Impact of microwave thermolysis energy levels on patient-reported outcomes for axillary hyperhidrosis and osmidrosis.

OBJECTIVE: Microwave thermolysis (MWT) is an emerging treatment for axillary hyperhidrosis reducing both sweat and odor. No prior studies have investigated and compared the different available energy settings of the MWT device. This study evaluated patient-reported outcome measures (PROMs) for axillary hyperhidrosis and osmidrosis following MWT treatment with two different energy levels. METHODS: Twenty adults with axillary hyperhidrosis and osmidrosis reported sweat on Hyperhidrosis Disease Severity scale (HDSS: 1-4) and odor on Odor scale (OS: 1-10), respectively, supplemented by overall Dermatology Life Quality Index (DLQI: 0-30). This was a prospective, randomized, patient-blinded and intraindividually controlled study with 3 months follow-up (FU). Randomization comprised MWT treatment of one axilla with a standard medium energy setting (energy level 3) and the contralateral axilla with a standard high energy setting (energy level 5). RESULTS: At baseline, patients reported substantial sweat and odor, negatively affecting their quality of life. At 3 months FU, PROMs showed improved quality of life with significantly reduced odor and sweat. Overall DLQI was reduced from a median of 10 to 4, with a median 6.5-point reduction (p = 0.0002). HDSS was reduced from a median of 4 to 2 on both sides, with a median reduction of 1 for medium energy level and 2 points for high energy level (p = 0.014). OS was reduced from a median of 8 to 3 for both energy levels, with a median reduction of 3.5 and 4.5 points for the medium and high energy level, respectively (p = 0.017). Local skin reactions were mild and transient, but slightly more pronounced following treatment with the high energy level. CONCLUSION: MWT effectively improved patients' quality of life, axillary sweat, and odor 3 months after on baseline treatment. Treatment with the high energy level presented a subtle but significant increase of efficacy based on PROMs for both sweat and odor. Patients were willing to accept a higher amount of temporary local skin reactions from a higher energy setting when experiencing greater odor and sweat reduction.

Childhood atopic dermatitis is associated with cardiovascular risk factors in young adulthood-A population-based cohort study.

BACKGROUND: Studies have indicated that atopic dermatitis (AD) is associated with an increased risk of cardiovascular disease (CVD). However, data are conflicting. Furthermore, the longitudinal effect of childhood AD on cardiovascular risk factors in young adulthood is less investigated. OBJECTIVES: To assess associations between AD in childhood and CVD risk factors in young adulthood. METHODS: The study encompasses longitudinal data from a population-based birth cohort. Participants with data up to age 24 years were included (n = 2270). The primary outcomes were body mass index (BMI), waist circumference (WC), body fat per cent (BF%) and blood pressure (BP) at 24 years. The secondary outcome was blood lipids. Severe AD was defined as AD in combination with sleep disturbance due to itching. RESULTS: In total, 18.6% (n = 420) had AD at 24 years. Males with AD had higher BMI (ßAdj. 0.81, 95% CI 0.15-1.47), BF% (ßAdj. 1.19, 95% CI 0.09-2.29), systolic BP (ßAdj. 1.92, 95% CI 0.02-3.82), total cholesterol (ßAdj. 0.14, 95% CI 0.00-0.28) and LDL cholesterol (ßAdj. 0.15, 95% CI 0.02-0.27) compared with males without AD. No associations were seen in females. Current AD with prepubertal onset was associated with increased BMI in both males (ßAdj. 0.89, 95% CI 0.11-1.67) and females (ßAdj. 0.72, 95% CI 0.11-1.33). At 24 years, 23.1% (n = 97) of all with AD, had severe disease, which was significantly associated with overweight in both sexes, with BMI (ßAdj. 1.83, 95% CI 0.72-2.94), WC (ßAdj. 4.03, 95% CI 1.54-6.52) and BF% (ßAdj. 2.49, 95% CI 0.60-4.39) in females and with BF% (ßAdj. 2.96, 95% CI 0.23-5.69) in males, compared with peers with mild to moderate AD. CONCLUSION: AD in males appears to be associated with CVD risk factors in young adulthood. The duration and severity of AD seem to be of importance in both sexes.

Tests of Lepton Universality Using B

Tests of lepton universality in B^{0}→K_{S}^{0}ℓ^{+}ℓ^{-} and B^{+}→K^{*+}ℓ^{+}ℓ^{-} decays where ℓ is either an electron or a muon are presented. The differential branching fractions of B^{0}→K_{S}^{0}e^{+}e^{-} and B^{+}→K^{*+}e^{+}e^{-} decays are measured in intervals of the dilepton invariant mass squared. The measurements are performed using proton-proton collision data recorded by the LHCb experiment, corresponding to an integrated luminosity of 9 fb^{-1} . The results are consistent with the standard model and previous tests of lepton universality in related decay modes. The first observation of B^{0}→K_{S}^{0}e^{+}e^{-} and B^{+}→K^{*+}e^{+}e^{-} decays is reported.

Angular Analysis of D

The first full angular analysis and an updated measurement of the decay-rate CP asymmetry of the D^{0}→π^{+}π^{-}µ^{+}µ^{-} and D^{0}→K^{+}K^{-}µ^{+}µ^{-} decays are reported. The analysis uses proton-proton collision data collected with the LHCb detector at center-of-mass energies of 7, 8, and 13 TeV. The dataset corresponds to an integrated luminosity of 9 fb^{-1}. The full set of CP -averaged angular observables and their CP asymmetries are measured as a function of the dimuon invariant mass. The results are consistent with expectations from the standard model and with CP symmetry.

Use of emollients and topical glucocorticoids among adolescents with eczema: data from the population-based birth cohort BAMSE.

BACKGROUND: Knowledge regarding how adolescents treat their eczema is sparse. OBJECTIVES: To explore the use of emollients and topical glucocorticoids in adolescents with eczema in relation to sex and disease severity, and to study dispensing patterns of topical glucocorticoids. METHODS: Questionnaire-based data on symptoms of eczema, eczema severity and treatment with emollients and topical glucocorticoids were obtained from 3108 adolescents in the Swedish population-based birth cohort BAMSE. Severity of reported eczema was evaluated with the BAMSE Eczema Severity Score (BESS) in a questionnaire and with the Patient-Oriented Eczema Measure in clinically examined patients with current eczema (n = 247). Information on dispensed topical glucocorticoids was obtained from the Swedish Prescribed Drug Register. RESULTS: In all, 10% of the adolescents reported eczema in the preceding year: 73% mild, 17% moderate and 10% severe according to BESS. Almost all used emollients, whereas use of topical glucocorticoids was reported by 55%, with no significant difference between sexes. The likelihood of treatment with emollients and topical glucocorticoids increased when the adolescents had symptoms of current eczema [adjusted odds ratio (OR) 5·95, 95% confidence interval (CI) 1·90-18·8], but not if they had more severe eczema compared with mild eczema (adjusted OR 1·57, 95% CI 0·58-4·25). Among those with reported eczema, 24% had a topical glucocorticoid dispensed in the preceding year, and among those with moderate-to-severe current eczema 24% had a dispensed potent topical glucocorticoid. CONCLUSIONS: This population-based study indicates that adolescents with eczema are undertreated or completely untreated, even those with severe eczema.

Prenatal maternal stress and atopic diseases in the child: a systematic review of observational human studies.

BACKGROUND: A growing number of studies suggest that maternal stress during pregnancy promotes atopic disorders in the offspring. This is the first systematic review to address prenatal maternal stress (PNMS) and the subsequent risk of atopy-related outcomes in the child. METHODS: The review was performed in accordance to the PRISMA criteria. We searched and selected studies in PubMed, Scopus, Embase and PsychINFO until November 2014. RESULTS: Sixteen (with 25 analyses) of 426 identified articles met the review criteria. Five main PNMS exposures (negative life events, anxiety/depression, bereavement, distress and job strain) and five main atopic outcomes (asthma, wheeze, atopic dermatitis, allergic rhinitis and IgE) were assessed across the studies. Overall, 21 of the 25 analyses suggested a positive association between PNMS and atopic outcomes. Of the 11 exposure-response analyses reported, six found statistically significant trends. CONCLUSION: This systematic review suggests a relationship between maternal stress during pregnancy and atopic disorders in the child. However, the existing studies are of diverse quality. The wide definitions of often self-reported stress exposures imply a substantial risk for information bias and false-positive results. Research comparing objective and subjective measures of PNMS exposure as well as objective measures for atopic outcome is needed.

Are allergic multimorbidities and IgE polysensitization associated with the persistence or re-occurrence of foetal type 2 signalling? The MeDALL hypothesis.

Allergic diseases [asthma, rhinitis and atopic dermatitis (AD)] are complex. They are associated with allergen-specific IgE and nonallergic mechanisms that may coexist in the same patient. In addition, these diseases tend to cluster and patients present concomitant or consecutive diseases (multimorbidity). IgE sensitization should be considered as a quantitative trait. Important clinical and immunological differences exist between mono- and polysensitized subjects. Multimorbidities of allergic diseases share common causal mechanisms that are only partly IgE-mediated. Persistence of allergic diseases over time is associated with multimorbidity and/or IgE polysensitization. The importance of the family history of allergy may decrease with age. This review puts forward the hypothesis that allergic multimorbidities and IgE polysensitization are associated and related to the persistence or re-occurrence of foetal type 2 signalling. Asthma, rhinitis and AD are manifestations of a common systemic immune imbalance (mesodermal origin) with specific patterns of remodelling (ectodermal or endodermal origin). This study proposes a new classification of IgE-mediated allergic diseases that allows the definition of novel phenotypes to (i) better understand genetic and epigenetic mechanisms, (ii) better stratify allergic preschool children for prognosis and (iii) propose novel strategies of treatment and prevention.

Depression and the risk of autoimmune disease: a nationally representative, prospective longitudinal study.

BACKGROUND: Autoimmune diseases are associated with substantial morbidity and mortality, yet the etiology remains unclear. Depression has been implicated as a risk factor for various immune-related disorders but little is known about the risk of autoimmune disease. This study examined the association between depression and the risk of autoimmune disease, and investigated the temporal and dose-response nature of these relationships. METHOD: A prospective population-based study including approximately 1.1 million people was conducted using linked Danish registries. Depression and autoimmune diseases were diagnosed by physicians and documented in medical records. In total, 145 217 individuals with depression were identified between 1995 and 2012. Survival analyses were used to estimate the relative risk of autoimmune disease among those with, compared to without, depression. Analyses were adjusted for gender, age, and co-morbid mental disorders. RESULTS: Depression was associated with a significantly increased risk of autoimmune disease [incidence rate ratio (IRR) 1.25, 95% CI 1.19-1.31], compared to those without a history of depression. Results suggest a general increased risk of autoimmune diseases following the onset of depression during first year (IRR 1.29, 95% CI 1.05-1.58), which remained elevated for the ensuing 11 years and beyond (IRR 1.53, 95% CI 1.34-1.76). Findings did not support a dose-response relationship. CONCLUSIONS: Depression appears to be associated with an increased risk of a range of autoimmune diseases. Depression may play a role in the etiology of certain autoimmune conditions. If replicated, findings could highlight additional clinical implications in the treatment and management of depression. Future studies are needed to investigate the possible social, genetic, and neurobiological underpinnings of these relationships.

Pulsar glitches: the crust is not enough.

Pulsar glitches are traditionally viewed as a manifestation of vortex dynamics associated with a neutron superfluid reservoir confined to the inner crust of the star. In this Letter we show that the nondissipative entrainment coupling between the neutron superfluid and the nuclear lattice leads to a less mobile crust superfluid, effectively reducing the moment of inertia associated with the angular momentum reservoir. Combining the latest observational data for prolific glitching pulsars with theoretical results for the crust entrainment, we find that the required superfluid reservoir exceeds that available in the crust. This challenges our understanding of the glitch phenomenon, and we discuss possible resolutions to the problem.

Ghanaian Female Adolescents Perceived Changes in Nutritional Behaviors and Social Environment After Creating Participatory Videos: A Most Significant Change Evaluation.

Background: Understanding the influence of participatory video-making on the nutrition-related behavior of video creators may help shape nutrition education interventions. Objectives: This study assessed the perceived value and influence of a participatory video intervention among participants and stakeholders. Methods: A 2018-2019 cluster randomized controlled trial (registered at clinicaltrials.gov as NCT03704649) selected 20 schools (10 intervention, n = 181; 10 control, n = 170) in 1 Ghanaian rural district, enrolled adolescent girls aged 13-16 y, and provided a nutrition curriculum. Each intervention school also participated in 2 series of activities designed to help adolescents plan, film, and screen 2 nutrition-related videos. The Most Significant Change method involved intervention participants and local stakeholders to assess the value and influence of the intervention - a secondary outcome of the trial. Project staff collected 116 stories of change from the adolescents. Stories described shifts in 4 domains: participant, peer, and family behavior, and structural changes in the school. The project team used a selection rubric to identify 14 stories that reflected heightened nutrition literacy. Staff conducted interviews with the 14 adolescents whose stories were selected to elaborate on details and perceived resonance. Finally, local stakeholders assessed the stories to identify the 4 most significant changes of the intervention - 1 per domain. A separate thematic analysis identified emerging patterns of motivation and action across the 14 interviews. Results: The chosen Most Significant Change stories revealed how adolescents found creative solutions to acquire iron-rich foods, encouraged neighbors to eat iron-rich foods, taught their family new agricultural practices, and promoted change in their school canteen. Local stakeholders valued stories that addressed common community nutrition issues in a creative and sustainable way, whereas adolescents prioritized stories that showed a change in health outcomes. Conclusion: Stories of change revealed that the intervention promoted a transformative influence; participants modified their eating habits, lifestyle, and their environment.

A variant near the interleukin-6 gene is associated with fat mass in Caucasian men.

CONTEXT: Regulation of fat mass appears to be associated with immune functions. Studies of knockout mice show that endogenous interleukin (IL)-6 can suppress mature-onset obesity. OBJECTIVE: To systematically investigate associations of single nucleotide polymorphisms (SNPs) near the IL-6 (IL6) and IL-6 receptor (IL6R) genes with body fat mass, in support for our hypothesis that variants of these genes can be associated with obesity. DESIGN AND STUDY SUBJECTS: The Gothenburg Osteoporosis and Obesity Determinants (GOOD) study is a population-based cross-sectional study of 18- to 20-year-old men (n=1049), from the Gothenburg area (Sweden). Major findings were confirmed in two additional cohorts consisting of elderly men from the Osteoporotic Fractures in Men (MrOS) Sweden (n=2851) and MrOS US (n=5611) multicenter population-based studies. MAIN OUTCOME: The genotype distributions and their association with fat mass in different compartments, measured with dual-energy X-ray absorptiometry. RESULTS: Out of 18 evaluated tag SNPs near the IL6 and IL6R genes, a recently identified SNP rs10242595 G/A (minor allele frequency=29%) 3' of the IL6 gene was negatively associated with the primary outcome total body fat mass (effect size -0.11 standard deviation (s.d.) units per A allele, P=0.02). This negative association with fat mass was also confirmed in the combined MrOS Sweden and MrOS US cohorts (effect size -0.05 s.d. units per A allele, P=0.002). When all three cohorts were combined (n=8927, Caucasian subjects), rs10242595(*)A showed a negative association with total body fat mass (effect size -0.05 s.d. units per A allele, P<0.0002). Furthermore, the rs10242595(*)A was associated with low body mass index (effect size -0.03, P<0.001) and smaller regional fat masses. None of the other SNPs investigated in the GOOD study were reproducibly associated with body fat. CONCLUSIONS: The IL6 gene polymorphism rs10242595(*)A is associated with decreased fat mass in three combined cohorts of 8927 Caucasian men.

Variants of the interleukin-1 receptor antagonist gene are associated with fat mass in men.

CONTEXT: Immune functions seem to have connections to variations in body fat mass. Studies of knockout mice indicate that endogenous interleukin (IL)-1 can suppress mature-onset obesity. OBJECTIVE: To systematically investigate our hypotheses that single-nucleotide polymorphisms (SNPs) and/or haplotypes variants in the IL-1 gene system are associated with fat mass. SUBJECTS: The Gothenburg osteoporosis and obesity determinants (GOOD) study is a population-based cross-sectional study of 18-20 year-old men (n=1068), from Gothenburg, Sweden. Major findings were confirmed in elderly men (n=3014) from the Swedish part of the osteoporotic fractures in men (MrOS) multicenter population-based study. MAIN OUTCOME MEASURE: The genotype distributions and their association with body fat mass in different compartments, measured with dual-energy X-ray absorptiometry (DXA). RESULTS: Out of 15 investigated SNPs in the IL-1 receptor antagonist (IL1RN) gene, a recently identified 3' untranslated region C>T (rs4252041, minor allele frequency=4%) SNP was associated with the primary outcome total fat mass (P=0.003) and regional fat masses, but not with lean body mass or serum IL-1 receptor 1 (IL1RN) levels. This SNP was also associated with body fat when correcting the earlier reported IL1RN+2018 T>C (rs419598) SNP (in linkage disequilibrium with a well-studied variable number tandem repeat of 86 bp). The association between rs4252041 SNP and body fat was confirmed in the older MrOS population (P=0.03). The rs4252041 SNP was part of three haplotypes consisting of five adjacent SNPs that were identified by a sliding window approach. These haplotypes had a highly significant global association with total body fat (P<0.001). None of the other investigated members of the IL-1 gene family displayed any SNPs that have not been described previously to be significantly associated with body fat. CONCLUSIONS: The IL1RN gene, shown to enhance obesity by suppressing IL-1 effects in experimental animals, have not [corrected] previously described gene polymorphisms and haplotypes that are associated with fat, but not lean mass in two populations of men.

Risk factors associated with recent transmission of tuberculosis: systematic review and meta-analysis.

A systematic review of published articles was performed to identify risk factors associated with recent transmission of tuberculosis (TB). The computerized search identified studies in PubMed, Ovid, CDSR, CINAHL and EMBASE published between 1994 and 2005. Of 137 articles, 30 satisfied all the inclusion criteria for meta-analysis. A random effects model estimated the odds ratio (OR), confidence interval (CI), and heterogeneity between studies. Recent transmission of TB was associated with: ethnic minority (OR 3.03, 95%CI 2.21- 4.16), being a native of the country (OR 2.33, 95%CI 1.76-3.08), residing in an urban area (OR 1.52, 95%CI 1.35-1.72), drug use (OR 3.01, 95%CI 2.14-4.22), excessive alcohol consumption (OR 2.27, 95%CI 1.69-3.06), homelessness (OR 2.87, 95%CI 2.04-4.02), previous incarceration (OR 2.21, 95%CI 1.71-2.86), human immunodeficiency virus infection/acquired immune-deficiency syndrome (OR 1.66, 95%CI 1.36-2.05), young age (OR 2.09, 95%CI 1.69-2.59), sputum smear positivity (OR 1.39, 95%CI 1.20-1.60) and male sex (OR 1.37, 95%CI 1.19-1.58). The results should be useful for improving prevention and control strategies, thus contributing to a reduction in Mycobacterium tuberculosis transmission.

Loneliness, health and mortality.

AIMS: Literature suggests an association between loneliness and mortality for both males and females. Yet, the linkage of loneliness to mortality is not thoroughly examined, and need to be replicated with a long follow-up time. This study assessed the association between loneliness and mortality, including associations to gender, in 1363 adult swedes. METHODS: This community-based prospective cohort study from the Swedish Lundby Study included 1363 individuals of whom 296 individuals (21.7%) were identified as lonely with use of semi-structured interviews in 1997. The cohort was followed until 2011 and survival analyses were used to estimate the relative risk of death. RESULTS: Death occurred with an incidence rate of 2.63 per 100 person-years and 2.09 per 100 person-years for lonely and non-lonely individuals, respectively. In crude analysis, loneliness was associated with a significant increased mortality risk of 27% compared with non-lonely individuals [hazard ratio (HR) 1.27; 95% CI 1.01-1.60]. Unadjusted, lonely females had a significant increased risk (HR 1.76; 95% CI 1.31-2.34) and adjusted insignificant increased mortality risk of 27% (HR 1.27; 95% CI 0.92-1.74), compared with non-lonely females. Lonely males were found to have an adjusted significant decreased risk of mortality (HR 0.50; 95% CI 0.32-0.80), compared with non-lonely males. CONCLUSIONS: Findings suggest an association between loneliness and increased risk of mortality and that gender differences may exist, which have not been previously reported. If replicated, our results indicate that loneliness may have differential physical implications in some subgroups. Future studies are needed to further investigate the influence of gender on the relationship.

Common themes and challenges in hemophilia care: a multinational perspective.

OBJECTIVE: To identify ways that provision of hemophilia care can be maximized at the local level, irrespective of available resources or cultural or geographic challenges. METHODS: The SHIELD group used its multinational experience to share examples of local initiatives that have been employed to deliver optimal hemophilia care. RESULTS: The examples were reviewed and categorized into four key themes: guidelines and algorithms for delivery of care; collaboration with patients and allied groups for care and education; registries for the monitoring of treatment and outcomes and health care planning and delivery; and opportunities for personalization of care. These themes were then incorporated into a road map for collaborative care in hemophilia that reflected the contribution of best practice. DISCUSSION: Differing healthcare reimbursement systems, budgetary constraints, and geographical and cultural factors make it difficult for any country to fully deliver ideal care for people with hemophilia. The SHIELD approach for collaborative care provides illustrative examples of how four key themes can be used to optimize hemophilia care in any setting. ABBREVIATIONS: AHCDC: Association of Hemophilia Clinic Directors of Canada; AICE: Italian Association of Hemophilia Centres; ATHN: American Thrombosis and Hemostasis Network; EAHAD: European Association for Haemophilia and Allied Disorders; EHC: European Hemophilia Consortium; FIX: Coagulation Factor IX; FVIII: Coagulation Factor VIII; HAL: Haemophilia Activity List; HJHS: Haemophilia Joint Health Score; HTC: Hemophilia Treatment Centre; HTCCNC: Hemophilia Treatment Centre Collaborative Network of China; MASAC: Medical and Scientific Advisory Council; MDT: Multidisciplinary team; NHD: National Haemophilia Database; NHF: National Hemophilia Foundation; PK: Pharmacokinetics; POCUS: Point of care ultrasound; PWH: People with haemophilia; SHIELD: Supporting Hemophilia through International Education, Learning and Development; WFH: World Federation of Hemophilia.

Identification of target cells for the genomic effects of estrogens in bone.

Estrogen has bone protective effects, but the exact mechanism behind these effects remains unclear. The aim of the present study was to identify the primary target cells in bone for the classical genomic effects of estrogens in vivo. For this purpose we have used reporter mice with a luciferase gene under the control of three estrogen-responsive elements (EREs), enabling detection of in vivo activation of gene transcription. Three-month-old ovariectomized mice were treated with a single dose (50 mug/kg) 17beta-estradiol (E2). Luciferase activity was analyzed in several tissues and in different bone marrow-derived lymphocyte enriched/depleted preparations using MacsMouse CD19 (for B lymphocytes) or CD90 (for T lymphocytes) MicroBeads (Miltenyi Biotec GmbH, Bergisch Gladbach, Germany). Histological characterization of cells with high luciferase content was performed using immunohistochemistry. Both cortical bone and bone marrow displayed a rapid (within 1 h) and pronounced E2-induced increase in luciferase activity. The luciferase activity in total bone marrow and in bone marrow depleted of lymphocytes was increased six to eight times more than in either B-lymphocyte or T-lymphocyte enriched cell fractions 4 h after the E2 injection, demonstrating that mature lymphocytes are not major direct targets for the genomic effect of estrogens in bone. Immunohistochemistry identified clear luciferase staining in hypertrophic growth plate chondrocytes, megakaryocytes, osteoblasts, and lining cells, whereas no staining was seen in proliferative chondrocyte. Although most of the osteocytes did not display any detectable luciferase staining, a subpopulation of osteocytes both in cortical and trabecular bone stained positive for luciferase. In conclusion, hypertrophic growth plate chondrocytes, megakaryocytes, osteoblasts, lining cells, and a subpopulation of osteocytes were identified to respond to estrogen via the classical ERE-mediated genomic pathway in bone. Furthermore, our findings indicate that possible direct estrogenic effects on the majority of osteocytes, not staining positive for luciferase, on proliferative chondrocytes and on mature lymphocytes are mediated by non-ERE actions.

Assessment of cerebrospinal fluid outflow conductance using an adaptive observer--experimental and clinical evaluation.

Idiopathic normal pressure hydrocephalus (INPH) patients have a disturbance in the dynamics of the cerebrospinal fluid (CSF) system. The outflow conductance, C, of the CSF system has been suggested to be prognostic for positive outcome after treatment with a CSF shunt. All current methods for estimation of C have drawbacks; these include lack of information on the accuracy and relatively long investigation times. Thus, there is a need for improved methods. To accomplish this, the theoretical framework for a new adaptive observer (OBS) was developed which provides real-time estimation of C. The aim of this study was to evaluate the OBS method and to compare it with the constant pressure infusion (CPI) method. The OBS method was applied to data from infusion investigations performed with the CPI method. These consisted of repeated measurements on an experimental set-up and 30 patients with suspected INPH. There was no significant difference in C between the CPI and the OBS method for the experimental set-up. For the patients there was a significant difference, -0.84+/-1.25 microl (s kPa)(-1), mean +/- SD (paired sample t-test, p<0.05). However, such a difference is within clinically acceptable limits. This encourages further development of this new real-time approach for estimation of the outflow conductance.

SHBG gene promoter polymorphisms in men are associated with serum sex hormone-binding globulin, androgen and androgen metabolite levels, and hip bone mineral density.

CONTEXT: SHBG regulates free sex steroid levels, which in turn regulate skeletal homeostasis. Twin studies have demonstrated that genetic factors largely account for interindividual variation in SHBG levels. Glucuronidated androgen metabolites have been proposed as markers of androgenic activity. OBJECTIVE: Our objective was to investigate whether polymorphisms in the SHBG gene promoter [(TAAAA)(n) microsatellite and rs1799941 single-nucleotide polymorphism] are associated with serum levels of SHBG, sex steroids, or bone mineral density (BMD) in men. DESIGN AND STUDY SUBJECTS: We conducted a population-based study of two cohorts of Swedish men: elderly men (MrOS Sweden; n congruent with 3000; average age, 75.4 yr) and young adult men (GOOD study; n = 1068; average age, 18.9 yr). MAIN OUTCOME MEASURES: We measured serum levels of SHBG, testosterone, estradiol, dihydrotestosterone, 5alpha-androstane-3alpha,17beta-diol glucuronides, androsterone glucuronide, and BMD determined by dual-energy x-ray absorptiometry. RESULTS: In both cohorts, (TAAAA)(n) and rs1799941 genotypes were associated with serum levels of SHBG (P < 0.001), dihydrotestosterone (P < 0.05), and 5alpha-androstane-3alpha,17beta-diol glucuronides (P < 0.05). In the elderly men, they were also associated with testosterone and BMD at all hip bone sites. The genotype associated with high levels of SHBG was also associated with high BMD. Interestingly, male mice overexpressing human SHBG had increased cortical bone mineral content in the femur, suggesting that elevated SHBG levels may cause increased bone mass. CONCLUSIONS: Our findings demonstrate that polymorphisms in the SHBG promoter predict serum levels of SHBG, androgens, and glucuronidated androgen metabolites, and hip BMD in men.