Neonatal Ultrasound and Radiographic Markers of Hip Dysplasia in Young Adults.

OBJECTIVES: To examine radiologic outcomes at skeletal maturity of sonographically normal, immature, mildly, and severely dysplastic newborn hips. METHODS: During 1988 to 1990, 11 925 newborns were enrolled in a randomized controlled trial examining screening strategies for developmental hip dysplasia. In total, 4469 were invited to clinical and radiologic follow-up 18 years later, of which 1735 had received neonatal ultrasound. Radiographic markers for dysplasia in left adult hips included the center-edge (CE) angle. RESULTS: At follow-up, 984 of 1735 (56.7%) with newborn ultrasound met, of which 966 (614 females) had valid radiographs and were thus included. For females, 34 (10.2%) and 1 (0.3%) of the 332 sonographically normal left neonatal hips were judged borderline (20°≤ CE <25°) or dysplastic (CE <20°) at skeletal maturity respectively. Corresponding numbers were 36 (19.7%) and 3 (1.6%) of the 183 immature, 12 (15.6%) and 2 (2.6%) of the 77 mildly dysplastic, and 3 (13.6%) and 3 (13.6%) of the 22 severely dysplastic neonatal left hips (P ≤ .001). In males, no associations were found. In females, adult joint hypermobility was associated with sonographic neonatal hip instability (P = .046), as well as with adult acetabular dysplasia (P = .024). CONCLUSIONS: Significant associations between neonatal hip phenotypes and adult dysplasia were revealed in females. This indicates the possibility of different mechanisms affecting the course of developmental dysplasia of the hip for females and males, prompting consideration of prolonged clinical and radiologic follow-up for females with dysplastic neonatal hips. Results in males are limited by low numbers of dysplastic hips. The significance of joint hypermobility warrants further investigation.

Co-occurring orchid species associated with different low-abundance mycorrhizal fungi from the soil in a high-diversity conservation area in Denmark.

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.

Translation, cross-cultural adaption, validity and reliability of a composite physical function scale for adults aged 65 + years in a Danish context.

BACKGROUND: To prevent or postpone dependence on help in everyday activities, early identification of adults aged 65 + years at risk of functional decline or with progressing functional decline is essential. The American Composite Physical Function (CPF) scale was developed to detect and prevent this age-conditioned decline. In this study, the aim was to translate and adapt the scale into a Danish version and assess the validity and reliability in Danish adults aged 65 + years. METHODS: A forward-backward translation procedure was used, followed by an expert panel review to finalise the Danish version of the CPF scale. In the subsequent pre-test, three-step cognitive interviews and hypotheses testing were performed to evaluate the validity, and a test-retest was done to assess reliability. RESULTS: In the pre-test, 47 adults participated in three-step cognitive interviews, and 45 adults answered an online version of the scale. In terms of content validity, the scale was relevant and easy to answer, although many informants skipped the instruction to the questionnaire, which may negatively impact face validity. Construct validity showed a significant difference in CPF scores in adults aged 65 + years by residence and activity level and a decreasing CPF score with increasing age. The reliability test showed an excellent kappa (0.92). CONCLUSION: The scale covering daily activities helps to identify adults aged 65 + years with reduced physical functions or at risk of loss of independence. Further research is needed to assess the CPF predictive value for adults aged 65 + years at risk of or with a progressing physical decline.

[Hip dysplasia in infants ­ screening, treatment and follow-up]. / Hofteleddsdysplasi hos spedbarn ­ screening, behandling og oppfølging.

BACKGROUND: Hip dysplasia occurs in up to 3 % of neonates and if untreated can lead to dislocated hip, osteoarthritis and the need for a hip prosthesis. The study aimed to identify routines for ultrasound screening, treatment and follow-up of hip dysplasia in Norwegian hospitals. MATERIAL AND METHOD: An online questionnaire was sent to radiologists responsible for paediatric examinations at all hospitals with paediatric departments. INTERPRETATION: Routines for screening, treatment and follow-up of hip dysplasia varied to a considerable degree between the hospitals.

Personalised exercise therapy and self-management support for people with multimorbidity: Development of the MOBILIZE intervention.

BACKGROUND: To our knowledge, there is no intervention which includes personalised exercise therapy and self-management support for people with multimorbidity, although these interventions may be as effective as for people with single chronic conditions. Therefore, we developed a novel intervention, including personalised exercise therapy and self-management support for people with multimorbidity. METHODS: We followed the Medical Research Council framework and conducted one scoping review, five systematic reviews, two registry-based studies, one qualitative interview study and a mixed-methods feasibility study. Following an iterative approach, together with feedback from people with multimorbidity and relevant stakeholders, we developed the MOBILIZE intervention. RESULTS: The intervention included 24 (60 minutes) sessions of personalised exercise therapy and 24 (30 minutes) sessions of self-management support twice a week for 12 weeks, delivered in small groups by specifically trained physiotherapists. The intervention targets physiological, psychosocial, behavioural, and contextual factors to improve health-related quality of life and physical function in people living with multimorbidity. CONCLUSIONS: We developed a personalised exercise therapy and self-management support programme for people with multimorbidity. The intervention will be tested for its safety and effectiveness in a randomised controlled trial.

Compensation claims in pediatric orthopedics in Norway between 2012 and 2018: a nationwide study of 487 patients.

Background and purpose - In Norway all compensation claims based on healthcare services are handled by a government agency (NPE, Norsk Pasientskade Erstatning). We provide an epidemiological overview of claims within pediatric orthopedics in Norway, and identify the most common reasons for claims and compensations.Patients and methods - All compensation claims handled by NPE from 2012 to 2018 within pediatric orthopedics (age 0 to 17 years) were reviewed. Data were analyzed with regard to patient demographics, diagnoses, type of injury, type of treatment, reasons for granted compensation, and total payouts.Results - 487 compensation claims (259 girls, 228 boys) within orthopedic surgery in patients younger than 18 years at time of treatment were identified. Mean age was 12 years (0-17). 150 out of 487 claims (31%) resulted in compensation, including 79 compensations for inadequate treatment, 58 for inadequate diagnostics, 12 for infections, and 1 based on the exceptional rule. Total payouts were US$8.45 million. The most common primary diagnoses were: upper extremity injuries (26%), lower extremity injuries (24%), congenital malformations and deformities (12%), spine deformities (11%), disorders affecting peripheral joints (9%), chondropathies (6%), and others (12%).Interpretation - Most claims were submitted and granted for mismanagement of fractures in the upper and lower extremity, and mismanagement of congenital malformations and disorders of peripheral joints. Knowledge of the details of malpractice claims should be implemented in educational programs and assist pediatric orthopedic surgeons to develop guidelines in order to improve patient safety and quality of care.

Fungal diversity driven by bark features affects phorophyte preference in epiphytic orchids from southern China.

Epiphytic orchids exhibit varying degrees of phorophyte tree specificity. We performed a pilot study to investigate why epiphytic orchids prefer or avoid certain trees. We selected two orchid species, Panisea uniflora and Bulbophyllum odoratissimum co-occurring in a forest habitat in southern China, where they showed a specific association with Quercus yiwuensis and Pistacia weinmannifolia trees, respectively. We analysed a number of environmental factors potentially influencing the relationship between orchids and trees. Difference in bark features, such as water holding capacity and pH were recorded between Q. yiwuensis and P. weinmannifolia, which could influence both orchid seed germination and fungal diversity on the two phorophytes. Morphological and molecular culture-based methods, combined with metabarcoding analyses, were used to assess fungal communities associated with studied orchids and trees. A total of 162 fungal species in 74 genera were isolated from bark samples. Only two genera, Acremonium and Verticillium, were shared by the two phorophyte species. Metabarcoding analysis confirmed the presence of significantly different fungal communities on the investigated tree and orchid species, with considerable similarity between each orchid species and its host tree, suggesting that the orchid-host tree association is influenced by the fungal communities of the host tree bark.

Athletes with valvular heart disease and competitive sports: a position statement of the Sport Cardiology Section of the European Association of Preventive Cardiology.

This article provides an overview of the recommendations from the Sports Cardiology section of the European Association of Preventive Cardiology on sports participation in individuals with valvular heart disease (VHD). The aim of these recommendations is to encourage regular physical activity including sports participation, with reasonable precaution to ensure a high level of safety for all affected individuals. Valvular heart disease is usually an age-related degenerative process, predominantly affecting individuals in their fifth decade and onwards. However, there is an increasing group of younger individuals with valvular defects. The diagnosis of cardiac disorders during routine cardiac examination often raises questions about on-going participation in competitive sport with a high dynamic or static component and the level of permissible physical effort during recreational exercise. Although the natural history of several valvular diseases has been reported in the general population, little is known about the potential influence of chronic intensive physical activity on valve function, left ventricular remodelling pulmonary artery pressure, and risk of arrhythmia. Due to the sparsity of data on the effects of exercise on VHD, the present document is largely based on clinical experience and expert opinion.

Temporal turnover in mycorrhizal interactions: a proof of concept with orchids.

Temporal turnover events in biotic interactions involving plants are rarely assessed, although such changes might afford a considerable acclimation potential to the plant. This could enable fairly rapid responses to short-term fluctuations in growth conditions as well as lasting responses to long-term climatic trends. Here, we present a classification of temporal turnover encompassing 11 possible scenarios. Using orchid mycorrhiza as a study model, we show that temporal changes are common, and discuss under which conditions temporal turnover of fungal symbiont is expected. We provide six research questions and identify technical challenges that we deem most important for future studies. Finally, we discuss how the same framework can be applied to other types of biotic interactions.

Partial mycoheterotrophy is common among chlorophyllous plants with Paris-type arbuscular mycorrhiza.

BACKGROUND AND AIMS: An arbuscular mycorrhiza is a mutualistic symbiosis with plants as carbon providers for fungi. However, achlorophyllous arbuscular mycorrhizal species are known to obtain carbon from fungi, i.e. they are mycoheterotrophic. These species all have the Paris type of arbuscular mycorrhiza. Recently, two chlorophyllous Paris-type species proved to be partially mycoheterotrophic. In this study, we explore the frequency of this condition and its association with Paris-type arbuscular mycorrhiza. METHODS: We searched for evidence of mycoheterotrophy in all currently published 13C, 2H and 15N stable isotope abundance patterns suited for calculations of enrichment factors, i.e. isotopic differences between neighbouring Paris- and Arum-type species. We found suitable data for 135 plant species classified into the two arbuscular mycorrhizal morphotypes. KEY RESULTS: About half of the chlorophyllous Paris-type species tested were significantly enriched in 13C and often also enriched in 2H and 15N, compared with co-occurring Arum-type species. Based on a two-source linear mixing model, the carbon gain from the fungal source ranged between 7 and 93 % with ferns > horsetails > seed plants. The seed plants represented 13 families, many without a previous record of mycoheterotrophy. The 13C-enriched chlorophyllous Paris-type species were exclusively herbaceous perennials, with a majority of them thriving on shady forest ground. CONCLUSIONS: Significant carbon acquisition from fungi appears quite common and widespread among Paris-type species, this arbuscular mycorrhizal morphotype probably being a pre-condition for developing varying degrees of mycoheterotrophy.

Decreased number of colonic tuft cells in quiescent ulcerative colitis patients.

BACKGROUND: Colonic tuft cells are epithelial chemosensory cells involved in barrier integrity, modulation of inflammatory responses and gut homeostasis. Recent evidence indicates an involvement of tuft cells in ulcerative colitis pathogenesis, though mechanisms remain largely unknown.Here, we quantified the colonic tuft cell population in patients with quiescent ulcerative colitis as compared to patients without identified colonic disease (controls). METHODS: In this retrospective study, we obtained endoscopic colonic sigmoid biopsies from 14 patients with quiescent ulcerative colitis and from 17 controls. In a blinded central-reading design, we identified tuft cells by immunohistochemistry using a cyclooxygenase-1 antibody as a marker and performed a simple counting by visual inspection. Poisson regression was employed for statistics and results were adjusted for gender, age and smoking status. RESULTS: Ulcerative colitis patients demonstrated a 55% reduced tuft cell count in colonic mucosa compared with the control group (95% confidence limit: range 31-71%, P = 0.0002). Ulcerative colitis patients had a mean tuft cells count of 46 tuft cells/mm2 (95% CI, 36-59), while controls demonstrated a mean of 104 tuft cells/mm2 (95% CI, 79-136). No interactions of other covariates, such as age, smoking status, total duration of ulcerative colitis disease and duration of clinical remission prior to study inclusion were detected between ulcerative colitis patients and controls. CONCLUSION: Quiescent ulcerative colitis patients have a relatively low number of colonic tuft cells. Further studies are warranted to explore the potential involvement of tuft cells in ulcerative colitis pathogenesis.

Altered Structural Expression and Enzymatic Activity Parameters in Quiescent Ulcerative Colitis: Are These Potential Normalization Criteria?

Mucosal healing determined by endoscopy is currently the remission standard for ulcerative colitis (UC). However, new criteria for remission are emerging, such as histologic normalization, which appears to correlate better to the risk of relapse. Here, we study mucosal healing on a molecular and functional level in quiescent UC. We obtained endoscopic biopsies from 33 quiescent UC patients and from 17 controls. Histology was assessed using Geboes score. Protein and mRNA levels were evaluated for the tight junction proteins claudin-2, claudin-4, occludin, and tricellulin, as well as Cl-/HCO3- exchanger DRA, and cyclo-oxygenase enzymes (COX-1, COX-2). The mucosal activity of COX-1 and COX-2 enzymes was assessed in modified Ussing chambers, measuring electrogenic ion transport (short-circuit current, SCC). Chronic inflammation was present in most UC patients. The protein level of claudin-4 was reduced, while mRNA-levels of claudin-2 and claudin-4 were upregulated in UC patients. Surprisingly, the mRNA level of COX-1 was downregulated, but was unaltered for COX-2. Basal ion transport was not affected, while COX-2 inhibition induced a two-fold larger decrease in SCC in UC patients. Despite being in clinical and endoscopic remission, quiescent UC patients demonstrated abnormal mucosal barrier properties at the molecular and functional level. Further exploration of mucosal molecular signature for revision of current remission standards should be considered.

Multiple Domains in the Kv7.3 C-Terminus Can Regulate Localization to the Axon Initial Segment.

The voltage-gated Kv7.2/Kv7.3 potassium channel is a critical regulator of neuronal excitability. It is strategically positioned at the axon initial segment (AIS) of neurons, where it effectively inhibits repetitive action potential firing. While the selective accumulation of Kv7.2/Kv7.3 channels at the AIS requires binding to the adaptor protein ankyrin G, it is currently unknown if additional molecular mechanisms contribute to the localization and fine-tuning of channel numbers at the AIS. Here, we utilized a chimeric approach to pinpoint regions within the Kv7.3 C-terminal tail with an impact upon AIS localization. This strategy identified two domains with opposing effects upon the AIS localization of Kv7.3 chimeras expressed in cultured hippocampal neurons. While a membrane proximal domain reduced AIS localization of Kv7.3 chimeras, helix D increased and stabilized chimera AIS localization. None of the identified domains were required for AIS localization. However, the domains modulated the relative efficiency of the localization raising the possibility that the two domains contribute to the regulation of Kv7 channel numbers and nanoscale organization at the AIS.

Electronic measures of movement impairment, repositioning, and posture in people with and without neck pain-a systematic review.

BACKGROUND: Neck pain is a major public health problem. Our objective was to describe differences in measures of movement and posture between people with and without neck pain. METHODS: PubMed and Embase were searched before 15 February 2019 for studies comparing people with neck pain with controls using electronic measurements of neck movement and/or posture. Data were extracted on participants, device, test methods, active range of motion (RoM) and quality of motion, joint positioning sense, and posture. Study quality was assessed using the quality assessment of studies of diagnostic accuracy included in systematic reviews (QUADAS) and Guidelines for Reporting Reliability and Agreement Studies (GRRAS) guidelines. RESULTS: Thirty-six studies were included: 24 studies included measurement of active RoM, 15 quality of motion, 12 joint positioning sense, and 5 cervical spine posture. Measurements and test methods were heterogeneous. The reporting of study populations and methods were poor, whereas devices and statistics were well described. All studies on RoM showed reduced active RoM in people with neck pain when compared with controls, 5 of 10 studies reported reduced movement speed for people with neck pain, and 5 of 9 studies reported significantly greater joint positioning error for people with neck pain compared with controls. Due to heterogeneous test parameters and methods, no conclusion regarding differences in conjunct motion, tracking a motion pattern, and measures of posture could be drawn. CONCLUSIONS: People with neck pain appear to have reduced active RoM, movement speed, and head repositioning accuracy when compared with controls. However, quality of reviewed studies was low and better descriptions of participants and methods are required before firm conclusions can be drawn.

Possible predisposition for colorectal carcinogenesis due to altered gene expressions in normal appearing mucosa from patients with colorectal neoplasia.

BACKGROUND: Investigations of colorectal carcinogenesis have mainly focused on examining neoplastic tissue. With our aim of identifying potentially cancer-predisposing molecular compositions, we chose a different approach by examining endoscopically normal appearing colonic mucosa of patients with and without colorectal neoplasia (CRN). Directed by this focus, we selected 18 genes that were previously found with altered expression in colorectal cancer affected mucosa. METHODS: Biopsies of colonic mucosa were sampled from 27 patients referred for colonoscopy on suspicion of colorectal disease. Of these, 14 patients had present or previous CRN and the remaining 13 patients served as controls. Using qPCR and Western blot technique, we investigated mRNA and protein expressions. Expressions were investigated for selected kinases in the extracellular signal-regulated kinase/mitogen activated protein kinase (ERK/MAPK), the phosphoinositide 3-kinase/Akt, and the Wnt/ß-catenin pathways as well as for selected phosphatases and several entities associated with prostaglandin E2 (PGE2) signaling. Colonic mucosal contents of PGE2 and PGE2 metabolites were determined by use of ELISA. RESULTS: We found up-regulation of ERK1, ERK2, Akt1, Akt2, PLA2G4A, prostanoid receptor EP3 and phosphatase scaffold subunit PPP2R1B mRNA expression in normal appearing colonic mucosa of CRN patients compared to controls. CONCLUSION: Present study supports that even normal appearing mucosa of CRN patients differs from that of non-CRN patients at a molecular level. Especially expression of ERK1 mRNA was increased (p = 0.007) in CRN group. ERK1 may therefore be considered a potential candidate gene as predictive biomarker for developing CRN. Further validation in larger cohorts are required to determine such predictive use in translational medicine and clinics.

Regulation of Kv1.4 potassium channels by PKC and AMPK kinases.

Over the last years extensive kinase-mediated regulation of a number of voltage-gated potassium (Kv) channels important in cardiac electrophysiology has been reported. This includes regulation of Kv1.5, Kv7.1 and Kv11.1 cell surface expression, where the kinase-mediated regulation appears to center around the ubiquitin ligase Nedd4-2. In the present study we examined whether Kv1.4, constituting the cardiac Ito,s current, is subject to similar regulation. In the epithelial Madin-Darby Canine Kidney (MDCK) cell line, which constitutes a highly reproducible model system for addressing membrane targeting, we find, by confocal microscopy, that Kv1.4 cell surface expression is downregulated by activation of protein kinase C (PKC) and AMP-activated protein kinase (AMPK). In contrast, manipulating the activities of phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K) and serum and glucocorticoid-regulated kinase 1 (SGK1) were without effect on channel localization. The PKC and AMPK-mediated downregulation of Kv1.4 membrane surface localization was confirmed by two-electrode voltage clamp in Xenopus laevis oocytes, where pharmacological activation of PKC and AMPK reduced Kv1.4 current levels. We further demonstrate that unlike related Kv channels, Kv1.4 current levels in Xenopus laevis oocytes are not reduced by co-expression of Nedd4-2, or the related Nedd4-1 ubiquitin ligase. In conclusion, we demonstrate that the surface expression of Kv1.4 is downregulated by the two kinases AMPK and PKC, but is unaffected by PI3K-SGK1 signaling, as well as Nedd4-1/Nedd4-2 activity. In the light of previous reports, our results demonstrate an impressive heterogeneity in the molecular pathways controlling the surface expression of highly related potassium channel subunits.

A Comprehensive Approach to Assess Feathermeal as an Alternative Protein Source in Aquafeed.

The effect of partially replacing fishmeal in aquafeed with feathermeal (FTH) at three levels (0%: FTH0, 8%: FTH8, 24%: FTH24) and two extrusion temperatures (100 and 130 °C) was evaluated in rainbow trout (Oncorhynchus mykiss) with respect to growth performance, metabolism response, and oxidative status of the feed proteins. Multivariate data analyses revealed that FTH24 correlated positively with high levels of oxidation products, amino acids (AA) racemization, glucogenic AAs level in liver, feed intake (FI), specific growth rate (SGR), and feed conversion ratio (FCR); and low AAs digestibility. Both FI and SGR were significantly increased when 8 and 24% feathermeal was included in the feed extruded at 100 °C, while there was a negative effect on FCR in fish fed FTH24. In conclusion, higher oxidation levels in FTH24 may give rise to metabolic alterations while lower levels of FTH may be considered as fishmeal substitute in aquafeed for rainbow trout.

Trafficking of Kv2.1 Channels to the Axon Initial Segment by a Novel Nonconventional Secretory Pathway.

Kv2.1 is a major delayed-rectifier voltage-gated potassium channel widely expressed in neurons of the CNS. Kv2.1 localizes in high-density cell-surface clusters in the soma and proximal dendrites as well as in the axon initial segment (AIS). Given the crucial roles of both of these compartments in integrating signal input and then generating output, this localization of Kv2.1 is ideal for regulating the overall excitability of neurons. Here we used fluorescence recovery after photobleaching imaging, mutagenesis, and pharmacological interventions to investigate the molecular mechanisms that control the localization of Kv2.1 in these two different membrane compartments in cultured rat hippocampal neurons of mixed sex. Our data uncover a unique ability of Kv2.1 channels to use two molecularly distinct trafficking pathways to accomplish this. Somatodendritic Kv2.1 channels are targeted by the conventional secretory pathway, whereas axonal Kv2.1 channels are targeted by a nonconventional trafficking pathway independent of the Golgi apparatus. We further identified a new AIS trafficking motif in the C-terminus of Kv2.1, and show that putative phosphorylation sites in this region are critical for the restricted and clustered localization in the AIS. These results indicate that neurons can regulate the expression and clustering of Kv2.1 in different membrane domains independently by using two distinct localization mechanisms, which would allow neurons to precisely control local membrane excitability.SIGNIFICANCE STATEMENT Our study uncovered a novel mechanism that targets the Kv2.1 voltage-gated potassium channel to two distinct trafficking pathways and two distinct subcellular destinations: the somatodendritic plasma membrane and that of the axon initial segment. We also identified a distinct motif, including putative phosphorylation sites, that is important for the AIS localization. This raises the possibility that the destination of a channel protein can be dynamically regulated via changes in post-translational modification, which would impact the excitability of specific membrane compartments.