Search

Introduction Identification of pregnant women suffering from depression or other mental disorders is a challenge for antenatal caregivers. The purpose of this case-control study was to describe mental disorders and the risk factors for mental disorders in women with depressive symptoms assessed with the Edinburgh Postnatal Depression Scale during the first trimester and to compare them with pregnant women without depressive symptoms. Material and methods In total, 2271 women answered the Edinburgh Postnatal Depression Scale at the first antenatal visit with a midwife. An Edinburgh Postnatal Depression Scale score of 13 or higher was considered to be screen-positive and these women were further assessed. Screen-negative pregnant women, matched for age and parity, were chosen as controls. Results In total, 149 (6.6%) women were found to be screen-positive. The majority (126, 85%) had at least one mental disorder or risk factor for mental disorder, such as depression (36.0%), anxiety (14.8%), or severe fear of childbirth (20.8%). The screen-positive women were more often smokers (16.1% vs 1.3%), unemployed (19.9% vs 1.3%), or on sick leave (25.3% vs 14.1%) during pregnancy and more often used selective serotonin reuptake inhibitor during pregnancy (14.2% vs 2.7%) compared with the screen-negative women (PFunding Agencies|ALF, Region Ostergotland [LIO-35 9731]

Background Next of kin to older adults over 65 years in municipal home care are concerned whether their older adults’ needs are being met. In municipal home care, the registered nurses’ leadership is important and complex, entailing multi-artist skills involving the older adults and their next of kin. Yet, little is known about next of kin’s experiences of registered nurses’ leadership. Thus, the aim of this study was to explore next of kin’s experiences of registered nurses’ leadership close to older adults in municipal home care. Methods Individual telephone interviews were conducted with next of kin (n = 11) of older adults from April to September 2020 in two municipalities in western Sweden. Data were analysed using qualitative content analysis. Results The results are presented with the theme, registered nurses do what they can, including two categories, interaction and competence, and the subcategories, relationship, communication, availability, responsibility, team leadership and cooperation. Registered nurses’ leadership was experienced as a balancing act between their commitments and what they were able to achieve. Conclusions Next of kin’s experiences of registered nurses’ leadership can contribute knowledge that will strengthen and prepare registered nurses for their leadership roles. This knowledge can support the development of policies for organisational preconditions that ensure quality and safe care to older adults in municipal home care.

Contains fulltext : 244306.pdf (Publisher’s version ) (Open Access) Patients are the stewards of their own care and hence their voice is important when designing and implementing research. Patients should be involved not only as participants in research that impacts their care, as the recipients of that care and any associated harms, but also as research collaborators in prioritising important questions from the patient perspective and designing the research and the ways in which is it most appropriate to involve patients. The PIONEER Consortium, an international multistakeholder collaboration lead by the European Association of Urology, has developed a core outcome set (COS) for localised and metastatic prostate cancer relevant to all stakeholders in particular patients. Throughout the work of PIONEER, patient representatives were involved as collaborators in setting the research agenda, and a wider group of patients was involved as participants in developing COSs, for instance in consensus meetings on choosing important outcomes and appropriate definitions. This publication showcases the process for COS development and highlights the most important recommendations to ultimately inform future research projects co-created between patients and other stakeholders. PATIENT SUMMARY: An important step in involving patients in the selection of outcomes for clinical trials, clinical audits, and real-world evidence is the development of a core outcome set (COS) that is relevant to all stakeholders. This report highlights the patient participation throughout our PIONEER COS development. TAKE HOME MESSAGE: An important step in involving patients in the selection of outcomes for clinical trials, clinical audits, and real-world evidence is to develop a core outcome set (COS) that is relevant to all stakeholders. As part of the work of the PIONEER Consortium, we aim to highlight the patient participation throughout our PIONEER COS development.

BACKGROUND: Norwegian social educator students' attitudes towards addressing sexual health are unknown, even if their future clients often have needs related to sexual issues.PURPOSE: To investigate social educator students' readiness to address sexual health in their future profession.METHODS: In 2019, 213 social educator students (response rate 34%) responded to the Students' Attitudes towards addressing Sexual Health Extended online questionnaire.RESULTS: Most of the social educator students felt comfortable and ready to address sexual health in their future profession, but thought they had insufficient competence and education concerning sexual health. There were gender and age differences when discussing sexual health among persons with intellectual disabilities.CONCLUSION: Despite most Norwegian social educator students feeling ready to address sexual health, they needed additional competences and education. Further research is needed concerning the effectiveness of educational interventions targeting competence in sexual health, to ensure sufficient support for clients in this field.

Objective: People with diabetes are at a significantly higher risk of cardiovascular disease, in part, due to accelerated atherosclerosis. Diabetic subjects have increased number of platelets that are activated, more reactive, and respond suboptimally to antiplatelet therapies. We hypothesized that reducing platelet numbers by inducing their premature apoptotic death would decrease atherosclerosis. Approach and Results: This was achieved by targeting the antiapoptotic protein Bcl-x L (B-cell lymphoma-extra large; which is essential for platelet viability) via distinct genetic and pharmacological approaches. In the former, we transplanted bone marrow from mice carrying the Tyr15 to Cys loss of function allele of Bcl-x (known as Bcl-x Plt20 ) or wild-type littermate controls into atherosclerotic-prone Ldlr +/− mice made diabetic with streptozotocin and fed a Western diet. Reduced Bcl-x L function in hematopoietic cells significantly decreased platelet numbers, exclusive of other hematologic changes. This led to a significant reduction in atherosclerotic lesion formation in Bcl-x Plt20 bone marrow transplanted Ldlr +/− mice. To assess the potential therapeutic relevance of reducing platelets in atherosclerosis, we next targeted Bcl-x L with a pharmacological strategy. This was achieved by low-dose administration of the BH3 (B-cell lymphoma-2 homology domain 3) mimetic, ABT-737 triweekly, in diabetic Apoe −/− mice for the final 6 weeks of a 12-week study. ABT-737 normalized platelet numbers along with platelet and leukocyte activation to that of nondiabetic controls, significantly reducing atherosclerosis while promoting a more stable plaque phenotype. Conclusions: These studies suggest that selectively reducing circulating platelets, by targeting Bcl-x L to promote platelet apoptosis, can reduce atherosclerosis and lower cardiovascular disease risk in diabetes. Graphic Abstract: A graphic abstract is available for this article.

Objective To investigate the impact of major depressive disorder (MDD) and antidepressant medication before and during pregnancy on obstetric and neonatal outcomes. Study design A national register‐based cohort study of pregnant women born in Sweden, and their first child born in 2012–2015 (n = 262 329). Women diagnosed with MDD and who had redeemed an antidepressant one year before becoming pregnant (“before pregnancy”) and women who were diagnosed with MDD and who had redeemed an antidepressant both before and during pregnancy (“before and during pregnancy”) were compared with each other and with women who had neither been diagnosed with MDD nor been prescribed antidepressants (population controls). Results In comparison to population controls, the “before pregnancy” and the “before and during pregnancy” groups had increased likelihoods of operative childbirth (aOR = 1.19, 95 % CI 1.12−1.27, aOR = 1.38, 95 % CI 1.28−1.48 respectively), and with an increased likelihood for the child being admitted to a neonatal intensive care unit (NICU) (aOR = 1.51, 95 % CI 1.17−1.95, aOR = 1.55, 95 % CI 1.14−2.11). Children born to mothers in the “before and during pregnancy” group had an increased likelihood of preterm birth (aOR = 1.72, 95 % CI 1.52−1.95,), while children to mothers in the “before pregnancy” group had an increased likelihood of low birthweight (aOR = 1.15, 95 % CI 1.00−1.33) compared to population controls. Women in the “before and during pregnancy” group had an increased likelihood for hyperemesis during pregnancy (aOR = 1.93, 95 % CI = 1.60–2.32), having an operative childbirth (aOR = 1.17, 95 % CI = 1.06–1.29) or a preterm birth (aOR = 1.53, 95 % CI = 1.28–1.81) compared to the “before pregnancy” group. Conclusions Women with MDD and antidepressant medication prior to becoming pregnant are at increased risk for adverse obstetric and neonatal outcomes compared to women without an MDD. Continuation of antidepressant medication during pregnancy somewhat increased the risk for adverse obstetric and neonatal outcomes.

Studies of thermally induced transport in nanostructures provide access to an exciting regime where fluctuations are relevant, enabling the investigation of fundamental thermodynamic concepts and the realization of thermal energy harvesters. We study a serial double quantum dot formed in an InAs/InP nanowire coupled to two electron reservoirs. By means of a specially designed local metallic joule-heater, the temperature of the phonon bath in the vicinity of the double quantum dot can be enhanced. This results in phonon-assisted transport, enabling the conversion of local heat into electrical power in a nano-sized heat engine. Simultaneously, the electron temperatures of the reservoirs are affected, resulting in conventional thermoelectric transport. By detailed modelling and experimentally tuning the interdot coupling we disentangle both effects. Furthermore, we show that phonon-assisted transport gives access to the energy of excited states. Our findings demonstrate the versatility of our design to study fluctuations and fundamental nanothermodynamics., 11 pages, 4 figures + SI

Leukocyte telomere length (LTL) is a proposed biomarker for aging-related disorders, including cognitive decline and dementia. Long-term longitudinal studies measuring intra-individual changes in both LTL and cognitive outcomes are scarce, precluding strong conclusions about a potential aging-related relationship between LTL shortening and cognitive decline. This study investigated associations between baseline levels and longitudinal changes in LTL and memory performance across an up to 20-year follow-up in 880 dementia-free participants from a population-based study (mean baseline age: 56.8 years, range: 40–80; 52% female). Shorter baseline LTL significantly predicted subsequent memory decline (r = .34, 95% confidence interval: 0.06, 0.82), controlling for age, sex, and other relevant covariates. No significant associations were however observed between intra-individual changes in LTL and memory, neither concurrently nor with a 5-year time-lag between LTL shortening and memory decline. These results support the notion of short LTL as a predictive factor for aging-related memory decline, but suggest that LTL dynamics in adulthood and older age may be less informative of cognitive outcomes in aging. Furthermore, the results highlight the importance of long-term longitudinal evaluation of outcomes in biomarker research.

Objectives: The aim of this nationwide study was to examine the association between age at retirement and dementia risk, with a follow-up period of up to 24 years. Methods/design: This cohort study comprised Swedish citizens born in 1930 who were alive in the year 1990 (n=63,505). The cohort was followed for incidents of dementia through data provided by the Swedish National Patient Register and the Cause of Death Register. Age at retirement and socioeconomic variables were retrieved from Statistics Sweden. Results: During the follow-up, 5,181 individuals received a dementia diagnosis. Competing risk regression models, adjusted for sex, education, marital status, occupation, and previous history of cardiovascular diseases, showed that later-than-average retirement age was associated with decreased dementia risk. Conclusions: The present results supports the idea that individuals who retired at an older age has a decrease risk of dementia. However, as this was an observation study, unmeasured factors, such as premorbid cognitive level and genetic predisposition, may have influenced our findings and remains to be elucidated in future studies.

Infections during first-line therapy for DLBCL are often associated with chemotherapy dose reductions and increased mortality. Systemic infections have also been suggested as beneficial promotors of immunological responses. However, whether there is an association between the timing of an infectious episode and outcome during treatment has not yet been clarified. We investigated how the occurrence and timing of infectious episodes during the first line of treatment for “de novo” DLBCL influenced patient outcome. We used data on DLBCL patients from the Danish Lymphoma Registry, the Danish National Patient Registry, and the Danish National Pathology Registry. Infections were categorized according to type (ICD-10) and time of occurrence after treatment start. “Early” infections were defined as occurring between days 7 and 42 and “late” infections between days 100 and 150 from treatment start. Patients experiencing both “early and late” infections were categorized separately. We used multivariable Cox regression and Kaplan-Meier estimates to assess the association between infections and survival adjusting for NCCN-IPI, sex, comorbidity, and rituximab treatment. We identified 3546 patients, median age 65 years (IQR 56,73). Infectious episodes occurred in 1171 (33%) patients, of which 666 had “early,” 303 “late,” and 202 both “early and late” events. Patients without registered infections had a 5-year overall survival (OS) rates of 74%. Those with “early,” “late,” or “early+late” had 5-year OS of 65%, 62%, and 53%, respectively. Compared with patients without any registered infections, hazard rate ratios (HR) were 1.24 (95% CI 1.05-1.47), 1.32 (95% CI 1.06–1.63), and 1.59 (95% CI 1.27-2.00), respectively, in the multivariable model. We observed that infectious episodes during first-line treatment for “de novo” DLBCL occurred in 44% of the patients. Irrespective of timing, patients with infectious episodes had an inferior outcome compared to those without. Outcome patterns were similar for patients registered with sepsis.

Background It is unclear whether the outcomes differ after different Horne and Tanzer types of olecranon fractures. Materials and methods We evaluated 40 men and 55 women with isolated olecranon fractures, journals and radiographs from fracture event. The fractures were classified according to Horne and Tanzer. After a mean 19 years after the fracture events, we evaluated subjective, clinical and radiographic outcomes, using the uninjured arms as controls. Results 95% of patients with type I fractures reported, at follow-up, no differences between the elbows, 80% with type II fractures and 95% with type III fractures (p = 0.43). The three types of fractures had no differences in elbow range of motion or hand grip strength (when comparing injured and uninjured arms) and the proportions of individuals with radiographic elbow degenerative changes or joint space reduction were no different (all p > 0.05). Individuals with elbow degenerative changes had no inferior subjective elbow function compared to individuals with normal radiographs (p = 0.66), in contrast to those with joint space reduction compared to individuals with normal radiographs (p Interpretation All types of Horne and Tanzer olecranon fractures have favourable long-term outcome. Elbow joint space reduction is associated with inferior subjective elbow function while degenerative changes are not.

Background Dosimetry for diagnostic agents is performed to assess the risk of radiation detriment (e.g., cancer) associated with the imaging agent and the risk is assessed by computing the effective dose coefficient, e. Stylized phantoms created by the MIRD Committee and updated by work performed by Cristy-Eckerman (CE) have been the standard in diagnostic dosimetry. Recently, the ICRP developed voxelized phantoms, which are described in ICRP Publication 110. These voxelized phantoms are more realistic and detailed in describing human anatomy compared with the CE stylized phantoms. Ideally, all tissues should be represented and their pharmacokinetics collected for an as accurate a dosimetric calculation as possible. As the number of source tissues included increases, the calculated e becomes more accurate. There is, however, a trade-off between the number of source tissues considered, and the time and effort required to measure the time-activity curve for each tissue needed for the calculations. In this study, we used a previously published 68Ga-DOTA-TATE data set to examine how the number of source tissues included for both the ICRP voxelized and CE stylized phantoms affected e. Results Depending upon the number of source tissues included e varied between 14.0–23.5 μSv/MBq for the ICRP voxelized and 12.4–27.7 μSv/MBq for the CE stylized phantoms. Furthermore, stability in e, defined as a < 10% difference between e obtained using all source tissues compared to one using fewer source tissues, was obtained after including 5 (36%) of the 14 source tissues for the ICRP voxelized, and after including 3 (25%) of the 12 source tissues for the CE stylized phantoms. In addition, a 2-fold increase in e was obtained when all source tissues where included in the calculation compared to when the TIAC distribution was lumped into a single reminder-of-body source term. Conclusions This study shows the importance of including the larger tissues like the muscles and remainder-of-body in the dosimetric calculations. The range of e based on the included tissues were less for the ICRP voxelized phantoms using tissue weighting factors from ICRP Publication 103 compared to CE stylized phantoms using tissue weighting factors from ICRP Publication 60.

ObjectiveTo determine whether patients with cluster headache have more sickness absence and disability pension days compared to matched references and possible associations with sociodemographic characteristics.MethodsWe performed a registry study of all patients who had received specialized health care for cluster headache (ICD-10 code G44.0) aged 16–64 years and living in Sweden in 2010 (n = 3,240; 34% women) and matched references from the total population (n = 16,200) regarding their sickness absence and disability pension days in 2010.ResultsMean number of sickness absence days in 2010 was 16.13 (95% confidence interval, 14.05–18.20) among patients with cluster headache and 6.54 (5.97–7.11) among references. When combining sickness absence and disability pension days, patients with cluster headache had 63.15 (58.84–67.45) days, references 34.08 (32.59–35.57) days. Among patients, women had twice as many sickness absence days than men: 23.71 (19.36–28.06) vs 12.41 (10.19–14.63). When adding disability pension days, those numbers were 83.71 (75.57–91.84) vs 52.56 (47.62–57.51). Patients with cluster headache had significantly more sickness absence days in all ages compared to the reference group. Patients with elementary education had more sickness absence/disability pension days (85.88 [75.34–96.42]) compared to those with high school (64.89 [58.82–70.97]) and college/university (41.42 [34.70–48.15]) education.ConclusionThis nationwide study shows that patients with cluster headache have significantly more sickness absence and disability pension days compared to matched references. Furthermore, among patients, women had more sickness absence and disability pension days than men.

Auger radiopharmaceutical therapy is a promising strategy for micrometastatic disease given high linear energy transfer and short range in tissues, potentially limiting normal tissue toxicities. We previously demonstrated anti-tumor efficacy of a small-molecule Auger electron emitter targeting the prostate-specific membrane antigen (PSMA), 2-[3-[1-carboxy-5-(4-[125I]iodo-benzoylamino)-pentyl]-ureido]-pentanedioic acid), or 125I-DCIBzL, in a mouse xenograft model. Here, we investigated the therapeutic efficacy, long-term toxicity, and biodistribution of 125I-DCIBzL in a micrometastatic model of prostate cancer (PC). Methods: To test the therapeutic efficacy of 125I-DCIBzL in micrometastatic PC, we used a murine model of human metastatic PC in which PSMA+ PC3-ML cells expressing firefly luciferase were injected intravenously in NSG mice to form micrometastatic deposits. One week later, 0, 0.37, 1.85, 3.7, 18.5, 37, or 111 MBq of 125I-DCIBzL was administered (intravenously). Metastatic tumor burden was assessed using bioluminescence imaging (BLI). Long-term toxicity was evaluated via serial weights and urinalysis of non-tumor-bearing mice over a 12-month period, as well as final necropsy. Results: In the micrometastatic PC model, activities of 18.5 MBq 125I-DCIBzL and above significantly delayed development of detectable metastatic disease by BLI and prolonged survival in mice. Gross metastases were detectable in control mice and those treated with 0.37-3.7 MBq 125I-DCIBzL at a median of 2 weeks post-treatment, versus 4 weeks for those treated with 18.5-111 MBq 125I-DCIBzL (P

This work is licensed under the Creative Commons Attribution-NonCommercial International License (CC BY-NC 4.0) Background: Sexual health needs are insufficiently met for persons living with rheumatological diseases and it is necessary to create better ways to meet these needs. Objective: To co-create a working model to improve sexual health for persons living with rheumatological diseases, that can be used by rheumatological teams in regular rheumatology practice. Design: This study applied a co-creation design with three key features: 1) it took a systems perspective with emergent multiple interactive entities; 2) the research process was viewed as a creative endeavour with strong links to design, while human imagination and the individual experience of patient and staff were at the core of the creative design effort; 3) the process of the co-creative efforts was as important as the generated product. Results: A model defining the role of the patient, the professionals, and the team in optimizing sexual health for persons living with rheumatological diseases was co-created. The model can be seen as a practice guideline, which includes the support needed from and to each participant in the process of promoting sexual health, while being within the professional scope of the professionals’ knowledge and capacity, and in line with the needs of the persons living with rheumatological diseases. Discussion and Conclusions: The co-creative work process identified crucial factors in promoting sexual health, resulting in a useful model for patients, professionals and teams. Co-creation was experienced to be a useful research design to improve rheumatological care, through valuing and using the competence of all research members equally. The study was funded by the Medical Research Council of Southeast Sweden, grant number FORSS701251.

Background Taxane treatment may be a suitable therapeutic option for patients with castration‐resistant prostate cancer and high expression of constitutively active androgen receptor variants (AR‐Vs). The aim of the study was to compare the effects of cabazitaxel and androgen deprivation treatments in a prostate tumor xenograft model expressing high levels of constitutively active AR‐V7. Furthermore, mechanisms behind acquired cabazitaxel resistance were explored. Methods Mice were subcutaneously inoculated with 22Rv1 cells and treated with surgical castration (n = 7), abiraterone (n = 9), cabazitaxel (n = 6), castration plus abiraterone (n = 8), castration plus cabazitaxel (n = 11), or vehicle and/or sham operation (n = 23). Tumor growth was followed for about 2 months or to a volume of approximately 1000 mm3. Two cabazitaxel resistant cell lines; 22Rv1‐CabR1 and 22Rv1‐CabR2, were established from xenografts relapsing during cabazitaxel treatment. Differential gene expression between the cabazitaxel resistant and control 22Rv1 cells was examined by whole‐genome expression array analysis followed by immunoblotting, immunohistochemistry, and functional pathway analysis. Results Abiraterone treatment alone or in combination with surgical castration had no major effect on 22Rv1 tumor growth, while cabazitaxel significantly delayed and in some cases totally abolished 22Rv1 tumor growth on its own and in combination with surgical castration. The cabazitaxel resistant cell lines; 22Rv1‐CabR1 and 22Rv1‐CabR2, both showed upregulation of the ATP‐binding cassette sub‐family B member 1 (ABCB1) efflux pump. Treatment with ABCB1 inhibitor elacridar completely restored susceptibility to cabazitaxel, while treatment with AR‐antagonists bicalutamide and enzalutamide partly restored susceptibility to cabazitaxel in both cell lines. The cholesterol biosynthesis pathway was induced in the 22Rv1‐CabR2 cell line, which was confirmed by reduced sensitivity to simvastatin treatment. Conclusions Cabazitaxel efficiently inhibits prostate cancer growth despite the high expression of constitutively active AR‐V7. Acquired cabazitaxel resistance involving overexpression of efflux transporter ABCB1 can be reverted by bicalutamide or enzalutamide treatment, indicating the great clinical potential for combined treatment with cabazitaxel and anti‐androgens.

The analysis of operator’s work patterns in safety-critical domains is increasingly assisted by eye-tracking technologies. A reason is a growing demand for empirically justified assurance to ascertain an equal level of safety after the implementation of new techniques and higher levels of automation. In the field and simulation studies, head-mounted eye-tracking devices are a preferred choice because of the easy, reliable and fast startup. The downside is time-consuming work to map gaze points to the world/workplace coordinates which makes head-mounted devices applicable to a small number of episodes to analyze. This paper presents a solution called AoI Mapping and Analysis Tool (AMAT) that relies on visual features provided by the integrated scene video camera. AoI-templates can be defined from the video recording and are constantly matched for an AoI-analysis. AMAT was evaluated with a field study example from Air Traffic Control (ATC) in the tower at Linkoping City airport and a training simulator study example from Vessel Traffic Service (VTS) in Gothenburg. Example situations demonstrate the capabilities of AMAT to define AoIs, evaluate the validity of the chosen set of AoIs and export to an example analysis program Eloquence for the visualization of results. The AoI-sequence of 4 vessels encounter in the Gothenburg archipelago was shown as well as the comparison of four tower controller’s sequences during the final approach. The final discussion highlights the capabilities and limitations of the implemented techniques that rely on the AKAZE point feature detection and linear homographic transformations. A major source of disturbance lies in the varying light conditions evoking under-exposure of the video camera and fast head movements.

Prostate Cancer Diagnosis and Treatment Enhancement Through the Power of Big Data in Europe (PIONEER) is a European network of excellence for big data in prostate cancer, consisting of 32 private and public stakeholders from 9 countries across Europe. Launched by the Innovative Medicines Initiative 2 and part of the Big Data for Better Outcomes Programme (BD4BO), the overarching goal of PIONEER is to provide high-quality evidence on prostate cancer management by unlocking the potential of big data. The project has identified critical evidence gaps in prostate cancer care, via a detailed prioritization exercise including all key stakeholders. By standardizing and integrating existing high-quality and multidisciplinary data sources from patients with prostate cancer across different stages of the disease, the resulting big data will be assembled into a single innovative data platform for research. Based on a unique set of methodologies, PIONEER aims to advance the field of prostate cancer care with a particular focus on improving prostate-cancer-related outcomes, health system efficiency by streamlining patient management, and the quality of health and social care delivered to all men with prostate cancer and their families worldwide.Prostate Cancer Diagnosis and Treatment Enhancement Through the Power of Big Data in Europe (PIONEER) is a European network of excellence for big data in prostate cancer, consisting of 32 private and public stakeholders from 9 countries across Europe. In this Perspectives article, the authors introduce the PIONEER project and describe its aims and plans for ultimately improving prostate cancer care through the use of big data.

Tumour vasculature supports the growth and progression of solid cancers with both angiogenesis (endothelial cell proliferation) and vasculogenic mimicry (VM, the formation of vascular structures by cancer cells themselves) predictors of poor patient outcomes. Increased circulating platelet counts also predict poor outcome for cancer patients but the influence of platelets on tumour vasculature is incompletely understood. Herein, we show with in vitro assays that platelets did not influence angiogenesis but did actively inhibit VM formation by cancer cell lines. Both platelet sized beads and the releasates from platelets were partially effective at inhibiting VM formation suggesting that direct contact maximises the effect. Platelets also promoted cancer cell invasion in vitro. B16F10 melanomas in Bcl-xPlt20/Plt20 thrombocytopenic mice showed a higher content of VM than their wildtype counterparts while angiogenesis did not differ. In a xenograft mouse model of breast cancer with low-dose aspirin to inactivate the platelets, the burden of MDA-MB-231-LM2 breast cancer cells was reduced and the gene expression profile of the cancer cells was altered; but no effect on tumour vasculature was observed. Taken together, this study provides new insights into the action of platelets on VM formation and their involvement in cancer progression.

Partial and/or heterogeneous irradiation of established (i.e., large, vascularized) tumors by α-particles that exhibit only a 4-5 cell-diameter range in tissue, limits the therapeutic effect, since regions not being hit by the high energy α-particles are likely not to be killed. This study aims to mechanistically understand a delivery strategy to uniformly distribute α-particles within established solid tumors by simultaneously delivering the same α-particle emitter by two diverse carriers, each killing a different region of the tumor: (1) the cancer-agnostic, but also tumor-responsive, liposomes engineered to best irradiate tumor regions far from the vasculature, and (2) a separately administered, antibody, targeting any cancer-cell's surface marker, to best irradiate the tumor perivascular regions. We demonstrate that on a prostate specific membrane antigen (PSMA)-expressing prostate cancer xenograft mouse model, for the same total injected radioactivity of the α-particle emitter Actinium-225, any radioactivity split ratio between the two carriers resulted in better tumor growth inhibition compared to the tumor inhibition when the total radioactivity was delivered by any of the two carriers alone. This finding was due to more uniform tumor irradiation for the same total injected radioactivity. The killing efficacy was improved even though the tumor-absorbed dose delivered by the combined carriers was lower than the tumor-absorbed dose delivered by the antibody alone. Studies on spheroids with different receptor-expression, used as surrogates of the tumors' avascular regions, demonstrated that our delivery strategy is valid even for as low as 1+ (ImmunoHistoChemistry score) PSMA-levels. The findings presented herein may hold clinical promise for those established tumors not being effectively eradicated by current α-particle radiotherapies.

OBJECTIVE To investigate laypeople and dental professionals' opinions of the aesthetic outcome from implant therapy (IT) and orthodontic space closure (SC) for missing maxillary lateral incisors. MATERIAL AND METHODS Evaluation was performed by three groups: laypeople 20-30 years of age (n = 26), laypeople 50-70 years of age (n = 26) and orthodontists (n = 25). The assessors viewed photographs of 44 different cases treated with IT or SC, and made an evaluation of the aesthetics. RESULTS The gingival color adjacent to the replaced tooth was rated as having better aesthetics in the SC cases (p = 0.000). The orthodontists preferred the aesthetics of the dentition in the SC cases (p = 0.042). The young laypeople, compared to the older laypeople and orthodontists, were more dissatisfied with the color of the tooth replacing the missing lateral incisor in SC cases (p = 0.043). CONCLUSION The color of the gingiva adjacent to the implant-supported crowns had a lower aesthetic rating than the SC group. Laypeople rated both treatments as equally good. The orthodontists had a slight preference for the aesthetics in the SC cases.

At the Swedish national forensic toxicology laboratory, a measured testosterone/epitestosterone (T/E) ratio ≥ 12 together with testosterone/luteinizing hormone (T/LH) in urine > 400 nmol/IU is considered as a proof of exogenous testosterone administration. However, according to the rules of the World Anti-Doping Agency (WADA), samples with T/E ratio > 4 are considered suspicious and shall be further analysed by gas chromatography-combustion-isotope ratio mass spectrometry (GC-C-IRMS) to confirm the origin of testosterone and its metabolites. The aim of this study was to investigate the possibility of false negative results and to estimate the frequency of negative results using the current criteria for detection of abuse of testosterone in forensic investigations. Urine and serum samples were collected by the police at suspected infringement of the doping law in Sweden. Fifty-eight male subjects were included in the study. Urinary testosterone was determined by gas chromatography-mass spectrometry (GC-MS), serum testosterone and LH-by immunoassay. The origin of testosterone and its metabolites was confirmed by means of GC-C-IRMS. Twenty-six of the 57 analysed subjects tested positive for exogenous testosterone using the criteria T/E ≥ 12 combined with T/LH > 400 nmol/IU. The IRMS analyses confirmed 47 positives; thus, 21 were considered false negatives. Negative predictive value was 32% (95% confidence interval [CI]: 16%-50%) and sensitivity 55%. No false positive subjects were found. The number of false negative cases using the current criteria for the detection of testosterone abuse and hence the low sensitivity indicates a need to discuss introduction of new strategies in forensic doping investigations.

Background Leukocyte telomere length (LTL) has been shown to predict Alzheimer’s disease (AD), albeit inconsistently. Failing to account for the competing risks between AD, other dementia types, and mortality, can be an explanation for the inconsistent findings in previous time-to-event analyses. Furthermore, previous studies indicate that the association between LTL and AD is non-linear and may differ depending on apolipoprotein E (APOE) ε4 allele carriage, the strongest genetic AD predictor. Methods We analyzed whether baseline LTL in interaction with APOE ε4 predicts AD, by following 1306 initially non-demented subjects for 25 years. Gender- and age-residualized LTL (rLTL) was categorized into tertiles of short, medium, and long rLTLs. Two complementary time-to-event models that account for competing risks were used; the Fine-Gray model to estimate the association between the rLTL tertiles and the cumulative incidence of AD, and the cause-specific hazard model to assess whether the cause-specific risk of AD differed between the rLTL groups. Vascular dementia and death were considered competing risk events. Models were adjusted for baseline lifestyle-related risk factors, gender, age, and non-proportional hazards. Results After follow-up, 149 were diagnosed with AD, 96 were diagnosed with vascular dementia, 465 died without dementia, and 596 remained healthy. Baseline rLTL and other covariates were assessed on average 8 years before AD onset (range 1–24). APOE ε4-carriers had significantly increased incidence of AD, as well as increased cause-specific AD risk. A significant rLTL-APOE interaction indicated that short rLTL at baseline was significantly associated with an increased incidence of AD among non-APOE ε4-carriers (subdistribution hazard ratio = 3.24, CI 1.404–7.462, P = 0.005), as well as borderline associated with increased cause-specific risk of AD (cause-specific hazard ratio = 1.67, CI 0.947–2.964, P = 0.07). Among APOE ε4-carriers, short or long rLTLs were not significantly associated with AD incidence, nor with the cause-specific risk of AD. Conclusions Our findings from two complementary competing risk time-to-event models indicate that short rLTL may be a valuable predictor of the AD incidence in non-APOE ε4-carriers, on average 8 years before AD onset. More generally, the findings highlight the importance of accounting for competing risks, as well as the APOE status of participants in AD biomarker research.

Background: It is unclear if the outcomes differ in different subtypes of olecranon fractures. Objective: Evaluate the outcomes of different Colton types of olecranon fractures, and if outcomes differ in dominant and non-dominant arms and in men and women. Methods: We evaluated primary journals and radiographs in 40 men and 55 women with isolated olecranon fractures and classified fractures according to Colton. Mean 19 years after fracture event, we re-examined subjective, clinical and radiographic outcomes in the former patients, using the uninjured arms as controls. Results: 89% of patients with Colton type I fractures reported at follow-up no subjective differences between the elbows, 84% with type II oblique/transverse fractures and 84% with type II comminuted fractures (p=0.91). The uninjured to former fractured arm differences in elbow range of motion and strength were no different in the 3 fracture types, the proportions of individuals with radiographic elbow degenerative changes were greater in type II than in type I factures (p Conclusion: There were no different outcomes after Colton type I, type II oblique/transverse or type II comminuted fractures, no different outcomes between fractures in dominant or non-dominant arms and no different outcomes in men and women.

Higher affinity of Ga compounds to somatostatin receptors (SSTRs) and PET better image resolution increased interest in Ga-labelled somatostatin analogs in the management of neuroendocrine tumours (NETs). This study aimed to evaluate the maximum standardized uptake value (SUVmax) variation in sequential somatostatin analogs-PET in NET patients and identify optimal tumour detection and characterization imaging time.Patients with histological or biochemical NET diagnosis performed two to three PET/computed tomography (CT) scans after intravenous injection of Ga-DOTATATE: Early PET [EarlyPET:15 minutes postinjection (p.i.)], diagnostic PET (DiagPET: 45-90 minutes p.i.) and delayed PET (DelayPE: 90-240 minutes p.i.). Up to five tumour sites and normal tissues had SUVmax determined. Time-SUVmax curves were created for the target lesions and normal organs. Ratios between tumour and liver SUVmax (SUVTU/Liver) and tumour/blood pool (SUVTU/BP) were also calculated.Twenty-nine patients were included, 16 female, mean age of 46.5 ± 14.3 years. Average administered activity was 129.5 ± 29.6 MBq. Kidneys SUVmax was higher in EarlyPET compared with DiagPET (P = 0.04) and DelayPET showed higher SUVmax compared with DiagPET for normal liver, pancreas and kidneys (P = 0.02). No differences were noted between EarlyPET, DiagPET and DelayPET in tumour SUVmax (P0.05). SUVTU/Liver and SUVTU/BP did not change between EarlyPET and DiagPET, with a slight decrease in DelayPET.Stability in tumour SUVmax values measured at different intervals independently of tumour location, as also in normal tissues as kidneys and liver suggest that a more flexible imaging protocol may be adopted.

ObjectiveTo estimate the prevalence of cluster headache in working-aged people, compare sickness absence rates and disability pension in cluster headache patients to rates in a matched comparison group, and explore associations of sociodemographic factors with such rates.MethodsThrough population-based registers, we identified 3,240 people aged 16–64, living in Sweden in 2010, who at least once during 2001–2010 received inpatient or specialized outpatient health care with cluster headache (ICD-10 code G44.0) as main diagnosis. A comparison group (n = 16,200), matched for age, sex, type of living area, and educational level, from the total population aged 16–64 (n = 5,945,895) was used. Outcomes were sickness absence (>14 days) and disability pension during 2010. Crude and adjusted prevalence rates and odds ratios with 95% confidence intervals were computed.ResultsThe prevalence of cluster headache in working-aged people was 0.054%. In 2010, 17.30% of the cluster headache group and 9.16% of the comparison group had been on sickness absence. In the cluster headache group, female patients had higher sickness absence rates (25.31%) and full-time disability pension (13.17%) than male patients (13.38% and 8.79%). Cluster headache patients older than 35 had higher rates than those of the same age in the comparison group. Further, cluster headache patients born outside Sweden were more likely to have full-time disability pension than patients born in Sweden.ConclusionsMuch higher rates of the patients had sickness absence or disability pension than in the comparison group. Further shown differences related to sex, age, and other sociodemographic factors need to be addressed.

BACKGROUND: Biofilms are involved in many Staphylococcus aureus infections. Relation of biofilm forming S. aureus strains and the infection types or the clinical outcomes remain unclear. METHODS: We measured biofilm formation, with a microtiter plate assay, of a collection of methicillin-sensitive clinical isolates from 159 invasive S. aureus infections, encompassing all cases occurring within a hospital catchment area during two years, and of additional 49 non-invasive skin infection isolates from the same region. These results were related to available clinical and microbiological documentation. RESULTS: Isolates from medical device infections (intravenous line-associated and prosthetic joint infections), as well as isolates from superficial skin infections, were particularly proficient in forming biofilms. No increased biofilm-forming capacity was seen in isolates from endocarditis, osteomyelitis, or from other infections. There was also a correlation of biofilm formation with the agr type of the isolates. Thicker biofilms appeared to be more resistant to antibiotic treatment in vitro. No correlation between biofilm formation and clinical outcomes was noted. CONCLUSIONS: S. aureus isolates from ‘classical’ biofilm-related infections, but also from superficial skin infections, are especially proficient in forming biofilms. There is, however, no obvious relation of biofilm-forming capacity of isolates and the clinical outcome of the infection, and more studies on this issue are needed.

T cells modified to express chimeric antigen receptor (CAR) targeting CD19 (CD19CAR) have produced remarkable clinical responses in patients with relapsed/refractory B-cell acute lymphoblastic leukemia. CD19CAR T-cell therapy has also demonstrated prominent effects in B-cell non-Hodgkin lymphoma (B-NHL) patients. However, a subset of patients who relapse after CD19CAR T-cell therapy have outgrowth of CD19− tumor cells. Hence, development of alternative CARs targeting other B-cell markers represents an unmet medical need for B-cell acute lymphoblastic leukemia and B-NHL. Here, we confirmed previous data by showing that, overall, B-NHL has high expression of CD37. A second-generation CD37CAR was designed, and its efficacy in T cells was compared with that of CD19CAR. In vitro assessment of cytotoxicity and T-cell function upon coculture of the CAR T cells with different target B-cell lymphoma cell lines demonstrated comparable efficacy between the 2 CARs. In an aggressive B-cell lymphoma xenograft model, CD37CAR T cells were as potent as CD19CAR T cells in controlling tumor growth. In a second xenograft model, using U2932 lymphoma cells containing a CD19− subpopulation, CD37CAR T cells efficiently controlled tumor growth and prolonged survival, whereas CD19CAR T cells had limited effect. We further show that, unlike CD19CAR, CD37CAR was not sensitive to antigen masking. Finally, CD37CAR reactivity was restricted to B-lineage cells. Collectively, our results demonstrated that CD37CAR T cells also can effectively eradicate B-cell lymphoma tumors when CD19 antigen expression is lost and support further clinical testing for patients with relapsed/refractory B-NHL.

Sexual health is an important area for social work. Social workers’ failure to address sexual health issues in social work practice, due to experienced discomfort, may create barriers toward clients, and lead to their decreased health. Investigating social work students’ attitudes toward sexual health, and their perceived competence in this area is crucial for developing social work education on sexual health issues. The aim of the present study was to explore Swedish social work students’ attitudes and perceived competence and educational needs regarding communicating about sexual health in their future profession. A quantitative study using the Students’ Attitudes toward Sexual Health (SA-SH) in a Swedish sample of 242 social work students. The students considered knowledge about sexual health as important for their future profession. The response patterns indicated that students considered themselves uncomfortable and insufficiently prepared to handle issues related to sexual health in their future profession, which may affect how they succeed in addressing the needs of their future clients. The conclusion of this study is that social work students are insufficiently prepared to address issues concerning sexual health in their future profession. Social work programs need to increase sexual health education as well as training in communicating about sexual health issues in order to meet the needs of the clients.

Based on gene-expression profiles, prostate tumors can be subdivided into subtypes with different aggressiveness and response to treatment. We investigated if similar clinically relevant subgroups can be identified simply by the combination of two immunohistochemistry markers: one for tumor cell differentiation (prostate specific antigen, PSA) and one for proliferation (Ki67). This was analyzed in men with prostate cancer diagnosed at transurethral resection of the prostate 1975-1991 (n = 331) where the majority was managed by watchful waiting. Ki67 and PSA immunoreactivity was related to outcome and to tumor characteristics previously associated with prognosis. Increased Ki67 and decreased PSA were associated with poor outcome, and they provided independent prognostic information from Gleason score. A combinatory score for PSA and Ki67 immunoreactivity was produced using the median PSA and Ki67 levels as cut-off (for Ki67 the upper quartile was also evaluated) for differentiation into subgroups. Patients with PSA low/Ki67 high tumors showed higher Gleason score, more advanced tumor stage, and higher risk of prostate cancer death compared to other patients. Their tumor epithelial cells were often ERG positive and expressed higher levels of ErbB2, phosphorylated epidermal growth factor receptor (pEGF-R) and protein kinase B (pAkt), and their tumor stroma showed a reactive response with type 2 macrophage infiltration, high density of blood vessels and hyaluronic acid, and with reduced levels of caveolin-1, androgen receptors, and mast cells. In contrast, men with PSA high/Ki67 low tumors were characterized by low Gleason score, and the most favorable outcome amongst PSA/Ki67-defined subgroups. Men with PSA low/Ki67 low tumors showed clinical and tumor characteristics intermediate of the two groups above. A combinatory PSA/Ki67 immunoreactivity score identifies subgroups of prostate cancers with different epithelial and stroma phenotypes and highly different outcome but the clinical usefulness of this approach needs to be validated in other cohorts.

Previous research regarding social work related to sexual health and sexuality shows the importance of competence in this field for social workers and therefore is a need to explore students´ attit ...

OBJECTIVES: To evaluate the intra- and inter-rater agreement for myometrial lesions using Morphologic Uterus Sonographic Assessment terminology. METHODS: Thirteen raters with high (n = 6) or medium experience (n = 7) assessed 30 3-dimensional ultrasound clips with (n = 20) and without (n = 10) benign myometrial lesions. Myometrial lesions were reported as poorly or well defined and then systematically evaluated for the presence of individual features. The clips were blindly assessed twice (at a 2-month interval). Intra- and inter-rater agreements were calculated with κ statistics. RESULTS: The reporting of poorly defined lesions reached moderate intra-rater agreement (κ = 0.49 [high experience] and 0.47 [medium experience]) and poor inter-rater agreement (κ = 0.39 [high experience] and 0.25 [medium experience]). The reporting of well-defined lesions reached good to very good intra-rater agreement (κ = 0.73 [high experience] and 0.82 [medium experience]) and good inter-rater agreement (κ = 0.75 [high experience] and 0.63 [medium experience]). Most individual features associated with ill-defined lesions reached moderate intra- and inter-rater agreement among highly experienced raters (κ = 0.41-0.60). The least reproducible features were myometrial cysts, hyperechoic islands, subendometrial lines and buds, and translesional flow (κ = 0.11-0.34). Most individual features associated with well-defined lesions reached moderate to good intra- and inter-rater agreement among all observers (κ = 0.41-0.80). The least reproducible features were a serosal contour, asymmetry, a hyperechoic rim, and fan-shaped shadows (κ = 0.00-0.35). CONCLUSIONS: The reporting of well-defined lesions showed excellent agreement, whereas the agreement for poorly defined lesions was low, even among highly experienced raters. The agreement on identifying individual features varied, especially for features associated with ill-defined lesions. Guidelines on minimum requirements for features associated with ill-defined lesions to be interpreted as poorly defined lesions may improve agreement., SCOPUS: ar.j, info:eu-repo/semantics/published

Triple-negative breast cancer (TNBC) is associated with a poorer prognosis, including a higher potential to metastasize and a decrease in the 5-year survival rate as compared to other breast cancer subtypes (77% vs. 93%). The poor prognosis is partially due to the lack of targeted treatments for TNBC, highlighting the need to develop targeted therapies for TNBC. Alpha-emitting radionuclides, such as Actinium-225, provide high linear energy transfer (LET) radiation. Clinical and pre-clinical studies have shown that targeted alpha-therapy is a highly potent treatment for metastatic cancer. Peptides and peptidomimetics are minimally immunogenic and have rapid tissue and tumor penetration, and rapid clearance from non-target tissues, providing an attractive platform for targeted therapeutic agent. The RGD peptide has been shown to have a high affinity for αvβ3, which has been implicated in TNBC. The purpose of these studies is to investigate the potential of modified RGD peptide scaffolds to deliver 225Ac to triple negative breast cancer cells for targeted alpha therapy. Methods DOTA-cyclo-RGD(fK) and DOTA-cyclo-RGD(fK) dimer were labeled with Indium-111, a SPECT imaging surrogate for 225Ac, and Actinium-225. The resulting labeled agents were evaluated in vitro, including binding affinity assays (111In) and colony formation assays (225Ac) that are underway using the MDA-MB-231 cell line. Biodistribution experiments were performed in athymic nude mice bearing MDA-MB-231 tumors to compare the distribution and pharmacokinetics of the 111In-labeled RGD peptide scaffolds in vivo. Alpha camera imaging evaluated the microscale distribution of 225Ac-DOTA-cyclo-RGD(fK) in non-tumor bearing mice. Results The saturation binding assay of 111In-labeled DOTA-cyclo-RGD(fK) and DOTA-cyclo-RGD(fK) dimer demonstrated selective binding and nanomolar affinity for αvβ3. Selective targeting of αvβ3was further demonstrated in vivo for both 111In-labeled RGD agents. The 111In-labeled DOTA-cyclo-RGD(fK) demonstrated significantly higher tumor uptake at 30 minutes compared to the dimer (5.3 ± 2.9 vs. 3.0 ± 1.4 %ID/g). The 111In-DOTA-cyclo-RGD(fK) dimer was better retained in the tumor over 6 hours with significantly higher uptake at the 6-hour time point (1.2 ± 0.4 vs. 2.8 ± 1.1 %ID/g). Furthermore, the dimer had significantly higher uptake in the kidney and liver over a 6-hour window as compared to 111In-DOTA-cyclo-RGD(fK). However, both 111In-labeled RGD agents demonstrated rapid clearance from normal organs. Alpha camera images of the 225Ac-labeled dimer supported the rapid clearance from the normal tissues, with the majority of the agents being cleared within the first 90 minutes. Conclusion Modified RGD peptides were successfully labeled with Indium-111 and Actinium-225. The resulting agents were shown to successfully target αvβ3 selectively both in vitro and in vivo. These studies provide encouraging data to support the development and optimization of the RGD platform for αvβ3-targeted alpha therapy to treat triple negative breast cancer. Future works will investigate the therapeutic efficacy, macro- and microscale dosimetry, and toxicity of the developed 225Ac-labeled αvβ3-targeted agents as well as explore the optimization of the RGD scaffold for improved pharmacokinetics with 225Ac. Citation Format: Nedrow JR, Cortez A, Josefsson A, Sgouros G. Development of peptide-based targeted α-therapy for triple negative breast cancer [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P3-12-21.

Herpes simplex virus (HSV) has been suggested to play a role in Alzheimer's disease (AD) development.The aim of the present study was to investigate the early AD-related symptom episodic memory decline in relation to HSV and carriage of allele 4 of the apolipoprotein E gene (APOEɛ4) in a large population-based cohort with a long follow-up time.The study included 3,413 persons, with longitudinal data available for 1,293 persons with a mean follow-up time of 11.6 years. The associations between HSV carriage, APOEɛ4 carriage, and episodic memory was investigated at baseline, as well as in longitudinal analyses where individuals with and without HSV antibodies (HSV1/2 non-specific) were matched and episodic memory decline compared.Cross-sectional analyses revealed an age-dependent association of HSV carriage with lower episodic memory function, particularly among APOEɛ4 carriers (p = 0.008). Longitudinal analyses showed an increased risk of episodic memory decline in HSV carriers (≥65 years: p 0.001, all ages: non-significant), and a significant interaction between HSV and APOEɛ4 for episodic memory decline (p 0.001).In this large population-based cohort study, both cross-sectional and longitudinal results support an association between HSV carriage and declining episodic memory function, especially among APOEɛ4 carriers. The results strengthen the hypothesis that HSV is associated with AD development.

IntroductionHerpes simplex virus type 1 (HSV1) in combination with genetic susceptibility has previously been implicated in Alzheimer's disease (AD) pathogenesis. MethodsPlasma from 360 AD cases, obtained on average 9.6years before diagnosis, and their age- and sex-matched controls, were analyzed for anti-HSV1 immunoglobulin (Ig) G with enzyme-linked immunosorbent assays (ELISAs). APOE genotype and nine other selected risk genes for AD were extracted from a genome-wide association study analysis by deCODE genetics, Reykjavik, Iceland. ResultsThe interaction between APOE epsilon 4 heterozygosity (APOE epsilon 2/epsilon 4 or epsilon 3/epsilon 4) and anti-HSV1 IgG carriage increased the risk of AD (OR 4.55, P=.02). A genetic risk score based on the nine AD risk genes also interacted with anti-HSV1 IgG for the risk of developing AD (OR 2.35, P=.01). DiscussionThe present findings suggest that the APOE epsilon 4 allele and other AD genetic risk factors might potentiate the risk of HSV1-associated AD.

mean age 46.7 years) were available for analysis. Symptom prevalence was 8.1% for globus, 6.5% for heartburn, 4.5% for dysphagia and 5.2% for chest pain, and 17.0% reported at least one oesophageal symptom. Oesophageal symptoms were independently associated with younger age, female gender, previous abdominal surgery and the presence of other functional GI disorders. Reporting oesophageal symptoms was associated with reduced quality of life. Conclusion: Oesophageal symptoms are common in the general population and important predictors include other functional GI disorders, age and gender. Oesophageal symptoms are associated with poorer quality of life., Background: The prevalence and frequency of oesophageal symptoms suggestive of a functional oesophageal disorder according to the Rome IV criteria are unknown. Objective: We aimed to describe the prevalence and risk factors for oesophageal symptoms compatible with functional oesophageal disorders in the general population. Methods: Data were analysed from a population-based online survey of 6300 individuals aged ≥ 18 years in the USA, UK and Canada with equal demographic proportions across countries. Questions included the Rome IV diagnostic questionnaire, demographics, medication, somatization, quality of life, and organic gastrointestinal (GI) disease. Multivariate analysis was used to identify factors independently related to oesophageal symptoms. Results: Data from 5177 participants (47.8% female

CC BY 4.0Correspondence: Alexandra Krettek, alexandra.krettek@his.se

ObjectivesThe main goal of the COVIDENZA trial is to evaluate if inhibition of testosterone signalling by enzalutamide can improve the outcome of patients hospitalized for COVID-19. The hypothesis is based on the observation that the majority of patients in need of intensive care are male, and the connection between androgen receptor signalling and expression of TMPRSS2, an enzyme important for SARS-CoV-2 host cell internalization.Trial designHospitalized COVID-19 patients will be randomised (2:1) to enzalutamide plus standard of care vs. standard of care designed to identify superiority.ParticipantsIncluded participants, men or women above 50 years of age, must be hospitalized for PCR confirmed COVID-19 symptoms and not in need of immediate mechanical ventilation. Major exclusion criteria are breast-feeding or pregnant women, hormonal treatment for prostate or breast cancer, treatment with immunosuppressive drugs, current symptomatic unstable cardiovascular disease (see additional file 1 for further details). The trial is registered at Umeå University Hospital, Region Västerbotten, Sweden and 8 hospitals are approved for inclusion in Sweden.Intervention and comparatorPatients randomised to the treatment arm will be treated orally with 160 mg (4x40 mg) enzalutamide (Xtandi®) daily, for five consecutive days. The study is not placebo controlled. The comparator is standard of care treatment for patients hospitalised with COVID-19.Main outcomesThe primary endpoints of the study are (time to) need of mechanical ventilation or discharge from hospital as assessed by a clinical 7-point ordinal scale (up to 30 days after inclusion).RandomisationRandomisation was stratified by center and sex. Each strata was randomized separately with block size six with a 2:1 allocation ratio (enzalutamide + “standard of care”: “standard of care”). The randomisation list, with consecutive subject numbers, was generated by an independent statistician using the PROC PLAN procedure of SAS version 9.4 software (SAS Institute, Inc, Cary, North Carolina)Blinding (masking)This is an open-label trial.Numbers to be randomised (sample size)The trial is designed to have three phases. The first, an exploration phase of 45 participants (30 treatment and 15 control) will focus on safety and includes a more extensive laboratory assessment as well as more frequent safety evaluation. The second prolongation phase, includes the first 100 participants followed by an interim analysis to define the power of the study. The third phase is the continuation of the study up to maximum 600 participants included in total.Trial StatusThe current protocol version is COVIDENZA v2.0 as of September 10, 2020. Recruitment started July 29, 2020 and is presently in safety pause after the first exploration phase. Recruitment is anticipated to be complete by 31 December 2021.Trial registrationEudract number 2020-002027-10ClinicalTrials.gov Identifier: NCT04475601, registered June 8, 2020

Given the portability and minimal intrusiveness of Near Infrared Spectroscopy (NIRS), there is potential for it to be used in an ecological setting, as compared to classical neuroimaging methods. In this paper, NIRS was used to assess the cognitive processes of operators performing complex, safety-critical Air Traffic Control (ATC) tasks. The haemodynamic response in the Prefrontal Cortex (PFC) was obtained from an event-based analysis of the NIRS recordings. Despite the relative complexity of the experimental scenario, grand-averaged results from the analysis showed an evident Haemodynamic Response Function (HRF) in the right PFC, specifically for events in which the operator provided instructions to arriving aircraft (e.g., clear-to-Iand or go-around). The HRF peak was observed before the event, suggesting that maximum cognitive processing of the operator occurred before instructions were actually given. Overall, the study supports the suitability of NIRS as a tool for assessing the cognitive processes of operators in ecological settings, demonstrating the potential validity of NIRS-based measurements for BCI systems in safety-critical operations.

IntroductionAs part of the PIONEER (Prostate Cancer Diagnosis and Treatment Enhancement Through the Power of Big Data in Europe) Consortium, we will explore which diagnostic and prognostic factors (DPFs) are currently being researched to previously defined clinical and patient-reported outcomes for prostate cancer (PCa).Methods and analysisThis research project will follow the following four steps: (1) a broad systematic literature review of DPFs for all stages of PCa, covering evidence from 2014 onwards; (2) discussion of systematic review findings by a multidisciplinary expert panel; (3) risk of bias assessment and applicability with Prediction model Risk Of Bias Assessment Tool criteria, Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) and the Quality In Prognosis Studies tool (QUIPS) and (4) additional quantitative assessments if required.Ethics and disseminationWe aim to develop an online tool to present the DPFs identified in this research and make them available across all stakeholders. There are no ethical implications.

Introduction In this nested case‐control study, we investigated if antiviral treatment given prior to onset of Alzheimer's disease (AD) could influence incident AD. Methods From a large population‐based cohort study in northern Sweden, 262 individuals that later developed AD were compared to a non‐AD matched control group with respect to prescriptions of herpes antiviral treatment. All included subjects were herpes simplex virus 1 (HSV1) carriers and the matching criteria were age, sex, apolipoprotein E genotype (ε4 allele carriership), and study sample start year. Results Among those who developed AD, 6 prescriptions of antivirals were found, compared to 20 among matched controls. Adjusted for length of follow‐up, a conditional logistic regression indicated a difference in the risk for AD development between groups (odds ratio for AD with an antiviral prescription 0.287, P = .018). Discussion Antiviral treatment might possibly reduce the risk for later development of HSV1‐associated AD.

Objectives Obstructive sleep apnea (OSA) has an impact on an individuals quality of life and general health, and can also affect their oral health. The patients experiences, together with intraoral signs and symptoms could indicate the presence of OSA. Knowledge that the patient has, or is at high risk for having OSA can help the dental healthcare provider maintain the oral health and general health for these patients. The purpose was to explore dentists and dental hygienists experiences when encountering adult patients with potential, untreated and treated OSA. Methods A qualitative inductive approach was used. Experienced dentists and dental hygienists working within Swedish Public Dental Service were strategically selected. Semi-structured face-to-face interviews were performed followed by qualitative content analysis. Results Interviews from 13 participants, seven dental hygienist and six dentists, led to three areas describing varied experience: Importance of the patient encounter and identifying intraoral signs both of which describe experiences related to the importance of the initial unstructured conversation and focused clinical assessments, and strategies for nurturing care which point to interest about care, treatment, and collaborations with medical health care providers. Conclusions Dental professionals are not able to consistently recognize patients who have, or are at high risk for OSA. During the patient encounter, is it important to determine if a patient is at risk for, or has oral signs of OSA. Funding Agencies|Public Dental Service in the county of south Sweden

Objective To investigate hair cortisol concentrations (HCC) monthly in pregnant women and to explore the effect of parity. Design Prospective cohort study from gestational week (GW) 26, at childbirth and postpartum. Setting An antenatal care clinic in southeast Sweden. Sample 390 pregnant women. Methods Cortisol was measured using radioimmunoassay in methanol extracts of ground hair samples. Main outcome measures Hair cortisol concentrations. Results Both primi‐ and multiparae exhibited an increase in HCC throughout pregnancy. Primiparae had significantly higher HCC in the latter part of the last trimester compared with multiparae (1 month P = 0.003, 2 months P = 0.038). The use of psychotropic medication in the first trimester correlated to HCC postpartum (P, Tweetable abstract Multiparae have a quicker suppression of hypothalamic CRH production by placenta CRH during pregnancy compared with primiparae.

Introduction Herpesviruses, including Herpes simplex virus type 1 (HSV1) and varicella zoster‐virus (VZV), have been implicated in Alzheimer's disease (AD) development. Likewise, antiviral treatment has been suggested to protect against dementia development in herpes‐infected individuals. Methods The study enrolled 265,172 subjects aged ≥ 50 years, with diagnoses of VZV or HSV, or prescribed antiviral drugs between 31 December 2005 and 31 December 2017. Controls were matched in a 1:1 ratio by sex and birth year. Results Antiviral treatment was associated with decreased risk of dementia (adjusted hazard ratio [HR] 0.89, 95% confidence interval [CI] 0.86 to 0.92), while herpes infection without antiviral drugs increased the risk of dementia (adjusted HR 1.50, 95% CI 1.29 to 1.74). Discussion Antiviral treatment was associated with a reduced long‐term risk of dementia among individuals with overt signs of herpes infection. This is consistent with earlier findings indicating that herpesviruses are involved in the pathogenesis of AD.

Background: Amyloid-beta (A beta), the key constituent of Alzheimer's disease (AD) plaques, has antimicrobial properties. Objective: To investigate the association between plasma A beta and antibodies against the AD-related pathogens herpes simplex virus (HSV), cytomegalovirus (CMV), and C. pneumoniae. Methods: Plasma from 339 AD cases, obtained on average 9.4 years (+/- 4.00) before diagnosis, and their matched controls were analyzed for A beta(40) and A beta(42) oncentrations with Luminex xMAP technology and INNOBIA plasma A beta-form assays. Enzyme-linked immunosorbent assays were utilized for analyses of anti-HSV immunoglobulin (Ig) G, anti-HSV1 IgG, anti-HSV2 IgG, anti-CMV IgG, and anti-C. pneumoniae IgG. Follow-up samples were available for 150 of the cases. Results: Presence and levels of anti-HSV1 IgG, anti-HSV2 IgG, anti-CMV IgG, and anti-C. pneumoniae IgG did not correlate with concentrations of A beta 42 or A beta 40 in cases or controls. Conclusion: Levels of plasma A beta were not associated with antibodies against different AD-related pathogens.