Levator ani muscle avulsion and subsequent vaginal delivery: 8-year longitudinal follow-up.

OBJECTIVES: To assess the evolution of levator ani muscle (LAM) avulsion from 1 year to 8 years after first delivery in women with and those without subsequent vaginal delivery. In addition, to assess whether women with full or partial avulsion 8 years after first delivery have larger LAM hiatal area and more symptoms of pelvic organ prolapse compared to women with normal LAM insertion. METHODS: In this single-center longitudinal study, 195 women who were primiparous at the start of the study were included and underwent transperineal ultrasound examination 1 year and 8 years after first delivery. Muscle insertion was assessed by tomographic ultrasound imaging in the axial plane. Full LAM avulsion was defined as abnormal muscle insertion in all three central slices. Partial LAM avulsion was defined as abnormal muscle insertion in one or two central slices. Eight years after the first delivery, LAM hiatal area was assessed at rest, during maximum pelvic floor muscle contraction and on maximum Valsalva maneuver. To assess symptoms of pelvic organ prolapse, the vaginal symptoms module of the International Consultation on Incontinence Questionnaire was used. RESULTS: At 1-year follow-up, 25 (12.8%) women showed signs of LAM avulsion, of whom 20 fulfilled the sonographic criteria of full avulsion and five of partial avulsion. Eight years after the first delivery, 35 (17.9%) women were diagnosed with avulsion, of whom 25 were diagnosed with full avulsion and 10 with partial avulsion. No woman with partial or full avulsion at 1 year had improved avulsion status at 8-year follow-up. Of the 150 women who had subsequent vaginal delivery, 21 (14.0%) women were diagnosed with partial or full LAM avulsion 1 year after first delivery, and 31 (20.7%) women were diagnosed with partial or full avulsion 8 years after first delivery. Of the 45 women without subsequent vaginal delivery, one woman with partial avulsion 1 year after first delivery was diagnosed with full avulsion at 8-year follow-up. All women with full avulsion at 1-year follow-up were diagnosed with full avulsion at 8-year follow-up regardless of whether they had subsequent vaginal delivery. At 8-year follow-up, women with full avulsion had statistically significantly larger LAM hiatal area compared to women with normal muscle insertion. Mean ± SD vaginal symptom scores ranged between 5.5 ± 5.7 and 6.0 ± 4.0 and vaginal symptom quality of life scores ranged between 0.9 ± 1.4 and 1.5 ± 2.2 and did not differ significantly between women with normal muscle insertion and women with partial or full avulsion at 8-year follow-up. CONCLUSIONS: More LAM avulsions were present 8 years compared with 1 year after first delivery in women with subsequent vaginal delivery. Except for one primipara, all women without subsequent vaginal delivery had unchanged LAM avulsion status between 1 year and 8 years after their first delivery. Larger LAM hiatal area was found in women with full avulsion compared to those with normal muscle insertion at 8-year follow-up. Vaginal symptoms scores were low and did not differ between women with normal muscle insertion and those with partial or full avulsion at 8-year follow-up. © 2024 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Occupational risk of COVID-19 in foreign-born employees in Denmark.

BACKGROUND: Foreign-born workers in high-income countries experience higher rates of COVID-19 but the causes are only partially known. AIMS: To examine if the occupational risk of COVID-19 in foreign-born workers deviates from the risk in native-born employees in Denmark. METHODS: Within a registry-based cohort of all residents employed in Denmark (n = 2 451 542), we identified four-digit DISCO-08 occupations associated with an increased incidence of COVID-19-related hospital admission during 2020-21 (at-risk occupations). The sex-specific prevalence of at-risk employment in foreign born was compared with the prevalence in native born. Moreover, we examined if the country of birth modified the risk of a positive SARS-CoV-2 polymerase chain reaction (PCR) test and COVID-19-related hospital admission in at-risk occupations. RESULTS: Workers born in low-income countries and male workers from Eastern Europe more often worked in at-risk occupations (relative risks between 1.16 [95% confidence interval {CI} 1.14-1.17] and 1.87 [95% CI 1.82-1.90]). Being foreign-born modified the adjusted risk of PCR test positivity (test for interaction P < 0.0001), primarily because of higher risk in at-risk occupations among men born in Eastern European countries (incidence rate ratio [IRR] 2.39 [95% CI 2.09-2.72] versus IRR 1.19 [95% CI 1.14-1.23] in native-born men). For COVID-19-related hospital admission, no overall interaction was seen, and in women, country of birth did not consistently modify the occupational risk. CONCLUSIONS: Workplace viral transmission may contribute to an excess risk of COVID-19 in male workers born in Eastern Europe, but most foreign-born employees in at-risk occupations seem not to be at higher occupational risk than native born.

Novel homozygous CD46 variant with C-isoform expression affects C3b inactivation in atypical hemolytic uremic syndrome.

Atypical hemolytic uremic syndrome (aHUS) is a thrombotic microangiopathy that may lead to organ failure. Dysregulation of the complement system can cause aHUS, and various disease-related variants in the complement regulatory protein CD46 are described. We here report a pediatric patient with aHUS carrying a hitherto unreported homozygous variant in CD46 (NM_172359.3:c.602C>T p.(Ser201Leu)). In our functional analyses, this variant caused complement dysregulation through three separate mechanisms. First, CD46 surface expression on the patient's blood cells was significantly reduced. Second, stably expressing CD46(Ser201Leu) cells bound markedly less to patterns of C3b than CD46 WT cells. Third, the patient predominantly expressed the rare isoforms of CD46 (C dominated) instead of the more common isoforms (BC dominated). Using BC1 and C1 expressing cell lines, we found that the C1 isoform bound markedly less C3b than the BC1 isoform. These results highlight the coexistence of multiple mechanisms that may act synergistically to disrupt CD46 function during aHUS development.

Anterior cingulate metabolite levels, memory, and inhibitory control in abstinent men and women with alcohol use disorder.

Alcohol use disorder (AUD) has been shown to have harmful cognitive and physiological effects, including altered brain chemistry. Further, although men and women may differ in vulnerability to the neurobiological effects of AUD, the results of existing studies have been conflicting. We examined brain metabolite levels and cognitive functions in a cross-section of men with AUD (AUDm) and women with AUD (AUDw) to determine the degree of abnormalities after extended periods of abstinence (mean, 6 years) and to evaluate gender differences in neuropsychological and metabolite measures. Participants were 40 abstinent individuals with AUD (22 AUDw, 18 AUDm) and 50 age-equivalent non-AUD comparison participants (26 NCw, 24 NCm). Proton magnetic resonance spectroscopy (MRS) was employed at 3 Tesla to acquire metabolite spectra from the dorsal anterior cingulate cortex (dACC). Brain metabolites N-acetyl aspartate (NAA), choline (Cho), myo-Inositol (mI), and glutamate & glutamine (Glx) were examined relative to measures of memory and inhibitory control. Metabolite levels did not differ significantly between AUD and NC groups. Memory and inhibitory-control impairments were observed in the AUD group. There also were significant group-specific associations between metabolite ratios and measures of inhibitory control. There were no group-by-gender interactions for the four metabolite ratios. These findings demonstrate that brain metabolite levels in men and women with AUD, following long-term abstinence, do not differ from individuals without AUD. The data also provide preliminary evidence of sustained associations between metabolite levels and measures of inhibitory control, a functional domain important for curtailing harmful drinking.

Age-dependent genetic and environmental variance of semen quality in Nordic Holstein bulls.

The aim of this study was to estimate genetic and environmental parameters, across bull's age, for semen quality traits including pre- and postcryopreservation semen concentration, sperm motility, and sperm viability as well as ejaculate volume and number of doses per ejaculate. A data set on 96,595 ejaculates from 2,831 Nordic Holstein bulls collected between 2006 and 2019 was used. Genetic and environmental parameters were estimated using a random regression model and applying the average-information REML approach. Spline functions were chosen to fit the additive genetic and permanent environmental effects across bull's age, and the optimal number of knots was chosen using cross validation. Residual variance heterogeneity was assumed in different bull age classes. The estimated repeatabilities of semen quality traits ranged from 0.16 to 0.85 across different ages of bulls. The estimated heritabilities of semen quality traits ranged from 0.02 to 0.56 across different ages of bulls. The results indicate possibilities for genetic improvement of semen quality traits through selective breeding.

A content review of state tobacco pre-emption laws in the US.

OBJECTIVES: State ceiling pre-emption laws effectively limit the authority of local governments to regulate numerous public health issues, including tobacco. While general trends in the number of state tobacco pre-emption laws have been well-documented, less is known about the specific content of these laws. This study provides a comprehensive analysis of the content of current state tobacco pre-emption laws and captures the salient features of these laws. STUDY DESIGN: This was a comparative analysis of tobacco pre-emption laws in the United States. METHODS: The study team collected data about tobacco pre-emption laws from the Centers for Disease Control and Prevention's State Tobacco Activities Tracking and Evaluation System. Trained legal researchers further verified and reviewed each law's content using the Westlaw database. A coding scheme was developed to capture and analyse these laws' most salient features. RESULTS: State tobacco pre-emption laws use various terms to indicate the pre-emption of a local authority, including supersede, pre-empt, uniform, exclusive, and consistent. State laws cover numerous general topics and vary widely in explicit terminology of authorities and fields pre-empted. Several state laws included grandfathering exceptions and a few allowed exceptions for particular local jurisdictions. CONCLUSIONS: State laws that undermine local tobacco control efforts from implementing more stringent laws pose a threat to public health. These laws vary widely in their scope across the U.S., and local jurisdictions should be empowered to enact and maintain tobacco control measures that protect their communities from the harms of tobacco use and exposure.

The association between the experience of lay responders and response interval to medical emergencies in a rural area: an observational study.

AIM: The aim of this retrospective observational study was to determine how response intervals correlated to the experience of the community first responders (CFRs) using data collected from the Danish Island of Langeland via a global positioning system (GPS)-based system. METHODS: All medical emergency calls involving CFRs in the time period from 21st of April 2012 to 31st of December 2017 were included. Each emergency call activated 3 CFRs. Response intervals were calculated using the time from when the system alerted the CFRs to CFR time of arrival at the emergency site measured by GPS. CFRs response intervals were grouped depending on their level of experience according to ≤ 10, 11-24, 25-49, 50-99, ≥ 100 calls accepted and arrived on-site. RESULTS: A total of 7273 CFR activations were included. Median response interval for the CFR arriving first on-site (n = 3004) was 4:05 min (IQR 2:42-6:01) and median response interval for the arrival of the CFR with an automated external defibrillator (n = 2594) was 5:46 min (IQR 3:59-8:05). Median response intervals were 5:53 min (3:43-8:29) for ≤ 10 calls (n = 1657), 5:39 min (3:49-8:01) for 11-24 calls (n = 1396), 5:45 min (3:49-8:00) for 25-49 calls (n = 1586), 5:07 min (3:38-7:26) for 50-99 calls (n = 1548) and 4:46 min (3:14-7:32) for ≥ 100 calls (n = 1086) (p < 0.001). There was a significant negative correlation between experience and response intervals (p < 0.001, Spearman's rho = -0.0914). CONCLUSION: This study found an inverse correlation between CFR experience and response intervals, which could lead to increased survival after a time-critical incident.

Baseline bone turnover marker levels can predict change in bone mineral density during antiresorptive treatment in osteoporotic patients: the Copenhagen bone turnover marker study.

Anti-resorptive osteoporosis treatment might be more effective in patients with high bone turnover. In this registry study including clinical data, high pre-treatment bone turnover measured with biochemical markers was correlated with higher bone mineral density increases. Bone turnover markers may be useful tools to identify patients benefitting most from anti-resorptive treatment. INTRODUCTION: In randomized, controlled trials of bisphosphonates, high pre-treatment levels of bone turnover markers (BTM) were associated with a larger increase in bone mineral density (BMD). The purpose of this study was to examine this correlation in a real-world setting. METHODS: In this registry-based cohort study of osteoporosis patients (n = 158) receiving antiresorptive therapy, the association between pre-treatment levels of plasma C-telopeptide of type I Collagen (CTX) and/or N-terminal propeptide of type I procollagen (PINP) and change in bone mineral density (BMD) at lumbar spine, total hip, and femoral neck upon treatment was examined. Patients were grouped according to their pre-treatment BTM levels, defined as values above and below the geometric mean for premenopausal women. RESULTS: Pre-treatment CTX correlated with annual increase in total hip BMD, where patients with CTX above the geometric mean experienced a larger annual increase in BMD (p = 0.008) than patients with CTX below the geometric mean. The numerical pre-treatment level of CTX showed a similar correlation at all three skeletal sites (total hip (p = 0.03), femoral neck (p = 0.04), and lumbar spine (p = 0.0003)). A similar association was found for PINP where pre-treatment levels of PINP above the geometric mean correlated with a larger annual increase in BMD for total hip (p = 0.02) and lumbar spine (p = 0.006). CONCLUSION: Measurement of pre-treatment BTM levels predicts osteoporosis patients' response to antiresorptive treatment. Patients with high pre-treatment levels of CTX and/or PINP benefit more from antiresorptive treatment with larger increases in BMD than patients with lower pre-treatment levels.

2021 European guideline on the management of Mycoplasma genitalium infections.

Mycoplasma genitalium infection contributes to 10-35% of non-chlamydial non-gonococcal urethritis in men. In women, M. genitalium is associated with cervicitis and pelvic inflammatory disease (PID) in 10-25%. Transmission of M. genitalium occurs through direct mucosal contact. CLINICAL FEATURES AND DIAGNOSTIC TESTS: Asymptomatic infections are frequent. In men, urethritis, dysuria and discharge predominate. In women, symptoms include vaginal discharge, dysuria or symptoms of PID - abdominal pain and dyspareunia. Symptoms are the main indication for diagnostic testing. Diagnosis is achievable only through nucleic acid amplification testing and must include investigation for macrolide resistance mutations. THERAPY: Therapy for M .genitalium is indicated if M. genitalium is detected. Doxycycline has a cure rate of 30-40%, but resistance is not increasing. Azithromycin has a cure rate of 85-95% in macrolide-susceptible infections. An extended course of azithromycin appears to have a higher cure rate, and pre-treatment with doxycycline may decrease organism load and the risk of macrolide resistance selection. Moxifloxacin can be used as second-line therapy but resistance is increasing. RECOMMENDED TREATMENT: Uncomplicated M. genitalium infection without macrolide resistance mutations or resistance testing: Azithromycin 500 mg on day one, then 250 mg on days 2-5 (oral). Second-line treatment and treatment for uncomplicated macrolide-resistant M. genitalium infection: Moxifloxacin 400 mg od for 7 days (oral). Third-line treatment for persistent M. genitalium infection after azithromycin and moxifloxacin: Doxycycline or minocycline 100 mg bid for 14 days (oral) may cure 40-70%. Pristinamycin 1 g qid for 10 days (oral) has a cure rate of around 75%. Complicated M. genitalium infection (PID, epididymitis): Moxifloxacin 400 mg od for 14 days. MAIN CHANGES FROM THE 2016 EUROPEAN M. GENITALIUM GUIDELINE: Due to increasing antimicrobial resistance and warnings against moxifloxacin use, indications for testing and treatment have been narrowed to primarily involve symptomatic patients. The importance of macrolide resistance-guided therapy is emphasised.

Macrolide resistance in Mycoplasma genitalium in Catalonia, Spain: a 1 year prospective study.

BACKGROUND: Mycoplasma genitalium is an emergent cause of sexually transmitted disease (STD). The first-line treatment is azithromycin, but macrolide resistance is increasing due to mutations in the 23S rRNA gene. OBJECTIVES: To determine the rates of M. genitalium infection and macrolide resistance in an area adjacent to Barcelona. METHODS: This 1 year prospective study was performed in a heterogenous population that included both low- and high-risk patients. M. genitalium was detected in all specimens sent to our institution for STD detection. Epidemiological and relevant clinical data were collected in the positive cases. Characterization of macrolide-associated resistance was performed by 23S rDNA sequencing. RESULTS: Of the 3540 patients included, 132 (3.7%) were positive for M. genitalium. Another sexually transmitted bacteria was detected in 20.4% of the M. genitalium cases, and Chlamydia trachomatis (11%) was the most frequently co-detected microorganism. Only 61.4% of patients received an adequate initial treatment against M. genitalium. The test of cure (TOC) was performed in 42% of patients, and therapeutic failure was detected in 10 cases. The rate of macrolide resistance was 12.6% and the most prevalent mutation was A2058G. There was an association between macrolide resistance and a previous history of M. genitalium detection (P < 0.001). CONCLUSIONS: Our results support the contribution of the previous use of macrolides in resistant strains. Given the difficulties in performing TOC in all patients, the inclusion of macrolide resistance in the detection test should be mandatory.

Bayesian estimation of genetic variance and response to selection on linear or ratio traits of feed efficiency in dairy cattle.

This study aimed to estimate genetic parameters of the linear trait genetic residual feed intake (RFI) and the ratio traits feed conversion ratio (FCR) and feed conversion efficiency (FCE) along with dry matter intake (DMI) and energy sink traits such as energy-corrected milk (ECM), body weight (BW), body condition score (BCS), and BW change (BWC) across different weeks in the first lactation of Danish Holstein cows. A second objective was to conduct a Bayesian analysis of direct and correlated superiority of the selected group when selecting on genetic RFI, FCR, or FCE. Feed intake and energy sink traits were recorded during wk 1 to 44 of lactation on 847 primiparous Danish Holstein cows. A Bayesian multivariate random regression animal model was used to analyze DMI, ECM, BW, and BCS in different weeks of lactation. Genetic RFI was obtained by conditioning DMI on ECM, BW, BCS, and BWC using genetic partial regression coefficients. The posterior distribution of the breeding values for FCR and FCE was derived from the posterior distribution of functions of "fixed" environmental effects and random additive genetic effects on DMI and ECM. Genetic superiority of the selected group was defined as the difference in additive genetic mean of the selected top individuals expected to be potential parents, and the total population after integrating genetic trends out of the posterior distribution of selection responses. Posterior means of heritability of genetic RFI ranged from 0.10 to 0.15, genetic variance of FCR and FCE ranged from 2.13 × 10-3 to 3.2 × 10-3 (kg2 DMI/kg2 ECM) and 6.11 × 10-3 to 2.4 × 10-2 (kg2 ECM/kg2 DMI), respectively. Selection against RFI showed a direct response of -1.01 to -2.23 kg/d RFI and correlated responses of -0.031 to -0.056 kg/kg for FCR, 0.104 to 0.160 kg/kg for FCE, and -0.316 to -1.057 kg/d for DMI in different weeks of lactation. Selection against RFI had no significant effect on production traits but selection for ratio traits reduced BW and BCS. Posterior means of genetic correlation between DMI and ratio traits were low. In conclusion, the Bayesian procedure allowed us to estimate genetic RFI without the need for separate multiple regression analysis and considered the non-normal posterior distribution of ratio traits. Selection against genetic RFI might be an effective means to improve feed efficiency compared with ratio traits for feed efficiency in dairy cattle.

Primary health care: an opportunity for early identification of people living with undiagnosed HIV infection.

OBJECTIVES: We aimed to determine the fraction of HIV-diagnosed individuals who had primary health care (PHC) contacts 3 years prior to HIV diagnosis and whether the risk of HIV diagnosis and degree of immunodeficiency were associated with the frequency of visits or procedures performed. METHODS: We used data from national registries to conduct a population-based nested case-control study. Cases were individuals diagnosed with HIV infection in Denmark from 1998 to 2016. Population controls were extracted from the general population matched 13:1 on gender and age. We used conditional logistic regression. As there was a statistically significant interaction, analyses were further stratified by gender and Danish/non-Danish origin. RESULTS: We identified 2784 cases and 36 192 controls. Ninety-three per cent of cases and 88% of controls attended PHC at least once in the 3 years prior to diagnosis, with a higher median number of visits to PHC (NVPC) for cases. We found a statistically significant positive association between NVPC and risk of subsequent HIV diagnosis in men and non-Danish women. A U-shaped association between NVPC and risk of HIV diagnosis among Danish women. No substantial association between NVPC and degree of immunodeficiency was found. Risk of HIV diagnosis and degree of immunodeficiency were weakly associated with type of procedures performed. CONCLUSIONS: For most HIV-infected individuals, there seem to be many opportunities for earlier diagnosis in PHC. In men and non-Danish women, the risk of HIV diagnosis but not the degree of immunodeficiency was related to NVPC. The results suggest that the type of medical procedure performed cannot not be used as a guide by the primary physician to indicate which patients to test.

Reproductive outcome of patients undergoing in vitro fertilisation treatment and diagnosed with bacterial vaginosis or abnormal vaginal microbiota: a systematic PRISMA review and meta-analysis.

BACKGROUND: Despite recent efforts, the risks associated with bacterial vaginosis (BV) or abnormal vaginal microbiota in IVF patients are not well-established. OBJECTIVES: We aimed to evaluate the risks associated with BV in IVF patients using meta-analysis. SEARCH STRATEGY: Following preliminary searches to find relevant keywords and MeSH terms, a systematic search was performed in PubMed (MEDLINE) in September 2017. SELECTION CRITERIA: The population was infertile women attending IVF treatment. The exposure was BV or abnormal vaginal microbiota. Outcomes included live birth rate, early spontaneous abortion rate and clinical pregnancy rate. DATA COLLECTION AND ANALYSIS: Data were collected for each study and for each outcome using a summary of findings table. If appropriate, data were quantitatively assessed using meta-analysis, sensitivity analysis, funnel plots and GRADE evidence assessment were performed for the above-mentioned outcomes. MAIN RESULTS: A total of 12 studies were eligible, comprising a total of 2980 patients. The prevalence of BV was 16% (95% CI 15-18%) in the general study population and tubal factor infertility was highly prevalent in patients diagnosed with BV compared with normal vaginal microbiota patients (P = 0.001). Despite a significant association with early spontaneous abortion [relative risk (RR) 1.68, 95% CI 1.24-2.27], BV did not significantly impact the live birth rate (RR 1.47, 95% CI 0.96-1.57) or the clinical pregnancy rate (RR 0.93, 95% CI 0.75-1.15). CONCLUSIONS: BV is associated with tubal factor infertility and early spontaneous abortion. However, the quality of evidence was very low and the equivocal results justify the need for further research. TWEETABLE ABSTRACT: Abnormal vaginal microbiota is associated with early spontaneous abortion in IVF patients.

In vitro activity of zoliflodacin (ETX0914) against macrolide-resistant, fluoroquinolone-resistant and antimicrobial-susceptible Mycoplasma genitalium strains.

Background: Mycoplasma genitalium is estimated to be the second most common cause of bacterial sexually transmitted infection in Europe. It is of increasing public health concern due to the rapid development of resistance to different antimicrobial classes, including the preferred first- and second-line treatments azithromycin and moxifloxacin. Thus, new antimicrobial agents are urgently needed, especially for the treatment of MDR strains. Methods: The in vitro activity of the new spiropyrimidinetrione zoliflodacin against 47 M. genitalium strains was assessed by growing M. genitalium in Vero cell culture and measuring growth by quantitative PCR. The collection included 34 moxifloxacin-susceptible (MIC <1 mg/L) and 13 moxifloxacin-resistant (MIC ≥1 mg/L) strains. Twenty-three of the strains were azithromycin resistant (MIC ≥16 mg/L) and 12 of these strains were MDR. Results: Only one (2.1%) strain with substantially increased MIC (4 mg/L) and potential resistance to zoliflodacin was found. Zoliflodacin was overall more potent than moxifloxacin (P = 0.009) and no cross-resistance was observed between the two drug classes of topoisomerase II inhibitors. Differences in the MICs of zoliflodacin and azithromycin were not statistically significant; however, 23 (48.9%) compared with potentially 1 (2.1%) of the strains were resistant to azithromycin and zoliflodacin, respectively. Conclusions: Zoliflodacin is a promising candidate for the treatment of M. genitalium and it is important to further develop and evaluate this drug.

Diminished CXCR5 expression in peripheral blood of patients with Sjögren's syndrome may relate to both genotype and salivary gland homing.

Genetic investigations of Sjögren's syndrome (SS) have identified a susceptibility locus at p23.3 of chromosome 11, which contains the CXCR5 gene. C-X-C motif chemokine receptor 5 (CXCR5) is a chemokine receptor expressed on B and T cell subsets, and binds the chemotactic ligand C-X-C motif chemokine ligand 13 (CXCL13). In this study we aimed to link the genetic association with functional effects and explore the CXCR5/CXCL13 axis in SS. Expression quantitative trait loci analysis of the 11q23.3 locus was performed using B cell mRNA expression data from genotyped individuals. Lymphocyte surface markers were assessed by flow cytometry, and CXCL13 levels by a proximity extension assay. CXCR5+ and CXCL13+ cells in minor salivary glands were detected using immunohistochemistry. Our results demonstrated that SS-associated genetic polymorphisms affected the expression of CXCR5 (P < 0·01). Notably, a decreased percentage of CXCR5+ cells, with lower CXCR5 expression, was observed for most circulating B and T cell subsets in SS patients, reaching statistical significance in CD19+ CD27+ immunoglobulin (Ig)D+ marginal zone (P < 0·001), CD19+ CD27+ IgD- memory (P < 0·05) and CD27-IgD double-negative (P < 0·01) B cells and CD4+ CXCR3- CCR6+ Th17 cells (P < 0·05). CXCL13 levels were increased in patient plasma (P < 0·001), and immunohistochemical staining revealed expression of CXCL13 and higher numbers of CXCR5+ cells (P < 0·0001) within focal infiltrates and interstitially in salivary glands of SS patients. In conclusion, we link a genetic susceptibility allele for SS to a functional phenotype in terms of decreased CXCR5 expression. The decrease of CXCR5+ cells in circulation was also related to homing of B and T cells to the autoimmune target organ. Therapeutic drugs targeting the CXCR5/CXCL13 axis may be useful in SS.

Osteogenesis imperfecta and the teeth, eyes, and ears-a study of non-skeletal phenotypes in adults.

Osteogenesis imperfecta (OI) is a disease causing bone fragility; however, it potentially affects all organs with a high content of collagen, including ears, teeth, and eyes. The study is cross-sectional and compares non-skeletal characteristics in adults with OI that clinicians should be aware of when caring for patients with OI. INTRODUCTION: Osteogenesis imperfecta (OI) is a hereditary connective tissue disorder. The skeletal fragility is pronounced; however, OI leads to a number of extra-skeletal symptoms related to the ubiquity of collagen type 1 throughout the human body. The vast majority of knowledge is derived from studies performed in the pediatric population. Thus, we aimed to investigate the nature and prevalence of ophthalmologic, odontologic, and otologic phenotypes in an adult population with OI. METHODS: The study population comprises 85 Danish OI patients (age 44.9 ± 15.9 years). Fifty-eight patients had OI type I, 12 OI type III, and 15 OI type IV according to the classification by Sillence. Audiometric evaluations and dental examinations were performed in 62 and 73 patients, respectively. Ophthalmologic investigations were performed in 64 patients, including measurements of the central corneal thickness. RESULTS: All patients, except two, had corneal thickness below the normal reference value. Patients with OI type I and patients with a quantitative collagen defect had thinner corneas compared to patients with OI type III and other patients with a qualitative collagen defect. One patient in this cohort was diagnosed with and treated for acute glaucoma. Dentinogenesis imperfecta was diagnosed in one fourth of the patients, based on clinical and radiographic findings. This condition was predominately seen in patients with moderate to severe OI. Hearing loss requiring treatment was found in 15 of 62 patients, of whom three were untreated. The most prevalent type of hearing loss (HL) was sensorineural hearing loss, whereas conductive HL was solely seen in patients with OI type III. The patients with the most severe degrees of HL were patients with mild forms of OI. Age was associated with increased HL. CONCLUSION: Although significant health problems outside the skeleton are frequent in adult patients with OI, the patients are not consistently monitored and treated for their symptoms. Clinicians treating adult patients with OI should be aware of non-skeletal health issues and consider including regular interdisciplinary check-ups in the management plan for adult OI patients.

First Accurate Normalization of the ß-delayed α Decay of

The ^{12}C(α,γ)^{16}O reaction plays a central role in astrophysics, but its cross section at energies relevant for astrophysical applications is only poorly constrained by laboratory data. The reduced α width, γ_{11}, of the bound 1^{-} level in ^{16}O is particularly important to determine the cross section. The magnitude of γ_{11} is determined via sub-Coulomb α-transfer reactions or the ß-delayed α decay of ^{16}N, but the latter approach is presently hampered by the lack of sufficiently precise data on the ß-decay branching ratios. Here we report improved branching ratios for the bound 1^{-} level [b_{ß,11}=(5.02±0.10)×10^{-2}] and for ß-delayed α emission [b_{ßα}=(1.59±0.06)×10^{-5}]. Our value for b_{ßα} is 33% larger than previously held, leading to a substantial increase in γ_{11}. Our revised value for γ_{11} is in good agreement with the value obtained in α-transfer studies and the weighted average of the two gives a robust and precise determination of γ_{11}, which provides significantly improved constraints on the ^{12}C(α,γ) cross section in the energy range relevant to hydrostatic He burning.

Cardiac repolarization and depolarization in people with Type 1 diabetes with normal ejection fraction and without known heart disease: a case-control study.

AIMS: To investigate depolarization and repolarization durations in people with Type 1 diabetes, including the relationship to age. METHODS: 855 persons with Type 1 diabetes without known heart disease were included and matched with 1710 participants from a general population study. Clinical examinations, questionnaires and biochemistry were assessed. A 10-second 12-lead ECG was performed and analysed digitally. RESULTS: QTc was longer in people with Type 1 diabetes compared to controls (414±16 vs. 411±19 ms, P <0.001), and particularly so in young people with Type 1 diabetes. The fully adjusted increase was 13.8 ms (95% confidence interval (CI): 8.6-19.0 ms, P <0.001) at age 20 years and 3.4 ms (CI: 1.5-5.3 ms, P<0.001) at age 40 years. The rate-corrected QRSc was increased in people with Type 1 diabetes (97±11 vs. 95±11 ms, P <0.001) and was age-independent (P =0.5). JTc was increased in the young people with Type 1 diabetes (10.7 ms (CI: 5.4-16.0 ms, P <0.001) at age 20 years), but not in older people with Type 1 diabetes (interaction age-diabetes, P <0.01). CONCLUSIONS: For people with Type 1 diabetes, cardiac depolarization is increased at all ages, whereas repolarization is increased only relatively in young people with Type 1 diabetes. Hence, young people with Type 1 diabetes may be more prone to ventricular arrhythmias. The findings contribute to the understanding of sudden cardiac death in young people with Type 1 diabetes.

Fluid accumulation during acute kidney injury in the intensive care unit.

INTRODUCTION: Fluid therapy is a ubiquitous intervention in patients admitted to the intensive care unit, but positive fluid balance may be associated with poor outcomes and particular in patients with acute kidney injury. Studies describing this have defined fluid overload either at specific time points or considered patients with a positive mean daily fluid balance as fluid overloaded. We wished to detail this further and performed joint model analyses of the association between daily fluid balance and outcome represented by mortality and renal recovery in patients admitted with acute kidney injury. METHOD: We did a retrospective cohort study of patients admitted to the intensive care unit with acute kidney injury during a 2-year observation period. We used serum creatinine measurements to identify patients with acute kidney injury and collected sequential daily fluid balance during the first 5 days of admission to the intensive care unit. We used joint modelling techniques to correlate the development of fluid overload with survival and renal recovery adjusted for age, gender and disease severity. RESULTS: The cohort contained 863 patients with acute kidney injury of whom 460 (53%) and 254 (29%) developed 5% and 10% fluid overload, respectively. We found that both 5% and 10% fluid overload was correlated with reduced survival and renal recovery. CONCLUSION: Joint model analyses of fluid accumulation in patients admitted to the intensive care unit with acute kidney injury confirm that even a modest degree of fluid overload (5%) may be negatively associated with both survival and renal recovery.

Simulation-based point-of-care ultrasound training: a matter of competency rather than volume.

BACKGROUND: Point-of-care ultrasonography plays an increasingly important role in the initial resuscitation of critically ill patients but acquisition of the skill is associated with long learning curves. The skills required to perform ultrasound examinations can be practiced in a simulated setting before being performed on actual patients. The aim of this study was to investigate the learning curves for novices training the FAST protocol on a virtual-reality simulator. METHODS: Ultrasound novices (N = 25) were instructed to complete a FAST training program on a virtual-reality ultrasound simulator. Participants were instructed to continue training until they reached a previously established mastery learning level, which corresponds to the performance level of a group of ultrasound experts. Performance scores and time used during each FAST examination were used to determine participants' learning curves. RESULTS: The participants attained the mastery learning level within a median of three (range two to four) attempts corresponding to a median of 1 h 46 min (range 1 h 2 min to 3 h 37 min) of simulation training. The ultrasound novices' examination speed improved significantly with training, and continued to improve even after they attained the mastery learning level (P = 0.011). Twenty-three participants attained the mastery learning level. CONCLUSION: Novices can attain mastery learning levels using simulation-based ultrasound training with less than, on average, 2 h of practice. However, we found large variations in the amount of training needed, which raises questions about the adequacy of current volume-based models for determining ultrasound competency.