Associations between bone material strength index and FRAX scores.

Introduction: Impact microindentation (IMI) measures bone material strength index (BMSi) in vivo. However, its ability to predict fractures is still uncertain. This study aimed to determine the association between BMSi and 10 year fracture probability, as calculated by the FRAX algorithm.

Reform of economic evaluation of medicines in Spain: proposals from the Advisory Committee for Pharmaceutical Financing.

This paper describes the reforms recommended by the Advisory Committee on the Financing of Pharmaceuticals (CAPF) for the National Health System (NHS) of Spain from 2019 to 2024 for the drug pricing and reimbursement process, to integrate economic evaluations and improve efficiency and sustainability. The CAPF has proposed a three-phase reform of the economic evaluation (EE) and budget impact analysis (BIA) processes. The first phase involves the mandatory submission of EE and BIA by applicants for new drugs.

Second-Line Treatment Options for Patients with Metastatic Triple-Negative Breast Cancer: A Review of the Clinical Evidence.

Metastatic triple-negative breast cancer has a poor prognosis and poses significant therapeutic challenges. Until recently, limited therapeutic options have been available for patients with advanced disease after failure of first-line chemotherapy. The aim of this review is to assess the current evidence supporting second-line treatment options in patients with metastatic triple-negative breast cancer.

Spontaneous and perturbation-based EEG cortical excitability markers are associated with plasma p-tau181 concentration in healthy middle-aged adults.

In early-stage Alzheimer's disease (AD) amyloid-β (Aβ) deposition can induce neuronal hyperactivity, thereby potentially triggering activity-dependent neuronal secretion of phosphorylated tau (p-tau), ensuing tau aggregation and spread. Therefore, cortical excitability is a candidate biomarker for early AD detection. Moreover, lowering neuronal excitability could potentially complement strategies to reduce Aβ and tau buildup.

Challenges in assessing national radiotherapy costs: application of the ESTRO-HERO model in Spain.

Background And Purpose: The aim was to estimate the cost of the external beam radiotherapy (EBRT) in public health care centers in Catalonia (Spain), according to the ESTRO-HERO costing model for 2018.

Materials And Methods: Personnel, equipment, and activity data from 2018 from the 11 RT centers were used, incorporating European mean values adapted to the Catalan context. Secondly, EBRT costs were estimated, incorporating 2023 fractionation technique and scheme usage percentages.

Air pollution exposure is associated with gene expression in children.

Environmental exposures, including air pollutants and lack of natural spaces, are associated with suboptimal health outcomes in children. We aimed to study the associations between environmental exposures and gene expression in children. Associations of exposure to particulate matter (PM) with diameter <2.

vCPP2319 interacts with metastatic breast cancer extracellular vesicles (EVs) and transposes a human blood-brain barrier model.

Brain metastases (BM) are frequently found in cancer patients and, though their precise incidence is difficult to estimate, there is evidence for a correlation between BM and specific primary cancers, such as lung, breast, and skin (melanoma). Among all these, breast cancer is the most frequently diagnosed among women and, in this case, BM cause a critical reduction of the overall survival (OS), especially in triple negative breast cancer (TNBC) patients. The main challenge of BM treatment is the impermeable nature of the blood-brain barrier (BBB), which shields the central nervous systems (CNS) from chemotherapeutic drugs.

LRH-1/NR5A2 targets mitochondrial dynamics to reprogram type 1 diabetes macrophages and dendritic cells into an immune tolerance phenotype.

Background: The complex aetiology of type 1 diabetes (T1D), characterised by a detrimental cross-talk between the immune system and insulin-producing beta cells, has hindered the development of effective disease-modifying therapies. The discovery that the pharmacological activation of LRH-1/NR5A2 can reverse hyperglycaemia in mouse models of T1D by attenuating the autoimmune attack coupled to beta cell survival/regeneration prompted us to investigate whether immune tolerisation could be translated to individuals with T1D by LRH-1/NR5A2 activation and improve islet survival.

Methods: Peripheral blood mononuclear cells (PBMCs) were isolated from individuals with and without T1D and derived into various immune cells, including macrophages and dendritic cells.

Complete hepatic caudate lobe resection: is robotic approach safe? Report from experienced centers.

Minimally invasive liver surgery has become widely accepted as a safe and effective approach, especially with experienced surgeons. Robotic hepatectomy may offer significant benefits in challenging procedures like caudate lobe resection. The caudate lobe's intricate anatomy and deep-seated location make its resection particularly challenging, with limited reports on minimally invasive techniques.

International consensus statement on microbiome testing in clinical practice.

There is growing interest in the potential exploitation of the gut microbiome as a diagnostic tool in medicine, but evidence supporting its clinical usefulness is scarce. An increasing number of commercial providers offer direct-to-consumer microbiome diagnostic tests without any consensus on their regulation or any proven value in clinical practice, which could result in considerable waste of individual and health-care resources and potential drawbacks in the clinical management of patients. We convened an international multidisciplinary expert panel to standardise best practices of microbiome testing for clinical implementation, including recommendations on general principles and minimum requirements for their provision, indications, pre-testing protocols, method of analyses, reporting of results, and potential clinical value.

Impact of HA-PCI on self-reported cognitive functioning and brain metastases in small-cell lung cancer: Pooled findings of NCT01780675 and PREMER trials.

Background: Cognitive decline is an arising concern in patients who need cranial irradiation. We used the pooled longitudinal individual patient data of two phase III trials: NCT01780675 and PREMER to investigate whether hippocampal avoidance (HA)-PCI is associated with improved self-reported cognitive functioning (SRCF) compared with PCI without increasing brain metastases (BM) development within the HA area.

Methods: Patients with stage I-IV small cell lung cancer (SCLC) were randomized to PCI or HA-PCI.

A Structural Mechanism for Noncanonical GPCR Signal Transduction in the Hedgehog Pathway.

The Hedgehog (Hh) signaling pathway is fundamental to embryogenesis, tissue homeostasis, and cancer. Hh signals are transduced via an unusual mechanism: upon agonist-induced phosphorylation, the noncanonical G protein-coupled receptor SMOOTHENED (SMO) binds the catalytic subunit of protein kinase A (PKA-C) and physically blocks its enzymatic activity. By combining computational structural approaches with biochemical and functional studies, we show that SMO mimics strategies prevalent in canonical GPCR and PKA signaling complexes, despite little sequence or secondary structural homology.

Communicating Probabilities of Cervical Cancer Screening Results with Icon Arrays or Tree Diagrams: A Longitudinal Experiment.

Simple graphical displays such as icon arrays and tree diagrams have been proposed for communicating health risks and supporting informed decisions. The UK's National Health Service (NHS) uses tree diagrams to communicate the chances of different cervical cancer screening results, but their effectiveness has not been compared to icon arrays. We conducted a well-powered longitudinal experiment involving 3,100 UK women eligible for cervical screening (25-64 years) to examine the effectiveness of icon arrays to communicate possible cervical screening results, relative to the UK NHS's tree diagram and to a numerical-only format.

Ambient air pollution, urban green space and childhood overweight and obesity: A health impact assessment for Barcelona, Spain.

Background: The burden of childhood overweight and obesity attributable to ambient air pollution and a lack of urban green spaces (UGS) remains unknown. This study aimed to estimate the attributable cases of childhood overweight and obesity due to air pollution and insufficient UGS exposure in Barcelona, Spain.

Methods: We applied a quantitative health impact assessment approach.

Competitive interactions shape brain dynamics and computation across species.

Adaptive cognition relies on cooperation across anatomically distributed brain circuits. However, specialised neural systems are also in constant competition for limited processing resources. How does the brain's network architecture enable it to balance these cooperative and competitive tendencies? Here we use computational whole-brain modelling to examine the dynamical and computational relevance of cooperative and competitive interactions in the mammalian connectome.

Selective Brain Activations and Connectivities Related to the Storage and Recall of Human Object-Location, Reward-Location, and Word-Pair Episodic Memories.

Different cortical systems to the hippocampus were activated using fMRI during different types of episodic memory task. For object with scene location episodic memory, the activations were high in cortical systems involved in spatial processing, including the ventromedial visual and medial parahippocampal system. These activations for the medial parahippocampal system were higher in the right hemisphere.

A SIRT7-dependent acetylation switch regulates early B cell differentiation and lineage commitment through Pax5.

B lymphopoiesis is orchestrated by lineage-specific transcription factors. In B cell progenitors, lineage commitment is mediated by Pax5, which is commonly mutated in B cell acute lymphoblastic leukemia. Despite its essential role in immunity, the mechanisms regulating Pax5 function remain largely unknown.

Location-biased β-arrestin conformations direct GPCR signaling.

β-arrestins are multifunctional intracellular proteins that regulate the desensitization, internalization and signaling of over 800 different G protein-coupled receptors (GPCRs) and interact with a diverse array of cellular partners. Beyond the plasma membrane, GPCRs can initiate unique signaling cascades from various subcellular locations, a phenomenon known as "location bias". Here, we investigate how β-arrestins direct location-biased signaling of the angiotensin II type I receptor (AT1R).