General somatic health and lifestyle habits in individuals with obsessive- compulsive disorder: an international survey.

BACKGROUND: Obsessive-compulsive disorder (OCD) has been associated with a broad range of health-related issues. Unhealthy lifestyle habits such as physical inactivity, an unhealthy diet, smoking, and alcohol consumption are hypothesized to contribute to this association. However, the lifestyle habits of individuals with OCD have been scarcely investigated. In this international survey, we explored the physical health and lifestyle habits of adults with a self-reported diagnosis of OCD. METHODS: An online global survey available in seven languages was disseminated through interest organizations and social media between July 2021 and March 2022. The survey included questions relating to socio-demographic variables and clinical characteristics (including OCD symptom severity - as measured with the 12-item self-report scale Obsessive-Compulsive Inventory [OCI-12] - and psychotropic medication), physical health, and lifestyle habits. Frequencies and percentages, or means and standard deviations, as appropriate, were calculated. Subgroup analyses by OCD symptom severity, gender, and age group were performed. RESULTS: A total of 496 individuals with OCD completed the survey and were included in the analyses (mean age = 36.0 years, SD = 12.5, range 18-79; 78.8% women). Most participants were from Europe (n = 245, 49.4%) and North America (n = 187, 37.7%). OCD symptom severity scores were on the moderate range (OCI-12 mean score = 21.2, SD = 9.1). A majority (n = 354, 71.4%) reported having comorbid somatic health issues, mainly allergies, gastrointestinal conditions, and cardiometabolic conditions. Nearly half of the sample (n = 236, 47.6%) reported a body mass index ≥ 25, corresponding to at least overweight. A significant proportion of the participants reported low physical activity (n = 271, 55.0%), unhealthy dietary habits (n = 182, 36.7%), risk consumption of alcohol (n = 111, 22.3%), and non-restorative sleep (n = 268, 54.0%). Subgroup analyses showed overall similar results across groups, with some exceptions. CONCLUSIONS: In this sample, individuals with OCD self-reported a range of health-related issues and a number of unhealthy lifestyle behaviors, most prominently a lack of physical activity. Interventions aimed at modifying unhealthy lifestyles to prevent or improve health conditions beyond the psychiatric symptoms should be considered.

Cervical cancer in Region Skåne, Sweden 2017-2020 after the implementation of primary HPV screening: A quality assurance audit.

INTRODUCTION: Primary human papilloma virus (HPV) screening to detect cervical cancer and dysplastic lesions was implemented in Region Skåne 2017 for women aged 30-70. The aim of this study was to characterize the screening history of women diagnosed with cervical cancer to evaluate the performance of the screening program, as well as to assess the cancer treatments given and shortcomings in the follow-up of women with cervical dysplasia. MATERIAL AND METHODS: We performed a quality assurance audit. The data was collected from the National Cervical Cancer Prevention Registry, Region Skåne Labmedicin database and the Melior Journal system in 2017-2020. RESULTS: We identified 247 women diagnosed with invasive cervical cancer in Region Skåne in 2017-2020. Of these, 35 (14.2%) had a screening history over at least two screening rounds before diagnosis. There were 25 (10.1%) women diagnosed with cervical cancer in between screening intervals, i.e., interval cancer. The most common screening history in women with cervical cancer was irregular screening (143, 57.9%), followed by women being above screening age (44, 17.8%). HPV was detected in 96% of the cases, either in cervical cytology or in the tumor tissue. The screening program detected the disease in 96 (38.9%) of the patients, 149 (60.3%) were diagnosed through symptoms and two (0.80%) as a result of incidental findings. CONCLUSIONS: The most powerful tool in the prevention of cervical cancer is screening program attendance. Prolongation with HPV screening among elderly women will also reduce the incidence of cervical cancer. Today, such cancers are usually discovered when symptoms appear.

Biofilm formation on three different endotracheal tubes: a prospective clinical trial.

BACKGROUND: Biofilm formation on endotracheal tubes (ETTs) is an early and frequent event in mechanically ventilated patients. The biofilm is believed to act as a reservoir for infecting microorganisms and thereby contribute to development and relapses of ventilator-associated pneumonia (VAP). Once a biofilm has formed on an ETT surface, it is difficult to eradicate. This clinical study aimed to compare biofilm formation on three widely used ETTs with different surface properties and to explore factors potentially predictive of biofilm formation. METHODS: We compared the grade of biofilm formation on ETTs made of uncoated polyvinyl chloride (PVC), silicone-coated PVC, and PVC coated with noble metals after > 24 h of mechanical ventilation in critically ill patients. The comparison was based on scanning electron microscopy of ETT surfaces, biofilm grading, surveillance and biofilm cultures, and occurrence of VAP. RESULTS: High-grade (score ≥ 7) biofilm formation on the ETTs was associated with development of VAP (OR 4.17 [95% CI 1.14-15.3], p = 0.031). Compared to uncoated PVC ETTs, the silicone-coated and noble-metal-coated PVC ETTs were independently associated with reduced high-grade biofilm formation (OR 0.18 [95% CI 0.06-0.59], p = 0.005, and OR 0.34 [95% CI 0.13-0.93], p = 0.036, respectively). No significant difference was observed between silicon-coated ETTs and noble-metal-coated ETTs (OR 0.54 [95% CI 0.17-1.65], p = 0.278). In 60% of the oropharyngeal cultures and 58% of the endotracheal cultures collected at intubation, the same microorganism was found in the ETT biofilm at extubation. In patients who developed VAP, the causative microbe remained in the biofilm in 56% of cases, despite appropriate antibiotic therapy. High-grade biofilm formation on ETTs was not predicted by either colonization with common VAP pathogens in surveillance cultures or duration of invasive ventilation. CONCLUSION: High-grade biofilm formation on ETTs was associated with development of VAP. Compared to the uncoated PVC ETTs, the silicone-coated and noble-metal-coated PVC ETTs were independently associated with reduced high-grade biofilm formation. Further research on methods to prevent, monitor, and manage biofilm occurrence is needed. TRIAL REGISTRATION: ClinicalTrials.gov NCT02284438 . Retrospectively registered on 21 October 2014.

75% success rate after open debridement, exchange of tibial insert, and antibiotics in knee prosthetic joint infections.

BACKGROUND AND PURPOSE: Prosthetic joint infection (PJI) is a leading cause of early revision after total knee arthroplasty (TKA). Open debridement with exchange of tibial insert allows treatment of infection with retention of fixed components. We investigated the success rate of this procedure in the treatment of knee PJIs in a nationwide material, and determined whether the results were affected by microbiology, antibiotic treatment, or timing of debridement. PATIENTS AND METHODS: 145 primary TKAs revised for the first time, due to infection, with debridement and exchange of the tibial insert were identified in the Swedish Knee Arthroplasty Register (SKAR). Staphylococcus aureus was the most common pathogen (37%) followed by coagulase-negative staphylococci (CNS) (23%). Failure was defined as death before the end of antibiotic treatment, revision of major components due to infection, life-long antibiotic treatment, or chronic infection. RESULTS: The overall healing rate was 75%. The type of infecting pathogen did not statistically significantly affect outcome. Staphylococcal infections treated without a combination of antibiotics including rifampin had a higher failure rate than those treated with rifampin (RR = 4, 95% CI: 2-10). In the 16 cases with more than 3 weeks of symptoms before treatment, the healing rate was 62%, as compared to 77% in the other cases (p = 0.2). The few patients with a revision model of prosthesis at primary operation had a high failure rate (5 of 8). INTERPRETATION: Good results can be achieved by open debridement with exchange of tibial insert. It is important to use an antibiotic combination including rifampin in staphylococcal infections.

A unique role of the cholera toxin A1-DD adjuvant for long-term plasma and memory B cell development.

Adjuvants have traditionally been appreciated for their immunoenhancing effects, whereas their impact on immunological memory has largely been neglected. In this paper, we have compared three mechanistically distinct adjuvants: aluminum salts (Alum), Ribi (monophosphoryl lipid A), and the cholera toxin A1 fusion protein CTA1-DD. Their influence on long-term memory development was dramatically different. Whereas a single immunization i.p. with 4-hydroxy-3-nitrophenyl acetyl (NP)-chicken γ-globulin and adjuvant stimulated serum anti-NP IgG titers that were comparable at 5 wk, CTA1-DD-adjuvanted responses were maintained for >16 mo with a half-life of anti-NP IgG ∼36 wk, but <15 wk after Ribi or Alum. A CTA1-DD dose-dependent increase in germinal center (GC) size and numbers was found, with >60% of splenic B cell follicles hosting GC at an optimal CTA1-DD dose. Roughly 7% of these GC were NP specific. This GC-promoting effect correlated well with the persistence of long-term plasma cells in the bone marrow and memory B cells in the spleen. CTA1-DD also facilitated increased somatic hypermutation and affinity maturation of NP-specific IgG Abs in a dose-dependent fashion, hence arguing that large GC not only promotes higher Ab titers but also high-quality Ab production. Adoptive transfer of splenic CD80(+), but not CD80(-), B cells, at 1 y after immunization demonstrated functional long-term anti-NP IgG and IgM memory cells. To our knowledge, this is the first report to specifically compare and document that adjuvants can differ considerably in their support of long-term immune responses. Differential effects on the GC reaction appear to be the basis for these differences.

Effectiveness of ciprofloxacin or linezolid in combination with rifampicin against Enterococcus faecalis in biofilms.

OBJECTIVES: To assess the in vitro antibiotic susceptibility of Enterococcus faecalis in biofilms. METHODS: E. faecalis isolates were from infections of prosthetic hip and knee joints. Minimal biofilm eradication concentrations (MBECs) for ampicillin, vancomycin, linezolid, ciprofloxacin and rifampicin, alone and in combinations, were determined. E. faecalis biofilms in microtitre plate wells or on beads of bone cement were treated with the same antibiotics for various times followed by plating to quantify surviving bacteria. RESULTS: The E. faecalis isolates displayed MBECs for the various antibiotics of between 64 and 512 mg/L. When combined with 8 mg/L rifampicin, MBECs for ciprofloxacin and linezolid dropped to 16-32 mg/L for the four isolates tested. In biofilms formed on a plastic surface and on bone cement beads significant bacterial killing (>2-3 log decrease in cfus) was seen after an 8 h exposure to antibiotics. For all isolates, the combination of ciprofloxacin and rifampicin, followed by linezolid and rifampicin, was most effective in reducing the number of bacteria. E. faecalis developed resistance to rifampicin in our system when biofilms were subjected to this antibiotic, alone or in combination with ampicillin. When bacteria were subjected to combinations with ciprofloxacin or linezolid development of resistance was reduced. CONCLUSIONS: Our results show that combinations of ciprofloxacin or linezolid with rifampicin have a good effect on E. faecalis biofilms in vitro. These combinations should be considered for testing in humans with early joint prosthesis infections with E. faecalis.

CD11c(high )dendritic cells are essential for activation of CD4+ T cells and generation of specific antibodies following mucosal immunization.

To generate vaccines that protect mucosal surfaces, a better understanding of the cells required in vivo for activation of the adaptive immune response following mucosal immunization is required. CD11c(high) conventional dendritic cells (cDCs) have been shown to be necessary for activation of naive CD8(+) T cells in vivo, but the role of cDCs in CD4(+) T cell activation is still unclear, especially at mucosal surfaces. The activation of naive Ag-specific CD4(+) T cells and the generation of Abs following mucosal administration of Ag with or without the potent mucosal adjuvant cholera toxin were therefore analyzed in mice depleted of CD11c(high) cDCs. Our results show that cDCs are absolutely required for activation of CD4(+) T cells after oral and nasal immunization. Ag-specific IgG titers in serum, as well as Ag-specific intestinal IgA, were completely abrogated after feeding mice OVA and cholera toxin. However, giving a very high dose of Ag, 30-fold more than required to detect T cell proliferation, to cDC-ablated mice resulted in proliferation of Ag-specific CD4(+) T cells. This proliferation was not inhibited by additional depletion of plasmacytoid DCs or in cDC-depleted mice whose B cells were MHC-II deficient. This study therefore demonstrates that cDCs are required for successful mucosal immunization, unless a very high dose of Ag is administered.

Association between SARS-CoV-2 and exposure risks in health care workers and university employees - a cross-sectional study.

BACKGROUND: In health care workers SARS-CoV-2 has been shown to be an occupational health risk, often associated with transmission between health care workers. Yet, insufficient information on transmission dynamics has been presented to elucidate the precise risk factors for contracting SARS-CoV-2 in this group. METHODS: In this cross-sectional study, we investigated association between questionnaire answers on potential exposure situations and SARS-CoV-2-positivity. Health care workers with and without COVID-19-patient contact at nine units at Skåne University Hospitals in Malmö and Lund, Sweden and university employees from Lund University, Sweden were enrolled. To limit impact of health care worker to health care worker transmission, units with known outbreaks were excluded. A SARS-CoV-2-positive case was defined by a previous positive PCR or anti-SARS-CoV-2 IgG in the ZetaGene COVID-19 Antibody Test. RESULTS: SARS-CoV-2-positivity was detected in 11/51 (22%) health care workers in COVID-19-units, 10/220 (5%) in non-COVID-19-units and 11/192 (6%) University employees (p = .001, Fischer's exact). In health care workers, SARS-CoV-2-positivity was associated with work in a designated COVID-19-unit (OR 5.7 (95CI 2.1-16)) and caring for COVID-19-patients during the majority of shifts (OR 5.4 (95CI 2.0-15)). In all participants, SARS-CoV-2-positivity was associated with a confirmed COVID-19 case (OR 10 (95CI 2.0-45)) in the household. CONCLUSION: Our study confirmed previous findings of elevated risk of acquiring SARS-CoV-2 in health care workers in COVID-19-units, despite exclusion of units with known outbreaks. Interestingly, health care workers in non-COVID-19-units had similar risk as University employees. Further measures to improve the safety of health care workers might be needed.KEY POINTSPrevious findings of elevated risk of contracting SARS-CoV-2 in health care workers with COVID-19 patient contact was confirmed, despite exclusion of wards with known SARS-CoV-2 outbreaks. Further measures to improve the safety of health care workers might be needed.

Post-outbreak serological screening for SARS-CoV-2 infection in healthcare workers at a Swedish University Hospital.

BACKGROUND: Nosocomial outbreaks of coronavirus disease 2019 (COVID-19) can have devastating consequences from both a resource cost and patient healthcare perspective. Relying on reverse transcription-polymerase chain reaction (RT-PCR) for identifying infected individuals may result in missed cases. Screening for antibodies after an outbreak can help to find missed cases and better illuminate routes of transmission. METHODS: In this study, we present the results of a serological screening of the healthcare workers (HCWs) on a ward for infectious diseases in Sweden with a point-of-care antibody test 8 weeks after an outbreak of COVID-19. In all, 107/123 (87%) of HCWs who were tested with RT-PCR in the outbreak investigation participated in this study on seroprevalence. Participants were also asked to fill out a questionnaire entailing epidemiological data. The cohort was stratified by RT-PCR result and the resulting groups were compared to each other. RESULTS: Six (8%) HCWs who were tested RT-PCR negative during the outbreak investigation had developed specific IgG antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). These HCWs had all worked shifts with colleagues who later were tested RT-PCR positive during the outbreak. CONCLUSIONS: Our results indicate that a serological follow-up screening after an outbreak may be used as a complement to virus detection in an outbreak situation. However, immunoglobulin (Ig) G-detection should also be performed at the start of an outbreak, to facilitate interpretation of the results.

Heterozygosity for a coding SNP in COL1A2 confers a lower BMD and an increased stroke risk.

Genetic variation plays an important role in osteoporosis and a prime candidate gene is Collagen alpha2(I) (COL1A2). A coding polymorphism (rs42524) in COL1A2 has previously been associated with intracranial aneurysms. Here the effects of this polymorphism have been studied in relation to bone mineral density (BMD) and prevalences of stroke and myocardial infarction (MI). rs42524 was genotyped in elderly men (n = 2004) from the Swedish MrOS cohort. Genotypes were analysed for association to BMD and certain health parameters. Significant associations (overall P < 0.05), were observed between rs42524 genotype and BMD at several skeletal sites. Surprisingly, the heterozygote genotype class exhibited lower BMD than either homozygote group. When subjects were classified as heterozygotes or homozygotes, the heterozygous genotype was found to confer a lower BMD at total hip, femoral neck and trochanter Furthermore, the heterozygote genotype had an increased risk of stroke and MI, with population Attributable Risks being 0.12 and 0.08, respectively.

Primary screening for increased fracture risk by the FRAX® questionnaire-uptake rates in relation to invitation method.

The aim of the study was to evaluate the feasibility and most efficient way of offering middle-aged Swedish women a primary fracture screening program via a questionnaire. Two out of five invited women returned the FRAX questionnaire and those contacted directly by mail were most prone to respond. PURPOSE: Osteoporosis and its associated fractures are increasing, and this study aims to explore ways to identify women at an increased risk of fracture using the FRAX® algorithm. METHODS: Three thousand middle-aged women were invited and presented a questionnaire distributed by three different methods-by mail, at routine mammography, or internet-based. RESULTS: In total, 1120 (37.3%) women responded to the questionnaire and agreed to participate. The response rates for the mail, mammography, and internet-based groups were 39.1%, 35.7%, and 25.2% respectively. Women in the mammography group weighed more, were slightly older than the other women, and also had a higher BMI than women from the mail and internet-based groups. No difference was observed between the groups regarding previous fracture, family history for fracture, current smoking, glucocorticoid use, and alcohol usage. The mammography group had a higher median (interquartile range) major osteoporotic FRAX® score (10.0% (7.8-17.0)) than the mail group (9.7% (7.1-15.0); p = 0.005) and the internet-based group (8.7% (6.7-14.0); p = 0.001). CONCLUSIONS: Two out of five early postmenopausal women returned the questionnaire and women contacted directly by mail were more prone to respond. Out of the participants, 26.6% had a 10-year fracture risk score ≥ 15% according to the FRAX® algorithm.

The COMT val158met polymorphism is associated with prevalent fractures in Swedish men.

INTRODUCTION: Sex steroids are important for growth and maintenance of the skeleton. Catechol-O-methyltransferase (COMT) is an estrogen degrading enzyme. The COMT val158met polymorphism results in a 60-75% difference in enzyme activity between the val (high activity=H) and met (low activity=L) variants. We have previously reported that this polymorphism is associated with bone mineral density (BMD) in young men. The aim of this study was to investigate associations between COMT val158met, BMD and fractures in elderly men. METHODS: Population-based study of Swedish men 75.4, SD 3.2, years of age. Fractures were reported using standardized questionnaires. Fracture and genotype data were available from 2,822 individuals. RESULTS: Total number of individuals with self-reported fracture was 989 (35.0%). Prevalence of >or=1 fracture was 37.2% in COMT(LL), 35.7% in COMT(HL) and 30.4% in COMT(HH) (p<0.05). Early fractures (50 years of age). The OR for fracture of the non-weight bearing skeleton in COMT(HH) compared with COMT(LL+HL) was 0.74 (95% CI 0.59-0.92). No associations between COMT val158met and BMD were found in this cohort of elderly men. CONCLUSIONS: The COMT val158met polymorphism is associated with life time fracture prevalence in elderly Swedish men. This association is mainly driven by early fractures (

Inducible Siphoviruses in superficial and deep tissue isolates of Propionibacterium acnes.

BACKGROUND: Propionibacterium acnes is a commensal of human skin but is also known to be involved in certain diseases, such as acne vulgaris and infections of orthopaedic implants. Treatment of these conditions is complicated by increased resistance to antibiotics and/or biofilm formation of P. acnes bacteria. P. acnes can be infected by bacteriophages, but until recently little has been known about these viruses. The aim of this study was to identify and characterize inducible phages from P. acnes on a genetic and morphological basis. RESULTS: More than 70% (65/92) of P. acnes isolates investigated have inducible phages, classified morphologically as Siphoviruses. The phages have a head of 55 nm in diameter and a tail of 145-155 nm in length and 9-10 nm in width. There was no difference in carriage rate of phages between P. acnes isolates from deep infections and isolates from skin. However, there was a significant lower carriage rate of phages in P. acnes biotype IB, mostly attributed to the low carriage rate of inducible phages in biotype IB isolated from deep tissue. Most phages have a strong lytic activity against all P. acnes isolates with inducible phages, but have less lytic activity against isolates that have no prophages. Phages only infected and lysed P. acnes and not other closely related propionibacteria. All phages could infect and lyse their non-induced parental host, indicating that these prophages do not confer superinfection immunity. The phages have identical protein pattern as observed on SDS-PAGE. Finally, sequencing of two phage genes encoding a putative major head protein and an amidase and showed that the phages could be divided into different groups on a genetic basis. CONCLUSION: Our findings indicate that temperate phages are common in P. acnes, and that they are a genetically and functionally homogeneous group of Siphoviruses. The phages are specific for P. acnes and do not seem to confer superinfection immunity.

Cardiovascular biomarkers and risk of low-energy fractures among middle-aged men and women-A population-based study.

BACKGROUND: Low-energy fractures are a growing health challenge as their incidence increases with advancing age. As cardiovascular instability may be associated with higher likelihood of traumatic falls, we aimed to investigate the associations between four cardiovascular biomarkers and the risk of low-energy fractures in a middle-aged population. METHODS: A total of 5291 individuals from the prospective Malmö Diet and Cancer (MDC) study (mean age, 57 years; 59% women) with data on baseline levels of four cardiovascular biomarkers: mid-regional-fragment of pro-adrenomedullin-peptide (MR-pro-ADM), mid-regional-fragment of pro-atrial-natriuretic-peptide (MR-proANP), N-terminal pro-brain natriuretic peptide (NT-pro-BNP) and C-terminal-pro-arginine-vasopressin (CT-pro-AVP/Copeptin) were included. The associations between biomarker levels and first incident low-energy fracture were tested in Cox proportional-hazard models, taking potential interactions and traditional risk factors into account. RESULTS: Participants were followed for a median time of 21.0 years, during which 1002 subjects (19%) experienced at least one low-energy fracture. Subjects with incident fracture were older, more likely to be women, had lower BMI and higher prevalence of previous fractures. Among biomarkers, there was a significant interaction between gender and MR-pro-ADM on the risk of fracture (p = 0.002). MR-pro-ADM predicted fractures in men only (hazard ratio, 1.23; 95% CI 1.09-1.40; p = 0.001), whereas there was no association among women. Levels of MR-pro-ANP, NT-pro-BNP and CT-pro-AVP did not predict fractures. CONCLUSIONS: Higher circulating levels of MR-pro-ADM predict low-energy fractures among middle-aged-men, whereas levels of MR-pro-ANP, NT-pro-BNP and CT-pro-AVP are not associated with increased fracture risk. Further controlled studies should test the hypothesis whether MR-pro-ADM may improve prediction of bone fractures.

Vitamin D receptor 3' haplotypes are unequally expressed in primary human bone cells and associated with increased fracture risk: the MrOS Study in Sweden and Hong Kong.

UNLABELLED: The VDR is a prime candidate gene for osteoporosis. Here, we studied three common VDR haplotypes in relation to bone phenotypes in 5014 participants of the global MrOS Study. We also studied the relative expression of the haplotypes in human bone cells. One haplotype was associated with increased fracture risk and differently expressed in primary human bone cells. INTRODUCTION: Vitamin D plays an essential role in skeletal metabolism by binding to its nuclear steroid receptor, the vitamin D receptor (VDR). The heritability of BMD is well established, and the VDR gene is considered a prime candidate suggested to partially account for genetically controlled BMD variance in the population. MATERIALS AND METHODS: Here, we reconstructed common haplotypes in the VDR 3' untranslated region (UTR) and studied the association to BMD and risk of vertebral fractures in elderly men from Sweden (n = 3014) and Hong Kong (n = 2000), all participants of the global MrOS Study. To assess any functional implications of the VDR polymorphisms, we studied allele-specific expressions of the different VDR 3' UTR haplotypes in the normal chromosomal context of 70 unrelated human trabecular bone samples. This was performed by quantitative genotyping of coding polymorphisms in RNA samples and in corresponding DNA samples isolated from the bone samples. RESULTS: Three major haplotypes were reconstructed and in agreement with the previously well-defined baT, BAt, and bAT haplotypes, herein denoted Hap1, Hap2, and Hap3. The Hap1 haplotype was independently associated with increased risk of vertebral fractures in Swedish men (OR, 1.655; 95% CI, 1.146-2.391; p < 0.01) and with lower lumbar spine BMD in elderly men from Sweden (p < 0.01) and Hong Kong (p < 0.05). The VDR gene was also shown to exhibit a 3' UTR haplotype dependent allelic imbalance, indicating that the VDR Hap1 allele was overexpressed in human trabecular bone samples. CONCLUSIONS: The results indicate that the relatively overexpressed VDR Hap1 haplotype could be considered a risk allele for osteoporosis regardless of ethnicity.

The impact of estradiol on bone mineral density is modulated by the specific estrogen receptor-alpha cofactor retinoblastoma-interacting zinc finger protein-1 insertion/deletion polymorphism.

CONTEXT: Estrogens regulate bone mass by binding to the estrogen receptor (ER)-alpha as well as ER-beta. The specific ERalpha cofactor retinoblastoma-interacting zinc finger protein (RIZ)-1 enhances ERalpha function in the presence of estrogen. OBJECTIVE: The objective of the study was to determine whether a RIZ P704 insertion (+)/deletion (-) (indel) polymorphism modulates the impact of estradiol on bone mineral density (BMD) and study the association between the polymorphism and BMD in elderly subjects. DESIGN: This was a population-based, prospective, and cross-sectional study, the Swedish MrOS Study, and the Malmö OPRA Study, respectively. SETTING: The study was conducted at three academic medical centers: Sahlgrenska Academy in Gothenburg, Malmö University Hospital, and Uppsala University Hospital. PARTICIPANTS: In total, 4058 men and women, aged 69-81 yr, were randomly selected from population registries. MAIN OUTCOME MEASURES: BMD (grams per square centimeter) was measured at femoral neck, trochanter, lumbar spine, and total body. RESULTS: The RIZ P704(+/+) genotype was associated with low BMD in both women (femoral neck, P < 0.001; trochanter, P < 0.01; lumbar spine, P < 0.05; total body, P < 0.01) and men (lumbar spine, P < 0.05). However, the association between the polymorphism and BMD was dependent on estradiol status. The positive correlation between serum estradiol and BMD was significantly modulated by the genotype with a stronger correlation in the P704(+/+) group than the P704(-/-) group (r = 0.19 vs. r = 0.08, P < 0.05). CONCLUSIONS: These large-scale studies of elderly men and women indicate that the ERalpha cofactor RIZ gene has a prominent effect on BMD, and the P704 genotype modulates the impact of estradiol on BMD. Further studies are required to determine whether this polymorphism modulates the estrogenic response to estradiol treatment.

The effects of saltwater acclimation on neurotransmitters in the lingual salt glands of the estuarine crocodile, Crocodylus porosus.

INTRODUCTION: Most avian and reptilian salt glands display marked phenotypic plasticity when animals are exposed to hyperosmotic conditions. In addition, the activity of most salt glands is under considerable control by the nervous system and nerves containing cholinergic, adrenergic and peptidergic neurotransmitters have been identified in avian and reptilian salt gland tissues. The present study sought to determine whether the salt glands of the estuarine crocodile, Crocodylus porosus contain the peptidergic neurotransmitters SP, CGRP, VIP, and PACAP and the gaseous neurotransmitter, NO. In addition, we sought to determine whether there was any evidence for the adaptation of the C. porosus salt gland nervous system to hyperosmotic conditions. METHODS: Salt glands from freshwater- and saltwater-acclimated C. porosus hatchlings were sectioned and examined immunohistochemically for neurotransmitters within the tissue. RESULTS: Neurons containing SP, CGRP, VIP, PACAP and NO synthase were identified within C. porosus salt glands. There was no difference in the overall number (density) of neurons within SW-acclimated tissues when compared with FW-acclimated animals. However, there was a significant reduction in density of neurons containing SP and PACAP in SW-acclimated animals. CONCLUSION: C. porosus salt glands display phenotypic plasticity following exposure to hyperosmotic conditions. In addition to cholinergic and adrenergic neurons, they contain a variety of peptidergic neurotransmitters and the gaseous neurotransmitter NO. Additionally, there appears to be some evidence of acclimation of the nervous system of C. porosus to hypersaline conditions, although the functional significance of these changes remains to be determined.

Free testosterone is an independent predictor of BMD and prevalent fractures in elderly men: MrOS Sweden.

UNLABELLED: The role of androgens for bone health in elderly men is unclear. We show that free testosterone within the normal range is a predictor of BMD at predominantly cortical bone sites and of previous osteoporosis-related fractures in elderly Swedish men. INTRODUCTION: Osteoporosis-related fractures constitute a major health concern not only in women but also in men. Previous studies have clearly shown that serum levels of estradiol are associated with BMD, whereas more conflicting data have been presented regarding the predictive value of testosterone (T) for bone health in elderly men. The aim of this study was to investigate if serum levels of T are associated with BMD and/or prevalent fractures in a large cohort of elderly men. MATERIALS AND METHODS: In the Swedish part of the MrOS study (n = 2908; average age, 75.4 years), bone parameters were measured using DXA, and prevalent fractures were recorded using standardized questionnaires and by vertebral X-ray analyses. Serum levels of total T, total estradiol (E2), and sex hormone-binding globulin (SHBG) were measured by radioimmunoassay, and free T (FT) and free E2 (FE2) were derived from the mass action equations. Height, weight, age, physical activity, smoking habits, and calcium intake were included together with FT and FE2 in regression models for BMD. RESULTS: FT was an independent positive predictor of BMD in total body, total hip, femur trochanter, and arm but not in the lumbar spine. The highest independent predictive value of FT was found in the arm and the hip (with a relatively high content of cortical bone). FE2 was an independent predictor of BMD at all bone sites studied, and the highest predictive value was seen for lumbar spine (with relatively high content of trabecular bone) BMD. FT but not FE2 was a positive predictor of total body bone area and BMC. FT levels below the median were independent predictors of prevalent osteoporosis-related fractures (OR, 1.56; 95% CI, 1.14-2.14; p < 0.01) and X-ray-verified vertebral fractures (OR, 2.00; 95% CI, 1.34-2.86; p < 0.001). The predictive value of FT for prevalent fractures was not affected by adjustment for BMD. CONCLUSIONS: These findings show that variation of FT within the normal range is an independent but modest predictor of BMD at predominantly cortical bone sites and of previous osteoporosis-related fractures in elderly men. Our data indicate that not only estrogens but also androgens are of importance for bone health in elderly men. Longitudinal studies investigating the predictive value of T for fracture risk in elderly men are required.

Mature biofilms of Enterococcus faecalis and Enterococcus faecium are highly resistant to antibiotics.

Enterococcus faecalis and Enterococcus faecium are important nosocomial pathogens that form biofilms on implanted materials. We compare the antibiotic sensitivity of bacteria in new (established during 24 hours) and mature (established during 120 hours) enterococcal biofilms. Mature biofilms contained more bacteria and were much more tolerant to antibiotics, including rifampicin-containing combinations, as judged by determination of minimal biofilm eradication concentrations and by time-kill experiments of bacteria in biofilms formed on beads of bone cement.

Orthostatic Hypotension and Elevated Resting Heart Rate Predict Low-Energy Fractures in the Population: The Malmö Preventive Project.

BACKGROUND: Autonomic disorders of the cardiovascular system, such as orthostatic hypotension and elevated resting heart rate, predict mortality and cardiovascular events in the population. Low-energy-fractures constitute a substantial clinical problem that may represent an additional risk related to such autonomic dysfunction. AIMS: To test the association between orthostatic hypotension, resting heart rate and incidence of low-energy-fractures in the general population. METHODS AND RESULTS: Using multivariable-adjusted Cox regression models we investigated the association between orthostatic blood pressure response, resting heart rate and first incident low-energy-fracture in a population-based, middle-aged cohort of 33 000 individuals over 25 years follow-up. The median follow-up time from baseline to first incident fracture among the subjects that experienced a low energy fracture was 15.0 years. A 10 mmHg orthostatic decrease in systolic blood pressure at baseline was associated with 5% increased risk of low-energy-fractures (95% confidence interval 1.01-1.10) during follow-up, whereas the resting heart rate predicted low-energy-fractures with an effect size of 8% increased risk per 10 beats-per-minute (1.05-1.12), independently of the orthostatic response. Subjects with a resting heart rate exceeding 68 beats-per-minute had 18% (1.10-1.26) increased risk of low-energy-fractures during follow-up compared with subjects with a resting heart rate below 68 beats-per-minute. When combining the orthostatic response and resting heart rate, there was a 30% risk increase (1.08-1.57) of low-energy-fractures between the extremes, i.e. between subjects in the fourth compared with the first quartiles of both resting heart rate and systolic blood pressure-decrease. CONCLUSION: Orthostatic blood pressure decline and elevated resting heart rate independently predict low-energy fractures in a middle-aged population. These two measures of subclinical cardiovascular dysautonomia may herald increased risks many years in advance, even if symptoms may not be detectable. Although the effect sizes are moderate, the easily accessible clinical parameters of orthostatic blood pressure response and resting heart rate deserve consideration as new risk predictors to yield more accurate decisions on primary prevention of low-energy fractures.