 years. Serum total cholesterol was found to be an independent osteoporotic fracture risk factor whose predictive power improves with time. INTRODUCTION: The purpose of this study was to evaluate long-term risk factors for osteoporotic fracture. METHODS: A population random sample of men and women aged 25-64 years (the Gothenburg WHO MONICA project, N = 1,396, 53% women) was studied prospectively. The 1985 baseline examination recorded physical activity at work and during leisure time, psychological stress, smoking habits, coffee consumption, BMI, waist/hip ratio, blood pressure, total, HDL and LDL cholesterol, triglycerides, and fibrinogen. Osteoporotic fractures over a period of 20 years were retrieved from the Gothenburg hospital registers. Poisson regression was used to analyze the predictive power for osteoporotic fracture of each risk factor. RESULTS: A total number of 258 osteoporotic fractures occurred in 143 participants (10.2%). As expected, we found that previous fracture, smoking, coffee consumption, and lower BMI each increase the risk for osteoporotic fracture independently of age and sex. More unexpectedly, we found that the gradient of risk of serum total cholesterol to predict osteoporotic fracture significantly increases over time (p = 0.0377). CONCLUSIONS: Serum total cholesterol is an independent osteoporotic fracture risk factor whose predictive power improves with time. High serum total cholesterol is a long-term cause of osteoporotic fracture.

Linkage scan of nicotine dependence in the University of California, San Francisco (UCSF) Family Alcoholism Study.

BACKGROUND: Nicotine dependence has been shown to represent a heritable condition, and several research groups have performed linkage analysis to identify genomic regions influencing this disorder though only a limited number of the findings have been replicated. METHOD: In the present study, a genome-wide linkage scan for nicotine dependence was conducted in a community sample of 950 probands and 1204 relatives recruited through the University of California, San Francisco (UCSF) Family Alcoholism Study. A modified version of the Semi-Structured Assessment for the Genetics of Alcoholism (SSAGA) with additional questions that probe nicotine use was used to derive DSM-IV nicotine dependence diagnoses. RESULTS: A locus on chromosome 2q31.1 at 184 centiMorgans nearest to marker D2S2188 yielded a logarithm (base 10) of odds (LOD) score of 3.54 (point-wise empirical p=0.000012). Additional peaks of interest were identified on chromosomes 2q13, 4p15.33-31, 11q25 and 12p11.23-21. Follow-up analyses were conducted examining the contributions of individual nicotine dependence symptoms to the chromosome 2q31.1 linkage peak as well as examining the relationship of this chromosomal region to alcohol dependence. CONCLUSIONS: The present report suggests that chromosome 2q31.1 confers risk to the development of nicotine dependence and that this region influences a broad range of nicotine dependence symptoms rather than a specific facet of the disorder. Further, the results show that this region is not linked to alcohol dependence in this population, and thus may influence nicotine dependence specifically.

Women who gave birth to girls with Turner syndrome: maternal and neonatal characteristics.

BACKGROUND: The aim was to identify maternal risk factors in women giving birth to girls with Turner syndrome (TS) and to describe the characteristics of newborns with TS. METHODS: The Swedish Genetic Turner Register was cross-linked with the Swedish Medical Birth Register. Between 1973 and 2005, 494 children with TS were born. Maternal age, parity, height, smoking habits and neonatal characteristics; mode of delivery, gestational age, size at birth and Apgar score, were compared with women in the general population who gave birth to girls during the same period. RESULTS: More women with advanced maternal age (40+) delivered girls with TS, 3.2% when compared with 1.8% in the general population [OR 1.83, 95% confidence interval (CI) 1.09-3.08, after adjustment for year of birth]. Maternal height was inversely associated with TS pregnancies (P = 0.005). Late preterm birth occurred in newborns with TS in 10.5% when compared with 4.8% in the general population (OR 2.23; 95% CI: 1.67-2.97, after adjustment for year of birth and maternal age). Newborns with TS had birthweight less than -2SD in 17.8% and birth length less than -2SD in 21.0% when compared with 3.5 and 3.4%, in the general population (OR 6.55; 95% CI: 5.12-8.38 and OR 8.69; 95% CI: 6.89-10.97, after adjustment for year of birth and maternal age). CONCLUSION: Advanced maternal age and short stature were risk factors for giving birth to a girl with TS. More TS girls were born late preterm and were smaller for gestational age than non-TS girls in the general population.

Male risk factors for hip fracture-a 30-year follow-up study in 7,495 men.

SUMMARY: Risk factors for hip fracture were studied in 7,495 randomly selected men during 30 years; 451 men had a hip fracture. High degree of leisure-time, but not work-related, physical activity, high occupational class, and high body mass index (BMI) protected against hip fracture. Smoking, tall stature, interim stroke, and dementia increased the risk. PURPOSE: The purpose was to prospectively study risk factors for hip fracture in men. METHODS: We studied midlife determinants of future hip fractures in 7,495 randomly selected men aged 46-56 years in Gothenburg, Sweden. The subjects were investigated in 1970-1973 and followed for over 30 years. Questionnaires were used regarding lifestyle factors, psychological stress, occupational class, and previous myocardial infarction, stroke, and diabetes mellitus. Alcohol problems were assessed with the aid of registers. Using the Swedish hospital discharge register, data were collected on intercurrent stroke and dementia diagnoses and on first hip fractures (X-ray-verified). RESULTS: Four hundred fifty-one men (6%) had a hip fracture. Age, tall stature, low occupational class, tobacco smoking, alcoholic intemperance, and interim stroke or dementia were independently associated with the risk of hip fracture. There were inverse associations with leisure-time physical activity, BMI, and coffee consumption. The gradient of risk for one standard deviation of multivariable risk decreased with time since measurement yet was a good alternative to dual energy X-ray absorptiometry measurements. CONCLUSIONS: High degree of leisure-time physical activity, high occupational class, and high BMI protected against hip fracture. However, work-related physical activity was not protective. Smoking, tall stature, and interim stroke or dementia increased the risk.

Effect of climate therapy at Gran Canaria on vitamin D production, blood glucose and lipids in patients with psoriasis.

BACKGROUND: Climate therapy (heliotherapy) of psoriasis is an effective and natural treatment. Ultraviolet radiation (UVB) from the sun improves psoriasis and induces vitamin D(3) synthesis. OBJECTIVE: The aim of the study was to investigate the effect of climate therapy on vitamin D(3) synthesis, blood glucose, lipids and vitamin B12 in psoriasis patients. METHODS: Twenty Caucasian patients (6 women and 14 men; mean age, 47.2 years; range, 24-65) with moderate to severe psoriasis [mean Psoriasis Area and Severity Index (PASI) score 9.8; range, 3.8-18.8] received climate therapy at the Gran Canarias for 3 weeks. Blood samples were drawn before and after 15 days of sun exposure. In addition, the patients' individual skin UV doses based on UV measurements were estimated. RESULTS: Sun exposure for 15 days lead to a 72.8% (+/- 18.0 SD) reduction in the PASI score in psoriasis patients. Although no direct correlation was observed between PASI score improvement and UVB dose, the sun exposure improved the vitamin D, lipid and carbohydrate status of the patients. The serum concentrations of 25-hydroxyvitamin D [25(OH)D] increased from 57.2 +/- 14.9 nmol/L before therapy to 104.5 +/- 15.8 nmol/L (P < 0.0001) after 15 days of sun exposure; the serum levels of 1,25-dihydroxyvitamin D [1,25(OH)(2)D] increased from 146.5 +/- 42.0 to 182.7 +/- 59.1 pmol/L (P = 0.01); the ratio of low-density lipoprotein cholesterol and high-density lipoprotein cholesterol decreased from 2.4 to 1.9 (P < 0.001); and the haemoglobin A(1)c (HbA(1)c) levels decreased from 5.6 +/- 1.7% to 5.1 +/- 0.3% (P < 0.0001). CONCLUSION: Climate therapy with sun exposure had a positive effect on psoriasis, vitamin D production, lipid and carbohydrate status.