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Abstract Tendon healing involves mechanosensitive cells that adapt to mechanical stimuli through mechanotransduction, resulting in increased tissue strength. However, detailed insights into this process in response to different loads remain limited. We aimed to investigate how different loading regimes impact the spatial composition of elastin and collagens during Achilles tendon healing. Histological analysis was conducted on healing rat Achilles tendons exposed to (1) full loading, (2) reduced loading, or (3) minimal loading. Histological analysis included Hematoxylin & Eosin and immunohistochemical staining targeting elastin, Collagen 1, Collagen 3, and CD31. Our results showed that the impact of mechanical stimuli on healing tendons varied with the degree of loading. Unexpectedly, minimal loading led to higher staining intensity for collagens and elastin. However, tendons exposed to minimal loading appeared thinner and exhibited a less organized matrix structure, with fewer, less aligned, and more rounded cells. Additionally, our findings indicated an inverse correlation between angiogenesis and load level, with more blood vessels in tendons subjected to less loading. Tissue integrity improved by 12 weeks post-injury, but the healing process continued and did not regain the structure seen in intact tendons even after 20 weeks. This study reveals a load-dependent effect on matrix alignment, cell density, and cell alignment.

Abstract To accurately capture the dynamic behavior of small nanoparticles in scanning transmission electron microscopy, high-quality data and advanced data processing is needed. The fast scan rate required to observe structural dynamics inherently leads to very noisy data where machine learning tools are essential for unbiased analysis. In this study, we develop a workflow based on two U-Net architectures to automatically localize and classify atomic columns at particle-support interfaces. The model is trained on non-physical image simulations, achieves sub-pixel localization precision, high classification accuracy, and generalizes well to experimental data. We test our model on both in situ and ex situ experimental time series recorded at 5 frames per second of small Pt nanoparticles supported on CeO2(111). The processed movies show sub-second dynamics of the nanoparticles and reveal site-specific movement patterns of individual atomic columns.

This study on technology education in preschool aims to explore how technology activities in preschool are enacted and what knowledge, related to the five dimensions of the nature of technology, is made possible for the children to learn when intersubjectivity is established in the interaction between the participants. The empirical data encompass three video-documented technology activities, involving five children and one preschool teacher. Drawing on the five dimensions of the nature of technology by DiGironimo, the participants' interactions were analysed using interaction analysis. The results showed that the teacher, through well-defined and sensitive orchestration, enacted goal-oriented activities by allowing a play-oriented approach, and that intersubjectivity on technology was established related to four of the five dimensions of technology. The lack of knowledge related to the historical dimension of technology suggests further scrutiny and is discussed as essential in ECE technology education for contemporary children, growing up in high-tech societies.

Abstract Inflammation, corticosteroids, and loading all affect tendon healing, with an interaction between them. However, underlying mechanisms behind the effect of corticosteroids and the interaction with loading remain unclear. The aim of this study was to investigate the role of dexamethasone during tendon healing, including specific effects on tendon cells. Rats (n = 36) were randomized to heavy loading or mild loading, the Achilles tendon was transected, and animals were treated with dexamethasone or saline. Gene and protein analyses of the healing tendon were performed for extracellular matrix-, inflammation-, and tendon cell markers. We further tested specific effects of dexamethasone on tendon cells in vitro. Dexamethasone increased mRNA levels of S100A4 and decreased levels of ACTA2/α-SMA, irrespective of load level. Heavy loading + dexamethasone reduced mRNA levels of FN1 and TenC (p 0.05). In contrast, mild loading + dexamethasone increased mRNA levels of resolution-related genes ANXA1, MRC1, PDPN, and PTGES (p

Abstract Premature death in diabetes is increasingly caused by cancer. The objectives were to estimate the excess mortality when individuals with type 2 diabetes(T2D) were diagnosed with cancer, and to examine the impact of modifiable diabetes-related risk factors. This longitudinal nationwide cohort study included individuals with T2D registered in the Swedish National Diabetes Register between 1998–2019. Poisson models were used to estimate mortality as a function of time-updated risk-factors, adjusted for sex, age, diabetes duration, marital status, country of birth, BMI, blood pressure, lipids, albuminuria, smoking, and physical activity. We included 690,539 individuals with T2D and during 4,787,326 person-years of follow-up 179,627 individuals died. Overall, the all-cause mortality rate ratio was 3.75 [95%confidence interval(CI):3.69–3.81] for individuals with T2D and cancer compared to those remaining free of cancer. The most marked risk factors associated to mortality among individuals with T2D and cancer were low physical activity, 1.59 (1.57–1.61) and smoking, 2.15 (2.08–2.22), whereas HbA1c, lipids, hypertension, and BMI had no/weak associations with survival. In a future with more patients with comorbid T2D and cancer diagnoses, these results suggest that smoking and physical activity might be the two most salient modifiable risk factors for mortality in people with type 2 diabetes and cancer.

Objectives: To investigate whether acid etch contamination of silane-treated composite influenced repair bond strength and whether silane contamination on dentin influenced composite bond strength to dentin. Materials and methods: Forty composite blocks stored in water for 4 weeks were divided into four groups. Specimens in groups 1–3 were coated with Bis-Silane and contaminated with acid etch + water spray (group 1) or water spray (group 2). Group 3 was not contaminated. Group 4 was untreated. The occlusal third of 60 third molars was cut off, ground flat, and divided into three groups. After etching, the surfaces in groups A and B were contaminated with Bis-silane. The contaminated surfaces in group A were re-etched. Each composite repair group and composite-dentin group was divided into two subgroups receiving Adper Scotchbond 1 XT or Clearfil SE Bond 2 adhesives followed by a composite build up. After ageing for 3 months, specimens were sectioned into 1.1 mm × 1.1 mm rods for tensile testing and strength calculated at fracture. The fracture was examined using microscope. Results: Bis-Silane surface treatment increased the repair bond strength. Contamination with acid reduced the strength of the repair bond. Similar results were obtained for both adhesives. Tooth surface contamination with silane reduced the bond strength between dentin and composite. Additional acid etching or water spray on silane contaminated dentin did not influence the weakened bond strength. Most fractures were adhesive type. Conclusions: Silane contamination on etched dentin and acid etch contamination on silanized composite surfaces significantly reduced tensile bond strength.

Technology education in early childhood education (ECE) has only recently been established internationally as a curriculum content area. The interdisciplinary character of technology education and its status as a field under development occasion a need to distinguish and define technology in the merging of disciplines. This literature review presents an overview of technology education in ECE in recent empirical studies. The literature review was carried out systematically, resulting in 23 studies that were scrutinised to present an overall picture regarding study design, findings and how technology is characterised. The analysis of the nature of technology in the reviewed studies builds on DiGironimo's (Int J Sci Education, 33(10):1337-1352. https://doi.org/10.1080/09500693.2010.495400, 2011) conceptual framework, representing five distinct but merging dimensions of an ever-changing human technological creation process. In the synthesised findings, four subthemes derived from the studies' overall themes were identified: two focusing on preschool teachers and pre-service teachers, and two focusing on technology activities with children. The aligned outcomes are discussed concerning the conceptual dimensions of technology, along with possibilities, challenges and implications for the current field of research on technology education in ECE.

Abstract Background Type 2 diabetes (T2D) and peripheral artery disease (PAD) are recognized as independent risk factors contributing to excess mortality. Contemporary observational studies exploring the associations of risk factors, and risk of all-cause and atherosclerotic cardiovascular disease mortality in persons with T2D following the onset of incident peripheral artery disease are limited. The objectives of this study were to investigate the associations of risk factors, and assess mortality risks in people with T2D compared with controls without T2D after the onset of PAD. Methods All persons with T2D (n = 150,215) registered in the Swedish National Diabetes Register between 2005 and 2009 were included, along with 346,423 controls without T2D matched for sex and age. Data were retrieved from several national registries, capturing information on risk factors, onset of incident peripheral artery disease, other comorbidities, socioeconomic factors, and outcomes. To compare persons with T2D and controls following the onset of peripheral artery disease regarding the risk of all-cause, and atherosclerotic cardiovascular disease mortality, Cox proportional hazard models and Kaplan-Meier curves were employed. A gradient-boosting model was utilized to estimate the relative statistical contribution of risk factors to the modeling of incident mortality risk in people with both T2D and peripheral artery disease. Results Crude rates of incident all-cause mortality were higher in individuals with T2D compared with controls, following the onset of PAD (600.4 (95% CI, 581.4-619.8) per 10,000 person-years versus 549.1 (95% CI, 532.1-566.5) per 10,000 person-years). Persons with T2D had an adjusted hazard ratio (HR) for all-cause mortality of 1.12 (95% CI, 1.05–1.19, P

Abstract Objectives This study aimed to retrospectively assess cardiac autonomic activity in children with LQTS, considering genotype, symptoms, sex, age, and beta‐blocker therapy (BB) and compare it to healthy controls. Methods Heart rate variability (HRV), using power spectrum analysis, was analyzed in 575 Holter recordings from 116 children with LQTS and in 69 healthy children. The data were categorized into four age‐groups and four heart rate (HR) ranges. Results In LQT1 and LQT2, increasing HR corresponded to significantly lower low (LF) and high frequency (HF) compared to controls. Total power (PTOT) was lower in all LQT1 age‐groups compared to controls at HR 120–140 bpm (1–15 years: p

IntroductionCampylobacter jejuni gastroenteritis is the most commonly reported zoonosis within the EU, with poultry products regarded as the primary source of transmission to humans. Therefore, finding strategies to reduce Campylobacter colonization in broilers holds importance for public health. Recent studies suggest that supplementation of broiler feed with brown algal extracts, particularly laminarin, can provide beneficial effects on broiler gut health, growth performance, and gut microbiota. However, its effect on gut microbiota development and subsequent reduction of Campylobacter loads in broiler caeca during the later stages of the birds' lives remains unclear.MethodsExperimental colonization of Ross 308 broilers with two different strains of C. jejuni was conducted, with groups fed either a basal diet or the same basal diet supplemented with 725 ppm algal extract from Saccharina latissima to provide 290 ppm laminarin. Fecal samples were collected for bacterial enumeration, and caecal samples were obtained before and after the C. jejuni challenge for the determination of microbiota development.Results and discussionNo significant differences in fecal C. jejuni concentrations between the groups fed different diets or exposed to different C. jejuni strains were observed. This suggests that both strains colonized the birds equally well and that the laminarin rich algal extract did not have any inhibitory effect on C. jejuni colonization. Notably, 16S rRNA amplicon sequencing revealed detailed data on the caecal microbiota development, likely influenced by both bird age and C. jejuni colonization, which can be valuable for further development of broiler feed formulations aimed at promoting gut health.

Abstract Background In conjunction with post placement in root‐filled teeth with periapical healthy conditions, root canal retreatment may be performed to improve the seal of the root canal. Whether root canal retreatment for technical reasons (retreatments in teeth without apical periodontitis (AP)) results in lower frequency of AP is unknown. Objective To examine whether there is a difference in frequency of AP between roots with root canals retreated for technical reasons, and roots with root canals not retreated before post placement, with a minimum follow‐up of 5 years. Also, to examine changes in root filling quality following root canal retreatment for technical reasons. Methods This retrospective study included radiographs of 441 root‐filled roots without periapical radiolucencies at baseline, scheduled for post and core treatment. Follow‐up data for a minimum of 5 years were available for 305 roots (loss to follow‐up 30.8%), 46 of which were retreated for technical reasons. Two calibrated observers assessed root filling sealing quality and length, respectively, and periapical status according to the Periapical Index. The main outcome of the study, AP, was used as the dependent variable and all analyses were performed at root level. Results The overall frequency of AP at follow‐up was 13.8%. The difference in frequency of AP between retreated (4.3%) and nonretreated (15.4%) root canals was not statistically significant, p = .061. Analyses including only roots with preoperatively inadequate root filling quality showed a statistically significant difference (p = .017) between the two treatment groups (2.4% vs. 22.9%). Conclusions Root canal retreatment for technical reasons before post and core placement significantly reduces the frequency of AP in roots with inadequate root filling quality.

Background The aim of this study was to investigate temporal trends in survival and subsequent cardiovascular events in a nationwide myocardial infarction population with and without diabetes. Methods and Results Between 2006 and 2020, we identified 2527 individuals with type 1 diabetes, 48 321 individuals with type 2 diabetes and 243 170 individuals without diabetes with first myocardial infarction in national health care registries. Outcomes were trends in all‐cause death after 30 and 365 days, cardiovascular death and major adverse cardiovascular events (ie, nonfatal stroke, nonfatal myocardial infarction, cardiovascular death, and heart failure hospitalization). Pseudo‐observations were used to estimate the mortality risk, with 95% CIs, using linear regression, adjusted for age and sex. Individuals with type 1 diabetes were younger (62±12.2 years) and more often women (43.6%) compared with individuals with type 2 diabetes (75±10.8 years; women, 38.1%), and individuals without diabetes (73±13.2 years; women, 38.4%). Early death decreased in people without diabetes from 23.1% to 17.5%, (annual change −0.48% [95% CI, −0.52% to −0.44%]) and in people with type 2 diabetes from 22.6% to 19.3% (annual change, −0.33% [95% CI, −0.43% to −0.24%]), with no such significant trend in people with type 1 diabetes from 23.8% to 21.7% (annual change, −0.18% [95% CI, −0.53% to 0.17%]). Similar trends were observed with regard to 1‐year death, cardiovascular death, and major adverse cardiovascular events. Conclusions During the past 15 years, the trend in survival and major adverse cardiovascular events in people with first myocardial infarction without diabetes and with type 2 diabetes have improved significantly. In contrast, a similar improvement was not seen in people with type 1 diabetes.

Abstract The study aimed to identify the most predictive factors for the development of type 2 diabetes. Using an XGboost classification model, we projected type 2 diabetes incidence over a 10-year horizon. We deliberately minimized the selection of baseline factors to fully exploit the rich dataset from the UK Biobank. The predictive value of features was assessed using shap values, with model performance evaluated via Receiver Operating Characteristic Area Under the Curve, sensitivity, and specificity. Data from the UK Biobank, encompassing a vast population with comprehensive demographic and health data, was employed. The study enrolled 450,000 participants aged 40–69, excluding those with pre-existing diabetes. Among 448,277 participants, 12,148 developed type 2 diabetes within a decade. HbA1c emerged as the foremost predictor, followed by BMI, waist circumference, blood glucose, family history of diabetes, gamma-glutamyl transferase, waist-hip ratio, HDL cholesterol, age, and urate. Our XGboost model achieved a Receiver Operating Characteristic Area Under the Curve of 0.9 for 10-year type 2 diabetes prediction, with a reduced 10-feature model achieving 0.88. Easily measurable biological factors surpassed traditional risk factors like diet, physical activity, and socioeconomic status in predicting type 2 diabetes. Furthermore, high prediction accuracy could be maintained using just the top 10 biological factors, with additional ones offering marginal improvements. These findings underscore the significance of biological markers in type 2 diabetes prediction.

Background and aims: Pediatric pacing is usually performed as epicardial pacing in small children in need of pacemaker therapy. Epicardial pacing compared with transvenous pacing for pediatric complete atrioventricular block (CAVB) has different strengths and weaknesses. The epicardial left ventricular wall position of the lead has been considered superior, in terms of contraction pattern, compared to a transvenous right ventricular stimulation. We aimed to compare QRS duration and cardiac function before and after the switch from epicardial to transvenous pacing in a pediatric population. Methods: Pediatric patients with congenital or acquired CAVB, who underwent a switch from epicardial-to transvenous pacing at our center from 2005 to 2021, were identified through the national ICD- and Pacemaker Registry. Data regarding clinical status, ECG, and echocardiography before and after the switch and at last follow-up were collected. Results: We included 15 children. The median age at the switch was 6.7 (4.4–11.7) years with a median weight of 21 (15–39) Kg. The median QRS duration with the transvenous systems was 136 (128–152) ms vs. a QRS duration during epicardial stimulation of 150 (144–170) ms with a median difference in QRS duration of 14 (6–20) ms. Children with a post-surgical AV block had a broader QRS duration, both with epicardial and endocardial stimulation. Before the switch, there was one patient with impaired left ventricular function (LVF) but with normal left ventricular end-diastolic diameters. After the switch, one patient developed symptomatic LV dysfunction with the recovery of LVF at the last follow-up after being implanted with a cardiac resynchronization therapy device. Conclusions: Our report of pediatric patients after switching from epicardial to transvenous pacing shows how transvenous pacing is not inferior to epicardial pacing in terms of QRS duration and no significant deterioration of cardiac function was detectable.

Abstract Epigenetic dysregulation may influence disease progression. Here we explore whether epigenetic alterations in human pancreatic islets impact insulin secretion and type 2 diabetes (T2D). In islets, 5,584 DNA methylation sites exhibit alterations in T2D cases versus controls and are associated with HbA1c in individuals not diagnosed with T2D. T2D-associated methylation changes are found in enhancers and regions bound by β-cell-specific transcription factors and associated with reduced expression of e.g. CABLES1, FOXP1, GABRA2, GLR1A, RHOT1, and TBC1D4. We find RHOT1 (MIRO1) to be a key regulator of insulin secretion in human islets. Rhot1-deficiency in β-cells leads to reduced insulin secretion, ATP/ADP ratio, mitochondrial mass, Ca2+, and respiration. Regulators of mitochondrial dynamics and metabolites, including L-proline, glycine, GABA, and carnitines, are altered in Rhot1-deficient β-cells. Islets from diabetic GK rats present Rhot1-deficiency. Finally, RHOT1methylation in blood is associated with future T2D. Together, individuals with T2D exhibit epigenetic alterations linked to mitochondrial dysfunction in pancreatic islets.