Video clips for patient comprehension of atrial fibrillation and deep vein thrombosis in emergency care. A randomised clinical trial.

Integrating video clips in the discharge process may enhance patients' understanding and awareness of their condition. To determine the effect of video clip-integrated discharge discussion on patient comprehension of atrial fibrillation (AF) and deep vein thrombosis (DVT), and their main complications (stroke and pulmonary embolism), we designed a multicentre, pragmatic, parallel groups, randomised clinical trial, that was conducted at two Emergency Units in Italy. A convenience sample of 144 adult patients (or their caregivers) discharged home with either AF or DVT were randomised to receive standard verbal instructions (control) or video clip-integrated doctor-patient discharge discussion. Participants were guided by the discharging physician through the clip. Mean score for primary outcome (knowledge of the diagnosis and its potential complication) (range 0-18) was 5.87 (95% CI, 5.02-6.72] in the control group and 8.28 (95% CI, 7.27-9.31) in the intervention group (mean difference, -2.41; 95% CI, -3.73 to -1.09; p < 0.001). Among secondary outcomes, mean score for knowledge of the prescribed therapy (range 0-6) was 2.98 (95% CI, 2.57-3.39) in the control group and 3.20 (95% CI, 2.73-3.67) in the study group (mean difference, -0.22; 95% CI, -0.84 to 0.39). Mean score for satisfaction (range 0-12) was 7.34 (95% CI, 6.45-8.23) in the control arm and 7.97 (95% CI, 7.15-8.78) in the intervention arm (mean difference, -0.625; 95% CI -1.82 to 0.57). Initiation rate of newly prescribed anticoagulants was 80% (36/45) in the control group and 90.2% (46/51) in the intervention group. Among 109 patients reached at a median follow up of 21 (IQR 16-28) months, 5.55% (3/54) in the control arm and 1.82% (1/55) in the intervention arm had developed stroke or pulmonary embolism. In this trial, video clip-integrated doctor-patient discharge discussion, improved participants comprehension of AF and DVT and their main complications. Physicians should consider integrating these inexpensive tools during the discharge process of patients with AF or DVT.Trial Registration: ClinicalTrials.gov Identifier "NCT03734406".

Prevalence of Scoliosis in Children and Adolescents with Cystic Fibrosis.

The prevalence of scoliosis in people with cystic fibrosis (CF) seems to be greater than in the normal population. Over the last two years, a screening for spinal deformities was carried out in patients with CF aged 5 to 18 years, followed up at the CF regional Centre in Parma (Italy). Forty-three patients (twenty-seven males, mean age: 11.8 ± 4.5 years) were enrolled in the study. Nine patients (20.9%) were diagnosed with scoliosis, with a mean Cobb angle of 20.8 ± 9.4 (12-38°). Five patients (11.6%) were diagnosed with a postural kyphosis attitude and one with pathological fixed kyphosis. All patients with scoliosis and postural kyphosis started daily physiotherapeutic scoliosis-specific exercises (PSSE). Compared to people without CF, the prevalence of scoliosis in our paediatric CF population seems to be higher and more present in males; the curves were thoracic and mostly right-sided. CF disease, hyposthenic postural attitude and sedentary lifestyle can contribute to the pathogenesis of this musculoskeletal alteration. Spinal deformities may negatively affect pulmonary function, resulting in disability, pain and a decreased quality of life. Since the prevention of musculoskeletal deformities is easier than restoration, in CF population targeted screening during growth and interventions, including regular physical exercise, are mandatory.

Sodium-glucose co-transporter 2 inhibitors in heart failure: an updated evidence-based practical guidance for clinicians.

The sodium-glucose co-transporter 2 (SGLT2) inhibitors have been shown to reduce risks of clinical events in patients with heart failure (HF), with early and sustained benefits regardless of ejection fraction, diabetic status, and care setting. As part and parcel of the modern foundational HF therapy, clinicians should be familiar with these drugs, in order to implement their use and limit the potential adverse effects. We present an up-to-date review of current evidence and a practical guide for the prescription of SGLT2 inhibitors in patients with HF, highlighting important elements for patient selection, treatment initiation, dosing, and problem solving.

Basic Motor Competencies of (Pre)School Children: The Role of Social Integration and Health-Related Quality of Life.

In (pre)school, children acquire and deepen their basic motor competencies (BMCs) and interact with peers and friends. BMCs are a central developmental goal in childhood and the prerequisite for participation in sportive aspects of social life. Both motor competencies and social integration are linked to children's health-related quality of life (HRQoL). The aim of the present study was to describe the connection between BMCs, social relationships, and aspects of HRQoL in (pre)school children. In this study, the BMCs of N = 1163 preschool children (M = 5.7 years, SD = 0.57, 52% boys) and N = 880 first and second graders (M = 7.5 years, SD = 0.58, 51% boys) were tested. The children's social integration was assessed by the teachers; the HRQoL was recorded from the parents' perspective. In both preschool and primary school, children with better BMCs also showed higher values in their social integration. Moreover, the results indicated a connection between BMCs and general HRQoL in primary school and BMCs and physical well-being in preschool. As BMCs, social integration, and HRQoL seem to be connected in (pre)school, this should be considered both from developmental and health-oriented perspectives, as well as for physical education (PE) lessons.

The Reliability of Anamnestic Data in the Management of Clostridium Tetani Infection in Elderly.

Background: Tetanus infection remains a significant complication of wounds. Because most tetanus treatment guidelines rely on anamnestic data collected directly from patients, the congruence between anamnesis and laboratory evidence must be verified, especially in the elderly population. Aim: Assess, in both the geriatric population (>65) and the non-geriatric one, the reliability of anamnestic data for managing patients with tetanus-risk wounds, identified categories of populations most exposed to non-vaccination coverage, and assessed the agreement of the Tetanos Quick Stick (TQS) results with the therapy performed (administration of tetanus vaccine or immunoglobulin). Methods: In this retrospective single-center observational study, patients were asked their immunization status against tetanus vaccination. The decision to administer a vaccine or immunoglobulin was therefore clinical and based on anamnestic criteria. The TQS test was then given to patients who were unaware of their immunity status. Patients who thought they knew it but were not sure were given the TQS test to determine whether the anamnestic collection was supported by the test. The TQS test results were compared with the anamnestic data. Results: Most patients, geriatric and not geriatric, did not know their immune status. Among those who reported knowing their immune status, there was no agreement between the vaccine coverage declared by patients and the TQS test results (p < 0.001), mainly in geriatric patients but also in the control group. Elderly and women had significantly lower positive TQS test results (p < 0.001). There was a statistically significant discrepancy (p < 0.001) between the therapy based on anamnestic data and the TQS test results. Conclusion: The reliability of anamnestic data for the management of patients with tetanus-risk wounds is low and decreases with age, becoming minimal in geriatric patients. Elderly and women are less likely to have an effective vaccination status against tetanus.

Sodium-glucose co-transporter-2 inhibitors eligibility in patients with heart failure with reduced ejection fraction.

BACKGROUND: The sodium-glucose co-transporter-2 (SGLT2) inhibitors dapagliflozin and empagliflozin have been demonstrated to reduce adverse cardiovascular outcomes in patients with heart failure with reduced ejection fraction (HFrEF). Limited data are available characterizing the generalizability of SGLT2 inhibitors treatment in the clinical practice. The aim of the study was to evaluate the proportion of outpatients with HFrEF that would be eligible for SGLT2 inhibitors in a contemporary real-world population. METHODS: We retrospectively evaluated patients with chronic stable HFrEF followed-up at the HF outpatient clinic of our institution. Patients' eligibility was assessed according to the entry criteria of DAPA-HF (dapagliflozin) and EMPEROR-Reduced (empagliflozin) trials and to US Food and Drug Administration (FDA) label criteria (only dapagliflozin). RESULTS: A total of 441 HFrEF patients was enrolled. According to the major inclusion and exclusion criteria from DAPA-HF and EMPEROR-Reduced trials, 198 (45%) patients would be candidates for initiation of both dapagliflozin and empagliflozin, 61 (14%) would be eligible only to dapagliflozin and 23 (5%) only to empagliflozin, without significant differences between diabetic and non-diabetic patients (p = 0.23). Among patients not suitable for gliflozins treatment (159 patients; 36%), the major determinant of ineligibility was the failure to achieve the predefined NT-proBNP inclusion threshold. Excluding NTproBNP as per FDA label criteria, dapagliflozin eligibility increased to 86%. CONCLUSIONS: In our real-world analysis a large proportion of HFrEF patients would be candidates for initiation of SGLT2 inhibitors, supporting its broad generalizability in clinical practice. This would be expected to reduce morbidity and mortality in eligible patients.

Effect of Rapid Respiratory Virus Testing on Antibiotic Prescribing Among Children Presenting to the Emergency Department With Acute Respiratory Illness: A Randomized Clinical Trial.

Importance: There is high usage of antibiotics in the emergency department (ED) for children with acute respiratory illnesses. Studies have reported decreased antibiotic use among inpatients with rapid respiratory pathogen (RRP) testing. Objective: To determine whether RRP testing leads to decreased antibiotic use and health care use among children with influenzalike illness (ILI) in an ED. Design, Setting, and Participants: A randomized clinical trial among children aged 1 month to 18 years presenting to an ED with ILI from December 1, 2018, to November 30, 2019, was conducted. Data were analyzed March 23, 2020, to April 2, 2021. All children received a nasopharyngeal swab for RRP testing and were randomized 1:1 to the intervention group or control group (results not given, routine clinical care). Results were available in 45 minutes. Intention-to-treat analyses and modified intention-to-treat (clinician knows results) analyses were conducted using multivariable Poisson regression. Interventions: Rapid respiratory pathogen test results given to clinicians. Main Outcomes and Measures: Antibiotic prescribing was the primary outcome; influenza antiviral prescribing, ED length of stay, hospital admission, and recurrent health care visits were the secondary outcomes. Results: Among 931 ED visits (intervention group, 452 children group and control group, 456 children after exclusion of those not meeting criteria or protocol violations), a total of 795 RRP test results (85%) were positive. The median age of the children was 2.1 years (interquartile range, 0.9-5.6 years); 509 (56%) were boys. Most children (478 [53%]) were Hispanic, 688 children (76%) received government insurance, and 314 (35%) had a high-risk medical condition. In the intention-to-treat intervention group, children were more likely to receive antibiotics (relative risk [RR], 1.3; 95% CI, 1.0-1.7), with no significant differences in antiviral prescribing, medical visits, and hospitalization. In inverse propensity-weighted modified intention-to-treat analyses, children with test results known were more likely to receive antivirals (RR, 2.6; 95% CI, 1.6-4.5) and be hospitalized (RR, 1.8; 95% CI, 1.4-2.5); there was no significant difference in antibiotic prescribing (RR, 1.1; 95% CI, 0.9-1.4). Conclusions and Relevance: The use of RRP testing in the ED for ILI did not decrease antibiotic prescribing in this randomized clinical trial. There is a limited role for RRP pathogen testing in children in this setting. Trial Registration: ClinicalTrials.gov Identifier: NCT03756753.

Acute atrial ischemia associates with early but not late new-onset atrial fibrillation in STEMI patients treated with primary PCI: relationship with in-hospital outcomes.

BACKGROUND: New-onset atrial fibrillation (NOAF), both early (EAF) or late (LAF), may complicate ST-segment elevation myocardial infarction (STEMI). The mechanisms underlying EAF or LAF are poorly described. We investigated atrial branch occlusion and EAF or LAF onset in STEMI patients undergoing primary percutaneous coronary intervention. METHODS: This was a retrospective cohort study including 155 STEMI patients. Patients were divided into 3 groups: sinus rhythm (SR), EAF, or LAF. Clinical characteristics, angiographic features including occlusion of atrial branches, namely ramus ostia cavae superioris (ROCS), atrio-ventricular node artery (AVNA), right intermediate atrial artery (RIAA), and left intermediate atrial artery, were assessed. We also investigated in-hospital adverse events (AEs) and death. RESULTS: Mean age was 63.8±11.9 years; 78.7% were men. NOAF was detected in 22 (14.2%) patients: 10 (6.4%) EAF and 12 LAF (7.7%). Compared to EAF, LAF patients were older (p=0.013), with higher GRACE risk score (p=0.014) and Killip class (p=0.015), depressed ejection fraction (p=0.007), elevated filling pressures (p=0.029), higher C-reactive protein (p=0.014) and more with thrombolysis in myocardial infarction flow <3 (p=0.015). Compared to SR, EAF was associated with higher prevalence of occluded ROCS (p=0.010), AVNA (p=0.005), and RIAA (p<0.001). Moreover, EAF patients had more frequently ≥2 diseased atrial branches than SR (19.5%, p<0.001) and LAF (25%, p<0.030) patients. LAF patients had a higher in-hospital AEs (p=0.019 vs SR; p=0.029 vs EAF) and death (p=0.004 vs SR). CONCLUSIONS: The occlusion of atrial branches is associated with EAF but not LAF following STEMI. LAF patients had worse in-hospital AEs and mortality.

Connection between Social Relationships and Basic Motor Competencies in Early Childhood.

In preschool, children build new contacts and social relationships with other people. They learn to cooperate with their peers and communicate in groups. In addition to social relationships, basic motor competencies (in German: Motorische Basiskompetenzen (MOBAK)) are also seen as a central developmental goal in early childhood and are necessary for participation in the culture of sports and movement. The aim of this paper is to describe the connection between social relationships and basic motor competencies in early childhood. In this present study, the motor competencies of N = 548 preschool children (51% girls, M = 68.0 months, SD = 6.8) were tested in the competence areas of self-movement and object movement. The children's perceived social relationships were recorded from teacher and parent perspectives. The results clearly show a connection between social relationships and motor competencies in early childhood, with a stronger connection observed in boys. This finding is relevant both from a developmental and a health-oriented perspective, as it points to a link between physical and mental health, as well as technical and interdisciplinary competencies, in early childhood.

Fundamental role of BMP15 in human ovarian folliculogenesis revealed by null and missense mutations associated with primary ovarian insufficiency.

Bone morphogenetic protein 15 (BMP15) encodes an oocyte factor with a relevant role for folliculogenesis as homodimer or cumulin heterodimer (BMP15-GDF9). Heterozygous BMP15 variants in the precursor or mature peptide had been associated with primary ovarian insufficiency (POI), but the underlying mechanism remains elusive and a double dose of BMP15 was suggested to be required for adequate ovarian reserve. We uncovered two homozygous BMP15 null variants found in two girls with POI and primary amenorrhea. Both heterozygous mothers reported physiological menopause. We then performed western blot, immunofluorescence, and reporter assays to investigate how previously reported missense variants, p.Y235C and p.R329C, located in the precursor or mature domains of BMP15, may affect protein function. The p.R329C variant demonstrates an impaired colocalization with growth/differentiation factor 9 (GDF9) at confocal images and diminished activation of the SMAD pathways at western blot and reporter assays in COV434 follicular cell line. In conclusion, BMP15 null mutations cause POI only in the homozygous state, thus discarding the possibility that isolated BMP15 haploinsufficiency can cause evident ovarian defects. Alternatively, heterozygous BMP15 missense variants may affect ovarian function by interfering with cumulin activity. Our data definitely support the fundamental role of BMP15 in human ovarian folliculogenesis.

Clinical frailty and triggers in Takotsubo syndrome: the notable role of a new classification.

AIMS: Takotsubo syndrome (TTS) is a mainly transient and acute heart failure mimicking an acute coronary syndrome. Originally described in postmenopausal women, over time TTS has been associated with an increasingly advanced age. Emotional and physical triggers precipitating TTS have been correlated in most cases. The aim of our work was to detect differences between patients with or without recognizable triggers preceding the onset of symptoms. METHODS: We enrolled 22 consecutive patients. They were all women with an average age of 71 ±â€Š12 (range 40-90) years. Twelve patients correlated the onset of TTS symptoms with a trigger (group 1) and 10 patients (group 2) denied any correlation with stressful events. RESULTS: Patients in group 1 showed a higher average age than group 2 (76 ±â€Š10 vs. 64 ±â€Š12 years; P = 0.023), a longer hospitalization period (22 ±â€Š12 vs. 11 ±â€Š10 days; P = 0.01) and greater value of frailty score (P = 0.004). Despite a decrease and subsequent recovery of systolic function, there was no significant difference between groups. Group 1 showed a longer corrected QT (QTc) (505 ±â€Š53 vs. 453 ±â€Š42 ms, P = 0.03), a greater decrease in QTc at discharge (-57 ±â€Š44 vs. 0.3 ±â€Š39 ms; P = 0.004), with the result that at discharge both groups showed a comparable QTc. CONCLUSION: Our results emphasized that typical TTS female patients with precipitating triggers have advanced age, clinical frailty and QTc abnormalities.

SOD1 stimulates lamellipodial protrusions in Neuro 2A cell lines.

We here investigated the effects of overexpressed superoxide dismutase (SOD)1 and amyotrophic lateral sclerosis (ALS)-linked SOD1 mutants G93A and G147S in Neuro 2A (N2A) cell lines, and found a three-fold increase in lamellipodia either in cells cultured under differentiated or undifferentiated growth conditions. In undifferentiated N2A cells, SOD1 constructs promoted lamellipodial protrusions to similar extent as the overexpression of Rac1, and SOD1-mediated lamellipodia were prevented by coexpression of the N17 dominant-negative form of Rac1, or shRNA for a downstream effector of Rac1, the insulin receptor tyrosine kinase substrate p53 (IRSp53) or its binding partner LIN7. Moreover, no additive effect was measured by coexpression of the SOD1 constructs with Rac1, IRSp53 or LIN7. Collectively these data support a role for SOD1 in the regulation of Rac1-mediated lamellipodia pathway, a property fully retained by the two SOD1 mutants.

Impaired protein stability and nuclear localization of NOBOX variants associated with premature ovarian insufficiency.

Premature ovarian insufficiency (POI) is a clinical syndrome defined by a loss of ovarian activity before the age of 40. Its pathogenesis is still largely unknown, but increasing evidences support a genetic basis in most cases. Among these, heterozygous mutations in NOBOX, a homeobox gene encoding a transcription factor expressed specifically by oocyte and granulosa cells within the ovary, have been reported in ∼6% of women with sporadic POI. The pivotal role of NOBOX in early folliculogenesis is supported by findings in knock-out mice. Here, we report the genetic screening of 107 European women with idiopathic POI, recruited in various settings, and the molecular and functional characterization of the identified variants to evaluate their involvement in POI onset. Specifically, we report the identification of two novel and two recurrent heterozygous NOBOX variants in 7 out of 107 patients, with a prevalence of 6.5% (upper 95% confidence limit of 11.17%). Furthermore, immunolocalization, Western Blot and transcriptional assays conducted in either HEK293T or CHO cells revealed that all the studied variants (p.R44L, p.G91W, p.G111R, p.G152R, p.K273*, p.R449* and p.D452N) display variable degrees of functional impairment, including defects in transcriptional activity, autophagosomal degradation, nuclear localization or protein instability. Several variants conserve the ability to interact with FOXL2 in intracellular aggregates. Their inability to sustain gene expression, together with their likely aberrant effects on protein stability and degradation, make the identified NOBOX mutations a plausible cause of POI onset.

The Role of Cyclo(His-Pro) in Neurodegeneration.

Neurodegenerative diseases may have distinct genetic etiologies and pathological manifestations, yet share common cellular mechanisms underpinning neuronal damage and dysfunction. These cellular mechanisms include excitotoxicity, calcium dysregulation, oxidative damage, ER stress and neuroinflammation. Recent data have identified a dual role in these events for glial cells, such as microglia and astrocytes, which are able both to induce and to protect against damage induced by diverse stresses. Cyclo(His-Pro), a cyclic dipeptide derived from the hydrolytic removal of the amino-terminal pyroglutamic acid residue of the hypothalamic thyrotropin-releasing hormone, may be important in regulating the nature of the glial cell contribution. Cyclo(His-Pro) is ubiquitous in the central nervous system and is a key substrate of organic cation transporters, which are strongly linked to neuroprotection. The cyclic dipeptide can also cross the brain-blood-barrier and, once in the brain, can affect diverse inflammatory and stress responses by modifying the Nrf2-NF-κB signaling axis. For these reasons, cyclo(His-Pro) has striking potential for therapeutic application by both parenteral and oral administration routes and may represent an important new tool in counteracting neuroinflammation-based degenerative pathologies. In this review, we discuss the chemistry and biology of cyclo(His-Pro), how it may interact with the biological mechanisms driving neurodegenerative disease, such as amyotrophic lateral sclerosis, and thereby act to preserve or restore neuronal function.

Novel localisation and possible function of LIN7 and IRSp53 in mitochondria of HeLa cells.

By means of immunofluorescence and subcellular fractionation experiments, we here demonstrate mitochondrial distribution of LIN7 and IRSp53 in HeLa cells. These peripheral proteins displayed a tight association with mitochondria and coimmunoprecipitated from mitochondrial fractions. In line with a role for LIN7 in the regulation of IRSp53 activity on actin dynamics, the morphology of mitochondria was similarly altered by changing the expression levels of either each protein or both, whereas mitochondrial morphology was preserved in cells overexpressing IRSp53 deleted of its binding domains for LIN7 (IRSp53Δ5) or for actin polymerisation modulators (IRSp53ΔSH3). In particular, the overexpression of full length LIN7 and/or IRSp53 increased the percentage of cells with short mitochondria, while downregulation of the endogenous proteins by shRNAs increased the amount of cells with elongated and perinuclear clustered mitochondria. These mitochondria were only partially resistant to fragmentation induced by dissipation of the mitochondrial membrane potential (i.e. treatment with sodium azide), whereas mitochondria were fully protected by the fission defective mutant Drp1 K38A. Overexpression of LIN7 or IRSp53 did not prevent the formation of hyperfused mitochondria in cells coexpressing the Drp1 K38A mutant, thus suggesting that LIN7-IRSp53 complex requires functional Drp1 to regulate mitochondrial morphology.

Recent Advances in Discovering the Role of CCL5 in Metastatic Breast Cancer.

A variety of therapeutic strategies are currently under investigation to inhibit factors that promote tumor invasion, as metastasis is the most common cause of mortality for cancer patients. Notably, considerable emphasis has been placed on studying metastasis as a dynamic process that is highly dependent on the tumor microenvironment. In regards to breast cancer, chemokine C-C motif ligand 5 (CCL5), which is produced by tumor-associated stromal cells, has been established as an important contributor to metastatic disease. This review summarizes recent discoveries uncovering the role of this chemokine in breast cancer metastasis, including conditions that increase the generation of CCL5 and effects induced by this signaling pathway. In particular, CCL-5-mediated cancer cell migration and invasion are discussed in the context of intertwined feedback loops between breast cancer cells and stromal cells. Moreover, the potential use of CCL5 and its receptor chemokine C-C motif receptor 5 (CCR5) as targets for preventing breast cancer metastasis is also reviewed.