The maturation state and density of human cartilage microtissues influence their fusion and development into scaled-up grafts.

Functional cartilaginous tissues can potentially be engineered by bringing together numerous microtissues (µTs) and allowing them to fuse and re-organize into larger, structurally organized grafts. The maturation level of individual microtissues is known to influence their capacity to fuse, however its impact on the long-term development of the resulting tissue remains unclear. The first objective of this study was to investigate the influence of the maturation state of human bone-marrow mesenchymal stem/stromal cells (hBM-MSCSs) derived microtissues on their fusion capacity and the phenotype of the final engineered tissue.

Treatment outcomes in adult patients experiencing dental anxiety: A comparative retrospective study.

Aims: To assess and compare the effectiveness of pharmacological and cognitive-behavioral modalities-behavioral methods (BM), nitrous oxide inhalation sedation (NOIS), and premedication with Diazepam-for alleviating anxiety during dental treatment, using completed treatment sessions and adverse outcomes as indicators.

Methods And Results: For 239 patients (515 dental records), 18-53 y/o, who underwent dental treatments under anxiety reduction measures, sessions under NOIS were categorized as "nitrous group" (456 sessions) versus premedication with Diazepam or behavioral strategies (control, 59 sessions). Outcomes were completed treatment sessions considering demographic and clinical parameters, and adverse outcomes during and between sessions.

Inhibition of aortic CX3CR1+ macrophages mitigates thoracic aortic aneurysm progression in Marfan syndrome in mice.

The pathogenesis of thoracic aortic aneurysm (TAA) in Marfan syndrome (MFS) is generally attributed to vascular smooth muscle cell (VSMC) pathologies. However, the role of immune cell-mediated inflammation remains elusive. Single-cell RNA sequencing identified a subset of CX3CR1+ macrophages mainly located in the intima in the aortic roots and ascending aortas of Fbn1C1041G/+ mice, further validated in MFS patients.

Associations of Social, Behavioral, and Clinical Factors With Sex Differences in Stroke Recurrence and Poststroke Mortality.

Background: Few population-based studies have assessed sex differences in stroke recurrence. In addition, contributors to sex differences in recurrence and poststroke mortality, including social factors, are unclear. We investigated sex differences in these outcomes and the contribution of social, clinical, and behavioral factors to the sex differences.

Radiomic signatures of brain metastases on MRI: utility in predicting pathological subtypes of lung cancer.

Background: The pathological sub-classification of lung cancer is crucial in diagnosis, treatment and prognosis for patients. Quick and timely identification of pathological subtypes from imaging examinations rather than histological tests could help guiding therapeutic strategies. The aim of the study is to construct a non-invasive radiomics-based model for predicting the subtypes of lung cancer on brain metastases (BMs) from multiple magnetic resonance imaging (MRI) sequences.

Imaging melanin-associated organelles in the retinal pigment epithelium via visible light OCT redshift.

The retinal pigment epithelium (RPE) performs a number of functions essential for retinal health. RPE dysregulation and degeneration can occur in diseases. Methods to image the human RPE directly are limited, as it is only about 10 µm thick and situated between the photoreceptor outer segments and Bruch's membrane (BM).

Recombinant Klotho administration after myocardial infarction reduces ischaemic injury and arrhythmias by blocking intracellular calcium mishandling and CaMKII activation.

Ischaemic heart disease (IHD) remains a major cause of death and morbidity. Klotho is a well-known anti-ageing factor with relevant cardioprotective actions, at least when renal dysfunction is present, but its actions are much less known when renal function is preserved. This study investigated Klotho as a biomarker and potential novel treatment of IHD-associated complications after myocardial infarction (MI) under preserved renal function.

Single and multitarget stereotactic radiosurgery (SRS) with single isocenter in the treatment of multiple brain metastases (BM): institutional experience.

Introduction: SRS for the treatment of limited brain metastases (BM) is widely accepted, but there are still limitations in the management of numerous BM. Frameless single-isocenter multitarget SRS is a novel technique that allows for rapid treatment delivery to multiple BM. We report our preliminary clinical, dosimetric, and patient´s shifts outcomes with this technique.

Association between patient perception of disease status and different components of the Minimal Disease Activity (MDA) criteria in psoriatic arthritis.

Objective: The aim of this analysis was to evaluate the relationship between the criteria met of the Minimal Disease Activity (MDA) score for psoriatic arthritis (PsA) and patient-perceived disease status.

Methods: We analysed data from the ReFlaP study (NCT03119805), a cross-sectional international study of adult patients with PsA. Patients self-reported if they felt their PsA was in remission (REM), low disease activity (LDA) or neither.

Fracture Prevention with Infrequent Zoledronate in Women 50 to 60 Years of Age.

Background: Zoledronate prevents fractures in older women when administered every 12 to 18 months, but its effects on bone density and bone turnover persist beyond 5 years. Whether infrequent zoledronate administration would prevent vertebral fractures in early postmenopausal women is unknown.

Methods: We conducted a 10-year, prospective, double-blind, randomized, placebo-controlled trial involving early postmenopausal women (50 to 60 years of age) with bone mineral density T scores lower than 0 and higher than -2.

An OMV-Based Nanovaccine as Antigen Presentation Signal Enhancer for Cancer Immunotherapy.

Antigen-presenting cells (APCs) process tumor vaccines and present tumor antigens as the first signals to T cells to activate anti-tumor immunity, which process requires the assistance of co-stimulatory second signals on APCs. The immune checkpoint programmed death ligand 1 (PD-L1) not only mediates the immune escape of tumor cells but also acts as a co-inhibitory second signal on APCs. The serious dysfunction of second signals due to the high expression of PD-L1 on APCs in the tumor body results in the inefficiency of tumor vaccines.

Modifiable risk factors and symptom progression in dementia over up to 8 years-Results of the DelpHi-MV trial.

Introduction: This study investigated the association between modifiable factors and symptom progression in dementia over up to 8 years.

Methods: Multilevel growth curve models assessed the role of modifiable risk factors (low education, hearing impairment and its treatment, depression, physical inactivity, diabetes and its treatment, smoking, hypertension and its treatment, obesity, alcohol consumption, social isolation, and visual impairment) on cognitive and functional trajectories in 353 people with dementia.

Results: Higher education was associated with higher initial cognitive status but faster decline.

Restoring hematopoietic stem and progenitor cell function in mice by delivery of RNA lipid nanoparticles.

Fanconi anemia (FA) is a congenital multisystem disorder characterized by early-onset bone marrow failure (BMF) and cancer susceptibility. While gene addition and repair therapies are being considered as treatment options, depleted hematopoietic stem cell (HSC) pools, poor HSC mobilization, compromised survival during transduction, and increased sensitivity to conventional conditioning strategies limit eligibility for FA patients to receive gene therapies. As an alternative approach, we explored protein replacement by mRNA delivery via lipid nanoparticles (LNPs).

Diagnostic potential of blood-based biomarkers in multiple sclerosis.

Multiple sclerosis (MS) is a chronic inflammatory disease affecting the central nervous system (CNS). There is a significant delay in diagnosing MS as the symptoms and tests overlap with other diseases. Blood-based biomarkers, which quantify fragments of proteins involved in MS pathophysiology, have the potential as diagnostic biomarkers.

Lactate accumulation promotes immunosuppression and fibrotic transformation of bone marrow microenvironment in myelofibrosis.

Background: Clonal myeloproliferation and fibrotic transformation of the bone marrow (BM) are the pathogenetic events most commonly occurring in myelofibrosis (MF). There is great evidence indicating that tumor microenvironment is characterized by high lactate levels, acting not only as an energetic source, but also as a signaling molecule.

Methods: To test the involvement of lactate in MF milieu transformation, we measured its levels in MF patients' sera, eventually finding a massive accumulation of this metabolite, which we showed to promote the expansion of immunosuppressive subsets.

Neutrophil gelatinase-associated lipocalin (NGAL) in lupus nephritis and beyond.

Objectives: To study neutrophil gelatinase-associated lipocalin (NGAL) levels in peripheral blood in SLE, and to propose a mechanism by which neutrophils secrete NGAL on stimulation with immune complexes (IC).

Methods: NGAL was measured by ELISA in two independent Swedish SLE cohorts acting as exploratory and validation cohort (n=124 and n=308, respectively), disease controls (n=38) and healthy controls (n=77). NGAL levels were measured in supernatant from IC-stimulated neutrophils in the presence or absence of a toll-like receptor 8 inhibitor (TLR8i).

The current clinical practice and experiences in buccal midazolam prescribing in community for status epilepticus termination in the United Kingdom: The Rescue Epilepsy Medication and Training (REMIT) study.

Background: Epilepsy is one of the commonest neurological conditions worldwide and confers a significant mortality risk, partly driven by status epilepticus (SE). Terminating SE is the goal of pharmaceutical rescue therapies. This survey evaluates UK-based healthcare professionals' clinical practice and experience in community-based rescue therapy prescribing.

Determinants of Racial and Ethnic Differences in Maternal Cardiovascular Health in Early Pregnancy.

Background: Suboptimal cardiovascular health (CVH) in pregnancy is associated with adverse maternal and offspring outcomes. To guide public health efforts to reduce disparities in maternal CVH, we determined the contribution of individual- and neighborhood-level factors to racial and ethnic differences in early pregnancy CVH.

Methods: We included nulliparous individuals with singleton pregnancies who self-identified as Hispanic, non-Hispanic Black (NHB), or non-Hispanic White (NHW) and participated in the nuMoM2b cohort study (Nulliparous Pregnancy Outcomes Study: Monitoring Mothers-to-Be).

Fluid Intake and Hydration Responses to Mass Participation Gravel Cycling.

Gravel cycling is a relatively new cycling discipline, with the Union Cycliste Internationale (UCI) hosting their first World Championships in 2022. Gravel races combine features of road racing, cyclocross, and mountain biking, including terrain of varying technical difficulty, long distances, substantial elevation gain, obstacles, and limited opportunities to stop for in-race nutrition. This study assessed hydration responses to gravel races of three different distances.

Global Perspectives on Returning Genetic Research Results in Parkinson Disease.

Background And Objectives: In the era of precision medicine, genetic test results have become increasingly relevant in the care of patients with Parkinson disease (PD). While large research consortia are performing widespread research genetic testing to accelerate discoveries, debate continues about whether, and to what extent, the results should be returned to patients. Ethically, it is imperative to keep participants informed, especially when findings are potentially actionable.

Survival and quality of life after first-time diagnosis of brain metastases: a multicenter, prospective, observational study.

Background: A major concern in anticancer treatment (ACT) of brain metastases (BM) is exposing patients with short expected survival to treatments that negatively impact on quality of life (QoL). Such futile ACT at the end of life is time-consuming and burdensome for patients and their families and entails unnecessary healthcare costs. Refraining from ACT is challenging for both physicians and patients.

Efficacy evaluation of prophylactic cranial irradiation for limited stage small‑cell lung cancer in the magnetic resonance imaging era: A meta‑analysis.

The role of prophylactic cranial irradiation (PCI) in patients with limited-stage small-cell lung cancer (LS-SCLC) remains controversial in the era of magnetic resonance imaging (MRI). The present study aimed to evaluate the effectiveness of PCI in the treatment of LS-SCLC in the era of MRI. The PubMed, EMBASE and Cochrane Library databases were searched from the time of database creation until May 24, 2023, to identify clinical studies that evaluated the effectiveness of PCI in patients with LS-SCLC in the MRI era.

Elevated Hepatic Copper Content in Porto-Sinusoidal Vascular Disorder (PSVD): Leading Down a Wrong Track.

Background And Aims: Porto-sinusoidal vascular disorder (PSVD) is a rare vascular liver disorder characterised by specific histological findings in the absence of cirrhosis, which is poorly understood in terms of pathophysiology. While elevated hepatic copper content serves as diagnostic hallmark in Wilson disease (WD), hepatic copper content has not yet been investigated in PSVD.

Methods: Patients with a verified diagnosis of PSVD at the Medical University of Vienna and available hepatic copper content at the time of diagnosis of PSVD were retrospectively included.