Should GPs provide spiritual care?

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Robotic Resistance/Assistance Training Improves Locomotor Function in Individuals Poststroke: A Randomized Controlled Study

Objective To determine whether providing a controlled resistance versus assistance to the paretic leg at the ankle during treadmill training will improve walking function in individuals poststroke. Design Repeated assessment of the same patients with parallel design and randomized controlled study between 2 groups. Setting Research units of rehabilitation hospitals. Participants Patients (N=30) with chronic stroke. Intervention Subjects were stratified based on self-selected walking speed and were randomly assigned to the resistance or assistance training group. For the resistance group, a controlled resistance load was applied to the paretic leg at the ankle to resist leg swing during treadmill walking. For the assistance group, a load that assists swing was applied. Main Outcome Measures Primary outcome measures were walking speed and 6-minute walking distance. Secondary measures included clinical assessments of balance, muscle tone, and quality of life. Outcome measures were evaluated before and after 6 weeks of training and at 8 weeks\u27 follow-up, and compared within group and between the 2 groups. Results After 6 weeks of robotic training, walking speed significantly increased for both groups, with no significant differences in walking speed gains observed between the 2 groups. In addition, 6-minute walking distance and balance significantly improved for the assistance group but not for the resistance group. Conclusions Applying a controlled resistance or an assistance load to the paretic leg during treadmill training may induce improvements in walking speed in individuals poststroke. Resistance training was not superior to assistance training in improving locomotor function in individuals poststroke

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

Loss of glutathione homeostasis associated with neuronal senescence facilitates TRPM2 channel activation in cultured hippocampal pyramidal neurons

<p>Abstract</p> <p>Background</p> <p>Glutathione (GSH) plays an important role in neuronal oxidant defence. Depletion of cellular GSH is observed in neurodegenerative diseases and thereby contributes to the associated oxidative stress and Ca²⁺dysregulation. Whether depletion of cellular GSH, associated with neuronal senescence, directly influences Ca²⁺permeation pathways is not known. Transient receptor potential melastatin type 2 (TRPM2) is a Ca²⁺permeable non-selective cation channel expressed in several cell types including hippocampal pyramidal neurons. Moreover, activation of TRPM2 during oxidative stress has been linked to cell death. Importantly, GSH has been reported to inhibit TRPM2 channels, suggesting they may directly contribute to Ca²⁺dysregulation associated with neuronal senescence. Herein, we explore the relation between cellular GSH and TRPM2 channel activity in long-term cultures of hippocampal neurons.</p> <p>Results</p> <p>In whole-cell voltage-clamp recordings, we observe that TRPM2 current density increases in cultured pyramidal neurons over time in vitro. The observed increase in current density was prevented by treatment with NAC, a precursor to GSH synthesis. Conversely, treatment of cultures maintained for 2 weeks in vitro with L-BSO, which depletes GSH by inhibiting its synthesis, augments TRPM2 currents. Additionally, we demonstrate that GSH inhibits TRPM2 currents through a thiol-independent mechanism, and produces a 3.5-fold shift in the dose-response curve generated by ADPR, the intracellular agonist for TRPM2.</p> <p>Conclusion</p> <p>These results indicate that GSH plays a physiologically relevant role in the regulation of TRPM2 currents in hippocampal pyramidal neurons. This interaction may play an important role in aging and neurological diseases associated with depletion of GSH.</p

Dependence of NMDA/GSK-3β Mediated Metaplasticity on TRPM2 Channels at Hippocampal CA3-CA1 Synapses

Transient receptor potential melastatin 2 (TRPM2) is a calcium permeable non-selective cation channel that functions as a sensor of cellular redox status. Highly expressed within the CNS, we have previously demonstrated the functional expression of these channels in CA1 pyramidal neurons of the hippocampus. Although implicated in oxidative stress-induced neuronal cell death, and potentially in neurodegenerative disease, the physiological role of TRPM2 in the central nervous system is unknown. Interestingly, we have shown that the activation of these channels may be sensitized by co-incident NMDA receptor activation, suggesting a potential contribution of TRPM2 to synaptic transmission. Using hippocampal cultures and slices from TRPM2 null mice we demonstrate that the loss of these channels selectively impairs NMDAR-dependent long-term depression (LTD) while sparing long-term potentiation. Impaired LTD resulted from an inhibition of GSK-3β, through increased phosphorylation, and a reduction in the expression of PSD95 and AMPARs. Notably, LTD could be rescued in TRPM2 null mice by recruitment of GSK-3β signaling following dopamine D2 receptor stimulation. We propose that TRPM2 channels play a key role in hippocampal synaptic plasticity

Strategies for Gait Retraining in a Collegiate Runner with Transfemoral Amputation: A Case Report

# Background More than fifty percent of people with limb amputations participate in sports or physical activity following amputation. Athletes with limb amputations may face additional challenges including phantom limb pain (PLP), psychological barriers, prosthetic complications, and gait abnormalities. Prevalence of PLP in the general amputee population is estimated to be as high as 85%. Despite the high prevalence of PLP, there is little research regarding the use of gait training as a treatment for PLP among both the general amputee population and athletes. # Case Description A 20-year old female collegiate track and field athlete presented with phantom knee pain brought on with running. The athlete demonstrated deficits in core and hip strength as well as decreased single leg stability bilaterally. Running gait analysis revealed circumduction with the prosthesis for limb advancement and increased vaulting with push off on the sound (uninvolved) limb. Gait retraining strategies were implemented to address video analysis findings and create a more efficient running gait and address phantom limb pain symptoms. # Outcomes Rehabilitation and gait retraining strategies were effective in improving several clinical and functional outcomes in this case. Significant improvements were noted in PLP, running gait mechanics, and the patient’s psychological and functional status as measured with a standardized outcome tool, the Patient-Reported Outcomes Measurement Information System^®^ (PROMIS^®^). # Discussion Running gait training following amputation could be a crucial component of rehabilitation for athletes in an attempt to lessen pain while running, especially in those experiencing phantom limb pain (PLP). Utilization of a multidisciplinary team in the gait retraining process is recommended. There is a need for further research to determine the effects of running gait retraining for management of PLP in athletes with amputation. # Level of Evidence

The Transient Receptor Potential Melastatin 2 (TRPM2) Channel Contributes to beta-Amyloid Oligomer-Related Neurotoxicity and Memory Impairment

In Alzheimer\u27s disease, accumulation of soluble oligomers of beta-amyloid peptide is known to be highly toxic, causing disturbances in synaptic activity and neuronal death. Multiple studies relate these effects to increased oxidative stress and aberrant activity of calcium-permeable cation channels leading to calcium imbalance. The transient receptor potential melastatin 2 (TRPM2) channel, a Ca2+-permeable nonselective cation channel activated by oxidative stress, has been implicated in neurodegenerative diseases, and more recently in amyloid-induced toxicity. Here we show that the function of TRPM2 is augmented by treatment of cultured neurons with beta-amyloid oligomers. Aged APP/PS1 Alzheimer\u27s mouse model showed increased levels of endoplasmic reticulum stress markers, protein disulfide isomerase and phosphorylated eukaryotic initiation factor 2 alpha, as well as decreased levels of the presynaptic marker synaptophysin. Elimination of TRPM2 in APP/PS1 mice corrected these abnormal responses without affecting plaque burden. These effects of TRPM2 seem to be selective for beta-amyloid toxicity, as ER stress responses to thapsigargin or tunicamycin in TRPM2(-/-) neurons was identical to that of wild-type neurons. Moreover, reduced microglial activation was observed in TRPM2(-/-)/APP/PS1 hippocampus compared with APP/PS1 mice. In addition, age-dependent spatial memory deficits in APP/PS1 mice were reversed in TRPM2(-/-)/APP/PS1 mice. These results reveal the importance of TRPM2 for beta-amyloid neuronal toxicity, suggesting that TRPM2 activity could be potentially targeted to improve outcomes in Alzheimer\u27s disease

The Prion Protein Ligand, Stress-Inducible Phosphoprotein 1, Regulates Amyloid-beta Oligomer Toxicity

In Alzheimer\u27s disease (AD), soluble amyloid-beta oligomers (A beta Os) trigger neurotoxic signaling, at least partially, via the cellular prion protein (PrPC). However, it is unknown whether other ligands of PrPC can regulate this potentially toxic interaction. Stress-inducible phosphoprotein 1 (STI1), an Hsp90 cochaperone secreted by astrocytes, binds to PrPC in the vicinity of the A beta O binding site to protect neurons against toxic stimuli. Here, we investigated a potential role of STI1 in A beta O toxicity. We confirmed the specific binding of A beta Os and STI1 to the PrP and showed that STI1 efficiently inhibited A beta O binding to PrP in vitro (IC50 of similar to 70 nM) and also decreased A beta O binding to cultured mouse primary hippocampal neurons. Treatment with STI1 prevented A beta O-induced synaptic loss and neuronal death in mouse cultured neurons and long-term potentiation inhibition in mouse hippocampal slices. Interestingly, STI1-haploinsufficient neurons were more sensitive to A beta O-induced cell death and could be rescued by treatment with recombinant STI1. Noteworthy, both A beta O binding to PrPC and PrPC-dependent A beta O toxicity were inhibited by TPR2A, the PrPC-interacting domain of STI1. Additionally, PrPC-STI1 engagement activated alpha 7 nicotinic acetylcholine receptors, which participated in neuroprotection against A beta O-induced toxicity. We found an age-dependent upregulation of cortical STI1 in the APPswe/PS1dE9 mouse model of AD and in the brains of AD-affected individuals, suggesting a compensatory response. Our findings reveal a previously unrecognized role of the PrPC ligand STI1 in protecting neurons in AD and suggest a novel pathway that may help to offset A beta O-induced toxicity

Outbreak of Neisseria meningitidis capsular group W among scouts returning from the World Scout Jamboree, Japan, 2015

The 23rd World Scout Jamboree was held in Japan from 28 July to 8 August 2015 and was attended by over 33,000 scouts from 162 countries. An outbreak of invasive meningococcal disease capsular group W was investigated among participants, with four confirmed cases identified in Scotland, who were all associated with one particular scout unit, and two confirmed cases in Sweden; molecular testing showed the same strain to be responsible for illness in both countries. The report describes the public health action taken to prevent further cases and the different decisions reached with respect to how wide to extend the offer of chemoprophylaxis in the two countries; in Scotland, chemoprophylaxis was offered to the unit of 40 participants to which the four cases belonged and to other close contacts of cases, while in Sweden chemoprophylaxis was offered to all those returning from the Jamboree. The report also describes the international collaboration and communication required to investigate and manage such multinational outbreaks in a timely manner

A global biodiversity observing system to unite monitoring and guide action

The rate and extent of global biodiversity change is surpassing our ability to measure, monitor and forecast trends. We propose an interconnected worldwide system of observation networks — a global biodiversity observing system (GBiOS) — to coordinate monitoring worldwide and inform action to reach international biodiversity targets.acceptedVersio