Spatial and temporal mapping of de novo mutations in schizophrenia to a fetal prefrontal cortical network.

Genes disrupted in schizophrenia may be revealed by de novo mutations in affected persons from otherwise healthy families. Furthermore, during normal brain development, genes are expressed in patterns specific to developmental stage and neuroanatomical structure. We identified de novo mutations in persons with schizophrenia and then mapped the responsible genes onto transcriptome profiles of normal human brain tissues from age 13 weeks gestation to adulthood. In the dorsolateral and ventrolateral prefrontal cortex during fetal development, genes harboring damaging de novo mutations in schizophrenia formed a network significantly enriched for transcriptional coexpression and protein interaction. The 50 genes in the network function in neuronal migration, synaptic transmission, signaling, transcriptional regulation, and transport. These results suggest that disruptions of fetal prefrontal cortical neurogenesis are critical to the pathophysiology of schizophrenia. These results also support the feasibility of integrating genomic and transcriptome analyses to map critical neurodevelopmental processes in time and space in the brain.

Amphetamine increases motivation of humans and mice as measured by breakpoint, but does not affect an Electroencephalographic biomarker.

Translation of drug targets from preclinical studies to clinical trials has been aided by cross-species behavioral tasks, but evidence for brain-based engagement during task performance is still required. Cross-species progressive ratio breakpoint tasks (PRBTs) measure motivation-related behavior and are pharmacologically and clinically sensitive. We recently advanced elevated parietal alpha power as a cross-species electroencephalographic (EEG) biomarker of PRBT engagement. Given that amphetamine increases breakpoint in mice, we tested its effects on breakpoint and parietal alpha power in both humans and mice. Twenty-three healthy participants performed the PRBT with EEG after amphetamine or placebo in a double-blind design. C57BL/6J mice were trained on PRBT with EEG (n = 24) and were treated with amphetamine or vehicle. A second cohort of mice was trained on PRBT without EEG (n = 40) and was treated with amphetamine or vehicle. In humans, amphetamine increased breakpoint. In mice, during concomitant EEG, 1 mg/kg of amphetamine significantly decreased breakpoint. In cohort 2, however, 0.3 mg/kg of amphetamine increased breakpoint consistent with human findings. Increased alpha power was observed in both species as they reached breakpoint, replicating previous findings. Amphetamine did not affect alpha power in either species. Amphetamine increased effort in humans and mice. Consistent with previous reports, elevated parietal alpha power was observed in humans and mice as they performed the PRBT. Amphetamine did not affect this EEG biomarker of effort. Hence, these findings support the pharmacological predictive validity of the PRBT to measure effort in humans and mice and suggest that this EEG biomarker is not directly reflective of amphetamine-induced changes in effort.

Early auditory processing abnormalities alter individual learning trajectories and sensitivity to computerized cognitive training in schizophrenia.

BACKGROUND: Auditory system plasticity is a promising target for neuromodulation, cognitive rehabilitation and therapeutic development in schizophrenia (SZ). Auditory-based targeted cognitive training (TCT) is a 'bottom up' intervention designed to enhance the speed and accuracy of auditory information processing, which has been shown to improve neurocognition in certain SZ patients. However, the dynamics of TCT learning as a function of training exercises and their impact on neurocognitive functioning and therapeutic outcomes are unknown. METHODS: Forty subjects (SZ, n = 21; healthy subjects (HS), n = 19) underwent comprehensive clinical, cognitive, and auditory assessments, including measurements of auditory processing speed (APS) at baseline and after 1-h of TCT. SZ patients additionally completed 30-hours of TCT and repeated assessments ~10-12 weeks later. RESULTS: SZ patients were deficient in APS at baseline (d = 0.96, p < 0.005) relative to HS. After 1-h of TCT, analyses revealed significant main effects of diagnosis (d = 1.75, p = 0.002) and time (d = 1.04, p < 0.001), and a diagnosis × time interaction (d = 0.85, p = 0.02) on APS. APS learning effects were robust after 1-h in SZ patients (d = 1.47, p < 0.001) and persisted throughout the 30-h of training. Baseline APS was associated with verbal learning gains after 30-h of TCT (r = 0.51, p = 0.02) in SZ. CONCLUSIONS: TCT learning metrics may have prognostic utility and aid in the prospective identification of individuals likely to benefit from TCT. Future experimental medicine studies may advance predictive algorithms that enhance TCT-related clinical, cognitive and functional outcomes.

Prepulse inhibition and the call alert in emergency medical services.

In emergency medical services, paramedics are informed of an emergency call by a high-intensity acoustic alarm called the "call alert." Sudden, loud sounds like the call alert may cause a startle response and be experienced as aversive. Studies have identified an association between the call alert and adverse health effects in first responders; conceivably, these adverse health effects might be reduced by modifying the call alert to blunt its startling and aversive properties. Here, we assessed whether the call alert causes a startle response and whether its startling and aversive properties are reduced when the call alert is preceded by a weak acoustic "prepulse," a process referred to as "prepulse inhibition" (PPI). Paramedics (n = 50; 34M:13F:3 not reported; ages 20-68) were exposed to four call alerts (two with and two without a prepulse) in counterbalanced order. Responses were measured using electromyography (measuring blink amplitude), visual analog scales (quantifying perceived call alert intensity and aversiveness), and an electrocardiogram (assessing heart rate). Paramedics responded to the call alert with a startle reflex blink and an increased heart rate. Acoustic prepulses significantly reduced the amplitude of the call alert-induced startle blink, the perceived sound intensity, and the perceived "dislike" of the call alert. These findings confirm that the call alert is associated with an acoustic startle response in paramedics; adding a prepulse to the call alert can reduce its startling and aversive properties. Conceivably, such reductions might also diminish adverse health effects associated with the call alert in first responders.

Changes in Hip and Knee Strength Are Not Associated With Improved Clinical Outcomes After Rehabilitation in Individuals With Patellofemoral Pain: A Critically Appraised Topic.

CLINICAL SCENARIO: Patellofemoral pain (PFP) is a widespread knee disorder encountered in clinical practice. Clinicians have often focused on strengthening hip and knee musculature to improve pain and disability, which are the ultimate clinical goals of PFP treatment. However, PFP literature has shown improvement in pain and disability without concurrent changes in lower-extremity strength after rehabilitation. Although some researchers have achieved a significant increase in strength after rehabilitation in PFP cohorts, there was no association with improved pain and disability. The inconsistent improvements in strength and the lack of association with clinical outcomes call for a critical appraisal of the available evidence to better understand the association between changes in hip and knee strength and improved clinical outcomes in individuals with PFP. CLINICAL QUESTION: Are changes in hip and knee strength associated with improved pain and disability after rehabilitation in individuals with PFP? SUMMARY OF KEY FINDINGS: Four studies met the inclusion criteria and were included in the appraisal. Following rehabilitation, one study achieved strength improvements in knee extension. One study achieved strength improvements in knee extension, but not in hip external rotation and hip abduction. Two studies did not achieve strength improvements in hip external rotation, hip abduction, hip extension, or knee extension. All included studies achieved improvements in pain or disability after rehabilitation. None of the studies found a significant association between changes in hip and knee strength (either improved or not) and improved pain and disability. CLINICAL BOTTOM LINE: There is consistent evidence that changes in hip and knee strength are not associated with improved clinical outcomes after rehabilitation in adults with PFP. STRENGTH OF RECOMMENDATION: Collectively, the body of evidence included is to answer the clinical question aligns with the strength of recommendation of B based on the Strength of Recommendation Taxonomy.

Nuclear translocation of the tagged endogenous MAPK MPK-1 denotes a subset of activation events in C. elegans development.

The extracellular signal-regulated kinases (ERKs) are mitogen-activated protein kinases (MAPKs) that are utilized downstream of Ras to Raf to MEK signaling to control activation of a wide array of targets. Activation of ERKs is elevated in Ras-driven tumors and RASopathies, and thus is a target for pharmacological inhibition. Regulatory mechanisms of ERK activation have been studied extensively in vitro and in cultured cells, but little in living animals. In this study, we tagged the Caenorhabditis elegans ERK-encoding gene, mpk-1. MPK-1 is ubiquitously expressed with elevated expression in certain contexts. We detected cytosol-to-nuclear translocation of MPK-1 in maturing oocytes and hence validated nuclear translocation as a reporter of some activation events. During patterning of vulval precursor cells (VPCs), MPK-1 is necessary and sufficient for the central cell, P6.p, to assume the primary fate. Yet MPK-1 translocates to the nuclei of all six VPCs in a temporal and concentration gradient centered on P6.p. This observation contrasts with previous results using the ERK nuclear kinase translocation reporter of substrate activation, raising questions about mechanisms and indicators of MPK-1 activation. This system and reagent promise to provide critical insights into the regulation of MPK-1 activation within a complex intercellular signaling network.

The Rheb-TORC1 signaling axis functions as a developmental checkpoint.

In many eukaryotes, the small GTPase Rheb functions as a switch to toggle activity of TOR complex 1 (TORC1) between anabolism and catabolism, thus controlling lifespan, development and autophagy. Our CRISPR-generated, fluorescently tagged endogenous Caenorhabditis elegans RHEB-1 and DAF-15/Raptor are expressed ubiquitously and localize to lysosomes. LET-363/TOR and DAF-15/Raptor are required for development beyond the third larval stage (L3). We observed that deletion of RHEB-1 similarly conferred L3 arrest. Unexpectedly, robust RNAi-mediated depletion of TORC1 components caused arrest at stages prior to L3. Accordingly, conditional depletion of endogenous DAF-15/Raptor in the soma revealed that TORC1 is required at each stage of the life cycle to progress to the next stage. Reversal of DAF-15 depletion permits arrested animals to recover to continue development. Our results are consistent with TORC1 functioning as a developmental checkpoint that governs the decision of the animal to progress through development.

Swine global genomic resources: insights into wild and domesticated populations.

Suids, both domesticated and wild, are found on all continents except for Antarctica and provide valuable food resources for humans in addition to serving as important models for biomedical research. Continuing advances in genome sequencing have allowed researchers to compare the genomes from diverse populations of suids helping to clarify their evolution and dispersal. Further analysis of these samples may provide clues to improve disease resistance/resilience and productivity in domestic suids as well as better ways of classifying and conserving genetic diversity within wild and captive suids. Collecting samples from diverse populations of suids is resource intensive and may negatively impact endangered populations. Here we catalog extensive tissue and DNA samples from suids in collections in both Europe and North America. We include samples that have previously been used for whole genome sequencing, targeted DNA sequencing, RNA sequencing, and reduced representation bisulfite sequencing (RRBS). This work provides an important centralized resource for researchers who wish to access published databases.

Search for Boosted Dark Matter in COSINE-100.

We search for energetic electron recoil signals induced by boosted dark matter (BDM) from the galactic center using the COSINE-100 array of NaI(Tl) crystal detectors at the Yangyang Underground Laboratory. The signal would be an excess of events with energies above 4 MeV over the well-understood background. Because no excess of events are observed in a 97.7 kg·yr exposure, we set limits on BDM interactions under a variety of hypotheses. Notably, we explored the dark photon parameter space, leading to competitive limits compared to direct dark photon search experiments, particularly for dark photon masses below 4 MeV and considering the invisible decay mode. Furthermore, by comparing our results with a previous BDM search conducted by the Super-Kamionkande experiment, we found that the COSINE-100 detector has advantages in searching for low-mass dark matter. This analysis demonstrates the potential of the COSINE-100 detector to search for MeV electron recoil signals produced by the dark sector particle interactions.

Auditory discrimination and frequency modulation learning in schizophrenia patients: amphetamine within-subject dose response and time course.

BACKGROUND: Auditory frequency modulation learning ('auditory learning') is a key component of targeted cognitive training (TCT) for schizophrenia. TCT can be effective in enhancing neurocognition and function in schizophrenia, but such gains require significant time and effort and elude many patients. METHODS: As a strategy to increase and/or accelerate TCT-induced clinical gains, we tested the dose- and time-course effects of the pro-attentional drug, amphetamine (AMPH; placebo, 2.5, 5 or 10 mg po; within-subject double-blind, order balanced) on auditory learning in schizophrenia patients [n = 32; M:F = 19:13; age 42.0 years (24-55)]. To understand predictors and/or mechanisms of AMPH-enhanced TCT, we also measured auditory fidelity (words-in-noise (WIN), quick speech-in-noise (QuickSIN)) and neurocognition (MATRICS comprehensive cognitive battery (MCCB)). Some measures were also acquired from age-matched healthy subjects (drug free; n = 10; M:F = 5:5). RESULTS: Patients exhibited expected deficits in neurocognition. WIN and QuickSIN performance at low signal intensities was impaired in patients with low v. high MCCB attention/vigilance (A/V) scores; these deficits were corrected by AMPH, maximally at 2.5-5 mg (d's = 0.79-1.29). AMPH also enhanced auditory learning, with maximal effects at 5 mg (d = 0.93), and comparable effects 60 and 210 min post pill. 'Pro-learning' effects of AMPH and AMPH-induced gains in auditory fidelity were most evident in patients with low MCCB A/V scores. CONCLUSIONS: These findings advance our understanding of the impact of pro-attentional interventions on auditory information processing and suggest dose- and time-course parameters for studies that assess the ability of AMPH to enhance the clinical benefits of TCT in schizophrenia patients.

Lower-extremity pressure, staging, and grading thresholds to identify chronic limb-threatening ischemia.

INTRODUCTION: The Society for Vascular Surgery Threatened Limb Classification System ('WIfI') is used to predict risk of limb loss and identify peripheral artery disease in patients with foot ulcers or gangrene. We estimated the diagnostic sensitivity of multiple clinical and noninvasive arterial parameters to identify chronic limb-threatening ischemia (CLTI). METHODS: We performed a single-center review of 100 consecutive patients who underwent angiography for foot gangrene or ulcers. WIfI stages and grades were determined for each patient. Toe, ankle, and brachial pressure measurements were performed by registered vascular technologists. CLTI severity was characterized using Global Limb Anatomic Staging System (GLASS stages) and angiosomes. Medial artery calcification in the foot was quantified on foot radiographs. RESULTS: GLASS NA (not applicable), I, II, and III angiographic findings were seen in 21, 21, 23, and 35 patients, respectively. A toe-brachial index < 0.7 and minimum ipsilateral ankle-brachial index < 0.9 performed well in identifying GLASS II and III angiographic findings, with sensitivity rates 97.8% and 91.5%, respectively. The diagnostic accuracy rates of noninvasive measures peaked at 74.7% and 89.3% for identifying GLASS II/III and GLASS I+ angiographic findings, respectively. The presence of medial artery calcification significantly diminished the sensitivity of most noninvasive parameters. CONCLUSIONS: The use of alternative noninvasive arterial testing parameters improves sensitivity for detecting PAD. Abnormal noninvasive results should suggest the need for diagnostic angiography to further characterize arterial anatomy of the affected limb. Testing strategies with better accuracy are needed.

Systematic reviews: A glossary for public health.

Literature reviews are conducted for a range of purposes, from providing an overview or primer of a novel topic, to providing a comprehensive, precise, and accurate estimate of an effect estimate. There is much confusion over nomenclature related to literature reviews, with the term 'systematic review' often used to mean any review based on some form of explicit methodology. However, guidance and minimum standards exist for these kinds of robust reviews that are intended to support evidence-informed decision-making, and reviewers must carefully ensure their syntheses are conducted and reported to a high standard if this is their objective. The diversity of names given to reviews is reflected in the diversity of methods used for these evidence syntheses: the result is a general confusion about what is important to ensure a review is fit-for-purpose, and many reviews are labelled as 'systematic reviews' when they do not follow standardised or replicable approaches. Here, we provide a glossary or typology that aims to highlight the importance of the reviewers' objectives in choosing and naming their review method. We focus on reviews in public health and provide guidance on selecting an objective, methodological guidance to follow, justifying and reporting the methods chosen, and attempting to ensure consistent and clear nomenclature. We hope this will help review authors, editors, peer-reviewers, and readers understand, interpret, and critique a review depending on its intended use.

Exercise-induced fatigue affects knee proprioceptive acuity and quadriceps neuromuscular function more in patients with ACL reconstruction or meniscus surgery than in healthy individuals.

PURPOSE: To observe how knee proprioceptive acuity and quadriceps neuromuscular function change during and after repeated isokinetic knee-extension exercise in patients with anterior cruciate ligament reconstruction (ACLR) or meniscus surgery. METHODS: Patients with ACLR or meniscus surgery and matched controls (n = 19 in each group) performed knee-flexion replication at 15° and 75°, and quadriceps peak torque (PT), central activation ratio (CAR) and rate of torque development (RTD) at baseline and immediately after every five sets of isokinetic knee-extension exercise (times 1-5). RESULTS: Compared to the baseline, the ACLR and control groups displayed errors in knee-flexion replication at 75° only at time 5 (115.9-155.6%; p ≤ 0.04, d ≥ 0.97), whereas the meniscus surgery group exhibited errors at all time points (142.5-265.6%; p ≤ 0.0003, d ≥ 1.4). Significant percentage reductions in quadriceps CAR were observed between times 4 and 5 in the ACLR group (-5.8%; p = 0.0002, d = 0.96), but not in the meniscus surgery (-1.4%; n.s.) and control (0.1%; n.s.) groups. Significant percentage reductions in quadriceps RTD were observed between times 4 and 5 in the ACLR (-24.2%; p = 0.007, d = 0.99) and meniscus surgery (-23.0%; p = 0.01, d = 0.85) groups, but not in the control group (-0.2%; n.s.). CONCLUSION: Patients with ACLR or meniscus surgery displayed a greater loss in knee proprioceptive acuity and quadriceps neuromuscular function during and after exercise than healthy individuals. Evidence-based interventions to enhance exercise-induced fatigue resistance should be implemented following ACLR or meniscus surgery, aiming to prevent proprioceptive and neuromuscular changes within the knee joint and quadriceps. LEVEL OF EVIDENCE: III.

Medical Students' Diagnostic Accuracy and Treatment Plans.

Physician-mentored patient rounds (PMPR) were used to assess diagnostic accuracy and treatment plans of preclinical medical students. During 4 PMPR sessions, students gathered patient history, observed a physical exam, analyzed diagnostic tests, and developed treatment plans for a patient with chronic obstructive pulmonary disease. Of 470 students, 99.4% correctly diagnosed the patient. Nearly 78% prescribed long-acting beta-agonists or long-acting muscarinic antagonists. Most included appropriate pharmacologic treatments. Only 47% included smoking cessation in their treatment.

Parallel Rap1>RalGEF>Ral and Ras signals sculpt the C. elegans nervous system.

Ras is the most commonly mutated oncogene in humans and uses three oncogenic effectors: Raf, PI3K, and RalGEF activation of Ral. Understanding the importance of RalGEF>Ral signaling in cancer is hampered by the paucity of knowledge about their function in animal development, particularly in cell movements. We found that mutations that disrupt function of RalGEF or Ral enhance migration phenotypes of mutants for genes with established roles in cell migration. We used as a model the migration of the canal associated neurons (CANs), and validated our results in HSN cell migration, neurite guidance, and general animal locomotion. These functions of RalGEF and Ral are specific to their control of Ral signaling output rather than other published functions of these proteins. In this capacity Ral functions cell autonomously as a permissive developmental signal. In contrast, we observed Ras, the canonical activator of RalGEF>Ral signaling in cancer, to function as an instructive signal. Furthermore, we unexpectedly identified a function for the close Ras relative, Rap1, consistent with activation of RalGEF>Ral. These studies define functions of RalGEF>Ral, Rap1 and Ras signaling in morphogenetic processes that fashion the nervous system. We have also defined a model for studying how small GTPases partner with downstream effectors. Taken together, this analysis defines novel molecules and relationships in signaling networks that control cell movements during development of the nervous system.

Racial and ethnic disparities in abdominal aortic aneurysm evaluation and treatment rates in Texas.

BACKGROUND: Screening identifies intact abdominal aortic aneurysms (iAAAs) before progression to ruptured AAAs (rAAAs). However, screening efforts have been limited by the low overall diagnostic yield and unequal screening among minority populations. The goal of the present study was to identify equitable AAA screening strategies for both majority and minority populations. METHODS: We performed epidemiologic and geospatial analyses of inpatient and outpatient procedures for iAAAs and rAAAs at Texas hospitals from 2006 through 2014 at all nonfederal hospitals and clinics in Texas. The data were aggregated by area (metropolitan statistical area vs rural region) and then supplemented by six additional data sources to estimate the AAA repair incidence rates, rates of AAA-related clinic and ultrasound visits, travel distance to providers, and the location and number of unrecognized AAAs. RESULTS: Most AAA repairs had occurred among men aged 65 to 84 years and categorized as White in large metropolitan areas. The area procedure rates for rAAAs and iAAAs were strongly correlated (R2 = 0.47). Two other variables-the proportions of persons categorized as White and those aged ≥65 years in a region-identified subgroups within the majority population with a high risk of iAAAs (R2 = 0.46). Lower rates of clinic visits and AAA ultrasound scans were seen among persons categorized as Black. Several areas with disproportionately higher rAAA/iAAA repair ratios were found, mainly affecting persons categorized as Black. CONCLUSIONS: Multiple focused AAA screening strategies could be required to address the disproportionately lower AAA identification among persons categorized as Black.

Hospital Payer Mix and Amputation Rates Among Patients with Peripheral Artery Disease Complications.

BACKGROUND: Studies have shown that Medicaid coverage is associated with higher rates of primary amputation among patients with peripheral artery disease (PAD). We sought to identify whether hospital payer makeup also influences outcomes among these patients. METHODS: Patients who underwent treatment for foot complications in Texas were identified and aggregated by hospital. Hospitals were grouped by payer mix: low-income payer predominant versus high-income payer predominant. Variance analyses were used to find differences between the groups. Individual and hospital-level regression analyses were used to find associations with amputation rates. RESULTS: Out of 21,592 patients, 9,098 (42%) underwent amputation. They presented to 337 hospitals out of which 49 (15%) had a low-income predominant payer mix, and 109 (32%) had a high-income predominant payer mix. Patients at low-income payer predominant hospitals were more likely to present with gangrene (0.74 vs. 0.65, P < 0.01), undergo emergency admissions (0.67 vs. 0.50, P < 0.01), undergo amputation (0.53 vs. 0.42, P < 0.05), and incur higher per-day charges ($8,145 vs. $6,790, P < 0.05). At the individual level, despite risk-adjusting for disease-specific factors, amputation rate was associated with hospital payer mixes with greater proportions of Medicaid and lower proportions of commercially insured patients. At the hospital level, amputation rate was associated with higher proportion of Medicaid patients in hospital payer mix, lower hospital volumes, lower per-day charges, and higher gangrene and osteomyelitis rates (R2 = 0.30, P < 0.01). CONCLUSIONS: Higher proportion of Medicaid patients in a hospital payer mix is associated with an increased risk of primary amputation for PAD patients regardless of insurance coverage.

Gender, racial and ethnic disparities in index hospitalization operations for symptomatic carotid stenosis in Texas hospitals.

BACKGROUND: Recent literature and societal recommendations support early revascularization of symptomatic carotid patients over the traditional six-week period. Nonetheless, the timing of these interventions can vary widely among populations. The goal of this study is to identify any factors influencing carotid revascularization during the index hospitalization for patients with symptomatic disease. METHODS: The Texas Department of State Health Services database was queried to identify all patients > 45 years old admitted to nonfederal Texas Hospitals between 2009 to 2013 with an admission diagnosis of carotid artery stenosis and either transient ischemic attack (TIA), cerebrovascular accident (CVA), or amaurosis fugax. Diagnoses codes and demographic data were also used to adjust for clinical, social, and demographic factors (including area of residence and treatment). Descriptive statistics and multivariable logistic regression were used to identify significant factors for index admission revascularization. RESULTS: A total of 29,046 symptomatic patients were identified among the 153,484 patients who had an eligible admission diagnosis. This included 16,244 (55.9%) males and 12,802 (44.1%) females. Only 4,594 (15.8%) patients were revascularized during the index hospitalization. The majority of these patients presented with amaurosis (OR 5.58; 95% CI 4.84-6.44) instead of CVAs (OR 0.48; 95% CI 0.45-0.51) or TIAs . Adjusting for hospital volume, insurance coverage, residence, and other clinical factors, rates of index admission carotid intervention remained significantly lower for women (OR 0.85; 95% CI 0.79-0.91), persons categorized as black (OR 0.60; 95% CI 0.53-0.69), and persons categorized as Hispanic (OR 0.77; 95% CI 0.70-0.86). CONCLUSIONS: Gender, race and ethnicity appear to correlate with rates of carotid intervention at index hospitalization despite thorough risk adjustment for clinical, social and demographic factors. Efforts should be directed towards reducing these disparities.

Neuromuscular function of the shoulder girdle and upper extremity musculature in individuals with a history of glenohumeral labral repair.

The purpose of this study was to compare neuromuscular function in the upper extremity musculature between individuals with glenohumeral labrum repair and uninjured controls. This cross-sectional study examined 16 individuals with a primary, unilateral glenohumeral labral repair (male/female: 13/3, age: 24.1 ± 5.0 years, time from surgery: 36.7 ± 33.3 months) and 14 uninjured individuals (male/female: 11/3, age: 23.8 ± 2.7 years) matched by age, sex, activity level, and limb dominance participated. Mass-normalized shoulder abduction and wrist flexion maximal voluntary isometric contraction (MVIC) torque, motoneuron pool excitability of the flexor carpi radialis (Hoffmann reflex), and corticospinal excitability of the upper trapezius, middle deltoid, and flexor carpi radialis (active motor threshold [AMT]) were evaluated. Dependent and independent t-tests were used to assess between-limb and between-group comparisons. Cohen's d effect sizes with 95% confidence intervals were used to quantify the magnitude of differences observed. Within the injured group, the involved limb had lesser shoulder abduction MVIC torque (p < 0.001, d = 1.16) and higher AMT for the upper trapezius (p = 0.01, d = 0.81) compared with the contralateral limb. The labral repair group had lesser shoulder abduction MVIC torque (p < 0.001, d = 1.17) and Hoffmann reflex (p = 0.01, d = 0.99), as well as higher AMT for the upper trapezius (p < 0.001, d = 1.23) in their involved limb compared with the control group. Large magnitude neuromuscular impairments are present beyond 6 months from glenohumeral labral repair, suggesting potential origins of impairments to be addressed during post-operative rehabilitation.

Nonlinear dynamics underlying sensory processing dysfunction in schizophrenia.

Natural systems, including the brain, often seem chaotic, since they are typically driven by complex nonlinear dynamical processes. Disruption in the fluid coordination of multiple brain regions contributes to impairments in information processing and the constellation of symptoms observed in neuropsychiatric disorders. Schizophrenia (SZ), one of the most debilitating mental illnesses, is thought to arise, in part, from such a network dysfunction, leading to impaired auditory information processing as well as cognitive and psychosocial deficits. Current approaches to neurophysiologic biomarker analyses predominantly rely on linear methods and may, therefore, fail to capture the wealth of information contained in whole EEG signals, including nonlinear dynamics. In this study, delay differential analysis (DDA), a nonlinear method based on embedding theory from theoretical physics, was applied to EEG recordings from 877 SZ patients and 753 nonpsychiatric comparison subjects (NCSs) who underwent mismatch negativity (MMN) testing via their participation in the Consortium on the Genetics of Schizophrenia (COGS-2) study. DDA revealed significant nonlinear dynamical architecture related to auditory information processing in both groups. Importantly, significant DDA changes preceded those observed with traditional linear methods. Marked abnormalities in both linear and nonlinear features were detected in SZ patients. These results illustrate the benefits of nonlinear analysis of brain signals and underscore the need for future studies to investigate the relationship between DDA features and pathophysiology of information processing.