The influence of dyad sex combination on patient self-care and caregiver contribution to self-care in multiple chronic conditions: An observational study.

INTRODUCTION: We know that patient and caregiver sex influence patient self-care and caregiver contribution to self-care in multiple chronic conditions. However, the role of dyad sex combination (e.g., male patient and female caregiver, female patient and male caregiver, male patient and caregiver, and female patient and caregiver) in influencing patient self-care and caregiver contribution to self-care remains unexplored. Our aim was to investigate the relationship between patient and caregiver sex combination and patient self-care and caregiver contribution to self-care in multiple chronic conditions. DESIGN: Multicentre cross-sectional study. METHODS: We enrolled patients with multiple chronic conditions and caregiver dyads in outpatient and community settings from April 2017 to December 2019. We used the Self-Care of Chronic Illness Inventory and the Caregiver Contribution to Self-Care of Chronic Illness Inventory that measure, from the patient and caregiver perspective, self-care maintenance (i.e., behaviors to maintain illness stability), self-care monitoring (i.e., monitoring of illness signs and symptoms), and self-care management (i.e., behaviors to manage signs and symptoms). We used multivariate analysis of covariance to evaluate the association between sex and self-care and caregiver contribution to self-care. RESULTS: We recruited 540 patient-caregiver dyads. Male patients cared by female caregivers performed higher self-care maintenance compared to female patients cared by female caregivers. Female caregivers caring for female patients performed higher caregiver contribution to self-care monitoring compared to male caregivers caring for female or male patients. CONCLUSIONS: Clinicians should consider the influence of patient and caregiver sex combination on self-care and caregiver contribution to self-care in multiple chronic conditions to provide tailored interventions. CLINICAL RELEVANCE: Healthcare professionals should consider the patient and caregiver sex combination in the dyad to tailor better interventions aimed at improving patient self-care and caregiver contribution to self-care in multiple chronic conditions.

Pediatric vital signs monitoring in hospital wards: Recognition systems and factors influencing nurses' attitudes and practices.

AIMS: To describe: 1) systems in place for recognition and response to deteriorating children in Italy, 2) attitudes and practices of registered nurses (RN) towards vital signs (VS) monitoring in pediatric wards, 3) the associations of nurses attitudes and pratices with nurses' and organizational characteristics. DESIGN AND METHODS: A multicentre cross-sectional correlational study. Data were collected between January-May 2020 using: an adapted version of the 'Survey on Recognition and Response Systems in Australia', and the 'Ped-V Scale'. Descriptive and adjusted linear regression analysis was performed, accounting for clustering. RESULTS: Ten Italian hospitals participated, 432 RNs responded to the Ped-V scale (response rate = 52%). Five (50%) hospitals had a VS policy in place, three hospitals (30%) had a Pediatric Early Warning System (PEWS), almost all hospitals had a system in place to respond to deteriorating children. Following multivariate regression analysis, having a PEWS was significantly associated with Ped-V scale 'Workload', 'Clinical competence', 'Standardization' dimensions; gender was associated with 'key indicators' and pediatric surgical ward with 'Clinical competence'. CONCLUSIONS: The use of VS policies and PEWS was not consistent across hospitals caring for children in Italy. Nurses' attitudes and practices (i.e., perception of workload, and clinical competence) were significantly lower in hospitals with increased complexity of care/PEWS. Gender was significantly associated with knowledge scores. PRACTICE IMPLICATIONS: System strategies to improve nurses' attitudes and practices towards VS monitoring and education are warranted to support effective behaviors towards VS monitoring, their interpretation, and appropriate communication to activate the efferent limb of the rapid response system.

Self-care of patients with multiple chronic conditions and their caregivers during the COVID-19 pandemic: A qualitative descriptive study.

AIMS: Explore the self-care experiences of patients with multiple chronic conditions (MCCs) and caregivers' contributions to patient self-care during COVID-19 pandemic. DESIGN: A descriptive qualitative design was used. The COREQ checklist was used for study reporting. METHODS: Individual semi-structured interviews were used to collect data from patients with MCCs and caregivers selected from the dataset of an ongoing longitudinal study. Data analysis was performed through deductive thematic analysis. The middle-range theory of self-care of chronic illness, which entails the three dimensions of self-care maintenance, monitoring and management, was used as a theoretical framework to guide data collection and analysis. RESULTS: A total of 16 patients and 25 caregivers were interviewed from May to June 2020. The participants were mainly women, with a mean age for patients of 76.25 years and caregivers of 45.76 years; the caregivers were mainly the patients' children (72%). During the pandemic, some patients reported remaining unchanged in their self-care maintenance, monitoring and management behaviours, others intensified their behaviours, and others decreased them. Caregivers played an important role in protecting patients from the risk of contagion COVID-19 and in ensuring patients' self-care of chronic diseases through direct and indirect interventions. CONCLUSIONS: Critical events can modify the self-care experiences of chronically ill patients and caregivers' contributions, leading to maintenance, increase or decrease of self-care and contributions to self-care behaviours. IMPACT: Patients with MCCs and their caregivers can react in different ways in their performances of self-care and contribution to patients' self-care behaviours when ordinary daily life is disrupted; therefore, nurses should assess such performances during critical events to identify the individuals at risk of reduced self-care and promote the most suitable healthcare services (e.g. eHealth) to implement individualised interventions.

Attitudes and practices towards vital signs monitoring on paediatric wards: Cross-validation of the Ped-V scale.

PURPOSE: To develop and psychometrically test an instrument measuring the attitudes and practices towards vital signs (VS) monitoring in nurses caring for children on paediatric wards (Ped-V scale). DESIGN AND METHODS: This is a multicentre cross-validation study with a cross-sectional design. The Ped-V scale was developed by adapting the V-scale to the paediatric context and administered to a convenience sample of clinical nurses working in paediatric wards from January to May 2020. The content validity of the Ped-V scale was evaluated by a group of 10 experts. The psychometric properties of the scale were tested through Exploratory Factor Analysis (EFA) and Confirmatory Factor Analysis (CFA). RESULTS: Overall, 10 Italian hospitals participated in the study, and 640 questionnaires were completed (87% female). At EFA a 30-item version of the scale and four factors emerged. This solution was confirmed at CFA: F1) 'Inaccuracy of VS monitoring and workload'; F2) 'Clinical competence and communication'; F3) 'Standardization and protocol adherence'; F4) 'Misconceptions about key indicators'. Cronbach's alpha ranged between 0.63 and 0.85. CONCLUSIONS: The Ped-V scale is valid and reliable for use in the paediatric context to identify barriers concerning nurses' self-efficacy, competences, and knowledge of clinical indicators of paediatric critical deterioration, attitudes towards accuracy, standardization, communication to senior team members and the appropriate use of technology in paediatric VS monitoring. PRACTICE IMPLICATIONS: The Ped-V scale may assist in identifying gaps in nurses' attitudes and devising strategies to change nurses' beliefs, knowledge, skills and decreasing individual, local cultural or organizational barriers towards VS monitoring.

Impact of telemedicine on health outcomes in children with medical complexity: an integrative review.

Children with medical complexity (CMC) are a high priority population with chronic illnesses dependent on the use of health services, on technological systems to support their vital functions and characterized by multiple health needs. One of the main challenges linked to chronic conditions is finding solutions to monitor CMC at home, avoiding re-hospitalization and the onset of complications. Telemedicine enables to remotely follow up patients and families. An integrative review was performed to assess whether telemedicine improves health outcomes for CMC. Medline/PubMed, CINAHL, Cochrane Library, Web of Science, and Scopus were searched to identify studies describing the effect of using telemedicine systems on health outcomes for CMC. The PRISMA guidelines were used to select the papers. The methodological quality of the studies was evaluated through the Johanna Briggs Institute critical appraisal tools and the Cochrane Collaboration ROB 2.0. A total of 17 papers met the quality criteria and were included. Specialized telemedicine systems (tele-visits), telehealth, and tele-monitoring have been reported to reduce unplanned hospitalizations and visits, decrease total costs for healthcare services and families, and increase satisfaction for family members. No effect was found on the quality of life in children and their families.Conclusion: Available evidence supporting the use of telemedicine in CMC is favorable but limited. High-quality methodological studies including other unexplored health outcomes such as mental health, hospital readmissions, mortality, caregiver competences, and self-efficacy are needed to confirm the effectiveness of telemedicine systems in improving health outcomes for CMC. What is Known: • CMC are an extremely fragile patient population with frequent access to healthcare services compared with other chronic conditions. • There is conflicting evidence of the effectiveness of telemedicine clinical outcomes, healthcare utilization, and costs in pediatrics. What is New: • There is some evidence that for CMC, telemedicine reduces unplanned hospitalizations, healthcare service costs, and financial burden for families, while increasing caregivers' satisfaction with care. • Further research is needed to confirm the effectiveness of telemedicine systems in improving health for CMC.

Adherence to the bedside paediatric early warning system (BedsidePEWS) in a pediatric tertiary care hospital.

BACKGROUND: The aim of this study is to describe the adherence to the Bedside Pediatric Early Warning System (BedsidePEWS) escalation protocol in children admitted to hospital wards in a large tertiary care children's hospital in Italy. METHODS: This is a retrospective observational chart review. Data on the frequency and accuracy of BedsidePEWS score calculations, escalation of patient observations, monitoring and medical reviews were recorded. Two research nurses performed weekly visits to the hospital wards to collect data on BedsidePEWS scores, medical reviews, type of monitoring and vital signs recorded. Data were described through means or medians according to the distribution. Inferences were calculated either with Chi-square, Student's t test or Wilcoxon-Mann-Whitney test, as appropriate (P < 0.05 considered as significant). RESULTS: A total of 522 Vital Signs (VS) and score calculations [BedsidePEWS documentation events, (DE)] on 177 patient clinical records were observed from 13 hospital inpatient wards. Frequency of BedsidePEWS DE occurred < 3 times per day in 33 % of the observations. Adherence to the BedsidePEWS documentation frequency according to the hospital protocol was observed in 54 % of all patients; in children with chronic health conditions (CHC) it was significantly lower than children admitted for acute medical conditions (47 % vs. 69 %, P = 0.006). The BedsidePEWS score was correctly calculated and documented in 84 % of the BedsidePEWS DE. Patients in a 0-2 BedsidePEWS score range were all reviewed at least once a day by a physician. Only 50 % of the patients in the 5-6 score range were reviewed within 4 h and 42 % of the patients with a score ≥ 7 within 2 h. CONCLUSIONS: Escalation of patient observations, monitoring and medical reviews matching the BedsidePEWS is still suboptimal. Children with CHC are at higher risk of lower compliance. Impact of adherence to predefined response algorithms on patient outcomes should be further explored.

Characteristics of dyadic care types among patients living with multiple chronic conditions and their informal caregivers.

AIMS: To examine the distribution of dyadic care types in multiple chronic conditions, compare self-care and caregiver contributions to patients' self-care in each care type and identify the patient and caregiver characteristics associated with each care type. DESIGN: Secondary analysis of a multicentre, cross-sectional study. METHODS: Patient-caregiver dyads were enrolled from outpatient clinics and community settings. The Dyadic Symptom Management Type Scale was used to categorize dyads by type. Self-care, self-efficacy, comorbidities and cognitive impairment were measured in patients, whereas caregiver contributions to patient self-care, self-efficacy, caregiver burden and hours of caregiving were measured in caregivers. Sociodemographic characteristics perceived social support and mutuality were measured in both patients and caregivers. Univariate and multivariate analyses were performed. RESULTS: A sample of 541 patient-caregiver dyads was examined. The most frequent dyadic care type was the collaborative-oriented (63%). In the patient-oriented type, patients scored higher on self-care compared with caregivers; in the caregiver-oriented and collaborative types, caregivers scored higher than patients supporting the typology. The patient-oriented type was associated with younger, healthier male patients with better cognitive status, who scored higher for mutuality and whose caregivers scored lower for burden. The caregiver-oriented type was associated with older, less educated patients, with caregivers experiencing higher burden and unemployment. The collaborative type was associated with sicker patients, with the caregiver more probably to be female and employed, with higher perceived social support, mutuality and burden. The incongruent dyadic care type was associated with lower caregiver mutuality. IMPACT: In the context of multiple chronic conditions, clinicians should consider targeting any educational interventions aimed at improving patient self-care and caregiver contributions to self-care by dyadic care types.

Traditional and Emerging Biomarkers in Asymptomatic Left Ventricular Dysfunction-Promising Non-Coding RNAs and Exosomes as Biomarkers in Early Phases of Cardiac Damage.

Heart failure (HF) is one of the major causes of morbidity and mortality worldwide and represents an escalating problem for healthcare systems. The identification of asymptomatic patients with underlying cardiac subclinical disease would create an opportunity for early intervention and prevention of symptomatic HF. Traditional biomarkers are very useful as diagnostic and prognostic tools in the cardiovascular field; however, their application is usually limited to overt cardiac disease. On the other hand, a growing number of studies is investigating the diagnostic and prognostic potential of new biomarkers, such as micro-RNAs (miRNA), long non-coding RNAs, and exosome cargo, because of their involvement in the early phases of cardiac dysfunction. Unfortunately, their use in asymptomatic phases remains a distant goal. The aim of this review is to gather the current knowledge of old and novel biomarkers in the early diagnosis of cardiac dysfunction in asymptomatic individuals.

Effects of SARS-CoV-2 on Cardiovascular System: The Dual Role of Angiotensin-Converting Enzyme 2 (ACE2) as the Virus Receptor and Homeostasis Regulator-Review.

Angiotensin-converting enzyme 2 (ACE2) is the entry receptor for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), the cause of Coronavirus Disease-2019 (COVID-19) in humans. ACE-2 is a type I transmembrane metallocarboxypeptidase expressed in vascular endothelial cells, alveolar type 2 lung epithelial cells, renal tubular epithelium, Leydig cells in testes and gastrointestinal tract. ACE2 mediates the interaction between host cells and SARS-CoV-2 spike (S) protein. However, ACE2 is not only a SARS-CoV-2 receptor, but it has also an important homeostatic function regulating renin-angiotensin system (RAS), which is pivotal for both the cardiovascular and immune systems. Therefore, ACE2 is the key link between SARS-CoV-2 infection, cardiovascular diseases (CVDs) and immune response. Susceptibility to SARS-CoV-2 seems to be tightly associated with ACE2 availability, which in turn is determined by genetics, age, gender and comorbidities. Severe COVID-19 is due to an uncontrolled and excessive immune response, which leads to acute respiratory distress syndrome (ARDS) and multi-organ failure. In spite of a lower ACE2 expression on cells surface, patients with CVDs have a higher COVID-19 mortality rate, which is likely driven by the imbalance between ADAM metallopeptidase domain 17 (ADAM17) protein (which is required for cleavage of ACE-2 ectodomain resulting in increased ACE2 shedding), and TMPRSS2 (which is required for spike glycoprotein priming). To date, ACE inhibitors and Angiotensin II Receptor Blockers (ARBs) treatment interruption in patients with chronic comorbidities appears unjustified. The rollout of COVID-19 vaccines provides opportunities to study the effects of different COVID-19 vaccines on ACE2 in patients on treatment with ACEi/ARB.

Cartilage to bone transformation during fracture healing is coordinated by the invading vasculature and induction of the core pluripotency genes.

Fractures heal predominantly through the process of endochondral ossification. The classic model of endochondral ossification holds that chondrocytes mature to hypertrophy, undergo apoptosis and new bone forms by invading osteoprogenitors. However, recent data demonstrate that chondrocytes transdifferentiate to osteoblasts in the growth plate and during regeneration, yet the mechanism(s) regulating this process remain unknown. Here, we show a spatially-dependent phenotypic overlap between hypertrophic chondrocytes and osteoblasts at the chondro-osseous border in the fracture callus, in a region we define as the transition zone (TZ). Hypertrophic chondrocytes in the TZ activate expression of the pluripotency factors [Sox2, Oct4 (Pou5f1), Nanog], and conditional knock-out of Sox2 during fracture healing results in reduction of the fracture callus and a delay in conversion of cartilage to bone. The signal(s) triggering expression of the pluripotency genes are unknown, but we demonstrate that endothelial cell conditioned medium upregulates these genes in ex vivo fracture cultures, supporting histological evidence that transdifferentiation occurs adjacent to the vasculature. Elucidating the cellular and molecular mechanisms underlying fracture repair is important for understanding why some fractures fail to heal and for developing novel therapeutic interventions.

Survival/Adaptation of Bone Marrow-Derived Mesenchymal Stem Cells After Long-Term Starvation Through Selective Processes.

After in vivo transplantation, mesenchymal stem cells (MSC) face an ischemic microenvironment, characterized by nutrient deprivation and reduced oxygen tension, which reduces their viability and thus their therapeutic potential. Therefore, MSC response to models of in vitro ischemia is of relevance for improving their survival and therapeutic efficacy. The aim of this study was to understand the survival/adaptive response mechanism that MSC use to respond to extreme culture conditions. Specifically, the effect of a long-term starvation on human bone marrow (hBM)-derived MSC cultured in a chemically defined medium (fetal bovine serum-free [SF] and human SF), either in hypoxic or normoxic conditions. We observed that hBM-MSC that were isolated and cultured in SF medium and subjected to a complete starvation for up to 75 days transiently changed their behavior and phenotype. However, at the end of that period, hBM-MSC retained their characteristics as determined by their morphology, DNA damage resistance, proliferation kinetic, and differentiation potential. This survival mode involved a quiescent state, confirmed by increased expression of cell cycle regulators p16, p27, and p57 and decreased expression of proliferating cell nuclear antigen (PCNA), Ki-67, mTOR, and Nanog. In addition, Jak/STAT (STAT6) antiapoptotic activity selected which cells conserved stemness and that supported metabolic, bioenergetic, and scavenging requirements. We also demonstrated that hBM-MSC exploited an autophagic process which induced lipid ß-oxidation as an alternative energy source. Priming MSC by concomitant starvation and culture in hypoxic conditions to induce their quiescence would be of benefit to increase MSC survival when transplanted in vivo. Stem Cells 2019;37:813-827.

Cardiac Tumors: Diagnosis, Prognosis, and Treatment.

PURPOSE OF REVIEW: Cardiac masses frequently present significant diagnostic and therapeutic clinical challenges and encompass a broad set of lesions that can be either neoplastic or non-neoplastic. We sought to provide an overview of cardiac tumors using a cardiac chamber prevalence approach and providing epidemiology, imaging, histopathology, diagnostic workup, treatment, and prognoses of cardiac tumors. RECENT FINDINGS: Cardiac tumors are rare but remain an important component of cardio-oncology practice. Over the past decade, the advances in imaging techniques have enabled a noninvasive diagnosis in many cases. Indeed, imaging modalities such as cardiac magnetic resonance, computed tomography, and positron emission tomography are important tools for diagnosing and characterizing the lesions. Although an epidemiological and multimodality imaging approach is useful, the definite diagnosis requires histologic examination in challenging scenarios, and histopathological characterization remains the diagnostic gold standard. A comprehensive clinical and multimodality imaging evaluation of cardiac tumors is fundamental to obtain a proper differential diagnosis, but histopathology is necessary to reach the final diagnosis and subsequent clinical management.

From Brain to Heart: Possible Role of Amyloid-ß in Ischemic Heart Disease and Ischemia-Reperfusion Injury.

Ischemic heart disease (IHD) is among the leading causes of death in developed countries. Its pathological origin is traced back to coronary atherosclerosis, a lipid-driven immuno-inflammatory disease of the arteries that leads to multifocal plaque development. The primary clinical manifestation of IHD is acute myocardial infarction (AMI),) whose prognosis is ameliorated with optimal timing of revascularization. Paradoxically, myocardium re-perfusion can be detrimental because of ischemia-reperfusion injury (IRI), an oxidative-driven process that damages other organs. Amyloid-ß (Aß) plays a physiological role in the central nervous system (CNS). Alterations in its synthesis, concentration and clearance have been connected to several pathologies, such as Alzheimer's disease (AD) and cerebral amyloid angiopathy (CAA). Aß has been suggested to play a role in the pathogenesis of IHD and cerebral IRI. The purpose of this review is to summarize what is known about the pathological role of Aß in the CNS; starting from this evidence, we will illustrate the role played by Aß in the development of coronary atherosclerosis and its possible implications in the pathophysiology of IHD and myocardial IRI. Better elucidation of Aß's contribution to the molecular pathways underlying IHD and IRI could be of great help in developing new therapeutic strategies.

Glycosylation of blood cells during the onset and progression of atherosclerosis and myocardial infarction.

Protein glycosylation controls cell-cell and cell-extracellular matrix (ECM) communication in immune, vascular, and inflammatory processes, underlining the critical role of this process in the identification of disease biomarkers and the design of novel therapies. Emerging evidence highlights the critical role of blood cell glycosylation in the pathophysiology of atherosclerosis (ATH) and myocardial infarction (MI). Here, we review the role of glycosylation in the interplay between blood cells, particularly erythrocytes, and endothelial cells (ECs), highlighting the involvement of this critical post/cotranslational modification in settings of cardiovascular disease (CVD). Importantly, we focus on emerging preclinical studies and clinical trials based on glycan-targeted drugs to validate their therapeutic potential. These findings may help establish new trends in preventive medicine and delineate novel targeted therapies in CVD.

Serine 111 phosphorylation regulates OCT4A protein subcellular distribution and degradation.

Embryonic stem cell self-renewal properties are attributed to critical amounts of OCT4A, but little is known about its post-translational regulation. Sequence analysis revealed that OCT4A contains five putative ERK1/2 phosphorylation sites. Consistent with the hypothesis that OCT4A is a putative ERK1/2 substrate, we demonstrate that OCT4A interacts with ERK1/2 by using both in vitro GST pulldown and in vivo co-immunoprecipitation assays. MS analysis identified phosphorylation of OCT4A at Ser-111. To investigate the possibility that ERK1/2 activation can enhance OCT4A degradation, we analyzed endogenous ubiquitination in cells transfected with FLAG-OCT4A alone or with constitutively active MEK1 (MEK1(CA)), and we observed that the extent of OCT4 ubiquitination was clearly increased when MEK1(CA) was coexpressed and that this increase was more evident after MG132 treatment. These results suggest an increase in OCT4A ubiquitination downstream of MEK1 activation, and this could account for the protein loss observed after FGF2 treatment and MEK1(CA) transfection. Understanding and controlling the mechanism by which stem cells balance self-renewal would substantially advance our knowledge of stem cells.

Considering the Value of 3D Cultures for Enhancing the Understanding of Adhesion, Proliferation, and Osteogenesis on Titanium Dental Implants.

BACKGROUND: Individuals with pathologic conditions and restorative deficiencies might benefit from a combinatorial approach encompassing stem cells and dental implants; however, due to the various surface textures and coatings, the influence of titanium dental implants on cells exhibits extensive, wide variations. Three-dimensional (3D) cultures of stem cells on whole dental implants are superior in testing implant properties and were used to examine their capabilities thoroughly. MATERIALS AND METHODS: The surface micro-topography of five titanium dental implants manufactured by sandblasting with titanium, aluminum, corundum, or laser sintered and laser machined was compared in this study. After characterization, including particle size distribution and roughness, the adhesion, proliferation, and viability of adipose-derived stem cells (ADSCs) cultured on the whole-body implants were tested at three time points (one to seven days). Finally, the capacity of the implant to induce ADSCs' spontaneous osteoblastic differentiation was examined at the same time points, assessing the gene expression of collagen type 1 (coll-I), osteonectin (osn), alkaline phosphatase (alp), and osteocalcin (osc). RESULTS: Laser-treated (Laser Mach and Laser Sint) implants exhibited the highest adhesion degree; however, limited proliferation was observed, except for Laser Sint implants, while viability differences were seen throughout the three time points, except for Ti Blast implants. Sandblasted surfaces (Al Blast, Cor Blast, and Ti Blast) outpaced the laser-treated ones, inducing higher amounts of coll-I, osn, and alp, but not osc. Among the sandblasted surfaces, Ti Blast showed moderate roughness and the highest superficial texture density, favoring the most significant spontaneous differentiation relative to all the other implant surfaces. CONCLUSIONS: The results indicate that 3D cultures of stem cells on whole-body titanium dental implants is a practical and physiologically appropriate way to test the biological characteristics of the implants, revealing peculiar differences in ADSCs' adhesion, proliferation, and activity toward osteogenic commitment in the absence of specific osteoinductive cues. In addition, the 3D method would allow researchers to test various implant surfaces more thoroughly. Integrating with preconditioned stem cells would inspire a more substantial combinatorial approach to promote a quicker recovery for patients with restorative impairments.

Reproducing extracellular matrix adverse remodelling of non-ST myocardial infarction in a large animal model.

The rising incidence of non-ST-segment elevation myocardial infarction (NSTEMI) and associated long-term high mortality constitutes an urgent clinical issue. Unfortunately, the study of possible interventions to treat this pathology lacks a reproducible pre-clinical model. Indeed, currently adopted small and large animal models of MI mimic only full-thickness, ST-segment-elevation (STEMI) infarcts, and hence cater only for an investigation into therapeutics and interventions directed at this subset of MI. Thus, we develop an ovine model of NSTEMI by ligating the myocardial muscle at precise intervals parallel to the left anterior descending coronary artery. Upon histological and functional investigation to validate the proposed model and comparison with STEMI full ligation model, RNA-seq and proteomics show the distinctive features of post-NSTEMI tissue remodelling. Transcriptome and proteome-derived pathway analyses at acute (7 days) and late (28 days) post-NSTEMI pinpoint specific alterations in cardiac post-ischaemic extracellular matrix. Together with the rise of well-known markers of inflammation and fibrosis, NSTEMI ischaemic regions show distinctive patterns of complex galactosylated and sialylated N-glycans in cellular membranes and extracellular matrix. Identifying such changes in molecular moieties accessible to infusible and intra-myocardial injectable drugs sheds light on developing targeted pharmacological solutions to contrast adverse fibrotic remodelling.

Adipose tissue-derived stem cell in vitro differentiation in a three-dimensional dental bud structure.

Tooth morphogenesis requires sequential and reciprocal interactions between the cranial neural crest-derived mesenchymal cells and the stomadial epithelium, which regulate tooth morphogenesis and differentiation. We show how mesenchyme-derived single stem cell populations can be induced to transdifferentiate in vitro in a structure similar to a dental bud. The presence of stem cells in the adipose tissue has been previously reported. We incubated primary cultures of human adipose tissue-derived stem cells in a dental-inducing medium and cultured the aggregates in three-dimensional conditions. Four weeks later, cells formed a three-dimensional organized structure similar to a dental bud. Expression of dental tissue-related markers was tested assaying lineage-specific mRNA and proteins by RT-PCR, immunoblot, IHC, and physical-chemical analysis. In the induction medium, cells were positive for ameloblastic and odontoblastic markers as both mRNAs and proteins. Also, cells expressed epithelial, mesenchymal, and basement membrane markers with a positional relationship similar to the physiologic dental morphogenesis. Physical-chemical analysis revealed 200-nm and 50-nm oriented hydroxyapatite crystals as displayed in vivo by enamel and dentin, respectively. In conclusion, we show that adipose tissue-derived stem cells in vitro can transdifferentiate to produce a specific three-dimensional organization and phenotype resembling a dental bud even in the absence of structural matrix or scaffold to guide the developmental process.

Understanding How Heart Metabolic Derangement Shows Differential Stage Specificity for Heart Failure with Preserved and Reduced Ejection Fraction.

Heart failure (HF) is a clinical condition defined by structural and functional abnormalities in the heart that gradually result in reduced cardiac output (HFrEF) and/or increased cardiac pressures at rest and under stress (HFpEF). The presence of asymptomatic individuals hampers HF identification, resulting in delays in recognizing patients until heart dysfunction is manifested, thus increasing the chance of poor prognosis. Given the recent advances in metabolomics, in this review we dissect the main alterations occurring in the metabolic pathways behind the decrease in cardiac function caused by HF. Indeed, relevant preclinical and clinical research has been conducted on the metabolite connections and differences between HFpEF and HFrEF. Despite these promising results, it is crucial to note that, in addition to identifying single markers and reliable threshold levels within the healthy population, the introduction of composite panels would strongly help in the identification of those individuals with an increased HF risk. That said, additional research in the field is required to overcome the current drawbacks and shed light on the pathophysiological changes that lead to HF. Finally, greater collaborative data sharing, as well as standardization of procedures and approaches, would enhance this research field to fulfil its potential.

Assessing the Efficacy of Whole-Body Titanium Dental Implant Surface Modifications in Inducing Adhesion, Proliferation, and Osteogenesis in Human Adipose Tissue Stem Cells.

BACKGROUND: Although the influence of titanium implants' micro-surface properties on titanium discs has been extensively investigated, the research has not taken into consideration their whole-body effect, which may be considered possible using a combinatorial approach. METHODS: Five titanium dental implants with a similar moderate roughness and different surface textures were thoroughly characterized. The cell adhesion and proliferation were assessed after adipose-tissue-derived stem cells (ADSCs) were seeded on whole-body implants. The implants' inductive properties were assessed by evaluating the osteoblastic gene expression. RESULTS: The surface micro-topography was analyzed, showing that hydroxyapatite (HA)-blasted and bland acid etching implants had the highest roughness and a lower number of surface particles. Cell adhesion was observed after 24 h on all the implants, with the highest score registered for the HA-blasted and bland acid etching implants. Cell proliferation was observed only on the laser-treated and double-acid-etched surfaces. The ADSCs expressed collagen type I, osteonectin, and alkaline phosphatase on all the implant surfaces, with high levels on the HA-treated surfaces, which also triggered osteocalcin expression on day seven. CONCLUSIONS: The findings of this study show that the morphology and treatment of whole titanium dental implants, primarily HA-treated and bland acid etching implants, impact the adherence and activity of ADSCs in osteogenic differentiation in the absence of specific osteo-inductive signals.