Arterial stiffness assessment in coronary microvascular dysfunction and heart failure with preserved ejection fraction: An initial report from the WISE-CVD continuation study.

Background: Heart failure with preserved ejection fraction (HFpEF) is the most common cardiac complication in patients with coronary microvascular dysfunction (CMD), yet its underlying pathways remain unclear. Aortic pulse-wave velocity (aPWV) is an indicator of large artery stiffness and a predictor for cardiovascular disease. However, aPWV in CMD and HFpEF is not well characterized and may provide understanding of disease progression. Methods: Among participants without obstructive coronary artery disease, we evaluated 51 women with suspected CMD and 20 women and men with evidence of HFpEF. All participants underwent aPWV measurement (SphygmoCor, Atcor Medical) with higher aPWV indicating greater vascular stiffness. Cardiac magnetic resonance imaging (CMRI) assessed left ventricular (LV) ejection fraction, CMD via myocardial perfusion reserve index (MPRI), and ventricular remodeling via LV mass-volume ratio. . Statistical analysis was performed using Wilcoxon rank sum tests, Pearson correlations and linear regression analysis. Results: Compared to the suspected CMD group, the HFpEF participants were older (65 ± 12 vs 56 ± 11 yrs., p = 0.002) had higher BMI (31.0 ± 4.3 vs 27.8 ± 6.7 kg/m2, p = 0.013), higher aPWV (10.5 ± 2.0 vs 8.0 ± 1.6 m/s, p = 0.05) and lower MPRI (1.5 ± 0.3 vs1.8 ± 0.3, p = 0.02), but not remodeling. In a model adjusted for cardiovascular risk factors, the HFpEF group had a lower LVEF (estimate -4.78, p = 0.0437) than the suspected CMD group. Conclusions: HFpEF participants exhibit greater arterial stiffness and lower myocardial perfusion reserve, with lower LVEF albeit not remodeling, compared to suspected CMD participants. These findings suggest arterial stiffness may contribute to progression from CMD to HFpEF. Prospective work is needed and ongoing.

Setting a direction for continuing professional development in anesthesiology: A synthesis of the outcome from an Utstein style meeting.

BACKGROUND: An Utstein style meeting of key stakeholders from the existing collaboration surrounding post-graduate training was arranged to set a direction for continuing professional development (CPD) of anesthesiologists in Denmark. A 2-day meeting was planned to guide discussions about competencies in anesthesiology, facilitate the development of a blueprint for a portfolio-based CPD program and provide examples of how a portfolio can be used in practice. METHODS: The meeting agenda was based on an adaptation of Kern's six-step approach to curriculum development. Twenty-four participants from the university hospitals in Denmark were invited. Prior to the meeting participants were informed of the objectives and the Utstein style process. RESULTS: Participants acknowledged a need for a more structured approach to CPD, preferably within the current organizational set up at the departmental level, and with a portfolio-based, individualized curriculum. It was recognized that CPD should contain an array of possibilities to accommodate needs and wants of both the individual and the department. It was emphasized that, while anesthesiologists are used to give feedback to trainees, many are less familiar in providing the same to peers, and psychological safety was identified as a prerequisite to support a culture where specialists can reflect openly on each other's performance. CONCLUSION: The results provide an insight into the attitudes, opportunities, and challenges of anesthesiologists in relation to continuing professional development in Denmark. Generally, participant suggestions are in line with the shift in medical education toward workplace-based learning, feedback and lifelong learning.

Dynamic changes in renal sodium handling during sympathetic stimulation in healthy human males.

The temporal response of changes in renal sodium reabsorption during increased renal sympathetic nerve activity has not been investigated. Central hypovolemia by application of lower-body negative-pressure (LBNP) elicits baroreceptor mediated sympathetic reflexes to maintain arterial blood pressure. We hypothesized, that during 90 min LBNP, the renal sodium retention would increase rapidly, remain increased during intervention, and return to baseline immediately after end of intervention. METHODS: 30 young, healthy, sodium loaded, non-obese males were exposed to -15 mmHg LBNP, -30 mmHg LBNP, -15 mmHg LBNP + renin blockade or time-control (0 mmHg LBNP) for 90 min. Urine was collected every 15 min during 90 min of intervention and 60 min of recovery to identify a possible relation between time of intervention and renal response. RESULTS: All intervention groups exhibited a comparable reduction in distal sodium excretion at the end of the intervention (P = 0.46 between groups; -15 mmHg: -3.1 ± 0.9 %, -30 mmHg: -2.9 ± 0.6 %, -15 mmHg + aslikiren: -1.8 ± 0.6 %). -15 mmHg+Aliskiren resulted in a slower onset, but all groups exhibited a continued reduction in sodium excretion after 1 h of recovery despite return to baseline of renin, aldosterone, diuresis and cardiovascular parameters. CONCLUSION: Sympathetic stimulation for 90 min via LBNP at -30 mmHg LBNP compared to -15 mmHg did not result in a greater response in fractional Na+ excretion, suggesting that additional baroreceptor unloading did not cause further increases in renal sodium reabsorption. Changes in distal Na+ excretion were linear with respect to time (dose) of intervention, but seem to exhibit a saturation-like effect at a level around 4 %. The lack of recovery after 1 h is also a new finding that warrants further investigation.

Linking the Mechanics of Chewing to Biology of the Junctional Epithelium.

The capacity of a tissue to continuously alter its phenotype lies at the heart of how an animal is able to quickly adapt to changes in environmental stimuli. Within tissues, differentiated cells are rigid and play a limited role in adapting to new environments; however, differentiated cells are replenished by stem cells that are defined by their phenotypic plasticity. Here we demonstrate that a Wnt-responsive stem cell niche in the junctional epithelium is responsible for the capability of this tissue to quickly adapt to changes in the physical consistency of a diet. Mechanical input from chewing is required to both establish and maintain this niche. Since the junctional epithelium directly attaches to the tooth surface via hemidesmosomes, a soft diet requires minimal mastication, and consequently, lower distortional strains are produced in the tissue. This reduced strain state is accompanied by reduced mitotic activity in both stem cells and their progeny, leading to tissue atrophy. The atrophied junctional epithelium exhibits suboptimal barrier functions, allowing the ingression of bacteria into the underlying connective tissues, which in turn trigger inflammation and mild alveolar bone loss. These data link the mechanics of chewing to the biology of tooth-supporting tissues, revealing how a stem cell niche is responsible for the remarkable adaptability of the junctional epithelium to different diets.

Prediction of Radiation-induced Lymphopenia following Exposure of the Thoracic Region and Associated Risk of Infections and Mortality.

AIMS: Large blood volumes are irradiated when the heart is exposed to radiation. The mean heart dose (MHD) may be a good surrogate for circulating lymphocytes exposure. We investigated the association between MHD and radiation-induced lymphopenia and explored the impact of the end-of-radiation-therapy (EoRT) lymphocyte count on clinical outcomes. MATERIALS AND METHODS: In total, 915 patients were analysed: 303 patients with breast cancer and 612 with intrathoracic tumours: oesophageal cancer (291), non-small cell lung cancer (265) and small cell lung cancer (56). Heart contours were generated using an interactive deep learning delineation process and an individual dose volume histogram for each heart was obtained. A dose volume histogram for the body was extracted from the clinical systems. We compared different models analysing the effect of heart dosimetry on the EoRT lymphocyte count using multivariable linear regression and assessed goodness of fit. We published interactive nomograms for the best models. The association of the degree of EoRT lymphopenia with clinical outcomes (overall survival, cancer treatment failure and infection) was investigated. RESULTS: An increasing low dose bath to the body and MHD were associated with a low EoRT lymphocyte count. The best models for intrathoracic tumours included dosimetric parameters, age, gender, number of fractions, concomitant chemotherapy and pre-treatment lymphocyte count. Models for patients with breast cancer showed no improvement when adding dosimetric variables to the clinical predictors. EoRT lymphopenia grade ≥3 was associated with decreased survival and increased risk of infections among patients with intrathoracic tumours. CONCLUSION: Among patients with intrathoracic tumours, radiation exposure to the heart contributes to lymphopenia and low levels of peripheral lymphocytes after radiotherapy are associated with worse clinical outcomes.

HIV Knowledge, Risk Behaviors, and Testing Among Chinese-, Korean-, and Vietnamese-American Women.

The relationship between HIV knowledge and testing behavior is poorly understood among young Chinese-, Korean-, and Vietnamese-American women. This study assesses: (1) levels of HIV/AIDS knowledge, (2) lifetime and annual prevalence of HIV testing, and (3) whether higher levels of HIV knowledge were associated with increased likelihood of testing after controlling for HIV risk behaviors. Fifty-one percent reported lifetime HIV testing (n=117); among those tested, 53% were tested within the past year. A significant and positive association between scores on the HIV Knowledge Questionnaire (HIV KQ-45) and HIV testing was identified. This association was no longer statistically significant after controlling for sexual risk behaviors. Participants were most knowledgeable about HIV symptoms (88.6%) and least knowledgeable about treatment options (56.8%). Future studies should further characterize cultural factors affecting these women's sexual practices, as well develop culturally adapted HIV educational interventions to increase HIV knowledge and testing rates.

Cold Pressor Testing and Sympathetic Nervous System Contribution to Ischemia with No Obstructive Coronary Artery Disease: Results from the Women's Ischemia Syndrome Evaluation-Coronary Vascular Dysfunction Project.

Study Objective: Cold Pressor Testing (CPT) is a known stimulus of the sympathetic nervous system (SNS). To better understand sympathetic contribution to coronary blood flow regulation in women with suspected ischemia and no obstructive coronary arteries (INOCA), we compared myocardial perfusion reserve during CPT stress cardiac magnetic resonance (CMR) imaging between women with suspected INOCA and reference subjects. Design: Prospective cohort. Setting: Academic hospital. Participants: 107 women with suspected INOCA and 21-age-matched reference women. Interventions: CPT stress CMR was performed with measurement of myocardial perfusion reserve index (MPRI), adjusted for rate pressure product (MPRIRPP). Invasive coronary function testing in a subset of INOCA women (n=42) evaluated for endothelial dysfunction in response to acetylcholine, including impaired coronary diameter response ≤0% and coronary blood flow response (ΔCBF) <50%. Main Outcome Measure: MPRIRPP. Results: Compared to reference women, the INOCA group demonstrated higher resting RPP (p=0.005) and CPT MPRIRPP (1.09±0.36 vs 0.83±0.18, p=0.002). Furthermore, INOCA women with impaired ΔCBF (n=23) had higher CPT MPRIRPP (p=0.044) compared to reference women despite lower left ventricular ejection fraction (64±7 % vs 69±2 %, p=0.005) and mass-to-volume ratio (0.79±0.15 vs 0.62±0.09, p<0.0001). These differences in CPT MPRIRPP did not persist after adjusting for age, body mass index, and history of hypertension. CPT MPRIRPP among INOCA women did not differ based on defined acetylcholine responses. Conclusions: Myocardial perfusion reserve to CPT stress is greater among women with INOCA compared to reference subjects. CPT induced a higher MPRIRPP also in women with coronary endothelial dysfunction, suggesting a greater contribution of the SNS to coronary flow than endothelial dysfunction. Further investigation in a larger cohort is needed.

Chemoautotrophy, symbiosis and sedimented diatoms support high biomass of benthic molluscs in the Namibian shelf.

The molluscs Lucinoma capensis, Lembulus bicuspidatus and Nassarius vinctus are highly abundant in Namibian oxygen minimum zone sediments. To understand which nutritional strategies allow them to reach such impressive abundances in this extreme habitat we investigated their trophic diversity, including a chemosymbiosis in L. capensis, focussing on nitrogen biochemical pathways of the symbionts. We combined results of bulk nitrogen and carbon (δ13C and δ15N) and of compound-specific isotope analyses of amino acid nitrogen (AAs-δ15NPhe and δ15NGlu), with 16S rRNA gene sequencing of L. capensis tissues and also with exploratory results of ammonium, nitrate and nitrite turnover. The trophic position (TP) of the bivalve L. capensis is placed between autotrophy and mixotrophy, consistent with its proposed symbiosis with sulfur-oxidizing Candidatus Thiodiazotropha sp. symbionts. The symbionts are here revealed to perform nitrate reduction and ammonium uptake, with clear indications of ammonium host-symbionts recycling, but surprisingly unable to fix nitrogen. The TP of the bivalve L. bicuspidatus is placed in between mixotrophy and herbivory. The TP of the gastropod N. vinctus reflected omnivory. Multiple lines of evidences in combination with current ecosystem knowledge point to sedimented diatoms as important components of L. bicuspidatus and N. vinctus' diet, likely supplemented at times with chemoautotrophic bacteria. This study highlights the importance of benthic-pelagic coupling that fosters the dietary base for macrozoobenthos in the OMZ. It further unveils that, in contrast to all shallow water lucinid symbionts, deeper water lucinid symbionts rely on ammonium assimilation rather than dinitrogen fixation to obtain nitrogen for growth.

[Dermatological care of elderly people with psoriasis before and after entering a nursing home : A qualitative analysis from the perspective of medical providers]. / Dermatologische Versorgung von älteren Menschen mit Psoriasis vor und nach Eintritt in ein Pflegeheim : Eine qualitative Analyse aus Sicht von medizinischen Versorgern.

BACKGROUND: Demographic changes are causing a rapid increase in the number of people over 65 years of age. This is associated with an increase in the number of multimorbid patients in need of care. Nationally as well as internationally, there is little information on the treatment of psoriasis patients in the nursing home setting and on the question of how this is influenced by entry into a nursing home. OBJECTIVE: The aim was to discuss the results of previous routine data analyses on the treatment of psoriasis patients in nursing homes with medical providers (dermatologists, general practitioners, nursing service managers, and nursing staff) on the basis of interviews and focus groups, to identify difficulties in the treatment and finally to derive recommendations for action regarding sustainable gerontodermatological treatment. MATERIALS AND METHODS: Qualitative guideline-based interviews and focus groups with dermatologists (n = 5), general practitioners (GPs, n = 7), nurses (n = 7), and care managers (n = 2) were conducted. The data were evaluated by content analysis. RESULTS: The analyses resulted in 344 statements, which could be categorized into 14 main topics. The results show that there is a need for improvement in the quality of care for people with skin diseases, especially psoriasis, in nursing homes. This is evident at both the medical and nursing levels. According to the providers (N = 21), this can be addressed in particular through increased remote consultations (telemedicine), dermatological training for GPs and nurses, and closer cooperation between the individual disciplines. CONCLUSION: Remote consultations, but also a specific guideline on the "skin of the ageing person" can be useful to improve the dermatological care situation in nursing homes and thus increase the well-being of those affected.

Telestration with augmented reality for visual presentation of intraoperative target structures in minimally invasive surgery: a randomized controlled study.

AIMS: In minimally invasive surgery (MIS), intraoperative guidance has been limited to verbal communication without direct visual guidance. Communication issues and mistaken instructions in training procedures can hinder correct identification of anatomical structures on the MIS screen. The iSurgeon system was developed to provide visual guidance in the operating room by telestration with augmented reality (AR). METHODS: Laparoscopic novices (n = 60) were randomized in two groups in a cross-over design: group 1 trained only with verbal guidance first and then with additional telestration with AR on the operative screen and vice versa for group 2. Training consisted of laparoscopic basic training and subsequently a specifically designed training course, including a porcine laparoscopic cholecystectomy (LC). Outcome included time needed for training, performance with Global Operative Assessment of Laparoscopic Skills (GOALS), and Objective Structured Assessment of Technical Skills (OSATS) score for LC, complications, and subjective workload (NASA-TLX questionnaire). RESULTS: Telestration with AR led to significantly faster total training time (1163 ± 275 vs. 1658 ± 375 s, p < 0.001) and reduced error rates. LC on a porcine liver was performed significantly better (GOALS 21 ± 5 vs. 18 ± 4, p < 0.007 and OSATS 67 ± 11 vs. 61 ± 8, p < 0.015) and with less complications (13.3% vs. 40%, p < 0.020) with AR. Subjective workload and stress were significantly reduced during training with AR (33.6 ± 12.0 vs. 30.6 ± 12.9, p < 0.022). CONCLUSION: Telestration with AR improves training success and safety in MIS. The next step will be the clinical application of telestration with AR and the development of a mobile version for remote guidance.

Global airways â€" a novel Standard Tests for Asthma, allergic Rhinitis, and chronic Rhinosinusitis (STARR-15).

BACKGROUND: Global airway disease, with symptoms from both upper and lower airways, is a challenging problem for clinicians. Our goal is to design one single standard test for the awareness of global airway diseases to be used in clinical setting. MATERIAL AND METHODS: During 2019, rhinologists and pulmonologists generated a pool of items based on literature, patient-reported outcome measures and clinical experience. The items were administered to 206 patients with known asthma, CRS, allergic rhinitis, or a combination thereof. The patients also completed the Asthma Control Questionnaire (ACQ-5) and the Sino-Nasal Outcome Test (SNOT-22). Using a mix of clinical knowledge and data-driven methods a global airways questionnaire was developed. RESULTS: Mean ACQ score was highest in patients with all three, whereas the highest SNOT-22 score was observed in patients with CRS and asthma. After the development process, analysis of responses from 206 patients to 44 items on a new global airway’s questionnaire led to identification of 15 items that form the STARR-15 questionnaire with three underlying domains (an allergic rhinitis sub-factor, a CRS sub-factor and an asthma sub-factor). CONCLUSION: STARR-15 represents the first global airways questionnaire, to be used when examining patients with upper and lower airways symptoms. Future analyses are warranted to evaluate the clinical and psychometric properties of STARR-15.

The novel genus, 'Candidatus Phosphoribacter', previously identified as Tetrasphaera, is the dominant polyphosphate accumulating lineage in EBPR wastewater treatment plants worldwide.

The bacterial genus Tetrasphaera encompasses abundant polyphosphate accumulating organisms (PAOs) that are responsible for enhanced biological phosphorus removal (EBPR) in wastewater treatment plants. Recent analyses of genomes from pure cultures revealed that 16S rRNA genes cannot resolve the lineage, and that Tetrasphaera spp. are from several different genera within the Dermatophilaceae. Here, we examine 14 recently recovered high-quality metagenome-assembled genomes from wastewater treatment plants containing full-length 16S rRNA genes identified as Tetrasphaera, 11 of which belong to the uncultured Tetrasphaera clade 3. We find that this clade represents two distinct genera, named here Ca. Phosphoribacter and Ca. Lutibacillus, and reveal that the widely used model organism Tetrasphaera elongata is less relevant for physiological predictions of this uncultured group. Ca. Phosphoribacter incorporates species diversity unresolved at the 16S rRNA gene level, with the two most abundant and often co-occurring species encoding identical V1-V3 16S rRNA gene amplicon sequence variants but different metabolic capabilities, and possibly, niches. Both Ca. P. hodrii and Ca. P. baldrii were visualised using fluorescence in situ hybridisation (FISH), and PAO capabilities were confirmed with FISH-Raman microspectroscopy and phosphate cycling experiments. Ca. Phosphoribacter represents the most abundant former Tetrasphaera lineage and PAO in EPBR systems in Denmark and globally.

Reasons for not reaching or using web-based self-management applications, and the use and evaluation of Oncokompas among cancer survivors, in the context of a randomised controlled trial.

INTRODUCTION: The web-based self-management application Oncokompas was developed to support cancer survivors to monitor health-related quality of life and symptoms (Measure) and to provide tailored information (Learn) and supportive care options (Act). In a previously reported randomised controlled trial (RCT), 68% of 655 recruited survivors were eligible, and of those 45% participated in the RCT. Among participants of the RCT that were randomised to the intervention group, 52% used Oncokompas as intended. The aim of this study was to explore reasons for not participating in the RCT, and reasons for not using Oncokompas among non-users, and the use and evaluation of Oncokompas among users. METHODS: Reasons for not participating were assessed with a study-specific questionnaire among 243 survivors who declined participation. Usage was investigated among 320 participants randomised to the intervention group of the RCT via system data and a study-specific questionnaire that was assessed during the 1 week follow-up (T1) assessment. RESULTS: Main reasons for not participating were not interested in participation in scientific research (40%) and not interested in scientific research and Oncokompas (28%). Main reasons for not being interested in Oncokompas were wanting to leave the period of being ill behind (29%), no symptom burden (23%), or lacking internet skills (18%). Out of the 320 participants in the intervention group 167 (52%) used Oncokompas as intended. Among 72 non-users, main reasons for not using Oncokompas were no symptom burden (32%) or lack of time (26%). Among 248 survivors that activated their account, satisfaction and user-friendliness were rated with a 7 (scale 0-10). Within 3 (IQR 1-4) sessions, users selected 32 (IQR 6-37) topics. Main reasons for not using healthcare options in Act were that the information in Learn was already sufficient (44%) or no supportive care needs (32%). DISCUSSION: Main reasons for not reaching or using Oncokompas were no symptom burden, no supportive care needs, or lack of time. Users selected many cancer-generic and tumour-specific topics to address, indicating added value of the wide range of available topics.

Testicular cancer survivors have shorter anogenital distance that is not increased by 1 year of testosterone replacement therapy.

STUDY QUESTION: Is anogenital distance (AGD) shorter in testicular cancer (TC) survivors than in men from the general population, and is AGD affected by testosterone replacement therapy in adulthood? SUMMARY ANSWER: AGD, measured as distance from anus to scrotum (AGDas), is shorter in TC survivors and does not change as a result of testosterone replacement therapy. WHAT IS KNOWN ALREADY: Animal studies have shown that AGD is a postnatal 'read-out' of foetal androgen action, and short AGD in male offspring is considered a sign of feminization caused by in utero disruption of the reproductive system. Likewise, measurement of AGD in human studies has suggested AGD to be part of the testicular dysgenesis syndrome hypothesis, which proposes that male reproductive disorders, such as hypospadias, cryptorchidism, some cases of impaired semen quality and TC, all share a common foetal origin. STUDY DESIGN, SIZE, DURATION: The aim was to assess AGD in men with a history of TC and controls, and furthermore to examine AGD during testosterone replacement therapy in adulthood. Study participants were TC survivors with a mild Leydig cell insufficiency who participated in a randomized double-blind study of testosterone replacement therapy versus placebo for 52 weeks (N = 69). Men from the general population were prospectively included from a study on testicular function as controls (N = 67). PARTICIPANTS/MATERIALS, SETTING, METHODS: We measured two variants of AGD; as our primary outcome the anoscrotal distance (AGDas) measured from the centre of the anus to the posterior base of the scrotum, and secondarily the anopenile distance (AGDap) measured from the anus to the cephalad insertion of the penis. Using multiple regression analysis, the mean difference in AGD between TC survivors and men from the general population was assessed, adjusted for height, BMI and examiner. Next, AGD was measured before and after 52 weeks of treatment with testosterone or placebo, and with covariance analysis differences between the two groups at follow-up was assessed after adjustment for baseline AGD, examiner, BMI and change in BMI during treatment. MAIN RESULTS AND THE ROLE OF CHANCE: TC survivors had a shorter AGDas (-0.84 cm, 95% CI: -1.31; -0.37) compared to men from the general population, and AGDas did not differ between the testosterone and placebo treated group at follow-up (0.11 cm, 95% CI: -0.22; 0.44). In contrast, AGDap was not shorter in TC survivors after adjustment (0.05 cm, 95% CI: -0.30; 0.39), and was 0.48 cm longer (95% CI: 0.13; 0.82) at follow-up in the testosterone treated compared to the placebo-treated group. LIMITATIONS, REASONS FOR CAUTION: A limitation of the study is that the number of included men was limited, and results need confirmation in a larger study. Furthermore, TC survivors were significantly older than controls. For the comparison of AGD in TC survivors and controls, it was not possible to conduct the examinations with the examiner being blinded to which group he was examining, and it cannot be excluded that this can cause a bias. WIDER IMPLICATIONS OF THE FINDINGS: The shorter AGDas in TC survivors compared to controls, which did not change upon adult testosterone replacement therapy, supports the hypothesis that reduced AGD is part of the testicular dysgenesis syndrome and may be a marker of disrupted foetal testicular development. By contrast, AGDap was not shorter in TC survivors and might be modestly sensitive to adult testosterone treatment, and thus inferior to AGDas as a constant postnatal marker of the foetal androgen environment. STUDY FUNDING/COMPETING INTEREST(S): Expenses were paid by the Department of Oncology, Copenhagen University Hospital, Rigshospitalet. Kiowa Kirin International covered expenses for Tostran and placebo. The Danish Cancer Society, The Danish Cancer Research Foundation, the Preben & Anna Simonsen Foundation, and Rigshospitalet have supported the study. L.P. was financed by the Research Fund of the Capital Region of Denmark. The authors have no competing interests. TRIAL REGISTRATION NUMBER: Part of the study is based on men participating in a randomized controlled trial registered at ClinicalTrials.gov, NCT02991209, 25 November 2016.

Prevalence, incidence and presence of comorbidities in patients with prurigo and pruritus in Germany: A population-based claims data analysis.

BACKGROUND: There are currently no published population-based data on prurigo and pruritus epidemiology in Germany. OBJECTIVES: We present the prevalence, incidence and comorbidity frequency of prurigo and pruritus in Germany. METHODS: This was a retrospective healthcare research study based on anonymized routine data from the German health insurance company DAK-Gesundheit. Evaluations were carried out for 2 006 003 adults who were insured as of 31 December 2010. Prurigo and pruritus diagnoses were based on International Classification of Diseases, Tenth Revision, German Modification (ICD-10-GM) codes. RESULTS: Prevalence was determined to be 0.21% (adjusted for sex and age 0.19%) for prurigo and 2.21% (adjusted 2.14%) for pruritus in 2010. The adjusted rates extrapolated to the total German population in 2010 show that 130 685 adults would have received a prurigo diagnosis and 1 461 024 a diagnosis of pruritus. In 2011, incidence of new prurigo and pruritus cases was 0.13% (adjusted 0.12%, extrapolated 77 263 cases) and 1.51% (adjusted 1.46%, extrapolated 978 885), respectively. Adults with prurigo suffered most frequently from hypertension (35.16%), hyperlipidaemia (24.95%) and depression (21.97%); all were reported more frequently in patients with prurigo compared with the general population (P < 0.001). Similarly, adults with pruritus suffered most frequently from hypertension (31.28%), hyperlipidaemia (23.52%) and depression (18.91%) compared with patients without pruritus (P < 0.001). CONCLUSIONS: Our data show that prurigo is a relatively rare but significant disease and that pruritus is frequent and very variable in appearance, and both have a high comorbidity burden.

Reduction of serum-induced endothelial STAT3(Y705) activation is associated with preeclampsia.

OBJECTIVES: Preeclampsia is associated with maternal morbidity and mortality during pregnancy, and also an increased cardiovascular disease (CVD) risk later in life. During preeclampsia, alterations in secreted placental factors leading to systemic maternal endothelial dysfunction are evident. However, little is known about the associated endothelial intracellular signaling. STAT3 is a latent cytoplasmic transcription factor involved in endothelial cell differentiation, survival, and angiogenesis. We aimed to test if preeclampsia and preeclampsia-related placental factors could alter serum-induced STAT3(Y705) activation in endothelial cells. Furthermore, if altered serum-induced endothelial STAT3 (Y705) activation is related to post-preeclamptic CVD risk. STUDY DESIGN: HUVECs were used as a model of maternal endothelium. Experiments entailed addition of 20% human pregnancy serum as well as addition of recombinant PlGF, sFLT1 and VEGF-A165a to the cells. MAIN OUTCOME MEASURES: Levels of pSTAT3(Y705) related to STAT3 levels were evaluated by immunoblotting analysis. RESULTS: Our results show that preeclamptic serum induces significantly lower STAT3(Y705) phosphorylation compared with uncomplicated pregnancy serum (P = 0.0089) in endothelial cells. Furthermore, STAT3(Y705) phosphorylation was not changed upon addition of PlGF, sFLT1, or VEGF-A165a together with pregnancy sera compared with sera alone. Finally, sera from women with previous preeclampsia and current hypertension and carotid atherosclerotic plaques show significantly lower STAT3(Y705) phosphorylation capabilities compared with healthy women with previous uncomplicated pregnancies 8-18 years after deliveries (P = 0.029). CONCLUSIONS: Reduction in serum-induced endothelial STAT3(Y705) activation may play an important role in the preeclampsia-associated endothelial dysfunction. Additionally, reduced endothelial STAT3(Y705) phosphorylation may contribute to increased post-preeclamptic CVD risk 8-18 years after delivery.

Wnt1 Promotes Cementum and Alveolar Bone Growth in a Time-Dependent Manner.

The WNT/ß-catenin signaling pathway plays a central role in the biology of the periodontium, yet the function of specific extracellular WNT ligands remains poorly understood. By using a Wnt1-inducible transgenic mouse model targeting Col1a1-expressing alveolar osteoblasts, odontoblasts, and cementoblasts, we demonstrate that the WNT ligand WNT1 is a strong promoter of cementum and alveolar bone formation in vivo. We induced Wnt1 expression for 1, 3, or 9 wk in Wnt1Tg mice and analyzed them at the age of 6 wk and 12 wk. Micro-computed tomography (CT) analyses of the mandibles revealed a 1.8-fold increased bone volume after 1 and 3 wk of Wnt1 expression and a 3-fold increased bone volume after 9 wk of Wnt1 expression compared to controls. In addition, the alveolar ridges were higher in Wnt1Tg mice as compared to controls. Nondecalcified histology demonstrated increased acellular cementum thickness and cellular cementum volume after 3 and 9 wk of Wnt1 expression. However, 9 wk of Wnt1 expression was also associated with periodontal breakdown and ectopic mineralization of the pulp. The composition of this ectopic matrix was comparable to those of cellular cementum as demonstrated by quantitative backscattered electron imaging and immunohistochemistry for noncollagenous proteins. Our analyses of 52-wk-old mice after 9 wk of Wnt1 expression revealed that Wnt1 expression affects mandibular bone and growing incisors but not molar teeth, indicating that Wnt1 influences only growing tissues. To further investigate the effect of Wnt1 on cementoblasts, we stably transfected the cementoblast cell line (OCCM-30) with a vector expressing Wnt1-HA and performed proliferation as well as differentiation experiments. These experiments demonstrated that Wnt1 promotes proliferation but not differentiation of cementoblasts. Taken together, our findings identify, for the first time, Wnt1 as a critical regulator of alveolar bone and cementum formation, as well as provide important insights for harnessing the WNT signal pathway in regenerative dentistry.

Assessment of the neuronal underpinnings of cognitive impairment in bipolar disorder with a picture encoding paradigm and methodological lessons learnt.

BACKGROUND: Mood disorders are often associated with persistent cognitive impairments. However, pro-cognitive treatments are essentially lacking. This is partially because of poor insight into the neurocircuitry abnormalities underlying these deficits and their change with illness progression. AIMS: This functional magnetic resonance imaging (fMRI) study investigates the neuronal underpinnings of cognitive impairments and neuronal change after mood episodes in remitted patients with bipolar disorder (BD) using a hippocampus-based picture encoding paradigm. METHODS: Remitted patients with BD (n=153) and healthy controls (n=52) were assessed with neuropsychological tests and underwent fMRI while performing a strategic picture encoding task. A subgroup of patients (n=43) were rescanned after 16 months. We conducted data-driven hierarchical cluster analysis of patients' neuropsychological data and compared encoding-related neuronal activity between the resulting neurocognitive subgroups. For patients with follow-up data, effects of mood episodes were assessed by comparing encoding-related neuronal activity change in BD patients with and without episode(s). RESULTS: Two neurocognitive subgroups were revealed: 91 patients displayed cognitive impairments while 62 patients were cognitively normal. No neuronal activity differences were observed between neurocognitive subgroups within the dorsal cognitive control network or hippocampus. However, exploratory whole-brain analysis revealed lower activity within a small region of middle temporal gyrus in impaired patients, which significantly correlated with poorer neuropsychological performance. No changes were observed in encoding-related neuronal activity or picture recall accuracy with the occurrence of mood episode(s) during the follow-up period. CONCLUSION: Memory encoding fMRI paradigms may not capture the neuronal underpinnings of cognitive impairment or effects of mood episodes.

Cost-utility of an eHealth application 'Oncokompas' that supports cancer survivors in self-management: results of a randomised controlled trial.

PURPOSE: The eHealth self-management application 'Oncokompas' was developed to support cancer survivors in monitoring health-related quality of life (HRQOL) and symptoms, and obtaining personalized feedback and options for supportive care. The aim of this study was to assess the cost-utility of Oncokompas compared with care as usual (CAU) among cancer survivors. METHODS: Survivors were randomly allocated to the intervention or control group. Direct (non-)medical, indirect non-medical costs, and HRQOL were measured at 3- and 6-month follow-up, using iMTA Medical Consumption and Productivity Costs and the EuroQol-5D questionnaires. Mean cumulative costs and quality-adjusted life-years (QALYs) were compared between both groups. RESULTS: In total, 625 survivors were randomized into intervention (n = 320) or control group (n = 305). Base case analysis showed that incremental costs from a societal perspective were - €163 (95% CI, - 665 to 326), and incremental QALYs were 0.0017 (95% CI, - 0.0121 to 0.0155) in the intervention group compared with those in the control group. The probability that, compared with CAU, Oncokompas is more effective was 60%, less costly 73%, and both more effective and less costly 47%. Sensitivity analyses showed that incremental costs vary between - €40 and €69, and incremental QALYs vary between - 0.0023 and - 0.0057. CONCLUSION: Oncokompas is likely to be equally effective on utilities, and not more expensive than CAU, and will therefore contribute to sustainable cancer survivorship care in a (cost-)effective manner. IMPLICATIONS FOR CANCER SURVIVORS: Oncokompas seems to improve HRQOL and reduces the burden of several tumour-specific symptoms, while costs from a societal perspective are similar to CAU.

Targeted next-generation sequencing of adult gliomas for retrospective prognostic evaluation and up-front diagnostics.

AIMS: We aimed to reclassify a population-based cohort of 529 adult glioma patients to evaluate the prognostic impact of the 2016 World Health Organization (WHO) central nervous system tumour classification. Moreover, we evaluated the feasibility of gene panel next-generation sequencing (NGS) in daily diagnostics of 225 prospective glioma patients. METHODS: The retrospective cohort was reclassified according to WHO 2016 criteria by immunohistochemistry for IDH-R132H, fluorescence in situ hybridization for 1p/19q-codeletion and gene panel NGS. All tumours of the prospective cohort were subjected to NGS analysis up-front. RESULTS: The entire population-based cohort was successfully reclassified according to WHO 2016 criteria. NGS results were obtained for 98% of the prospective patients. Survival analyses in the population-based cohort confirmed three major prognostic subgroups, that is, isocitrate dehydrogenase (IDH)-mutant and 1p/19q-codeleted oligodendrogliomas, IDH-mutant astrocytomas and IDH-wildtype glioblastomas. The distinction between WHO grade II and III was prognostic in patients with IDH-mutant astrocytoma. The survival of patients with IDH-wildtype diffuse astrocytomas carrying TERT promoter mutation and/or EGFR amplification overlapped with the poor survival of IDH-wildtype glioblastoma patients. CONCLUSIONS: Gene panel NGS proved feasible in daily diagnostics. In addition, our study confirms the prognostic role of glioma classification according to WHO 2016 in a large population-based cohort. Molecular features of glioblastoma in IDH-wildtype diffuse glioma were linked to poor survival corresponding to IDH-wildtype glioblastoma patients. The distinction between WHO grade II and III retained prognostic significance in patients with IDH-mutant diffuse astrocytic gliomas.