Stress Among Bachelor Physical Therapy Students in Israel during Clinical Practice and Its Association with Academic Achievements– Results of a Longitudinal Study

Purposes: This study aimed 1) to evaluate perceived stress of a cohort of bachelor physical therapy (PT) students from Ariel University in Israel across three clinical practice periods; 2) to evaluate the relationship between perceived stress and academic achievements; 3) to evaluate the relationship between students\u27 perceived stress and clinical practice periods\u27 order and content; and 4) to identify clinical and socio-demographic variables related to perceived stress. Methods: A longitudinal study was conducted among a cohort of undergraduate PT students during their first, second, and third clinical practice assignments. Data were collected using an online questionnaire. The Perceived Stress Scale 10 (PSS) and the Scale for Assessing Academic Stress (SAAS) were used to evaluate perceived stress. A ten-degree Visual Analogue Scale (VAS) was used to evaluate perceived difficulty. Students\u27 grade point averages from the first three years of study were considered academic achievements. An ANOVA was used to evaluate the relationship between perceived stress and academic achievements, and between clinical practice order and area and the socio-demographic characteristics. Results: A total of 39 undergraduate physical therapy students participated in the study. The degrees of PSS and SAAS were higher than those reported previously in undergraduate PT students. Perceived stress was not related to academic achievement, clinical practice order or area, or to socio-demographic characteristics. Conclusions: Participation in clinical practice in general might be a stressful situation, but no specific clinical or socio-demographic factors that might be a source of higher levels of perceived stress were identified. As undergraduate students are away from the campus during clinical practice periods, it is suggested that clinical instructors, who are in daily contact with the students, should receive guidance regarding the ways to identify individuals who present signs of increased stress and the types of strategies that can help students cope with stress in real time

Neuroprotective Effect of Transplanted Human Embryonic Stem Cell-Derived Neural Precursors in an Animal Model of Multiple Sclerosis

BACKGROUND: Multiple sclerosis (MS) is an immune mediated demyelinating disease of the central nervous system (CNS). A potential new therapeutic approach for MS is cell transplantation which may promote remyelination and suppress the inflammatory process. METHODS: We transplanted human embryonic stem cells (hESC)-derived early multipotent neural precursors (NPs) into the brain ventricles of mice induced with experimental autoimmune encephalomyelitis (EAE), the animal model of MS. We studied the effect of the transplanted NPs on the functional and pathological manifestations of the disease. RESULTS: Transplanted hESC-derived NPs significantly reduced the clinical signs of EAE. Histological examination showed migration of the transplanted NPs to the host white matter, however, differentiation to mature oligodendrocytes and remyelination were negligible. Time course analysis of the evolution and progression of CNS inflammation and tissue injury showed an attenuation of the inflammatory process in transplanted animals, which was correlated with the reduction of both axonal damage and demyelination. Co-culture experiments showed that hESC-derived NPs inhibited the activation and proliferation of lymph node-derived T cells in response to nonspecific polyclonal stimuli. CONCLUSIONS: The therapeutic effect of transplantation was not related to graft or host remyelination but was mediated by an immunosuppressive neuroprotective mechanism. The attenuation of EAE by hESC-derived NPs, demonstrated here, may serve as the first step towards further developments of hESC for cell therapy in MS

Physical exercise therapy for autoimmune neuroinflammation : Application of knowledge from animal models to patient care.

Physical exercise (PE) impacts various autoimmune diseases. Accordingly, clinical trials demonstrated the safety of PE in multiple sclerosis (MS) patients and indicated beneficial outcomes. There is also an increasing body of research on the beneficial effects of exercise on experimental autoimmune encephalomyelitis (EAE), the animal model of MS, and various mechanisms underlying these effects were suggested. However, despite the documented favorable impact of PE on our health, we still lack a thorough understanding of its effects on autoimmune neuroinflammation and specific guidelines of PE therapy for MS patients are lacking. To that end, current findings on the impact of PE on autoimmune neuroinflammation, both in human MS and animal models are reviewed. The concept of personalized PE therapy for autoimmune neuroinflammation is discussed, and future research for providing biological rationale for clinical trials to pave the road for precise PE therapy in MS patients is described

Presymptomatic Treatment with Acetylcholinesterase Antisense Oligonucleotides Prolongs Survival in ALS (G93A-SOD1) Mice

Objective. Previous research suggests that acetylcholinesterase (AChE) may be involved in ALS pathogenesis. AChE enzyme inhibitors can upregulate AChE transcription which in certain contexts can have deleterious (noncatalytic) effects, making them theoretically harmful in ALS, whilst AChE antisense-oligonucleotides (mEN101), which downregulate AChE may be beneficial. Our aim was to investigate whether downregulation of AChE using mEN101 is beneficial in an ALS mouse model. Methods. ALS (G93A-SOD1) mice received saline, mEN101, inverse-EN101, or neostigmine. Treatments were administered from 5 weeks. Disease-onset and survival were recorded. Additional mice were sacrificed for pathological analysis at 15 weeks of age. In a follow-up experiment treatment was started at the symptomatic stage at a higher dose. Results. mEN101 given at the presymptomatic (but not symptomatic) stage prolonged survival and attenuated motor-neuron loss in ALS mice. In contrast, neostigmine exacerbated the clinical parameters. Conclusions. These results suggest that AChE may be involved in ALS pathogenesis. The accelerated disease course with neostigmine suggests that any beneficial effects of mEN101 occur through a non-catalytic rather than cholinergic mechanism

Fatal Neurological Disease in Scrapie-Infected Mice Induced for Experimental Autoimmune Encephalomyelitis▿

During the years or decades of prion disease incubation, at-risk individuals are certain to encounter diverse pathological insults, such as viral and bacterial infections, autoimmune diseases, or inflammatory processes. Whether prion disease incubation time and clinical signs or otherwise the pathology of intercurrent diseases can be affected by the coinfection process is unknown. To investigate this possibility, mice infected with the scrapie agent at both high and low titers were subsequently induced for experimental autoimmune encephalomyelitis, an immune system-mediated model of central nervous system (CNS) inflammation. We show here that coinduced mice died from a progressive neurological disease long before control mice succumbed to classical scrapie. To investigate the mechanism of the coinduced syndrome, we evaluated biochemical and pathological markers of both diseases. Brain and spleen PrPSc levels in the dying coinduced mice were comparable to those observed in asymptomatic scrapie-infected animals, suggesting that coinduced disease is not an accelerated form of scrapie. In contrast, inflammatory markers, such as demyelination, immune cell infiltrates, and gliosis, were markedly increased in coinduced mouse spinal cords. Activated astrocytes were especially elevated in the medulla oblongata. Furthermore, PrPsc depositions were found in demyelinated white matter areas in coinduced mouse spinal cords, suggesting the presence of activated infected immune cells that infiltrate into the CNS to facilitate the process of prion neuroinvasion. We hypothesize that inflammatory processes affecting the CNS may have severe clinical implications in subjects incubating prion diseases

Histopathological analyses of inflammatory parameters, demyelination and axonal damage in the spinal cord of C57BL/6 mice at 10, 13, 20 and 50 days after MOG35–55 EAE induction.

<p>Histopathological analyses of inflammatory parameters, demyelination and axonal damage in the spinal cord of C57BL/6 mice at 10, 13, 20 and 50 days after MOG35–55 EAE induction.</p

Attenuation of the progression of inflammation and tissue damage in the CNS of NPs-transplanted mice.

<p>Pathological examination of spinal cord sections from NP-transplanted and control mice were performed at 10, 13, 20 and 50 days post EAE induction to evaluate CNS inflammation, demyelination and axonal damage. In NP-transplanted mice an attenuation of the number of immune-cell infiltrates (A), T cells (D) and macrophages/activated microglia (G) per mm² was evident from day 13 post EAE induction and became significant at days 20 and 50. Demyelination and axonal damage, which were analyzed by loss of Kluver Barrera (J), and Bielschowsky staining (M), respectively, were both significantly reduced at day 20 and 50 post EAE induction. The differences between the study and control groups in the severity of all parameters gradually increased with time. Representative day 20 images of H&E staining (B, C), immunostaining for CD3 (E, F) and Mac3 (H, I), Kluver Barrera staining (K, L) and Bielschowsky silver staining (N, O). * P<0.05. Scale bars: 100 µm.</p

The clinical course of EAE is attenuated after transplantation of hESC-derived NPs.

<p>hESC-derived NPs were transplanted into the lateral brain ventricles of EAE mice and the severity of clinical signs was scored daily. A significant attenuation of the clinical score was observed in NPs-transplanted animals (▪) in comparison to vehicle-transplanted control animals (▴). The reduced severity of clinical scores in NP-transplanted animals was evident as early as the acute phase of the disease (day 19 post-EAE induction). See <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0003145#s4" target="_blank">material and methods</a> section for details regarding the clinical scoring system.</p

The extent of the inflammatory process strongly correlates with the severity of tissue damage in the acute phase of EAE.

<p>NP- transplanted and control mice were sacrificed at 10, 13, 20 and 50 days post EAE induction for pathological analysis of inflammation and tissue damage. Linear-regression analysis of the numbers of inflammatory cells and the extent of axonal loss in both NP-transplanted and control EAE mice at 13 and 20 days post EAE induction showed a strong correlation between the numbers of T cells and macrophages per mm² and the percentage of axonal loss.</p