Isokinetic strengthening and neuromuscular electrical stimulation protocol impact on physical performances,functional status and quality of life in knee osteoarthritis overweight/obese women

BackgroundKnee muscle weakness associated with overweight/obesity can lead to impairment of vital daily function in knee osteoarthritis patients. This study investigated the effect of a knee eccentric isokinetic muscle strength (IMS) training program combined with neuromuscular electrical stimulation (NMES) on muscle strength and flexibility, joint ROM, functional status, physical performance, and quality of life in knee osteoarthritis overweight/obese women.MethodsThirty-six women were randomized into three groups, two experimental groups (EG) and a control group following a classic rehabilitation program. During 6 weeks of two sessions/week, one of the two EGs performed an IMS program (ISO.G); the other underwent combined IMS and NMES training (ISO + NMES.G). All patients were evaluated with clinical examination, isokinetic test at 60°/s and 240°/s speeds, physical performance tests related to activities of daily living, and Knee injury and Osteoarthritis Outcome Score (KOOS) quality of life questionnaire, before and after the intervention.ResultsIn the 10-m walk, chair stand, stair climb and monopodal stance tests, muscle flexibility and quality of life scores showed significant improvement for ISO.G (P = 0.000) and ISO + NMES.G (P = 0.000). Concentric strength at 240°/s was improved in ISO + NMES.G (P = 0.000) unlike the muscle strength at 60°/s (quadriceps, P = 0.104; hamstrings, P = 0.171), force asymmetry (P = 0.481) and post-intervention joint ROM (P = 0.309).ConclusionsThe combination of IMS and NMES shows significant superiority over the usual rehabilitation program for the majority of the parameters measured for optimal management of knee osteoarthritis.     

Stability of phantom limb phenomena after upper limb amputation: a longitudinal study

Amputees may experience stump pain (SP), phantom limb (PL) sensations, pain, and/or a general awareness of the missing limb. The mechanisms underlying these perceptions could involve nervous system neuroplasticity and be reflected in altered sensory function of the residual limb. Since little is known about the progression of post-amputation sensory phenomena over time, we longitudinally evaluated the stability of, and relationships among: 1) subjective reports of PL sensations, pain, awareness, and SP, 2) stump tactile and tactile spatial acuity thresholds, and 3) use of a functional vs. a cosmetic prosthesis in 11 otherwise healthy individuals with recent unilateral, traumatic upper-extremity amputation. Subjects were evaluated within 6 months and at 1-3 years after amputation. Processing of tactile sensory information from the stump remained stable over the study time period. PL awareness was frequent, stable over time, intense, and occurred with or without PL sensations. Functional prosthetic use correlated with stable vividness of PL awareness whereas subjects who used a cosmetic prosthesis had less vivid PL awareness at follow-up. Initial SP correlated with follow-up SP, the initial PL pain correlated with follow-up PL pain but neither initial nor follow-up SP appear to be related to follow-up PL pain after accounting for initial PL pain intensity. Neither limb temperature nor prosthesis-use correlated with the initial vs. follow-up change in PL pain intensity. These data provide evidence that PL pain described 1-3 years after an amputation is not related in any simple way to peripheral sensory function, SP, or limb temperature; and PL awareness but not PL pain may be influenced by the frequent use of a functional prosthesis.     

Phantom limb pain – A phenomenon of proprioceptive memory?

Despite the amount of research that has been conducted on phantom limb pain (PLP), the etiology of the condition remains unknown, and treatment options are limited. After an individual loses a limb, the brain continues to detect the presence of the missing limb even though it is no longer attached to the body, likely through proprioceptive signals. The majority of patients with amputations either report the feeling of volitional control over their phantom or a phantom limb that is frozen in a specific position. Many patients also experience PLP. Here we propose a new theory, termed “proprioceptive memory,” which may explain some of the unique experiences amputees encounter. We also suggest that memories of the limb’s position prior to amputation remain embedded within an individual’s subconscious, and pain memories that may be associated with each limb position contribute not only to PLP, but to the experience of a fixed or frozen limb. We suspect that there are memory networks for pain – and other sensations, either positive or negative – that are associated with each limb position, and propose that these memories evolved to protect our bodies from repeated injury. A discussion of mirror therapy as a treatment option for PLP is also provided, as well as an explanation for the efficacy of mirror therapy. The paper offers a unique insight into how and why amputees experience these unusual phenomena.     

Mobilization without immune depletion fails to restore immunological tolerance or preserve beta cell function in recent onset type 1 diabetes

Granulocyte colony‐stimulating factor (G‐CSF) has been used to restore immune competence following chemoablative cancer therapy and to promote immunological tolerance in certain settings of autoimmunity. Therefore, we tested the potential of G‐CSF to impact type 1 diabetes (T1D) progression in patients with recent‐onset disease [n = 14; n = 7 (placebo)] and assessed safety, efficacy and mechanistic effects on the immune system. We hypothesized that pegylated G‐CSF (6 mg administered subcutaneously every 2 weeks for 12 weeks) would promote regulatory T cell (T_reg) mobilization to a degree capable of restoring immunological tolerance, thus preventing further decline in C‐peptide production. Although treatment was well tolerated, G‐CSF monotherapy did not affect C‐peptide production, glycated haemoglobin (HbA1c) or insulin dose. Mechanistically, G‐CSF treatment increased circulating neutrophils during the 12‐week course of therapy (P < 0·01) but did not alter T_reg frequencies. No effects were observed for CD4⁺ : CD8⁺ T cell ratio or the ratio of naive : memory (CD45RA⁺/CD45RO⁺) CD4⁺ T cells. As expected, manageable bone pain was common in subjects receiving G‐CSF, but notably, no severe adverse events such as splenomegaly occurred. This study supports the continued exploration of G‐CSF and other mobilizing agents in subjects with T1D, but only when combined with immunodepleting agents where synergistic mechanisms of action have previously demonstrated efficacy towards the preservation of C‐peptide.     

Novel assessment of microvascular changes in idiopathic restless legs syndrome (Willis–Ekbom disease)

Many patients with restless legs syndrome (Willis–Ekbom disease) complain of burning sensations in their feet associated with the desire to move, such that they seek cooler environments. This pilot study aimed to characterise the microvascular skin changes in 12 patients with restless legs syndrome compared with 12 age‐ and sex‐matched controls. Patients with moderate or severe restless legs syndrome and controls underwent detailed thermovascular assessment in a controlled temperature room at three different stages (normothermic phase 23 °C, hot phase 30 °C, cold phase 18 °C). Microvascular activity was recorded during all phases by bilateral great toe laser‐Doppler flowmetry and also by whole‐body thermography. Patient and control measurements were compared. The study protocol was well tolerated. Parameters extracted from the laser‐Doppler flowmetry measurements were used to model a logistic function using binary logistic regression. This demonstrated a statistically significant difference between patients with restless legs syndrome and healthy controls (P < 0.001). Visual inspection of the body thermography image sequences showed increased lower limb movement in patients with restless legs syndrome patients compared with controls. Thermography analysis also showed significant differences between foot temperatures in patients with restless legs syndrome compared with controls during the hot phase (P = 0.011). Notably, patients with restless legs syndrome had more uniform foot temperatures, whereas controls had a wider variability in surface temperature across the feet. This novel study demonstrates impaired microvascular circulation in patients with restless legs syndrome in comparison to matched controls and a potential mechanism for the sensation of burning feet. The protocol also provides an experimental paradigm to test therapeutic interventions for the future.     

Neuromuscular electrical stimulation has a global effect on corticospinal excitability for leg muscles and a focused effect for hand muscles

The afferent volley generated during neuromuscular electrical stimulation (NMES) can increase the excitability of human corticospinal (CS) pathways to muscles of the leg and hand. Over time, such increases can strengthen CS pathways damaged by injury or disease and result in enduring improvements in function. There is some evidence that NMES affects CS excitability differently for muscles of the leg and hand, although a direct comparison has not been conducted. Thus, the present experiments were designed to compare the strength and specificity of NMES-induced changes in CS excitability for muscles of the leg and hand. Two hypotheses were tested: (1) For muscles innervated by the stimulated nerve (target muscles), CS excitability will increase more for the hand than for the leg. (2) For muscles not innervated by the stimulated nerve (non-target muscles), CS excitability will increase for muscles of the leg but not muscles of the hand. NMES was delivered over the common peroneal (CP) nerve in the leg or the median nerve at the wrist using a 1-ms pulse width in a 20 s on, 20 s off cycle for 40 min. The intensity was set to evoke an M-wave that was ~15% of the maximal M-wave in the target muscle: tibialis anterior (TA) in the leg and abductor pollicis brevis (APB) in the hand. Ten motor-evoked potentials (MEPs) were recorded from the target muscles and from 2 non-target muscles of each limb using transcranial magnetic stimulation delivered over the “hotspot” for each muscle before and after the NMES. MEP amplitude increased significantly for TA (by 45 ± 6%) and for APB (56 ± 8%), but the amplitude of these increases was not different. In non-target muscles, MEPs increased significantly for muscles of the leg (42 ± 4%), but not the hand. Although NMES increased CS excitability for target muscles to the same extent in the leg and hand, the differences in the effect on non-target muscles suggest that NMES has a “global” effect on CS excitability for the leg and a “focused” effect for the hand. These differences may reflect differences in the specificity of afferent projections to the cortex. Global increases in CS excitability for the leg could be advantageous for rehabilitation as NMES applied to one muscle could strengthen CS pathways and enhance function for multiple muscles.     

Cortical reorganization and phantom phenomena in congenital and traumatic upper-extremity amputees

The relationship between phantom limb phenomena and cortical reorganization was examined in five subjects with congenital absence of an upper limb and nine traumatic amputees. Neuromagnetic source imaging revealed minimal reorganization of primary somatosensory cortex in the congenital amputees (M=0.69 cm, SD 0.24) and the traumatic amputees without phantom limb pain (M=0.27 cm, SD 0.25); the amputees with phantom limb pain showed massive cortical reorganization (M=2.22 cm, SD 0.78). Phantom limb pain and nonpainful phantom limb phenomena were absent in the congenital amputees. Whereas phantom limb pain was positively related to cortical reorganization (r=0.87), nonpainful phantom phenomena were not significantly correlated with cortical reorganization (r=0.34). Sensory discrimination was normal and mislocalization (referral of stimulation-induced sensation to a phantom limb) was absent in the congenital amputees. The role of peripheral and central factors in the understanding of phantom limb pain and phantom limb phenomena is discussed in view of these findings. Received: 4 June 1997 / Accepted: 13 September 1997     

Construction and Immunogenicity of the DNA Vaccine of Mycobacterium Tuberculosis Dormancy Antigen Rv1733c

We aimed to construct the DNA vaccine encoding Mycobacterium Tuberculosis (Mtb) dormancy antigen Rv1733c and investigate its immunogenicity in mice. The recombinant plasmid pcDNA‐Rv1733c was transfected into P815 cells and its product was detected by indirect immunofluorescence. The mice were immunized once every 2 weeks by intramuscular injection of pcDNA‐Rv1733c plasmid for a total of three times. The specific antibodies in the serum of the immunized mice were detected by enzyme‐linked immunosorbent assay at the indicted time. Enzyme‐linked immunosorbent spot was applied to determine the levels of IFN‐γ, IL‐2 and IL‐4 secreted by splenic lymphocytes. Total cytotoxicity T lymphocyte (CTL) active of the splenic lymphocytes was detected by lactate dehydrogenase assay. Additionally, we analysed the percentages of CD4⁺ and CD8⁺ T cells in splenic lymphocytes using flow cytometry. The specific antibody was detected at 2 weeks after the first immunization, and the antibody titre was increased with time which was reached to 1:1600 at 8 weeks. The stimulation index of spleen lymphocytes and the levels of IFN‐γ, IL‐2 and IL‐4 of pcDNA‐Rv1733c‐immunized mice were both higher than those of saline‐immunized mice (P < 0.05). However, no difference was found in the percentages of CD4⁺ and CD8⁺ T cells and the activity of CTL between the pcDNA‐Rv1733c‐ and saline‐immunized mice (P > 0.05). So we got the conclusion that the plasmid pcDNA‐Rv1733c DNA could induce specific humoral and cellular immunity in mice. Improving the immune effect of Rv1733c by several strategies, such as choosing appropriate immunization route and adjuvant, would be significant for Rv1733c as new tuberculosis vaccine.     

Pain management coaching: The missing link in the care of individuals living with chronic pain

This article describes the preliminary findings on the efficacy of a Comprehensive Telephonic Pain Self‐Management Coaching Program (CTPSCP ) in improving pain‐related outcomes for adults being treated for chronic pain. Analyses of pain‐related data collected by administering the Pain Outcomes Questionnaire‐For Civilians (POQ ‐C ) to participants in a CTPSCP at intake, at the 6‐month mid‐point (n  = 51), and at the 12‐month completion of the program (n  = 33). A paired‐sample t test was conducted to evaluate whether there was a reduction in scores on the POQ ‐C . The results indicated that there was a significant reduction in the POQ ‐C scores from intake to 6‐ and 12‐months follow‐up. The total scores on the POQ ‐C dropped from the 50%–74% range of pain to the 10%–24% range. Separate score decreases in the six subscales were statistically significant as well. These findings support the implementation of a CTPSCP as an effective adjunctive intervention, potentiating the standard medical treatments. Future studies should focus on direct comparisons between telephonic coaching and face‐to‐face coaching, and between pain management coaching and cognitive‐behavioral therapy. What makes a good CTPSCP candidate and “optimal treatment dose” need to be elucidated. Finally, comparative cost‐effectiveness and reimbursement models from insurance carriers should be explored as well.     

Placebo expectations and the detection of somatic information

In a laboratory study we examined the hypothesis that placebo expectations enhance the initial identification of placebo-relevant sensations over placebo-irrelevant sensations. Participants (N = 102) were randomly assigned to one of three expectation groups. In the first group, participants ingested a placebo capsule and were told it was caffeine (deceptive expectation). In a second group, participants ingested a placebo capsule and were told it may be caffeine or it may be a placebo (double-blind expectation). Participants in the third group were given no expectation. All participants then tallied the placebo-relevant and placebo-irrelevant sensations they experienced during a 7-min period. Participants in the deceptive expectation group identified more placebo-relevant sensations than placebo-irrelevant sensations. No-expectation participants identified more placebo-irrelevant sensations than placebo-relevant sensations. Participants given the double-blind expectation identified an equal amount of placebo-relevant and irrelevant sensations. The amount of both placebo-relevant and placebo-irrelevant sensations detected mediated the relationship between the expectation manipulation and subsequent symptom reports. These data support the position that expectations cause placebo responding, in part, by altering how one identifies bodily sensations.     

Development of a 7 T RF coil system for breast imaging

In ultrahigh‐field MRI, such as 7 T, the signal‐to‐noise ratio (SNR) increases while transmit (Tx) field (B₁⁺) can be degraded due to inhomogeneity and elevated specific absorption rate (SAR). By applying new array coil concepts to both Tx and receive (Rx) coils, the B₁⁺ homogeneity and SNR can be improved. In this study, we developed and tested in vivo a new RF coil system for 7 T breast MRI. An RF coil system composed of an eight‐channel Tx‐only array based on a tic‐tac‐toe design (can be combined to operate in single‐Tx mode) in conjunction with an eight‐channel Rx‐only insert was developed. Characterizations of the B₁⁺ field and associated SAR generated by the developed RF coil system were numerically calculated and empirically measured using an anatomically detailed breast model, phantom and human breasts. In vivo comparisons between 3 T (using standard commercial solutions) and 7 T (using the newly developed coil system) breast imaging were made. At 7 T, about 20% B₁⁺ inhomogeneity (standard deviation over the mean) was measured within the breast tissue for both the RF simulations and 7 T experiments. The addition of the Rx‐only array enhances the SNR by a factor of about three. High‐quality MR images of human breast were acquired in vivo at 7 T. For the in vivo comparisons between 3 T and 7 T, an approximately fourfold increase of SNR was measured with 7 T imaging. The B₁⁺ field distributions in the breast model, phantom and in vivo were in reasonable agreement. High‐quality 7 T in vivo breast MRI was successfully acquired at 0.6 mm isotropic resolution using the newly developed RF coil system.     

Characteristics of Schistosoma japonicum infection induced IFN‐γ and IL‐4 co‐expressing plasticity Th cells

Schistosoma japonicum infection can induce granulomatous inflammation and cause tissue damage in the mouse liver. The cytokine secretion profile of T helper (Th) cells depends on both the nature of the activating stimulus and the local microenvironment (e.g. cytokines and other soluble factors). In the present study, we found an accumulation of large numbers of IFN‐γ⁺ IL‐4⁺ CD4⁺ T cells in mouse livers. This IFN‐γ⁺ IL‐4⁺ cell population increased from 0·68 ± 0·57% in uninfected mice to 7·05 ± 3·0% by week 4 following infection and to 9·6 ± 5·28% by week 6, before decreasing to 6·3 ± 5·9% by week 8 in CD4 T cells. Moreover, IFN‐γ⁺ IL‐4⁺ Th cells were also found in mouse spleen and mesenteric lymph nodes 6 weeks after infection. The majority of the IFN‐γ⁺ IL‐4⁺ Th cells were thought to be related to a state of immune activation, and some were memory T cells. Moreover, we found that these S. japonicum infection‐induced IFN‐γ⁺ IL‐4⁺ cells could express interleukin‐2 (IL‐2), IL‐9, IL‐17 and high IL‐10 levels at 6 weeks after S. japonicum infection. Taken together, our data suggest the existence of a population of IFN‐γ⁺ IL‐4⁺ plasticity effector/memory Th cells following S. japonicum infection in C57BL/6 mice.     

A rehabilitation exercise program to remediate skeletal muscle atrophy in an estrogen-deficient organism may be ineffective

To determine rehabilitation exercise program effects under hormone deficient (ovariectomy or OVX) and hormone supplemented [OVX + 17-beta estradiol (E2)] conditions. Mature female rats (n = 123) were assigned to OVX or OVX + E2-supplemented groups. OVX and OVX + E2 groups were allocated to one of four conditions: (1) control, (2) hindlimb unweighted (HLU) for 4 weeks to induce muscle atrophy, (3) cage Recovery for 2 weeks after HLU, and (4) Recovery with 2 weeks of rehabilitation exercise program after 4 weeks of HLU. Atrophy following HLU was comparable for OVX and OVX + E2-supplemented rats and was significant in all muscles examined (soleus, tibialis anterior, plantaris, gastrocnemius, quadriceps). Also significant with HLU was the decline in muscle force (P < 0.05) in soleus, plantaris, gastrocnemius and tibialis anterior (quadriceps not tested). There were trends toward return of muscle mass in Recovery OVX and Recovery OVX + E2 groups but only the E2 supplemented OVX rats had return of muscle mass (4/5 muscles studied) with exercise. Peak tetanic tension (Po) returned to control values in the E2 supplemented Exercise rats but not in the unsupplemented Exercise group. For example, gastrocnemius Po for OVX HLU, OVX Recovery and OVX-Exercise groups was 82%*, 82%* and 76%* of control. Gastrocnemius Po for E2 supplemented HLU, Recovery and Exercise groups was 72%*, 95% and 106% of control (*P < 0.05 compared to control). H&E cross-sections from OVX-Exercise rats showed central nuclei. In conclusion, a rehabilitation exercise program to remediate acute atrophy in females appears more effective if E2 is present.     

Immune Response of Healthy Adults to the Ingested Probiotic Lactobacillus casei Shirota

Daily ingestion of a probiotic drink containing Lactobacillus casei Shirota (LcS; 1.3 × 10¹⁰ live cells) by healthy adults for (1) 4‐week LcS, (2) 6‐week discontinuation of LcS and (3) a final 4 weeks of LcS was investigated. There was a significant increase in expression of the T cell activation marker CD3⁺CD69⁺ in ex vivo unstimulated blood cells at weeks 10 and 14, and there was a significant increase in the NK cell marker CD3⁺CD16/56⁺ in ex vivo unstimulated blood cells at weeks 4, 10 and 14. Expression of the NK cell activation marker CD16/56⁺CD69⁺ in ex vivo unstimulated blood cells was 62% higher at week 10 and 74% higher at week 14. Intracellular staining of IL‐4 in ex vivo unstimulated and PMA‐/ionomycin‐stimulated CD3⁺ β7⁺ integrin blood cells was significantly lower at weeks 10 and 14. Intracellular staining of IL‐12 in ex vivo unstimulated and LPS‐stimulated CD14⁺ blood cells was significantly lower at weeks 4, 10 and 14. Intracellular staining of TNF‐α in LPS‐stimulated CD14⁺ blood cells was significantly lower at weeks 4, 10 and 14. Mucosal salivary IFN‐γ, IgA1 and IgA2 concentrations were significantly higher at week 14, but LcS did not affect systemic circulating influenza A‐specific IgA or IgG and tetanus‐specific IgG antibody levels. In addition to the decrease in CD3⁺β7⁺ integrin cell IL‐4 and a reduced CD14⁺ cell pro‐inflammatory cytokine profile, at week 14 increased expression of activation markers on circulating T cells and NK cells and higher mucosal salivary IgA1 and IgA2 concentration indicated a secondary boosting effect of LcS.     

Remote activation of referred phantom sensation and cortical reorganization in human upper extremity amputees

Phantom limb sensation, whether painful or not, frequently occurs after peripheral nerve lesions. It can be elicited by stimulating body parts adjacent to the amputation site (referred to as phantom sensation) and it is often similar in quality to the stimulation at the remote site. The present study induced referred phantom sensations in two upper limb amputees. Neuroelectric source imaging (ESI) as well as functional magnetic resonance imaging (fMRI) was used to assess reorganization in primary somatosensory cortex (SI). Whereas recent studies found mislocalization of sensation related to stimulation mainly in regions adjacent and ipsilateral to the amputation site, we report here the elicitation of phantom sensation in the arm by stimulation in the lower body part both ipsi- and contralateral to the amputation in two arm amputees. The fMRI evaluation of one patient showed no shift in the location of the foot whereas ESI revealed major reorganization of the mouth region in primary somatosensory cortex in both patients. These data suggest that cortical structures other than SI might be contributing to the phenomenon of referred sensation. Candidate structures are the thalamus, secondary somatosensory cortex, posterior parietal cortex and prefrontal cortex.     

Quantitative susceptibility mapping and 23Na imaging‐based in vitro characterization of blood clotting kinetics

Blood clotting is a fundamental biochemical process in post‐hemorrhagic hemostasis. Although the varying appearance of coagulating blood in T₁‐ and T₂‐weighted images is widely used to qualitatively determine bleeding age, the technique permits only a rough discrimination of coagulation stages, and it remains difficult to distinguish acute and chronic hemorrhagic stages because of low T₁‐ and T₂‐weighted signal intensities in both instances. To investigate new biomedical parameters for magnetic resonance imaging‐based characterization of blood clotting kinetics, sodium imaging and quantitative susceptibility mapping (QSM) were compared with conventional T₁‐ and T₂‐weighted imaging, as well as with biochemical hemolysis parameters. For this purpose, a blood‐filled spherical agar phantom was investigated daily for 14 days, as well as after 24 days at 7 T after initial preparation with fresh blood. T₁‐ and T₂‐weighted sequences, a three‐dimensional (3D) gradient echo sequence and a density‐adapted 3D radial projection reconstruction pulse sequence for ²³Na imaging were applied. For hemolysis estimations, free hemoglobin and free potassium concentrations were measured photometrically and with the direct ion‐selective electrode method, respectively, in separate heparinized whole‐blood samples along the same timeline. Initial mean susceptibility was low (0.154 ± 0.020 ppm) and increased steadily during the course of coagulation to reach up to 0.570 ± 0.165 ppm. The highest total sodium (NaT) values (1.02 ± 0.06 arbitrary units) in the clot were observed initially, dropped to 0.69 ± 0.13 arbitrary units after one day and increased again to initial values. Compartmentalized sodium (NaS) showed a similar signal evolution, and the NaS/NaT ratio steadily increased over clot evolution. QSM depicts clot evolution in vitro as a process associated with hemoglobin accumulation and transformation, and enables the differentiation of the acute and chronic coagulation stages. Sodium imaging visualizes clotting independent of susceptibility and seems to correspond to clot integrity. A combination of QSM and sodium imaging may enhance the characterization of hemorrhage.     

Multiple Antigen Peptide Containing B and T Cell Epitopes of F1 Antigen of Yersinia pestis Showed Enhanced Th1 Immune Response in Murine Model

Yersinia pestis is a facultative bacterium that can survive and proliferate inside host macrophages and cause bubonic, pneumonic and systemic infection. Apart from humoral response, cell‐mediated protection plays a major role in combating the disease. Fraction 1 capsular antigen (F1‐Ag) of Y. pestis has long been exploited as a vaccine candidate. In this study, F1‐multiple antigenic peptide (F1‐MAP or MAP)‐specific cell‐mediated and cytokine responses were studied in murine model. MAP consisting of three B and one T cell epitopes of F1‐antigen with one palmitoyl residue was synthesized using Fmoc chemistry. Mice were immunized with different formulations of MAP in poly DL‐lactide‐co‐glycolide (PLGA) microspheres. F1‐MAP with CpG oligodeoxynucleotide (CpG‐ODN) as an adjuvant showed enhanced in vitro T cell proliferation and Th1 (IL‐2, IFN‐γ and TNF‐α) and Th17 (IL‐17A) cytokine secretion. Similar formulation also showed significantly higher numbers of cytokine (IL‐2, IFN‐γ)‐secreting cells. Moreover, F1‐MAP with CpG formulation showed significantly high (P < 0.001) percentage of CD4⁺ IFN‐γ⁺ cells as compared to CD8⁺ IFN‐γ⁺ cells, and also more (CD4‐ IFN‐γ)⁺ cells secrete perforin and granzyme as compared to (CD8‐ IFN‐γ)⁺ showing Th1 response. Thus, the study highlights the importance of Th1 cytokine and existence of CD4⁺ and CD8⁺ immune response. This study proposes a new perspective for the development of vaccination strategies for Y. pestis that trigger T cell immune response.     

The relationship of perceptual phenomena and cortical reorganization in upper extremity amputees

In this study 16 unilateral upper extremity amputees participated in a comprehensive psychophysiological examination that included the assessment of painful and non-painful phantom and stump sensations, thermal and electric perception as well as two-point discrimination thresholds, the detailed analysis of referred sensation and the measurement of reorganizational changes in primary somatosensory cortex using neuroelectric source imaging. Reorganization of the primary somatosensory cortex was associated with increased habitual phantom limb pain, telescoping, non-painful stump sensations and painful referred sensation induced by painful stimulation. It was unrelated to non-painful phantom sensations, non-painful referred sensation elicited by painful or non-painful stimulation, painful referred sensation elicited by non-painful stimulation, perception thresholds and stump pain.These data substantiate the hypothesis that painful and non-painful phantom phenomena are mediated by different neural substrates.