ROCKing Regeneration: Rho Kinase Inhibition as Molecular Target for Neurorestoration

Regenerative failure in the CNS largely depends on pronounced growth inhibitory signaling and reduced cellular survival after a lesion stimulus. One key mediator of growth inhibitory signaling is Rho-associated kinase (ROCK), which has been shown to modulate growth cone stability by regulation of actin dynamics. Recently, there is accumulating evidence the ROCK also plays a deleterious role for cellular survival. In this manuscript we illustrate that ROCK is involved in a variety of intracellular signaling pathways that comprise far more than those involved in neurite growth inhibition alone. Although ROCK function is currently studied in many different disease contexts, our review focuses on neurorestorative approaches in the CNS, especially in models of neurotrauma. Promising strategies to target ROCK by pharmacological small molecule inhibitors and RNAi approaches are evaluated for their outcome on regenerative growth and cellular protection both in preclinical and in clinical studies

Computer-assisted surgery for placing toggle constructs across the coxofemoral joints of small equids using a minimally invasive approach-A proof-of-concept cadaveric study.

OBJECTIVE To develop a minimally invasive technique for placing a toggle construct across the coxofemoral joint of small equids using computer-assisted surgery. STUDY DESIGN Experimental cadaveric study. SAMPLE POPULATION Three pilot specimens: One donkey, one Shetland pony and one Warmblood foal. Six main study specimens: Three Shetland ponies, one American Miniature Horse, one Warmblood foal and one donkey. METHODS Experimental surgeries were performed on both coxofemoral joints of each cadaver. Using a minimally invasive surgical approach, 5.5 mm bone canals were drilled through the femur and acetabulum, traversing the coxofemoral joint. Intraoperative guidance was provided by a cone-beam computed tomography (CBCT)-coupled surgical navigation system. A toggle construct was introduced through the bone canals. Surgical accuracy aberrations (SAA) were measured at the femoral entry and exit points and at the acetabular entry point on merged pre- and postoperative CBCT scans. The coxofemoral joint was assessed for articular cartilage damage by gross dissection. RESULTS A toggle construct was placed across all 18 coxofemoral joints. The overall median SAA in the main study was 2.8 mm (range: 0.4-8.0 mm). No cartilage damage was found in the cadaveric specimens of the main study. CONCLUSION The described technique allowed for the placement of a toggle construct across the coxofemoral joint of small equid cadaveric specimens without prior coxofemoral luxation. CLINICAL RELEVANCE This technique may serve as an option for surgical stabilization of coxofemoral joints in small equids. Further biomechanical investigations are required to assess optimal implant positioning and toggle constructs

Intra-abdominal adipose tissue of laboratory mice adapted to different temperature regimes

For the first time the presence of beige adipocytes, cellularity, basic metabolic parameters of perigonadal abdominal fat have studied in autbred laboratory mice kept at different temperature regimes: 1) 30°С (thermoneutral zone) and 2) regular daily 8-hour cold exposures. Unlike brown fat in the abdominal depot, temperature-dependent changes of these parameters were not detected. The functions of the beige adipocytes of the abdominal depot were discussed

Performance of international medical students in psychosocial medicine

Background: Particularly at the beginning of their studies, international medical students face a number of language-related, social and intercultural challenges. Thus, they perform poorer than their local counterparts in written and oral examinations as well as in Objective Structured Clinical Examinations (OSCEs) in the fields of internal medicine and surgery. It is still unknown how international students perform in an OSCE in the field of psychosocial medicine compared to their local fellow students. Methods: All students (N = 1033) taking the OSCE in the field of psychosocial medicine and an accompanying written examination in their eighth or ninth semester between 2012 and 2015 were included in the analysis. The OSCE consisted of four different stations, in which students had to perform and manage a patient encounter with simulated patients suffering from 1) post-traumatic stress disorder, 2) schizophrenia, 3) borderline personality disorder and 4) either suicidal tendency or dementia. Students were evaluated by trained lecturers using global checklists assessing specific professional domains, namely building a relationship with the patient, conversational skills, anamnesis, as well as psychopathological findings and decision-making. Results: International medical students scored significantly poorer than their local peers (p < .001; η2 = .042). Within the specific professional domains assessed, they showed poorer scores, with differences in conversational skills showing the highest effect (p < .001; η2 = .053). No differences emerged within the multiple-choice examination (p = .127). Conclusion: International students showed poorer results in clinical-practical exams in the field of psychosocial medicine, with conversational skills yielding the poorest scores. However, regarding factual and practical knowledge examined via a multiple-choice test, no differences emerged between international and local students. These findings have decisive implications for relationship building in the doctor-patient relationship

High-Resolution Optical Functional Mapping of the Human Somatosensory Cortex

Non-invasive optical imaging of brain function has been promoted in a number of fields in which functional magnetic resonance imaging (fMRI) is limited due to constraints induced by the scanning environment. Beyond physiological and psychological research, bedside monitoring and neurorehabilitation may be relevant clinical applications that are yet little explored. A major obstacle to advocate the tool in clinical research is insufficient spatial resolution. Based on a multi-distance high-density optical imaging setup, we here demonstrate a dramatic increase in sensitivity of the method. We show that optical imaging allows for the differentiation between activations of single finger representations in the primary somatosensory cortex (SI). Methodologically our findings confirm results in a pioneering study by Zeff et al. (2007) and extend them to the homuncular organization of SI. After performing a motor task, eight subjects underwent vibrotactile stimulation of the little finger and the thumb. We used a high-density diffuse-optical sensing array in conjunction with optical tomographic reconstruction. Optical imaging disclosed three discrete activation foci one for motor and two discrete foci for vibrotactile stimulation of the first and fifth finger, respectively. The results were co-registered to the individual anatomical brain anatomy (MRI) which confirmed the localization in the expected cortical gyri in four subjects. This advance in spatial resolution opens new perspectives to apply optical imaging in the research on plasticity notably in patients undergoing neurorehabilitation

第840回千葉医学会整形外科例会 47.

In the “loud-tone” procedure, a series of brief, loud, pure-tone stimuli are presented in a task-free situation. It is an established paradigm for measuring autonomic sensitization in posttraumatic stress disorder (PTSD). Successful use of this procedure during fMRI requires elicitation of brain responses that have sufficient signal-noise ratios when recorded in a supine, rather than sitting, position. We investigated the modulating effects of posture and stimulus spectral composition on peripheral psychophysiological responses to loud sounds. Healthy subjects (N = 24) weekly engaged in a loud-tone-like procedure that presented 500 msec, 95 dB sound pressure level, pure-tone or white-noise stimuli, either while sitting or supine and while peripheral physiological responses were recorded. Heart rate, skin conductance, and eye blink electromyographic responses were larger to white-noise than pure-tone stimuli (p’s < 0.001, generalized eta squared 0.073–0.076). Psychophysiological responses to the stimuli were similar in the sitting and supine position (p’s ≥ 0.082). Presenting white noise, rather than pure-tone, stimuli may improve the detection sensitivity of the neural concomitants of heightened autonomic responses by generating larger responses. Recording in the supine position appears to have little or no impact on psychophysiological response magnitudes to the auditory stimuli