Evaluation of the Concept of Value-Based Healthcare Applied to an Integrated Palliative Care Program in Colombia.

Objective: This study aimed to evaluate the "Value-Based Healthcare" concept of an integrated palliative care (PC) program in Bogotá, Colombia, through the measurement of health outcomes and care costs in the last 3 months of life.

Methods: A multicenter, retrospective cohort study that included patients ≥18 years old who died in 2020 due to medical conditions amenable to PC. The measured health outcomes included pain, wellbeing, comfort, quality of life (QOL), and satisfaction.

Neuronal hyperexcitability and ion channel dysfunction in CDKL5-deficiency patient iPSC-derived cortical organoids.

Early epilepsy is a prominent feature in patients with CDKL5-deficiency disorder (CDD). The underlying mechanism for excessive excitability in CDD is largely unknown. The brain organoid model has been recently developed to resemble many critical features of early human brain development.

Hierarchical Catalysts Prepared by Interzeolite Transformation.

Interzeolite transformation has been used to produce a novel family of hierarchical catalysts featuring excellent textural properties, strong acidity, and superior catalytic performance for the Friedel-Crafts alkylation of indole with benzhydrol, the Claisen-Schmidt condensation of benzaldehyde and hydroxyacetophenone, and the cracking of polystyrene. Intermediate solids of the FAU interzeolite transformation into BEA display both increased accessibility─due to the development of mesoporosity─and strong acidity─caused by the presence of ultrasmall crystals or zeolitic fragments in their structure. The use of surfactants allows for the development of the hierarchical catalysts with very narrow pore size distribution.

Nocturnal Light Pollution Induces Weight Gain in Mice and Reshapes the Structure, Functions, and Interactions of Their Colonic Microbiota.

In mammals, the daily variation in the ecology of the intestinal microbiota is tightly coupled to the circadian rhythm of the host. On the other hand, a close correlation between increased body weight and light pollution at night has been reported in humans and animal models. However, the mechanisms underlying such weight gain in response to light contamination at night remain elusive.

Response to Comment on "Reintroduction of the archaic variant of in cortical organoids alters neurodevelopment".

Maricic . performed an undisclosed in silico–only whole-exome sequencing analysis of our data and found genomic alterations previously undetected in some clones. Some of the predicted alterations, if true, could change the original genotype of the clones.

Cortical organoids model early brain development disrupted by 16p11.2 copy number variants in autism.

Reciprocal deletion and duplication of the 16p11.2 region is the most common copy number variation (CNV) associated with autism spectrum disorders. We generated cortical organoids from skin fibroblasts of patients with 16p11.

All-Optical Electrophysiology in hiPSC-Derived Neurons With Synthetic Voltage Sensors.

Voltage imaging and "all-optical electrophysiology" in human induced pluripotent stem cell (hiPSC)-derived neurons have opened unprecedented opportunities for high-throughput phenotyping of activity in neurons possessing unique genetic backgrounds of individual patients. While prior all-optical electrophysiology studies relied on genetically encoded voltage indicators, here, we demonstrate an alternative protocol using a synthetic voltage sensor and genetically encoded optogenetic actuator that generate robust and reproducible results. We demonstrate the functionality of this method by measuring spontaneous and evoked activity in three independent hiPSC-derived neuronal cell lines with distinct genetic backgrounds.

MeCP2 controls neural stem cell fate specification through miR-199a-mediated inhibition of BMP-Smad signaling.

Rett syndrome (RTT) is a severe neurological disorder, with impaired brain development caused by mutations in MECP2; however, the underlying mechanism remains elusive. We know from previous work that MeCP2 facilitates the processing of a specific microRNA, miR-199a, by associating with the Drosha complex to regulate neuronal functions. Here, we show that the MeCP2/miR-199a axis regulates neural stem/precursor cell (NS/PC) differentiation.

Altered network and rescue of human neurons derived from individuals with early-onset genetic epilepsy.

Early-onset epileptic encephalopathies are severe disorders often associated with specific genetic mutations. In this context, the CDKL5 deficiency disorder (CDD) is a neurodevelopmental condition characterized by early-onset seizures, intellectual delay, and motor dysfunction. Although crucial for proper brain development, the precise targets of CDKL5 and its relation to patients' symptoms are still unknown.

Autism-linked Cullin3 germline haploinsufficiency impacts cytoskeletal dynamics and cortical neurogenesis through RhoA signaling.

E3-ubiquitin ligase Cullin3 (Cul3) is a high confidence risk gene for autism spectrum disorder (ASD) and developmental delay (DD). To investigate how Cul3 mutations impact brain development, we generated a haploinsufficient Cul3 mouse model using CRISPR/Cas9 genome engineering. Cul3 mutant mice exhibited social and cognitive deficits and hyperactive behavior.

Norm-focused nudges influence pro-environmental choices and moderate post-choice emotional responses.

In this paper, we use choice architecture techniques to activate both social and personal norms, seeking to increase pro-environmental choices and to better understand the effect of such norm types on post-choice emotional responses. In four experiments, we make different social or personal norms salient by aligning choice environments with psychosocial mechanisms that activate different types of norms. We use different choice architecture techniques to change information, alter product sets, and generate the social consequences of choices.

Pharmacological reversal of synaptic and network pathology in human MECP2-KO neurons and cortical organoids.

Duplication or deficiency of the X-linked MECP2 gene reliably produces profound neurodevelopmental impairment. MECP2 mutations are almost universally responsible for Rett syndrome (RTT), and particular mutations and cellular mosaicism of MECP2 may underlie the spectrum of RTT symptomatic severity. No clinically approved treatments for RTT are currently available, but human pluripotent stem cell technology offers a platform to identify neuropathology and test candidate therapeutics.

Modeling Rett Syndrome With Human Patient-Specific Forebrain Organoids.

Engineering brain organoids from human induced pluripotent stem cells (hiPSCs) is a powerful tool for modeling brain development and neurological disorders. Rett syndrome (RTT), a rare neurodevelopmental disorder, can greatly benefit from this technology, since it affects multiple neuronal subtypes in forebrain sub-regions. We have established dorsal and ventral forebrain organoids from control and RTT patient-specific hiPSCs recapitulating 3D organization and functional network complexity.

Methadone Suppresses Neuronal Function and Maturation in Human Cortical Organoids.

Accumulating evidence has suggested that prenatal exposure to methadone causes multiple adverse effects on human brain development. Methadone not only suppresses fetal neurobehavior and alters neural maturation, but also leads to long-term neurological impairment. Due to logistical and ethical issues of accessing human fetal tissue, the effect of methadone on brain development and its underlying mechanisms have not been investigated adequately and are therefore not fully understood.

RNA processing in neurological tissue: development, aging and disease.

Gene expression comprises a diverse array of enzymes, proteins, non-coding transcripts, and cellular structures to guide the transfer of genetic information to its various final products. In the brain, the coordination among genes, or lack thereof, characterizes individual brain regions, mediates a variety of brain-related disorders, and brings light to fundamental differences between species. RNA processing, occurring between transcription and translation, controls an essential portion of gene expression through splicing, editing, localization, stability, and interference.

Zika Virus Targets Glioblastoma Stem Cells through a SOX2-Integrin αβ Axis.

Zika virus (ZIKV) causes microcephaly by killing neural precursor cells (NPCs) and other brain cells. ZIKV also displays therapeutic oncolytic activity against glioblastoma (GBM) stem cells (GSCs). Here we demonstrate that ZIKV preferentially infected and killed GSCs and stem-like cells in medulloblastoma and ependymoma in a SOX2-dependent manner.

An examination of the association between early initiation of substance use and interrelated multilevel risk and protective factors among adolescents.

One of the major goals of drug use prevention programs is to delay the age of onset of substance use. What is called early initiation, usually occurring in adolescents under the age of 15, is a salient predictor of Substance Use Disorders later in adulthood. The causes of early initiation are complex and multifaceted and this has led to the identification of a rich set of risk and protective factors that influence age of onset.

Complex Oscillatory Waves Emerging from Cortical Organoids Model Early Human Brain Network Development.

Structural and transcriptional changes during early brain maturation follow fixed developmental programs defined by genetics. However, whether this is true for functional network activity remains unknown, primarily due to experimental inaccessibility of the initial stages of the living human brain. Here, we developed human cortical organoids that dynamically change cellular populations during maturation and exhibited consistent increases in electrical activity over the span of several months.

The complementary role of affect-based and cognitive heuristics to make decisions under conditions of ambivalence and complexity.

Little is known about the interplay between affective and cognitive processes of decision making within the bounded rationality perspective, in particular for the debate on adaptive decision making and strategy selection. This gap in the knowledge is particularly important as affect and deliberation may direct preferences in opposite directions. How do decision makers solve such dissonance? In this paper, we address this question by exploring the use of integral affect as a choice heuristic in comparison with and in conjunction to "take the best," and weighted addition of attributes (WADD).