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Abstract Background Most western countries provide funded legal representation (LR) for involuntarily admitted psychiatric patients appearing before judicial committees. In 2004, an amendment to the Israeli Mental Health Act granted this right to involuntarily committed psychiatric patients. Psychiatrists then voiced concerns that LR may increase rates of premature discharge and compromise patients’ safety and well-being. These worries have not been sufficiently addressed to date. This study aimed to provide answers to their concerns. Methods This study included 3124 and 3434 inpatients involuntarily admitted to psychiatric facilities in 2000 and in 2010 (respectively), prior to and after the introduction of LR in Israel. Data were acquired from the Israeli National Psychiatric Hospitalization Registry. Clinical measures included percentage of discharges by the District Psychiatric Board (DPB), duration of involuntary hospitalization and rates of readmissions within thirty days and six months of discharge by treating psychiatrists (TP) or DPB. Results The odds ratio (OR) of discharge by a DPB in 2010 (n = 221) compared to 2000 (n = 93) was 2.2 [95%CI 1.72–2.82]. The OR was similar for readmissions within thirty days or six months among patients discharged by TP and a DPB (OR = 1.08, p = 0.697 and OR = 0.92, p = 0.603, respectively) as well as between the two time points (p = 0.486 and p = 0.618). The duration of hospitalizations terminated by a DPB was significantly shorter than those terminated by TP, with no difference between the study time points. The mean hospitalization duration in 2010 was 21% shorter compared to 2000 among patients discharged by TP. Conclusions The number of DPB proceedings and the number of involuntarily hospitalized psychiatric patients discharged by DPBs increased considerably after the advent of state-funded legal representation in 2004. We found that this did not compromise beneficence and non-malfeasance of patient care. Our results emphasize the feasibility of affording even the most severely mentally ill patients the rights to due process. These findings may relieve concerns about state-funded LR procedures in involuntary psychiatric hospitalizations.

During rest and sleep, memory traces replay in the brain. The dialogue between brain regions during replay is thought to stabilize labile memory traces for long-term storage. However, because replay is an internally driven, spontaneous phenomenon, it does not have a ground truth - an external reference that can validate whether a memory has truly been replayed. Instead, replay detection is based on the similarity between the sequential neural activity comprising the replay event and the corresponding template of neural activity generated during active locomotion. If the statistical likelihood of observing such a match by chance is sufficiently low, the candidate replay event is inferred to be replaying that specific memory. However, without the ability to evaluate whether replay detection methods are successfully detecting true events and correctly rejecting non-events, the evaluation and comparison of different replay methods is challenging. To circumvent this problem, we present a new framework for evaluating replay, tested using hippocampal neural recordings from rats exploring two novel linear tracks. Using this two-track paradigm, our framework selects replay events based on their temporal fidelity (sequence-based detection), and evaluates the detection performance using each event’s track discriminability, where sequenceless decoding across both tracks is used to quantify whether the track replaying is also the most likely track being reactivated.

Abstract Epilepsy is a prevalent disorder involving neuronal network hyperexcitability, yet existing therapeutic strategies often fail to provide optimal patient outcomes. Chemogenetic approaches, where exogenous receptors are expressed in defined brain areas and specifically activated by selective agonists, are appealing methods to constrain overactive neuronal activity. We developed BARNI (Bradanicline- and Acetylcholine-activated Receptor for Neuronal Inhibition), an engineered channel comprised of the α7 nicotinic acetylcholine receptor ligand-binding domain coupled to an α1 glycine receptor anion pore domain. Here we demonstrate that BARNI activation by the clinical stage α7 nicotinic acetylcholine receptor-selective agonist bradanicline effectively suppressed targeted neuronal activity, and controlled both acute and chronic seizures in male mice. Our results provide evidence for the use of an inhibitory acetylcholine-based engineered channel activatable by both exogenous and endogenous agonists as a potential therapeutic approach to treating epilepsy.

Abstract During sleep, recent memories are replayed by the hippocampus, leading to their consolidation, with a higher priority given to salient experiences. To examine the role of replay in the selective strengthening of memories, we recorded large ensembles of hippocampal place cells while male rats ran repeated spatial trajectories on two linear tracks, differing in either their familiarity or number of laps run. We observed that during sleep, the rate of replay events for a given track increased proportionally with the number of spatial trajectories run by the animal. In contrast, the rate of sleep replay events decreased if the animal was more familiar with the track. Furthermore, we find that the cumulative number of awake replay events occurring during behavior, influenced by both the novelty and duration of an experience, predicts which memories are prioritized for sleep replay, providing a more parsimonious neural correlate for the selective strengthening of memories.

Abstract Our brain’s capacity for memory storage may be vast but is still finite. Given that we cannot remember the entirety of our experiences, how does our brain select what to remember and what to forget? Much like the triage of a hospital’s emergency room, where urgent cases are prioritized and less critical patients receive delayed or even no care, the brain is believed to go through a similar process of memory triage. Recent salient memories are prioritized for consolidation, which helps create stable, long-term representations in the brain; less salient memories receive a lower priority, and are eventually forgotten if not sufficiently consolidated (Stickgold and Walker in Nat Neurosci 16(2):139–145, 2013). While rodents are a primary model for studying memory consolidation, common behavioral tests typically rely on a limited number of items or contexts, well within the memory capacity of the subject. A memory test allowing us to exceed an animal’s memory capacity is key to investigating how memories are selectively strengthened or forgotten. Here we report a new serial novel object recognition task designed to measure memory capacity and prioritization, which we test and validate using female mice.

The p53 pathway is a universal tumor suppressor mechanism that limits tumor progression by triggering apoptosis or permanent cell cycle arrest, called senescence. In recent years, efforts to reactivate p53 function in cancer have proven to be a successful therapeutic strategy in murine models and have gained traction with the development of a range of small molecules targeting mutant p53. However, knowledge of the downstream mediators of p53 reactivation in different oncogenic contexts has been limited. Here, we utilized a panel of murine cancer cell lines from three distinct tumor types susceptible to alternative outcomes following p53 restoration to define unique and shared p53 transcriptional signatures. While we found that the majority of p53-bound sites and p53-responsive transcripts are tumor-type specific, analysis of shared targets identified a core signature of genes activated by p53 across all contexts. Furthermore, we identified repression of E2F and Myc target genes as a key feature of senescence. Characterization of p53-induced transcripts revealed core and senescence-specific long noncoding RNAs (lncRNAs) that are predominantly chromatin associated and whose production is coupled to cis-regulatory activities. Functional investigation of the contributions of p53-induced lncRNAs to p53-dependent outcomes highlighted Pvt1b, the p53-dependent isoform of Pvt1, as a mediator of p53-dependent senescence via Myc repression. Inhibition of Pvt1b led to decreased activation of senescence markers and increased levels of markers of proliferation. These findings shed light on the core and outcome-specific p53 restoration signatures across different oncogenic contexts and underscore the key role of the p53-Pvt1b-Myc regulatory axis in mediating proliferative arrest.

While animals navigating the real world face a barrage of sensory input, their brains evolved to perceptually compress multidimensional information by selectively extracting the features relevant for survival. Notably, communication signals supporting social interactions in several mammalian species consist of acoustically complex sequences of vocalisations. However, little is known about what information listeners extract from such time-varying sensory streams. Here, we utilise female mice’s natural behavioural response to male courtship songs to identify the relevant acoustic dimensions used in their social decisions. We found that females were highly sensitive to disruptions of song temporal regularity and preferentially approached playbacks of intact over rhythmically irregular versions of male songs. In contrast, female behaviour was invariant to manipulations affecting the songs’ sequential organisation or the spectro-temporal structure of individual syllables. The results reveal temporal regularity as a key acoustic cue extracted by mammalian listeners from complex vocal sequences during goal-directed social behaviour.

Cross-species research is key to fully understanding brain function. Here, the authors present the ferret as a species for hippocampal research and show that, in stark contrast to rats, ferrets have robust theta oscillations during immobility.

I. INTRODUCTION II. STANDING IN ISRAEL III. DEVELOPMENT OF ISRAELI CONSTITUTIONAL AND ADMINISTRATIVE LAW AS A RESULT OF THE BROAD STANDING POLICY A. Examples of the Israeli Supreme Court Granting [...], The Article suggests that broad standing rights in Israel not only have contributed to the development of constitutional and administrative law, but also encourage the establishment of public interest organizations whose activities focus on filing petitions in those areas. Many of these petitions deal with issues that have significant political implications. This Article presents the broad standing rights in Israel, indicates the role of broad compliance in the development of Israeli constitutional and administrative law, describes the contribution of the broad standing in Israel to the establishment of public interest organizations and civic groups, and offers explanations of the dominance of these organizations and groups in filing petitions on issues which do not involve claims of violation of human rights or of individual interests.

Background: Underdiagnosis of relevant risk factors has contributed to the increasing stroke incidence in young adults. Blood pressure cut-off values for adolescents are neither sex specific nor based on cardiovascular outcomes. Methods: This nationwide, population-based, retrospective cohort study included all Israeli adolescents 16-19 years of age who were medically evaluated before compulsory military service from 1985 to 2013, including routine blood pressure measurements. The primary outcome was the first occurrence of a stroke (ischemic or hemorrhagic) at a young age (≤52 years), as documented in the Israeli National Stroke Registry. Cox proportional hazard models were stratified by sex and adjusted for birth year, sociodemographic variables, and adolescent body mass index. Results: The cohort comprised 1,897,048 adolescents (42.4% women). During 11,355,476 person-years of follow-up, there were 1470 first stroke events at a young age. In men, an adolescent diastolic blood pressure value of ≥80 mmHg, compared with the reference group (diastolic blood pressure value of <70 mmHg), was associated with an increased risk of stroke (adjusted hazard ratio 1.28; 95% confidence interval [CI], 1.04 to 1.58), while a diastolic blood pressure value of 70-79 mmHg was not associated with an increased risk of stroke (adjusted hazard ratio 1.11; 95% CI 0.90 to 1.34). Among women, an adolescent diastolic blood pressure value of ≥80 mmHg, compared with the reference group (diastolic blood pressure value of <70 mmHg) was associated with an increased risk of stroke at a young age (adjusted hazard ratio 1.38; 95% CI 1.03 to 1.88), as was a diastolic blood pressure value of 70-79 mmHg (adjusted hazard ratio 1.41; 95% CI 1.09 to 1.81). Elevated adolescent systolic blood pressure values (≥120 mmHg) were not associated with an increased risk of stroke. Conclusions: Diastolic blood pressure values of ≥80 mmHg in adolescence were associated with an increased risk of stroke at a young age in both men and women. No similar association was observed for elevated systolic blood pressure. [ABSTRACT FROM AUTHOR]