Search

Aim: To map COVID‐19‐specific worries and overall psychosocial health among people with diabetes in the initial phase of the COVID‐19 pandemic in Denmark, and to explore characteristics of people with diabetes and high levels of worries related to the COVID‐19 pandemic. Methods: A cross‐sectional survey was conducted by distributing online questionnaires to 2430 adult members (> 18 years) of two user panels consisting of people with diabetes who have volunteered to share information about their life with diabetes. The questionnaire included items on COVID‐19‐specific worries as well as such worries related to diabetes, sociodemographic and health status, social relations, diabetes‐specific social support, diabetes distress and changes in diabetes‐specific behaviours. Responses were analysed with descriptive statistics and logistic regressions. Results: People with diabetes have COVID‐19‐specific worries related to their diabetes. More than half were worried about being overly affected due to diabetes if infected with COVID‐19, about one‐third about being characterized as a risk group due to diabetes and not being able to manage diabetes if infected. Logistic regressions showed that being female, having type 1 diabetes, diabetes complications and diabetes distress, feeling isolated and lonely, and having changed diabetes behaviours were associated with being more worried about COVID‐19 and diabetes. Conclusion: People with diabetes have COVID‐19‐specific worries related to their diabetes which is associated with poorer psychosocial health. These worries should be addressed through support targeting specific questions and needs of individuals with diabetes as well as frequent updates on new knowledge regarding COVID‐19 and diabetes. What's new?: Little is known about how worldwide pandemics affect the psychosocial health of people with diabetes.This study showed a high prevalence of diabetes‐specific worries related to COVID‐19, especially fear of being overly affected by the virus, labelling of people with diabetes as a high‐risk group, and inability to manage diabetes if infected.Female gender, type 1 diabetes, diabetes complications, isolation, loneliness, high diabetes distress and behaviour changes were associated with being more worried about COVID‐19 and diabetes.When providing information and support to people with diabetes in time of crisis, attention should be payed to crisis‐specific worries in specific groups. [ABSTRACT FROM AUTHOR]

Background: After initial diagnosis of cervical cancer, patients are staged and clinically evaluated with PET/CT in order to assess disease extent. Patients with Stage IB1 disease usually undergo definitive surgery. The present authors' objective was to evaluate the diagnostic value of PET/CT in cervical cancer Stage IB1. Materials and Methods: By searching the Danish Gynecological Database (DGCD) the authors identified 144 patients treated for cervical cancer Stage IB1 from 2012-2015 at Rigshospitalet, University Hospital Copenhagen, Denmark. Patients who underwent a PET/CT scan and either definitive surgery or diagnostic laparoscopy were included for further analysis. Results: One hundred forty patients had a PET/CT scan and results were available for 136 patients, six of which had suspicious lymph nodes; three patients did not have metastases and three patients did. One hundred thirty patients did not have suspicious lymph nodes on PET/CT. Histological results were available for 106 of these patients and 97 of these did not have metastases and nine patients did. Out of all the 12 patients with metastatic lymph nodes, 11 had pelvic, none had para-aortic disease, and data regarding localization was missing for the last patient. Regarding PET/CT detection of pelvic lymph nodes, the sensitivity was 25%, specificity 97%, positive predictive value 50%, and negative predictive value 92%. Conclusion: The sensitivity and positive predictive value of PET/CT in cervical cancer Stage IB1 patients were low. PET/CT cannot replace surgical lymphadenectomy and histologic examination in these patients. [ABSTRACT FROM AUTHOR]

Aim: Time preferences, i.e. individuals' degree of patience/impatience in intertemporal choice, have been found to be associated with suboptimal health behaviours and health outcomes such as smoking, physical inactivity, unhealthy food intake and obesity. In this systematic review, we aimed to synthesise reported associations between time preferences, diabetes self‐management behaviours, including use of diabetes technology, and outcomes. Methods: We searched MEDLINE, EMBASE, PsycINFO, CINAHL, EconLit and all databases in the Web of Science Core Collection. Peer‐reviewed studies of people with diabetes that included at least one diabetes‐related behaviour or outcome and a measure of time preferences were included. Non‐English language studies were excluded. Results: A total of 961 records were identified, of which 12 articles were included. Three studies analysed both time‐consistent and time‐inconsistent preferences, three studies solely analysed time‐inconsistent preferences and six studies did not explicitly define a time preference model. Measured outcomes across studies included self‐care activities, such as medication‐taking, exercising and eating a healthy diet, and biomedical outcomes, such as HbA1c and diabetes‐related complications. There were 10 cross‐sectional studies and two panel‐data studies. No studies explicitly analysed the relationship between time preferences and diabetes technology use. Conclusions: Associations between measures of time preferences, diabetes self‐management behaviours and clinical outcomes exist. Higher discount rates determined by both time‐consistent and time‐inconsistent models predict less diabetes‐related self‐care and worse outcomes. These findings may add to explanations of the observed variation in diabetes‐related health and provide new insights for tailoring interventions and policies aimed at improving diabetes self‐management. What's new?: Time preferences, i.e. individuals' degree of patience/impatience in intertemporal choice, have been found to be associated with suboptimal health behaviours and health outcomes such as smoking, physical inactivity and obesity.This review provides the first synthesis of the associations between time preferences, diabetes self‐management behaviours and outcomes. A limited number of studies indicate that time preference measures, such as higher discount rate and present bias variables, are associated with worse diabetes self‐management behaviours and outcomes.Time preferences seem to represent a promising framework for improving diabetes‐related health and may inform interventions and policies aimed at changing behaviour. [ABSTRACT FROM AUTHOR]

STUDY QUESTION Is there an association between the length of in vitro culture, mode of ART and the initial endogenous hCG rise, in cycles with a foetal heartbeat after single embryo transfer (ET) and implantation? SUMMARY ANSWER Both the length of in vitro culture and the mode of ART have an impact on the initial endogenous rise in hCG in singleton pregnancies. WHAT IS KNOWN ALREADY Different factors have been identified to alter the kinetics of hCG in pregnancies. Current studies show conflicting results regarding the kinetics of hCG after different types of ART (fresh vs frozen ET (FET)), the inclusion or not of preimplantation genetic testing (PGT), and the length of time in in vitro culture. STUDY DESIGN, SIZE, DURATION This was a multicentre cohort study, using prospectively collected data derived from 4938 women (5524 treatment cycles) undergoing IUI (cycles, n = 608) or ART (cycles, n = 4916) treatments, resulting a in singleton ongoing pregnancy verified by first-trimester ultrasound scan. Data were collected from the Danish Medical Data Centre, used by the three participating Danish public fertility clinics at Copenhagen University hospitals: Herlev Hospital, Hvidovre Hospital, and Rigshospitalet, from January 2014 to December 2021. PARTICIPANTS/MATERIALS, SETTING, METHODS The fresh ET cycles included cleavage-stage (2 or 3 days in vitro) and blastocyst (5 days in vitro) transfers. FET cycles included cleavage-stage (3 days in vitro before cryopreservation) or blastocyst (5 or 6 days in vitro before cryopreservation) transfers. The IUI cycles represented no time in vitro. To attain a comparable interval for serum-hCG (s-hCG), the ovulation induction time was identical: 35–37 h before oocyte retrieval or IUI. The conception day was considered as: the insemination day for pregnancies conceived after IUI, the oocyte retrieval day for fresh ET, or the transfer day minus 3 or 5 as appropriate for FET of Day 3 or 5 embryos. Multiple linear regression analysis was used, including days post-conception for the hCG measurement as a covariate, and was adjusted for the women's age, the cause of infertility, and the centre. For FET, a sensitivity analysis was used to adjust for endometrial preparation. MAIN RESULTS AND THE ROLE OF CHANCE The study totally includes 5524 cycles: 2395 FET cycles, 2521 fresh ET cycles, and 608 IUI cycles. Regarding the length of in vitro culture, with IUI as reference (for no time in in vitro culture), we found a significantly lower s-hCG in pregnancies achieved after fresh ET (cleavage-stage ET or blastocyst transfer). S-hCG was 18% (95% CI: 13–23%, P  < 0.001) lower after fresh cleavage-stage ET, and 23% (95% CI: 18–28%, P  < 0.001) lower after fresh blastocyst transfer compared to IUI. In FET cycles, s-hCG was significantly higher after blastocyst transfers compared to cleavage-stage FET, respectively, 26% (95% CI: 13–40%, P  < 0.001) higher when cryopreserved on in vitro Day 5, and 14% (95% CI: 2–26%, P  = 0.02) higher when cryopreserved on in vitro Day 6 as compared to Day 3. Regarding the ART treatment type, s-hCG after FET blastocyst transfer (Day 5 blastocysts) cycles was significantly higher, 33% (95% CI: 27–45%, P  < 0.001), compared to fresh ET (Day 5 blastocyst), while there was no difference between cleavage-stage FET (Days 2 + 3) and fresh ET (Days 2 + 3). S-hCG was 12% (95% CI: 4–19%, 0.005) lower in PGT FET (Day 5 blastocysts) cycles as compared to FET cycles without PGT (Day 5 blastocysts). LIMITATIONS, REASONS FOR CAUTION The retrospective design is a limitation which introduces the risk of possible bias and confounders such as embryo score, parity, and ovarian stimulation. WIDER IMPLICATIONS OF THE FINDINGS This study elucidates how practices in medically assisted reproduction treatment are associated with the hCG kinetics, underlining a potential impact of in vitro culture length and mode of ART on the very early embryo development and implantation. The study provides clinicians knowledge that the type of ART used may be relevant to take into account when evaluating s-hCG for the prognosis of the pregnancy. STUDY FUNDING/COMPETING INTEREST(S) No funding was received for this study. AP has received consulting fees, research grants, or honoraria from the following companies: Preglem, Novo Nordisk, Ferring Pharmaceuticals, Gedeon Richter, Cryos, Merck A/S, and Organon. AZ has received grants and honoraria from Gedeon Richter. NLF has received grants from Gedeon Richter, Merck A/S, and Cryos. MLG has received honoraria fees or research grants from Gedeon Richter, Merck A/S, and Cooper Surgical. CB has received honoraria from Merck A/S. MB has received research grants and honoraria from IBSA. MPR, KM, and PVS all report no conflicts of interest. TRIAL REGISTRATION NUMBER The study was registered and approved by the Danish Protection Agency, Capital Region, Denmark (Journal-nr.: 21019857). No approval was required from the regional ethics committee according to Danish law. [ABSTRACT FROM AUTHOR]

The pathogenesis of sepsis involves a dual inflammatory response, with a hyperinflammatory phase followed by, or in combination with, a hypoinflammatory phase. The adhesion molecules lymphocyte function-associated antigen (LFA-1) (CD11a/CD18) and macrophage-1 (Mac-1) (CD11b/CD18) support leucocyte adhesion to intercellular adhesion molecules and phagocytosis through complement opsonization, both processes relevant to the immune response during sepsis. Here, we investigate the role of soluble (s)CD18 in sepsis with emphasis on sCD18 as a mechanistic biomarker of immune reactions and outcome of sepsis. sCD18 levels were measured in 15 septic and 15 critically ill non-septic patients. Fifteen healthy volunteers served as controls. CD18 shedding from human mononuclear cells was increased in vitro by several proinflammatory mediators relevant in sepsis. sCD18 inhibited cell adhesion to the complement fragment iC3b, which is a ligand for CD11b/CD18, also known as Mac-1 or complement receptor 3. Serum sCD18 levels in sepsis non-survivors displayed two distinct peaks permitting a partitioning into two groups, namely sCD18 'high' and sCD18 'low', with median levels of sCD18 at 2158 mU/ml [interquartile range (IQR) 2093-2811 mU/ml] and 488 mU/ml (IQR 360-617 mU/ml), respectively, at the day of intensive care unit admission. Serum sCD18 levels partitioned sepsis non-survivors into one group of 'high' sCD18 and low CRP and another group with 'low' sCD18 and high C-reactive protein. Together with the mechanistic data generated in vitro, we suggest the partitioning in sCD18 to reflect a compensatory anti-inflammatory response syndrome and hyperinflammation, respectively, manifested as part of sepsis. [ABSTRACT FROM AUTHOR]

We demonstrate a single-photon collection efficiency of (44.3 ± 2.1)% from a quantum dot in a low-Q mode of a photonic-crystal cavity with a single-photon purity of g(2)(0) = (4 ± 5)% recorded above the saturation power. The high efficiency is directly confirmed by detecting up to 962 ± 46 kilocounts per second on a single-photon detector on another quantum dot coupled to the cavity mode. The high collection efficiency is found to be broadband, as is explained by detailed numerical simulations. Cavity-enhanced efficient excitation of quantum dots is obtained through phonon-mediated excitation and under these conditions, single-photon indistinguishability measurements reveal long coherence times reaching 0.77 ±0.19 ns in a weak-excitation regime. Our work demonstrates that photonic crystals provide a very promising platform for highly integrated generation of coherent single photons including the efficient out-coupling of the photons from the photonic chip. [ABSTRACT FROM AUTHOR]

The present study evaluated the physical demands imposed on female elite team handball players in relation to playing position. Female elite team handball field players were examined during match-play over a 5-year period using video based computerized locomotion analysis of tournament matches. In addition, physiological measurements during match-play and in separate physical tests were carried out. A total distance of 4 002 ± 551m (group means ± SD) was covered per match with a total effective playing time of 50:42 ± 5:50 min:s, while fulltime players covered 4 693 ± 333 m. On average, each player (n = 83) performed 663.8 ± 99.7 activity changes per match, and the mean speed was 5.31 ± 0.33 km • h− 1 . High-intensity running constituted 0.8 ± 0.5 % of total effective playing time per match corresponding to 2.5 ± 1.8 % of the total distance covered. The amount of high-intensity running was reduced (p < 0.05) 21.9 % in the second half (44.9 ± 16.8 m) compared to the first (57.5 ± 21.3 m). Maximal oxygen uptake (VO2 –max) was 3.49 ± 0.37 l O2 • min−1 corresponding to 49.6 ± 4.8 ml O2 • min−1 • kg−1 . Mean relative workload during match-play was 79.4 ± 6.4 % of VO 2 -max. Mean total running distance in the Yo-Yo intermittent recovery test (level 1) was 1 436 ± 222 m, which was greater in wing players (1 516 ± 172 m, p < 0.05) than pivots (1 360 ± 118 m) and backcourt players (1 352 ± 148 m). In conclusion, modern female elite team handball is a physically demanding intermittent team sport, where players are exposed to high relative workloads with substantial estimated aerobic energy expenditure interspersed by short periods of dominant anaerobic energy production as reflected by the limited amount of high-intensity running. Indications of fatigue and a resulting decline in physical performance were identified, since the amount of high-intensity running and the relative workload levels decreased in the second half. Positional differences were observed, with wing players covering a greater total distance than backcourt players, performing more high-intensity running and demonstrating a better intermittent recovery capacity (Yo-Yo test outcome) compared to both backcourt players and pivots. [ABSTRACT FROM AUTHOR]

The present study evaluated the physical demands imposed on female elite team handball players in relation to playing position. Female elite team handball field players were examined during match-play over a 5-year period using video based computerized locomotion analysis of tournament matches. In addition, physiological measurements during match-play and in separate physical tests were carried out. A total distance of 4 002 ± 551m (group means ± SD) was covered per match with a total effective playing time of 50:42 ± 5:50 min:s, while fulltime players covered 4 693 ± 333 m. On average, each player (n = 83) performed 663.8 ± 99.7 activity changes per match, and the mean speed was 5.31 ± 0.33 km • h− 1 . High-intensity running constituted 0.8 ± 0.5 % of total effective playing time per match corresponding to 2.5 ± 1.8 % of the total distance covered. The amount of high-intensity running was reduced (p < 0.05) 21.9 % in the second half (44.9 ± 16.8 m) compared to the first (57.5 ± 21.3 m). Maximal oxygen uptake (VO2–max) was 3.49 ± 0.37 l O2 • min−1 corresponding to 49.6 ± 4.8 ml O2 • min−1 • kg−1 . Mean relative workload during match-play was 79.4 ± 6.4 % of VO2–max. Mean total running distance in the Yo-Yo intermittent recovery test (level 1) was 1 436 ± 222 m, which was greater in wing players (1 516 ± 172 m, p < 0.05) than pivots (1 360 ± 118 m) and backcourt players (1 352 ± 148 m). In conclusion, modern female elite team handball is a physically demanding intermittent team sport, where players are exposed to high relative workloads with substantial estimated aerobic energy expenditure interspersed by short periods of dominant anaerobic energy production as reflected by the limited amount of high-intensity running. Indications of fatigue and a resulting decline in physical performance were identified, since the amount of high-intensity running and the relative workload levels decreased in the second half. Positional differences were observed, with wing players covering a greater total distance than backcourt players, performing more high-intensity running and demonstrating a better intermittent recovery capacity (Yo-Yo test outcome) compared to both backcourt players and pivots. [ABSTRACT FROM AUTHOR]

We employ detuning-dependent decay-rate measurements of a quantum dot in a photonic-crystal cavity to study the influence of phonon dephasing in a solid-state quantum-electrodynamics experiment. The experimental data agree with a microscopic non-Markovian model accounting for dephasing from longitudinal acoustic phonons, and the analysis explains the difference between nonresonant cavity feeding in different nanocavities. From the comparison between experiment and theory we extract the effective phonon density of states experienced by the quantum dot in the nanocavity. This quantity determines all phonon dephasing properties of the system and is found to be described well by a theory of bulk phonons. [ABSTRACT FROM AUTHOR]

Adverse events during foetal development can predispose the individual for cardiovascular disease later in life, a correlation known as foetal programming of adult hypertension. The 'programming' events have been associated with the kidneys due to the significant role in extracellular volume control and long-term blood pressure regulation. Previously, nephron endowment and functional consequences of a low nephron number have been extensively investigated without achieving a full explanation of the underlying pathophysiological mechanisms. In this review, we will focus on mechanisms of postnatal development in the renal medulla with regard to the programming effects. The renin-angiotensin system is critically involved in mammalian kidney development and impaired signalling gives rise to developmental renal lesions that have been associated with hypertension later in life. A consistent finding in both experimental animal models and in human case reports is atrophy of the renal medulla with developmental lesions to both medullary nephron segments and vascular development with concomitant functional disturbances reaching into adulthood. A review of current knowledge of the role of the renin-angiotensin system for renal medullary development will be given. [ABSTRACT FROM AUTHOR]

We present detuning-dependent spectral and decay-rate measurements to study the difference between the spectral and dynamical properties of single quantum dots embedded in micropillar and photonic crystal cavities. For the micropillar cavity, the dynamics is well described by the dissipative Jaynes-Cummings model, whereas systematic deviations are observed for the emission spectra. The discrepancy for the spectra is attributed to the coupling of other exciton lines to the cavity and interference of different propagation paths toward the detector of the fields emitted by the quantum dot. In contrast, quantitative information about the system can readily be extracted from the dynamical measurements. In the case of photonic crystal cavities, we observe an anti-crossing in the spectra when detuning a single quantum dot through resonance, which is the spectral signature of a strong coupling. However, time-resolved measurements reveal that the actual coupling strength is significantly smaller than anticipated from the spectral measurements and that the quantum dot is rather weakly coupled to the cavity. We suggest that the observed Rabi splitting is due to cavity feeding by other quantum dots and/or multi-exciton complexes giving rise to collective emission effects. [ABSTRACT FROM AUTHOR]

Defects in intestinal barrier function are associated with diseases of the gastrointestinal (GI) tract. There is growing evidence that increases in intestinal permeability plays a pathogenic role in diseases, such as inflammatory bowel disease (IBD) and celiac disease, and functional bowel disorders, such as irritable bowel syndrome (IBS). This review takes a unique translational approach to discuss the physiological and pathophysiological mechanisms involved in the regulation of intestinal barrier function in IBS. The review summarizes the components of the intestinal barrier including the tight junction complex within the epithelium, and the methods used to assess gut permeability both in vitro and in vivo. Throughout the review, the authors have attempted to critically review the latest research from both experimental animal models and human studies to appraise whether intestinal barrier dysfunction is a primary cause of functional GI disorders, such as IBS.... [ABSTRACT FROM AUTHOR]

The aim of this study was to evaluate the effect of carbohydrate supplementation on free plasma DNA and conventional markers of training and tissue damage in long-distance runners undergoing an overload training program. Twenty-four male runners were randomly assigned to two groups (CHO group and control group). The participants were submitted to an overload training program (days 1-8), followed by a high-intensity intermittent running protocol (10 × 800 m) on day 9. The runners received maltodextrin solution (CHO group) or zero energy placebo solution as the control equivalent before, during, and after this protocol. After 8 days of intensive training, baseline LDH levels remained constant in the CHO group (before: 449.1 ± 18.2, after: 474.3 ± 22.8 U/L) and increased in the control group (from 413.5 ± 23.0 to 501.8 ± 24.1 U/L, p < 0.05). On day 9, LDH concentrations were lower in the CHO group (509.2 ± 23.1 U/L) than in the control group (643.3 ± 32.9 U/L, p < 0.01) post-intermittent running. Carbohydrate ingestion attenuated the increase of free plasma DNA post-intermittent running (48,240.3 ± 5,431.8 alleles/mL) when compared to the control group (73,751.8 ± 11,546.6 alleles/mL, p < 0.01). Leukocyte counts were lower in the CHO group than in the control group post-intermittent running (9.1 ± 0.1 vs. 12.2 ± 0.7 cells/µL; p < 0.01) and at 80 min of recovery (10.6 ± 0.1 vs. 13.9 ± 1.1 cells/µL; p < 0.01). Cortisol levels were positively correlated with free plasma DNA, leukocytes, and LDH (all r > 0.4 and p < 0.001). The results showed that ingestion of a carbohydrate beverage resulted in less DNA damage and attenuated the acute post-exercise inflammation response, providing better recovery during intense training. [ABSTRACT FROM AUTHOR]

Fatigue is frequent in cancer patients undergoing chemotherapy. Erythropoietins (EPO) have shown well-documented effects on these patients, and administered in pharmacological doses, may reduce the need for transfusion of blood cells and improve quality of life (QoL). An explorative, descriptive, non-randomised intervention study using semi-structured interviews was conducted with the aim to gain an insight into the effects and experiences associated with EPO treatment in combination with a structured 6-week physical exercise intervention. Sixteen cancer patients with evidence of disease, who had received at least one cycle chemotherapy, participated. Participants received 500 μg Darbepoetin Alfa (DA) every 3 weeks during the intervention. Four typologies of patients were identified with regard to DA effects. The interviews revealed that eleven patients experienced some kind of immediate improvement in cognitive and emotional functioning, and subjective daily well-being. Furthermore physical improvement and changes in QoL outcomes showed no significant differences between the study group and a reference group. A significant increase in the hemoglobin concentration (7.14-7.87 mmol/L, P<0.05) was found in the study group. The future use of EPO in cancer patients is hampered by the reported negative influence of EPO on the prognosis in some diagnoses and should be based on randomized studies. [ABSTRACT FROM AUTHOR]

MADSEN K. & POULSEN H.S. (2011) European Journal of Cancer Care, 33-43 The purpose of this paper is to undertake a review of the everyday lives and the need for support felt by relatives of adults with malignant cerebral glioma. Through electronic literature searches we identified studies with qualitative, quantitative or mixed method designs. Fourteen studies were identified. They indicated that a relative often assumes the caregiver's role, taking over responsibility for the patient's illness and survival, and that the relative is often overwhelmingly exhausted by this task. The ever-changing circumstances left the relatives fearful, anxious and apprehensive. The relatives lacked information about how to provide day-to-day care and how to manage psychoses and neuropsychiatric problems at home. Likewise, they needed help from the professionals to talk with each other about potentially reduced life expectancy. Most relatives appeared to value specialist nurse support highly, and they found support groups helpful. Relatively few studies were identified, and extant research was found to be diverse in purpose, study design and study population. The majority of the studies focused only on the parts of the relatives' everyday lives in which they were taking care of and supporting the patient. Further research focusing on the impact of the illness on different part of relative's everyday life is needed. [ABSTRACT FROM AUTHOR]

The 5-HT4 receptor may play a role in memory and learning and 5-HT4 receptor activation has been suggested to modulate acetylcholine release and to reduce amyloid-β (Aβ) accumulation. The aim of this study was for the first time to investigate the in vivo cerebral 5-HT4 receptor binding in early Alzheimer disease (AD) patients in relation to cortical Aβ burden. Eleven newly diagnosed untreated AD patients (mean MMSE 24, range 19-27) and twelve age- and gender-matched healthy controls underwent a two-hour dynamic [11C]SB207145 PET scan to measure the binding potential of the 5-HT4 receptor. All AD patients and eight healthy controls additionally underwent a [11C]PIB PET scan to measure the cortical Aβ burden. When AD patients were defined on clinical criteria, no difference in cerebral 5-HT4 receptor binding between AD patients and healthy controls was found (p = 0.54). However, when individuals were reassigned to groups according to their amyloid status, the PIB-positive individuals had 13% higher 5-HT4 receptor levels than PIB-negative individuals (p = 0.02) and the importance of classification of groups is emphasized. The 5-HT4 receptor binding was a positively correlated to Aβ burden (p = 0.03) and negatively to MMSE score of the AD patients (p = 0.02). Our data suggests that cerebral 5-HT4 receptor upregulation starts at a preclinical stage of and continues while dementia is still at a mild stage, which contrasts other receptor subtypes. We speculate that this may either be a compensatory effect of decreased levels of interstitial 5-HT, an attempt to improve cognitive function, increase acetylcholine release or to counteract Aβ accumulation. [ABSTRACT FROM AUTHOR]

Background: Defects in the small intestinal epithelial barrier have been associated with inflammatory bowel disease but their role in the causation of disease is still a matter of debate. In some models of disease increased permeability appears to be a very early event. The interleukin 10 (IL10) gene-deficient mouse spontaneously develops colitis after 12 weeks of age. These mice have been shown to have increased small intestinal permeability that appears early in life. Furthermore, the development of colitis is dependent upon luminal agents, as animals do not develop disease if raised under germ- free conditions. Aims: To determine if the elevated small bowel permeability can be prevented, and if by doing so colonic disease is prevented or attenuated. Methods: IL10 gene-deficient (IL10-/-( mice) were treated with AT-1001 (a zonulin peptide inhibitor), a small peptide previously demonstrated to reduce small intestinal permeability. Small intestinal permeability was measured, in vivo, weekly from 4 to 17 weeks of age. Colonic disease was assessed at 8 weeks in Ussing chambers, and at 17 weeks of age inflammatory cytokines and myeloperoxidase were measured in the colon. Colonic permeability and histology were also endpoints. Results: Treated animals showed a marked reduction in small intestinal permeability. Average area under the lactulose/mannitol time curve: 5.36 (SE 0.08) in controls vs 3.97 (SE 0.07) in the high-dose AT-1001 group, p<0.05. At 8 weeks of age there was a significant reduction of colonic mucosal permeability and increased electrical resistance. By 17 weeks of age, secretion of tumour necrosis factor c (TNFα) from a colonic explant was significantly lower in the treated group (25.33 (SE 4.30( pg/mg vs 106.93 (SE 17.51) pg/ml in controls, p<0.01). All other markers also demonstrated a clear reduction of colitis in the treated animals. Additional experiments were performed which demonstrated that AT-1001 was functionally active only in the small intestine. Conclusions: This work suggests that increased intestinal permeability may be an important aetiological event in the development of colitis in IL10-/- mice. [ABSTRACT FROM AUTHOR]

Abstract: Previous studies of patients with Alzheimer''s disease (AD) have described reduced brain serotonin 2A (5-HT2A) receptor density. It is unclear whether this abnormality sets in early in the course of the disease and whether it is related to early cognitive and neuropsychiatric symptoms. We assessed cerebral 5-HT2A receptor binding in patients with mild cognitive impairment (MCI) and related 5-HT2A receptor binding to clinical symptoms. Sixteen patients with MCI of the amnestic type (mean age 73, mean MMSE 26.1) and 17 age and sex matched control subjects were studied with MRI and [18F]altanserin PET in a bolus–infusion approach. A significant global reduction of 20–30% in 5-HT2A binding (atrophy corrected) was found in most neocortical areas. Reduced 5-HT2A binding in the striatum correlated significantly with Neuropsychiatric Inventory depression and anxiety scores. We conclude that widespread reductions in 5-HT2A receptor binding were found in amnestic MCI, pointing at the presence of serotonergic dysfunction in prodromal AD. This may provide some of the pathophysiological background for the neuropsychiatric symptoms found in early AD. [Copyright &y& Elsevier]

The objective of the present investigation was to evaluate the effects of acidic pH of the perfusate and presence of lipopolysaccharide (LPS) on permeability of rumen and colon mucosal tissues to mannitol and LPS using the Using chamber system. Rumen and colon tissues (n = 8), obtained from slaughtered feedlot steers, were tested for changes in permeability to ³H-mannitol under pH of 4.5, 5.5, and 6.5 for rumen and at 5.5, 6.5, and 7.4 for colon, with or without LPS from Escherichia coli B:055 at 500 µg/mL. The ³H-Mannitol was added at 10 ILL (525.4 GBq/mmol) on the mucosal side of the Using chamber to detect changes in permeability, and 4 samples were taken at 20, 25, 30, and 35 min from the serosal side. Permeability of rumen and colon mucosa to ³H-mannitol increased 6- and 5-fold, respectively, at acidic pH values of 4.5 and 5.5 and in the presence of 500 µg/mL of LPS. In contrast, LPS did not affect rumen and colon permeability at pH that ranged from 5.5 and 7.4. Translocation of LPS across the rumen and colon mucosa of cattle was not pH dependent. The LPS translocated through these tissues if present at the mucosal side. In conclusion, the permeability of rumen and colon tissues to ³H-mannitol increased in presence of LPS and under acidic pH, whereas LPS permeated through mucosal tissues independently of the pH of the perfusate. Further research is warranted to understand the mechanism(s) by which acidic pH of the rumen digesta and presence of LPS make rumen and colon tissues "leaky". [ABSTRACT FROM AUTHOR]

We have tested the hypothesis that the altered muscle contractility after lengthening contractions (LC) is caused by altered calcium (Ca2+) kinetics. Subjects ( n = 8) performed 100 drop jumps and muscle contractility was measured pre- and post-exercise by maximal voluntary contraction (MVC) and transcutaneous electrical stimulation (1, 20 and 50 Hz). Muscle biopsies were analysed for muscle metabolites, rates of SR Ca2+ uptake (CaU) and release (CaR) and myosin heavy chain (MHC) composition. The rates of torque relaxation and CaU were positively related to muscle fibre type composition (% MHC II). Muscle creatine (Cr) decreased and the ratio between phosphocreatine (PCr) and Cr increased 3 and 24 h post-exercise ( P < 0.05 vs. pre-exercise). LC resulted in reduced MVC (−19%), twitch torque (−41%) and 20/50 Hz torque ratio (−30%) and a faster relaxation rate ( P < 0.05). The contractile parameters recovered partially but remained altered 24 h post-exercise ( P < 0.05). The average CaR was unchanged after LC ( P > 0.05). However, the response varied between subjects and the relative post-exercise CaR was significantly related to the degree of LFF (post/pre 20/50 Hz force ratio) and to the decline in twitch force (post/pre twitch ratio). CaU was lower in seven of eight subjects after LC ( P > 0.05). The decline in torque after LC could not be explained by metabolic factors since PCr/Cr ratio increased. The relation between CaR and fatigue suggests that the mechanism of fatigue in part may be attributed to intrinsic changes in the SR Ca2+ release channel. The faster torque relaxation after LC could not be explained by an increased rate of CaU. [ABSTRACT FROM AUTHOR]

A quadratic spline is a differentiable piecewise quadratic function. Many problems in the numerical analysis and optimization literature can be reformulated as unconstrained minimizations of quadratic splines. However, only special cases of quadratic splines have been studied in the existing literature and algorithms have been developed on a case-by-case basis. There lacks an analytical representation of a general or even convex quadratic spline. The current paper fills this gap by providing an analytical representation of a general quadratic spline. Furthermore, for a convex quadratic spline, it is shown that the representation can be refined in the neighborhood of a nondegenerate point and a set of nondegenerate minimizers. Based on these characterizations, many existing algorithms for specific convex quadratic splines are also finitely convergent for a general convex quadratic spline. Finally, we study the relationship between the convexity of a quadratic spline function and the monotonicity of the corresponding linear complementarity problem. It is shown that, although both conditions lead to easy solvability of the problem, they are different in general. [ABSTRACT FROM AUTHOR]

The pathogenesis of Crohn's disease likely involves multifactorial interactions between genetic factors and environmental triggers. The most recent studies suggest that luminal bacteria are a significant factor in the onset and chronicity of inflammation. In interleukin-10 (IL-10) gene-deficient mice a Crohn's-like colitis develops when the mice are raised under conventional animal care facilities but fails to develop when they are raised under germ-free conditions. These mice demonstrate significant alterations in the species and the levels of bacteria colonizing the colon, suggesting that genetic factors in the host may be critical in controlling bacterial colonization. In addition, early treatment of IL-10 gene-deficient mice with antibiotics can prevent the development of colitis in later life, suggesting that early events during the neonatal period can influence later disease progression. Recent work has focused on using probiotic bacterial mixtures to alter the microbial balance in the colon in attempts to reduce inflammation. The use of the VSL-3 probiotic mixture in the IL-10 gene-deficient mouse resulted in a complete normalization of physiological transport function and barrier integrity, in conjunction with a reduction in mucosal secretion of TNF-alpha and IFN-gamma. Further, it would appear that a soluble factor is released from a bacterium found in the VSL-3 mixture that can act directly on the epithelium to enhance barrier integrity. Results from animal models of inflammatory bowel disease suggest that genetically susceptible hosts can mount a pathogenic cellular immune response to specific nonpathogenic bacterial species, as a consequence of defective immunologic tolerance and lack of appropriate mucosal defences. Probiotic bacteria appear to be a promising new alternative for the treatment of clinical conditions that are associated with alterations in gut barrier function, including Crohn' s disease. INSET: The Joe Doupe Young Investigator's Award. [ABSTRACT FROM AUTHOR]

Summary: A bronchopleural fistula (BPF) consists of a direct communication between the bronchial tree and the pleural space, which can develop secondary to (pleuro) pneumonia. Thoracotomy has been reported as a viable treatment option in cases of nonresponsive pleuropneumonia, pleural abscess formation and necrotising pneumonia. The presence of a BPF can delay and even prevent healing of the thoracotomy site, with clinical signs of coughing and putrid purulent nasal discharge often seen. In this case report, we describe the diagnosis and localisation of a bronchopleural fistula using retrograde instillation of methylene blue through the thoracotomy site, followed by the successful closure of the BPF using endoscopic application of acrylate co‐monomer glue (Glubran 2®). [ABSTRACT FROM AUTHOR]

Examines glycogen synthesis and glycogneogenesis from lactate in humans in recovery from intense exercise when muscle glycogen concentration was low and the arterial lactate levels were either moderate or high. Evidence for the occurrence of muscle glyconeogenesis in humans; Role of lactate as substrate; Blood glucose as the most important precursor for post-exercise muscle glycogen synthesis.

The effect of glyphosate on weeds was evaluated in greenhouse bioassays with five weed species and compared with a commercial mixture of phenmedipham and ethofumesate. Glyphosate was more active than a mixture of phenmedipham and ethofumesate on the weeds. Solanum nigrum was the most sensitive species to both herbicide treatments. The relative potency of glyphosate between the weeds showed consistency at 50% and 90% control levels for four out of five weed species, which could be ranked independently of control level because of similar response curves. In a field trial on sugarbeet genetically engineered to acquire glyphosate tolerance, a total of 720 g a.i. ha-1 of glyphosate applied in one, two or three applications gave similar or superior control of weeds to a total of 3.17 kg a.i. ha-1 mixture of metamitron, phenmedipham and ethofumesate applied in three repeated applications. [ABSTRACT FROM AUTHOR]

Variable fluorescence and carbon dioxide exchange rate (CER) were measured in intact leaves of glyphosate-treated sugarbeet plants, to investigate rapid effects on photosynthesis. In one experiment, a significant effect on variable fluorescence and CER was found within 8 h after herbicide application. The effect on stomatal conductance was not significant. In a second experiment, the effects of light or dark conditions during herbicide application and 24 h later were evaluated. Under light conditions glyphosate significantly reduced variable fluorescence after 4 h. However under initial conditions of 24 h darkness, followed by alternating 8 h light/8 h dark, the effect was not significant until 44 h after treatment, by which time the plants had received several hours of light. The effect on variable fluorescence 8 h after herbicide application correlated positively with plant survival 7 days later. [ABSTRACT FROM AUTHOR]

Presents a study which examines the role of lactate and glucose as substrates for glyconeogenesis in muscle in recovery from high-intensity exercise in human. Reference to previous studies; Detailed information on the methodology used to conduct the study; Results of the study; Discussion surrounding the results of the study.

Cord entanglement in monochorionic monoamniotic (MCMA) pregnancy with a lethal discordant anomaly or twin reversed arterial perfusion (TRAP) sequence can lead to strangulation, preterm labor and demise of the healthy twin[1]. Cord to deceased twin is clearly visible as a thin band. gl The fourth case was a MCMA pregnancy complicated by cord entanglement, with one twin diagnosed with acrania, which presented at 17 weeks' gestation. GRAPH: Videoclip S1 Intraoperative fetoscopic video showing cord ablation and division at 22 weeks' gestation in monochorionic monoamniotic twin pregnancy complicated by twin reversed arterial perfusion sequence with cord strangulation at the placental insertion site. [Extracted from the article]

In patients with epithelial ovarian cancer (EOC), the clinical efficacy of monotherapy with immune checkpoint inhibitors (ICIs) against PD-1/PD-L1 is modest. To enhance response rates to these immunotherapeutic agents and broaden the indications for their use, new approaches involving combinational therapy are needed. The immune regulator CD73 is a potential target, as it promotes tumor escape by producing immunosuppressive extracellular adenosine in the tumor microenvironment. Here, we present the results from the NSGO-OV-UMB1/ENGOT-OV-30 trial evaluating the activity of combining the anti-CD73 antibody oleclumab with the anti-PD-L1 checkpoint inhibitor durvalumab in patients with recurrent EOC. In this phase II open-label non-randomized study, patients with CD73-positive relapsed EOC were intravenously administered oleclumab (3000 mg, Q2W) and durvalumab (1500 mg, Q4W). The primary endpoint was disease control rate (DCR) at 16 weeks. The expression of PD-L1 and CD8 was assessed by immunohistochemistry of archival tumors. This trial included 25 patients with a median age of 66 years (47–77 years). Twenty-two patients were evaluable for treatment activity analysis. The DCR was 27%, the median progression-free survival was 2.7 months (95% CI: 2.2–4.2) and the median overall survival was 8.4 months (95% CI: 5.0–13.4). Infiltration of CD8+ cells and PD-L1 expression on tumor cells were observed in partially overlapping sets of 74% of the tumor samples. Neither CD8- nor PD-L1-positivity were significantly associated with better DCR. Combined treatment with oleclumab and durvalumab was safe and demonstrated limited anti-tumor activity in patients with recurrent EOC. [Display omitted] • This trial is the first to report on the efficacy and safety of PD-L1 and CD73 inhibition in recurrent ovarian cancer. • The combination of oleclumab and durvalumab showed limited clinical activity in relapsed epithelial ovarian cancer. • Treatment- and immune-related adverse events were rare, and no new safety signals were reported for the treatment regimen. [ABSTRACT FROM AUTHOR]

Constraining the primary growth channel of supermassive black holes (SMBHs) remains one the most actively debated questions in the context of cosmological structure formation. Owing to the expected connection between SMBH spin parameter evolution and the accretion and merger history of individual black holes, population spin measurements offer a rare observational window into the cosmic growth of SMBHs. As of today, the most common method for estimating SMBH spin relies on modeling the relativistically broaden atomic profiles in the reflection spectrum observed in X-rays. In this paper, we study the observational requirements needed to confidently distinguish between the primary SMBH growth channels based on their distinct spin-mass distributions predicted by the Horizon-AGN cosmological simulation. Indoing so, we characterize outstanding limitations associated with the existing measurements and discuss the landscape of future observational campaigns which could be planned and executed with future X-ray observatories. We focus our attention on the High-Energy X-ray Probe (HEX-P), a proposed probe-class mission designed to serve the high- energy community in the 2030s. [ABSTRACT FROM AUTHOR]

Since the discovery of the cosmic X-ray background (CXB), astronomers have strived to understand the accreting supermassive black holes (SMBHs) contributing to its peak in the 10-40 keV band. Existing soft X-ray telescopes could study this population up to only 10 keV, and, while NuSTAR (focusing on 3-24 keV) made great progress, it also left significant uncertainties in characterizing the hard X-ray population, crucial for calibrating current population synthesis models. This paper presents an in-depth analysis of simulations of two extragalactic surveys (deep and wide) with the High-Energy X-ray Probe (HEX-P), each observed for 2 Ms. Applying established source detection techniques, we show that HEX-P surveys will reach a flux of ~10-15 erg s-1 cm-2 in the 10-40 keV band, an order of magnitude fainter than current NuSTAR surveys. With the large sample of new hard X-ray detected sources (~2000), we showcase HEX-Ps ability to resolve more than 80% of the CXB up to 40 keV into individual sources. The expected precision of HEX-Ps resolved background measurement will allow us to distinguish between population synthesis models of SMBH growth. HEX-P will leverage accurate broadband (0.5-40 keV) spectral analysis and the combination of soft and hard X-ray colors to provide obscuration constraints even for the fainter sources, with the overall objective of measuring the Compton-thick fraction. With unprecedented sensitivity in the 10-40 keV band, HEX-P will explore the hard X-ray emission from AGN to flux limits never reached before, thus expanding the parameter space for serendipitous discoveries. Consequently, it is plausible that new models will be needed to capture the population HEX-P will unveil. [ABSTRACT FROM AUTHOR]

Semiconductor quantum dots embedded in photonic-crystal nanostructures have been the subject of intense study. In this context, quantum dots are often considered to be simple two-level emitters, i.e., the complexities arising from the internal fine structure are neglected. We show that due to the intricate spatial variations of the electric field polarization found in photonic crystal, the two orthogonal fine-structure states of quantum dots in general both couple significantly to a cavity mode, implying that the two-level description is not sufficient. As a consequence the emission dynamics and spectra, which are often recorded in experiments, are modified both in the weak- and strong-coupling regimes. The proposed effects are found to be significant for system parameters of current state-of-the-art photonic-crystal cavities. [ABSTRACT FROM AUTHOR]

Accreting neutron stars (NSs) represent a unique laboratory for probing the physics of accretion in the presence of strong magnetic fields (B > 108 G). Additionally, the matter inside the NS itself exists in an ultra-dense, cold state that cannot be reproduced in Earth-based laboratories. Hence, observational studies of these objects are a way to probe the most extreme physical regimes. Here we present an overview of the field and discuss the most important outstanding problems related to NS accretion. We show how these open questions regarding accreting NSs in both low-mass and high-mass X-ray binary systems can be addressed with the High-Energy X-ray Probe (HEX-P) via simulated data. In particular, with the broad X-ray passband and improved sensitivity afforded by a low X-ray background, HEX-P will be able to 1) distinguish between competing continuum emission models; 2) provide tighter upper limits on NS radii via reflection modeling techniques that are independent and complementary to other existing methods; 3) constrain magnetic field geometry, plasma parameters, and accretion column emission patterns by characterizing fundamental and harmonic cyclotron lines and exploring their behavior with pulse phase; 4) directly measure the surface magnetic field strength of highly magnetized NSs at the lowest accretion luminosities; as well as 5) detect cyclotron line features in extragalactic sources and probe their dependence on luminosity in the super-Eddington regime in order to distinguish between geometrical evolution and accretion-induced decay of the magnetic field. In these ways HEX-P will provide an essential new tool for exploring the physics of NSs, their magnetic fields, and the physics of extreme accretion. [ABSTRACT FROM AUTHOR]

Safety evaluation of a muramidase produced by a Trichoderma reesei strain (safe lineage), expressing a muramidase gene isolated from Acremonium alcalophilum is presented. Intended use in feed of this enzyme is as digestive aid in broiler chickens. Muramidase 007, was non-mutagenic and non-clastogenic in vitro , and no adverse effects were observed in 90-day subchronic toxicity studies in rats at doses up to 1132 mg TOS/kg body weight/day. The enzyme did not exhibit, in vitro , skin, nor eye irritation potential. Acute aquatic toxicity evaluated on daphnia and algae showed absence of effect of the enzyme at the standard doses tested. Muramidase 007 was fully tolerated by broiler chickens in a 6-weeks tolerance study showing no adverse effects in any of the dietary treatments (0, 1×, 5× and 10× maximum recommended dose). In conclusion, Muramidase 007 is found to be toxicologically inert, and there are no worker's safety concerns if standard precautions are instituted and a non-dusty formulation is employed. Muramidase 007 is well tolerated by the target species (broiler chickens) and cause no harm to the environment. The beneficial safety evaluation of Muramidase 007 is in line with this type of enzyme that is found ubiquitously in nature. [ABSTRACT FROM AUTHOR]

The article presents the study "A Population-Based Study of Measles, Mumps, and Rubella (MMR) Vaccination and Autism" by K. M. Madsen and colleagues. It examines the association of MMR vaccine to autism in children in a population-based cohort study in Denmark. It indicates that MMR vaccination is not associated with autistic spectrum disorder in children.

Studies whether the combined measles, mumps and rubella vaccination is associated with autism. Design of the study; Setting; Participants; Assessment of risk factors; Main outcome measures; Lack of evidence that the combined vaccination is associated with the development of autism.

Objective The neurobiological mechanisms mediating an increased risk to develop affective disorders remain poorly understood. In a group of individuals with a family history of major depressive ( MDD) or bipolar disorder ( BD), we investigated the microstructural properties of white matter fiber tracts, that is, cingulum bundle, uncinate fasciculus, anterior limb of the internal capsule, and corpus callosum, that facilitate the communication between brain regions implicated in affective disorders. Method Eighty-nine healthy mono- or dizygotic twins with a co-twin diagnosed with MDD or BD (high-risk) and 57 healthy twins with a co-twin with no familial history of affective disorders (low-risk) were included in a diffusion tensor imaging study. Result The high-risk group showed decreased fractional anisotropy ( FA), a measure of water diffusion directionality, and increased radial diffusivity in the anterior region of corpus callosum compared to the low-risk group. This abnormality was not associated with zygosity or type of depressive disorder of co-twin. Conclusion The observed decreased anterior callosal fiber FA in the high-risk group may be indicative of a compromised interhemispheric communication between left and right frontal regions critically involved in mood regulation. Reduced anterior callosal FA may act as a vulnerability marker for affective disorders in individuals at familial risk. [ABSTRACT FROM AUTHOR]

The purpose of this study was to determine the physical demands and match-induced impairments in physical performance in male elite Team Handball (TH) players in relation to playing position. Male elite TH field players were closely observed during 6 competitive seasons. Each player (wing players: WP, pivots: PV, backcourt players: BP) was evaluated during match-play using video recording and subsequently performing locomotion match analysis. A total distance of 3 627 ± 568 m (group means ± SD) was covered per match with a total effective playing time (TPT) of 53:51 ± 5:52 min:s, while full-time players covered 3 945 ± 538 m. The mean speed was 6.40 ± 1.01 km · h-1. High-intensity running constituted only 1.7 ± 0.9 % of TPT per match corresponding to 7.9 ± 4.9 % of the total distance covered. An average of 1 482.4 ± 312.6 activity changes per player (n = 82) with 53.2 ± 14.1 high-intensity runs were observed per match. Total distance covered was greater in BP (3 765 ± 532 m) and WP (3 641 ± 501 m) than PV (3 295 ± 495 m) (p < 0.05), and WP performed more high-intensity running (10.9 ± 5.7 % of total distance covered) than PV (8.5 ± 4.3 %, p < 0.05) and BP (6.2 ± 3.2 %, p < 0.01). The amount of high-intensity running was lower (p < 0.05) in the second (130.4 ± 38.4 m) than in the first half (155.3 ± 47.6 m) corresponding to a decrease of 16.2 %. In conclusion, modern male elite TH is a complex team sport that comprises several types of movement categories, which during match-play place moderate-to-high demands on intermittent endurance running capacity and where the amount of high-intensity running may be high during brief periods of the match. Signs of fatigue-related changes were observed in terms of temporary impaired physical performance, since the amount of high-intensity running was reduced in the second half. Notably, physical demands differed between playing positions, with WP demonstrating a more intensive activity pattern than BP and PV, respectively. [ABSTRACT FROM AUTHOR]