Isogenic human iPSC Parkinson's model shows nitrosative stress-induced dysfunction in MEF2-PGC1α transcription.

Parkinson's disease (PD) is characterized by loss of A9 dopaminergic (DA) neurons in the substantia nigra pars compacta (SNpc). An association has been reported between PD and exposure to mitochondrial toxins, including environmental pesticides paraquat, maneb, and rotenone. Here, using a robust, patient-derived stem cell model of PD allowing comparison of A53T α-synuclein (α-syn) mutant cells and isogenic mutation-corrected controls, we identify mitochondrial toxin-induced perturbations in A53T α-syn A9 DA neurons (hNs). We report a pathway whereby basal and toxin-induced nitrosative/oxidative stress results in S-nitrosylation of transcription factor MEF2C in A53T hNs compared to corrected controls. This redox reaction inhibits the MEF2C-PGC1α transcriptional network, contributing to mitochondrial dysfunction and apoptotic cell death. Our data provide mechanistic insight into gene-environmental interaction (GxE) in the pathogenesis of PD. Furthermore, using small-molecule high-throughput screening, we identify the MEF2C-PGC1α pathway as a therapeutic target to combat PD.

Dysregulation of miRNA expression and excitation in MEF2C autism patient hiPSC-neurons and cerebral organoids.

MEF2C is a critical transcription factor in neurodevelopment, whose loss-of-function mutation in humans results in MEF2C haploinsufficiency syndrome (MHS), a severe form of autism spectrum disorder (ASD)/intellectual disability (ID). Despite prior animal studies of MEF2C heterozygosity to mimic MHS, MHS-specific mutations have not been investigated previously, particularly in a human context as hiPSCs afford. Here, for the first time, we use patient hiPSC-derived cerebrocortical neurons and cerebral organoids to characterize MHS deficits. Unexpectedly, we found that decreased neurogenesis was accompanied by activation of a micro-(mi)RNA-mediated gliogenesis pathway. We also demonstrate network-level hyperexcitability in MHS neurons, as evidenced by excessive synaptic and extrasynaptic activity contributing to excitatory/inhibitory (E/I) imbalance. Notably, the predominantly extrasynaptic (e)NMDA receptor antagonist, NitroSynapsin, corrects this aberrant electrical activity associated with abnormal phenotypes. During neurodevelopment, MEF2C regulates many ASD-associated gene networks, suggesting that treatment of MHS deficits may possibly help other forms of ASD as well.

Soluble α-synuclein-antibody complexes activate the NLRP3 inflammasome in hiPSC-derived microglia.

Parkinson's disease is characterized by accumulation of α-synuclein (αSyn). Release of oligomeric/fibrillar αSyn from damaged neurons may potentiate neuronal death in part via microglial activation. Heretofore, it remained unknown if oligomeric/fibrillar αSyn could activate the nucleotide-binding oligomerization domain (NOD)-like receptor (NLR) family pyrin domain-containing 3 (NLRP3) inflammasome in human microglia and whether anti-αSyn antibodies could prevent this effect. Here, we show that αSyn activates the NLRP3 inflammasome in human induced pluripotent stem cell (hiPSC)-derived microglia (hiMG) via dual stimulation involving Toll-like receptor 2 (TLR2) engagement and mitochondrial damage. In vitro, hiMG can be activated by mutant (A53T) αSyn secreted from hiPSC-derived A9-dopaminergic neurons. Surprisingly, αSyn-antibody complexes enhanced rather than suppressed inflammasome-mediated interleukin-1ß (IL-1ß) secretion, indicating these complexes are neuroinflammatory in a human context. A further increase in inflammation was observed with addition of oligomerized amyloid-ß peptide (Aß) and its cognate antibody. In vivo, engraftment of hiMG with αSyn in humanized mouse brain resulted in caspase-1 activation and neurotoxicity, which was exacerbated by αSyn antibody. These findings may have important implications for antibody therapies aimed at depleting misfolded/aggregated proteins from the human brain, as they may paradoxically trigger inflammation in human microglia.

The impact of clinical risk conditions on influenza and pneumonia diagnoses in England: a nationally representative retrospective cohort study, 2010-2019.

The impact of influenza and pneumonia on individuals in clinical risk groups in England has not previously been well characterized. Using nationally representative linked databases (Clinical Practice Research Database (CPRD), Hospital Episode Statistics (HES) and Office for National Statistics (ONS)), we conducted a retrospective cohort study among adults (≥ 18 years) during the 2010/2011-2019/2020 influenza seasons to estimate the incidence of influenza- and pneumonia-diagnosed medical events (general practitioner (GP) diagnoses, hospitalisations and deaths), stratified by age and risk conditions. The study population included a seasonal average of 7.2 million individuals; approximately 32% had ≥1 risk condition, 42% of whom received seasonal influenza vaccines. Medical event incidence rates increased with age, with ~1% of adults aged ≥75 years hospitalized for influenza/pneumonia annually. Among individuals with vs. without risk conditions, GP diagnoses occurred 2-5-fold more frequently and hospitalisations were 7-10-fold more common. Among those with obesity, respiratory, kidney or cardiovascular disorders, hospitalisation were 5-40-fold more common than in individuals with no risk conditions. Though these findings likely underestimate the full burden of influenza, they emphasize the concentration of disease burden in specific age and risk groups and support existing recommendations for influenza vaccination.

Optic Perineuritis Presenting as the Initial Manifestation of Central Nervous System Involvement in Rai Stage 0 Chronic Lymphocytic Leukemia.

BACKGROUND: To describe the first case of optic perineuritis because of meningeal involvement of early stage chronic lymphocytic leukemia (CLL). METHODS: A case report and review of the literature. RESULTS: A case of unilateral optic neuropathy associated with enhancement of the optic nerve sheath is described in a patient with a prior 2-year history of Rai Stage 0 CLL. Lumbar puncture revealed a lymphocytic pleocytosis. Cerebrospinal fluid flow cytometry revealed a monoclonal expansion of CD5+ B cells compatible with CLL, matching the flow cytometry characteristics of his peripheral blood. CONCLUSIONS: Optic perineuritis is often initially diagnosed as optic neuritis, yet the 2 have different etiologies and follow a different clinical course. Orbital MRI with contrast structurally separates the 2, revealing a characteristic pattern of peripheral optic nerve sheath rather than primary optic nerve enhancement. Etiologies of optic perineuritis are varied and include inflammatory, infectious, neoplastic, and toxic entities. Central nervous system (CNS) involvement by chronic lymphocytic leukemia is unusual, but cranial nerve and meningeal involvement have been reported. This case adds central nervous system chronic lymphocytic leukemia to the list of differential diagnostic possibilities for optic perineuritis. It also alerts clinicians to consider optic perineuritis as a potential presenting feature of CNS involvement in otherwise asymptomatic and stable CLL.

Genetic skin disorders: The value of a multidisciplinary clinic.

Genodermatoses are inherited disorders with skin manifestations and can present with multisystem involvement, resulting in challenges in diagnosis and treatment. To address this, the expertise of dermatology and clinical genetics through a multidisciplinary clinic (Genodermatoses Clinic) were combined. A retrospective cohort study of 45 children seen between March 2018 and February 2019 in the Genodermatoses Clinic at The Children's Hospital of Philadelphia was performed. Patient demographics, referral information, genetic testing modality, diagnoses, and patient satisfaction scores were evaluated to assess the clinic's impact. The majority of patients (42.2%) were referred from Dermatology and 86.7% were referred for diagnosis. Two-thirds of the patients were recommended genetic testing, and subsequently 73.3% completed testing. Nearly three-quarters, 26 out of 36 patients (72.2%), of our undiagnosed patients received a clinical and/or molecular diagnosis, which is imperative in managing their care. Twenty-two individuals pursued genetic testing. In eight individuals (36%), molecular testing was diagnostic. However, in two individuals the molecular diagnosis did not completely explain the phenotype. However, there are still obstacles to genetic testing, such as cost of testing and insurance barriers. Almost all (91.4%) rated the Genodermatoses Clinic as "Very Good," the top Press Ganey score. High patient satisfaction scores suggest a positive impact of the Genodermatoses clinic, emphasizing the importance to increase support for the clinical and administrative time needed for patients with genodermatoses.

Continuous transversus abdominis plane blocks in patients undergoing minimally invasive colorectal surgery: a randomized pilot study.

PURPOSE: Transversus abdominis plane (TAP) blocks are used in an attempt to decrease narcotic use and its subsequent consequences. The primary goal of this study was to see if TAP blocks decreased narcotic use in patients undergoing minimally invasive colorectal surgery. METHODS: A randomized pilot study was conducted. The amount of narcotic used examined in morphine milligram equivalents (MME) was collected for the first 4 post-operative days (PODs). Demographic data, length of stay (LOS), readmission rate, and 90-day mortality was also examined. Statistical analysis of the data was performed with a p < 0.05 determined to be significant. RESULTS: Eighty-eight patients were included. Forty-seven were randomized to the TAP group and 41 to the no TAP group. There was no difference in age, race, gender, indication for operation, or Charlson Comorbidity Index (p > 0.05). The median MME for each POD was similar for POD 1 (22.5 vs 37.5; p = 0.054), POD 3 (15 vs 22.5; p = 0.48), and POD 4 (22.5 vs 10.5; p = 0.42) on bivariate analysis. On POD 2, the TAP group had significantly less narcotic intake than the no TAP group (17.5 vs 30; p = 0.047). However, on multivariate analysis when controlling for other variables, there was no statistical difference between the groups. Median LOS was 3 days for both groups. Readmissions, post-operative complications, and mortality were also similar between the two groups (p > 0.05). CONCLUSION: Our findings indicate that continuous TAP blocks do not decrease the amount of MME used during the first 4 post-operative days compared to patient receiving traditional pain control measures.

Influenza vaccine uptake among at-risk adults (aged 16-64 years) in the UK: a retrospective database analysis.

BACKGROUND: In the UK, annual influenza vaccination is currently recommended for adults aged 16-64 years who are in a clinical at-risk group. Despite recommendations, rates of vaccine uptake in the UK have historically been low and below national and international targets. This study aims to analyse vaccine uptake among adults in clinical at-risk groups from the 2015-2016 influenza season to the present. METHODS: A retrospective analysis of influenza vaccine coverage in the UK was conducted using data extracted from publicly available sources. Clinically at-risk individuals (as defined by Public Health England), including pregnant women, aged 16-64 years, were included in this study. RESULTS: Influenza vaccination coverage rates across the UK in adults aged 16-64 years in a clinical at-risk group have been consistently low over the past 5 years, with only 48.0, 42.4, 44.1 and 52.4% of eligible patients in England, Scotland, Wales and Northern Ireland receiving their annual influenza vaccination during the 2018-2019 influenza season. Influenza vaccine coverage was lowest in patients with morbid obesity and highest in patients with diabetes in 2018-2019. Coverage rates were below current national ambitions of ≥75% in all clinical risk groups. In these clinical at-risk groups, influenza vaccine coverage decreased between 2015 and 2019, and there was considerable regional variation. CONCLUSIONS: Uptake of the influenza vaccine by adults aged 16-64 years in a clinical at-risk group was substantially below the national ambitions. As a result, many individuals in the UK remain at high risk of developing severe influenza or complications. Given that people who are vulnerable to COVID-19 are also at increased risk of complications from influenza, during the 2020-2021 season, there is a heightened need for healthcare professionals across the UK to address suboptimal vaccine uptake, particularly in at-risk patients. Healthcare professionals and policymakers should consider measures targeted at increasing access to and awareness of the clinical benefits of the influenza vaccine.

Stability and Change in Trait Emotional Intelligence in Emerging Adulthood: A Four-Year Population-Based Study.

Trait Emotional Intelligence (EI)-related competencies are in growing demand in educational and vocational settings. The present study assesses the developmental dynamics of trait EI in emerging adulthood by capitalizing on the inclusion of a measure of trait EI in the National Longitudinal Survey of Children and Youth (NLSCY) called the Emotional Quotient Inventory: Mini (EQ-i: Mini). A sample of 1064 young adults (50% female) from ages 20-21 to 24-25 years was used to assess 4-year rank-order stability and mean-level change of trait EI, as well as whether the EQ-i: Mini functions equivalently over time (longitudinal measurement invariance). Results revealed full configural, partial metric, and scalar invariance of the construct for this time period. The Stress Management subscale achieved invariance at the residual level. After controlling for partial non-invariance, moderate levels of rank-order stability coefficients were found, suggesting malleability of the construct during emerging adulthood. Consistent with the maturity principle, there was a moderate increase in trait EI (specifically in the Interpersonal and Adaptability subscales). The malleability of trait EI suggests opportunities for enhancing socioemotional competencies in emerging adults, such as through formal and continuing education programing, on-the-job training, and targeted employment interventions.

Pedal to the Metal: Velocity and Power in High-Level Golfers.

ABSTRACT: Parker, J, and Lundgren, LE. Pedal to the metal: Velocity and power in high-level golfers. J Strength Cond Res 35(12): 3425-3431, 2021-In most rotational power assessments, discrete variables are used for subsequent examination; however, movements are continuous, and data can be collected in time series. The purpose of this investigation was to examine the velocity- and power-time series characteristics of a standing rotation test and identify relationships with golf performance. Thirty-one golfers performed a golf-specific rotation test (GSRT) with 3 different resistances (6, 10, and 14 kg) in a robotic engine system. Time series of velocity and power was calculated from the raw data, and each repetition was then normalized to 0-100%. Principal component analyses (PCAs) were performed on velocity and power waveforms. The PCA used an eigenvalue analysis of the data covariance matrix. The relationship between clubhead speed (CHS) and all principal components (PC) was examined using linear regression. Ten velocity parameters and 6 power parameters explained 80% of the variance in the data. For velocity, the first 2 PCs identified both magnitude and phase shift features while PCs 3-5 identified difference features. For power, the first 2 PCs identified both magnitude and phase shift features, the third PC identified a phase shift feature, and the fourth PC identified a difference feature. The highest relationship with CHS was shown for GSRT with 14 kg in PC2 for power (R2 = 0.48, p < 0.001). The PCA of the GSRT power test could distinguish intraindividual differences, external loads, and sex-based differences. Athletes should focus on accelerating smoothly through the movement, particularly with heavier loads, and not pulling aggressively at the beginning of the rotational movement to achieve maximum power.

Role of sulfiredoxin as a peroxiredoxin-2 denitrosylase in human iPSC-derived dopaminergic neurons.

Recent studies have pointed to protein S-nitrosylation as a critical regulator of cellular redox homeostasis. For example, S-nitrosylation of peroxiredoxin-2 (Prx2), a peroxidase widely expressed in mammalian neurons, inhibits both enzymatic activity and protective function against oxidative stress. Here, using in vitro and in vivo approaches, we identify a role and reaction mechanism of the reductase sulfiredoxin (Srxn1) as an enzyme that denitrosylates (thus removing -SNO) from Prx2 in an ATP-dependent manner. Accordingly, by decreasing S-nitrosylated Prx2 (SNO-Prx2), overexpression of Srxn1 protects dopaminergic neural cells and human-induced pluripotent stem cell (hiPSC)-derived neurons from NO-induced hypersensitivity to oxidative stress. The pathophysiological relevance of this observation is suggested by our finding that SNO-Prx2 is dramatically increased in murine and human Parkinson's disease (PD) brains. Our findings therefore suggest that Srxn1 may represent a therapeutic target for neurodegenerative disorders such as PD that involve nitrosative/oxidative stress.

Centrifugal microfluidics for sorting immune cells from whole blood.

Sorting and enumeration of immune cells from blood are critical operations involved in many clinical applications. Conventional methods for sorting and counting immune cells from blood, such as flow cytometry and hemocytometers, are tedious, inaccurate, and difficult for implementation for point-of-care (POC) testing. Herein we developed a microscale centrifugal technology termed Centrifugal Microfluidic Chip (CMC) capable of sorting immune cells from blood and in situ cellular analysis in a laboratory setting. Operation of the CMC entailed a blood specimen layered on a density gradient medium and centrifuged in microfluidic channels where immune cell subpopulations could rapidly be sorted into distinct layers according to their density differentials. We systematically studied effects of different blocking molecules for surface passivation of the CMC. We further demonstrated the applicability of CMCs for rapid separation of minimally processed human whole blood without affecting immune cell viability. Multi-color imaging and analysis of immune cell distributions and enrichment such as recovery and purity rates of peripheral blood mononuclear cells (PBMCs) were demonstrated using CMCs. Given its design and operation simplicity, portability, blood cell sorting efficiency, and in situ cellular analysis capability, the CMC holds promise for blood-based diagnosis and disease monitoring in POC applications.

Enhancement of the seed-target recognition step in RNA silencing by a PIWI/MID domain protein.

Target recognition in RNA silencing is governed by the "seed sequence" of a guide RNA strand associated with the PIWI/MID domain of an Argonaute protein in RISC. Using a reconstituted in vitro target recognition system, we show that a model PIWI/MID domain protein confers position-dependent tightening and loosening of guide-strand-target interactions. Over the seed sequence, the interaction affinity is enhanced up to approximately 300-fold. Enhancement is achieved through a reduced entropy penalty for the interaction. In contrast, interactions 3' of the seed are inhibited. We quantified mismatched target recognition inside and outside the seed, revealing amplified discrimination at the third position in the seed mediated by the PIWI/MID domain. Thus, association of the guide strand with the PIWI/MID domain generates an enhanced affinity anchor site over the seed that can promote fidelity in target recognition and stabilize and guide the assembly of the active silencing complex.

Hydrogel for Simultaneous Tunable Growth Factor Delivery and Enhanced Viability of Encapsulated Cells in Vitro.

Poor cell survival in vitro and in vivo is one of the key challenges in tissue engineering. Prosurvival therapeutic proteins, such as insulin-like growth factor-1 (IGF-1), can promote cell viability but require controlled delivery systems due to their short half-lives and rapid clearance. Biocompatible materials are commonly used for drug delivery platforms or to encapsulate cells for increased viability, but few materials have been used for both applications simultaneously. In this work, we present a dual-use platform. A blend of hyaluronan and methylcellulose, known to promote cell survival, was covalently modified with Src homology 3 (SH3)-binding peptides and demonstrated tunable, affinity-based release of the prosurvival fusion protein SH3-IGF-1. The material also significantly increased the viability of retinal pigment epithelium cells under anchorage-independent conditions. This novel platform is applicable to a broad range of cells and protein therapeutics and is a promising drug delivery/cell transplantation strategy to increase the viability of both exogenous and endogenous cells in tissue engineering applications.

Aß induces astrocytic glutamate release, extrasynaptic NMDA receptor activation, and synaptic loss.

Synaptic loss is the cardinal feature linking neuropathology to cognitive decline in Alzheimer's disease (AD). However, the mechanism of synaptic damage remains incompletely understood. Here, using FRET-based glutamate sensor imaging, we show that amyloid-ß peptide (Aß) engages α7 nicotinic acetylcholine receptors to induce release of astrocytic glutamate, which in turn activates extrasynaptic NMDA receptors (eNMDARs) on neurons. In hippocampal autapses, this eNMDAR activity is followed by reduction in evoked and miniature excitatory postsynaptic currents (mEPSCs). Decreased mEPSC frequency may reflect early synaptic injury because of concurrent eNMDAR-mediated NO production, tau phosphorylation, and caspase-3 activation, each of which is implicated in spine loss. In hippocampal slices, oligomeric Aß induces eNMDAR-mediated synaptic depression. In AD-transgenic mice compared with wild type, whole-cell recordings revealed excessive tonic eNMDAR activity accompanied by eNMDAR-sensitive loss of mEPSCs. Importantly, the improved NMDAR antagonist NitroMemantine, which selectively inhibits extrasynaptic over physiological synaptic NMDAR activity, protects synapses from Aß-induced damage both in vitro and in vivo.

Electromyographic Patterns during Golf Swing: Activation Sequence Profiling and Prediction of Shot Effectiveness.

This study analyzes muscle activity, recorded in an eight-channel electromyographic (EMG) signal stream, during the golf swing using a 7-iron club and exploits information extracted from EMG dynamics to predict the success of the resulting shot. Muscles of the arm and shoulder on both the left and right sides, namely flexor carpi radialis, extensor digitorum communis, rhomboideus and trapezius, are considered for 15 golf players (∼5 shots each). The method using Gaussian filtering is outlined for EMG onset time estimation in each channel and activation sequence profiling. Shots of each player revealed a persistent pattern of muscle activation. Profiles were plotted and insights with respect to player effectiveness were provided. Inspection of EMG dynamics revealed a pair of highest peaks in each channel as the hallmark of golf swing, and a custom application of peak detection for automatic extraction of swing segment was introduced. Various EMG features, encompassing 22 feature sets, were constructed. Feature sets were used individually and also in decision-level fusion for the prediction of shot effectiveness. The prediction of the target attribute, such as club head speed or ball carry distance, was investigated using random forest as the learner in detection and regression tasks. Detection evaluates the personal effectiveness of a shot with respect to the player-specific average, whereas regression estimates the value of target attribute, using EMG features as predictors. Fusion after decision optimization provided the best results: the equal error rate in detection was 24.3% for the speed and 31.7% for the distance; the mean absolute percentage error in regression was 3.2% for the speed and 6.4% for the distance. Proposed EMG feature sets were found to be useful, especially when used in combination. Rankings of feature sets indicated statistics for muscle activity in both the left and right body sides, correlation-based analysis of EMG dynamics and features derived from the properties of two highest peaks as important predictors of personal shot effectiveness. Activation sequence profiles helped in analyzing muscle orchestration during golf shot, exposing a specific avalanche pattern, but data from more players are needed for stronger conclusions. Results demonstrate that information arising from an EMG signal stream is useful for predicting golf shot success, in terms of club head speed and ball carry distance, with acceptable accuracy. Surface EMG data, collected with a goal to automatically evaluate golf player's performance, enables wearable computing in the field of ambient intelligence and has potential to enhance exercising of a long carry distance drive.

Role of positively charged residues of the second transmembrane domain in the ion transport activity and conformation of human uncoupling protein-2.

Residing at the inner mitochondrial membrane, uncoupling protein-2 (UCP2) mediates proton transport from the intermembrane space (IMS) to the mitochondrial matrix and consequently reduces the rate of ATP synthesis in the mitochondria. The ubiquitous expression of UCP2 in humans can be attributed to the protein's multiple physiological roles in tissues, including its involvement in protective mechanisms against oxidative stress, as well as glucose and lipid metabolisms. Currently, the structural properties and ion transport mechanism of UCP2 and other UCP homologues remain poorly understood. UCP2-mediated proton transport is activated by fatty acids and inhibited by di- and triphosphate purine nucleotides. UCP2 also transports chloride and some other small anions. Identification of key amino acid residues of UCP2 in its ion transport pathway can shed light on the protein's ion transport function. On the basis of our previous studies, the second transmembrane helix segment (TM2) of UCP2 exhibited chloride channel activity. In addition, it was suggested that the positively charged residues on TM2 domains of UCPs 1 and 2 were important for their chloride transport activity. On this basis, to further understand the role of these positively charged residues on the ion transport activity of UCP2, we recombinantly expressed four TM2 mutants: R76Q, R88Q, R96Q, and K104Q. The wild type UCP2 and its mutants were purified and reconstituted into liposomes, and their conformation and ion (proton and chloride) transport activity were studied. TM2 Arg residues at the matrix interface of UCP2 proved to be crucial for the protein's anion transport function, and their absence resulted in highly diminished Cl(-) transport rates. On the other hand, the two other positively charged residues of TM2, located at the UCP2-IMS interface, could participate in the salt-bridge formation in the protein and promote the interhelical tight packing in the UCP2. Absence of these residues did not influence Cl(-) transport rates, but disturbed the dense packing in UCP2 and resulted in higher UCP2-mediated proton transport rates in the presence of long chain fatty acids. Overall, the outcome of this study provides a deeper and more detailed molecular image of UCP2's ion transport mechanism.

Protection from cyanide-induced brain injury by the Nrf2 transcriptional activator carnosic acid.

Cyanide is a life-threatening, bioterrorist agent, preventing cellular respiration by inhibiting cytochrome c oxidase, resulting in cardiopulmonary failure, hypoxic brain injury, and death within minutes. However, even after treatment with various antidotes to protect cytochrome oxidase, cyanide intoxication in humans can induce a delayed-onset neurological syndrome that includes symptoms of Parkinsonism. Additional mechanisms are thought to underlie cyanide-induced neuronal damage, including generation of reactive oxygen species. This may account for the fact that antioxidants prevent some aspects of cyanide-induced neuronal damage. Here, as a potential preemptive countermeasure against a bioterrorist attack with cyanide, we tested the CNS protective effect of carnosic acid (CA), a pro-electrophilic compound found in the herb rosemary. CA crosses the blood-brain barrier to up-regulate endogenous antioxidant enzymes via activation of the Nrf2 transcriptional pathway. We demonstrate that CA exerts neuroprotective effects on cyanide-induced brain damage in cultured rodent and human-induced pluripotent stem cell-derived neurons in vitro, and in vivo in various brain areas of a non-Swiss albino mouse model of cyanide poisoning that simulates damage observed in the human brain. Cyanide, a potential bioterrorist agent, can produce a chronic delayed-onset neurological syndrome that includes symptoms of Parkinsonism. Here, cyanide poisoning treated with the proelectrophillic compound carnosic acid, results in reduced neuronal cell death in both in vitro and in vivo models through activation of the Nrf2/ARE transcriptional pathway. Carnosic acid is therefore a potential treatment for the toxic central nervous system (CNS) effects of cyanide poisoning. ARE, antioxidant responsive element; Nrf2 (NFE2L2, Nuclear factor (erythroid-derived 2)-like 2).

Gambling Related Cognitive Distortions in Adolescence: Relationships with Gambling Problems in Typically Developing and Special Needs Students.

The present study examined the link between problematic gambling and gambling related cognitions (GRCs) in a large sample of adolescents with (N = 266) and without (N = 1,738) special education needs (SEN) between the ages of 14 and 18 years attending several high schools in eastern central Ontario. The adolescents with SENs were identified as having various learning disorders and/or internalizing and externalizing problems [e.g., attention deficit hyperactivity disorder (ADHD)]. All adolescents completed a self-report questionnaire package that included the GRC Scale (GRCS; Raylu and Oei in Addiction 99:757-769, 2004), as well as measures of problem gambling, negative affect, and ADHD symptomatology. Results showed that adolescents with SEN hold more erroneous beliefs about gambling and had a higher risk of developing problematic patterns of gambling behaviour than their typically developing peers. Moreover, the GRCS subscales were found to be strong predictors of problem gambling among adolescents both with and without SEN, accounting for a substantial amount of the variance even when controlling for the effects of age, gender, ADHD, and negative affect. It is suggested that intervention and prevention programs aimed at adolescent gambling need to give particular attention to those with SEN.

Reversible strain-induced electron-hole recombination in silicon nanowires observed with femtosecond pump-probe microscopy.

Strain-induced changes to the electronic structure of nanoscale materials provide a promising avenue for expanding the optoelectronic functionality of semiconductor nanostructures in device applications. Here we use pump-probe microscopy with femtosecond temporal resolution and submicron spatial resolution to characterize charge-carrier recombination and transport dynamics in silicon nanowires (NWs) locally strained by bending deformation. The electron-hole recombination rate increases with strain for values above a threshold of ∼1% and, in highly strained (∼5%) regions of the NW, increases 6-fold. The changes in recombination rate are independent of NW diameter and reversible upon reduction of the applied strain, indicating the effect originates from alterations to the NW bulk electronic structure rather than introduction of defects. The results highlight the strong relationship between strain, electronic structure, and charge-carrier dynamics in low-dimensional semiconductor systems, and we anticipate the results will assist the development of strain-enabled optoelectronic devices with indirect-bandgap materials such as silicon.