The neural correlates of mindfulness-induced depression reduction in adults with autism spectrum disorder: A pilot study.

Adults with autism spectrum disorder (ASD) experience high rates of depression and anxiety, and some evidence suggests mindfulness-based stress reduction (MBSR) is effective in reducing these symptoms. However, the neural mechanisms of symptom alleviation, and benefit of MBSR beyond education/support groups are unknown. Maladaptive forms of self-reflection are linked to ASD, depression, and anxiety. In this pilot study, we hypothesized (a) MBSR would reduce depression and anxiety in adults with ASD and (b) a mechanism of symptom alleviation would be increased blood oxygen level-dependent signal in neural self-reflection hubs. Twenty-eight adults were randomly assigned to an 8-week MBSR group (n = 15) or a support group (n = 13) that met for the same amount of time with relaxation education materials. Based on previous self-reflection literature in ASD, regions of interest (ROIs) were middle cingulate cortex (MCC) and ventromedial prefrontal cortex (vmPFC). Only the MBSR group demonstrated significant reductions in depression, and neither group significantly changed in anxiety. Only the MBSR group increased activity of right MCC during self-reflection, and the increase correlated with depression alleviation. There were no changes in vmPFC for the MBSR group or either ROI for the support/education group. Seed-to-voxel connectivity analysis revealed that only the MBSR group increased functional connectivity between right MCC and pre/postcentral gyrus, suggesting MBSR may increase primary sensorimotor input to higher order cognitive brain regions. Taken together, MBSR may be effective for reducing depression in adults with ASD, and the neural mechanism may be increasing frontal circuit involvement during self-directed thought.

Significance of oliguria in critically ill patients with chronic liver disease.

Clinical guidelines recommend using Kidney Disease Improving Global Outcomes (KDIGO) criteria for the diagnosis and classification of acute kidney injury (AKI) in patients with chronic liver disease (CLD). Concerns have been raised about the use of urine output (UO) criteria in CLD. We examined the significance of oliguria meeting the urine output criteria for AKI (AKI-UO) and examined its association with clinical outcomes in CLD patients. Using an 8-year clinical database from a large university medical center, 3458 patients with CLD were identified. AKI occurred in 2854 (82.5%) patients when they fulfilled any KDIGO criteria. When serum creatinine (SC) and UO criteria were used, 604 patients (17.5%) had no evidence of AKI and had the lowest hospital mortality rate (5%). Using AKI-UO criteria alone, 2103 patients (60.8%) were classified as stage 2-3 AKI. When only SC criteria were applied, 1281 (61%) of those patients with stage 2-3 AKI-UO were misclassified as either no AKI or AKI stage 1. Patients reclassified with AKI according to UO criteria (AKI-UO) had nearly a 3-fold increased rate of hospital mortality compared with patients without any AKI (14.6% versus 5%; P < 0.001) and more than a 50% increased mortality compared with stage 1 AKI-SC (14.6% versus 9%; P < 0.001). Patients with transient oliguria (AKI-UO stage 1) had increased mortality rates compared with patients without oliguria (14.9% versus 6.9%; P < 0.001). CONCLUSION: CLD patients have a high incidence of AKI. Compared with creatinine criteria alone, incorporating UO into the diagnostic criteria increased the measured incidence of AKI. Stage 2-3 AKI-UO has a high negative impact on hospital mortality. (Hepatology 2017;66:1592-1600).

Chloride Content of Fluids Used for Large-Volume Resuscitation Is Associated With Reduced Survival.

OBJECTIVE: We sought to investigate if the chloride content of fluids used in resuscitation was associated with short- and long-term outcomes. DESIGN: We identified patients who received large-volume fluid resuscitation, defined as greater than 60 mL/kg over a 24-hour period. Chloride load was determined for each patient based on the chloride ion concentration of the fluids they received during large-volume fluid resuscitation multiplied by the volume of fluids. We compared the development of hyperchloremic acidosis, acute kidney injury, and survival among those with higher and lower chloride loads. SETTING: University Medical Center. PATIENTS: Patients admitted to ICUs from 2000 to 2008. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Among 4,710 patients receiving large-volume fluid resuscitation, hyperchloremic acidosis was documented in 523 (11%). Crude rates of hyperchloremic acidosis, acute kidney injury, and hospital mortality all increased significantly as chloride load increased (p < 0.001). However, chloride load was no longer associated with hyperchloremic acidosis or acute kidney injury after controlling for total fluids, age, and baseline severity. Conversely, each 100 mEq increase in chloride load was associated with a 5.5% increase in the hazard of death even after controlling for total fluid volume, age, and severity (p = 0.0015) over 1 year. CONCLUSIONS: Chloride load is associated with significant adverse effects on survival out to 1 year even after controlling for total fluid load, age, and baseline severity of illness. However, the relationship between chloride load and development of hyperchloremic acidosis or acute kidney injury is less clear, and further research is needed to elucidate the mechanisms underlying the adverse effects of chloride load on survival.

Electrical conduction block in large nerves: high-frequency current delivery in the nonhuman primate.

Recent studies have made significant progress toward the clinical implementation of high-frequency conduction block (HFB) of peripheral nerves. However, these studies were performed in small nerves, and questions remain regarding the nature of HFB in large-diameter nerves. This study in nonhuman primates shows reliable conduction block in large-diameter nerves (up to 4.1 mm) with relatively low-threshold current amplitude and only moderate nerve discharge prior to the onset of block.

Transdermal Electrical Neuromodulation for Anxiety and Sleep Problems in High-Functioning Autism Spectrum Disorder: Feasibility and Preliminary Findings.

BACKGROUND: Autism spectrum disorder (ASD) is associated with anxiety and sleep problems. We investigated transdermal electrical neuromodulation (TEN) of the cervical nerves in the neck as a safe, effective, comfortable and non-pharmacological therapy for decreasing anxiety and enhancing sleep quality in ASD. METHODS: In this blinded, sham-controlled study, seven adolescents and young adults with high-functioning ASD underwent five consecutive treatment days, one day of the sham followed by four days of subthreshold TEN for 20 min. Anxiety-provoking cognitive tasks were performed after the sham/TEN. Measures of autonomic nervous system activity, including saliva α-amylase and cortisol, electrodermal activity, and heart rate variability, were collected from six participants. RESULTS: Self-rated and caretaker-rated measures of anxiety were significantly improved with TEN treatment as compared to the sham, with effect sizes ranging from medium to large depending on the rating scale. Sleep scores from caretaker questionnaires also improved, but not significantly. Performance on two of the three anxiety-provoking cognitive tasks and heart rate variability significantly improved with TEN stimulation as compared to the sham. Four of the seven (57%) participants were responders, defined as a ≥ 30% improvement in self-reported anxiety. Salivary α-amylase decreased with more TEN sessions and decreased from the beginning to the end of the session on TEN days for responders. TEN was well-tolerated without significant adverse events. CONCLUSIONS: This study provides preliminary evidence that TEN is well-tolerated in individuals with ASD and can improve anxiety.

Conduction block of peripheral nerve using high-frequency alternating currents delivered through an intrafascicular electrode.

Many diseases are characterized by undesired or pathological neural activity. The local delivery of high-frequency currents has been shown to be an effective method for blocking neural conduction in peripheral nerves and may provide a therapy for these conditions. To date, all studies of high-frequency conduction block have utilized extraneural (cuff) electrodes to achieve conduction block. In this study we show that high-frequency conduction block is feasible using intrafascicular electrodes.

Temporary persistence of conduction block after prolonged kilohertz frequency alternating current on rat sciatic nerve.

OBJECTIVE: Application of kilohertz frequency alternating current (KHFAC) waveforms can result in nerve conduction block that is induced in less than a second. Conduction recovers within seconds when KHFAC is applied for about 5-10 min. This study investigated the effect of repeated and prolonged application of KHFAC on rat sciatic nerve with bipolar platinum electrodes. APPROACH: Varying durations of KHFAC at signal amplitudes for conduction block with intervals of no stimulus were studied. Nerve conduction was monitored by recording peak Gastrocnemius muscle force utilizing stimulation electrodes proximal (PS) and distal (DS) to a blocking electrode. The PS signal traveled through the block zone on the nerve, while the DS went directly to the motor end-plate junction. The PS/DS force ratio provided a measure of conduction patency of the nerve in the block zone. MAIN RESULTS: Conduction recovery times were found to be significantly affected by the cumulative duration of KHFAC application. Peak stimulated muscle force returned to pre-block levels immediately after cessation of KHFAC delivery when it was applied for less than about 15 min. They fell significantly but recovered to near pre-block levels for cumulative stimulus of 50 ± 20 min, for the tested On/Off times and frequencies. Conduction recovered in two phases, an initial fast one (60-80% recovery), followed by a slower phase. No permanent conduction block was seen at the end of the observation period during any experiment. SIGNIFICANCE: This carry-over block effect may be exploited to provide continuous conduction block in peripheral nerves without continuous application of KHFAC.

Intensive Monitoring of Urine Output Is Associated With Increased Detection of Acute Kidney Injury and Improved Outcomes.

BACKGROUND: Urine output (UO) is a vital sign for critically ill patients, but standards for monitoring and reporting vary widely between ICUs. Careful monitoring of UO could lead to earlier recognition of acute kidney injury (AKI) and better fluid management. We sought to determine if the intensity of UO monitoring is associated with outcomes in patients with and those without AKI. METHODS: This was a retrospective cohort study including 15,724 adults admitted to ICUs from 2000 to 2008. Intensive UO monitoring was defined as hourly recordings and no gaps > 3 hours for the first 48 hours after ICU admission. RESULTS: Intensive monitoring for UO was conducted in 4,049 patients (26%), and we found significantly higher rates of AKI (OR, 1.22; P < .001) in these patients. After adjustment for age and severity of illness, intensive UO monitoring was associated with improved survival but only among patients experiencing AKI. With or without AKI, patients with intensive monitoring also had less cumulative fluid volume (2.98 L vs 3.78 L; P < .001) and less fluid overload (2.49% vs 5.68%; P < .001) over the first 72 hours of ICU stay. CONCLUSIONS: In this large ICU population, intensive monitoring of UO was associated with improved detection of AKI and reduced 30-day mortality in patients experiencing AKI, as well as less fluid overload for all patients. Our results should help inform clinical decisions and ICU policy about frequency of monitoring of UO, especially for patients at high risk of AKI or fluid overload, or both.

Psychometric properties of the children's sleep habits questionnaire in children with autism spectrum disorder.

BACKGROUND AND PURPOSE: Sleep disturbances in autism spectrum disorder (ASD) are very common. Psychometrically sound instruments are essential to assess these disturbances. Children's Sleep Habit Questionnaire (CSHQ) is a widely used measure in ASD. The purpose of this study was to explore the psychometric properties of the CSHQ in a sample of children with ASD. PARTICIPANTS AND METHODS: Parents/caregivers of 310 children (mean age: 4.7) with ASD completed the CSHQ at study enrollment. Correlations between intelligence quotient (IQ) scores and the original CSHQ scales were calculated. Item endorsement frequencies and percentages were also calculated. A principal component analysis (PCA) was performed, and internal consistency was assessed for the newly extracted components. RESULTS: Correlations between IQ scores and CSHQ subscales and total scores ranged from .015 to .001 suggesting a weak, if any, association. Item endorsement frequencies were high for bedtime resistance items, but lower for parasomnia and sleep-disordered breathing items. A PCA suggested that a five-component solution best fits the data. Internal consistency of the newly extracted five components ranged α = .87-.50. CONCLUSIONS: Item endorsement frequencies were highest for bedtime resistance items. A PCA suggested a five-component solution. Three of the five components (Sleep Routine Problems, Insufficient Sleep, and Sleep-onset Association Problems) were types of sleep disturbances commonly reported in ASD, but the other two components (Parasomnia/Sleep-disordered Breathing and Sleep Anxiety) were less clear. Internal consistencies ranged from mediocre to good. Further development of this measure for use in children with ASD is encouraged.

Psychometric Properties of the Brief Autism Mealtime Behaviors Inventory.

The purpose of this study was to explore the psychometric properties of the Brief Autism Mealtime Behaviors Inventory (BAMBI). In a sample of 273 well-characterized children with ASD, we explored the factor structure of the BAMBI, determined the internal consistency of a newly derived factor structure and provide an empirically derived cut-off for the BAMBI total score. The new psychometrically identified structure consists of 4 factors: (1) Food Selectivity, (2) Disruptive Mealtime Behaviors, (3) Food Refusal and (4) Mealtime Rigidity. Internal consistency was acceptable. A cut off score of 34 is suggested based on our results. The new 15-item BAMB with an alternative 4-factor structure with clinical utility is promising in assessing feeding and mealtime problems in children with ASD.