Various three-dimensional (3D) culture methods have been introduced to overcome the limitations of in vitro culture and mimic in vivo conditions. This study aimed to evaluate two microsphere-forming culture methods and a monolayer culture method. We evaluated cell morphology, viability, osteo-, adipo-, and chondrogenic differentiation potential of dental pulp stem cells (DPSCs) cultured in 3D culture plates: ultra-low attachment (ULA) and U-bottomed StemFit 3D (SF) plates, and a two-dimensional (2D) monolayer plate. RNA sequencing (RNA-seq) revealed differentially expressed gene (DEG) profiles of the DPSCs. In contrast to an increasing pattern in the 2D group, cell viability in 3D groups (ULA and SF) showed a decreasing pattern; however, high multilineage differentiation was observed in both the 3D groups. RNA-seq showed significantly overexpressed gene ontology categories including angiogenesis, cell migration, differentiation, and proliferation in the 3D groups. Hierarchical clustering analysis revealed a similar DEG regulation pattern between the 3D groups; however, a comparatively different DEG was observed between the 2D and 3D groups. Taken together, this study shows that DPSCs cultured in microsphere-forming plates present superior multilineage differentiation capacities and demonstrate higher DEG expression in regeneration-related gene categories compared to that in DPSCs cultured in a conventional monolayer plate. Full article

Over 26 million people worldwide suffer from heart failure, a disease associated with a 1 year mortality rate of 22%. Half of these patients present heart failure with preserved ejection fraction (HFpEF), for which there is no available therapy to improve prognosis. HFpEF is strongly associated with aging, inflammation, and comorbid burden, which are thought to play causal roles in disease development. Mesenchymal stromal/stem cells (MSCs) have potent immunomodulatory actions and promote tissue healing, thus representing an attractive therapeutic option in HFpEF. In this review, we summarize recent data suggesting that a two-hit model of immune dysregulation lies at the heart of the HFpEF. A first hit is represented by genetic mutations associated with clonal hematopoiesis of indeterminate potential (CHIP), which skew immune cells toward a pro-inflammatory phenotype, are associated with HFpEF development in animal models, and with immune dysregulation and risk of HF hospitalization in patients. A second hit is induced by cardiovascular risk factors, which cause subclinical cardiac dysfunction and production of danger signals. In mice, these attract proinflammatory macrophages, Th1 and Th17 cells into the myocardium, where they are required for the development of HFpEF. MSCs have been shown to reduce the pro-inflammatory activity of immune cell types involved in murine HFpEF in vitro, and to reduce myocardial fibrosis and improve diastolic function in vivo, thus they may efficiently target immune dysregulation in HFpEF and stop disease progression. Full article

Primary insulin-like growth factor-I (IGF-I) deficiency is a synonym of growth hormone (GH) insensitivity (GHI), however the necessity of direct confirmation of GH resistance by IGF-I generation test (IGF-GT) is discussed. GHI may disturb intrauterine growth, nevertheless short children born small for gestational age (SGA) are treated with GH. We tested the hypothesis that children with appropriate birth size (AGA), height standard deviation score (SDS) <−3.0, GH peak in stimulation tests (stimGH) ≥10.0 µg/L, IGF-I <2.5 centile, and excluded GHI may benefit during GH therapy. The analysis comprised 21 AGA children compared with 6 SGA and 20 GH-deficient ones, with height SDS and IGF-I as in the studied group. All patients were treated with GH up to final height (FH). Height velocity, IGF-I, and IGF binding protein-3 (IGFBP-3) concentrations before and during first year of treatment were assessed. Effectiveness of therapy was better in GHD than in IGF-I deficiency (IGFD), with no significant difference between SGA and AGA groups. All but two AGA children responded well to GH. Pretreatment IGF-I and increase of height velocity (HV) during therapy but not the result of IGF-GT correlated with FH. As most AGA children with apparent severe IGFD benefit during GH therapy, direct confirmation of GHI seems necessary to diagnose true primary IGFD in them. Full article

Background: Parkinson’s disease (PD) is a common neurodegenerative disease associated with progressive gray matter atrophy. In addition to motor function disorder, frailty and decreased muscle mass potentially contribute to increased morbidity risk. Objective: This study aimed to investigate the associations between lean muscle loss and gray matter volume (GMV) in PD patients. Methods: Thirty patients with PD and fifteen healthy controls underwent brain and bilateral thigh MRIs. The IDEAL sequence was employed, measuring the regions of interest (ROI) of fat percentage at the 50% point of femur length. Voxel-base morphometry (VBM) was used to assess regional gray matter volume differences between groups. Further correlation analysis was performed to evaluate the changes between gray matter volume and fatty percentage of the bilateral thigh after adjusting for age and gender. Multiple linear regression analysis was applied to evaluate the risk factor of core muscle loss in PD patients. Results: Compared with controls, patients with PD had significantly higher thigh fat percentage and smaller gray matter volume of several brain locations of the default mode network (DMN), specifically the left superior temporal gyrus, right uncus, and left inferior temporal gyrus, revealing association with higher thigh fat percentage. Further multiple linear regression analysis indicated that higher thigh fat percentage is associated with gender (female), increased disease duration, and smaller gray matter volume of the left superior temporal gyrus and right uncus in PD patients. Conclusions: Patients with PD experience core muscle loss in the thigh, associated with default mode network (DMN) degeneration, longer disease duration, and female gender. Identification of risk factors associated with lean muscle mass loss may assist in early prevention of comorbidities such as sarcopenia. Full article

Objectives: In the prehospital setting, endotracheal intubation (ETI) is sometimes required to secure a patient’s airways. Emergency ETI in the field can be particularly challenging, and success rates differ widely depending on the provider’s training, background, and experience. Our aim was to evaluate the ETI success rate in a resident-staffed and specialist-physician-supervised emergency prehospital system. Methods: This retrospective study was conducted on data extracted from the Geneva University Hospitals’ institutional database. In this city, the prehospital emergency response system has three levels of expertise: the first is an advanced life-support ambulance staffed by two paramedics, the second is a mobile unit staffed by an advanced paramedic and a resident physician, and the third is a senior emergency physician acting as a supervisor, who can be dispatched either as backup for the resident physician or when a regular Mobile Emergency and Resuscitation unit (Service Mobile d’Urgence et de Réanimation, SMUR) is not available. For this study, records of all adult patients taken care of by a second- and/or third-level prehospital medical team between 2008 and 2018 were screened for intubation attempts. The primary outcome was the success rate of the ETI attempts. The secondary outcomes were the number of ETI attempts, the rate of ETI success at the first attempt, and the rate of ETIs performed by a supervisor. Results: A total of 3275 patients were included in the study, 55.1% of whom were in cardiac arrest. The overall ETI success rate was 96.8%, with 74.4% success at the first attempt. Supervisors oversaw 1167 ETI procedures onsite (35.6%) and performed the ETI themselves in only 488 cases (14.9%). Conclusion: A resident-staffed and specialist-physician-supervised urban emergency prehospital system can reach ETI success rates similar to those reported for a specialist-staffed system. Full article

Successful implementation of postpartum lifestyle interventions first requires the identification of effective core components, such as strategies for behavioural change. This systematic review and meta-analysis aimed to describe the associations between behavioural strategies and changes in weight, diet, and physical activity in postpartum women. Databases MEDLINE, CINAHL, EMBASE, and PsycINFO were searched for randomised controlled trials of lifestyle interventions in postpartum women (within 2 years post-delivery). Strategies were categorised according to the Behaviour Change Technique Taxonomy (v1). Forty-six articles were included (n = 3905 women, age 23–36 years). Meta-analysis showed that postpartum lifestyle interventions significantly improved weight (mean difference −2.46 kg, 95%CI −3.65 to −1.27) and physical activity (standardised mean difference 0.61, 95%CI 0.20 to 1.02) but not in energy intake. No individual strategy was significantly associated with weight or physical activity outcomes. On meta-regression, strategies such as problem solving (β = −1.74, P = 0.045), goal setting of outcome (β = −1.91, P = 0.046), reviewing outcome goal (β = −3.94, P = 0.007), feedback on behaviour (β = −2.81, P = 0.002), self-monitoring of behaviour (β = −3.20, P = 0.003), behavioural substitution (β = −3.20, P = 0.003), and credible source (β = −1.72, P = 0.033) were associated with greater reduction in energy intake. Behavioural strategies relating to self-regulation are associated with greater reduction in energy intake. Full article

Due to the widespread use of ultrasound, small thyroid nodules (TNs) ≤ 10 mm are common findings. Standardized approaches for the risk stratification of TNs with Thyroid Imaging Reporting and Data Systems (TIRADS) were evaluated for the clinical routine. With TIRADS, the risk of malignancy in TNs is calculated by scoring the number or combination of suspicious ultrasound features, leading to recommendations for further diagnostic steps. However, there are only scarce data on the performance of TIRADS for small TNs. The aim was to compare three different TIRADS for risk stratification of small TNs in routine clinical practice. We conducted a retrospective cohort analysis of TNs ≤ 10 mm and their available histology. Nodules were classified according to three different TIRADS. In the study, 140 patients (n = 113 female) with 145 thyroid nodules (n = 76 malignant) were included. Most of the malignant nodules were papillary carcinoma (97%), and the remaining 3% were medullary carcinoma. For all tested TIRADS, the prevalence of malignancy rose with increasing category levels. The highest negative predictive value was found for ACR TI-RADS and the highest positive predictive value for Kwak-TIRADS. All tested variants of TIRADS showed comparable diagnostic performance for the risk stratification of small TNs. TIRADS seems to be a promising tool to reliably assess the risk of malignancy of small TNs. Full article

Complete reosseointegration after treatment of periimplantitis was never published yet. This short scientific communication reports about results of a randomized controlled preclinical study. An electrolytic approach was compared to a classical modality (ablative, cotton pellets soaked with sodium chloride solution and H₂O₂. For electrolytic cleaning a complete reosseointegration was achieved in several cases serving as a proof of concept. Full article

Attention-deficit-hyperactivity disorder (ADHD) is closely associated with deficits in cognitive control. It seems, however, that the degree of deficits strongly depends on the examined subprocess, with the resolution of stimulus–stimulus conflicts being particularly difficult for patients with ADHD. The picture is far less clear regarding stimulus–response conflicts. The current study provides multi-level behavioural and neurophysiological data on this type of conflict monitoring in children with ADHD compared to healthy controls. To account for the potentially strong effects of intra-individual variability, electroencephalogram (EEG) signal decomposition methods were used to analyze the data. Crucially, none of the analyses (behavioural, event-related potentials, or decomposed EEG data) show any differences between the ADHD group and the control group. Bayes statistical analysis confirmed the high likelihood of the null hypothesis being true in all cases. Thus, the data provide multi-level evidence showing that conflict monitoring processes are indeed partly intact in ADHD, even when eliminating possible biasing factors such as intra-individual variability. While stimulus–stimulus conflict processing has been shown to be consistently dysfunctional in ADHD, the resolution of stimulus–response conflicts is not deficient in this patient group. In comparison to other studies, the results provide novel theoretical insights into the nature of conflict control deficits in childhood ADHD. Full article

Dietary intake potentially modifies the prevalence or severity of asthma. The prevalence of asthma is higher in women with polycystic ovary syndrome (PCOS); it is not known if diet confounds or modifies the association between asthma and PCOS. The aims of this study were: (i) To determine if the association of PCOS and asthma is independent of dietary pattern and (ii) to determine if dietary pattern modifies the association between PCOS and asthma. Women in this study were from the Australian Longitudinal Study on Women’s Health (ALSWH) cohort born between 1973 to 1978 and aged 18 to 23 years (n = 7382). Logistic regression was used to assess the association between PCOS and asthma, adjusting for the following: (i) Potential confounders identified a priori and (ii) dietary patterns (z-score) identified by principle component analysis. In the adjusted analysis, women with PCOS were more likely to have asthma than the women without PCOS (OR 1.35 and 95% CI, 1.02 and 1.78). This relationship was not altered by further adjustment for dietary patterns (non-core food, meats and takeaway, or Mediterranean-style pattern). In the interaction analysis, only the women consuming less than the median intake of non-core foods (i.e., lower intake of discretionary or unhealthy foods) and with PCOS were more likely to have asthma (OR 1.91 and 95% CI, 1.29 and 2.82). Dietary intake did not confound the relationship between PCOS and asthma. Other mechanistic pathways are likely responsible for the asthma and PCOS association, and further studies assessing factors such as oral contraceptive use and sex steroid hormones warrant investigation. Full article

The benefit of complete revascularization (CR) in ST-segment elevation myocardial infarction (STEMI) patients with left ventricular (LV) dysfunction is uncertain. A total of 1314 STEMI patients with multivessel coronary artery disease were analyzed. CR was defined angiographically and by a residual Synergy between PCI with Taxus and Cardiac Surgery trial (SYNTAX) score (SS) <8. Patients with a left ventricular ejection fraction (LVEF) <40% were classified as the reduced LVEF group. The major study endpoints were patient-oriented composite outcome (POCO) and cardiac death during three-year follow-up. Overall, patients that received angiographic CR (579 patients, 44.1%) had significantly lower three-year clinical events compared with incomplete revascularization (iCR). CR reduced three-year POCO and cardiac death rates in the preserved LVEF group (POCO: 13.2% vs. 21.9%, p < 0.001, cardiac death: 1.8% vs. 6.5%, p < 0.001, respectively) but not in the reduced LVEF group (POCO: 26.0% vs. 33.1%, p = 0.275, cardiac death: 15.1% vs. 19.0%, p = 0.498, respectively). Multivariate analysis showed that CR significantly reduced three-year POCO (hazard ration (HR) 0.59, 95% confidence interval (CI) 0.43–0.82) and cardiac death (HR 0.34, 95% CI 0.14–0.80), only in the preserved LVEF group. Additionally, the results were corroborated using the SS-based CR definition. In STEMI patients with multivessel disease, CR did not improve clinical outcomes in those with reduced LVEF. Full article

Background: Respiratory muscle dysfunction is an important health problem with high morbidity and mortality and associated costs in patients with bronchiectasis (BC). The aim of this study was to analyse the effects of therapeutic respiratory muscle training (RMT) interventions on improving sputum clearance, ventilator function, muscle strength and functional capacity in BC. Methods: Systematic review and meta-analysis were conducted following PRISMA guidelines. Two independent investigators searched using several electronic databases. The methodological quality of nine studies was assessed using the PEDro scale. Study selection/eligibility criteria: The following were included: randomised controlled trials, randomised crossover trials and pilot studies of patients with BC that used the intervention as RMT (inspiratory/expiratory) and evaluations of respiratory muscle strength (maximal expiratory pressure/maximal inspiratory pressure). This systematic review was registered in PROSPERO (CRD42017075101). Nine studies were included, five of which obtained an A recommendation grade, three with B, and one with C. Study quality was poor to good (mean PEDro Score of 6.375 out of 10). Studies had small sample sizes (8–98). Results show improvements on PImax in favour of therapeutic respiratory muscle training intervention (MD = 6.08; 95% CI = 1.38, 10.77; p < 0.01; I² = 92%). However, high heterogeneity was identified on meta-analysis. Full article

Background: Pneumonia is a frequent infection. Chronic obstructive pulmonary disease (COPD) can present with comorbidities, including pneumonia. It is known that COPD worsens the evolution of pneumonia, but few studies describe the impact of pneumonia on COPD evolution. This study analyzes the influence of pneumonia on the survival of COPD patients. Methods: Observational study of a cohort of 273 patients with COPD who attended spirometry in 2011, with a prospective follow-up of six years. Patients were divided into two groups according to their acquisition of pneumonia during follow-up. The difference in survival between the two groups was analyzed. Results: Survival was lower in the group with pneumonia compared with that without pneumonia (p = 0.000), both globally and after stratification by COPD phenotype. Pneumonia (Hazard Ratio -HR- 2.65; 95% Confidence Interval -CI- 1.57–4.48), advanced age (HR 1.08; 95% CI 1.03–1.09), and high Charlson index (HR 1.31; 95% CI 1.17–1.47) were identified as risk factors independently associated with mortality, while a high body mass index (HR 0.92; 95% CI 0.87–0.96) was identified as a protective factor. Conclusions: Pneumonia is associated with worse prognosis in COPD patients. It is important to take into account this comorbidity for a comprehensive care of these patients. Full article

(1) Objective: To use optical coherence tomography angiography (OCTA) and microperimetry (MP) to evaluate the correlation between retinal structure and function in patients with idiopathic, full-thickness macular holes (FTMHs) (2) Methods: This prospective, observational study included 11 eyes of 10 patients with FTMHs evaluated before surgery using OCTA and MP. MP sensitivity maps were superimposed and registered on slabs corresponding to superficial capillary plexus (SCP) and deep capillary plexus (DCP) on OCTA, and on the outer plexiform layer (OPL) and the Henle fiber layer (HFL) complex in en face OCT. On these maps, mean retinal sensitivity was calculated at 2° and 4°, all centered on the FTMH. Cystic cavity extension was assessed on the slab corresponding to the OPL + HFL complex in en face OCT and DCP in OCTA using the Image J software (Version 1.49v; National Institutes of Health, Bethesda, MD, USA); (3) Results: Absolute scotomas were observed corresponding to the FTMH. Additionally, rings of relative scotoma in the perilesional area were detected and correlated to the cystic spaces on en face OCT and OCTA. There was a significant correlation between reduced retinal sensitivity at 2° and 4° diameters around the FTMH and the extension of cystic areas (p < 0.01). There was a significant correlation between the extension of cystic cavities and BCVA (p < 0.01). (4) Conclusions: Morpho-functional analysis of FTMH using OCTA and MP, and the correlation between vascular abnormalities and impaired retinal sensitivity, may provide new, useful information. This integrated evaluation of FTMH may be useful to determine the function–structure correlation before and after vitreoretinal surgery, in order to gain a better understanding of the functional consequences induced by the morphological alterations, assessing outcomes in a more objective way, and potentially adding new surgical prognostic factors. Full article

Almost 60% of children with profound prelingual hearing loss (HL) have a genetic determinant of deafness, most frequently two DFNB1 locus (GJB2/GJB6 genes) recessive pathogenic variants. Only few studies combine HL etiology with cochlear implantation (CI) outcome. Patients with profound prelingual HL who received a cochlear implant before 24 months of age and had completed DFNB1 genetic testing were enrolled in the study (n = 196). LittlEARS questionnaire scores were used to assess auditory development. Our data show that children with DFNB1-related HL (n = 149) had good outcome from the CI (6.85, 22.24, and 28 scores at 0, 5, and 9 months post-CI, respectively). A better auditory development was achieved in patients who receive cochlear implants before 12 months of age. Children without residual hearing presented a higher rate of auditory development than children with responses in hearing aids over a wide frequency range prior to CI, but both groups reached a similar level of auditory development after 9 months post-CI. Our data shed light upon the benefits of CI in the homogenous group of patients with HL due to DFNB1 locus pathogenic variants and clearly demonstrate that very early CI is the most effective treatment method in this group of patients. Full article