Search

Fine particles of ash emitted during volcanic eruptions may sporadically influence cloud properties on a regional or global scale as well as influencing the dynamics of volcanic clouds and the subsequent dispersion of volcanic aerosol and gases. It has been shown that volcanic ash can trigger ice nucleation, but ash from relatively few volcanoes has been studied for its ice nucleating ability. In this study we quantify the efficiency with which ash from the Soufriere Hills volcano on Montserrat nucleates ice when immersed in supercooled water droplets. Using an ash sample from the 11th February 2010 eruption, we report ice nucleating efficiencies from 246 to 265 K. This wide range of temperatures was achieved using two separate droplet freezing instruments, one employing nanolitre droplets, the other using microlitre droplets. Soufriere Hills volcanic ash was significantly more efficient than all other ash samples that have been previously examined. At present the reasons for these differences are not understood, but may be related to mineralogy, amorphous content and surface chemistry., Competing Interests: The authors have declared that no competing interests exist.

Posttraumatic stress disorder (PTSD) is associated with executive functioning deficits, including disruptions in working memory (WM). Recent studies suggest that attention training reduces PTSD symptomatology, but the underlying neural mechanisms are unknown. We used high-density magnetoencephalography (MEG) to evaluate whether attention training modulates brain regions serving WM processing in PTSD. Fourteen veterans with PTSD completed a WM task during a 306-sensor MEG recording before and after 8 sessions of attention training treatment. A matched comparison sample of 12 combat-exposed veterans without PTSD completed the same WM task during a single MEG session. To identify the spatiotemporal dynamics, each group's data were transformed into the time-frequency domain, and significant oscillatory brain responses were imaged using a beamforming approach. All participants exhibited activity in left hemispheric language areas consistent with a verbal WM task. Additionally, veterans with PTSD and combat-exposed healthy controls each exhibited oscillatory responses in right hemispheric homologue regions (e.g., right Broca's area); however, these responses were in opposite directions. Group differences in oscillatory activity emerged in the theta band (4-8 Hz) during encoding and in the alpha band (9-12 Hz) during maintenance and were significant in right prefrontal and right supramarginal and inferior parietal regions. Importantly, following attention training, these significant group differences were reduced or eliminated. This study provides initial evidence that attention training improves aberrant neural activity in brain networks serving WM processing.

We examined two groups of combat veterans, one with post-traumatic stress disorder (PTSD) (n = 27) and another without PTSD (n = 16), using an emotional Stroop task (EST) with word lists matched across a series of lexical variables (e.g. length, frequency, neighbourhood size, etc.). Participants with PTSD exhibited a strong EST effect (longer colour-naming latencies for combat-relevant words as compared to neutral words). Veterans without PTSD produced no such effect, t < .918, p > .37. Participants with PTSD then completed eight sessions of attention training (Attention Control Training or Attention Bias Modification Training) with a dot-probe task utilising threatening and neutral faces. After training, participants-especially those undergoing Attention Control Training-no longer produced longer colour-naming latencies for combat-related words as compared to other words, indicating normalised attention allocation processes after treatment.

There is currently a void in the scientific literature on the cortical beta oscillatory activity that is associated with the production of leg motor actions. In addition, we have limited data on how these cortical oscillations may progressively change as a function of development. This study began to fill this vast knowledge gap by using high-density magnetoencephalography to quantify the beta cortical oscillatory activity over a cross-section of typically developing children as they performed an isometric knee target matching task. Advanced beamforming methods were used to identify the spatiotemporal changes in beta oscillatory activity during the motor planning and motor action time frames. Our results showed that a widespread beta event-related desynchronization (ERD) was present across the pre/postcentral gyri, supplementary motor area, and the parietal cortices during the motor planning stage. The strength of this beta ERD sharply diminished across this fronto-parietal network as the children initiated the isometric force needed to match the target. Rank order correlations indicated that the older children were more likely to initiate their force production sooner, took less time to match the targets, and tended to have a weaker beta ERD during the motor planning stage. Lastly, we determined that there was a relationship between the child's age and the strength of the beta ERD within the parietal cortices during isometric force production. Altogether our results suggest that there are notable maturational changes during childhood and adolescence in beta cortical oscillatory activity that are associated with the planning and execution of leg motor actions.

Magnetoencephalography (MEG) is a noninvasive, silent, and totally passive neurophysiological imaging method with excellent temporal resolution (∼1 ms) and good spatial precision (∼3-5 mm). In a typical experiment, MEG data are acquired as healthy controls or patients with neurologic or psychiatric disorders perform a specific cognitive task, or receive sensory stimulation. The resulting data are generally analyzed using standard electrophysiological methods, coupled with advanced image reconstruction algorithms. To date, the total number of MEG instruments and associated users is significantly smaller than comparable human neuroimaging techniques, although this is likely to change in the near future with advances in the technology. Despite this small base, MEG research has made a significant impact on several areas of translational neuroscience, largely through its unique capacity to quantify the oscillatory dynamics of activated brain circuits in humans. This review focuses on the clinical areas where MEG imaging has arguably had the greatest impact in regard to the identification of aberrant neural dynamics at the regional and network level, monitoring of disease progression, determining how efficacious pharmacologic and behavioral interventions modulate neural systems, and the development of neural markers of disease. Specifically, this review covers recent advances in understanding the abnormal neural oscillatory dynamics that underlie Parkinson's disease, autism spectrum disorders, human immunodeficiency virus (HIV)-associated neurocognitive disorders, cerebral palsy, attention-deficit hyperactivity disorder, cognitive aging, and post-traumatic stress disorder. MEG imaging has had a major impact on how clinical neuroscientists understand the brain basis of these disorders, and its translational influence is rapidly expanding with new discoveries and applications emerging continuously., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Parkinson's disease (PD) is a common neurodegenerative disorder characterized primarily by motor symptoms such as bradykinesia, muscle rigidity, and resting tremor. It is now broadly accepted that these motor symptoms frequently co-occur with cognitive impairments, with deficits in working memory and attention being among the most common cognitive sequelae associated with PD. While these cognitive impairments are now recognized, the underlying neural dynamics and precise regions involved remain largely unknown. To this end, we examined the oscillatory dynamics and interregional functional connectivity that serve working memory processing in a group of unmedicated adults with PD and a matched group without PD. Each participant completed a high-load, Sternberg-type working memory task during magnetoencephalography (MEG), and we focused on the encoding and maintenance phases. All data were transformed into the time-frequency domain and significant oscillatory activity was imaged using a beamforming approach. Phase-coherence (connectivity) was also computed among the brain subregions exhibiting the strongest responses. Our most important findings were that unmedicated patients with PD had significantly diminished working memory performance (i.e., accuracy), and reduced functional connectivity between left inferior frontal cortices and left supramarginal-superior temporal cortices compared to participants without PD during the encoding phase of working memory processing. We conclude that patients with PD have reduced neural interactions between left prefrontal executive circuits and temporary verbal storage centers in the left supramarginal/superior temporal cortices during the stimulus encoding phase, which may underlie their diminished working memory function. Hum Brain Mapp 37:3224-3235, 2016. © 2016 Wiley Periodicals, Inc., (© 2016 Wiley Periodicals, Inc.)

Previous research has connected a specific pattern of beta oscillatory activity to proper motor execution, but no study to date has directly examined how resting beta levels affect motor-related beta oscillatory activity in the motor cortex. Understanding this relationship is imperative to determining the basic mechanisms of motor control, as well as the impact of pathological beta oscillations on movement execution. In the current study, we used magnetoencephalography (MEG) and a complex movement paradigm to quantify resting beta activity and movement-related beta oscillations in the context of healthy aging. We chose healthy aging as a model because preliminary evidence suggests that beta activity is elevated in older adults, and thus by examining older and younger adults we were able to naturally vary resting beta levels. To this end, healthy younger and older participants were recorded during motor performance and at rest. Using beamforming, we imaged the peri-movement beta event-related desynchronization (ERD) and extracted virtual sensors from the peak voxels, which enabled absolute and relative beta power to be assessed. Interestingly, absolute beta power during the pre-movement baseline was much stronger in older relative to younger adults, and older adults also exhibited proportionally large beta desynchronization (ERD) responses during motor planning and execution compared to younger adults. Crucially, we found a significant relationship between spontaneous (resting) beta power and beta ERD magnitude in both primary motor cortices, above and beyond the effects of age. A similar link was found between beta ERD magnitude and movement duration. These findings suggest a direct linkage between beta reduction during movement and spontaneous activity in the motor cortex, such that as spontaneous beta power increases, a greater reduction in beta activity is required to execute movement. We propose that, on an individual level, the primary motor cortices have an absolute threshold of beta power that must be reached in order to move, and that an inability to suppress beta power to this threshold results in an increase in movement duration., (Copyright © 2016 Elsevier Inc. All rights reserved.)

In humans, there is a strong beta (15-30 Hz) event-related desynchronization (ERD) that begins before movement, which has been tentatively linked to motor planning operations. The dynamics of this response are strongly modulated by whether a pending movement is cued and the inherent parameters of the cue. However, previous studies have focused on the information content of cues and not on parameters such as the timing of the cue relative to other events. Variations in such timing are critical, as they directly impact the amount of time that participants have to plan pending movements. In this study, participants performed finger-tapping sequences during magnetoencephalography, and we manipulated the amount of time (i.e., "long" vs. "short") between the presentation of the to-be-executed sequence and the cue to initiate the sequence. We found that the beta ERD was stronger immediately after the cue to move in the contralateral postcentral gyrus and bilateral parietal cortices during the short compared with long planning time condition. During movement execution, the beta ERD was stronger in the premotor cortex and the SMA in the short relative to long condition. Finally, peak latency in the SMA significantly correlated with RT, such that the closer the peak beta ERD was to the cue to move, the quicker the participant responded. The results of this study establish that peri-movement beta ERD activity across the cortical motor circuit is highly sensitive to cue-related temporal factors, with a direct link to motor performance.

Background: Posttraumatic stress disorder (PTSD) is associated with executive functioning deficits, including disruptions in working memory. In this study, we examined the neural dynamics of working memory processing in veterans with PTSD and a matched healthy control sample using magnetoencephalography (MEG)., Methods: Our sample of recent combat veterans with PTSD and demographically matched participants without PTSD completed a working memory task during a 306-sensor MEG recording. The MEG data were preprocessed and transformed into the time-frequency domain. Significant oscillatory brain responses were imaged using a beamforming approach to identify spatiotemporal dynamics., Results: Fifty-one men were included in our analyses: 27 combat veterans with PTSD and 24 controls. Across all participants, a dynamic wave of neural activity spread from posterior visual cortices to left frontotemporal regions during encoding, consistent with a verbal working memory task, and was sustained throughout maintenance. Differences related to PTSD emerged during early encoding, with patients exhibiting stronger α oscillatory responses than controls in the right inferior frontal gyrus (IFG). Differences spread to the right supramarginal and temporal cortices during later encoding where, along with the right IFG, they persisted throughout the maintenance period., Limitations: This study focused on men with combat-related PTSD using a verbal working memory task. Future studies should evaluate women and the impact of various traumatic experiences using diverse tasks., Conclusion: Posttraumatic stress disorder is associated with neurophysiological abnormalities during working memory encoding and maintenance. Veterans with PTSD engaged a bilateral network, including the inferior prefrontal cortices and supramarginal gyri. Right hemispheric neural activity likely reflects compensatory processing, as veterans with PTSD work to maintain accurate performance despite known cognitive deficits associated with the disorder.

Working memory is central to the execution of many daily functions and is typically divided into three phases: encoding, maintenance, and retrieval. While working memory performance has been repeatedly shown to decline with age, less is known regarding the underlying neural processes. We examined age-related differences in the neural dynamics that serve working memory by recording high-density magnetoencephalography (MEG) in younger and older adults while they performed a modified, high-load Sternberg working memory task with letters as stimuli. MEG data were evaluated in the time-frequency domain and significant oscillatory responses were imaged using a beamformer. A hierarchical regression was performed to investigate whether age moderated the relationship between oscillatory activity and accuracy on the working memory task. Our results indicated that the spatiotemporal dynamics of oscillatory activity in language-related areas of the left fronto-temporal cortices were similar across groups. Age-related differences emerged during early encoding in the right-hemispheric homologue of Wernicke's area. Slightly later, group differences emerged in the homologue of Broca's area and these persisted throughout memory maintenance. Additionally, occipital alpha activity during maintenance was stronger, occurred earlier, and involved more cortical tissue in older adults. Finally, age significantly moderated the relationship between accuracy and neural activity in the prefrontal cortices. In younger adults, as prefrontal activity decreased, accuracy tended to increase. Our results are consistent with predictions of the compensation-related utilization of neural circuits hypothesis (CRUNCH). Such differences in the oscillatory dynamics could reflect compensatory mechanisms, which would aid working memory performance in older age. Hum Brain Mapp 37:2348-2361, 2016. © 2016 Wiley Periodicals, Inc., (© 2016 Wiley Periodicals, Inc.)

The 18th and 19th centuries were beset with new religious movements in the United States: Shakers, Latter Day Saints, Millerites, and Seventh Day Adventists to name a few. One group, Christian Science, held radically different views than their counterparts and their origins lay in the most unlikely of places, a perpetually ill and poor woman from New Hampshire. Much has been said about Mary Baker Eddy: some say that she was a prophet, others that she was a fraud. Herein no such judgments are made. This study seeks to look into the life of Mary Baker Eddy from a psychological lens in the hopes that insight can be gained into the founding of the First Church of Jesus Christ Scientist and perhaps to allay the binary of Mrs. Eddy as either prophet or fanatic.

Hypertension Canada's Canadian Hypertension Education Program Guidelines Task Force provides annually updated, evidence-based recommendations to guide the diagnosis, assessment, prevention, and treatment of hypertension. This year, we present 4 new recommendations, as well as revisions to 2 previous recommendations. In the diagnosis and assessment of hypertension, automated office blood pressure, taken without patient-health provider interaction, is now recommended as the preferred method of measuring in-office blood pressure. Also, although a serum lipid panel remains part of the routine laboratory testing for patients with hypertension, fasting and nonfasting collections are now considered acceptable. For individuals with secondary hypertension arising from primary hyperaldosteronism, adrenal vein sampling is recommended for those who are candidates for potential adrenalectomy. With respect to the treatment of hypertension, a new recommendation that has been added is for increasing dietary potassium to reduce blood pressure in those who are not at high risk for hyperkalemia. Furthermore, in selected high-risk patients, intensive blood pressure reduction to a target systolic blood pressure ≤ 120 mm Hg should be considered to decrease the risk of cardiovascular events. Finally, in hypertensive individuals with uncomplicated, stable angina pectoris, either a β-blocker or calcium channel blocker may be considered for initial therapy. The specific evidence and rationale underlying each of these recommendations are discussed. Hypertension Canada's Canadian Hypertension Education Program Guidelines Task Force will continue to provide annual updates., (Copyright © 2016 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.)

Introduction: Low socioeconomic status (SES) should be a robust predictor of medication nonadherence because it shares key features with the theoretical origins of this phenomenon. However, population-based studies have demonstrated weak associations overall, possibly because SES is inadequately represented. We compared the performance of multiple versus single-domain measures of SES as predictors of statin adherence., Methods: This retrospective cohort study used population-based administrative data mapped to area-level census information of individuals who received a statin medication following a hospitalization for coronary heart disease. One-year adherence was calculated by dividing the sum of all tablets dispensed by the total number of days in the observation period (365 d following the first statin dispensation). Logistic regression models were constructed and the relative impact of each SES measure was assessed by its adjusted odds ratio (OR) and improvement over the predictive accuracy of a reference model that included non-SES factors only., Results: More than two thirds (ie, 68.8%; 6517/9478) of eligible individuals exhibited optimal adherence (ie, ≥80%). The estimated impact of SES on optimal adherence differed depending on the SES measure tested. The highest performing single-domain measure, household income (OR=0.75; 95% confidence interval, 0.63-0.90; model c-statistic improvement 0.5%, P=0.04) generated a similar result to the multiple-domain measure (adjusted OR=0.74; 95% confidence interval, 0.62-0.88; model c-statistic improvement 0.7%, P=0.01)., Conclusion: Multidomain measurements of SES using administrative databases mapped to census data are not associated with better performance in predicting statin medication adherence compared with single-domain measures such as household income.

Inadequate access to medical care in underserved and geographically isolated rural communities may limit the delivery of quality screening care to miners. Use of mobile screening clinics, manned by a physician assistant or nurse practitioner, is one way to improve their access. Miners demonstrate a high level of satisfaction with services provided by the mobile screening clinic. The addition of telemedicine to mobile screening clinics allows miners to have access to university-based specialist care and provides an opportunity to specialists to tele-mentor other providers. Although inadequately studied, limited data suggest that miners accept telemedicine consultation. We expect that the innovative use of mobile screening clinics with telemedicine technology might allow efficient utilization of resources to meet the medical screening needs of a large number of miners in geographically remote locations in the United States.

A rare case of Bacillus panophthlamitis with extension to the prechiasmatic optic nerve secondary to hematogenous spreading after intravenous drug use is presented. A 27-year-old man with a recent history of trauma to the left eye presented with severe left eye pain following a binge of intravenous drug use. Visual acuity (VA) was LP. On examination he had chemosis, proptosis, elevated intraocular pressure, and a complete hyphema. CT-scan identified preseptal swelling, but no evidence of any posterior extension of the anterior process or orbital fractures. Topical and systemic therapy were initiated. On follow-up clinical examination less than 12 hours after presentation he had signs of a keratitis with worsening ophthalmoplegia and repeat imaging demonstrated posterior extension to the prechiasmatic optic nerve. Shortly after the cornea ruptured with cultures growing Bacillus . The patient underwent enucleation and has had no further progression of infection. To the best of our knowledge, this is the first report of Bacillus panophthalmitis presenting with signs of trauma with posterior extension to the prechiasmatic optic nerve., Competing Interests: The authors declare that there is no conflict of interests regarding the publication of this paper.

Background: There is a paucity of literature on the chest radiographic findings in uranium workers., Objective: To characterize the chest radiographic findings of pneumoconiosis in a New Mexican cohort of uranium workers., Methods: The most recent results from chest radiographs were abstracted in this cross-sectional study., Results: Radiographs showed small pneumoconiotic opacities of profusion score of ≥ 1/0 in 155/429 (36.1%) uranium workers. The most common shape/size of the primary and secondary opacities was s (90.3%) and t (83.7%) types, respectively. Lower lung zones were the most affected. American Indians were the population group at greatest odds for having profusion score ≥ 1/0 (O.R. 2.65, 95% C.I. 1.61, 4.36)., Conclusions: Uranium workers' pneumoconiosis is associated with predominantly lower lobe, irregular, and small opacities. Clinical providers and policymakers must consider uranium workers' pneumoconiosis in the differential diagnosis for lower lobe-predominant interstitial lung disease, in the appropriate exposure setting.

Cortical oscillatory dynamics are known to be critical for human movement, although their functional significance remains unclear. In particular, there is a strong beta (15-30 Hz) desynchronization that begins before movement onset and continues during movement, before rebounding after movement termination. Several studies have connected this response to motor planning and/or movement selection operations, but to date such studies have examined only the early aspects of the response (i.e., before movement) and a limited number of parameters. In this study, we used magnetoencephalography (MEG) and a novel motor sequence paradigm to probe how motor plan complexity modulates peri-movement beta oscillations, and connectivity within activated circuits. We also examined the dynamics by imaging beta activity before and during movement execution and extracting virtual sensors from key regions. We found stronger beta desynchronization during complex relative to simple sequences in the right parietal and left dorsolateral prefrontal cortex (DLPFC) during movement execution. There was also an increase in functional connectivity between the left DLPFC and right parietal shortly after movement onset during complex but not simple sequences, which produced a significant conditional effect (i.e., complex > simple) that was not attributable to differences in response amplitude. This study is the first to demonstrate that complexity modulates the dynamics of the peri-movement beta ERD, which provides crucial new data on the functional role of this well-known oscillatory motor response. These data further suggest that execution of complex motor behavior may recruit key regions of the fronto-parietal network, in addition to traditional sensorimotor regions., (© 2015 Wiley Periodicals, Inc.)

Numerous clinical investigations have reported that children with cerebral palsy (CP) have tactile discrimination deficits that likely limit their ability to plan and manipulate objects. Despite this clinical awareness, we still have a substantial knowledge gap in our understanding of the neurological basis for these tactile discrimination deficits. Previously, we have shown that children with CP have aberrant theta-alpha (4-14 Hz) oscillations in the somatosensory cortices following tactile stimulation of the foot. In this investigation, we evaluated if these aberrant theta-alpha oscillations also extend to the hand. Magnetoencephalography was used to evaluate event-related changes in the theta-alpha and beta (18-34 Hz) somatosensory cortical oscillations in groups of children with CP and typically developing (TD) children following tactile stimulation of their hands. Our results showed that the somatosensory theta-alpha oscillations were relatively intact in children with CP, which is in contrast to our previous results for foot tactile stimulations. We suspect that these inter-study differences may be related to the higher probability that the neural tracts serving the lower extremities are damaged in children with CP, compared to those serving the upper extremities. This inference is plausible since the participating children with CP had Manual Ability Classification System (MACS) levels between I and II. In contrast to the theta-alpha results, children with CP did exhibit a sharp increase in beta activity during the same time period, which was not observed in TD children. This suggests that children with CP still have deficits in the computational aspect of somatosensory processing., (Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.)

The amount of ice present in clouds can affect cloud lifetime, precipitation and radiative properties. The formation of ice in clouds is facilitated by the presence of airborne ice-nucleating particles. Sea spray is one of the major global sources of atmospheric particles, but it is unclear to what extent these particles are capable of nucleating ice. Sea-spray aerosol contains large amounts of organic material that is ejected into the atmosphere during bubble bursting at the organically enriched sea-air interface or sea surface microlayer. Here we show that organic material in the sea surface microlayer nucleates ice under conditions relevant for mixed-phase cloud and high-altitude ice cloud formation. The ice-nucleating material is probably biogenic and less than approximately 0.2 micrometres in size. We find that exudates separated from cells of the marine diatom Thalassiosira pseudonana nucleate ice, and propose that organic material associated with phytoplankton cell exudates is a likely candidate for the observed ice-nucleating ability of the microlayer samples. Global model simulations of marine organic aerosol, in combination with our measurements, suggest that marine organic material may be an important source of ice-nucleating particles in remote marine environments such as the Southern Ocean, North Pacific Ocean and North Atlantic Ocean.

Posttraumatic stress disorder (PTSD) is a severe psychiatric disorder prevalent in combat veterans. Previous neuroimaging studies have demonstrated that patients with PTSD exhibit abnormal responses to non-threatening visual and auditory stimuli, but have not examined somatosensory processing. Thirty male combat veterans, 16 with PTSD and 14 without, completed a tactile stimulation task during a 306-sensor magnetoencephalography (MEG) recording. Significant oscillatory neural responses were imaged using a beamforming approach. Participants also completed clinical assessments of PTSD, combat exposure, and depression. We found that veterans with PTSD exhibited significantly reduced activity during early (0-125 ms) tactile processing compared with combat controls. Specifically, veterans with PTSD had weaker activity in the left postcentral gyrus, left superior parietal area, and right prefrontal cortex in response to nonthreatening tactile stimulation relative to veterans without PTSD. The magnitude of activity in these brain regions was inversely correlated with symptom severity, indicating that those with the most severe PTSD had the most abnormal neural responses. Our findings are consistent with a resource allocation view of perceptual processing in PTSD, which directs attention away from nonthreatening sensory information., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Many electrophysiology studies have examined neural oscillatory activity during the encoding, maintenance, and/or retrieval phases of various working memory tasks. Together, these studies have helped illuminate the underlying neural dynamics, although much remains to be discovered and some findings have not replicated in subsequent work. In this study, we examined the oscillatory dynamics that serve visual working memory operations using high-density magnetoencephalography (MEG) and advanced time-frequency and beamforming methodology. Specifically, we recorded healthy adults while they performed a high-load, Sternberg-type working memory task, and focused on the encoding and maintenance phases. We found significant 9-16 Hz desynchronizations in the bilateral occipital cortices, left dorsolateral prefrontal cortex (DLPFC), and left superior temporal areas throughout the encoding phase. Our analysis of the dynamics showed that the left DLPFC and superior temporal desynchronization became stronger as a function of time during the encoding period, and was sustained throughout most of the maintenance phase until sharply decreasing in the milliseconds preceding retrieval. In contrast, desynchronization in occipital areas became weaker as a function of time during encoding and eventually evolved into a strong synchronization during the maintenance period, consistent with previous studies. These results provide clear evidence of dynamic network-level processes during the encoding and maintenance phases of working memory, and support the notion of a dynamic pattern of functionally-discrete subprocesses within each working memory phase. The presence of such dynamic oscillatory networks may be a potential source of inconsistent findings in this literature, as neural activity within these networks changes dramatically with time., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

We report a Rh-catalyzed, enantioselective silylation of arene C-H bonds directed by a (hydrido)silyl group. (Hydrido)silyl ethers that are formed in situ by hydrosilylation of benzophenone or its derivatives undergo asymmetric C-H silylation in high yield with excellent enantioselectivity in the presence of [Rh(cod)Cl]2 and a chiral bisphosphine ligand. The stereoselectivity of this process also allows enantioenriched diarylmethanols to react with site selectivity at one aryl group over the other. Enantioenriched benzoxasiloles from the silylation process undergo a range of transformations to form C-C, C-O, C-I, or C-Br bonds.

Background: The Night Float system (NFS) is often used in residency training programs to meet work hour regulations. The purpose of this study was to examine resident and attendings' perceptions of the NFS on issues of resident learning, well-being, work, non-educational activities and the health care system (patient safety and quality of care, inter-professional teams, workload on attendings and costs of on-call coverage)., Methods: A survey questionnaire with closed and open-ended questions (26 residents and eight attendings in an Internal Medicine program), informal discussions with the program and moonlighting and financial data were collected., Results and Discussion: The main findings included, (i) an overall congruency in opinions between resident and attendings across all mean comparisons, (ii) perceptions of improvement for most aspects of resident well-being (e.g. stress, fatigue) and work environment (e.g. supervision, support), (iii) a neutral effect on the resident learning environment, except resident opinions on an increase in opportunities for learning, (iv) perceptions of improved patient safety and quality of care despite worsened continuity of care, and (v) no increases in work-load on attendings or the health care system (cost-neutral call coverage). Patient safety, handovers and increased utilization of moonlighting opportunities need further exploration.

The Canadian Hypertension Education Program reviews the hypertension literature annually and provides detailed recommendations regarding hypertension diagnosis, assessment, prevention, and treatment. This report provides the updated evidence-based recommendations for 2015. This year, 4 new recommendations were added and 2 existing recommendations were modified. A revised algorithm for the diagnosis of hypertension is presented. Two major changes are proposed: (1) measurement using validated electronic (oscillometric) upper arm devices is preferred over auscultation for accurate office blood pressure measurement; (2) if the visit 1 mean blood pressure is increased but < 180/110 mm Hg, out-of-office blood pressure measurements using ambulatory blood pressure monitoring (preferably) or home blood pressure monitoring should be performed before visit 2 to rule out white coat hypertension, for which pharmacologic treatment is not recommended. A standardized ambulatory blood pressure monitoring protocol and an update on automated office blood pressure are also presented. Several other recommendations on accurate measurement of blood pressure and criteria for diagnosis of hypertension have been reorganized. Two other new recommendations refer to smoking cessation: (1) tobacco use status should be updated regularly and advice to quit smoking should be provided; and (2) advice in combination with pharmacotherapy for smoking cessation should be offered to all smokers. The following recommendations were modified: (1) renal artery stenosis should be primarily managed medically; and (2) renal artery angioplasty and stenting could be considered for patients with renal artery stenosis and complicated, uncontrolled hypertension. The rationale for these recommendation changes is discussed., (Copyright © 2015 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.)

The noted disruption of thalamocortical connections and abnormalities in tactile sensory function has resulted in a new definition of cerebral palsy (CP) that recognizes the sensorimotor integration process as central to the motor impairments seen in these children. Despite this updated definition, the connection between a child's motor impairments and somatosensory processing remains almost entirely unknown. In this investigation, we explored the relationship between the magnitude of neural activity within the somatosensory cortices, the strength of the ankle plantarflexors, and the gait spatiotemporal kinematics of a group of children with CP and a typically developing matched cohort. Our results revealed that the magnitude of somatosensory cortical activity in children with CP had a strong positive relationship with the ankle strength, step length, and walking speed. These results suggest that stronger activity within the somatosensory cortices in response to foot somatosensations was related to enhanced ankle plantarflexor strength and improved mobility in the children with CP. These results provide further support for the notion that children with CP exhibit, not only musculoskeletal deficits, but also somatosensory deficits that potentially contribute to their overall functional mobility and strength limitations., (Copyright © 2015 the American Physiological Society.)

Combination antiretroviral therapy transformed human immunodeficiency virus (HIV)-infection from a terminal illness to a manageable condition, but these patients remain at a significantly elevated risk of developing cognitive impairments and the mechanisms are not understood. Some previous neuroimaging studies have found hyperactivation in frontoparietal networks of HIV-infected patients, whereas others reported aberrations restricted to sensory cortices. In this study, we utilize high-resolution structural and neurophysiological imaging to determine whether alterations in brain structure, function, or both contribute to HIV-related cognitive impairments. HIV-infected adults and individually matched controls completed 3-Tesla structural magnetic resonance imaging (sMRI) and a mechanoreception task during magnetoencephalography (MEG). MEG data were examined using advanced beamforming methods, and sMRI data were analyzed using the latest voxel-based morphometry methods with DARTEL. We found significantly reduced theta responses in the postcentral gyrus and increased alpha activity in the prefrontal cortices of HIV-infected patients compared with controls. Patients also had reduced gray matter volume in the postcentral gyrus, parahippocampal gyrus, and other regions. Importantly, reduced gray matter volume in the left postcentral gyrus was spatially coincident with abnormal MEG responses in HIV-infected patients. Finally, left prefrontal and postcentral gyrus activity was correlated with neuropsychological performance and, when used in conjunction, these two MEG findings had a sensitivity and specificity of over 87.5% for HIV-associated cognitive impairment. This study is the first to demonstrate abnormally increased activity in association cortices with simultaneously decreased activity in sensory areas. These MEG findings had excellent sensitivity and specificity for HIV-associated cognitive impairment, and may hold promise as a potential disease marker., (© 2014 Wiley Periodicals, Inc.)

Children who receive treatment for medulloblastoma have a high survival rate, but also a high likelihood of developing posterior fossa syndrome, a condition that includes devastating balance and motor problems. This case series used 2 novel neuromodulation devices in conjunction with an intensive physical therapy intervention for 2 children who were 5 years post tumor treatment with a diagnosis of posterior fossa syndrome. Pre- and postclinical measures, in addition to magnetoencephalography brain imaging, describe positive behavioral and neuroplastic changes resulting from the intervention. The positive outcomes in these cases suggest that further study is needed using neuromodulatory devices and long-term rehabilitation in children with balance and movement disorders resulting from cancer treatment.

Previous electrophysiological investigations have evaluated movement-related beta (14-28 Hz) oscillatory activity in healthy participants. These studies have described an abrupt decrease in beta activity that starts before movement onset, and a sharp increase in beta power that peaks after movement termination. These neural responses have been respectively termed the event-related beta desynchronization or pre-movement beta ERD, and the post-movement beta rebound (PMBR). Previous studies have shown that a variety of movement parameters and demographic factors (e.g., age) modulate the amplitude of these oscillatory responses, and in the current study we evaluated whether the amplitudes follow a biological temporal rhythm (e.g., circadian), as it is known that spontaneous beta levels increase from morning to afternoon in some brain areas. To this end, we used magnetoencephalography (MEG) to evaluate oscillatory activity during a right hand finger-tapping task in four participants who were recorded at three different times (09:00, 12:00, 16:00) on three consecutive days (i.e., 36 total MEG sessions). All MEG data were corrected for head motion and examined in the time-frequency domain using beamforming methods. We found a significant linear increase in beta ERD amplitude from 09:00 to 16:00 h in the left precentral gyrus, left premotor cortices, left supplementary motor area (SMA), and right precentral and postcentral gyri. In contrast, the amplitude of the PMBR was very steady across the day in all brain regions except the left SMA, which exhibited a linear increase from morning to afternoon. Finally, beta levels during the baseline period also increased from 09:00 to 16:00 in most regions of the cortical sensorimotor network. These data show that both the pre-movement beta ERD and spontaneous beta levels strongly increase from morning to afternoon in the motor cortices, which may indicate that the amplitude of the beta ERD response is determined by the spontaneous beta level during the motor planning period., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Aim: This investigation used magnetoencephalography (MEG) to examine the neural oscillatory responses of the sensorimotor cortices during the motor planning and movement execution stages of children with typical development and children with cerebral palsy (CP)., Method: The study involved 13 children with CP (nine males, four females; mean [SD] age 14y 3mo [9mo], range 10-18y; height 1.61m [0.08m]; weight 52.65kg [13kg]), and 13 age- and sex-matched typically developing children (height 1.64m [0.06m]; weight 56.88kg [10kg]). The experiment required the children to extend their knee joint as whole-head MEG recordings were acquired. Beamformer imaging methods were employed to quantify the source activity of the beta-frequency (14-28Hz) event-related desynchronization (ERD) that occurs during the motor planning period, and the gamma-frequency (~50Hz) event-related synchronization (ERS) that occurs at the motor execution stage., Results: The children with CP had a stronger mean beta ERD during the motor planning phase and reduced mean gamma ERS at the onset of movement., Interpretation: The uncharacteristic beta ERD in the children with CP suggests that they may have greater difficulty planning knee joint movements. We suggest that these aberrant beta ERD oscillations may have a cascading effect on the gamma ERS, which ultimately affects the execution of the motor command., (© 2014 Mac Keith Press.)

Objective: The primary aim of this exploratory investigation was to determine if there are differences in cortical activation of children with spastic diplegic cerebral palsy (CP) and typically developing children during gait., Methods: Functional near-infrared spectroscopy was used to measure the concentration of oxygenated hemoglobin that was present in the supplementary motor area, pre-central gyrus, post-central gyrus and superior parietal lobule as the children walked on a treadmill. A sagittal plane video was concurrently collected and later digitized to quantify the temporal gait variations., Results: (1) The children with CP had an increased amount of activation in the sensorimotor cortices and superior parietal lobule during gait, (2) the children with CP had a greater amount of variability or error in their stride time intervals, and (3) an increased amount of error in the temporal gait kinematics was associated with an increased amount of activity across the cortical network., Conclusion: Our results suggest that the perinatal damage and subsequent neural reorganization that occurs with spastic diplegic CP may impact the functional cortical activity for controlling gait. Furthermore, our results imply the increased cortical activity of the somatosensory cortices and superior parietal cortices may underlie the greater amount of error in the temporal gait kinematics., (Copyright © 2014 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.)

Parkinson's disease (PD) is a progressive debilitating neurodegenerative disorder clinically manifest by motor, posture and gait abnormalities. Human neurophysiological studies recording local field potentials within the subthalamic nucleus and scalp-based electroencephalography have shown pathological beta synchrony throughout the basal ganglia-thalamic-cortical motor network in PD. Notably, suppression of this pathological beta synchrony by dopamine replacement therapy or deep-brain stimulation has been associated with improved motor function. However, due to the invasive nature of these studies, it remains unknown whether this "pathological beta" is actually stronger than that observed in healthy demographically matched controls. We used magnetoencephalography to investigate neuronal synchrony and oscillatory amplitude in the beta range and lower frequencies during the resting state in patients with PD and a matched group of patients without neurological disease. Patients with PD were studied both in the practically defined drug "OFF" state, and after administration of dopamine replacements. We found that beta oscillatory amplitude was reduced bilaterally in the primary motor regions of unmedicated patients with PD compared with controls. Administration of dopaminergic medications significantly increased beta oscillatory activity, thus having a normalizing effect. Interestingly, we also found significantly stronger beta synchrony (i.e., hypersynchrony) between the primary motor regions in unmedicated patients with PD compared with controls, and that medication reduced this coupling which is in agreement with the intraoperative studies. These results are consistent with the known functionality of the basal ganglia-thalamic-cortical motor circuit and the likely consequences of beta hypersynchrony in the subthalamic nucleus of patients with PD., (Copyright © 2014 the American Physiological Society.)

Raltegravir (RAL) is a first clinically approved integrase (IN) inhibitor for the treatment of HIV but rapid mutation of the virus has led to chemo-resistant strains. Therefore, there is a medical need to develop new IN inhibitors to overcome drug resistance. At present, several IN inhibitors are in different phases of clinical trials and few have been discontinued due to toxicity and lack of efficacy. The development of potent second-generation IN inhibitors with improved safety profiles is key for selecting new clinical candidates. In this article, we report the design and synthesis of potent 5-hydroxy-6-oxo-1,6-dihydropyrimidine-4-carboxamide analogues as second-generation IN inhibitors. These compounds satisfy two structural requirements known for potent inhibition of HIV-1 IN catalysis: a metal chelating moiety and a hydrophobic functionality necessary for selectivity against the strand transfer reaction. Most of the new compounds described herein are potent and selective for the strand transfer reaction and show antiviral activity in cell-based assays. Furthermore, this class of compounds are drug-like and suitable for further optimization and preclinical studies., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Parkinson's disease (PD) is a neurodegenerative disorder associated with debilitating motor, posture, and gait abnormalities. Human studies recording local field potentials within the subthalamic nucleus and scalp-based electroencephalography have shown pathological beta synchronization throughout the cortical-basal ganglia motor network in PD. Suppression of such pathological beta synchronization has been associated with improved motor function, which may explain the effectiveness of deep-brain stimulation. We used magnetoencephalography (MEG) to investigate neural population-level beta responses, and other oscillatory activity, during a motor task in unmedicated patients with PD and a matched group of healthy adults. MEG is a noninvasive neurophysiological technique that permits the recording of oscillatory activity during movement planning, execution, and termination phases. Each of these phases was independently examined using beamforming to distinguish the brain areas and movement phases, where pathological oscillations exist during motor control. Patients with PD exhibited significantly diminished beta desynchronization compared with controls prior to and during movement, which paralleled reduced alpha desynchronization. This study is the first to systematically investigate neural oscillatory responses in PD during distinct stages of motor control (e.g. planning, execution, and termination) and indicates that these patients have significant difficulty suppressing cortical beta synchronization during movement planning, which may contribute to their diminished movement capacities., (© The Author 2013. Published by Oxford University Press.)

Purpose: Health care workers, including physicians, have adopted more casual dress. The appearance of a physician may influence patients' opinion of physician knowledge, competence and trustworthiness. We hypothesized that medical inpatients and outpatients would rate these attributes higher in residents who dressed and acted in a more formal manner., Methods: Prospective cohort included both inpatients and outpatients. One hundred thirty three patients, aged 62.3 ± 16 years, 49% of whom were female, were surveyed. One of two male resident physicians approached each patient, ostensibly to obtain consent to a brief mini-mental status examination. The physician was dressed, and acted, either "formally" (F) or "informally" (I). Patients then completed a six item questionnaire, using a 5 point Likert scale, to assess their confidence in the resident. Total scores could be 6 to 30. Total scores were compared using one-way ANOVA., Results: Patients' perceptions were high for both F and I: 25.5 ± 3.1 vs. 24.1 ± 3.0, respectively (p=0.013). This difference was driven by the "lab coat" question: patients generally preferred physicians to wear a lab coat (3.9 ± 1.0 vs. 2.8 ± 1.3, p < 0.0001). Responses to four of the other five questions were numerically, but not statistically, higher in F. There was no difference in preference between the two residents: 24.6 ± 2.8 vs. 24.9 ± 3.5, p=0.56., Conclusion: More formal dress and demeanor by residents leads to a modest, but significant, increase in patient perception of the resident's value. Wearing a white lab coat, in particular, has a positive effect.

Silyl ketene imines derived from a variety of α-branched nitriles have been developed as highly useful reagents for the construction of quaternary stereogenic centers via the aldol addition reaction. In the presence of SiCl4 and the catalytic action of a chiral phosphoramide, silyl ketene imines undergo extremely rapid and high yielding addition to a wide variety of aromatic aldehydes with excellent diastereo- and enantioselectivity. Of particular note are the high yields and selectivities obtained from electron-rich, electron-poor, and hindered aldehydes. Linear aliphatic aldehydes did react with good diastereo- and enantioselectivity in the presence of nBu4N(+)I(-), but branched aldehydes were much less reactive. Semiempirical calculations provided a rationalization of the observed diastereo- and enantioselectivity via open transitions states., (© 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Herein, updated evidence-based recommendations for the diagnosis, assessment, prevention, and treatment of hypertension in Canadian adults are detailed. For 2014, 3 existing recommendations were modified and 2 new recommendations were added. The following recommendations were modified: (1) the recommended sodium intake threshold was changed from ≤ 1500 mg (3.75 g of salt) to approximately 2000 mg (5 g of salt) per day; (2) a pharmacotherapy treatment initiation systolic blood pressure threshold of ≥ 160 mm Hg was added in very elderly (age ≥ 80 years) patients who do not have diabetes or target organ damage (systolic blood pressure target in this population remains at < 150 mm Hg); and (3) the target population recommended to receive low-dose acetylsalicylic acid therapy for primary prevention was narrowed from all patients with controlled hypertension to only those ≥ 50 years of age. The 2 new recommendations are: (1) advice to be cautious when lowering systolic blood pressure to target levels in patients with established coronary artery disease if diastolic blood pressure is ≤ 60 mm Hg because of concerns that myocardial ischemia might be exacerbated; and (2) the addition of glycated hemoglobin (A1c) in the diagnostic work-up of patients with newly diagnosed hypertension. The rationale for these recommendation changes is discussed. In addition, emerging data on blood pressure targets in stroke patients are discussed; these data did not lead to recommendation changes at this time. The Canadian Hypertension Education Program recommendations will continue to be updated annually., (Copyright © 2014 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.)

The ability to attend to particular stimuli while ignoring others is crucial in goal-directed activities and has been linked with prefrontal cortical regions, including the dorsolateral prefrontal cortex (DLPFC). Both hyper- and hypo-activation in the DLPFC has been reported in patients with attention-deficit/hyperactivity disorder (ADHD) during many different cognitive tasks, but the network-level effects of such aberrant activity remain largely unknown. Using magnetoencephalography (MEG), we examined functional connectivity between regions of the DLPFC and the modality-specific auditory cortices during an auditory attention task in medicated and un-medicated adults with ADHD, and those without ADHD. Participants completed an attention task in two separate sessions (medicated/un-medicated), and each session consisted of two blocks (attend and no-attend). All MEG data were coregistered to structural MRI, corrected for head motion, and projected into source space. Subsequently, we computed the phase coherence (i.e., functional connectivity) between DLPFC regions and the auditory cortices. We found that un-medicated adults with ADHD exhibited greater phase coherence in the beta (14-30Hz) and gamma frequency (30-56Hz) range in attend and no-attend conditions compared to controls. Stimulant medication attenuated these differences, but did not fully eliminate them. These results suggest that aberrant bottom-up processing may engulf executive resources in ADHD., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

Background: Although conventional wisdom suggests that low socioeconomic status (SES) is a robust predictor of medication nonadherence, the strength of this association remains unclear., Objectives: 1) To estimate the proportion of studies that identified SES as a potential risk indicator of nonadherence, 2) to describe the type of SES measurements, and 3) to quantify the association between SES and nonadherence to antihypertensive pharmacotherapy., Methods: A systematic review and meta-analysis research design was used. We searched multiple electronic databases for studies in English or French examining nonadherence to antihypertensive medications measured by electronic prescription databases where explanatory factors were considered. Two authors independently assessed quality, described the SES measure(s), and recorded its association with nonadherence to antihypertensives. A random-effects model meta-analysis was performed, and heterogeneity was examined by using the I(2) statistic., Results: Fifty-six studies with 4,780,293 subjects met the inclusion criteria. Twenty-four of these studies (43%) did not report any SES measures. When it was reported (n = 32), only seven (13%) examined more than one component but none performed a multidimensional assessment. Most of the studies relied on income or income-related measures (such as prescription-drug benefits or co-payments) (27 of 32 [84%]). Meta-analysis could be quantified in 40 cohorts reported in 30 studies. Overall, the pooled adjusted risk estimate for nonadherence according to SES (high vs. low) was 0.89 (95% confidence interval 0.87-0.92; I(2) = 95%; P < 0.001). Similar patterns were observed in all subgroups examined., Conclusions: Published studies have not found a strong association between low SES and nonadherence to antihypertensive medications. However, important limitations in the assessment of SES can be identified in virtually all studies. Future studies are required to ascertain whether a stronger association is observed when SES is determined by comprehensive measures., (Copyright © 2014 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.)

Cerebral palsy (CP) results from a perinatal brain injury that often results in sensory impairments and greater errors in motor performance. Although these impairments have been well catalogued, the relationship between sensory processing networks and errors in motor performance has not been well explored. Children with CP and typically developing age-matched controls participated in this investigation. We used high-density magnetoencephalography to measure event-related oscillatory changes in the somatosensory cortices following tactile stimulation to the bottom of the foot. In addition, we quantified the amount of variability or errors in the isometric ankle joint torques as these children attempted to match a target. Our results showed that neural populations in the somatosensory cortices of children with CP were desynchronized by the tactile stimulus, whereas those of typically developing children were clearly synchronized. Such desynchronization suggests that children with CP were unable to fully integrate the external stimulus into ongoing sensorimotor computations. Our results also indicated that children with CP had a greater amount of errors in their motor output when they attempted to match the target force, and this amount of error was negatively correlated with the degree of synchronization present in the somatosensory cortices. These results are the first to show that the motor performance errors of children with CP are linked with neural synchronization within the somatosensory cortices.

Bimanual movements can be performed by flexing and extending the target effectors (e.g., hand muscles) in unison, or by flexing units on one side in unison with extension of the same units on the opposite side. The former movement patterns are generally referred to as in-phase or parallel, whereas the latter patterns are often termed anti-phase movements. It is well known that anti-phase patterns are unstable and tend to spontaneously transition to in-phase movements at higher repetition rates, but the mechanisms and brain regions involved are not fully understood. In the current study, we utilized functional near-infrared spectroscopy (fNIRS) to evaluate whether anterior/posterior subdivisions of the supplementary motor complex (SMA) have distinct functional roles in maintaining in-phase and anti-phase movement patterns. Twelve healthy adult participants completed a bimanual coordination task comprised of anti-phase and in-phase trials as 24-channel fNIRS data was recorded from dorsal-medial motor areas. We examined the relative concentrations of oxygenated and deoxygenated hemoglobin in the channels that were located over the anterior SMA (e.g., pre-SMA) and the SMA proper. Our most interesting results indicated that oxygenated hemoglobin responses were greater in the anterior SMA during performance of anti-phase compared to in-phase movements. In the SMA proper, oxygenated hemoglobin responses did not differ between the two movement patterns. These data suggest that the anterior SMA is critical to programming and maintaining the less stable anti-phase movement patterns, and support the conceptual framework of an anterior-directed gradient of progressively more complex functionality in the SMA., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Objectives: Publically accessible blood pressure monitors are widely used, but little information is available on their accuracy. We compared blood pressure readings of 17 drug store monitors with those obtained using a validated home monitor (Omron BP742CAN) and both with those taken at home using the Canadian Hypertension Education Program protocol., Materials and Methods: Duplicate readings were taken using the drug store monitor (VitaStat, n=6, and PharmaSmart, n=11) on the left arm and the Omron on the right in three participants: two normal and one untreated hypertensive patient. We used Bland-Altman methods for comparison. We explored the correlation with average home blood pressure readings., Results: Home average blood pressure for our three participants was 121±6/73±5, 106±6/62±4, and 142±8/81±7 mmHg. The mean systolic blood pressure difference (drug store-Omron) was -1.8±8.2 mmHg. Diastolic pressure difference was 1.7±5.6. Individual paired systolic differences varied from -19 to 14 mmHg. For the participant who required a large cuff, drug store systolic readings tended to be higher (4.1±6.7). In our three participants, drug store monitors as a group read higher than home systolic blood pressure: 7.5 [95% confidence interval (CI) 1.5-13.4], 1.2 (95% CI -4.0 to 6.4), and 1.0 (95% CI -2.5 to 4.4) mmHg. Diastolic blood pressure and heart rate differences were similar in magnitude., Conclusion: On average, drug store monitors recorded lower systolic blood pressures and higher diastolic blood pressures than a validated monitor, but the difference was neither statistically nor clinically significant. Single reading comparisons showed a much broader range. In three participants, drug store monitors did reflect the average home blood pressure.

The introduction of combination antiretroviral therapy significantly reduced the prevalence of the most severe form of HIV-associated neurocognitive disorders (HAND). Despite this decline, 35-70 % of HIV-infected patients continue to develop mild motor and cognitive impairments. Although neuropsychological studies have shown that HAND affects a wide array of cognitive functions, a formal diagnosis is still based on the exclusion of opportunistic infections and other common ailments, as no specific tests or biomarkers are currently available. In this study, we used magnetoencephalography (MEG) to measure neural activity during the resting-state in 15 HIV-infected older patients and a demographically matched group of 15 uninfected controls. MEG is a noninvasive and direct measure of neural activity with excellent spatiotemporal resolution. All MEG data were coregistered to structural magnetic resonance images, corrected for head motion, fitted to a regional-level source model, and subjected to spectral analyses to quantify population-level neural oscillatory activity. We found that HIV-infected persons exhibited decreased beta oscillations in the supplementary motor area bilaterally, paracentral lobule, posterior cingulate, and bilateral regions of the superior parietal lobule relative to healthy controls. Beta oscillations in the posterior cingulate, a critical component of the default mode network, were also positively correlated with patient scores on the memory recall aspect of the Hopkins Verbal Learning Test-Revised. These results demonstrate that chronic HIV infection does not uniformly disturb cortical function, and that neuronal populations in dorsomedial motor and parietal cortices are especially affected. These findings also suggest that resting-state MEG recordings may hold significant promise as a functional biomarker for identifying HAND and monitoring disease progression.

A series of novel pyrimidone analogues have been designed and synthesized as HIV-1 integrase (IN) inhibitors. This study demonstrated that introducing a substituent in the N1-position of the pyrimidone scaffold does not significantly influence IN inhibitory activity. Molecular docking studies showed these compounds could occupy the IN active site and form pi-pi interactions with viral DNA nucleotides DC16 and DA17 to displace reactive viral DNA 3'OH and block intasome activity., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Objective: Attention-deficit/hyperactivity disorder (ADHD) is a common and extensively treated psychiatric disorder in children, which often persists into adulthood. The core diagnostic symptoms include inappropriate levels of hyperactivity, impulsivity, and/or pervasive inattention. Another crucial aspect of the disorder involves aberrations in temporal perception, which have been well documented in behavioral studies and, recently, have been the focus of neuroimaging studies. These functional magnetic resonance imaging studies have shown reduced activation in anterior cingulate and prefrontal cortices in ADHD using a time-interval discrimination task, whereby participants distinguish intervals differing by only hundreds of milliseconds., Method: We used magnetoencephalography (MEG) to evaluate the cortical network serving temporal perception during a continuous, long-duration (in minutes) time estimation experiment. Briefly, medicated and unmedicated persons with ADHD, and a control group responded each time they estimated 60 s had elapsed for an undisclosed amount of time in two separate MEG sessions. All MEG data were transformed into regional source activity, and subjected to spectral analyses to derive amplitude estimates of gamma-band activity., Results: Compared to controls, unmedicated patients were less accurate time estimators and had weaker gamma activity in the anterior cingulate, supplementary motor area, and left prefrontal cortex. After medication, these patients exhibited small but significant increases in gamma across these same neural regions and significant improvements in time estimation accuracy, which correlated with the gamma activity increases., Conclusion: We found deficient gamma activity in brain areas known to be crucial for timing functions, which may underlie the day-to-day abnormalities in time perception that are common in ADHD., (PsycINFO Database Record (c) 2013 APA, all rights reserved.)

Despite the availability of combination antiretroviral therapy, at least mild cognitive dysfunction is commonly observed in HIV-infected patients, with an estimated prevalence of 35-70 %. Neuropsychological studies of these HIV-associated neurocognitive disorders (HAND) have documented aberrations across a broad range of functional domains, although the basic pathophysiology remains unresolved. Some of the most common findings have been deficits in fine motor control and reduced psychomotor speed, but to date no neuroimaging studies have evaluated basic motor control in HAND. In this study, we used magnetoencephalography (MEG) to evaluate the neurophysiological processes that underlie motor planning in older HIV-infected adults and a matched, uninfected control group. MEG is a noninvasive and direct measure of neural activity with good spatiotemporal precision. During the MEG recording, participants fixated on a central crosshair and performed a finger-tapping task with the dominant hand. All MEG data was corrected for head movements, preprocessed, and imaged in the time-frequency domain using beamforming methodology. All analyses focused on the pre-movement beta desynchronization, which is known to be an index of movement planning. Our results demonstrated that HIV-1-infected patients have deficient beta desynchronization relative to controls within the left/right precentral gyri, and the supplementary motor area. In contrast, HIV-infected persons showed abnormally strong beta responses compared to controls in the right dorsolateral prefrontal cortex and medial prefrontal areas. In addition, the amplitude of beta activity in the primary and supplementary motor areas correlated with scores on the Grooved Pegboard test in HIV-infected adults. These results demonstrate that primary motor and sensory regions may be particularly vulnerable to HIV-associated damage, and that prefrontal cortices may serve a compensatory role in maintaining motor performance levels in infected patients.

Background: Dysfunction in the default mode network (DMN), a group of cortical areas more active during the resting state, has been linked to attentional deficits and symptoms associated with attention-deficit/hyperactivity disorder (ADHD). Prior imaging studies have shown decreased functional connectivity between DMN nodes in patients with ADHD, primarily between anterior and posterior regions. Using magnetoencephalography (MEG), we evaluated phase coherence (i.e., functional connectivity) among regions of the DMN in healthy controls and adults with ADHD before and after stimulant therapy., Methods: We obtained a resting-state MEG recording for all participants. Magnetoencephalography data were transformed into a ~30 node regional source model using inverse spatial filtering, including regions corresponding to the DMN. We computed the zero-lag phase coherence between these regions pairwise for 5 distinct frequency bands, and we assessed group and medication effects., Results: Twelve adults with and 13 without ADHD participated in our study. Functional connectivity was stronger between particular node pairs and showed frequency-specific effects. Unmedicated patients showed reduced phase locking between posterior cingulate/precuneus regions (PCC) and right inferior parietal cortices (RIPL), and between medial prefrontal regions (MPFC) and the left inferior parietal region (LIPL) and the PCC. Unmedicated patients had increased phase locking between the RIPL and LIPL regions compared with controls. Administration of stimulants improved phase locking abnormalities along the MPFC-PCC and LIPL-RIPL pathways in patients with ADHD., Limitations: Modest sample size and lack of duration of patient treatment history may limit the generalizability of our findings., Conclusion: Adults with ADHD exhibit hyper- and hypoconnectivity between regions of the DMN during rest, which were suppressed after stimulant medication administration.

Objective: Shortly after infection, HIV enters the brain and causes widespread inflammation and neuronal damage, which ultimately leads to neuropsychological impairments. Despite a large body of neuroscience and imaging studies, the pathophysiology of these HIV-associated neurocognitive disorders (HAND) remains unresolved. Previous neuroimaging studies have shown greater activation in HIV-infected patients during strenuous tasks in frontal and parietal cortices, and less activation in the primary sensory cortices during rest and sensory stimulation., Methods: High-density magnetoencephalography (MEG) was utilized to evaluate the basic neurophysiology underlying attentive, visual processing in older HIV-infected adults and a matched non-infected control group. Unlike other neuroimaging methods, MEG is a direct measure of neural activity that is not tied to brain metabolism or hemodynamic responses. During MEG, participants fixated on a centrally-presented crosshair while intermittent visual stimulation appeared in their top-right visual-field quadrant. All MEG data was imaged in the time-frequency domain using beamforming., Results: Uninfected controls had increased neuronal synchronization in the 6-12 Hz range within the right dorsolateral prefrontal cortex, right frontal eye-fields, and the posterior cingulate. Conversely, HIV-infected patients exhibited decreased synchrony in these same neural regions, and the magnitude of these decreases was correlated with neuropsychological performance in several cortical association regions., Conclusions: MEG-based imaging holds potential as a noninvasive biomarker for HIV-related neuronal dysfunction, and may help identify patients who have or may develop HAND. Reduced synchronization of neural populations in the association cortices was strongly linked to cognitive dysfunction, and likely reflects the impact of HIV on neuronal and neuropsychological health.

The analysis of interictal epileptiform discharges (IEDs) using magnetoencephalography (MEG) is utilized for the localization of seizure onset zones in the presurgical planning of epilepsy patients. Additionally, resting-state functional connectivity analyses using the IED area may provide novel insight into the underlying brain networks. In this study, we evaluate whether chronicity of seizures is related to whole-brain functional connectivity metrics using the area of IED generation (derived from MEG) as the seed region. We found a positive correlation between the duration of seizures and beta-band functional connectivity between the epileptogenic zone and other brain areas. This suggests the presence of inhibitory GABAergic modulation of distal brain regions in response to chronic epileptiform activity., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)

We updated the evidence-based recommendations for the diagnosis, assessment, prevention, and treatment of hypertension in adults for 2013. This year's update includes 2 new recommendations. First, among nonhypertensive or stage 1 hypertensive individuals, the use of resistance or weight training exercise does not adversely influence blood pressure (BP) (Grade D). Thus, such patients need not avoid this type of exercise for fear of increasing BP. Second, and separately, for very elderly patients with isolated systolic hypertension (age 80 years or older), the target for systolic BP should be < 150 mm Hg (Grade C) rather than < 140 mm Hg as recommended for younger patients. We also discuss 2 additional topics at length (the pharmacological treatment of mild hypertension and the possibility of a diastolic J curve in hypertensive patients with coronary artery disease). In light of several methodological limitations, a recent systematic review of 4 trials in patients with stage 1 uncomplicated hypertension did not lead to changes in management recommendations. In addition, because of a lack of prospective randomized data assessing diastolic BP thresholds in patients with coronary artery disease and hypertension, no recommendation to set a selective diastolic cut point for such patients could be affirmed. However, both of these issues will be examined on an ongoing basis, in particular as new evidence emerges., (Copyright © 2013 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.)