Effectiveness of Briefer Coping-Focused Psychotherapy for Common Mental Complaints on Work-Participation and Mental Health: A Pragmatic Randomized Trial with 2-Year Follow-Up.

Purpose The aim of this study was to assess short and long-term effectiveness of brief coping-focused psychotherapy (Brief-PsT) compared with short-term psychotherapy (Short-PsT) on work-participation (WP) and mental health. Both treatments were preceded by group education. Methods All participants were on, or at risk of, sick leave due to common mental complaints. Patients were selected for inclusion in this study based on levels of self-reported symptoms ('some' or 'seriously affected') of anxiety and depression. They were randomized to Brief-PsT (n = 141) or Short-PsT with a more extended focus (n = 143). Primary outcome was the transition of WP-state from baseline to 3 months follow-up. In addition, WP at 12 and 24 months follow-up were assessed. The secondary outcome, clinical recovery rate (CR-rate) was obtained from the Beck Depression and Beck Anxiety Inventories, at 2-year follow-up. In addition, self-reported mental health symptom severity, self-efficacy, subjective health complaints and life satisfaction were assessed. Results At 3 months follow-up, the increase in WP was significantly greater in Brief-PsT than in Short-PsT (p = 0.039). At 3 months, 60% in Brief-PsT and 51% in Short-PsT was at work, partial or full. Thereafter, these differences diminished, 84% and 80% were at work at 2-year follow up. The 2-year follow-up of the secondary outcome measurements was completed by 53% in Brief-PsT and 57% in Short PsT. CR-rate was significantly greater in Brief-PsT compared with the Short-PsT (69% vs. 51%, p = 0.024). Furthermore, there was a greater reduction in the number of subjective health complaints in Brief-PsT (4.0 vs. 1.9 p = 0.012). All other measurements favoured Brief-PsT as well, but did not reach statistical significance. Conclusions Brief coping-focused psychotherapy added to group education for persons with depression or anxiety complaints seemed more effective in enhancing early work participation compared with additional short-term psychotherapy of standard duration with more extended focus. Clinical recovery rate and decline of comorbid subjective health complaints at 2-year follow-up were also in favour of the brief coping-focused program.

Risk profiling based on p16 and HPV DNA more accurately predicts location of disease relapse in patients with oropharyngeal squamous cell carcinoma.

BACKGROUND: In the era of precision medicine and HPV-related oropharyngeal squamous cell carcinoma (OPSCC), it is relevant to assess the risk of not only survival, but also the risk of local, regional, or distant treatment failure. The UICC 8th edition uses the surrogate marker p16 to stratify for HPV association but discordance between p16 status and HPV association has been shown. The purpose of this study was to develop a prognostic model to predict the risk of local, regional, and distant metastases and non-cancer-related death for patients with OPSCC, test the prognostic relevance of adding HPV DNA and p16 status, and validate the findings in an independent external dataset. PATIENTS AND METHODS: Consecutive patients diagnosed with OPSCC and treated with curative radiotherapy with or without cisplatin in eastern Denmark from 2000 to 2014 were included. Characteristics included age, gender, TNM stage, smoking habits, performance status, and HPV status assessed with p16 and HPV DNA. The information was used to develop a prognostic model for first site of failure with four competing events: recurrence in T-, N-, and M-site, and death with no evidence of disease. RESULTS: Overall 1243 patients were eligible for the analysis. A prognostic model with the four events was developed and externally validated in an independent dataset with a heterogeneously treated patient population from another institution. The individual prognostication from the competing risk analysis is displayed in a user friendly online tool (https://rasmussen.shinyapps.io/OPSCCmodelHPV_p16/). Replacing p16 status with the combined variable HPV/p16 status influenced the HR and patients with HPV-/p16+ had significantly higher HR of M-site recurrence than HPV+/p16+ with a HR = 2.56; CI [1.30; 5.02]; P = 0.006 (P = 0.013 in the validation cohort). CONCLUSION: Patients with HPV-/p16+ have significantly higher risk of M-site recurrence and could potentially be relevant candidates for clinical trials testing systemic treatments in combination with conventional treatments.

Using landscape scenarios to improve local nitrogen management and planning.

Scenario-building is a widely used tool to initiate discussions on future land uses. In scenarios possible futures can be explored and peoples' ideas as well as societal trends can be visualized by the use of maps, pictures and figures. With focus on agricultural nitrogen management, and point of departure in the farmers' decisions-regarding fertilizer inputs, crop rotations, land use, and drainage, landscape scenarios are formulated based on local ideas for future nitrogen management and general prospects for local development. The key research question addressed in this paper is how landscape scenarios can guide farmers to improve nitrogen management in smaller catchments dominated by farming. Participatory modelling was used to develop landscape scenarios, depicting the change of nitrogen emission as a result of changes in landscape management and agricultural practices. In the development of the scenarios we used an ArcMap based tool combining statistical data, experimental knowledge, nitrate leaching modelling and input from local stakeholders on biophysical as well as land use and farm management issues. The scenarios presented are the result of a collaborative planning experiment within the frames of the dNmark research alliance on nitrogen. Three different types of scenarios are presented and discussed and their effects in terms of N reduction are estimated. The three scenarios were called: River valley set-aside, constructed wetlands, and land zonation. All the modelled scenarios are estimated to have a positive effect i.e. a reduction of the level of N leached to the root zone. Based on the experience gathered in the project, the feasibility of using scenarios for future environmental planning in the agricultural landscapes is discussed. Further, this is related to the current discussion in Denmark on geographically targeted nitrogen regulation. It is concluded that the co-creative approach to formulation of scenarios can be an effective way of increasing the knowledge and ownership of possible future solutions, however the cost associated with this planning approach is likely to substantially higher that more traditional planning approaches. Consequently, the estimated transactions costs should be weighed against the expected benefits in terms of more successful implementation.

Natural Variation in the Distribution and Abundance of Transposable Elements Across the Caenorhabditis elegans Species.

Transposons are mobile DNA elements that generate both adaptive and deleterious phenotypic variation thereby driving genome evolution. For these reasons, genomes have mechanisms to regulate transposable element (TE) activity. Approximately 12-16% of the Caenorhabditis elegans genome is composed of TEs, of which the majority are likely inactive. However, most studies of TE activity have been conducted in the laboratory strain N2, which limits our knowledge of the effects of these mobile elements across natural populations. We analyzed the distribution and abundance of TEs in 208 wild C. elegans strains to better understand how transposons contribute to variation in natural populations. We identified 3,397 TEs as compared with the reference strain, of which 2,771 are novel insertions and 241 are TEs that have been excised in at least one wild strain. Likely because of their hypothesized deleterious effects, we find that TEs are found at low allele frequencies throughout the population, and we predict functional effects of TE insertions. The abundances of TEs reflect their activities, and these data allowed us to perform both genome-wide association mappings and rare variant correlations to reveal several candidate genes that impact TE regulation, including small regulatory piwi-interacting RNAs and chromatin factors. Because TE variation in natural populations could underlie phenotypic variation for organismal and behavioral traits, the transposons that we identified and their regulatory mechanisms can be used in future studies to explore the genomics of complex traits and evolutionary changes.

Acute flaccid myelitis in childhood: a retrospective cohort study.

BACKGROUND AND PURPOSE: Clusters of acute limb weakness in paediatric patients have been linked to outbreaks of non-polio enteroviruses, termed acute flaccid myelitis (AFM). Outside these clusters, in countries where polio is not endemic, this poliomyelitic-like illness is rare in childhood and its natural history is not well defined. We describe presenting features, investigation findings and long-term outcome of a series of children with AFM. METHODS: This was a retrospective cohort study. RESULTS: Eight children (six females) aged 3 months to 8 years (median age 5 years) met case criteria. Initial symptoms were pain (n = 7) followed by limb weakness with hypotonia (n = 8). Flaccid paralysis occurred in only three patients. Two had cranial nerve dysfunction. Magnetic resonance imaging of the spinal cord demonstrated grey matter involvement particularly affecting the anterior cord, with longitudinally extensive changes in three children. Cerebrospinal fluid examination showed pleocytosis in six children with raised cerebrospinal fluid protein in five. Nerve conduction and electromyography findings were consistent with a motor neuronopathy. Residual deficits were common, with moderate to severe weakness seen in five patients. Median follow-up was 28 months (range 17-108 months, 30.4 patient years in total). CONCLUSIONS: Acute flaccid myelitis is an uncommon condition in childhood with a high rate of significant long-term morbidity. AFM should be considered in children presenting with acute limb pain and weakness.

Prognostic factors for survival after salvage total laryngectomy following radiotherapy or chemoradiation failure: a 10-year retrospective longitudinal study in eastern Denmark.

OBJECTIVE: The primary aims were to determine the rates of and prognostic factors for overall survival, disease-specific survival and disease-free survival following salvage total laryngectomy. DESIGN: Retrospective longitudinal study. SETTING: Tertiary medical centres. PARTICIPANTS: A total of 142 patients in eastern Denmark undergoing salvage total laryngectomy for squamous cell carcinoma of the larynx or hypopharynx. MAIN OUTCOME MEASURES: 5-year overall survival, 5-year disease-specific survival, 5-year disease-free survival and prognostic factors for these outcomes. RESULTS: 5-year overall survival, disease-specific survival and disease-free survival were 37.7%, 54.9% and 55.3%, respectively. N classification at primary diagnosis, lymph node excision and postoperative complications within 1 year after salvage total laryngectomy were prognostic factors for shorter overall survival, disease-specific survival and disease-free survival. Residual tumour/recurrence was negatively associated with overall survival, close or involved resection margins with disease-specific survival, and second primary cancer was associated with longer disease-specific survival and disease-free survival. Nine per cent of all patients had residual tumour and 33.8% developed a recurrence. CONCLUSION: Our overall survival, disease-specific survival and disease-free survival findings are in accordance with previous studies. With the purpose of identifying recurrent tumour, we suggest extra attention being given to patients with higher N classification and need for lymph node excision during salvage total laryngectomy along with use of frozen sections. The high number of patients with recurrence within 1 year after salvage total laryngectomy occurred although thorough and regular follow-up visits were performed.

Muscle wound healing in rainbow trout (Oncorhynchus mykiss).

We followed the progression of healing of deep excisional biopsy punch wounds over the course of 365 days in rainbow trout (Oncorhynchus mykiss) by monitoring visual wound healing and gene expression in the healing muscle at regular intervals (1, 3, 7, 14, 38 and 100 days post-wounding). In addition, we performed muscle texture analysis one year after wound infliction. The selected genes have all previously been investigated in relation to vertebrate wound healing, but only few specifically in fish. The selected genes were interleukin (IL)-1ß, IL-6, transforming growth factor (TGF)-ß1 and -ß3, matrix metalloproteinase (MMP) -9 and -13, inducible nitric oxide synthase (iNOS), fibronectin (FN), tenascin-C (TN-C), prolyl 4-hydroxylase α1-chain (P4Hα1), lysyl oxidase (LOX), collagen type I α1-chain (ColIα1), CD41 and CD163. Wound healing progressed slowly in the presented study, which is at least partially due to the low temperature of about 8.5 °C during the first 100 days. The inflammation phase lasted more than 14 days, and the genes relating to production and remodeling of new extracellular matrix (ECM) exhibited a delayed but prolonged upregulation starting 1-2 weeks post-wounding and lasting until at least 100 days post-wounding. The gene expression patterns and histology reveal limited capacity for muscle regeneration in rainbow trout, and muscle texture analyses one year after wound infliction confirm that wounds heal with fibrosis. At 100 dpw epidermis had fully regenerated, and dermis partially regenerated. Scales had not regenerated even after one year. CD163 is a marker of "wound healing"-type M2c macrophages in mammals. M2 macrophage markers are as yet poorly described in fish. The pattern of CD163 expression in the present study is consistent with the expected timing of presence of M2c macrophages in the wound. CD163 may thus potentially prove a valuable marker of M2 macrophages - or a subset hereof - in fish. We subjected a group of fish to bathing in an immunomodulatory ß-glucan product during wound healing, but found this to have very limited effect on wound healing in contrast to a previously published study on common carp.

Increasing incidence of base of tongue cancers from 2000 to 2010 due to HPV: the largest demographic study of 210 Danish patients.

BACKGROUND: We assessed the development in the number of new base of tongue squamous-cell carcinoma (BSCC) cases per year in eastern Denmark from 2000 to 2010 and whether HPV may explain any observable increased incidence. METHODS: We performed HPV DNA PCR and p16 immunohistochemistry analysis for all (n=210) BSCCs registered in the Danish Head and Neck Cancer Group (DAHANCA) and the Danish Pathology Data Bank, and genotyped all HPV-positive specimens with amplicon-based next-generation sequencing. RESULTS: The overall crude incidence of BSCCs increased significantly (5.4% per year) during the study period. This was explained by a significant increase in the number of HPV-positive BSCCs (8.1% per year), whereas the number of HPV-negative BSCCs did not increase significantly. The overall HPV prevalence was 51%, with HPV16 as the predominant HPV type. CONCLUSIONS: The increased number of HPV-positive BSCCs may explain the increasing incidence of BSCCs in eastern Denmark, 2000-2010.

Risk of all-type cancer, hepatocellular carcinoma, non-Hodgkin lymphoma and pancreatic cancer in patients infected with hepatitis B virus.

The increased risk of hepatocellular carcinoma (HCC) among patients infected with hepatitis B virus (HBV) is well established; however, long-term risk estimates are needed. Recently, it has been suggested that HBV is associated with non-Hodgkin lymphoma (NHL) and pancreatic cancer (PC). The aim of this Danish nationwide cohort study was to evaluate the association between HBV infection and all-type cancer, HCC, NHL and PC. A cohort of patients infected with HBV (n = 4345) and an age- and sex-matched population-based comparison cohort of individuals (n = 26,070) without a positive test for HBV were linked to The Danish Cancer Registry to compare the risk of all-type cancer, HCC, NHL and PC among the two groups. The median observation period was 8.0 years. Overall, the incidence rate ratio (IRR) for all-type cancer among HBV-infected patients was 1.1 (95% confidence intervals (CI) 0.9-1.3). The IRR of HCC was 17.4 (CI 5.5-54.5), whereas the IRR of PC and NHL was 0.9 (CI 0.3-2.5) and 1.2 (CI 0.4-3.6), respectively. HBV-infected patients had a 10-year risk of 0.24% (Cl 0.12-0.44) for HCC, whereas the comparison cohort had a 10-year risk of 0.03% (Cl 0.02-0.07) for HCC. The risk of all-type cancer, NHL and PC was not higher in the HBV-infected cohort compared to non-HBV infected. We found a 17-fold higher risk of HCC for HBV-infected individuals.

Risk factors for postoperative complications after total laryngectomy following radiotherapy or chemoradiation: a 10-year retrospective longitudinal study in Eastern Denmark.

OBJECTIVES: To determine the rates of and risk factors for postoperative complications following total laryngectomy in patients treated with radiotherapy or chemoradiation. DESIGN: Retrospective longitudinal study. SETTING: Tertiary medical centres. PARTICIPANTS: A total of 143 patients undergoing total laryngectomy for squamous cell carcinoma of the larynx or hypopharynx. MAIN OUTCOME MEASURES: Overall postoperative complications and fistula formation. RESULTS: Overall postoperative complications, fistula formation, wound infection, bleeding and wound necrosis within one year after total laryngectomy occurred in 56.6%, 42.3%, 31.0%, 11.3% and 9.2% of patients, respectively. Stenosis of the pharynx/oesophagus and stoma shrinkage within five years after surgery were each seen in 18.2% of cases. In 66.7% of cases, conservative treatment of the fistulas was chosen. Rehospitalisations within five years occurred for 44.8% with a median rate of 1.5 (range 1-11). Smoking status (P = 0.005 and 0.013) and chronic obstructive pulmonary disease (COPD) (P = 0.013 and 0.011) were significant risk factors for both overall postoperative complications and fistula formation in uni- and multivariate analysis. Tumour localisation in the hypopharynx was associated with overall postoperative complications (P = 0.036). Residual tumour or cancer recurrence was associated with late-onset fistulas (P < 0.001). CONCLUSION: The frequencies of postoperative complications after total laryngectomy were comparable with similar international studies, although fistula formation rate is increasing in Denmark. We suggest optimising treatment of COPD and to further encourage to smoking cessation. We propose that development of fistulas >2 months after surgery prompts immediate biopsies. Additionally, we suggest standardised registration of surgical techniques to identify variables affecting the frequency of postoperative complications.

Macrophage-related serum biomarkers soluble CD163 (sCD163) and soluble mannose receptor (sMR) to differentiate mild liver fibrosis from cirrhosis in patients with chronic hepatitis C: a pilot study.

Macrophages regulate the fibrotic process in chronic liver disease. The aim of the present pilot study was to evaluate two new macrophage-specific serum biomarkers [soluble CD163 (sCD163) and soluble mannose receptor (sMR, sCD206)] as potential fibrosis markers in patients chronically infected with hepatitis C virus (HCV). Forty patients with chronic hepatitis C were included from two hospital clinics. On the day of inclusion, transient elastography (TE) was performed to assess the fibrosis stage, and blood samples were collected for the measurement of sCD163 and sMR. The plasma concentrations of both biomarkers were significantly higher in patients infected with HCV and with cirrhosis compared to those with no/mild liver fibrosis (5.77 mg/l vs. 2.49 mg/l and 0.44 mg/l vs. 0.30 mg/l for sCD163 and sMR, respectively). The best separation between groups was obtained by sCD163 [area under the receiver operating characteristic curve (AUC) 0.89 (95 % confidence interval [CI] 0.79-0.99)] as compared to sMR [AUC 0.75 (95 % CI 0.61-0.90)]. sCD163 and sMR correlated significantly (r (2) = 0.53, p < 0.0001). Interestingly, sCD163 also correlated significantly with TNF-α (presented in a previous publication), which is shed to serum by the same mechanism as sCD163 (r (2) = 0.40, p < 0.0001). In conclusion, the macrophage-related markers sCD163 and sMR are significantly higher in patients chronically infected with HCV and with cirrhosis than in those with no/mild fibrosis. sCD163 is a promising new fibrosis marker in patients infected with HCV.

Effectiveness of offering healthy labelled meals in improving the nutritional quality of lunch meals eaten in a worksite canteen.

Healthier meal selections at restaurants and canteens are often limited and not actively promoted. In this Danish study the effectiveness of a healthy labelling certification program in improving dietary intake and influencing edible plate waste was evaluated in a quasi-experimental study design. Employees from an intervention worksite canteen and a matched control canteen were included in the study at baseline (February 2012), after completing the certification process (end-point) and six month from end-point (follow-up) (total n=270). In order to estimate nutrient composition of the consumed lunch meals and plate waste a validated digital photographic method was used combining estimation of food intake with food nutrient composition data. Food satisfaction was rated by participants using a questionnaire. Several significant positive nutritional effects were observed at the intervention canteen including a mean decrease in energy density in the consumed meals from 561kJ/100g at baseline to 368 and 407kJ/100g at end-point and follow-up, respectively (P<0.001). No significant changes were seen with regard to food satisfaction and plate waste. In the control canteen no positive nutritional effects were observed. The results of the study highlight the potential of using healthy labelling certification programs as a possible driver for increasing both the availability and awareness of healthy meal choices, thereby improving dietary intake when eating out.

Adult granulosa cell tumor of the ovary: a retrospective study of 37 cases.

AIM: to evaluate the recurrence rate and the overall survival in women with adult granulosa cell tumor (AGCT), who were treated at the Department of Obstetrics and Gynecology, Aalborg University Hospital during the period January 1985 to January 2010. MATERIALS AND METHODS: Data from 38 women with AGCT were collected retrospectively. The histological slides were re-evaluated by a gynecologic pathologist. Surgical and pathological characteristics were analyzed. Results: Thirty-seven women with AGCT were diagnosed. 92% were diagnosed in FIGO Stage I and 8% in Stage II. The majority of patients (27 patients, 73%) were treated with total abdomi- nal hysterectomy and bilateral salpingooophorectomy. Only one patient received postoperative pelvic irradiation. The recurrence rate was 5.6%. CONCLUSION: The recurrent rate was 5.6%, which is low according to the literature. Primary surgical treatment with radical removal of tumor seemed to be appropriate treatment.

Sustainability in healthcare by reducing low-value imaging - A narrative review.

OBJECTIVES: This narrative review aims to present the concept of value in imaging and explore why we conduct low-value procedures, how to reduce this wasteful use, and what we could gain from reducing low-value imaging. KEY FINDINGS: Imaging of low value to the patient contributes to thousands of metric tons of CO2 emissions, costing several billion US dollars annually. With a 20% reduction in low-value imaging, we would reduce the waste of resources related to 7.2 million procedures and, at the same time, reduce the risk of incidentalomas, overdiagnosis, and overtreatment and reduce wait times for patients in need of imaging services of high value. Multi-component initiatives targeting barriers in all levels of society and healthcare are needed to reduce low-value imaging. Radiographers are key actors in medical imaging and can make substantial contributions to this effort by, together with the radiologists, referrers, and managers, ensuring that all imaging procedures conducted are sustainable along four dimensions of sustainability: value, cost, risk, and environment. CONCLUSION: Efforts to secure sustainable imaging considering the four crucial dimensions (value, cost, radiation, and environment) should be made at all levels of society and healthcare, from governmental management to the individual healthcare worker. Radiographers are vital in obtaining sustainability to ensure only sustainable imaging procedures are conducted. IMPLICATIONS FOR PRACTICE: When assessing the appropriateness of imaging procedures, we need to consider the environment, safety, effectiveness, and efficiency. To obtain this, we need a collective and coordinated effort locally, nationally, and internationally to deliver sustainable imaging services.

Impact of changes in metabolic control on progression to photocoagulation for clinically significant macular oedema: a 20 year study of type 1 diabetes.

AIMS/HYPOTHESIS: Although increasing hyperglycaemia, arterial hypertension and longer duration of diabetes raise the risk of progression of diabetic retinopathy, short-term benefits in terms of improved metabolic control and lowered blood pressure have not been demonstrated. We therefore examined the effect of changes in glycaemia and arterial blood pressure on the incidence of clinically significant macular oedema in a population of diabetic patients. METHODS: We performed a retrospective review of all patients with type 1 diabetes who attended the retinopathy screening clinic at the Steno Diabetes Center from 1988 to 2008, using the endpoint referral to first photocoagulation treatment for clinically significant diabetic macular oedema. The analysis included 1,878 patients (median observation, 8 years). Changes were defined as the inter-visit change; in the case of an event the last event-free interval before referral, where the median screening interval was 6 months. RESULTS: Risk of progression to photocoagulation for macular oedema increased with duration of diabetes (p < 0.001), current HbA1c (p < 0.0001) and with the magnitude of changes in HbA1c (p = 0.0002) and systolic blood pressure (p < 0.0001) in a multiple regression model. A recent decrease of ≥ 0.5 percentage points or an increase in HbA1c of >0.5 percentage points per 6 months was associated with HRs of 3.04 and 1.28, respectively, compared with lesser changes in HbA1c. CONCLUSIONS/INTERPRETATION: In this study, large recent changes in metabolic control and systolic blood pressure, irrespective of direction, were independent risk factors for progression to photocoagulation for diabetic macular oedema. The effects of metabolic and haemodynamic stability on diabetic retinopathy should be examined in prospective studies.

Trimethoprim use in early pregnancy and the risk of miscarriage: a register-based nationwide cohort study.

The antibiotic trimethoprim acts as a folate antagonist. Since trophoblasts are very sensitive to drugs that interfere with the folic acid cycle and thereby inhibit DNA synthesis, use of trimethoprim during the first trimester could be associated with miscarriage. A nationwide cohort study including all women in Denmark with a registered pregnancy between 1997 and 2005 was conducted. We used nationwide registers to identify all women giving birth, having a record of miscarriage or induced abortion. Data on exposure to trimethoprim were obtained from the National Prescription Register. Cox proportional hazard regression analysis with exposure to trimethoprim as a time-dependent variable was used to estimate the risk of miscarriage. The adjusted hazard ratio of having a miscarriage after exposure to trimethoprim in the first trimester compared to non-exposure was 2∙04 (95% confidence interval 1∙43-2∙91). Our results indicate that trimethoprim exposure in the first trimester is associated with a doubling of the hazard of miscarriage.

In human granulosa cells from small antral follicles, androgen receptor mRNA and androgen levels in follicular fluid correlate with FSH receptor mRNA.

Human small antral follicles (diameter 3-9 mm) were obtained from ovaries surgically removed for fertility preservation. From the individual aspirated follicles, granulosa cells and the corresponding follicular fluid were isolated in 64 follicles, of which 55 were available for mRNA analysis (24 women). Expressions of androgen receptor (AR) mRNA levels in granulosa cells, and of androstenedione and testosterone in follicular fluid, were correlated to the expression of the FSH receptor (FSHR), LH receptor (LHR), CYP19 and anti-Müllerian Hormone-receptor II (AMHRII) mRNA in the granulosa cells and to the follicular fluid concentrations of AMH, inhibin-B, progesterone and estradiol. AR mRNA expression in granulosa cells and the follicular fluid content of androgens both showed a highly significant positive association with the expression of FSHR mRNA in granulosa cells. AR mRNA expression also correlated significantly with the expression of AMHRII, but did not correlate with any of the hormones in the follicular fluid. These data demonstrate an intimate association between AR expression in immature granulosa cells, and the expression of FSHR in normal small human antral follicles and between the follicular fluid levels of androgen and FSHR expression. This suggests that follicular sensitivity towards FSH stimulation may be augmented by stimulation of androgens via the AR.

Germ cell numbers in human embryonic and fetal gonads during the first two trimesters of pregnancy: analysis of six published studies.

BACKGROUND: The number of germ cells in human embryonic and fetal ovaries in relation to age is currently based on volumetric estimations from one study including a total of 12 ovaries. Six recent publications present stereological estimations of the number of germ cells in ovaries and testes for the first two trimesters. METHODS: Germ cell numbers from 103 human first and second trimester gonads aged 37-133 days post-conception (p.c.), obtained after legal termination of pregnancy, were collected from six independent studies that all used similar validated stereological methods for estimating germ cell numbers as well as somatic cell numbers. RESULTS: Statistically, the six studies estimated similar number of germ cells (P > 0.05) and no interaction between the studies and age was found (P > 0.05), indicating that the increase in cell numbers in relation to age was of comparable magnitude in each study. The number of germ cells increased from a mean of 7200 to 4,933,000 in fetal ovaries and from 3700 to 1,417,000 in fetal testes, from week 5 to week 19 p.c. A higher rate of increase was found for female germ cells as compared with males (P = 0.004). During the same period, the number of somatic cells increased from a mean of 158,000 to 1,017,000 in ovaries and from 154,000 to 2,035,000 in testes, respectively. CONCLUSIONS By the use of validated stereological methods, this study provides more accurate and improved information on human germ and somatic cell numbers in ovaries and testes during the first two trimesters of pregnancy.

Previously unrecognized advanced liver disease unveiled by transient elastography in patients with Haemophilia and chronic hepatitis C.

Before the introduction of viral inactivation procedures and viral screening of plasma-products, haemophiliacs were at high risk of infection with HCV. Those who acquired HCV infection in the 1980s, and are still alive today, may have developed significant liver fibrosis or cirrhosis. However, liver biopsy has not routinely been utilized in the evaluation of haemophiliacs with HCV in Denmark. The aim of this study was to investigate the prevalence of significant fibrosis/cirrhosis among haemophiliacs as evaluated by transient elastography (TE). Cross-sectional investigation of adult patients with haemophilia A or B. TE with liver stiffness measurements (LSM) ≥ 8 kPa were repeated after 4-6 weeks. Significant fibrosis and cirrhosis was defined as measurements ≥ 8 kPa or ≥ 12 kPa respectively. Among 307 patients with haemophilia A or B registered at the two Haemophilia centres, 141(46%) participate in this study. Forty (28.4%) had chronic hepatitis C, 33 (23.4%) past hepatitis C and 68 (48.2%) had never been infected, at screening LSM ≥ 8 kPa were found in 45.7%, 24.7% and 4.6% respectively. Among patients with chronic hepatitis C significant fibrosis was confirmed in 17.1% and cirrhosis in 2.9% by repeated LSM ≥ 8 and ≥ 12 kPa respectively. The median TE-value in never HCV-infected haemophiliacs was comparable with what has been found in healthy non-haemophiliacs. In Danish haemophiliacs where liver biopsy has not routinely been used for assessing severity of liver fibrosis, LSM identified advanced liver disease in one-fifth of cases that had not been recognized during clinical follow-up.