DNA-PK inhibition shows differential radiosensitization in orthotopic GBM PDX models based on DDR pathway deficits.

Glioblastoma (GBM) remains one of the most therapy-resistant malignancies with frequent local failures despite aggressive surgery, chemotherapy, and ionizing radiation (IR). Small molecule inhibitors of DNA-dependent protein kinase (DNA-PKi's) are potent radiosensitizers currently in clinical trials. Determining which patients may benefit from radiosensitization with DNA-PKi's is critical to avoid unnecessary increased risk of normal tissue toxicity. In this study we used GBM patient derived xenografts (PDXs) in orthotopic murine models to study the relationship between molecular features, pharmacokinetics, and the radiosensitizing potential of the DNA-PKi peposertib. We show that peposertib radiosensitizes established and PDX GBM lines in vitro at 300nM and above, with significant increase in radiosensitization by maintaining post-IR exposure for >12 hours. Radiosensitization by peposertib is mediated by catalytic inhibition of DNA-PK, and knock-down of DNA-PK by short hairpin RNA (shRNA) largely abolished the radiosensitizing effect. Peposertib decreased auto-phosphorylation of DNA-PKcs after IR in a dose-dependent manner with delay in resolution of γH2AX foci at 24 hours. The addition of peposertib to IR significantly increased survival in GBM120 orthotopic xenografts, but not in GBM10. There was no difference in plasma or average tumor concentrations of peposertib in the two cohorts. While the mechanism underpinning this discordant effect in vitro vs. in vivo is not clear, there was an association for greater sensitization in TP53 mutant lines. Transfection of a dominant-negative TP53 mutant in baseline TP53 wildtype GBM lines significantly delayed growth and decreased NHEJ efficiency (but not Homologous Recombination), after peposertib exposure.

Everyday home radon exposure is associated with altered structural brain morphology in youths.

The refinement of brain morphology extends across childhood, and exposure to environmental toxins during this period may alter typical trends. Radon is a highly common radiologic toxin with a well-established role in cancer among adults. However, effects on developmental populations are understudied in comparison. This study investigated whether home radon exposure is associated with altered brain morphology in youths. Fifty-four participants (6-14 yrs, M=10.52 yrs, 48.15% male, 89% White) completed a T1-weighted MRI and home measures of radon. We observed a significant multivariate effect of home radon concentrations, which was driven by effects on GMV. Specifically, higher home radon was associated with smaller GMV (F=6.800, p=.012, ηp2=.13). Conversely, there was a trending radon-by-age interaction on WMV, which reached significance when accounting for the chronicity of radon exposure (F=4.12, p=.049, ηp2=.09). We found that youths with above-average radon exposure showed no change in WMV with age, whereas low radon was linked with normative, age-related WMV increases. These results suggest that everyday home radon exposure may alter sensitive structural brain development, impacting developmental trajectories in both gray and white matter.

Anterior pituitary gland volume mediates associations between pubertal hormones and changes in transdiagnostic symptoms in youth.

The pituitary gland (PG) plays a central role in the production and secretion of pubertal hormones, with documented links to the emergence and increase in mental health symptoms known to occur during adolescence. Although much of the literature has focused on examining whole PG volume, recent findings suggest that there are associations among pubertal hormone levels, including dehydroepiandrosterone (DHEA), subregions of the PG, and elevated mental health symptoms (e.g., internalizing symptoms) during adolescence. Surprisingly, studies have not yet examined associations among these factors and increasing transdiagnostic symptomology, despite DHEA being a primary output of the anterior PG. Therefore, the current study sought to fill this gap by examining whether anterior PG volume specifically mediates associations between DHEA levels and changes in dysregulation symptoms in an adolescent sample ( N = 114, 9 - 17 years, M age = 12.87, SD = 1.88). Following manual tracing of the anterior and posterior PG, structural equation modeling revealed that greater anterior, not posterior, PG volume mediated the association between greater DHEA levels and increasing dysregulation symptoms across time, controlling for baseline dysregulation symptom levels. These results suggest specificity in the role of the anterior PG in adrenarcheal processes that may confer risk for psychopathology during adolescence. This work not only highlights the importance of separately tracing the anterior and posterior PG, but also suggests that transdiagnostic factors like dysregulation are useful in parsing hormone-related increases in mental health symptoms in youth.

Open preperitoneal inguinal hernia repair has superior 1-year patient-reported outcomes compared to Shouldice non-mesh repair.

INTRODUCTION: The Shouldice method for inguinal hernia repair remains the gold standard for prosthesis-free repairs. Nonetheless, international guidelines have favored posterior mesh reinforcement as the standard of care for inguinal hernia repair due to lower risk of recurrence and chronic pain, avoidance of general anesthesia, and favorable biomechanical properties. Recent publications have shown the benefits of an open approach to posterior repairs. Herein, we use the Abdominal Core Health Quality Collaborative (ACHQC) registry to compare patient-reported outcomes after a Shouldice no-mesh repair versus open preperitoneal (OPP) mesh repair. METHODS: We performed a propensity score matched analysis to compare patient-reported quality of life (QoL) and peri/postoperative outcomes after a Shouldice repair versus OPP. Data from 2012 to 2022 were obtained from the ACHQC, and 1:1 optimal matching was performed. EuraHS scores were used to estimate QoL, and further analysis on the EuraHS domains of pain, aesthetics, and activity restriction were performed between the two cohorts. RESULTS: Matching resulted in 257 participants in each, Shouldice and OPP cohorts. OPP was associated with a better QoL score compared to Shouldice at 30 days after surgery (Median (IQR) 7.75 (2.0-17.0) vs 13.0 (4.0-26.1); OR 0.559 [0.37, 0.84]; p = 0.003). This difference persisted at 6 months and 1 year postoperatively (OR 0.447 [0.26, 0.75] and 0.492 [0.26, 0.93], respectively). We did not observe any significant differences in hernia recurrence risk at 1-year, or rates of 30-day SSOs/SSIs, postoperative bleeding, peripheral nerve injury, DVTs, or UTIs. CONCLUSION: Our data suggest that OPP is associated with significantly better patient-reported QoL, in the first month after surgery and up to 1 year postoperatively, especially with respect to lesser pain, when compared to the Shouldice repair. In specialized inguinal hernia practices, open posterior mesh repairs may lead to better outcomes than non-mesh repairs. We encourage more training in both repairs to facilitate larger prospective studies and evaluation of the generalizability of these results to all surgeons performing IHR.

Dehydroepiandrosterone mediates associations between trauma-related symptoms and anterior pituitary volume in children and adolescents.

INTRODUCTION: The anterior pituitary gland (PG) is a potential locus of hypothalamic-pituitary-adrenal (HPA) axis responsivity to early life stress, with documented associations between dehydroepiandrosterone (DHEA) levels and anterior PG volumes. In adults, elevated anxiety/depressive symptoms are related to diminished DHEA levels, and studies have shown a positive relationship between DHEA and anterior pituitary volumes. However, specific links between responses to stress, DHEA levels, and anterior pituitary volume have not been established in developmental samples. METHODS: High-resolution T1-weighted MRI scans were collected from 137 healthy youth (9-17 years; Mage = 12.99 (SD = 1.87); 49% female; 85% White, 4% Indigenous, 1% Asian, 4% Black, 4% multiracial, 2% not reported). The anterior and posterior PGs were manually traced by trained raters. We examined the mediating effects of salivary DHEA on trauma-related symptoms (i.e., anxiety, depression, and posttraumatic) and PG volumes as well as an alternative model examining mediating effects of PG volume on DHEA and trauma-related symptoms. RESULTS: DHEA mediated the association between anxiety symptoms and anterior PG volume. Specifically, higher anxiety symptoms related to lower DHEA levels, which in turn were related to smaller anterior PG. CONCLUSIONS: These results shed light on the neurobiological sequelae of elevated anxiety in youth and are consistent with adult findings showing suppressed levels of DHEA in those with greater comorbid anxiety and depression. Specifically, adolescents with greater subclinical anxiety may exhibit diminished levels of DHEA during the pubertal window, which may be associated with disruptions in anterior PG growth.

Developmental changes in endogenous testosterone have sexually-dimorphic effects on spontaneous cortical dynamics.

The transition from childhood to adolescence is associated with an influx of sex hormones, which not only facilitates physical and behavioral changes, but also dramatic changes in neural circuitry. While previous work has shown that pubertal hormones modulate structural and functional brain development, few of these studies have focused on the impact that such hormones have on spontaneous cortical activity, and whether these effects are modulated by sex during this critical developmental window. Herein, we examined the effect of endogenous testosterone on spontaneous cortical activity in 71 typically-developing youth (ages 10-17 years; 32 male). Participants completed a resting-state magnetoencephalographic (MEG) recording, structural MRI, and provided a saliva sample for hormone analysis. MEG data were source-reconstructed and the power within five canonical frequency bands (delta, theta, alpha, beta, and gamma) was computed. The resulting power spectral density maps were analyzed via vertex-wise ANCOVAs to identify spatially specific effects of testosterone and sex by testosterone interactions, while covarying out age. We found robust sex differences in the modulatory effects of testosterone on spontaneous delta, beta, and gamma activity. These interactions were largely confined to frontal cortices and exhibited a stark switch in the directionality of the correlation from the low (delta) to high frequencies (beta/gamma). For example, in the delta band, greater testosterone related to lower relative power in prefrontal cortices in boys, while the reverse pattern was found for girls. These data suggest testosterone levels are uniquely related to the development of spontaneous cortical dynamics during adolescence, and such levels are associated with different developmental patterns in males and females within regions implicated in executive functioning.

Primary Tissue Repair for Inguinal Hernias: The Shouldice Repair Technique and Patient Selection.

It is estimated that approximately one in four men and one in 20 women will develop an inguinal hernia over the course of their lifetime. A non-mesh inguinal hernia repair via the Shouldice technique is a unique approach that necessitates dissection of the entire groin region as well as careful assessment for any secondary hernias. Subsequently, a pure tissue laminated closure allows the repair to be performed without tension. Herein, the authors describe a brief overview of inguinal hernias and discuss the relevant patient evaluation, operative steps of the Shouldice procedure, and postoperative considerations.

Developmental alterations in the neural oscillatory dynamics underlying attentional reorienting.

The neural and cognitive processes underlying the flexible allocation of attention undergo a protracted developmental course with changes occurring throughout adolescence. Despite documented age-related improvements in attentional reorienting throughout childhood and adolescence, the neural correlates underlying such changes in reorienting remain unclear. Herein, we used magnetoencephalography (MEG) to examine neural dynamics during a Posner attention-reorienting task in 80 healthy youth (6-14 years old). The MEG data were examined in the time-frequency domain and significant oscillatory responses were imaged in anatomical space. During the reorienting of attention, youth recruited a distributed network of regions in the fronto-parietal network, along with higher-order visual regions within the theta (3-7 Hz) and alpha-beta (10-24 Hz) spectral windows. Beyond the expected developmental improvements in behavioral performance, we found stronger theta oscillatory activity as a function of age across a network of prefrontal brain regions irrespective of condition, as well as more limited age- and validity-related effects for alpha-beta responses. Distinct brain-behavior associations between theta oscillations and attention-related symptomology were also uncovered across a network of brain regions. Taken together, these data are the first to demonstrate developmental effects in the spectrally-specific neural oscillations serving the flexible allocation of attention.

Improved patient-reported outcomes after open preperitoneal inguinal hernia repair compared to anterior Lichtenstein repair: 10-year ACHQC analysis.

INTRODUCTION: The Lichtenstein repair has been synonymous with "open" inguinal hernia repair (IHR) for 40 years. However, international guidelines have suggested that posterior mesh placement results in advantageous biomechanics and reduced risk of nerve-related chronic pain. Additionally, the use of local anesthetics has been shown to reduce postoperative pain and complication risks. An open transrectus preperitoneal/open preperitoneal (TREPP/OPP) repair combines posterior mesh placement with the use of local anesthetic and as such could be the ideal repair for primary inguinal hernia. Using the Abdominal Core Health Quality Collaborative (ACHQC) registry, we compared open anterior mesh with open posterior mesh repairs. METHODS: We performed a propensity score matched analysis of patients undergoing open IHR between 2012 and 2022 in the ACHQC. After 1:1 optimal matching, both the TREPP/OPP and Lichtenstein cohorts were balanced with 451 participants in each group. Outcomes included patient-reported quality of life (QoL), hernia recurrence, and postoperative opioid use. RESULTS: Improvement was seen after TREPP/OPP in EuraHS QoL score at 30 days (OR 0.558 [0.408, 0.761]; p = 0.001), and the difference persisted at 1 year (OR 0.588 [0.346, 0.994]; p = 0.047). Patient-reported opioid use at 30-day follow-up was significantly lower in the TREPP/OPP cohort (OR 0.31 [0.20, 0.48]; p < 0.001). 30-day frequency of surgical-site occurrences was significantly higher in the Lichtenstein repair cohort (OR 0.22 [0.06-0.61]; p = 0.007). There were no statistically significant differences in hernia recurrence risk at 1 year, or rates of postoperative bleeding, peripheral nerve injury, DVTs, or UTIs. CONCLUSION: Our analysis demonstrates a benefit of posterior mesh placement (TREPP/OPP) over anterior mesh placement (Lichtenstein) in open inguinal hernia repair in patient-reported QoL and reduced opioid use.

Aberrant age-related alterations in spontaneous cortical activity in participants with cerebral palsy.

Introduction: Cerebral Palsy (CP) is the most common neurodevelopmental motor disability, resulting in life-long sensory, perception and motor impairments. Moreover, these impairments appear to drastically worsen as the population with CP transitions from adolescents to adulthood, although the underlying neurophysiological mechanisms remain poorly understood. Methods: We began to address this knowledge gap by utilizing magnetoencephalographic (MEG) brain imaging to study how the amplitude of spontaneous cortical activity (i.e., resting state) is altered during this transition period in a cohort of 38 individuals with spastic diplegic CP (Age range = 9.80-47.50 years, 20 females) and 67 neurotypical controls (NT) (Age range = 9.08-49.40 years, Females = 27). MEG data from a five-minute eyes closed resting-state paradigm were source imaged, and the power within the delta (2-4 Hz), theta (5-7 Hz), alpha (8-12 Hz), beta (15-29 Hz), and gamma (30-59 Hz) frequency bands were computed. Results: For both groups, the delta and theta spontaneous power decreased in the bilateral temporoparietal and superior parietal regions with age, while alpha, beta, and gamma band spontaneous power increased in temporoparietal, frontoparietal and premotor regions with age. We also found a significant group x age interaction, such that participants with CP demonstrated significantly less age-related increases in the spontaneous beta activity in the bilateral sensorimotor cortices compared to NT controls. Discussion: Overall, these results demonstrate that the spontaneous neural activity in individuals with CP has an altered trajectory when transitioning from adolescents to adulthood. We suggest that these differences in spontaneous cortical activity may play a critical role in the aberrant motor actions seen in this patient group, and may provide a neurophysiological marker for assessing the effectiveness of current treatment strategies that are directed at improving the mobility and sensorimotor impairments seen in individuals with CP.

Developmental differences in functional organization of multispectral networks.

Assessing brain connectivity during rest has become a widely used approach to identify changes in functional brain organization during development. Generally, previous works have demonstrated that brain activity shifts from more local to more distributed processing from childhood into adolescence. However, the majority of those works have been based on functional magnetic resonance imaging measures, whereas multispectral functional connectivity, as measured using magnetoencephalography (MEG), has been far less characterized. In our study, we examined spontaneous cortical activity during eyes-closed rest using MEG in 101 typically developing youth (9-15 years old; 51 females, 50 males). Multispectral MEG images were computed, and connectivity was estimated in the canonical delta, theta, alpha, beta, and gamma bands using the imaginary part of the phase coherence, which was computed between 200 brain regions defined by the Schaefer cortical atlas. Delta and alpha connectivity matrices formed more communities as a function of increasing age. Connectivity weights predominantly decreased with age in both frequency bands; delta-band differences largely implicated limbic cortical regions and alpha band differences in attention and cognitive networks. These results are consistent with previous work, indicating the functional organization of the brain becomes more segregated across development, and highlight spectral specificity across different canonical networks.

Spontaneous cortical dynamics from the first years to the golden years.

In the largest and most expansive lifespan magnetoencephalography (MEG) study to date (n = 434, 6 to 84 y), we provide critical data on the normative trajectory of resting-state spontaneous activity and its temporal dynamics. We perform cutting-edge analyses to examine age and sex effects on whole-brain, spatially-resolved relative and absolute power maps, and find significant age effects in all spectral bands in both types of maps. Specifically, lower frequencies showed a negative correlation with age, while higher frequencies positively correlated with age. These correlations were further probed with hierarchical regressions, which revealed significant nonlinear trajectories in key brain regions. Sex effects were found in absolute but not relative power maps, highlighting key differences between outcome indices that are generally used interchangeably. Our rigorous and innovative approach provides multispectral maps indicating the unique trajectory of spontaneous neural activity across the lifespan, and illuminates key methodological considerations with the widely used relative/absolute power maps of spontaneous cortical dynamics.

Impacts of adrenarcheal DHEA levels on spontaneous cortical activity during development.

Dehydroepiandrosterone (DHEA) production is closely associated with the first pubertal hormonal event, adrenarche. Few studies have documented the relationships between DHEA and functional brain development, with even fewer examining the associations between DHEA and spontaneous cortical activity during the resting-state. Thus, whether DHEA levels are associated with the known developmental shifts in the brain's idling cortical rhythms remains poorly understood. Herein, we examined spontaneous cortical activity in 71 typically-developing youth (9-16 years; 32 male) using magnetoencephalography (MEG). MEG data were source imaged and the power within five canonical frequency bands (delta, theta, alpha, beta, gamma) was computed to identify spatially- and spectrally-specific effects of salivary DHEA and DHEA-by-sex interactions using vertex-wise ANCOVAs. Our results indicated robust increases in power with increasing DHEA within parieto-occipital cortices in all frequency bands except alpha, which decreased with increasing DHEA. In the delta band, DHEA and sex interacted within frontal and temporal cortices such that with increasing DHEA, males exhibited increasing power while females showed decreasing power. These data suggest that spontaneous cortical activity changes with endogenous DHEA levels during the transition from childhood to adolescence, particularly in sensory and attentional processing regions. Sexually-divergent trajectories were only observed in later-developing frontal cortical areas.

Eyes-closed versus eyes-open differences in spontaneous neural dynamics during development.

BACKGROUND: Assessing brain activity during rest has become a widely used approach in developmental neuroscience. Extant literature has measured resting brain activity both during eyes-open and eyes-closed conditions, but the difference between these conditions has not yet been well characterized. Studies, limited to fMRI and EEG, have suggested that eyes-open versus -closed conditions may differentially impact neural activity, especially in visual cortices. METHODS: Spontaneous cortical activity was recorded using MEG from 108 typically developing youth (9-15 years-old; 55 female) during separate sessions of eyes-open and eyes-closed rest. MEG source images were computed, and the strength of spontaneous neural activity was estimated in the canonical delta, theta, alpha, beta, and gamma bands, respectively. Power spectral density maps for eyes-open were subtracted from eyes-closed rest, and then submitted to vertex-wise regression models to identify spatially specific differences between conditions and as a function of age and sex. RESULTS: Relative alpha power was weaker in the eyes-open compared to -closed condition, but otherwise eyes-open was stronger in all frequency bands, with differences concentrated in the occipital cortex. Relative theta power became stronger in the eyes-open compared to the eyes-closed condition with increasing age in frontal cortex. No differences were observed between males and females. CONCLUSIONS: The differences in relative power from eyes-closed to -open conditions are consistent with changes observed in task-based visual sensory responses. Age differences occurred in relatively late developing frontal regions, consistent with canonical attention regions, suggesting that these differences could be reflective of developmental changes in attention processes during puberty. Taken together, resting-state paradigms using eyes-open versus -closed produce distinct results and, in fact, can help pinpoint sensory related brain activity.

Altered spontaneous cortical activity predicts pain perception in individuals with cerebral palsy.

Cerebral palsy is the most common paediatric neurological disorder and results in extensive impairment to the sensorimotor system. However, these individuals also experience increased pain perception, resulting in decreased quality of life. In the present study, we utilized magnetoencephalographic brain imaging to examine whether alterations in spontaneous neural activity predict the level of pain experienced in a cohort of 38 individuals with spastic diplegic cerebral palsy and 67 neurotypical controls. Participants completed 5 min of an eyes closed resting-state paradigm while undergoing a magnetoencephalography recording. The magnetoencephalographic data were then source imaged, and the power within the delta (2-4 Hz), theta (5-7 Hz), alpha (8-12 Hz), beta (15-29 Hz), low gamma (30-59 Hz) and high gamma (60-90 Hz) frequency bands were computed. The resulting power spectral density maps were analysed vertex-wise to identify differences in spontaneous activity between groups. Our findings indicated that spontaneous cortical activity was altered in the participants with cerebral palsy in the delta, alpha, beta, low gamma and high gamma bands across the occipital, frontal and secondary somatosensory cortical areas (all p FWE < 0.05). Furthermore, we also found that the altered beta band spontaneous activity in the secondary somatosensory cortices predicted heightened pain perception in the individuals with cerebral palsy (P = 0.039). Overall, these results demonstrate that spontaneous cortical activity within individuals with cerebral palsy is altered in comparison to their neurotypical peers and may predict increased pain perception in this patient population. Potentially, changes in spontaneous resting-state activity may be utilized to measure the effectiveness of current treatment approaches that are directed at reducing the pain experienced by individuals with cerebral palsy.

Construct validity of the NIH toolbox cognitive domains: A comparison with conventional neuropsychological assessments.

OBJECTIVE: Previous studies have assessed the construct validity of individual subtests in the National Institutes of Health (NIH) Toolbox Cognition Battery (NIHTB-CB), though none have examined the construct validity of the cognitive domains. Importantly, the original NIHTB-CB validation studies were administered on a desktop computer, though the NIHTB-CB is now solely administered via an iPad. We examined the construct validity of each cognitive domain assessed in the NIHTB-CB, including a motor dexterity domain using the iPad application compared to a neuropsychological battery in a sample of healthy adults. METHOD: Eighty-three adults aged 20-66 years (M = 44.35 ± 13.41 years) completed the NIHTB-CB and a comprehensive neuropsychological assessment. Domain scores for each of six cognitive domains (attention and executive function, episodic memory, working memory, processing speed, language, and motor dexterity) and the fluid composite were computed for both batteries. We then assessed the construct validity using Pearson correlations and intraclass correlation coefficients (ICCs) for both demographically corrected and uncorrected domains. RESULTS: We found the attention and executive function, episodic memory, and processing speed domains had poor-to-adequate construct validity (ICCConsistency = -0.029 to 0.517), the working memory and motor dexterity domains and the fluid composite had poor-to-good construct validity (ICCConsistency = 0.215-0.801), and the language domain had adequate-to-good construct validity (ICCConsistency = 0.408-0.829). CONCLUSION: The NIHTB-CB cognitive domains have poor-to-good construct validity, thus researchers should be aware that some tests representing cognitive constructs may not fully reflect the cognitive domain of interest. Future investigation of the construct validity and reliability of the NIHTB-CB administered using the iPad is recommended. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Spontaneous cortical MEG activity undergoes unique age- and sex-related changes during the transition to adolescence.

BACKGROUND: While numerous studies have examined the developmental trajectory of task-based neural oscillations during childhood and adolescence, far less is known about the evolution of spontaneous cortical activity during this time period. Likewise, many studies have shown robust sex differences in task-based oscillations during this developmental period, but whether such sex differences extend to spontaneous activity is not understood. METHODS: Herein, we examined spontaneous cortical activity in 111 typically-developing youth (ages 9-15 years; 55 male). Participants completed a resting state magnetoencephalographic (MEG) recording and a structural MRI. MEG data were source imaged and the power within five canonical frequency bands (delta, theta, alpha, beta, gamma) was computed. The resulting power spectral density maps were analyzed via vertex-wise ANCOVAs to identify spatially-specific effects of age, sex, and their interaction. RESULTS: We found robust increases in power with age in all frequencies except delta, which decreased over time, with findings largely confined to frontal cortices. Sex effects were distributed across frontal and temporal regions; females tended to have greater delta and beta power, whereas males had greater alpha. Importantly, there was a significant age-by-sex interaction in theta power, such that males exhibited decreasing power with age while females showed increasing power with age in the bilateral superior temporal cortices. DISCUSSION: These data suggest that the strength of spontaneous activity undergoes robust change during the transition from childhood to adolescence (i.e., puberty onset), with intriguing sex differences in some cortical areas. Future developmental studies should probe task-related oscillations and spontaneous activity in parallel.

Three-year reliability of MEG resting-state oscillatory power.

INTRODUCTION: Resting-state oscillatory activity has been extensively studied across a wide array of disorders. Establishing which spectrally- and spatially-specific oscillatory components exhibit test-retest reliability is essential to move the field forward. While studies have shown short-term reliability of MEG resting-state activity, no studies have examined test-retest reliability across an extended period of time to establish the stability of these signals, which is critical for reproducibility. METHODS: We examined 18 healthy adults age 23 - 61 who completed three visits across three years. For each visit, participants completed both a resting state MEG and structural MRI scan. MEG data were source imaged, and the cortical power in canonical frequency bands (delta, theta, alpha, beta, low gamma, high gamma) was computed. Intra-class correlation coefficients (ICC) were then calculated across the cortex for each frequency band. RESULTS: Over three years, power in the alpha and beta bands displayed the highest reliability estimates, while gamma showed the lowest estimates of three-year reliability. Spatially, delta, alpha, and beta all showed the highest degrees of reliability in the parietal cortex. Interestingly, the peak signal for each of these frequency bands was located outside of the parietal cortex, suggesting that reliability estimates were not solely dependent on the signal-to-noise ratio. CONCLUSION: Oscillatory resting-state power in parietal delta, posterior beta, and alpha across most of the cortex are reliable across three years and future MEEG studies may focus on these measures for the development of specific markers.

Patient-reported opioid analgesic requirements after elective inguinal hernia repair: A call for procedure-specific opioid-administration strategies.

BACKGROUND: A better understanding of the analgesia needs of patients who undergo common operative procedures is necessary as we address the growing opioid public health crisis in the United States. The aim of this study was to evaluate patient experience with our opioid prescribing practice after elective inguinal hernia repairs. METHODS: A prospective, observational study was conducted between October 1, 2015, and September 30, 2016, in a single-surgeon, high-volume, practice of inguinal hernia operation. Adult patients undergoing elective inguinal herniorrhaphy under local anesthesia with intravenous sedation were invited to participate. All patients were prescribed 10 opioid analgesic tablets postoperatively and were counseled to reserve opioids for pain not controlled by nonopioid analgesics. Their experience was captured by completing a questionnaire 2 to 3 weeks postoperatively during their postoperative visit. RESULTS: A total of 185 patients were surveyed. The majority of the participants were males (177, 95.7%) and ≥60 years old (96, 51.9%). Of the 185 patients, 159 (85.9%) reported using ≤4 opioid tablets; 110 patients (59.5%) reported that they used no opioid analgesics postoperatively. None of the patients was taking opioids within 7 days of their postoperative appointment. Of the 147 patients who were employed, 111 (75.5%) reported missing ≤3 work days, 57 of whom (51.4%) missed no work at all. Patients who were employed were more likely to take opioid analgesics postoperatively (P = .049). Patients who took no opioid analgesics experienced less maximum (P < .001) and persistent groin pain (P = .037). Pain interfered less with daily activities (P = .012) and leisure activities (P = .018) for patients who did not use opioids. CONCLUSION: The majority of our patients reported that they did not require any opioid analgesics, and nearly all of those who thought that they did need opioids used <5 tablets. Our data suggest that for elective inguinal hernia repair under a local anesthetic with intravenous sedation, a policy of low opioid analgesic prescribing is achievable; these findings call for further investigation of how to best prescribe opioid medications to patients after an inguinal herniorrhaphy.

Effectiveness of Exercise Programs for Management of Shoulder Pain in Manual Wheelchair Users With Spinal Cord Injury.

BACKGROUND AND PURPOSE: Shoulder pain is prevalent in manual wheelchair users (MWUs) with spinal cord injury (SCI). Therapeutic exercise has been demonstrated to be an effective, conservative approach to treating shoulder pain in able-bodied individuals. We sought to evaluate literature on the effectiveness of exercise programs on the reduction of shoulder pain in MWUs with SCI. METHODS: We searched the literature, using search terms related to SCI, manual wheelchairs, and shoulder pain. Eligibility criteria included prospective study design, exercise intervention for MWUs with shoulder pain, and use of the Wheelchair User's Shoulder Pain Index as an outcome measure. We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and assessed study quality. RESULTS: Three randomized control trials and 4 cohort studies met inclusion criteria. Two studies were rated as good quality and 5 as fair quality. Three interventions were evaluated in the included studies: arm ergometry, resistive strengthening with or without electromyographic biofeedback, and stretching that targeted the muscles of the shoulder girdle. Across the 7 studies, the exercise intervention was associated with reduction in shoulder pain that exceeded the estimated minimal detectable change of 5.10 points for the Wheelchair Users' Shoulder Pain Index. DISCUSSION AND CONCLUSION: Exercise is a feasible, conservative, therapeutic intervention for the treatment of shoulder pain among MWUs. Additional studies are needed to differentiate techniques for the reduction of shoulder pain, to determine the most effective duration of intervention, and to estimate the magnitude of effect associated with therapeutic exercise for shoulder pain among MWUs.Video Abstract available for more insights from the authors (see Supplemental Digital Content 1, http://links.lww.com/JNPT/A116).