Inhibition of experimental autoimmune encephalomyelitis in Lewis rats by nasal administration of encephalitogenic MBP peptides: synergistic effects of MBP 68-86 and 87-99

Induction of mucosal tolerance by inhalation of soluble peptides with defined T cell epitopes is receiving much attention as a means of specifically down-regulating pathogenic T cell reactivities in autoimmune and allergic disorders. Experimental autoimmune encephalomyelitis (EAE) induced in the Lewis rat by immunization with myelin basic protein (MBP) and Freund's adjuvant (CFA) is mediated by CD4+ T cells specific for the MBP amino acid sequences 68-86 and 87-99. To further define the principles of nasal tolerance induction, we generated three different MBP peptides (MBP 68-86, 87-99 and the non- encephalitogenic peptide 110-128), and evaluated whether their nasal administration on day -11, -10, -9, -8 and -7 prior to immunization with guinea pig MBP (gp-MBP) + CFA confers protection to Lewis rat EAE. Protection was achieved with the encephalitogenic peptides MBP 68-86 and 87-99, MBP 68-86 being more potent, but not with MBP 110-128. Neither MBP 68-86 nor 87-99 at doses used conferred complete protection to gp-MBP-induced EAE. In contrast, nasal administration of a mixture of MBP 68-86 and 87-99 completely blocked gp-MBP-induced EAE even at lower dosage compared to that being used for individual peptides. Rats tolerized with MBP 68-86 + 87-99 nasally showed decreased T cell responses to MBP reflected by lymphocyte proliferation and IFN-gamma ELISPOT assays. Rats tolerized with MBP 68-86 + 87-99 also had abrogated MBP-reactive IFN-gamma and tumor necrosis factor-alpha mRNA expression in lymph node cells compared to rats receiving MBP 110-128 nasally, while similar low levels of MBP-reactive transforming growth factor-beta and IL-4 mRNA expressing cells were observed in the two groups. Nasal administration of MBP 68-86 + 87-99 only slightly inhibited guinea pig spinal cord homogenate-induced EAE, and passive transfer of spleen mononuclear cells from MBP 68-86 + 87-99-tolerized rats did not protect naive rats from EAE. Finally, we show that nasal administration of MBP 68-86 + 87-99 can reverse ongoing EAE induced with gp-MBP, although higher doses are required compared to the dosage needed for prevention. In conclusion, nasal administration of encephalitogenic MBP peptides can induce antigen-specific T cell tolerance and confer incomplete protection to gp-MBP-induced EAE, and MBP 68-86 and 87-99 have synergistic effects. Non-regulatory mechanisms are proposed to be responsible for tolerance development after nasal peptide administration.      

Analysis of the ST-segment in terms of principal components: application on multichannel magnetocardiographic recordings

Parameterization of the ST-segment is used as a tool for risk stratification for patients to suffer from ventricular tachycardia. This parameterization is performed in terms of Principal Component Analysis (PCA) applied on multichannel magnetocardiographic (MCG) recordings. 55-channel MCG was recorded from 14 normal persons, 10 patients with CHD, 14 patients with MI, and six patients with VT. We found a significantly (p?<?0.05) lower PCA-score in patients with MI compared to normals. The lowest PCA-score was found in VT patients. Significant differences can be found between VT patients and normals and also between VT patients and CHD patients.     

Therapeutic Interventions for Increasing Ankle Dorsiflexion After Ankle Sprain: A Systematic Review

Context:

Clinicians perform therapeutic interventions, such as stretching, manual therapy, electrotherapy, ultrasound, and exercises, to increase ankle dorsiflexion. However, authors of previous studies have not determined which intervention or combination of interventions is most effective.

Objective:

To determine the magnitude of therapeutic intervention effects on and the most effective therapeutic interventions for restoring normal ankle dorsiflexion after ankle sprain.

Data Sources:

We performed a comprehensive literature search in Web of Science and EBSCO HOST from 1965 to May 29, 2011, with 19 search terms related to ankle sprain, dorsiflexion, and intervention and by cross-referencing pertinent articles.

Study Selection:

Eligible studies had to be written in English and include the means and standard deviations of both pretreatment and posttreatment in patients with acute, subacute, or chronic ankle sprains. Outcomes of interest included various joint mobilizations, stretching, local vibration, hyperbaric oxygen therapy, electrical stimulation, and mental-relaxation interventions.

Data Extraction:

We extracted data on dorsiflexion improvements among various therapeutic applications by calculating Cohen d effect sizes with associated 95% confidence intervals (CIs) and evaluated the methodologic quality using the Physiotherapy Evidence Database (PEDro) scale.

Data Synthesis:

In total, 9 studies (PEDro score = 5.22 ± 1.92) met the inclusion criteria. Static-stretching interventions with a home exercise program had the strongest effects on increasing dorsiflexion in patients 2 weeks after acute ankle sprains (Cohen d = 1.06; 95% CI = 0.12, 2.42). The range of effect sizes for movement with mobilization on ankle dorsiflexion among individuals with recurrent ankle sprains was small (Cohen d range = 0.14 to 0.39).

Conclusions:

Static-stretching intervention as a part of standardized care yielded the strongest effects on dorsiflexion after acute ankle sprains. The existing evidence suggests that clinicians need to consider what may be the limiting factor of ankle dorsiflexion to select the most appropriate treatments and interventions. Investigators should examine the relationship between improvements in dorsiflexion and patient progress using measures of patient self-reported functional outcome after therapeutic interventions to determine the most appropriate forms of therapeutic interventions to address ankle-dorsiflexion limitation.Key Words: chronic ankle instability, range of motion, stretching, joint mobilization

Key Points

• A static-stretching intervention as part of a standardized home exercise program had the strongest effects on ankle-dorsiflexion improvement after acute ankle sprains.
• Clinicians need to consider what may be the limiting factor of ankle dorsiflexion to select the most appropriate treatments and interventions.
• Investigators should examine the long-term effects of treatments on ankle dorsiflexion and a relationship between an improvement in ankle dorsiflexion and measures of patient self-reported and physical function to determine the most appropriate forms of therapeutic interventions to address limited dorsiflexion.

Lateral ankle sprain has been documented to be the most common lower extremity injury sustained during sport participation.^1–4 Approximately 85% of all ankle sprains result from an inversion mechanism and damage to the lateral ligamentous complex of the ankle.⁵ Injury to the lateral ligamentous complex at the ankle joint results in pain, swelling, and limited osteokinematics.⁶ A loss of normal ankle dorsiflexion usually is observed at the talocrural joint after lateral ankle sprain.^7–12The amount of available ankle dorsiflexion plays a key role in the cause of lower extremity injuries.^7,13–22 Limitation of dorsiflexion may be a predisposition to reinjury of the ankle^11,16 and several future lower limb injuries, including plantar fasciopathy,^13,20,21 lateral ankle sprains,^13,15,17,19 iliotibial band syndrome,¹⁴ patellofemoral pain syndrome,¹⁸ patellar tendinopathy,²² and medial tibial stress syndrome.¹⁴The importance of restoring ankle dorsiflexion after an acute ankle sprain often is emphasized in rehabilitation guidelines,⁹ and proper recovery of ankle dorsiflexion is a vital component of ankle rehabilitation. Inadequate restoration of ankle dorsiflexion may increase the risk of developing recurrent ankle sprain^11,16 and limit functional activities, such as walking, with long-term pain and disability.²³ Limited ankle-dorsiflexion range of motion (ROM) after lateral ankle sprain has been considered a predisposing factor for recurrent ankle sprain because diminished dorsiflexion prevents the ankle from reaching its closed-pack position by holding the ankle in a hypersupinated position. Therefore, ensuring appropriate restoration of ankle dorsiflexion after ankle sprain has important clinical implications for restoring full functional abilities, ultimately leading to reduced risk of recurrent ankle sprain.Clinicians perform several therapeutic interventions, such as stretching, manual therapy, electrotherapy, ultrasound, and exercises, to increase ankle dorsiflexion. However, the intervention or combination of interventions that most effectively improves ankle dorsiflexion has not been established. In previous systematic reviews,^24–26 researchers have examined the effects of specific intervention techniques of manipulative therapy on various outcome variables. In addition, Bleakley et al²⁷ conducted a systematic review with a comprehensive search of various therapeutic interventions to provide evidence for the management of ankle sprains and the prevention of long-term complications; however, the authors focused only on patients with an acute ankle sprain. Therefore, the purpose of this systematic review was to determine the magnitude of therapeutic intervention effects on and the most effective therapeutic interventions for restoring normal ankle dorsiflexion after ankle sprain. In contrast to previous reviews,^24–26 we comprehensively searched the existing literature to determine the effectiveness of various therapeutic intervention techniques in restoring ankle dorsiflexion in patients with acute, subacute, or recurrent ankle sprains. By providing a quantitative estimate of the magnitude of the effect of therapeutic interventions, our review provides a new perspective on the evidence of interventions to restore ankle dorsiflexion in various stages of ankle-sprain conditions.     

Different Modes of Feedback and Peak Vertical Ground Reaction Force During Jump Landing: A Systematic Review

Context:

Excessive ground reaction force when landing from a jump may result in lower extremity injuries. It is important to better understand how feedback can influence ground reaction force (GRF) and potentially reduce injury risk.

Objective:

To determine the effect of expert-provided (EP), self-analysis (SA), and combination EP and SA (combo) feedback on reducing peak vertical GRF during a jump-landing task.

Data Sources:

We searched the Web of Science database on July 1, 2011; using the search terms ground reaction force, landing biomechanics, and feedback elicited 731 initial hits.

Study Selection:

Of the 731 initial hits, our final analysis included 7 studies that incorporated 32 separate data comparisons.

Data Extraction:

Standardized effect sizes and 95% confidence intervals (CIs) were calculated between pretest and posttest scores for each feedback condition.

Data Synthesis:

We found a homogeneous beneficial effect for combo feedback, indicating a reduction in GRF with no CIs crossing zero. We also found a homogeneous beneficial effect for EP feedback, but the CIs from 4 of the 10 data comparisons crossed zero. The SA feedback showed strong, definitive effects when the intervention included a videotape SA, with no CIs crossing zero.

Conclusions:

Of the 7 studies reviewed, combo feedback seemed to produce the greatest decrease in peak vertical GRF during a jump-landing task.Key Words: injury prevention, knee, feedback, landing biomechanics

Key Points

• All modes of feedback effectively reduced ground reaction force during a jump-landing task.
• Combination feedback demonstrated the strongest effect sizes for reducing ground reaction force compared with expert-provided and self-analysis feedback.
• More high-quality studies are needed to support the use of feedback interventions for altering lower extremity landing forces and decreasing lower extremity injury risk.

Landing is an essential athletic task used during many different sporting activities, including basketball, volleyball, and gymnastics.^1–3 The act of jumping and landing during these different sporting activities involves different magnitudes of ground reaction forces (GRFs).⁴ The GRF magnitudes have been reported to be greatest during the landing phase of a jump when the knee is between 0° and 25° of flexion, a point at which the knee must resist a rapid change in kinetic energy.⁵ Excessive GRFs may result in lower extremity injuries.^3,6–8The knee is largely responsible for energy attenuation of the lower extremity when landing from a jump,^9,10 so this joint may have increased susceptibility to injury during such a task. Researchers have identified the presence of damage to the subchondral bone, cartilage, and soft tissue due to extreme forces imposed on the lower extremity during selected landing activities.¹¹ A positive moderate correlation between increased vertical GRF and increased anterior tibial acceleration when landing from a jump supports the hypothesis that individuals landing with greater impact loads could have an increased risk of anterior cruciate ligament (ACL) injury.¹² Given that the main function of the ACL is preventing anterior translation of the tibia, landing with increased GRF and thus increased anterior tibial acceleration may place more strain on the ligament, increasing the likelihood of ligament rupture.To reduce the risk of injury associated with increased GRF during landing, different interventions have been used to decrease GRF by altering lower extremity biomechanics during landing. To our knowledge, no researchers have evaluated whether reducing an individual''s GRF decreases his or her risk of injury, but compelling data have suggested that higher GRF and other factors may increase the risk of substantially injuring the knee.¹³ Specifically, prospective data have shown that GRF during a jump-landing task was 20% higher in female athletes who sustained an ACL rupture than in athletes who did not.¹³ These data spark a compelling but unsubstantiated theory that reducing high GRFs may coincide with a decreased risk of knee injury. Clinical trials to evaluate the true prophylactic capabilities of reducing GRF to limit knee injuries are likely expensive and logistically difficult to conduct. Therefore, successfully identifying an intervention that can manipulate GRF is important before these studies are performed.Various methods have been implemented to teach proper landing biomechanics to prevent future injury.¹⁴ For example, feedback is a modality used to prompt an individual to correct potentially harmful biomechanics and reduce high GRF. Feedback can be defined as sensory information made available to the participant during or after a task in an attempt to alter a movement.¹⁵ It can include information related to the sensations associated with the movement (eg, the feel or sound the participant experiences while performing the task) or related to the result of the action with respect to the environmental goal.¹⁵ Different modes of feedback have been reported and include (1) expert-provided (EP) feedback through oral correction,¹⁶ oral instruction,^17,18 or visual demonstration¹⁶; (2) self-analysis (SA) feedback conducted with videotape correction^19,20 or self-correction from previous trials¹⁷; and (3) combination (combo) feedback that uses both EP and SA feedback.^19,21 Through EP feedback, professionals can analyze movements and provide various forms of oral and visual feedback to alter that task, whereas SA feedback requires the participant to identify movement characteristics that need to be altered and to adjust to change that specific task.Recently, a surge of injury-prevention programs have been implemented to reduce the risk of ACL injury in athletes.^22,23 These programs often incorporate feedback techniques and aim to reduce the risk of injury by teaching athletes to land properly to reduce stress on the lower extremity and potentially prevent acute and chronic lower extremity injuries.¹⁹ Altering the landing phase of a jump via various feedback methods could result in decreased GRFs and increased flexion angles at the knee, which may decrease the risk of lower extremity injury.Although programs incorporating feedback are increasing in popularity, the magnitude of the effect that different types of feedback have on reducing GRF has not been evaluated systematically. Knowledge of the efficacy of feedback on reducing potentially harmful GRF may help clinicians determine whether feedback should be incorporated into jump-landing training programs. Therefore, the purpose of our study was to systematically evaluate the current literature to determine the magnitude of immediate and delayed effects of EP, SA, and combo feedback interventions on reducing peak vertical GRF during a jump-landing task in healthy individuals.     

Quadriceps neural alterations in anterior cruciate ligament reconstructed patients: A 6‐month longitudinal investigation

The purpose of this investigation was to evaluate differences in quadriceps corticospinal excitability, spinal‐reflexive excitability, strength, and voluntary activation before, 2 weeks post and 6 months post‐anterior cruciate ligament reconstruction (ACLr). This longitudinal, case‐control investigation examined 20 patients scheduled for ACLr (11 females, 9 males; age: 20.9 ± 4.4 years; height:172.4 ± 7.5 cm; weight:76.2 ± 11.8 kg) and 20 healthy controls (11 females, 9 males; age:21.7 ± 3.7 years; height: 173.7 ± 9.9 cm; weight: 76.1 ± 19.7 kg). Maximal voluntary isometric contractions (MVIC), central activation ratio (CAR), normalized Hoffmann spinal reflexes, active motor threshold (AMT), and normalized motor‐evoked potential (MEP) amplitudes at 120% of AMT were measured in the quadriceps muscle at the specific time points. ACLr patients demonstrated bilateral reductions in spinal‐reflexive excitability compared with controls before surgery (P = 0.02) and 2 weeks post‐surgery (P ≤ 0.001). ACLr patients demonstrated higher AMT at 6 months post‐surgery (P ≤ 0.001) in both limbs. No MEP differences were detected. Quadriceps MVIC and CAR were lower in both limbs of the ACLr group before surgery and 6 months post‐surgery (P ≤ 0.05) compared with controls. Diminished excitability of spinal‐reflexive and corticospinal pathways are present at different times following ACLr and occur in combination with clinical deficits in quadriceps strength and activation. Early rehabilitation strategies targeting spinal‐reflexive excitability may help improve postoperative outcomes, while later‐stage rehabilitation may benefit from therapeutic techniques aimed at improving corticospinal excitability.