MASP2 levels are elevated in thrombotic microangiopathies: association with microvascular endothelial cell injury and suppression by anti-MASP2 antibody narsoplimab.

Involvement of the alternative complement pathway (AP) in microvascular endothelial cell (MVEC) injury characteristic of a thrombotic microangiopathy (TMA) is well documented. However, the role of the lectin pathway (LP) of complement has not been explored. We examined mannose-binding lectin associated serine protease (MASP2), the effector enzyme of the LP, in thrombotic thrombocytopenic purpura, atypical hemolytic uremic syndrome and post-allogeneic hematopoietic stem cell transplantation (alloHSCT) TMAs. Plasma MASP2 and terminal complement component sC5b-9 levels were assessed by enzyme-linked immunosorbent assay (ELISA). Human MVEC were exposed to patient plasmas, and the effect of the anti-MASP2 human monoclonal antibody narsoplimab on plasma-induced MVEC activation was assessed by caspase 8 activity. MASP2 levels were highly elevated in all TMA patients versus controls. The relatively lower MASP2 levels in alloHSCT patients with TMAs compared to levels in alloHSCT patients who did not develop a TMA, and a significant decrease in variance of MASP2 levels in the former, may reflect MASP2 consumption at sites of disease activity. Plasmas from 14 of the 22 TMA patients tested (64%) induced significant MVEC caspase 8 activation. This was suppressed by clinically relevant levels of narsoplimab (1·2 µg/ml) for all 14 patients, with a mean 65·7% inhibition (36.8-99.4%; P < 0·0001). In conclusion, the LP of complement is activated in TMAs of diverse etiology. Inhibition of MASP2 reduces TMA plasma-mediated MVEC injury in vitro. LP inhibition therefore may be of therapeutic benefit in these disorders.

Predictors of decline in verbal fluency after frontal lobe epilepsy surgery.

Few studies have focused on language changes following frontal lobe epilepsy (FLE) surgery. The aim of the current study is to quantify the role of resection location and size in verbal fluency decline after FLE surgery and to examine its predictors. A retrospective chart review identified 36 adult patients who underwent FLE surgery. Verbal fluency was assessed using the Controlled Oral Word Association Test (COWAT). Nine (25%) of the patients had significant decline. Binary logistic regression incorporating side of resection and preoperative COWAT score significantly predicted decline and accounted for 25% of the variance. A trend was also noted for decliners to have higher postoperative seizure recurrence (p=0.067). There was no effect of size of resection. Patients undergoing FLE surgery are at risk of verbal fluency decline, especially if they have a high presurgical verbal fluency score, undergo a frontal lobe resection in the language dominant hemisphere, and have poor seizure outcome.

Role of cortisol in mood and memory in patients with intractable temporal lobe epilepsy.

OBJECTIVE: This study prospectively examined the relationships among late night salivary cortisol (NSC) levels and depressive symptoms, memory performance, and hippocampal volumes in patients with medically intractable temporal lobe epilepsy (TLE) and the potential mediating effects of cortisol in the relationships between these variables. METHODS: Participants included 24 adults with well-characterized medically refractory TLE (right = 11; left = 12; bitemporal = 1). All patients provided saliva samples and completed measures of mood, anxiety, and memory (objective and subjective). MRI-based volumetric analyses of the hippocampi were also conducted. RESULTS: As hypothesized, cortisol was found to be negatively related to several memory measures such that patients with higher cortisol levels demonstrated lower memory performance. However, unexpectedly, cortisol was not related to current symptoms of depression or anxiety, subjective memory ratings, or hippocampal volumes. Consistent with previous findings in the literature, a number of other relationships among the study variables were observed (objective memory and hippocampal volume; subjective memory and mood/anxiety). Results of mediator analyses suggested that cortisol does not mediate the relationship between depression and memory dysfunction or the relationship between depression and hippocampal atrophy. CONCLUSIONS: While cortisol may play a role in memory performance in patients with TLE, it does not fully explain the relationship between depression and mesial temporal dysfunction, likely reflecting the complex and multifactorial relationships among these variables. Results confirm the relationship between memory performance and structural brain integrity and provide further support for a role of depression in subjective memory complaints.

The care of adolescents by obstetrician-gynecologists: a first look.

STUDY OBJECTIVE: To determine whether obstetrician-gynecologists who typically care for adolescent patients, what this care entails, and the adequacy of training opportunities in adolescent health care. DESIGN: A questionnaire designed to elicit information regarding practice patterns of obstetrician-gynecologists mailed to the American College of Obstetricians and Gynecologists Collaborative Ambulatory Practice Network. PARTICIPANTS: Obstetrician-gynecologists whose patient populations included girls under the age of 18. MAIN OUTCOME MEASURES: Items in the questionnaire were generated to determine what care obstetrician-gynecologists are providing to adolescents, whether this care meets practice guidelines of major medical organizations, and whether obstetrician-gynecologists are receiving adequate training to provide this care. RESULTS: Obstetrician-gynecologists frequently care for adolescent patients, with 72.6% seeing adolescents either monthly or weekly. The most frequently cited service needs pertained to reproductive health. Obstetrician-gynecologists also provide primary care, with 55.2% currently providing immunizations to adolescent patients. Nearly all (96.5%) plan to provide HPV immunizations. Most (80% or more) considered their residency training in obstetrics-gynecology on reproductive health to be adequate, but many reported inadequate or no training on primary care. CONCLUSIONS: Obstetrician-gynecologists are an important part of the health care team caring for female adolescent patients. There is a lack of training during residency in obstetrics-gynecology in adolescent primary care issues. Increased training of obstetrician-gynecologists in all aspects of adolescent health care may increase the pool of health care providers who care for adolescents adequately. Collaborative efforts among all adolescent health care providers can improve access to quality health care for adolescents and the health of this population.

Priorities for Standards and Measurements to Accelerate Innovations in Nano-Electrotechnologies: Analysis of the NIST-Energetics-IEC TC 113 Survey.

In 2008, the National Institute of Standards and Technology and Energetics Incorporated collaborated with the International Electrotechnical Commission Technical Committee 113 (IEC TC 113) on nano-electrotechnologies to survey members of the international nanotechnologies community about priorities for standards and measurements to accelerate innovations in nano-electrotechnologies. In this paper, we analyze the 459 survey responses from 45 countries as one means to begin building a consensus on a framework leading to nano-electrotechnologies standards development by standards organizations and national measurement institutes. The distributions of priority rankings from all 459 respondents are such that there are perceived distinctions with statistical confidence between the relative international priorities for the several items ranked in each of the following five Survey category types: 1) Nano-electrotechnology Properties, 2) Nano-electrotechnology Taxonomy: Products, 3) Nano-electrotechnology Taxonomy: Cross-Cutting Technologies, 4) IEC General Discipline Areas, and 5) Stages of the Linear Economic Model. The global consensus prioritizations for ranked items in the above five category types suggest that the IEC TC 113 should focus initially on standards and measurements for electronic and electrical properties of sensors and fabrication tools that support performance assessments of nano-technology enabled sub-assemblies used in energy, medical, and computer products.

The prevalence of undiagnosed pulmonary arterial hypertension in subjects with connective tissue disease at the secondary health care level of community-based rheumatologists (the UNCOVER study).

OBJECTIVE: Most of the data about the prevalence of pulmonary arterial hypertension (PAH) are from tertiary centers that are biased toward seeing more severe cases; therefore, the true prevalence of PAH among patients with connective tissue disease is unknown. We sought to determine the point prevalence of undiagnosed PAH in community-based rheumatology practices. METHODS: The study design was a multicenter, prospective and retrospective survey and analysis of clinical cases in 50 community rheumatology practices. We evaluated a total of 909 patients with either scleroderma (systemic sclerosis [SSc]) or mixed connective tissue disease (MCTD). If a subject had not been diagnosed as having PAH, then a new Doppler echocardiogram was obtained to measure cardiac parameters, including estimated right ventricular systolic pressure (ERVSP), and a full review of medical records was done. RESULTS: Of 909 screened patients, 791 were evaluable and completed the study; 669 had not previously been studied for PAH. Of these 669 patients, 89 (13.3%) were found by Doppler echocardiography to have an ERVSP of > or = 40 mm Hg. Of these 89 patients, 82 (92.1%) had SSc and 7 (7.9%) had MCTD. The total prevalence of PAH in the survey was 26.7% (211 of 791 patients, including 122 with known PAH and 89 newly diagnosed as having PAH). Doppler echocardiographic data showed 20 of 89 patients (22.5%) with ERVSP of > or = 50 mm Hg, 20 of 89 patients (22.5%) with increased RV dimension, and 25 of 89 patients (28.1%) with right atrial enlargement. Patients with ERVSP > or = 40 mm Hg had decreased exercise tolerance compared with those with ERVSP <40 mm Hg (27% compared with 9.5%, respectively, were severely symptomatic). CONCLUSION: A significant number of patients with SSc or MCTD (13.3%) followed up in a community rheumatology practice setting have undiagnosed elevated ERVSP consistent with PAH.

Distinct temporal activity patterns in the rat M1 and red nucleus during skilled versus unskilled limb movement.

The mammalian motor system contains multiple interconnected supraspinal networks, but little is known about their relative roles in producing different movements and behaviors, particularly given their apparently fused activity in primates. We tested whether the task context, as well as using a phylogenetically older mammal, rats, could distinguish the separate contributions of these networks. We obtained simultaneous multi-single neuron recordings from the forelimb motor cortex and magnocellular red nucleus as rats performed two contextually different, but kinematically similar, forelimb reach-like tasks: highly learned, skilled reaching for food through a narrow slot, a task requiring extensive training, versus the swing phases of treadmill locomotion. In both the M1 and the mRN, large subpopulations of neurons peaked in their spike firing rates near the onset and the end of the swing phase during treadmill locomotion. In contrast, neural subgroups in the two areas displayed different temporal sequences of activity during the skilled reaching task. In the mRN, the majority of task-modulated neurons peaked in their firing rate in the middle of the reach when the rat was preparing to project the arm through the slot, whereas large subgroups of M1 neurons displayed elevated firing rates during the initial and terminal phases of the reach. These results suggest that motor-behavioral context can alter the degree of overlapping activity in different supraspinal sensorimotor networks. Moreover, results for the skilled reaching task in rats may have highlighted a distinct processing role of the rubral complex: adapting natural muscle synergies across joints and limbs to novel task demands, in concert with cortically based learning.

Platelet-derived growth factor-alpha receptor-positive oligodendroglia are frequent in multiple sclerosis lesions.

Platelet-derived growth factor (PDGF) ligand is a potent glial cell mitogen. When its cognate receptor (PDGF-alphaR) is expressed on oligodendroglial lineage cells, such cells are considered capable of division, and the receptor thus serves as a phenotypic marker for oligodendrocyte precursor cells. Here we identify using immunohistochemistry a considerably enlarged, PDGF-alphaR-expressing oligodendrocyte cell population within multiple sclerosis (MS) white matter lesions compared to control brains. Numerous PDGF-alphaR-positive oligodendroglia also colabel heavily with the nuclear cell proliferation marker antibody Ki-67. Our finding of large numbers of proliferating oligodendroglia in MS brains expressing up-regulated PDGF-alphaR suggests that these progenitor-like cells represent an important source of regenerating cells for the healing MS lesion.

Seasonal abundance of aphids (Homoptera: Aphididae) in wheat and their role as barley yellow dwarf virus vectors in the South Carolina coastal plain.

Aphid (Homoptera: Aphididae) seasonal flight activity and abundance in wheat, Triticum aestivum L., and the significance of aphid species as vectors of barley yellow dwarf virus were studied over a nine-year period in the South Carolina coastal plain. Four aphid species colonized wheat in a consistent seasonal pattern. Greenbug, Schizaphis graminum (Rondani), and rice root aphid, Rhopalosiphum rufiabdominalis (Sasaki), colonized seedlingwheat immediately after crop emergence, with apterous colonies usually peaking in December or January and then declining for the remainder of the season. These two aphid species are unlikely to cause economic loss on wheat in South Carolina, thus crop managers should not have to sample for the subterranean R. rufiabdominalis colonies. Bird cherry-oat aphid, Rhopalosiphum padi (L.), was the second most abundant species and the most economically important. Rhopalosiphum padi colonies usually remained below 10/row-meter until peaking in February or March. Barley yellow dwarf incidence and wheat yield loss were significantly correlated with R. padi peak abundance and aphid-day accumulation on the crop. Based on transmission assays, R. padi was primarily responsible for vectoring the predominant virus serotype (PAV) we found in wheat. Pest management efforts should focus on sampling for and suppressing this aphid species. December planting reduced aphid-day accumulation and barley yellow dwarf incidence, but delayed planting is not a practical management option. English grain aphid, Sitobion avenae (F.), was the last species to colonize wheat each season, and the most abundant. Sitobion avenae was responsible for late-season virus transmission and caused direct yield loss by feeding on heads and flag leaves during an outbreak year.

Real-time prediction of hand trajectory by ensembles of cortical neurons in primates.

Signals derived from the rat motor cortex can be used for controlling one-dimensional movements of a robot arm. It remains unknown, however, whether real-time processing of cortical signals can be employed to reproduce, in a robotic device, the kind of complex arm movements used by primates to reach objects in space. Here we recorded the simultaneous activity of large populations of neurons, distributed in the premotor, primary motor and posterior parietal cortical areas, as non-human primates performed two distinct motor tasks. Accurate real-time predictions of one- and three-dimensional arm movement trajectories were obtained by applying both linear and nonlinear algorithms to cortical neuronal ensemble activity recorded from each animal. In addition, cortically derived signals were successfully used for real-time control of robotic devices, both locally and through the Internet. These results suggest that long-term control of complex prosthetic robot arm movements can be achieved by simple real-time transformations of neuronal population signals derived from multiple cortical areas in primates.

Neural prosthetic devices for quadriplegia.

Research into the use of neural prosthetic devices to treat paralysing disorders is expanding rapidly. Functional electrical stimulation of muscles is now used to activate electrically paralysed muscles to restore movements such as the hand-grasp. Sensory feedback signals recorded from peripheral nerves are used to improve the control of functional electrical stimulation systems. Functional electrical stimulation may also be used to stimulate neural circuits in the spinal cord. Electrical recordings from the brain will soon improve patients' control of neural prostheses. Non-invasive electroencephalographic recordings can currently be used to move a cursor across a computer screen. The restoration of near-to-normal limb movement control will, however, require recordings from large numbers of neurons within the brain. Preliminary feasibility has been demonstrated in experimental animals.

Adolescent sex and mass media: a developmental approach.

Media critics point to adolescents' exposure to "sexy" television and popular music. Developmental transitions lead to increased information seeking, and developmental tasks force adolescents to find information sources other than their parents, implying a link between sexy media and adolescent development. Media research informed by knowledge of adolescent development may be able to clarify this connection, and model development is discussed here.