Retrieval Trials Research Articles

Word-learning trajectories influence long-term recall in children with developmental language disorder and typical development

IntroductionChildren with developmental language disorder (DLD) have difficulties learning words. However, the severity of these difficulties can be reduced through word learning procedures that incorporate repeated spaced retrieval (RSR). Previous studies have shown positive outcomes with RSR but we still know very little about how learning unfolds with this procedure. In this study, we focus on the process of learning under RSR. MethodsWe analyze the learning data from children with DLD and with typical development (TD) from three recent studies using RSR. We fit growth curves to the trial-by-trial learning data for immediate and spaced retrieval trials and use the characteristics of children's individual word-learning trajectories to predict their long-term recall. ResultsWe found that children in both groups demonstrated linear growth during learning, despite breaks within and across days. Success on early immediate retrieval trials promoted success on subsequent spaced retrieval trials. Children's trial-by-trial RSR learning trajectories were related to their long-term recall: both cumulative success and growth over time on the spaced retrieval trials positively predicted long-term recall. Consecutive success was also highly correlated with growth over time. ConclusionsRepeated spaced retrieval supplemented with immediate retrieval trials during learning promotes long-term recall.

Single-neuron correlate of epilepsy-related cognitive deficits in visual recognition memory in right mesial temporal lobe.

ObjectiveImpaired memory is a common comorbidity of refractory temporal lobe epilepsy (TLE) and often perceived by patients as more problematic than the seizures themselves. The objective of this study is to understand what the relationship of these behavioral impairments is to the underlying pathophysiology, as there are currently no treatments for these deficits, and it remains unknown what circuits are affected.MethodsWe recorded single neurons in the medial temporal lobes (MTLs) of 62 patients (37 with refractory TLE) who performed a visual recognition memory task to characterize the relationship between behavior, tuning, and anatomical location of memory selective and visually selective neurons.ResultsSubjects with a seizure onset zone (SOZ) in the right but not left MTL demonstrated impaired ability to recollect as indicated by the degree of asymmetry of the receiver operating characteristic curve. Of the 1973 recorded neurons, 159 were memory selective (MS) and 366 were visually selective (VS) category cells. The responses of MS neurons located within right but not left MTL SOZs were impaired during high‐confidence retrieval trials, mirroring the behavioral deficit seen both in our task and in standardized neuropsychological tests. In contrast, responses of VS neurons were unimpaired in both left and right MTL SOZs. Our findings show that neuronal dysfunction within SOZs in the MTL was specific to a functional cell type and behavior, whereas other cell types respond normally even within the SOZ. We show behavioral metrics that detect right MTL SOZ‐related deficits and identify a neuronal correlate of this impairment.SignificanceTogether, these findings show that single‐cell responses can be used to assess the causal effects of local circuit disruption by an SOZ in the MTL, and establish a neural correlate of cognitive impairment due to epilepsy that can be used as a biomarker to assess the efficacy of novel treatments.

The Association of Family Eating Behaviors With Children’s Cognitive Functioning: A Cross-Sectional Study Among 3–6-Year-Old Mexican Children

ObjectivesLittle is known about the association of family eating behaviors with young children’s cognitive development, particularly among non-White populations. The objective of this study is to determine if healthier family eating behaviors are associated with young Mexican children’s cognitive functioning. MethodsWe used cross-sectional data from a convenience sample of low-income child-mother dyads recruited from a public preschool in San Luis Potosi, S.L.P., Mexico. Using the Family Nutrition and Physical Activity (FNPA) questionnaire, mothers were asked to report the frequency of ten family eating behaviors (e.g., frequency of breakfast intake, family mealtimes, etc.). Children completed two cognitive tests: a working memory test of their ability to recall four words after a timed distraction (i.e., delayed recall); and a verbal fluency test, examined with a 60-second trial of word retrieval in response to “things people eat”. The associations of family eating behaviors with children’s working memory and verbal fluency were examined using multiple linear regression models adjusting for child sex, age, mother’s age, education, and subjective socioeconomic status. ResultsStudy included 85 child-mother dyads; children’s ages ranged from 3 to 6 years (4.58 ± 0.58) and mothers from 19 to 55 years (30.92 ± 8.49). Children had a mean working memory score of 2.24 ± 0.99 words recalled and retrieved a mean of 20.06 ± 5.26 words in the verbal fluency tests. Higher frequency of breakfast intake was associated with higher working memory scores (β = 0.56, P = 0.013). No other family eating practices were significantly associated with children’s working memory. Children’s verbal fluency scores were not significantly associated with family eating practices. ConclusionsFrequent breakfast intake was associated with young children’s memory maintenance. Future research is needed to examine the mechanisms through which breakfast intake could benefit children’s neurodevelopmental health. Funding SourcesThis study was supported by the training grant “Illinois Transdisciplinary Obesity Prevention Program (I-TOPP)” funded by the National Institute of Food and Agriculture, United States Department of Agriculture (USDA) and support from the NIDDK.

Spatiotemporal dynamics between interictal epileptiform discharges and ripples during associative memory processing.

We describe the spatiotemporal course of cortical high-gamma activity, hippocampal ripple activity and interictal epileptiform discharges during an associative memory task in 15 epilepsy patients undergoing invasive EEG. Successful encoding trials manifested significantly greater high-gamma activity in hippocampus and frontal regions. Successful cued recall trials manifested sustained high-gamma activity in hippocampus compared to failed responses. Hippocampal ripple rates were greater during successful encoding and retrieval trials. Interictal epileptiform discharges during encoding were associated with 15% decreased odds of remembering in hippocampus (95% confidence interval 6-23%). Hippocampal interictal epileptiform discharges during retrieval predicted 25% decreased odds of remembering (15-33%). Odds of remembering were reduced by 25-52% if interictal epileptiform discharges occurred during the 500-2000 ms window of encoding or by 41% during retrieval. During encoding and retrieval, hippocampal interictal epileptiform discharges were followed by a transient decrease in ripple rate. We hypothesize that interictal epileptiform discharges impair associative memory in a regionally and temporally specific manner by decreasing physiological hippocampal ripples necessary for effective encoding and recall. Because dynamic memory impairment arises from pathological interictal epileptiform discharge events competing with physiological ripples, interictal epileptiform discharges represent a promising therapeutic target for memory remediation in patients with epilepsy.

Disrupting Reconsolidation by Systemic Inhibition of mTOR Kinase via Rapamycin Reduces Cocaine-Seeking Behavior.

Drug addiction is considered maladaptive learning, and drug-related memories aroused by the presence of drug related stimuli (drug context or drug-associated cues) promote recurring craving and reinstatement of drug seeking. The mammalian target of rapamycin signaling pathway is involved in reconsolidation of drug memories in conditioned place preference and alcohol self-administration (SA) paradigms. Here, we explored the effect of mTOR inhibition on reconsolidation of addiction memory using cocaine self-administration paradigm. Rats received intravenous cocaine self-administration training for 10 consecutive days, during which a light/tone conditioned stimulus was paired with each cocaine infusion. After acquisition of the stable cocaine self-administration behaviors, rats were subjected to nosepoke extinction (11 days) to extinguish their behaviors, and then received a 15 min retrieval trial with or without the cocaine-paired tone/light cue delivery or without. Immediately or 6 h after the retrieval trial, rapamycin (10 mg/kg) was administered intraperitoneally. Finally, cue-induced reinstatement, cocaine-priming-induced reinstatement and spontaneous recovery of cocaine-seeking behaviors were assessed in rapamycin previously treated animals, respectively. We found that rapamycin treatment immediately after a retrieval trial decreased subsequent reinstatement of cocaine seeking induced by cues or cocaine itself, and these effects lasted at least for 28 days. In contrast, delayed intraperitoneal injection of rapamycin 6 h after retrieval or rapamycin injection without retrieval had no effects on cocaine-seeking behaviors. These findings indicated that mTOR inhibition within the reconsolidation time-window impairs the reconsolidation of cocaine associated memory, reduces cocaine-seeking behavior and prevents relapse, and these effects are retrieval-dependent and temporal-specific.

Levels of retrieval and the testing effect.

Retrieval enhances subsequent memory more than restudy (i.e., the testing effect), demonstrating the encoding (or reencoding) effects of retrieval. It is important to delineate the nature of the encoding effects of retrieval especially in comparison to traditional encoding processes. The current study examined if the level of retrieval, analogous to the level of processing during encoding, has an effect on subsequent memory. In 4 experiments, participants studied short lists of words, each followed by a retrieval or restudy trial. A final free recall test was given at the end of the experiment. The level of retrieval was manipulated by asking participants to retrieve words with a semantic or phonemic cue in the retrieval trial. In order to isolate the effects of retrieval per se, the semantic or phonemic cue was also presented in the restudy trial. Experiment 1 manipulated levels of retrieval (and restudy) between subjects while Experiment 2 manipulated levels within subjects. Experiment 3 sought to enhance the levels effect by adding an overt levels judgment, and Experiment 4 sought to rule out an alternative account of the equality of the testing effects across levels by increasing the list length. In all 4 experiments, a robust testing effect was obtained but it was not moderated by level of retrieval, a result supported by a small-scale meta-analysis, which demonstrated an overall effect of levels and testing condition, but no interaction. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Incomplete reminder cues trigger memory reconsolidation and sustain learned immune responses

Peripheral immune responses can be modulated by taste-immune associative learning where the presentation of a sweet taste as conditioned stimulus (CS) is paired with the injection of an immunosuppressive substance as unconditioned stimulus (US). Previous findings demonstrate conditioned immunopharmacological properties of the mechanistic target of rapamycin (mTOR)-inhibitor rapamycin, a drug used to ameliorate neurological diseases and for the prevention of graft rejection. However, conditioned responses gradually weaken over time and eventually disappear following repeated exposure to the CS in the absence of the US. Thus, in order to employ learning paradigms in clinical conditions as supportive immunopharmacological therapy it is important to understand the central and peripheral mechanisms of how learned immune responses can be protected from extinction. Against this background, the present study used a taste-immune learning paradigm with rapamycin as US (5 mg/kg). By applying only 10% (0.5 mg/kg) of the therapeutic dose rapamycin together with the CS (taste stimulus) during eight retrieval trials, conditioned animals still displayed suppressed interleukin-10 production and T cell proliferation in splenocytes as well as diminished activity of the mTOR target protein p70s6k in amygdala tissue samples. Together, these findings indicate that reminder cues in form of only 10% (0.5 mg/kg) of the therapeutic dose rapamycin together with the CS (taste stimulus) at retrieval preserved the memory of conditioned properties of rapamycin, characterizing this approach as a potential supportive tool in peripheral and central pharmacotherapy with the aim to maximize the therapeutic outcome for the patient’s benefit.

Protective effect of Prunus amygdalus nut extract on chronic unpredictable stress (CUS) induced memory deficits and biochemical alterations in rats

Stress intervenes in the brain’s capability to encode and regain information from a person, it alters the biochemical parameters in specific regions of the brain can cause long-term damage to various parts of brain. The present investigations aid in understanding the effect of the Prunus amygdalus nut extract on CUS induced memory deficits in rats. The methanolic extract with an antioxidant potential (~ 60%) and was selected for in vivo analysis. CUS was induced in rats using different stress paradigms for 10 days. On day 11 and 12, acquisition trials for memory evaluation were performed using Morris Water Maze. On day 13 and 10 days later on, i.e. day 23, short-term and long-term memory retrievals trials were evaluated, respectively. Treatment groups were given test methanolic extract an hour before the subjection of CUS. Biochemical estimations and histopathological studies were carried out using brain tissue homogenate and brain tissue section, respectively. CUS altered the Transfer Latency time in both acquisition and retrieval trials, indicating memory impairment, which was reduced significantly in extract-treated groups. Administration of P. amygdalus nut methanolic extract protected the rat brains against CUS-induced neuroinflammatory changes. The observed beneficial effects could be attributed to the antioxidant potential of P. amygdalus.

EVALUATION OF NEUROPROTECTIVE EFFECT OF AZILSARTAN AS MEMORY ENHANCER AGAINST SCOPOLAMINE AND SODIUM NITRITE-INDUCED AMNESIA IN SWISS ALBINO MALE RATS

Objective: The objective of the study was to assess the neuroprotective effect of azilsartan as a memory enhancer against scopolamine-induced amnesia in rats.
 Methods: Albino Swiss male rats in equal numbers per group (n=6) were taken. Scopolamine hydrobromide was administered to induce amnesia within the rats. Control group rats were administered normal, negative control groups were administered with scopolamine to induce amnesia and nitrite during trials, positive control group rats were administered piracetam+ scopolamine and piracetam nitrite during trials, and test control group rats were administered azilsartan +sodium nitrite and azilsartan nitrite. Exteroceptive behavioral models just like the elevated plus-maze model, Morris water maze model, acquisition trials, and retrieval trial were wont to evaluate the neuroprotective effect of azilsartan.
 Results: The scopolamine and azilsartan have a significantly decreasing effect on time spent within the target quadrant (TSTQ) but piracetam has an increasing effect. The effect of azilsartan on transfer latency time (TLT) was observed against scopolamine-induced amnesia in rats using the elevated plus-maze test. Piracetam was found to decrease the TLT and restore memory function at a better dose. Within the case of scopolamine treated rats, a big increase in TLT was noted. Azilsartan treated group also increased TLT within the elevated plus maze. It is noted that the scopolamine features a significantly increasing effect on escape latency time (ELT). Piracetam features a decreasing effect on ELT. A rise in ELT was seen because of azilsartan.
 Conclusion: This study suggested that the azilsartan features a significant decreasing effect on TSTQ, azilsartan treated group also increased TLT and ELT.

Automatic vs. Manual Detection of High Frequency Oscillations in Intracranial Recordings From the Human Temporal Lobe.

Background: High frequency oscillations (HFOs) have attracted great interest among neuroscientists and epileptologists in recent years. Not only has their occurrence been linked to epileptogenesis, but also to physiologic processes, such as memory consolidation. There are at least two big challenges for HFO research. First, detection, when performed manually, is time consuming and prone to rater biases, but when performed automatically, it is biased by artifacts mimicking HFOs. Second, distinguishing physiologic from pathologic HFOs in patients with epilepsy is problematic. Here we automatically and manually detected HFOs in intracranial EEGs (iEEG) of patients with epilepsy, recorded during a visual memory task in order to assess the feasibility of the different detection approaches to identify task-related ripples, supporting the physiologic nature of HFOs in the temporal lobe.Methods: Ten patients with unclear seizure origin and bilaterally implanted macroelectrodes took part in a visual memory consolidation task. In addition to iEEG, scalp EEG, electrooculography (EOG), and facial electromyography (EMG) were recorded. iEEG channels contralateral to the suspected epileptogenic zone were inspected visually for HFOs. Furthermore, HFOs were marked automatically using an RMS detector and a Stockwell classifier. We compared the two detection approaches and assessed a possible link between task performance and HFO occurrence during encoding and retrieval trials.Results: HFO occurrence rates were significantly lower when events were marked manually. The automatic detection algorithm was greatly biased by filter-artifacts. Surprisingly, EOG artifacts as seen on scalp electrodes appeared to be linked to many HFOs in the iEEG. Occurrence rates could not be associated to memory performance, and we were not able to detect strictly defined “clear” ripples.Conclusion: Filtered graphoelements in the EEG are known to mimic HFOs and thus constitute a problem. So far, in invasive EEG recordings mostly technical artifacts and filtered epileptiform discharges have been considered as sources for these “false” HFOs. The data at hand suggests that even ocular artifacts might bias automatic detection in invasive recordings. Strict guidelines and standards for HFO detection are necessary in order to identify artifact-derived HFOs, especially in conditions when cognitive tasks might produce a high amount of artifacts.

Ten Years’ Experience in Vena Cava Filter Placement – Sample Characterization and Long-term Follow-up

Introduction: Vena cava filter (VCF) has been widely used since it was introduced in 1967. However, there is a general lack of information regarding VCF holders characteristics and their long-term outcomes, and there is not a standardized clinical or imagiological follow-up of these patients. Methods: This is a retrospective analysis of patients who had a VCF placed from 2008 to 2018 at Santa Marta Hospital (Lisbon, PT). Variables collected were patient demographics, indication for filter, filter used. Primary end-point was global survival. Secondary end-point was filter related complications. A substudy was performed to determine late filter related complications in alive patients by abdominal venous duplex ultrasound and abdominal x-ray. Cumulative rates of events were determined by Kaplan-Meier method. Results: From 2008 to 2018, 124 patients underwent VCF placement. Male:female ratio was 1:1. 104 patients (84%) had active venous thromboembolic event (VTE) at time of VCF placement. The most prevalent VTE risk factors were: previous documented VTE (38; 31%), recent hospitalization (63; 51%) and active neoplasm (46; 37%). The most common indications for VCF placement were: anticoagulant contraindication (69; 56%) and persisting pulmonary embolism (PE) despite anticoagulation (29; 23%). Excluding patients whose access site was not specified (16), femoral vein was punctured in 96 patients (89%) and internal jugular vein in 12 patients (11%). VCF was placed on infrarrenal inferior vena cava (IVC) in 100% of patients. Excluding patients whose filter type was not specified, permanent filter was placed in 66 patients (80%). VenaTech LP (B-Braun®) was placed in 34 patients and TrapEase (Cordis®) in 17 patients. A retrievable filter was placed in 17 patients (20%). Celect (Cook®) was placed in 2 patients and OptEase (Cordis®) in 15 patients. There was a VCF retrieval trial in 5 patients, three with success. Survival rate was 86.0±3.2% at 1 month, 63.3±4.5% at 1 year and 55.4±4.8% at 5 years. We found no PE events or VCF related-mortality during follow-up. Patients with active cancer had lower survival rates (28.7±8.5% at 5 years; p<0.001). Survival rates were similar regardless other VTE risk factors and filter indication or type. At present time of our substudy, 32 alive patients were evaluated at median time of 58 months after VCF placement. 2 patients had lower limb DVT in the meantime, one of which have active and the other previous colorrectal cancer. There were no signs of PE. 18 patients (56%) are anticoagulated, 10 with a DOAC (56%). We documented 5 asymptomatic VCF complications: 2 filter occlusions (with patent IVC proximal and distal to VCF), 3 filter tilts (one in a patient that underwent a trial of VCF retrieval). There was no documented filter fracture, penetration or migration. Conclusion: Main absolute indications for VCF placement continue to be VTE in presence of contraindication for anticoagulation and persisting PE despite anticoagulation. Persistent VTE and risk factors for recurrence, lack of follow-up and reported complications of filter retrieval may account for increased use of permanent VCF and retrievable VCF left permanently in place. In spite of known long-term adverse events of VCF (migration, fracture, tilt, penetration, thrombosis), their low incidence and absence of related symptoms challenge a standard of care follow-up for VCF holders. Very low survival rates of VCF holders who have active neoplasm challenge the benefits of VCF placement in patients with dismal prognosis.

Extent of Single-Neuron Activity Modulation by Hippocampal Interictal Discharges Predicts Declarative Memory Disruption in Humans.

Memory deficits are common in epilepsy patients. In these patients, the interictal EEG commonly shows interictal epileptiform discharges (IEDs). While IEDs are associated with transient cognitive impairments, it remains poorly understood why this is. We investigated the effects of human (male and female) hippocampal IEDs on single-neuron activity during a memory task in patients with medically refractory epilepsy undergoing depth electrode monitoring. We quantified the effects of hippocampal IEDs on single-neuron activity and the impact of this modulation on subjectively declared memory strength. Across all recorded neurons, the activity of 50 of 728 neurons were significantly modulated by IEDs, with the strongest modulation in the medial temporal lobe (33 of 416) and in particular the right hippocampus (12 of 58). Putative inhibitory neurons, as identified by their extracellular signature, were more likely to be modulated by IEDs than putative excitatory neurons (19 of 157 vs 31 of 571). Behaviorally, the occurrence of hippocampal IEDs was accompanied by a disruption of recognition of familiar images only if they occurred up to 2 s before stimulus onset. In contrast, IEDs did not impair encoding or recognition of novel images, indicating high temporal and task specificity of the effects of IEDs. The degree of modulation of individual neurons by an IED correlated with the declared confidence of a retrieval trial, with higher firing rates indicative of reduced confidence. Together, these data link the transient modulation of individual neurons by IEDs to specific declarative memory deficits in specific cell types, thereby revealing a mechanism by which IEDs disrupt medial temporal lobe-dependent declarative memory retrieval processes.SIGNIFICANCE STATEMENT Interictal epileptiform discharges (IEDs) are thought to be a cause of memory deficits in chronic epilepsy patients, but the underlying mechanisms are not understood. Utilizing single-neuron recordings in epilepsy patients, we found that hippocampal IEDs transiently change firing of hippocampal neurons and disrupted selectively the retrieval, but not encoding, of declarative memories. The extent of the modulation of the individual firing of hippocampal neurons by an IED predicted the extent of reduction of subjective retrieval confidence. Together, these data reveal a specific kind of transient cognitive impairment caused by IEDs and link this impairment to the modulation of the activity of individual neurons. Understanding the mechanisms by which IEDs impact memory is critical for understanding memory impairments in epilepsy patients.

An interventional image-guided microdevice implantation and retrieval method for in-vivo drug response assessment.

Recently developed implantable microdevices can perform multi-drug response assessment of cancer drugs in-vivo, with potential to develop highly optimized personalized cancer treatment strategies. However, minimally invasive/interventional image-guided methods of in-vivo microdevice implantation, securement, and retrieval are needed for broad clinical translation. Here we demonstrate proof-of-concept of an interventional microdevice implantation and retrieval method for personalized drug response assessment, using ex-vivo phantom, ex-vivo tissue, and in-vivo murine models. A method for minimally-invasive microdevice implantation and retrieval was developed, by which a custom-prototyped 6mm retrievable microdevice can be implanted into a live tumor, deliver drugs into 10 discrete regions of adjacent tissue, and retrieved along with the adjacent drug-exposed tissue with a custom-prototyped retrieval needle device to allow in-vivo multi-drug response assessment. Computed tomography (CT) and ultrasound (US)-guided minimally invasive microdevice implantation and retrieval were tested in ex-vivo phantom and tissue models. Successful retrieval was defined as retrieval of the microdevice and adjacent core phantom/tissue sample containing at least 4/10 drug delivery sites. Subsequently, 10 implantation and retrieval trials in phantom models were performed using bi-axial and tri-axial retrieval needles; success rates were calculated and compared using a two-proportion z-test and the number of successfully retrieved drug release sites per microdevice was calculated and compared using a one-tailed independent t-test. Finally, five microdevices, each containing ten reservoirs preloaded with chemotherapy agent Doxorubicin, were implanted into mouse tumors in-vivo, secured for 24-h during drug release, and microdevice/tissue retrieval was performed under ultrasound guidance. Fluorescence microscopy of the retrieved tissue was used to confirm drug delivery and apoptosis staining assessed in-vivo tissue response; correlation of drug release and apoptosis staining were used to assess in-vivo drug efficacy. Image-guided microdevice implantation and retrieval were successful in ex-vivo phantom and tissue models with both US and CT guidance. Bi-axial retrieval success rate was significantly higher than triaxial retrieval in ex-vivo phantom trials (90% vs 50%, z=1.95, P=0.026), and had nonsignificantly higher number of retrieved drug-release sites per microdevice (8.3 vs 7.0, t=1.37, P=0.097). Bi-axial retrieval was successful in all five in-vivo mouse tumor models, and allowed in-vivo drug response assessment at up to ten discrete drug delivery sites per microdevice. An average of 6.8/10 discrete tumor sites containing micro-doses of delivered drug were retrieved per in-vivo attempt (min 5, max 10, std 1.93). Tissue regions of drug delivery, as assessed with fluorescent Doxorubicin drug signal, correlated with regions of apoptosis staining in all in-vivo models, indicating drug efficacy. No bleeding, microdevice migration, or other complications were noted during implantation, 24-h observation, or retrieval. The demonstrated image-guided minimally invasive microdevice implantation and retrieval method is similar to routine outpatient biopsy procedures, obviates the need for surgery, and can be performed at varying depths under CT and/or US guidance. There is potential for this method to enable clinical translation of in-vivo personalized drug response assessment/prediction in a much larger number of patients than currently possible.

A systematic review of mobile health interventions in China: Identifying gaps in care

Introduction Mobile health has a promising future in the healthcare system in most developed countries. China’s rapidly developing mobile technology infrastructure offers an unprecedented opportunity for wide adoption of mobile health interventions in the delivery of effective and timely healthcare services. However, there is little data on the current extent of the mobile health landscape in China. The aim of this study was to systematically review the existing mobile health initiatives in China, characterise the technology used, disease categories targeted, location of the end user (urban versus rural), and examine the potential effects of mobile health on health system strengthening in China. Furthermore, we identified gaps in development and evaluation of the effectiveness of mobile health interventions. Methods A systematic review of the literature published from 18 December 2015 – 3 April 2019 was conducted and yielded 2863 articles from English and Chinese retrieval database and trial registries, including PubMed, EMBASE, China National Knowledge of Infrastructure and World Health Organization International Clinical Trials Registry Platform. Studies were included if they used mobile health to support patient healthcare outcomes. Results A total of 1129 full-text articles were assessed and 338 were included in this study. The review found that most studies targeted client education and behaviour change via applications (apps) (65.4%), including WeChat, and text messaging (short text messages) (19.8%) to improve patient medical treatment outcomes such as compliance and appointment reminders. The most common disease-specific mobile health interventions focused primarily on chronic disease management and behaviour change in cardiology (13.3%), endocrinology/diabetes (12.1%), behavioural health (11.8%), oncology (11.2%) and neurology (6.8%). The mobile health interventions related to nutrition (0.6%) and chronic respiratory diseases (1.6%) are underrepresented in mobile health in comparison to the burden of disease in China. The majority (90.0%) of the mobile health interventions were conducted exclusively in urban areas, with few opportunities reaching rural populations. Conclusions Overall, mobile health has a promising future in China, with recent rapid growth in initiatives. The majority are focused on education and behaviour change in the realm of chronic diseases and target patients in urban areas. The imbalance in mobile health between the urban and rural areas, as well as between population disease spectrum and health service delivery, pose substantial dilemmas. However, mobile health may be redirected to correct this imbalance, possibly improving access to healthcare services, and filling the gaps in order to improve health equity for the underserved populations in China.

Combination Treatment of Preoperative Embryo Cryopreservation and Endoscopic Surgery (Surgery-ART Hybrid Therapy) in Infertile Women with Diminished Ovarian Reserve and Uterine Myomas or Ovarian Endometriomas

To analyze the clinical outcomes of and predictive factors for the therapeutic effect of combination treatment of preoperative embryo cryopreservation and endoscopic surgery (surgery-assisted reproductive technology [ART] hybrid therapy) in infertile women with diminished ovarian reserve (DOR) with uterine fibroids and/or ovarian endometriomas. Retrospective cohort study. Data from all patients who underwent surgery-ART hybrid therapy at Juntendo University Hospital and Sugiyama Clinic between 2014 and 2016 were analyzed retrospectively. We compared women who experienced live birth (success group) and implantation failure or miscarriage (failure group) after surgery-ART hybrid therapy and evaluate the predictive factors for live birth. A total of 39 infertile women underwent surgery-ART hybrid therapy with 86 embryo transfer cycles. All women underwent ART treatment for embryo cryopreservation preoperatively, reproductive surgery, and warmed embryo transfer after the postoperative contraceptive interval (surgery-ART hybrid therapy) for women with DOR (anti-Müllerian hormone <1.0 ng/mL) and/or advanced reproductive age (>40 years) with uterine myomas and/or ovarian endometriomas who required surgery. Among 39 women underwent surgery-ART hybrid therapy, 1 woman acquired no embryo after oocyte retrieval trials and abandoned efforts to conceive, 14 experienced childbirth (success group) and 24 (63.2%) experienced implantation failure or miscarriage (failure group) after surgery-ART hybrid therapy. The median patient age was 40 years (interquartile range [IQR], 38-41 years) in the success group and 41.5 years (IQR, 41-42 years) in the failure group (p = .032). The respective serum anti-Müllerian hormone levels were 2.5 ng/mL (range, 0.1-8.6 ng/mL) and 1.3 ng/mL (range, 0.1-4.2 ng/mL) (p = .396), and the respective numbers of preoperative frozen were 5.0 (range, 4.0-6.0) and 2.0 (range, 1.0-3.0) (p < .001). There were no significant differences in surgical findings of myomas and endometriosis between the 2 groups. Compared with the 24 women who experienced hybrid therapy failure, the 14 who underwent successful surgery-ART hybrid therapy were significantly younger and had a greater number of cryopreserved embryos. Successful surgery-ART hybrid therapy requires a sufficient preoperative age-specific number of frozen embryos, establishment of ART treatment with stable pregnancy outcomes and skillful reproductive surgery, and a strong desire of the patient and doctor for pregnancy.

The role of prediction error and memory destabilization in extinction of cued-fear within the reconsolidation window

Extinction of a cued-fear memory within the reconsolidation window has been proposed to prevent fear reacquisition by reconsolidation interference. This ‘retrieval-extinction’ procedure has received interest for its therapeutic potential to reduce the impact of fear memories on behavior. To fully exploit its therapeutic potential, it is critical to understand the mechanisms that underlie the ‘retrieval-extinction’ effect. If the effect depends upon reconsolidation of the original memory, then it would be predicted that destabilization, induced by prediction error, would be critical for observing the effect. Here, the dependency of the retrieval-extinction effect on memory destabilization or prediction error was investigated in pavlovian cued-fear conditioned adult male rats. The requirement for memory destabilization, and thus reconsolidation, for the retrieval-extinction effect was subsequently investigated using region-specific pharmacological blockade of dopamine D1-receptors. Intra-basolateral amygdala antagonism of dopamine D1-receptors did not prevent the reacquisition of fear associated with the retrieval-extinction procedure. The requirement for prediction error was assessed by using a reinforced or non-reinforced memory retrieval trial before extinction, compared to a no-retrieval, extinction-only control. Both the reinforced (no prediction error) and non-reinforced retrieval sessions led to a decrease in fear reacquisition, suggesting that engagement of prediction error does not influence the occurrence of retrieval-extinction. Together, these data suggest that retrieval-extinction does not require memory destabilization, since behavioral or pharmacological interventions that prevent destabilization did not disrupt any capacity to attenuate fear.

Correspondence Between Resting-State and Episodic Memory-Task Related Networks in Elderly Subjects.

Resting-state fMRI studies demonstrated temporally synchronous fluctuations in brain activity among ensembles of brain regions, suggesting the existence of intrinsic functional networks. A spatial match between some of the resting-state networks and regional brain activation during cognitive tasks has been noted, suggesting that resting-state networks support particular cognitive abilities. However, the spatial match and predictive value of any resting-state network and regional brain activation during episodic memory is only poorly understood. In order to address this research gap, we obtained fMRI acquired both during rest and a face-name association task in 38 healthy elderly subjects. In separate independent component analyses, networks of correlated brain activity during rest or the episodic memory task were identified. For the independent components identified for task-based fMRI, the design matrix of successful encoding or retrieval trials was regressed against the time course of each of the component to identify significantly activated networks. Spatial regression was used to assess the match of resting-state networks against those related to successful memory encoding or retrieval. We found that resting-state networks covering the medial temporal, middle temporal, and frontal areas showed increased activity during successful encoding. Resting-state networks located within posterior brain regions showed increased activity during successful recognition. However, the level of resting-state network connectivity was not predictive of the task-related activity in these networks. These results suggest that a circumscribed number of functional networks detectable during rest become engaged during successful episodic memory. However, higher intrinsic connectivity at rest may not translate into higher network expression during episodic memory.

Female mound-building mice prefer males that invest more in building behavior, even when this behavior is not observed

Through behavioral correlations, mate choice could influence the evolution of traits that are not directly selected for, or even observed. We addressed whether mound building, a unique collective behavior observed in Mus spicilegus, could be favored by female mate choice, irrespective of whether females were able to observe the behavior. First, we introduced mixed sex groups of wild-born mice in large terraria with building materials and assessed male variation in building investment. Second, we presented females with a choice between males that invested the most versus the least in building. Females were either able to observe the males during building or not. Third, because overwintering juveniles rely on mound protection, we hypothesized that building could be a form of paternal care, and assessed whether males that invested more in building also invested more in direct offspring care. We showed that females were more attracted to males that invested the most in building, even when these behaviors were not observed. In addition, direct offspring care was negatively correlated with males’ investment in building, suggesting that two alternative paternal care strategies (mound building versus direct offspring care) may exist. Our study supports the hypothesis that building could be detectable by phenotypic cues that differ from building behavior per se and that mate choice may influence the evolution and maintenance of mound building that several authors describe as a common good. In the mound-building mouse, individuals gather to build a common mound within which juveniles will spend the winter months. As some males invest more in building than others, we questioned whether females would prefer males that invest more in building behaviors, even though females could not observe males’ building behaviors before mate choice. We assessed male investment in building and conducted choice tests. Females were more attracted to males that invested more in building, even when building was not observed. Hence, building investment seems detectable by phenotypic cues that differ from building behavior per se. Further, the males’ investment in building was negatively correlated with their direct offspring care assessed during retrieval trials. Our findings indicate that two alternative paternal care strategies may exist in this species, and that mate choice might influence the evolution of their remarkable collective building.

High red blood cell composition in clots is associated with successful recanalization during intra-arterial thrombectomy.

We evaluated the composition of individual clots retrieved during intra-arterial thrombectomy in relation to recanalization success, stroke subtype, and the presence of clot signs on initial brain images. We analyzed clot and interventional data from 145 retrieval trials performed for 37 patients (69.5±14.0 years, 20 men, large artery atherosclerosis, n = 7; cardioembolism, n = 22; undetermined etiology, n = 8) who had undergone intra-arterial thrombectomy. Rates of clot retrieval and successful recanalization (Arterial Occlusive Lesion score of 2–3) for separate retrieval trials were evaluated. The area occupied by red blood cell (RBC), fibrin/platelets, and white blood cell (WBC) was measured from digitized images of hematoxylin-eosin stained clots. Compositional differences were compared according to recanalization success, stroke subtype, and the presence of hyperdense clot sign on initial computed tomography and/or blooming artifact on magnetic resonance image. Of the 145 total retrieval trials (3.4±2.4 times per patient), clot was retrieved in 93 trials (64%), while recanalization was successful in 73 (50%). Fibrin/platelets (63%) occupied the greatest area in retrieved clots, followed by RBCs (33%) and WBCs (4%). Clots retrieved from successful recanalization exhibited higher RBC composition (37%) than those retrieved from non-recanalization trials (20%, p = 0.001). RBC composition was higher in cardioembolic stroke (38%) rather than large artery atherosclerosis (23%) and undetermined etiology (26%, p = 0.01). Clots exhibiting clot signs (40%) had higher RBC composition than those without clot signs (19%, p = 0.001). RBC-rich clots were associated with successful recanalization of intra-arterial thrombectomy, cardioembolic stroke, and the presence of clot-signs on initial brain images.

Is it possible to modify fear memories in humans with extinction training within a single day?

Extinction procedures have been used widely in the study of fear memories, and different positions have been adopted regarding the efficacy of such procedures and the mechanisms involved. It has been argued that extinction may interfere with the consolidation of the fear memory if the procedure is applied with the appropriate timing after acquisition. However, the opposite position is also held, that is, that the extinction does not achieve an elimination of the fear response. The aim of the present study is to test the short-term effects of immediate extinction in fear reduction when this extinction is preceded by a retrieval trial. For this, a procedure similar to that employed by Schiller et al. (Nature 463(7277): 49-53, 2010) was used, but in a single day and with white noise as an aversive unconditioned stimulus. The results indicate that a CS+ single retrieval trial before the extinction procedure after acquisition was more effective in fear reduction than standard immediate extinction.