Determinants of Fatigue in the Biceps Brachii During Blood Flow Restriction Training

poster abstractTraining loads of 60% - 80% of maximum are traditionally recommended for increasing muscular strength. Lifting lighter loads (~20% of 1RM) with concomitant blood flow restriction (BFR) can also increase muscle strength. It is unknown if adaptation with BFR is limited to the muscle or also due to changes in the nervous system. We examined changes in the output of the motor cortex and the muscle with stimulation, when subjects perform 1.) Training with light loads, 2.) Training with light loads with BFR, and 3.) Training with moderate loads. 5 subjects completed three training sessions with the elbow flexor muscles. Maximal strength was measured before and after each training session. Voluntary activation was tested with cortical stimulation (TMS) and with electrical stimulation of the biceps during additional MVCs. Subjects trained with a block of 4 isometric contractions at 20% MVC (120s, 60s, 60s, 60s durations) or at 60% MVC (40s, 20s, 20s, 20s durations). Fatigue (% decrease in MVC after training) was similar between 20% with BFR and 60% conditions (18.6% and 16%) and less in the 20% without BFR condition (9.7%). Cortical voluntary activation decreased similarly between the 20% BFR and 60% conditions (-3.6% and -3.3%) and showed less change with 20% without BFR (-1.8%). Alternatively, with electrical stimulation of the muscle, both 20% training conditions showed a decline in voluntary activation (-3.1% and -5.15), while voluntary activation increased by 8% after the 60% condition. Similar levels of fatigue occur at different contraction intensities when BFR is applied during the lighter contraction. Both 20% with BFR and 60% loading causes deficits in cortical activation, though the limiting factor in the 20% BFR condition is a decrease in activation of the muscle directly, while in the 60% contraction it is due to an inability to drive the motorneuron pool sufficiently

Proposal for a low cost close air support aircraft for the year 2000: The Raptor

The Raptor is a proposed low cost Close Air Support (CAS) aircraft for the U.S. Military. The Raptor incorporates a 'cranked arrow' wing planform, and uses canards instead of a traditional horizontal tail. The Raptor is designed to be capable of responsive delivery of effective ordnance in close proximity to friendly ground forces during the day, night, and 'under the weather' conditions. Details are presented of the Raptor's mission, configuration, performance, stability and control, ground support, manufacturing, and overall cost to permit engineering evaluation of the proposed design. A description of the design process and analysis methods used is also provided

Cutaneous Silent Period Characteristics are Dependent on the Organization of Upper Limb Muscles

abstractCutaneous silent periods (CSPs) are inhibitory spinal reflexes mediated by small diameter A-δ fibers, serving to protect the body from harmful stimuli (Leis et al., 1992; Kofler, 2003). Currently, CSPs are believed to only inhibit the extensor muscles of the upper limb halting motions such as reaching, while exciting flexor muscles to withdraw the limb. The present study sought to determine if CSPs could be evoked in both extensor and flexor muscles of the upper limb, thereby providing further insight into the organization of the spinal circuitry associated with this reflex. 22 subjects performed contractions with seven muscles from the hand, forearm, upper arm, and shoulder while muscle activity was recorded with electromyography. Subjects were electrically stimulated (10x perceptual threshold) with 20 individual pulses delivered to each digit II (radial nerve) and digit V (ulnar nerve) of the right hand during each contraction. Results demonstrated significant main effects (p<0.001) across muscles for the key dependent variables of the CSP: onsets (F[6,21] = 15.42, p <0.001), durations (F[6,21] = 65.39, p <0.001), and % of suppression (F[6,21] = 91, p <0.001), similarly for both nerves stimulated. Distal muscles presented with the earliest onset times, longest duration of inhibition, and largest amount of inhibition. Moving proximally, the onset times became later with duration and the amount of inhibition decreasing. Linear regressions showed that the distance of the muscle from the spinal cord (cm) was a significant predictor of the duration (digit II r2 = 0.43; digit V r2 = 0.46) and amount of inhibition (digit II r2 = 0.51; digit V r2 = 0.48). The results demonstrate the occurrence of CSPs throughout the upper limb, with the greatest inhibition of distal muscles, leading us to hypothesize that the corticospinal tract, specifically direct cortico-motorneuronal connections, are directly influenced by the inhibitory input

Cortical Representation and Excitability Increases for a Thenar Muscle Mediate Improvement in Short-Term Cellular Phone Text Messaging Ability

Cortical representations expand during skilled motor learning. We studied a unique model of motor learning with cellular phone texting, where the thumbs are used exclusively to interact with the device and the prominence of use can be seen where 3200 text messages are exchanged a month in the 18–24 age demographic. The purpose of the present study was to examine the motor cortex representation and input–output (IO) recruitment curves of the abductor pollicis brevis (APB) muscle of the thumb and the ADM muscle with transcranial magnetic stimulation (TMS), relative to individuals’ texting abilities and short-term texting practice. Eighteen individuals performed a functional texting task (FTT) where we scored their texting speed and accuracy. TMS was then used to examine the cortical volumes and areas of activity in the two muscles and IO curves were constructed to measure excitability. Subjects also performed a 10-min practice texting task, after which we repeated the cortical measures. There were no associations between the cortical measures and the FTT scores before practice. However, after practice the APB cortical map expanded and excitability increased, whereas the ADM map constricted. The increase in the active cortical areas in APB correlated with the improvement in the FTT score. Based on the homogenous group of subjects that were already good at texting, we conclude that the cortical representations and excitability for the thumb muscle were already enlarged and more receptive to changes with short-term practice, as noted by the increase in FTT performance after 10-min of practice

Cortical Representation and Excitability Increases for a Thenar Muscle Mediate Improvement in Short-Term Cellular Phone Text Messaging Ability

Cortical representations expand during skilled motor learning. We studied a unique model of motor learning with cellular phone texting, where the thumbs are used exclusively to interact with the device and the prominence of use can be seen where 3200 text messages are exchanged a month in the 18-24 age demographic. The purpose of the present study was to examine the motor cortex representation and input-output (IO) recruitment curves of the abductor pollicis brevis (APB) muscle of the thumb and the ADM muscle with transcranial magnetic stimulation (TMS), relative to individuals' texting abilities and short-term texting practice. Eighteen individuals performed a functional texting task (FTT) where we scored their texting speed and accuracy. TMS was then used to examine the cortical volumes and areas of activity in the two muscles and IO curves were constructed to measure excitability. Subjects also performed a 10-min practice texting task, after which we repeated the cortical measures. There were no associations between the cortical measures and the FTT scores before practice. However, after practice the APB cortical map expanded and excitability increased, whereas the ADM map constricted. The increase in the active cortical areas in APB correlated with the improvement in the FTT score. Based on the homogenous group of subjects that were already good at texting, we conclude that the cortical representations and excitability for the thumb muscle were already enlarged and more receptive to changes with short-term practice, as noted by the increase in FTT performance after 10-min of practice

Hybrid Theory: Creation of a Faculty Position That Allows Half-Time Hospice Employment Alongside Academic Palliative Care

BACKGROUND: The specialty of hospice and palliative medicine struggles to merge the fast-paced technological consultative work of acute hospital palliative care with slower paced and home-based hospice. Each has equal if different merits. Here, we describe creation of a position that allowed half-time hospice employment, alongside academic hospital-based palliative care. METHODS: Johns Hopkins Medicine and Gilchrist, Inc., a large nonprofit hospice, partnered to form a joint position with time spent equally between the two locations. RESULTS: Created as a university position with leasing to the hospice, specific attention has been paid to mentoring at both sites to allow professional advancement. Both organizations have benefited in terms of recruitment, and more physicians have chosen this dual pathway suggesting that it is working well. DISCUSSION: Hybrid positions are possible and may be desired by those who wish to practice both palliative medicine and hospice. Creation of one successful position helped recruit a second and a third candidate a year later. The original recipient has been promoted within Gilchrist to direct the inpatient unit. Such positions require careful mentoring and coordination to allow success at both sites and this can be done with foresight

Potent and Broad Inhibition of HIV-1 by a Peptide from the gp41 Heptad Repeat-2 Domain Conjugated to the CXCR4 Amino Terminus.

HIV-1 entry can be inhibited by soluble peptides from the gp41 heptad repeat-2 (HR2) domain that interfere with formation of the 6-helix bundle during fusion. Inhibition has also been seen when these peptides are conjugated to anchoring molecules and over-expressed on the cell surface. We hypothesized that potent anti-HIV activity could be achieved if a 34 amino acid peptide from HR2 (C34) were brought to the site of virus-cell interactions by conjugation to the amino termini of HIV-1 coreceptors CCR5 or CXCR4. C34-conjugated coreceptors were expressed on the surface of T cell lines and primary CD4 T cells, retained the ability to mediate chemotaxis in response to cognate chemokines, and were highly resistant to HIV-1 utilization for entry. Notably, C34-conjugated CCR5 and CXCR4 each exhibited potent and broad inhibition of HIV-1 isolates from diverse clades irrespective of tropism (i.e., each could inhibit R5, X4 and dual-tropic isolates). This inhibition was highly specific and dependent on positioning of the peptide, as HIV-1 infection was poorly inhibited when C34 was conjugated to the amino terminus of CD4. C34-conjugated coreceptors could also inhibit HIV-1 isolates that were resistant to the soluble HR2 peptide inhibitor, enfuvirtide. When introduced into primary cells, CD4 T cells expressing C34-conjugated coreceptors exhibited physiologic responses to T cell activation while inhibiting diverse HIV-1 isolates, and cells containing C34-conjugated CXCR4 expanded during HIV-1 infection in vitro and in a humanized mouse model. Notably, the C34-conjugated peptide exerted greater HIV-1 inhibition when conjugated to CXCR4 than to CCR5. Thus, antiviral effects of HR2 peptides can be specifically directed to the site of viral entry where they provide potent and broad inhibition of HIV-1. This approach to engineer HIV-1 resistance in functional CD4 T cells may provide a novel cell-based therapeutic for controlling HIV infection in humans

Criteria for the diagnosis of corticobasal degeneration

Current criteria for the clinical diagnosis of pathologically confirmed corticobasal degeneration (CBD) no longer reflect the expanding understanding of this disease and its clinicopathologic correlations. An international consortium of behavioral neurology, neuropsychology, and movement disorders specialists developed new criteria based on consensus and a systematic literature review. Clinical diagnoses (early or late) were identified for 267 nonoverlapping pathologically confirmed CBD cases from published reports and brain banks. Combined with consensus, 4 CBD phenotypes emerged: corticobasal syndrome (CBS), frontal behavioral-spatial syndrome (FBS), nonfluent/agrammatic variant of primary progressive aphasia (naPPA), and progressive supranuclear palsy syndrome (PSPS). Clinical features of CBD cases were extracted from descriptions of 209 brain bank and published patients, providing a comprehensive description of CBD and correcting common misconceptions. Clinical CBD phenotypes and features were combined to create 2 sets of criteria: more specific clinical research criteria for probable CBD and broader criteria for possible CBD that are more inclusive but have a higher chance to detect other tau-based pathologies. Probable CBD criteria require insidious onset and gradual progression for at least 1 year, age at onset ≥50 years, no similar family history or known tau mutations, and a clinical phenotype of probable CBS or either FBS or naPPA with at least 1 CBS feature. The possible CBD category uses similar criteria but has no restrictions on age or family history, allows tau mutations, permits less rigorous phenotype fulfillment, and includes a PSPS phenotype. Future validation and refinement of the proposed criteria are needed

Interactions of Bacillus Mojavensis and Fusarium Verticillioides With a Benzoxazolinone (Boa) and Its Transformation Product, Apo

En:Journal of Chemical Ecology (2007, vol. 33, n. 10, p. 1885-1897)The benzoxazolinones, specifically benzoxazolin-2(3H)-one (BOA), are important transformation products of the benzoxazinones that can serve as allelochemicals providing resistance to maize from pathogenic bacteria, fungi, and insects. However, maize pathogens such as Fusarium verticillioides are capable of detoxifying the benzoxazolinones to 2-aminophenol (AP), which is converted to the less toxic N-(2-hydroxyphenyl) malonamic acid (HPMA) and 2-acetamidophenol (HPAA). As biocontrol strategies that utilize a species of endophytic bacterium, Bacillus mojavensis, are considered efficacious as a control of this Fusarium species, the in vitro transformation and effects of BOA on growth of this bacterium was examined relative to its interaction with strains of F. verticillioides. The results showed that a red pigment was produced and accumulated only on BOA-amended media when wild type and the progeny of genetic crosses of F. verticillioides are cultured in the presence of the bacterium. The pigment was identified as 2-amino-3H-phenoxazin-3-one (APO), which is a stable product. The results indicate that the bacterium interacts with the fungus preventing the usual transformation of AP to the nontoxic HPMA, resulting in the accumulation of higher amounts of APO than when the fungus is cultured alone. APO is highly toxic to F. verticillioides and other organisms. Thus, an enhanced biocontrol is suggested by this in vitro study. =580 $aEn:Journal of Chemical Ecolog

Aberrant developmental titin splicing and dysregulated sarcomere length in Thymosin β4 knockout mice

Sarcomere assembly is a highly orchestrated and dynamic process which adapts, during perinatal development, to accommodate growth of the heart. Sarcomeric components, including titin, undergo an isoform transition to adjust ventricular filling. Many sarcomeric genes have been implicated in congenital cardiomyopathies, such that understanding developmental sarcomere transitions will inform the aetiology and treatment. We sought to determine whether Thymosin β4 (Tβ4), a peptide that regulates the availability of actin monomers for polymerization in non-muscle cells, plays a role in sarcomere assembly during cardiac morphogenesis and influences adult cardiac function. In Tβ4 null mice, immunofluorescence-based sarcomere analyses revealed shortened thin filament, sarcomere and titin spring length in cardiomyocytes, associated with precocious up-regulation of the short titin isoforms during the postnatal splicing transition. By magnetic resonance imaging, this manifested as diminished stroke volume and limited contractile reserve in adult mice. Extrapolating to an in vitro cardiomyocyte model, the altered postnatal splicing was corrected with addition of synthetic Tβ4, whereby normal sarcomere length was restored. Our data suggest that Tβ4 is required for setting correct sarcomere length and for appropriate splicing of titin, not only in the heart but also in skeletal muscle. Distinguishing between thin filament extension and titin splicing as the primary defect is challenging, as these events are intimately linked. The regulation of titin splicing is a previously unrecognised role of Tβ4 and gives preliminary insight into a mechanism by which titin isoforms may be manipulated to correct cardiac dysfunction