Brain Activation During Passive and Volitional Pedaling After Stroke

Background: Prior work indicates that pedaling-related brain activation is lower in people with stroke than in controls. We asked whether this observation could be explained by between-group differences in volitional motor commands and pedaling performance. Methods: Individuals with and without stroke performed passive and volitional pedaling while brain activation was recorded with functional magnetic resonance imaging. The passive condition eliminated motor commands to pedal and minimized between-group differences in pedaling performance. Volume, intensity, and laterality of brain activation were compared across conditions and groups. Results: There were no significant effects of condition and no Group × Condition interactions for any measure of brain activation. Only 53% of subjects could minimize muscle activity for passive pedaling. Conclusions: Altered motor commands and pedaling performance are unlikely to account for reduced pedaling-related brain activation poststroke. Instead, this phenomenon may be due to functional or structural brain changes. Passive pedaling can be difficult to achieve and may require inhibition of excitatory descending drive

Observation of Amounts of Movement Practice Provided during Stroke Rehabilitation

Objective To investigate how much movement practice occurred during stroke rehabilitation, and what factors might influence doses of practice provided. Design Observational survey of stroke therapy sessions. Setting Seven inpatient and outpatient rehabilitation sites. Participants We observed a convenience sample of 312 physical and occupational therapy sessions for people with stroke. Interventions Not applicable. Main Outcome Measures We recorded numbers of repetitions in specific movement categories and data on potential modifying factors (patient age, side affected, time since stroke, FIM item scores, years of therapist experience). Descriptive statistics were used to characterize amounts of practice. Correlation and regression analyses were used to determine whether potential factors were related to the amount of practice in the 2 important categories of upper extremity functional movements and gait steps. Results Practice of task-specific, functional upper extremity movements occurred in 51% of the sessions that addressed upper limb rehabilitation, and the average number of repetitions/session was 32 (95% confidence interval [CI]=20–44). Practice of gait occurred in 84% of sessions that addressed lower limb rehabilitation and the average number of gait steps/session was 357 (95% CI=296–418). None of the potential factors listed accounted for significant variance in the amount of practice in either of these 2 categories. Conclusions The amount of practice provided during poststroke rehabilitation is small compared with animal models. It is possible that current doses of task-specific practice during rehabilitation are not adequate to drive the neural reorganization needed to promote function poststroke optimally

Terror from the Sky: Unconventional Linguistic Clues to the Negrito Past

Within recorded history. most Southeast Asian peoples have been of southern Mongoloid physical type, whether they speak Austroasiatic, Tibeto-Burman, Austronesian, Tai-Kadai, or Hmong-Mien languages. However, population distributions suggest that this is a post-Pleistocene phenomenon and that for tens of millennia before the last glaciation ended Greater Mainland Southeast Asia, which included the currently insular world that rests on the Sunda Shelf, was peopled by short, dark-skinned, frizzy-haired foragers whose descendants in the Philippines came to be labeled by the sixteenth-century Spanish colonizers as negritos, a term that has since been extended to similar groups throughout the region. There are three areas in which these populations survived into the present so as to become part of written history: the Philippines, the Malay Peninsula, and the Andaman Islands. All Philippine negritos speak Austronesian languages, and all Malayan negritos speak languages in the nuclear Mon-Khmer branch of Austroasiatic, but the linguistic situation in the Andamans is a world apart. Given prehistoric language shifts among both Philippine and Malayan negritos, the prospects of determining whether disparate negrito populations were once a linguistically or culturally unified community would appear hopeless. Surprisingly, however, some clues to a common negrito past do survive in a most unexpected way

Supported discharge service versus Inpatient care Evaluation (SITE): a randomised controlled trial comparing effectiveness of an intensive community care service versus inpatient treatment as usual for adolescents with severe psychiatric disorders: self-harm, functional impairment, and educational and clinical outcomes.

Background: Clinical guidelines recommend intensive community care service treatment (ICCS) to reduce adolescent psychiatric inpatient care. We have previously reported that the addition of ICCS led to a substantial decrease in hospital use and improved school re-integration. Aim: To undertake a randomised controlled trial (RCT) comparing an inpatient admission followed by an early discharge supported by ICCS with usual inpatient admission (treatment as usual; TAU). In this paper, we report the impact of ICCS on self-harm and other clinical and educational outcomes. Method: 106 patients aged 12-18 admitted for psychiatric inpatient care were randomised (1:1) to either ICCS or TAU. Six months after randomization, we compared the two treatment arms on the number and severity of self-harm episodes, the functional impairment, severity of psychiatric symptoms, clinical improvement, reading and mathematical ability, weight, height and the use of psychological therapy and medication. Results: At six-month follow-up, there were no differences between the two groups on most measures. Patients receiving ICCS were significantly less likely to report multiple episodes (5 or more) of self-harm (OR=0·18, 95% CI: 0·05 to 0·64). Patients admitted to private inpatient units spent on average 118.4 (95% CI: 28·2 to 208.6) fewer days in hospitals if they were in the ICCS group compared to TAU. Conclusion: The addition of ICCS to TAU may lower the risk of multiple self-harm and may reduce the duration of inpatient stay, especially in those patients admitted for private care. Early discharge with ICCS appears to be a viable alternative to standard inpatient treatment

Shape memory characteristics of woven glass fibre fabric reinforced epoxy composite in flexure

Shape memory characteristics of a woven glass fibre (GF) fabric reinforced epoxy composite (reinforcement content: 38 vol.%) were assessed in three point bending mode in a dynamic-mechanical analysis device and compared to those of the parent epoxy resin (EP). From unconstrained tests the shape fixity and recovery ratios and the recovery rate, whereas from constrained tests the recovery stress were determined. The shape fixity and recovery rate decreased due to the GF reinforcement which had, however, no effect on the shape recovery. Major benefit of the woven GF fabric was that the recovery stress could be enhanced by two orders of magnitude in comparison to the neat EP. GF reinforcement was accompanied with a substantial decrease in the failure-free flexural deformability of the composite specimen

Protein and small non-coding RNA-enriched extracellular vesicles are released by the pathogenic blood fluke Schistosoma mansoni

Background: Penetration of skin, migration through tissues and establishment of long-lived intravascular partners require Schistosoma parasites to successfully manipulate definitive host defences. While previous studies of larval schistosomula have postulated a function for excreted/secreted (E/S) products in initiating these host-modulatory events, the role of extracellular vesicles (EVs) has yet to be considered. Here, using preparatory ultracentrifugation as well as methodologies to globally analyse both proteins and small non-coding RNAs (sncRNAs), we conducted the first characterization of Schistosoma mansoni schistosomula EVs and their potential host-regulatory cargos. Results: Transmission electron microscopy analysis of EVs isolated from schistosomula in vitro cultures revealed the presence of numerous, 30–100 nm sized exosome-like vesicles. Proteomic analysis of these vesicles revealed a core set of 109 proteins, including homologs to those previously found enriched in other eukaryotic EVs, as well as hypothetical proteins of high abundance and currently unknown function. Characterization of E/S sncRNAs found within and outside of schistosomula EVs additionally identified the presence of potential gene-regulatory miRNAs (35 known and 170 potentially novel miRNAs) and tRNA-derived small RNAs (tsRNAs; nineteen 5′ tsRNAs and fourteen 3′ tsRNAs). Conclusions: The identification of S. mansoni EVs and the combinatorial protein/sncRNA characterization of their cargo signifies that an important new participant in the complex biology underpinning schistosome/host interactions has now been discovered. Further work defining the role of these schistosomula EVs and the function/stability of intra- and extra-vesicular sncRNA components presents tremendous opportunities for developing novel schistosomiasis diagnostics or interventions

Trypanocidal and leishmanicidal activity of six limonoids

Six limonoids [kotschyienone A and B (1, 2), 7-deacetylgedunin (3), 7-deacetyl-7-oxogedunin (4), andirobin (5) and methyl angolensate (6)] were investigated for their trypanocidal and leishmanicidal activities using bloodstream forms of Trypanosoma brucei and promastigotes of Leishmania major. Whereas all compounds showed anti-trypanosomal activity, only compounds 1–4 displayed anti-leishmanial activity. The 50% growth inhibition (GI 50) values for the trypanocidal and leishmanicidal activity of the compounds ranged between 2.5 and 14.9 μM. Kotschyienone A (1) was found to be the most active compound with a minimal inhibition concentration (MIC) value of 10 μM and GI 50 values between 2.5 and 2.9 μM. Only compounds 1 and 3 showed moderate cytotoxicity against HL-60 cells with MIC and GI 50 values of 100 μM and 31.5–46.2 μM, respectively. Compound 1 was also found to show activity against intracellular amastigotes of L. major with a GI 50 value of 1.5 μM. The results suggest that limonoids have potential as drug candidates for the development of new treatments against trypanosomiasis and leishmaniasis

A structurally distinct TGF-β mimic from an intestinal helminth parasite potently induces regulatory T cells

Helminth parasites defy immune exclusion through sophisticated evasion mechanisms, including activation of host immunosuppressive regulatory T (Treg) cells. The mouse parasite Heligmosomoides polygyrus can expand the host Treg population by secreting products that activate TGF-β signalling, but the identity of the active molecule is unknown. Here we identify an H. polygyrus TGF-β mimic (Hp-TGM) that replicates the biological and functional properties of TGF-β, including binding to mammalian TGF-β receptors and inducing mouse and human Foxp3+ Treg cells. Hp-TGM has no homology with mammalian TGF-β or other members of the TGF-β family, but is a member of the complement control protein superfamily. Thus, our data indicate that through convergent evolution, the parasite has acquired a protein with cytokine-like function that is able to exploit an endogenous pathway of immunoregulation in the host