A Structure-Function Substrate of Memory for Spatial Configurations in Medial and Lateral Temporal Cortices.

Prior research has shown a role of the medial temporal lobe, particularly the hippocampal-parahippocampal complex, in spatial cognition. Here, we developed a new paradigm, the conformational shift spatial task (CSST), which examines the ability to encode and retrieve spatial relations between unrelated items. This task is short, uses symbolic cues, incorporates two difficulty levels, and can be administered inside the scanner. A cohort of 48 healthy young adults underwent the CSST, together with a set of behavioral measures and multimodal magnetic resonance imaging (MRI). Inter-individual differences in CSST performance correlated with scores on an established spatial memory paradigm, but neither with episodic memory nor mnemonic discrimination, supporting specificity. Analyzing high-resolution structural MRI data, individuals with better spatial memory showed thicker medial and lateral temporal cortices. Functional relevance of these findings was supported by task-based functional MRI analysis in the same participants and ad hoc meta-analysis. Exploratory resting-state functional MRI analyses centered on clusters of morphological effects revealed additional modulation of intrinsic network integration, particularly between lateral and medial temporal structures. Our work presents a novel spatial memory paradigm and supports an integrated structure-function substrate in the human temporal lobe. Task paradigms are programmed in python and made open access.

Toward patient-centered treatment goals for duchenne muscular dystrophy: insights from the "Your Voice" study.

BACKGROUND: Patient-centered research has emerged as critically important for understanding the impact of treatments on key stakeholders. The subjective experience of quality of life (QOL) is increasingly recognized as fundamental to delineating treatment goals. The present study utilized content analysis of qualitative data and quantitative analysis to highlight important domains of disease burden and underlying reasons for their importance, and to characterize goals for new treatments for Duchenne Muscular Dystrophy (DMD). RESULTS: The study sample reflected the perspectives of DMD patients and caregivers representing ambulatory, transitional, and non-ambulatory stages of disability progression (n = 20 per category). Open-ended interviews were content-analyzed and non-parametric statistical tests were used to compare ambulation groups. As patients progressed in disability, the noted DMD burdens reflected some differences in functional areas. While daily functioning and sports/recreation remained the most important priority areas across ambulation groups, "health" became less prominent as the disability progressed from ambulatory to transitional to non-ambulatory phases of disability; whereas relationships became more prominent as one progressed to the non-ambulatory phase from the ambulatory or transitional phases (Kruskall Wallis H = 12.24 and 5.28, p = 0.002 and 0.02, respectively). When asked why their burdens were important to them and how it impacted their or their child's life, self-esteem/confidence was most important for ambulatory patients, and became less prominent for patients in the transitional and non-ambulatory phases of disability (Kruskall Wallis H = 9.46, p = 0.009). In contrast, independence was less important for ambulatory patients, and became increasing prominent for patients in the transitional and non-ambulatory phases of disability (Kruskall Wallis H = 7.35, p = 0.025). Emotional functioning was most prominent for all ambulation groups on their best and worst days. Goals for new DMD treatments focused on functional goals, general QOL goals, and concerns about safety, ease of use, and effectiveness. CONCLUSION: This study provides useful information about treatment goals for DMD from the perspective of patients and their caregivers. It highlights some consistent values across the disability trajectory, as well as introducing an evolution of priorities as the person with DMD becomes more disabled. Results provide a roadmap for patient-centered DMD drug development.

Treatment of sleep disturbance following stroke and traumatic brain injury: a systematic review of conservative interventions.

PURPOSE: Sleep disorders are common following stroke and traumatic brain injury. We present a systematic review of the literature investigating conservative interventions to improve sleep in these populations. MATERIALS AND METHODS: The PRISMA statement was used. Embase, PubMed, and the Cochrane library were searched for all experimental studies published prior to 28th March 2020 that assessed conservative interventions to improve the sleep or sleep disorders of adults with a history of stroke or traumatic brain injury (TBI). Two authors reviewed publications of interest and risk of bias assessments were performed using the Cochrane Risk of Bias Tool or the Methodological Index for Non-Randomised Studies instrument. RESULTS: Twenty-three publications were included in this systematic review. Meta-analyses were not performed due to study heterogeneity. Psychotherapy-based approaches might be useful for sleep disturbance after TBI and acupuncture may help improve insomnia or sleep disturbance following stroke or TBI, respectively. The evidence was less clear for morning bright light therapy and exercise. Limitations included a single author performing primary searches, only English publications, the reporting of secondary outcome measures, and sleep disorder diagnoses. CONCLUSIONS: Some conservative interventions might be useful for improving sleep disturbance or disorders in these populations, but further research is required.IMPLICATIONS FOR REHABILITATIONSleep disturbance is common following stroke and traumatic brain injury, with insomnia and obstructive sleep apnoea being the most frequently diagnosed sleep disorders.Psychotherapy-based approaches might be useful for sleep disturbance after TBI and acupuncture may help improve insomnia or sleep disturbance following stroke or TBI, respectively.Morning bright light therapy appeared to be more beneficial for fatigue rather than sleep disturbance after TBI, and the evidence for exercise was less clear.

Sleep disturbance and recovery during rehabilitation after traumatic brain injury: a systematic review.

Purpose: Sleep disturbance is well recognized following traumatic brain injury, but less is known about the potential effects of this on patients and their recovery. We review the recent literature that investigates the relationship between sleep disturbance in adult patients following a traumatic brain injury and their functioning, disability, and health.Materials and methods: The PRISMA statement was used as a guide to report the systematic review. Embase, PubMed, and the Cochrane library were searched for all research articles published (or in press) in the 10 y prior to 25 May 2018 that investigated the relationship between the development (or treatment) of sleep disturbance of adult patients with a history of traumatic brain injury and patient outcomes, according to the domains of the International Classification of Functioning, Disability, and Health Core Sets for persons with sleep disorders. Two authors independently assessed all identified studies by title and abstract and were included following article review and discussion. Study quality was assessed using the evidence-based library and information practice critical appraisal checklist.Results: Our search identified 27 studies with a wide range in patient populations and assessment measures. Results suggested that sleep disturbance in patients with a history of traumatic brain injury may be associated with the resolution of post-traumatic amnesia and specific impairments of cognition, affective disorders, fatigue, and pain. Some studies indicated that sleep disturbance could be related to an impaired functional ability and reduced quality of life. Limitations of the systematic review included strict inclusion and exclusion criteria and reporting of secondary outcome measures.Conclusions: These findings highlight the relationship between sleep disturbance and patient rehabilitation and outcomes, and therefore the importance of assessing sleep in patients following a traumatic brain injury. Further research is required with more focused patient populations that combine both subjective and objective assessments of sleep to help clarify this relationship.Implications for rehabilitationSleep disturbance following traumatic brain injury may be related to the resolution of post-traumatic amnesia, cognitive and affective disorders, fatigue, and pain.Those with a history of traumatic brain injury and sleep disturbance may demonstrate a worse functional ability and report a poorer satisfaction with life.It is important for rehabilitation professionals to take sleep disturbance into account in those patients with a history of traumatic brain injury.

Reducing sound and light exposure to improve sleep on the adult intensive care unit: An inclusive narrative review.

PURPOSE: Sleep disturbance is common in intensive care units. It is associated with detrimental psychological impacts and has potential to worsen outcome. Irregular exposure to sound and light may disrupt circadian rhythm and cause frequent arousals from sleep. We sought to review the efficacy of environmental interventions to reduce sound and light exposure with the aim of improving patient sleep on adult intensive care units. METHODS: We searched both PubMed (1966-30 May 2017) and Embase (1974-30 May 2017) for all relevant human (adult) studies and meta-analyses published in English using search terms ((intensive care OR critical care), AND (sleep OR sleep disorders), AND (light OR noise OR sound)). Bibliographies were explored. Articles were included if reporting change in patient sleep in response to an intervention to reduce disruptive intensive care unit sound /light exposure. RESULTS: Fifteen studies were identified. Nine assessed mechanical interventions, four of which used polysomnography to assess sleep. Five studies looked at environmental measures to facilitate sleep and a further two (one already included as assessing a mechanical intervention) studied the use of sound to promote sleep. Most studies found a positive impact of the intervention on sleep. However, few studies used objective sleep assessments, sample sizes were small, methodologies sometimes imperfect and analysis limited. Data are substantially derived from specialist (neurosurgical, post-operative, cardiothoracic and cardiological) centres. Patients were often at the 'less sick' end of the spectrum in a variety of settings (open ward beds or side rooms). CONCLUSIONS: Simple measures to reduce intensive care unit patient sound/light exposure appear effective. However, larger and more inclusive high-quality studies are required in order to identify the measures most effective in different patient groups and any impacts on outcome.

A transgene with repeated DNA causes high frequency, post-transcriptional suppression of ACC-oxidase gene expression in tomato.

Gene silencing with sense genes is an important method for down-regulating the expression of endogenous plant genes, but the frequency of silencing is unpredictable. Fifteen per cent of tomato plants transformed with a 35S-ACC-oxidase ( ACO 1) sense gene had reduced ACC-oxidase activity. However, 96% of plants transformed with an ACC-oxidase sense gene, containing two additional upstream inverted copies of its 5' untranslated region, exhibited reduced ACC-oxidase activity compared to wild-type plants. In the three plants chosen for analysis, there were substantially reduced amounts of both endogenous and transgenic ACO RNA, indicating that this was an example of co-suppression. Ribonuclease protection assays using probes spanning intron-exon borders showed that the reduced accumulation of endogenous ACO mRNA occurred post-transcriptionally since the abundance of unprocessed transcripts was not affected. The ACO1 transgene with the repeated 5'UTR also strongly inhibited the accumulation of RNA from the related ACO 2 gene in flowers, although there is little homology between the 5'UTRs of ACO 1 and ACO 2. These results indicate that although repeated DNA in a transgene greatly enhances the probability of gene silencing of an endogenous gene, it also involves generation of a trans -acting silencing signal produced, at least partly, from sequences external to the repeat.

The propensity of individuals to deposit DNA and secondary transfer of low level DNA from individuals to inert surfaces.

We have shown that there is a difference between individuals in their tendency to deposit DNA on an item when it is touched. While a good DNA shedder may leave behind a full DNA profile immediately after hand washing, poor DNA shedders may only do so when their hands have not been washed for a period of 6h. We have also demonstrated that transfer of DNA from one individual (A) to another (B) and subsequently to an object is possible under specific laboratory conditions using the AMPFISTR SGM Plus multiplex at both 28 and 34 PCR cycles. This is a form of secondary transfer. If a 30 min or 1h delay was introduced before contact of individual B with the object then at 34 cycles a mixture of profiles from both individuals was recovered. We have also determined that the quantity and quality of DNA profiles recovered is dependent upon the particular individuals involved in the transfer process. The findings reported here are preliminary and further investigations are underway in order to further add to understanding of the issues of DNA transfer and persistence.

Can sleep disturbance in depression predict repetitive transcranial magnetic stimulation (rTMS) treatment response?

Treatment for depression is not effective in all patients and it is therefore important to identify factors that can be used to tailor treatments. One potential factor is insomnia. Several repetitive transcranial magnetic stimulation (rTMS) studies have reported on this symptom, however, they did not take into account the presence of hypersomnia or that insomnia was related to their outcome measure. Our aim was to investigate whether baseline sleep disruption was related to rTMS treatment response. We pooled data from four clinical trials using rTMS to treat depression, including 139 subjects in data analysis. Insomnia was measured using the Hamilton Depression Rating Scale (HamD) sleep questions and hypersomnia from the Beck Depression Inventory (BDI). To reduce the possible impact of insomnia on our treatment response outcome we created an adjusted HamD score which omitted sleep items. Sleep disturbances were common in our study: 66% had insomnia and 38% hypersomnia. Using regression analysis with our adjusted HamD score we found no relation between baseline insomnia or hypersomnia and rTMS treatment response. Our data are consistent with previous studies; however, this is the first rTMS study to our knowledge that has attempted to dissociate baseline insomnia from the HamD outcome measure and to report no relationship between hypersomnia and rTMS outcome.

Periodic limb movements in sleep exhibit a circadian rhythm that is maximal in the late evening/early night.

OBJECTIVE: Periodic limb movements in sleep (PLMS) show a time-of-night pattern, with most movements at the beginning of the night. Our study aimed to determine whether this pattern is due to an endogenous circadian rhythm, like that in the related movement disorder Restless Legs Syndrome (RLS). METHODS: Four healthy older adults with a screening PLMI>20 were studied in an inpatient forced desynchrony protocol with an imposed sleep-wake cycle of 20 h for 12 "nights," allowing separation of circadian and sleep homeostatic influences on leg movements. We recorded sleep polysomnographically throughout each scheduled episode, including left and right anterior tibialis EMG. RESULTS: PLMS in Stage 2 showed both a significant time-within-sleep pattern and a significant circadian rhythm. The circadian rhythm in PLMS peaked at the circadian phases when usual sleep onset occurs, preceding the evening rise in melatonin secretion. CONCLUSIONS: In our subjects, the circadian pattern of PLMs expression was very similar to that previously reported in patients with RLS. This evidence for a circadian rhythm in PLMS has implications for treatment and provides direction for future studies of the pathophysiology of this movement disorder.

Rapid mass spectrometric identification of human genomic polymorphisms using multiplexed photocleavable mass-tagged probes and solid phase capture.

A mass spectrometric approach for rapid and simultaneous detection of several single nucleotide polymorphisms (SNPs) is reported. Oligonucleotide single base extension (SBE) primers, labelled at the 5'-end with photocleavable, quaternised and brominated peptidic mass tags, are extended by a mixture of the four dideoxynucleotides of which one is biotinylated. The 3'-biotinylated extension products are captured by streptavidin-coated solid phase magnetic beads, whilst non-biotinylated extension products and unreacted primers are washed away. Quaternised and brominated mass tags, cleaved from captured extension products during analysis by matrix-assisted laser desorption/ionisation-time-of-flight (MALDI-TOF) MS, are detected at pmol levels. This method is applied to the analysis of mitochondrial DNA polymorphisms for the purpose of human identification.