Receptor for Complement Peptide C3a: A Therapeutic Target for Neonatal Hypoxic-Ischemic Brain Injury.

Receptor for complement peptide C3a: a therapeutic target for neonatal hypoxic-ischemic brain injury.

FASEB J. 2013 Jun 4;
Järlestedt K, Rousset CI, Ståhlberg A, Sourkova H, Atkins AL, Thornton C, Barnum SR, Wetsel RA, Dragunow M, Pekny M, Mallard C, Hagberg H, Pekna M

Complement is an essential component of inflammation that plays a role in ischemic brain injury. Recent reports demonstrate novel functions of complement in normal and diseased CNS, such as regulation of neurogenesis and synapse elimination. Here, we examined the role of complement-derived peptide C3a in unilateral hypoxia-ischemia (HI), a model of neonatal HI encephalopathy. HI injury was induced at postnatal day 9 (P9), and loss of hippocampal tissue was determined on P31. We compared WT mice with transgenic mice expressing C3a under the control of glial fibrillary acidic protein promoter, which express biologically active C3a only in CNS and without the requirement of a priori complement activation. Further, we injected C3a peptide into the lateral cerebral ventricle of mice lacking the C3a receptor (C3aR) and WT mice and assessed HI-induced memory impairment 41 d later. We found that HI-induced tissue loss in C3a overexpressing mice was reduced by 50% compared with WT mice. C3a peptide injected 1 h after HI protected WT but not C3aR-deficient mice against HI-induced memory impairment. Thus, C3a acting through its canonical receptor ameliorates behavioral deficits after HI injury, and C3aR is a novel therapeutic target for the treatment of neonatal HI encephalopathy.-Järlestedt, K., Rousset, C. I., Ståhlberg, A., Sourkova, H., Atkins, A. L., Thornton, C., Barnum, S. R., Wetsel, R. A., Dragunow, M., Pekny, M., Mallard, C., Hagberg, H., Pekna, M. Receptor for complement peptide C3a: a therapeutic target for neonatal hypoxic-ischemic brain injury. HubMed – rehab


Place of death, and its relation with underlying cause of death, in Parkinson’s disease, motor neurone disease, and multiple sclerosis: A population-based study.

Palliat Med. 2013 Jun 4;
Sleeman KE, Ho YK, Verne J, Glickman M, Silber E, Gao W, Higginson IJ,

Background:Little is known about place of death in chronic neurological diseases. Mortality statistics are ideal for examining trends in place of death, but analyses are limited by coding rule changes.Aim:To examine the relationship between place of death and underlying cause of death in Parkinson’s disease, multiple sclerosis and motor neurone disease and the impact of coding rule changes on analysis of place of death.Design:Population-based study. Proportion ratios for death in hospice, home, care home and hospital were calculated according to underlying cause of death, using multivariable Poisson regression.Participants:Deaths in England (1993-2010) with any mention of Parkinson’s disease, multiple sclerosis or motor neurone disease as a cause of death, identified from national mortality data.Results:In this study, 125,242 patients with Parkinson’s disease, 23,501 with multiple sclerosis, and 27,030 with motor neurone disease were included. Home deaths ranged from 9.7% (Parkinson’s disease) to 27.1% (motor neurone disease), hospice deaths ranged from 0.6% (Parkinson’s disease) to 11.2% (motor neurone disease) and hospital deaths ranged from 43.4% (Parkinson’s disease) to 55.8% (multiple sclerosis). In Parkinson’s disease and multiple sclerosis, cancer as underlying cause of death increased likelihood of hospice death (proportion ratio (PR): 18.8, 95% confidence interval (CI) = 16.1-22.0; 8.88, 95% CI = 7.49-10.5) and home death (PR: 1.91, 95% CI = 1.80-2.04; 1.71, 95% CI = 1.56-1.88). Dementia as underlying cause of death increased likelihood of care home death in Parkinson’s disease (PR: 1.25, 95% CI = 1.19-1.32), multiple sclerosis (PR: 1.73, 95% CI = 1.22-2.45) and motor neurone disease (PR: 2.36, 95% CI = 1.31-4.27).Conclusions:Underlying cause of death has a marked effect on place of death. The effects of coding rule changes are an essential consideration for all research using underlying cause of death to study place of death. HubMed – rehab


Rehabilitation needs after bariatric surgery.

Eur J Phys Rehabil Med. 2013 Jun; 49(3): 431-437
Faintuch J, Souza SA, Fabris SM, Cecconello I, Capodaglio P

Background: Bariatric surgery has grown from an obscure experimental procedure to one of the most popular operations in the world. Such accelerated progress left many gaps, notably concerning subsequent rehabilitation needs of this population. Aim: In the present study, a brief description of both the patients and the interventions is provided, along with potentially disabling features especially concerning the locomotor system, which has received comparatively little attention . Design: Based on reported protocols and actual experience, major issues are addressed. Setting: Bariatric patients are initially managed in the hospital, however long-term and even lifetime needs may be recognized, requiring major lifestyle and physical activity changes. These have to be focused in all settings, inside and outside the healthcare institutions. Population: Initially only adults were considered bariatric candidates, however currently also adolescents and the elderly are admitted in many centers. Results: Bariatric weight loss is certainly successful for remission or prevention of metabolic, cardiovascular and cancer comorbidities. Yet benefits for bones, joints and muscles, along with general physical performance are still incompletely established. This should be no reason for denying continued care to such individuals, within the context of well-designed protocols, as available evidence points toward favorable rehabilitation in the realms of physical, social and workplace activities. Conclusion: The importance of a physiatric curriculum in medical schools has been emphasized. Even more crucial is the presence of such a specialists in obesity and bariatric teams, a requirement recognized in a few countries but not in others. Clinical Rehabilitation Impact: The relevance of obesity as a disabling condition is reviewed, along with the positive changes induced by surgical weight loss. Although obesity alleviation is a legitimate end-point it is not a sufficient one. The shortcomings of such result from the point of view of physical normalization are outlined, and recommendations are suggested. HubMed – rehab


Outpatient rehabilitation outcomes in obese patients with orthopedic conditions.

Eur J Phys Rehabil Med. 2013 Jun; 49(3): 419-29
Vincent HK, Seay AN, Montero C, Vincent KR

Background: Obesity is related to the development of functional and mobility impairment, musculoskeletal pain and orthopedic problems. Irrespective of age, obese children and adults have impaired walking capacity and body transfer ability, and difficulties navigating obstacle courses or community spaces. Obesity is related to relative strength deficits, musculoskeletal pain, kinesiophobia, low self-efficacy and a decline in quality of life. Aim: This review provides an update of the available evidence for the efficacy of outpatient rehabilitation programs for the treatment of disabling obesity. Results: Outpatient rehabilitation programs can effectively improve muscle strength, self-confidence and physical function. Key rehabilitation components should include aerobic exercise (AX), resistance exercise (RX) and cognitive strategies to cope with the unique challenges posed by obesity. Available high quality evidence indicates that 3-18 month rehabilitation programs that included aerobic and strengthening exercise (2-3 days per week) with caloric restriction (typically 500-750 kcal deficit/ day), elicited the best changes in functional performance measures compared with exercise or diet alone. Conclusion: Comprehensive outpatient rehabilitation interventions coupled with diet can catalyze lifestyle patterns that improve and preserve physical function over the life span. HubMed – rehab