Search

Abstract Aims Veno‐arterial extracorporeal membrane oxygenation (VA‐ECMO) with profound left ventricular (LV) failure is associated with inadequate LV emptying. To unload the LV, VA‐ECMO can be combined with Impella CP (ECMELLA). We hypothesized that ECMELLA improves cardiac energetics compared with VA‐ECMO in a porcine model of cardiogenic shock (CS). Methods and results Land‐race pigs (weight 70 kg) were instrumented, including a LV conductance catheter and a carotid artery Doppler flow probe. CS was induced with embolization in the left main coronary artery. CS was defined as reduction of ≥50% in cardiac output or mixed oxygen saturation (SvO2) or a SvO2

Inter‐alpha‐trypsin inhibitor heavy chain 5 (ITIH5) has been identified as a metastasis suppressor gene in pancreatic cancer. Here, we analyzed ITIH5 promoter methylation and protein expression in The Cancer Genome Atlas (TCGA) dataset and three tissue microarray cohorts (n = 618), respectively. Cellular effects, including cell migration, focal adhesion formation and protein tyrosine kinase activity, induced by forced ITIH5 expression in pancreatic cancer cell lines were studied in stable transfectants. ITIH5 promoter hypermethylation was associated with unfavorable prognosis, while immunohistochemistry demonstrated loss of ITIH5 in the metastatic setting and worsened overall survival. Gain‐of‐function models showed a significant reduction in migration capacity, but no alteration in proliferation. Focal adhesions in cells re‐expressing ITIH5 exhibited a smaller and more rounded phenotype, typical for slow‐moving cells. An impressive increase of acetylated alpha‐tubulin was observed in ITIH5‐positive cells, indicating more stable microtubules. In addition, we found significantly decreased activities of kinases related to focal adhesion. Our results indicate that loss of ITIH5 in pancreatic cancer profoundly affects its molecular profile: ITIH5 potentially interferes with a variety of oncogenic signaling pathways, including the PI3K/AKT pathway. This may lead to altered cell migration and focal adhesion formation. These cellular alterations may contribute to the metastasis‐inhibiting properties of ITIH5 in pancreatic cancer.

Abstract Objective This study aims to elucidate the long‐term benefit of newborn screening (NBS) for individuals with long‐chain 3‐hydroxy‐acyl‐CoA dehydrogenase (LCHAD) and mitochondrial trifunctional protein (MTP) deficiency, inherited metabolic diseases included in NBS programs worldwide. Methods German national multicenter study of individuals with confirmed LCHAD/MTP deficiency identified by NBS between 1999 and 2020 or selective metabolic screening. Analyses focused on NBS results, confirmatory diagnostics, and long‐term clinical outcomes. Results Sixty‐seven individuals with LCHAD/MTP deficiency were included in the study, thereof 54 identified by NBS. All screened individuals with LCHAD deficiency survived, but four with MTP deficiency (14.8%) died during the study period. Despite NBS and early treatment neonatal decompensations (28%), symptomatic disease course (94%), later metabolic decompensations (80%), cardiomyopathy (28%), myopathy (82%), hepatopathy (32%), retinopathy (17%), and/or neuropathy (22%) occurred. Hospitalization rates were high (up to a mean of 2.4 times/year). Disease courses in screened individuals with LCHAD and MTP deficiency were similar except for neuropathy, occurring earlier in individuals with MTP deficiency (median 3.9 vs. 11.4 years; p = 0.0447). Achievement of dietary goals decreased with age, from 75% in the first year of life to 12% at age 10, and consensus group recommendations on dietary management were often not achieved. Interpretation While NBS and early treatment result in improved (neonatal) survival, they cannot reliably prevent long‐term morbidity in screened individuals with LCHAD/MTP deficiency, highlighting the urgent need of better therapeutic strategies and the development of disease course‐altering treatment.

Background Thresholds of aortic valve calcification (AVC) to define hemodynamically moderate aortic stenosis (AS) from mild are lacking. We aimed to establish a novel grading classification of AVC as quantified by computed tomography and determine its prognostic value. Methods and Results This study included 915 patients with at least mild AS (mean age 70±12 years, 30% women) from a multicenter prospective registry. All patients underwent Doppler‐echocardiography and noncontrast computed tomography within 3 months. Primary end point was the occurrence of all‐cause death. Receiver operating characteristic curves analyses were used to determine the sensitivity and specificity of sex‐specific thresholds of AVC to identify hemodynamically moderate AS. Optimal thresholds (ie, with best sensitivity/specificity) of AVC to distinguish moderate (aortic valve area 1.0–1.5 cm2 and mean gradient 20–39 mm Hg) from mild AS (aortic valve area >1.5 cm2 and mean gradient

Abstract Aquaculture industries face challenges in fish production, primarily due to disease occurrence. Clinical manifestations of these diseases often indicate a considerable advancement in the pathological process. Infected fish often experience morbidity, leading to compromised welfare and substantial economic losses for production facilities. Therefore, prophylaxis and early detection of the pathogens could allow the facility managers to intervene or treat the disease before clinical disease signs occur. For the first time, environmental DNA/RNA (collectively eNA) was used to detect the salmonid pathogen Aeromonas salmonicida subsp. salmonicida in the water hosting rainbow trout (Oncorhynchus mykiss). This took place under controlled experimental conditions, before the occurrence of clinical outcome and mortality. The concentration of bacteria in the water was determined by using a standard curve. To determine the window of possible intervention, bacterial concentration was measured from an early stage of disease and throughout when fish became moribund. Furthermore, the acute phase protein, serum amyloid A produced by rainbow trout, was detected in the water and was found to be up‐regulated 4 days post challenge. It was thereby shown that it is possible to detect strong immune responses in the fish in a non‐invasive manner. The detection of eNA from the water can be used as a tool to detect pathogens in the early phase of infection before the disease becomes severe. This will facilitate interventions to limit the disease and increase the welfare of the fish, which is becoming a requirement for a more sustainable and ethical animal production.

Background Wild‐type transthyretin amyloid (ATTRwt) cardiomyopathy is increasingly recognized in the development of heart failure. The link between cardiac performance, hemodynamics, and mitochondrial function in disease stages of ATTRwt has not previously been studied but may provide new insights into the pathophysiology and clinical performance of the patients. Methods and Results The study investigated 47 patients diagnosed with ATTRwt at Aarhus University Hospital, Denmark. Patients were stratified according to the disease stages of the National Amyloidosis Centre (NAC) as NAC I with low levels of NT‐proBNP (N‐terminal pro‐B‐type natriuretic peptide) (NAC I‐L, n=14), NAC I with high levels NT‐proBNP (NAC I‐H, n=20), and NAC II‐III (n=13). Exercise testing with simultaneous right heart catheterization was performed in all patients. Endomyocardial biopsies were collected from the patients and the mitochondrial oxidative phosphorylation capacity was assessed. All NAC disease groups, even in the NAC I‐L group, a significant abnormal increase in biventricular filling pressures were noted during exercise while the filling pressures was normal or near normal at rest. The inotropic response to exercise was reduced with diminished increase in cardiac output which was significantly more pronounced in the NAC I‐H (Diff. ‐2.4, 95% CI (−4.2: −0.7), P=0.00) and the NAC II‐III group (Diff: −3.1 L/min, 95% CI (−5.2: −1.1), P=0.00) compared with the NAC I‐L group. The pulmonary artery wedge pressure to cardiac output ratio at peak exercise was significantly different between NAC I‐L and NAC II‐III (Diff: 1.6 mm Hg*min/L, 95% CI (0.01:3.3, P=0.04)). Patients with ATTRwt had a reduced oxidative phosphorylation capacity which correlated to left ventricular mass but not to cardiac output capacity. Conclusions An abnormal restrictive left ventricle and right ventricle response to exercise was demonstrated, even present in patients with early‐stage ATTRwt. In more advanced disease stages a progressive impairment of the pressure‐flow relationship was noted. The myocyte energetics is deranged but not associated to the contractile reserve or restrictive filling characteristics in ATTRwt.

Abstract Outcomes of 2‐year survivours undergoing allo‐haematopoietic stem cell transplantation at Oslo University Hospital were retrospectively assessed with the objectives of identification of risk factors for late death as possible means for precautionary measures and interventions to improve long‐term survival. 421 patients with haematological malignancy, transplanted between 2005 and 2019, alive and free of disease after 2 years were included with data reported from The OUS‐HSCT registry. Median follow‐up was 6.2 years (2.016.1), and 232 patients (55%) were observed for minimum 5 years. The probability of being alive 5 and 10 years after HSCT was 86% and 76%. Primary risk factors for late death included initial diagnosis of age ≥ 60 years, chronic lymphocytic leukaemia (CLL), previous blood stream‐ or invasive fungal infection (BSI, IFI), and chronic graft‐versus‐host disease (cGVHD). Transplant‐related mortality (TRM) and relapse at 5 years were 9.0% and 7.7%, respectively. Two factors were associated with the latter: cytomegalovirus (CMV) seronegative donor and CLL. Compared with the age‐ and gender‐matched Norwegian general population, life expectancy was lower for each disease, except for CML. The prospect for the long‐term survival is good for 2‐year survivors of the allogeneic hematopoietic stem cell transplantation. However, life expectancy remains inferior to the age‐ and gender‐matched general population. Optimising prophylaxis and treatment for chronic GVHD, BSI and IFI are needed along with the improved adherence to guidelines for early detection of secondary malignancies. Measures to improve immune reconstitution, possibly the microbiota, and the use of CMV seropositive donors regardless of recipient sero‐status may be warranted and should be addressed in further studies.

Background Cardiac troponins are the preferred biomarkers for the diagnosis of acute myocardial infarction. Although sex‐specific 99th percentile thresholds of troponins are recommended in international guidelines, the clinical effect of their use is poorly investigated. The DANSPOT Study (The Danish Study of Sex‐ and Population‐Specific 99th percentile upper reference limits of Troponin) aims to evaluate the clinical effect of a prospective implementation of population‐ and sex‐specific diagnostic thresholds of troponins into clinical practice. Methods This study is a nationwide, multicenter, stepped‐wedge cluster‐randomized trial of the implementation of population‐ and sex‐specific thresholds of troponins in 22 of 23 clinical centers in Denmark. We established sex‐specific thresholds for 5 different troponin assays based on troponin levels in a healthy Danish reference population. Centers will sequentially cross over from current uniform manufacturer‐derived thresholds to the new population‐ and sex‐specific thresholds. The primary cohort is defined as patients with symptoms suggestive of acute coronary syndrome having at least 1 troponin measurement performed within 24 hours of arrival with a peak troponin value between the current uniform threshold and the new sex‐specific female and male thresholds. The study will compare the occurrence of the primary outcome, defined as a composite of nonfatal myocardial infarction, unplanned revascularization, and all‐cause mortality within 1 year, separately for men and women before and after the implementation of the new sex‐specific thresholds. Conclusions The DANSPOT Study is expected to show the clinical effects on diagnostics, treatment, and clinical outcomes in patients with myocardial infarction of implementing sex‐specific diagnostic thresholds for troponin based on a national Danish reference population. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT05336435.

Abstract Background A child's socioeconomic environment can shape central aspects of their life, including vulnerability to mental disorders. Negative environmental influences in youth may interfere with the extensive and dynamic brain development occurring at this time. Indeed, there are numerous yet diverging reports of associations between parental socioeconomic status (SES) and child cortical brain morphometry. Most of these studies have used single metric‐ or unimodal analyses of standard cortical morphometry that downplay the probable scenario where numerous biological pathways in sum account for SES‐related cortical differences in youth. Methods To comprehensively capture such variability, using data from 9758 children aged 8.9–11.1 years from the ABCD Study®, we employed linked independent component analysis (LICA) and fused vertex‐wise cortical thickness, surface area, curvature and grey‐/white‐matter contrast (GWC). LICA revealed 70 uni‐ and multimodal components. We then assessed the linear relationships between parental education, parental income and each of the cortical components, controlling for age, sex, genetic ancestry, and family relatedness. We also assessed whether cortical structure moderated the negative relationships between parental SES and child general psychopathology. Results Parental education and income were both associated with larger surface area and higher GWC globally, in addition to local increases in surface area and to a lesser extent bidirectional GWC and cortical thickness patterns. The negative relation between parental income and child psychopathology were attenuated in children with a multimodal pattern of larger frontal‐ and smaller occipital surface area, and lower medial occipital thickness and GWC. Conclusion Structural brain MRI is sensitive to SES diversity in childhood, with GWC emerging as a particularly relevant marker together with surface area. In low‐income families, having a more developed cortex across MRI metrics, appears beneficial for mental health.

Abstract Background Arabic‐speaking men are a sparsely investigated population in health promotion and disease prevention. This may hamper their ability to achieve the highest obtainable health due to less accessibility and acceptability of preventive measures. Aim We explored Arabic‐speaking (Palestinian, Iraqi and Somali) male immigrants' perceptions of preventive initiatives in general and such initiatives for cardiovascular diseases (CVD) in particular to understand how to address inequalities in engagement in prevention. Methods This qualitative study employed content analysis of semistructured interviews with 60–66‐year‐old Arabic‐speaking men living in Denmark. Supplementary, structured data, for example, health data, were collected. From June to August 2020, 10 men were interviewed. Findings Preventive initiatives were found ethically and culturally acceptable alongside personally and socially relevant; they were perceived as humanitarian and caring for the participants' health, respecting of their self‐determination and enabling their empowerment. Thus, the participants entreated that their fellow countrymen be assisted in achieving the prerequisite coping capabilities to address inequality in access, perceived acceptance and relevance. This led us to define one main category ‘Preventive initiatives ‐ Caring and humanitarian aid empower us’ with the underlying subcategories: ‘We are both hampered and strengthened by our basic assumptions’ and ‘We need help to achieve coping capabilities enabling us to engage in preventive initiatives’. Conclusion Prevention was perceived as acceptable and relevant. Even so, Arabic‐speaking men may be a hard‐to‐reach group due to their basic assumptions and impaired capabilities for engaging in prevention. Addressing inequality in accessibility, acceptability and relevance in regard to prevention may be promoted through a person‐centred approach embracing invitees' preferences, needs and values; and by strengthening invitees' health literacy through efforts at the structural, health professional and individual levels. Public Contribution This study was based on interviews. The interviewees were recruited as public representatives to assist us in building an understanding of Arabic‐speaking male immigrants' perceptions of preventive initiatives in general and preventive initiatives for CVD in particular.

Abstract Objective The objective was to examine the prevalence of pain from the face and temporomandibular joint (TMJ) and oral function in adolescents and contribute to more focus on this patient group. Methods A total of 957 adolescents were included in this study, in age cohorts 18, 16, and 14, scheduled for a dental recall examination. Clinical data were collected as a part of the routine clinical examination. All participants also answered a survey. Results Almost half of the participants had experienced facial pain in the last 3 months, headache being the most prevalent site reported. A significantly higher prevalence was found for females for all pain sites, and facial pain was significantly higher among the oldest. A reduced maximal incisal opening was significantly associated with higher reported facial/jaw pain, with increased mouth opening pain and chewing pain. Fifty‐seven percent of the participants reported the use of nonprescription painkillers, highest among females, and in the oldest age cohort, mainly caused by nonfeverish headaches. General health was found to be negatively correlated to facial pain, headache, pain intensity, and duration, pain upon oral function, and oral movement, as well as the use of nonprescriptive drugs. Females in the older age group, experience less quality of life in general, as they felt more worried, anxious, lonely, and sad, compared to males. Conclusion Facial‐ and TMJ pain was higher in females, and higher with increasing age. Almost half of the participants had experienced facial pain in the last 3 months, headache being the most prevalent site reported. General health was found to be negatively correlated to facial pain.

Abstract Plant–fungal interactions are ubiquitous across ecosystems and contribute significantly to plant ecology and evolution. All orchids form obligate symbiotic relationships with specific fungi for germination and early growth, and the distribution of terrestrial orchid species has been linked to occurrence and abundance of specific orchid mycorrhizal fungi (OMF) in the soil. The availability of OMF can therefore be a habitat requirement that is relevant to consider when establishing management and conservation strategies for threatened orchid species, but knowledge on the spatial distribution of OMF in soil is limited. We here studied the mycorrhizal associations of three terrestrial orchid species (Anacamptis pyramidalis, Orchis purpurea and Platanthera chlorantha) found in a local orchid diversity hotspot in eastern Denmark, and investigated the abundance of the identified mycorrhizal fungi in the surrounding soil. We applied ITS metabarcoding to samples of orchid roots, rhizosphere soil and bulk soil collected at three localities, supplemented with standard barcoding of root samples with OMF specific primers, and detected 22 Operational Taxonomic Units (OTUs) putatively identified as OMF. The three orchid species displayed different patterns of OMF associations, supporting the theory that association with specific fungi constitutes part of an orchid's ecological niche allowing co‐occurrence of many species in orchid‐rich habitats. The identified mycorrhizal partners in the basidiomycete families Tulasnellaceae and Ceratobasidiaceae (Cantharallales) were detected in low abundance in rhizosphere soil, and appeared almost absent from bulk soil at the localities. This finding highlights our limited knowledge of the ecology and trophic mode of OMF outside orchid tissues, as well as challenges in the detection of specific OMF with standard methods. Potential implications for management and conservation strategies are discussed.

Background Screening for cardiovascular disease is currently recommended before kidney transplantation. The present study aimed to validate the proposed algorithm by the American Heart Association (AHA‐2022) considering cardiovascular findings and outcomes in kidney transplant candidates, and to compare AHA‐2022 with the previous recommendation (AHA‐2012). Methods and Results We applied the 2 screening algorithms to an observational cohort of kidney transplant candidates (n=529) who were already extensively screened for coronary heart disease by referral to cardiac computed tomography between 2014 and 2019. The cohort was divided into 3 groups as per the AHA‐2022 algorithm, or into 2 groups as per AHA‐2012. Outcomes were degree of coronary heart disease, revascularization rate following screening, major adverse cardiovascular events, and all‐cause death. Using the AHA‐2022 algorithm, 69 (13%) patients were recommended for cardiology referral, 315 (60%) for cardiac screening, and 145 (27%) no further screening. More patients were recommended cardiology referral or screening compared with the AHA‐2012 (73% versus 53%; P

Abstract Background An individual's overall burden of behavioural and emotional problems across childhood is associated with increased likelihood of later mental health conditions. However, the relative extent of behavioural versus emotional problems ‐ that is, the extent to which the domains are differentiated from one another ‐ may provide additional information about who is at risk of developing a mental health condition. Here, we seek to validate differentiation as an independent predictor of later mental health conditions, and to explore its aetiology. Methods We analysed data from ~79,000 children in the population‐based Norwegian Mother, Father, and Child Cohort Study, and linked health‐care registries. In preregistered analyses, we modelled the extent and rate of differentiation of behavioural and emotional problems between ages 1.5–5 years, and estimated associations with later symptoms (age 8) and diagnoses (after age 8). We also explored the aetiology of differentiation by estimating associations with early life exposures and, in a subset of 23,945 full siblings, assessing the impact of accounting for unobserved familial confounding. Results Differentiation of behavioural and emotional problems was associated with later symptoms and diagnoses of mental health conditions, independent of total problems. Maternal at‐risk drinking (β = 0.04 [0.02, 0.06]) and parental relationship problems (β = 0.04 [0.02, 0.05]) were associated with higher behavioural relative to emotional problems at age 5. Maternal prenatal distress (|β| = 0.04 [0.03, 0.06]), concurrent distress (|β| = 0.04 [0.02, 0.06]) and parental education (|β| = 0.05 [0.04, 0.07]) predicted higher emotional relative to behavioural problems at age 5. Estimates for maternal prenatal distress and at‐risk drinking were consistent across both unadjusted and adjusted analyses accounting for unobserved familial risk. Conclusions Differentiation of behavioural and emotional problems in early childhood represents a valid source of inter‐individual variability linked to the later emergence of psychopathology and may be relevant for early detection and prevention strategies for mental health.

Abstract Aims Familial hypertrophic cardiomyopathy (HCM) is the most common form of inherited cardiac disease. It is characterized by myocardial hypertrophy and diastolic dysfunction, and can lead to severe heart failure, arrhythmias, and sudden cardiac death. Cardiac fibrosis, defined by excessive accumulation of extracellular matrix (ECM) components, is central to the pathophysiology of HCM. The ECM proteoglycan lumican is increased during heart failure and cardiac fibrosis, including HCM, yet its role in HCM remains unknown. We provide an in‐depth assessment of lumican in clinical and experimental HCM. Methods Left ventricular (LV) myectomy specimens were collected from patients with hypertrophic obstructive cardiomyopathy (n = 15), and controls from hearts deemed unsuitable for transplantation (n = 8). Hearts were harvested from a mouse model of HCM; Myh6 R403Q mice administered cyclosporine A and wild‐type littermates (n = 8–10). LV tissues were analysed for mRNA and protein expression. Patient myectomy or mouse mid‐ventricular sections were imaged using confocal microscopy, direct stochastic optical reconstruction microscopy (dSTORM), or electron microscopy. Human foetal cardiac fibroblasts (hfCFBs) were treated with recombinant human lumican (n = 3) and examined using confocal microscopy. Results Lumican mRNA was increased threefold in HCM patients (P

Abstract Background Achieving complete remission (CR) is the main goal in AML treatment and a prerequisite for successful autologous stem cell transplantation (ACT). Methods Comparing results of peripheral blood ACT in patients with AML in CR1 attained following 1 versus 2 chemotherapy courses transplanted in 2000–2019. Results Patients 1532 (84%) with one and 293 (16%) patients with two induction chemotherapies courses (a total of 1825 patients) were included in the study. Follow‐up was 7.9 (95% CI: 7.4–8.4) and 7.7 (95% CI: 7.0–8.6) years (p = 0.8). Time from diagnosis to ACT was 4.7 (range, 3.9–5.8) versus 5.7 (range, 4.7–7.1) months (p

Abstract Background Prognostic markers of survival have been identified in wild‐type transthyretin amyloidosis (ATTRwt), but limited data exist with respect to hospitalizations with worsening heart failure (WHF). Predictive markers of WHF have yet to be identified. Methods From April 2017 to February 2021, 104 patients with ATTRwt were diagnosed and prospectively followed from the time of diagnosis to the time of death or the censoring date of 1 February 2021. Baseline patient characteristics, biomarkers, and advanced echocardiography were used to predict hospitalization with WHF. Results During the median follow‐up period of 23 months, 51% of patients were hospitalized due to WHF. Seventy‐three per cent of patients with WHF were admitted at least twice. Patients with WHF during the first year had significantly poorer survival (P

Key Clinical Message There is no effective treatment that reduces both the severity and duration of a common cold episode. SJP − 002 (naproxen and fexofenadine) reduced symptom severity by two‐third, and the duration of the common cold episode approximately by half. Abstract The common cold is one of the most frequently experienced immune‐related complaints. At present, available treatments have limited efficacy in inhibiting symptoms associated with upper respiratory tract infection, nor do they significantly shorten the duration of common cold episodes. Four case reports are presented of individuals with a common cold. Three of them self‐administered the combination of naproxen and fexofenadine (SJP − 002). Results of one individual were compared to her spouse, who did not take SJP − 002 to treat common cold, while two other individuals took SJP − 002 and compared symptom severity with another common cold episode they experienced previously without taking SJP − 002. SJP − 002 reduced the severity of symptoms associated with upper respiratory tract infection by two‐third and reduced the duration of the common cold episode approximately by half. In conclusion, SJP − 002 reduced the severity and duration of common cold episodes. These findings warrant further investigation of SJP − 002 in double‐blind, placebo‐controlled clinical trials.

Abstract Background Slaughterhouses can provide valuable information about animal diseases and their epidemiology. Objectives The current study was designed to examine the health and economic burden of pathological lesions in livers and lungs of slaughtered sheep at Mosul abattoir, Iraq. Methods Mosul abattoir records for sheep slaughtered between 2011 and 2013 were considered for inclusion in this study. The direct financial loss due to liver and lung lesions was estimated considering the average number of slaughtered sheep per year, the average percentage of liver lesions per year, and the average percentage of lung lesions per year. Monetary values of the liver and lung were obtained from local butcheries. Results The analysis indicated that the percentage of lesions observed in the liver and lung per year was 6.9% and 5.8%, respectively. Hydatid cyst followed by hepatitis was the most frequent lesions identified in the liver, while pneumonia then hydatid cyst were detected in the lung, followed by worms, abscess, and miscellaneous lesions. Hydatid cyst was the most frequently observed lesions. The average total loss was 35,232 USD per year (mostly due to liver lesions), with ±7046 USD sensitivity to the price change. Conclusions The percentage of lesions observed in the liver and lung per year is not negligible and can cause considerable economic losses.

Abstract The purpose of this study was to investigate the effects of loading conditions and left ventricular (LV) contractility on mitral annular dynamics. In 10 anesthetized pigs, eight piezoelectric transducers were implanted equidistantly around the mitral annulus. High‐fidelity catheters measured left ventricular pressures and the slope of the end‐systolic pressure‐volume relationship (Ees) determined LV contractility. Adjustments of pre‐ and afterload were done by constriction of the inferior caval vein and occlusion of the descending aorta. Mitral annulus area indexed to body surface area (MAAi), annular circularity index (ACI), and non‐planarity angle (NPA) were calculated by computational analysis. MAAi was more dynamic in response to loading interventions than ACI and NPA. However, MAAi maximal cyclical reduction (−Δr) and average deformational velocity (−v¯) did not change accordingly (p = 0.31 and p = 0.22). Reduced Ees was associated to attenuation in MAAi‐Δr and MAAi‐v¯ (r2 = 0.744; p = 0.001 and r2 = 0.467; p = 0.029). In conclusion, increased cardiac load and reduced LV contractility may cause deterioration of mitral annular dynamics, likely impairing coaptation and increasing susceptibility to valvular incompetence.

Background Thiamine supplementation has demonstrated protective effects in a mouse model of cardiac arrest. The aim of this study was to investigate the neuroprotective effects of thiamine in a clinically relevant large animal cardiac arrest model. The hypothesis was that thiamine reduces neurological injury evaluated by neuron‐specific enolase levels. Methods and Results Pigs underwent myocardial infarction and subsequently 9 minutes of untreated cardiac arrest. Twenty minutes after successful resuscitation, the pigs were randomized to treatment with either thiamine or placebo. All pigs underwent 40 hours of intensive care and were awakened for assessment of functional neurological outcome up until 9 days after cardiac arrest. Nine pigs were included in both groups, with 8 in each group surviving the entire intensive care phase. Mean area under the curve for neuron‐specific enolase was similar between groups, with 81.5 μg/L per hour (SD, 20.4) in the thiamine group and 80.5 μg/L per hour (SD, 18.3) in the placebo group, with an absolute difference of 1.0 (95% CI, −57.8 to 59.8; P=0.97). Likewise, there were no absolute difference in neurological deficit score at the end of the protocol (2 [95% CI, −38 to 42]; P=0.93). There was no absolute mean group difference in lactate during the intensive care period (1.1 mmol/L [95% CI, −0.5 to 2.7]; P=0.16). Conclusions In this randomized, blinded, placebo‐controlled trial using a pig cardiac arrest model with myocardial infarction and long intensive care and observation for 9 days, thiamine showed no effect in changes to functional neurological outcome or serum levels of neuron‐specific enolase. Thiamine treatment had no effect on lactate levels after successful resuscitation.

Abstract Aim This study describes the examination practices and clinical evaluation processes that Registered Nurses in Norway perform in the community healthcare sector. Design A qualitative exploratory design. Methods Twenty interviews were conducted with Registered Nurses employed in the community healthcare sector in Norway. The data were analysed using a thematic analysis. Results We found four major themes: (1) evaluations are embedded in nurses’ daily work, (2) significance of a Registered Nurse's clinical competency, (3) different tasks require various roles and (4) access to resources and equipment. Registered Nurses possess several skills in a range of different examination techniques and clinical evaluation processes in the community healthcare sector. They perform complex assessments in their daily work and must rely on other healthcare professionals, facilities and equipment to provide high‐quality care. Ongoing education and training will enable Registered Nurses to complete accurate assessments in their community healthcare practice.

Abstract Purpose We investigate the impact of severe sensorineural hearing loss (SNHL) and for the first time evaluate the effect of unilateral versus bilateral SNHL on intellectual outcome in a cohort of children with embryonal brain tumors treated with and without radiation. Methods Data were from 94 childhood survivors of posterior fossa (PF) embryonal brain tumors who were treated with either: (1) chemotherapy alone (n = 16, 7.11 [3.41] years, 11M/5F), (2) standard‐dose craniospinal irradiation (CSI) and/or large boost volumes (n = 44, 13.05 [3.26] years, 29M/15F), or (3) reduced‐dose CSI with a boost restricted to the tumor bed (n = 34, 11.07 [3.80] years, 19M/15F). We compared intellectual outcome between children who: (1) did and did not develop SNHL and (2) developed unilateral versus bilateral SNHL. A Chang grade of ≥2b that required the use of a hearing aid was considered severe SNHL. Comparisons were made overall and within each treatment group separately. Results Patients who developed SNHL had lower full scale IQ (p = 0.007), verbal comprehension (p = 0.003), and working memory (p = 0.02) than patients without SNHL. No differences were observed between patients who had unilateral versus bilateral SNHL (all p > 0.05). Patients treated with chemotherapy alone who developed SNHL had lower mean working memory (p = 0.03) than patients who did not develop SNHL. Among patients treated with CSI, no IQ indices differed between those with and without SNHL (all p > 0.05). Conclusions Children treated for embryonal brain tumors who develop severe SNHL have lower intellectual outcome than patients with preserved hearing: this association is especially profound in young children treated with radiation sparing approaches. We also demonstrate that intellectual outcome is similarly impaired in patients who develop unilateral versus bilateral SNHL. These findings suggest that early intervention to preserve hearing is critical.

Objective With a vaccine effectiveness of 95% for preventing coronavirus disease 2019 (COVID‐19), Pfizer‐BioNTech BNT162b2 (BNT162b2) was the first vaccine against severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) to be approved. However, immunosuppressive therapy was an exclusion criterion in the phase 3 trial that led to approval. Thus, extrapolation of the trial results to patients with rheumatic diseases treated with immunosuppressive drugs warrants caution. Methods Patients with systemic lupus erythematosus (SLE; n = 61) and rheumatoid arthritis (RA; n = 73) were included from the COPANARD (Corona Pandemic Autoimmune Rheumatic Disease) cohort, followed since the beginning of the COVID‐19 pandemic. Patients received the BNT162b2 vaccine between December 2020 and April 2021. All patients had total antibodies against SARS‐CoV‐2 measured before vaccination and 1 week after the second vaccination (VITROS Immunodiagnostic Products). Results Of 134 patients (median age, 70 years), 77% were able to mount a detectable serological response to the vaccine. Among patients treated with rituximab, only 24% had detectable anti–SARS‐CoV‐2 antibodies in their serum after vaccination. The time since the last rituximab treatment did not seem to influence the vaccine response. No significant difference was observed between patients with RA or SLE when adjusting for treatment, and no correlation between antibody levels and age was detected (r = −0.12; P = 0.18). Conclusion Antibody measurements against SARS‐CoV‐2 in patients with RA and SLE after two doses of the BNT162b2 vaccine demonstrated that 23% of patients could not mount a detectable serological response to the vaccine. B cell–depleting therapy (BCDT) is of specific concern, and our findings call for particular attention to the patients receiving BCDT.

Abstract The main objective of the study conducted here was to estimate the concentration of 2,3‐Bisphosphoglycerate (2,3‐BPG), 1,3‐Bisphosphoglycerate (1,3‐BPG), bisphospho‐glycerate mutase (BPGM) and 3‐phosphoglycerate (3PG) in cattle clinically diagnosed with acute ruminal acidosis. A secondary objective was to examine the physical and chemical characteristics of the ruminal fluid in affected cattle. A total of 20 cattle clinically diagnosed with acute ruminal acidosis and eight clinically normal cattle were included in this study. The results showed that decrease of ruminal pH changed the ruminal fluid colour, odour and consistency, as well as decreased the sedimentation time, increased the methylene blue reduction time, and decreased ruminal microflora motility. The study indicated that the concentration of 2,3‐BPG, BPGM and BPGP decreased with the decrease of ruminal pH, while 3‐PG concentration was not affected with the decrease of ruminal pH. In conclusion, 2,3‐BPG could play a role in the pathogenesis of ruminal acidosis, and thus, the intravenous administration of sodium bicarbonate is important, particularly in severe cases, to correct any systemic acidosis that can decrease 2,3‐BPG concentration and results in tissue hypoxia.

Abstract Background Several risk factors for asthma have been proposed; however, the causality of these associations is sometimes unclear. Mendelian randomization is a powerful epidemiological approach that can help elucidate the causality of risk factors. The aim of the present study was to identify causal risk factors for asthma through Mendelian Randomization studies. Methods A systematic search of PubMed and EMBASE was conducted, to identify studies investigating risk factors for asthma or respiratory allergies through Mendelian Randomization. When two or more studies investigated the same risk factor a meta‐analysis was conducted. Of 239 studies initially identified, 41 were included. Results A causal association between adiposity and adult asthma risk was found in 10 out of 12 studies with a summary risk ratio of 1.05 per kg/m2 increase in BMI (95% CI: 1.03–1.07). Puberty timing (n = 3), alcohol (n = 2), and linoleic acid (n = 1) had causal effects on asthma risk, while vitamins/minerals (n = 6) showed no consistent effect on asthma. The effect of smoking on adult asthma conflicted between studies. Several of the significant associations of asthma with immune related proteins (n = 5) and depression (n = 2) investigated through multiple traits analyses could generally benefit from replications in independent datasets. Conclusion This systematic review and meta‐analysis found evidence for causal effects of adiposity, puberty timing, linoleic acid, alcohol, immune related proteins, and depression on risk of asthma.

Summary Virus detection methods are important to cope with the SARS‐CoV‐2 pandemics. Apart from the lung, SARS‐CoV‐2 was detected in multiple organs in severe cases. Less is known on organ tropism in patients developing mild or no symptoms, and some of such patients might be missed in symptom‐indicated swab testing. Here, we tested and validated several approaches and selected the most reliable RT‐PCR protocol for the detection of SARS‐CoV‐2 RNA in patients’ routine diagnostic formalin‐fixed and paraffin‐embedded (FFPE) specimens available in pathology, to assess (i) organ tropism in samples from COVID‐19‐positive patients, (ii) unrecognized cases in selected tissues from negative or not‐tested patients during a pandemic peak, and (iii) retrospectively, pre‐pandemic lung samples. We identified SARS‐CoV‐2 RNA in seven samples from confirmed COVID‐19 patients, in two gastric biopsies, one small bowel and one colon resection, one lung biopsy, one pleural resection and one pleural effusion specimen, while all other specimens were negative. In the pandemic peak cohort, we identified one previously unrecognized COVID‐19 case in tonsillectomy samples. All pre‐pandemic lung samples were negative. In conclusion, SARS‐CoV‐2 RNA detection in FFPE pathology specimens can potentially improve surveillance of COVID‐19, allow retrospective studies, and advance our understanding of SARS‐CoV‐2 organ tropism and effects.

Abstract Background Knowledge is lacking about how to increase uptake among people with type 2 diabetes (T2D) invited to preventive initiatives like cardiovascular screening. Aim To explore how to improve participation of people with T2D in cardiovascular screening using patient and public involvement (PPI). Methods Patient and public involvement was included in a qualitative research design. From April to October 2019, we invited 40‐ to 60‐year‐old people with T2D (n = 17) to individual consultative meetings, using an interviewing approach. Before the interviews, participants were asked to read a proposed invitation letter to be used in a cardiovascular screening programme. Inductive content analysis was undertaken. Results Participants considered cardiovascular screening important and beneficial from both a personal and social perspective. We found that the relational interaction between the person with T2D and the health‐care professional was key to participation and that nudging captured through the design of the screening programme and the wording of the invitation letter was requested. Conclusion In preventive initiatives perceived as meaningful by the invitee, a focus on recruitment is crucial to facilitate participation. This study contributed with knowledge about how to promote participation by involving health‐care professionals in recruitment initiatives and through nudging. This knowledge may assist researchers, policymakers and ethicists' understanding and assessment of the ethical appropriateness and public acceptability of nudging in cardiovascular screening. Patient or public contribution By consulting 17 people with T2D, we are now in a position to suggest how a screening initiative should be altered because tools to improve uptake have been identified.

Abstract In two cases, cell‐based noninvasive prenatal testing (cbNIPT) detected pathogenic copy number variations (CNVs) in the fetal genome. cbNIPT may potentially be an improved noninvasive alternative for the detection of smaller CNVs.

Abstract Repeated climatic and vegetation changes during the Pleistocene have shaped biodiversity in Northern Europe including Denmark. The Northern Birch Mouse (Sicista betulina) was one of the first small rodent species to colonize Denmark after the Late Glacial Maximum. This study analyses complete mitochondrial genomes and two nuclear genes of the Northern Birch Mouse to investigate the phylogeographical pattern in North‐western Europe and test whether the species colonized Denmark through several colonization events. The latter was prompt by (i) the present‐day distinct northern and southern Danish distribution and (ii) the subfossil record of Northern Birch Mouse, supporting early Weichselian colonization. Samples from Denmark, Norway, Sweden, Russia, Latvia, Estonia, and Slovakia were included. Mitogenomes were obtained from 54 individuals, all representing unique mitogenomes supporting high genetic variation. Bayesian phylogenetic analysis identified two distinct evolutionary linages in Northern Europe diverging within the Elster glaciation period. The results of the two nuclear genomes showed lower genetic differentiation but supported the same evolutionary history. This suggests an allopatric origin of the clades followed by secondary contact. Individuals from southern Denmark were only found in one clade, while individuals from other areas, including northern Denmark, were represented in both clades. Nevertheless, we found no evidence for repeated colonization's explaining the observed fragmented distribution of the species today. The results indicated that the mitogenome pattern of the Northern Birch Mouse population in southern Denmark was either (i) due to the population being founded from northern Denmark, (ii) a result of climatic and anthropogenic effects reducing population size increasing genetic drift or (iii) caused by sampling bias.