Generation of Humanized Zebrafish Models for the In Vivo Assessment of Antisense Oligonucleotide-Based Splice Modulation Therapies.

Antisense oligonucleotide (AON)-based splice modulation is the most widely used therapeutic approach to redirect precursor messenger RNA (pre-mRNA) splicing. To study the functional effect of human mutations affecting pre-mRNA splicing for which AON-based splice redirection would be a potential therapeutic option, humanized knock-in animal models are pivotal. A major limitation of using humanized animal models for this purpose is the reported poor recognition of human splice sites by the splicing machineries of other species.

Effect of Antihypertensive Treatment on Cerebral Blood Flow in Older Adults: a Systematic Review and Meta-Analysis.

Background: In older age, the benefits of antihypertensive treatment (AHT) become less evident, with greater associated risk. Of particular concern is compromising cerebral blood flow (CBF), especially in those with cognitive impairment.

Methods: We created a synthesis of the published evidence by searching multiple electronic databases from 1970 to May 2021.

Acute ischaemic stroke and its challenges for the intensivist.

Acute ischaemic stroke (AIS) is responsible for almost 90% of all strokes and is one of the leading causes of death and disability. Acute ischaemic stroke is caused by a critical alteration in focal cerebral blood flow (ischaemia) from a variety of causes, resulting in infarction. The primary cerebral injury due to AIS occurs in the first hours, therefore early reperfusion importantly impacts on patient outcome ('Time is brain' concept).

Generalist-Specialist Collaboration in Primary Care for Frail Older Persons: A Promising Model for the Future.

Objectives: The complex care needs of frail older persons living at home is a major challenge for health care systems worldwide. One possible solution is to employ a primary care physician (PCP) with additional geriatric expertise. In the Netherlands, elderly care physicians (ECPs), who traditionally work in nursing homes, are increasingly encouraged to utilize their expertise within primary care.

Care Integration in Primary Dementia Care Networks: A Longitudinal Mixed-Methods Study.

Introduction: Currently, care integration for community-dwelling persons with dementia is poor and knowledge on how to effectively facilitate development of integrated dementia care is lacking. The DementiaNet program aims to overcome this with a focus on interprofessional collaboration. The objective of this study is to investigate how care integration in interprofessional primary dementia care networks matures and to identify factors associated with (un)successfully maturation.

Postural freezing relates to startle potentiation in a human fear-conditioning paradigm.

Freezing to impending threat is a core defensive response. It has been studied primarily using fear conditioning in non-human animals, thwarting advances in translational human anxiety research that has used other indices, such as skin conductance responses. Here we examine postural freezing as a human conditioning index for translational anxiety research.

Day-To-Day Home Blood Pressure Variability and All-Cause Mortality in a Memory Clinic Population.

Background: High day-to-day blood pressure variability (BPV) has been associated with an increased risk for cognitive decline and mortality in the general population. Whether BPV is associated with increased all-cause mortality in older people with cognitive impairment is unknown.

Objective: To investigate the association between day-to-day home BPV and all-cause mortality in older patients attending a memory clinic.

Dietary lipids from body to brain.

Dietary habits have drastically changed over the last decades in Western societies. The Western diet, rich in saturated fatty acids (SFA), trans fatty acids (TFA), omega-6 polyunsaturated fatty acids (n-6 PUFA) and cholesterol, is accepted as an important factor in the development of metabolic disorders, such as obesity and diabetes type 2. Alongside these diseases, nutrition is associated with the prevalence of brain disorders.

Determining the effectiveness of cognitive behavioural therapy in improving quality of life in patients undergoing endometriosis surgery: a study protocol for a randomised controlled trial.

Introduction: Endometriosis can cause chronic pain and subfertility thereby negatively affecting quality of life (QoL). Surgical removal of endometriosis lesions leads to improved health-related QoL, although not to the level of QoL of healthy controls. Pain intensity and cognitions regarding pain can play a crucial role in this health-related QoL following surgical treatment.

Ripple band phase precession of place cell firing during replay.

Neuronal "replay," in which place cell firing during rest recapitulates recently experienced trajectories, is thought to mediate the transmission of information from hippocampus to neocortex, but the mechanism for this transmission is unknown. Here, we show that replay uses a phase code to represent spatial trajectories by the phase of firing relative to the 150- to 250-Hz "ripple" oscillations that accompany replay events. This phase code is analogous to the theta phase precession of place cell firing during navigation, in which place cells fire at progressively earlier phases of the 6- to 12-Hz theta oscillation as their place field is traversed, providing information about self-location that is additional to the rate code and a necessary precursor of replay.

Hyper-alignment: Great mice think alike.

Can the neural activity expressing the same mental processes in two different individuals be somehow aligned? Recent evidence suggests that in some cases it can, in mice, at least when they think about space, but possibly even when conjuring up something more abstract.

Do you listen to music while studying? A portrait of how people use music to optimize their cognitive performance.

The effect of background music (BGM) on cognitive task performance is a popular topic. However, the evidence is not converging: experimental studies show mixed results depending on the task, the type of music used and individual characteristics. Here, we explored how people use BGM while optimally performing various cognitive tasks in everyday life, such as reading, writing, memorizing, and critical thinking.

Efficient Generation of Knock-In Zebrafish Models for Inherited Disorders Using CRISPR-Cas9 Ribonucleoprotein Complexes.

CRISPR-Cas9-based genome-editing is a highly efficient and cost-effective method to generate zebrafish loss-of-function alleles. However, introducing patient-specific variants into the zebrafish genome with CRISPR-Cas9 remains challenging. Targeting options can be limited by the predetermined genetic context, and the efficiency of the homology-directed DNA repair pathway is relatively low.

Zebrafish as a Model to Evaluate a CRISPR/Cas9-Based Exon Excision Approach as a Future Treatment Option for -Associated Retinitis Pigmentosa.

Retinitis pigmentosa (RP) is an inherited retinal disease (IRD) with an overall prevalence of 1 in 4000 individuals. Mutations in () are among the most frequent causes of non-syndromic autosomal recessively inherited RP and act via a loss-of-function mechanism. In light of the recent successes for other IRDs, we investigated the therapeutic potential of exon skipping for -associated RP.

Does the temporal cortex make us human? A review of structural and functional diversity of the primate temporal lobe.

Temporal cortex is a primate specialization that shows considerable variation in size, morphology, and connectivity across species. Human temporal cortex is involved in many behaviors that are considered especially well developed in humans, including semantic processing, language, and theory of mind. Here, we ask whether the involvement of temporal cortex in these behaviors can be explained in the context of the 'general' primate organization of the temporal lobe or whether the human temporal lobe contains unique specializations indicative of a 'step change' in the lineage leading to modern humans.

Rivastigmine for minor visual hallucinations in Parkinson's disease: A randomized controlled trial with 24 months follow-up.

Background: Visual hallucinations are common in patients with Parkinson's disease and represent probably the major independent predictor for cognitive deterioration and nursing home placement.

Objective: To investigate if treatment of minor visual hallucinations in Parkinson's disease with rivastigmine delays the progression to psychosis.

Methods: A multicenter, randomized, double-blind, placebo-controlled trial was conducted which aimed to recruit 168 patients with Parkinson's disease reporting minor visual hallucinations 4 weeks before it.

Effects of early-life stress on peripheral and central mitochondria in male mice across ages.

Exposure to early-life stress (ES) increases the vulnerability to develop metabolic diseases as well as cognitive dysfunction, but the specific biological underpinning of the ES-induced programming is unknown. Metabolic and cognitive disorders are often comorbid, suggesting possible converging underlying pathways. Mitochondrial dysfunction is implicated in both metabolic diseases and cognitive dysfunction and chronic stress impairs mitochondrial functioning.

Longitudinal changes in the control mechanisms for blood pressure and cerebral blood flow in Alzheimer's disease: Secondary results of a randomized controlled trial.

Objective: Dynamic cerebral autoregulation (dCA) and baroreflex sensitivity (BRS) are key mechanisms involved in the homeostasis of blood pressure (BP) and cerebral blood flow. We assessed changes in these mechanisms in Alzheimer's disease (AD) during a 1.5 year follow-up.

Molecular Inversion Probe-Based Sequencing of Exons and Splice Sites as a Cost-Effective Screening Tool in USH2 and arRP Cases.

A substantial proportion of subjects with autosomal recessive retinitis pigmentosa (arRP) or Usher syndrome type II (USH2) lacks a genetic diagnosis due to incomplete screening in the early days of genetic testing. These cases lack eligibility for optimal genetic counseling and future therapy. defects are the most frequent cause of USH2 and are also causative in individuals with arRP.

Sniffing submissiveness? Oxytocin administration in severe psychopathy.

Psychopathy is a personality disorder associated with criminal behavior and violent recidivism, and therefore a burden to society. Social dominance is one of the characteristics of psychopathy that might contribute to these problems. Nevertheless, only few studies have objectively measured the relationship between socially dominant behavior and psychopathy.

Implementation of a diagnostic decision aid for people with memory complaints and their general practitioners: a protocol of a before and after pilot trial.

Introduction: Researchers, policy-makers and healthcare professionals often stress the importance of an early dementia diagnosis. Empirical evidence, however, is scarce leading to a lack of consensus on the necessity of diagnosing dementia early. We emphasise the need for a 'timely' diagnosis, that is, one that occurs at the right moment for a person with memory complaints and his/her significant other.

14-3-3ζ is crucial for the conversion of labile short-term object recognition memory into stable long-term memory.

The consolidation of new memories into long-lasting memories is multistage process characterized by distinct temporal dynamics. However, our understanding on the initial stage of transformation of labile memory of recent experience into stable memory remains elusive. Here, with the use of rats and mice overexpressing a memory enhancer called regulator of G protein signaling 14 of 414 amino acids (RGS14 ) as a tool, we show that the expression of RGS14 in male rats' perirhinal cortex (PRh), which is a brain area crucial for object recognition memory (ORM), enhanced the ORM to the extent that it caused the conversion of labile short-term ORM (ST-ORM) expected to last for 40 min into stable long-term ORM (LT-ORM) traceable after a delay of 24 hr, and that the temporal window of 40 to 60 min after object exposure not only was key for this conversion but also was the time frame when a surge in 14-3-3ζ protein was observed.

Temporally delayed linear modelling (TDLM) measures replay in both animals and humans.

There are rich structures in off-task neural activity which are hypothesized to reflect fundamental computations across a broad spectrum of cognitive functions. Here, we develop an analysis toolkit - temporal delayed linear modelling (TDLM) - for analysing such activity. TDLM is a domain-general method for finding neural sequences that respect a pre-specified transition graph.

Characterization of the GHB Withdrawal Syndrome.

The gamma-hydroxybutyric acid (GHB) withdrawal syndrome can have a fulminant course, complicated by severe complications such as delirium or seizures. Detoxification by tapering with pharmaceutical GHB is a safe way to manage GHB withdrawal. However, a detailed description of the course of the GHB withdrawal syndrome is currently lacking.

Behavioural and neurophysiological signatures in the retrieval of individual memories of recent and remote real-life routine episodic events.

Autobiographical memory (AM) has been largely investigated as the ability to recollect specific events that belong to an individual's past. However, how we retrieve real-life routine episodes and how the retrieval of these episodes changes with the passage of time remain unclear. Here, we asked participants to use a wearable camera that automatically captured pictures to record instances during a week of their routine life and implemented a deep neural network-based algorithm to identify picture sequences that represented episodic events.