The direction of the postural response to a vestibular perturbation is mediated by the cerebellar vermis.

When an electrical stimulus is applied to perturb the vestibular system, a postural response is generated orthogonal to head orientation. It has previously been shown that there is a convergence of neck proprioceptive and vestibular input within the cerebellum to provide a head-on-body reference frame (Manzoni et al. in Neuroscience 93:1095-1107, 1999). The objective of this experiment was to determine whether the direction of the postural response to a vestibular perturbation is modulated when function of the cerebellar vermis is temporarily depressed. Twenty participants were randomly assigned to a SHAM group (paired-pulse transcranial magnetic stimulation) or a TEST group (continuous theta burst stimulation). Stochastic vestibular stimulation (SVS) was applied to standing subjects with their head facing forward or over their left shoulder. Cumulant density traces were established between the SVS and shear force over 180°, and the peak amplitude determined the direction of sway. There were no significant changes in sway direction when the head was facing forward for either stimulation (TEST or SHAM; p = 0.889) or when the head was facing over the shoulder for the SHAM condition (p = 0.954). There was, however, a significant change in sway direction when the head was turned with a depressed cerebellum (p = 0.018); from the expected antero-posterior direction, orthogonal to head orientation, to one slightly more mediolateral with respect to the feet. These results suggest the cerebellum plays a role in the integration of input to generate an appropriately directed postural response relative to the head position.

Reduced input from foot sole skin through cooling differentially modulates the short latency and medium latency vestibular reflex responses to galvanic vestibular stimulation.

Sensory afferent information from the skin of the foot sole and information from the vestibular system converge within the central nervous system; however, their mode of interaction remains unknown. The purpose of this study was to investigate the effect of reduced cutaneous foot sole information on the ability of the vestibular system to evoke short latency (SL) and medium latency (ML) lower limb muscle reflex responses. Galvanic vestibular stimulation (GVS; bipolar; binaural; 25 ms; 2 mA square-wave pulse) was applied to standing human subjects (four women, eight men, average age 21.1 ± 3.0 years) both before and after cooling the foot soles in 1°C ice water (15 min initially, followed by 5 min between blocks of 200 GVS pulses). Changes in soleus reflex amplitude were examined. Following ice water immersion, there was a 35.16% increase in the size of the ML response in the soleus muscle when expressed as a percentage of pre-stimulus electromyographic (EMG) activity (control 26.48 ± 4.91%; ice 36.16 ± 6.52%) with no change in size of the SL response (control 7.42 ± 1.12%; ice 8.72 ± 1.10%). These results support the previously proposed dissociation of the SL and ML responses with respect to their circuitry and functions. The results also suggest a greater role for cutaneous-vestibular interaction in the modulation of the ML than the SL response and at a location prior to the motoneuron pool.

Building successful and sustainable academic health science partnerships: exploring perspectives of hospital leaders.

BACKGROUND: Clinical work-based internships form a key component of health professions education. Integral to these internships, academic health science partnerships (AHSPs) exist between universities and teaching hospitals. Our qualitative descriptive study explored the perspectives of hospital leadership on AHSPs: what they are composed of, and the facilitators and barriers to establishing and sustaining these partnerships. METHODS: Fifteen individuals in a variety of hospital leadership positions were purposively sampled to participate in face-to-face interviews, after which a thematic analysis was conducted. RESULTS: Participants reported that healthcare and hospital infrastructure shapes and constrains the implementation of clinical education. The strength of the hospitals' relationship with the medical profession facilitated the partnership, however other health professions' partnerships were viewed less favourably. Participants emphasized the value of hospital leaders prioritizing education. Further, our findings highlighted that communication, collaboration, and involvement are considered as both facilitators and barriers to active engagement. Lastly, opportunities stemming from the partnership were identified as research, current best practice, improved patient care, and career development. CONCLUSION: Our study found that AHSPs involve the drive of the university and hospitals to gain valued capital, or opportunities. Reciprocal communication, collaboration, and involvement are modifiable components that are integral to optimizing AHSPs.

The relationship between childhood abuse and suicidality in adult bipolar disorder.

This study evaluates the effect of childhood sexual and physical abuse on suicidality in adults with bipolar disorder. We conducted a retrospective chart review of adult outpatients (N= 381) with DSM-IV-TR-defined bipolar disorder seeking evaluation and treatment at an academic specialty research program (i.e., Mood Disorders Pharmacology Unit, University Health Network, University of Toronto) between October 2002 and November 2005. Eighteen percent (n = 68) of adult patients with bipolar disorder had a recorded history of childhood abuse (p = 0.009). Sixty-three percent (n = 43) of bipolar patients with a history of childhood abuse reported lifetime suicidality (chi2 = 6.885, df= 1, p = 0.009). Logistic regression analysis indicated that Childhood abuse was a significant predictor of lifetime suicidality in adult bipolar patients (OR = 2.05, CI = 1.19-3.510). Childhood abuse is associated with suicidal ideation and suicide attempts in adults with bipolar disorder. Anamnestic inquiry regarding childhood maltreatment is salient to risk assessment, illness management planning, preventative strategies, and treatment interventions in bipolar disorder.

The medium latency muscle response to a vestibular perturbation is increased after depression of the cerebellar vermis.

INTRODUCTION: Galvanic vestibular stimulation (GVS) is able to evoke distinct responses in the muscles used for balance. These reflexes, termed the short (SL) and medium latency (ML) responses, can be altered by sensory input; decreasing in size when additional sensory cues are available. Although much is known about these responses, the origin and role of the responses are still not fully understood. It has been suggested that the cerebellum, a structure that is involved in postural control and sensory integration, may play a role in the modulation of these reflexes. METHODS: The cerebellar vermis was temporarily depressed using continuous theta burst stimulation and SL, ML and overall vestibular electromyographic and force plate shear response amplitudes were compared before and after cerebellar depression. RESULTS: There were no changes in force plate shear amplitude and a non-significant increase for the SL muscle response (p = .071), however, we did find significant increases in the ML and overall vestibular muscle response amplitudes after cerebellar depression (p = .026 and p = .016, respectively). No changes were evoked when a SHAM stimulus was used. DISCUSSION: These results suggest that the cerebellar vermis plays a role in the modulation of vestibular muscle reflex responses to GVS.

Thresholds of skin sensitivity are partially influenced by mechanical properties of the skin on the foot sole.

Across the foot sole, there are vibration and monofilament sensory differences despite an alleged even distribution of cutaneous afferents. Mechanical property differences across foot sole sites have been proposed to account for these differences. Vibration (VPT; 3 Hz, 40 Hz, 250 Hz), and monofilament (MF) perception threshold measurements were compared with skin hardness, epidermal thickness, and stretch response across five foot sole locations in young healthy adults (n = 22). Perceptual thresholds were expected to correlate with all mechanical property measurements to help address sensitivity differences between sites. Following this hypothesis, the MedArch was consistently found to be the thinnest and softest site and demonstrated the greatest sensitivity. Conversely, the Heel was found to be the thickest and hardest site, and was relatively insensitive across perceptual tests. Site differences were not observed for epidermal stretch response measures. Despite an apparent trend of elevated sensory threshold at harder and thicker sites, significant correlations between sensitivity measures and skin mechanical properties were not observed. Skin hardness and epidermal thickness appeared to have a negligible influence on VPT and minor influence on MF within this young healthy population. When normalized (% greater or smaller than subject mean) to the subject mean for each variable, significant positive correlations were observed between MF and skin hardness (R(2) = 0.422, P < 0.0001) and epidermal thickness (R(2) = 0.433, P < 0.0001) providing evidence that skin mechanics can influence MF threshold. In young healthy adults, differences in sensitivity are present across the foot sole, but cannot solely be accounted for by differences in the mechanical properties of the skin.

Increasing insulin resistance contributes to worsening glycaemic and lipid profiles in older Chinese subjects.

OBJECTIVE: To investigate the impact of insulin resistance on cardiovascular risk factors in the elderly. RESEARCH DESIGN AND METHODS: A cross-sectional, community-based study of 225 older Chinese participants (65-74 years, 55.6% female) recruited from community centres for the elderly in Shatin. Anthropometric measures and DXA body fat, blood pressure, insulin sensitivity (fasting insulin, fasting insulin-glucose product, short insulin tolerance test (SITT)), glycaemic (fasting glucose, glycated haemoglobin A1c) and lipid (total, HDL-, and LDL-cholesterol, triglycerides) indices and albuminuria (24h albumin-to-creatinine ratio) were measured. RESULTS: There was a close correlation between the SITT and insulin-glucose product indices of insulin resistance. Decreasing tertiles of insulin sensitivity were associated with increasing indices of glycaemic control, and general and central obesity, including DXA lean and fat mass, albuminuria, and triglycerides, with decreasing HDL-cholesterol. There were no differences in blood pressure or electrolyte levels between these tertile groups. These subjects were more insulin resistant than a group of younger diabetics. CONCLUSIONS: Insulin resistance was associated with indices of obesity and an atherogenic lipid and hyperglycaemic profile and may in part contribute to the high frequency of metabolic syndrome components in these older Chinese subjects.

Differentiation potential of mesenchymal progenitor cells following transplantation into calvarial defects.

The complexity of stem cell lineage commitment requires studies to investigate the intrinsic and extrinsic regulatory events during differentiation. The objective of this long-term in vivo study was to investigate cellular differentiation and tissue formation of transplanted undifferentiated bone-marrow-derived mesenchymal progenitor cells (BMPCs) in combination with a medical grade polycaprolactone (mPCL) scaffold and to compare them to osteoblasts; a more differentiated cell type in a calvarial defect model. Tissue formation was assessed via histology, mechanical and radiological methods after 3 12, and 24 months. After 3 months our results indicated that transplanted mesenchymal progenitor cells were influenced by the niche of the host environment. Scaffold/BMPCs formed islands of bone tissue inside the defect area. However when the surrounding host calvarium contained a high content of fatty tissue, the fat content in the defect areas was also significantly higher. In contrast, defects repaired with scaffold/cOBs did not show this phenomenon. Analysis after 12 and 24 months confirmed these observations indicating that a predominantly fatty environment leads to adipogenic development in the progenitor group. Biomechanical data revealed that the tissue was less firm in the BMPC group compared to the cOB seeded group. Evaluation of cell plasticity in vivo has important consequences in clinical cell transplantation protocols. This study indicates that cell fate decisions are partially regulated by extrinsic control mechanisms of the immediate environment suggesting that induction of BMPCs into a specific lineage could be beneficial prior transplantation.

Study of the destructive effect to inherent quality of Angelicae dahuricae radix (Baizhi) by sulfur-fumigated process using chromatographic fingerprinting analysis.

The after-harvesting sun-dried process of Angelicae dahuricae radix (Chinese name: Baizhi) was previously the traditional treatment for commodity. Over recent decades the natural drying process for some fleshy roots or rhizomes of Chinese materia medica has been replaced by sulfur-fumigation for curtailing the drying duration and pest control. We used high performance liquid chromatography (HPLC) and high performance thin-layer chromatography (HPTLC) fingerprinting analysis to investigate the potential damaging effect of the sulfur-fumigating process. The experimental conditions were as follows. HPTLC analysis was carried out on pre-coated silica-gel 60 plate, twice development was performed with two solvent systems (mobile phase) A, chloroform-ethyl acetate (10:1) and B, hexane-chloroform-ether (4:1:2); the fluorescent images were observed under UV 365 nm. HPLC was preceeded on Zorbax SB-C(18) column; the linear gradient elution was conducted with mobile phase prepared from methanol-0.5% acetic acid; column temperature was at 25 degrees C; the detection wavelength was 250 nm. We found serious degradation of the majority of coumarins in sulfur-fumigated Baizhi. The destructive effect was manifested by the defaced chromatographic profile and verified by imitating the sulfur dioxide reaction with the constituents in Baizhi in the laboratory. It is suggested that sulfur-fumigation process is an unacceptable approach for processing herbal drugs.

Effects of Tai Chi and resistance training on cardiovascular risk factors in elderly Chinese subjects: a 12-month longitudinal, randomized, controlled intervention study.

BACKGROUND: Tai Chi is rapidly gaining in popularity, worldwide. This study was performed to assess its impact on cardiovascular risk factors in comparison with resistance training exercises in elderly Chinese subjects. METHODS: A total of 207 healthy elderly participants (65-74 years, 113/207 (55%) men) were randomly assigned to one of three intervention groups: (1) Tai Chi, three times/week for 1 h/session (n = 64); (2) resistance training exercise, three times/week for 1 h/session (n = 65); (3) usual level of physical activity control group (n = 78). Anthropometric measures, dual X-ray densitometry body composition, blood pressure, lipids, glycaemic and insulin sensitivity indices were measured at baseline and 12 months. Repeated-measures analysis of variance (anova) was used to assess the between-group changes using a last-observation-carried-forward intention-to-treat approach. RESULTS: A total of 180 (87.0%) subjects completed the study. No significant changes were identified in the Tai Chi group compared to the resistance training or control group. Of the primary outcomes, only the improvement in the insulin sensitivity index differed, being significantly greater in the resistance training than in the control group [mean difference 0.018 (95% confidence interval ( CI) 0.000-0.037) mmol glucose/min, P = 0.02), and tending to be greater than in the Tai Chi group (mean difference 0.019 (95% CI 0.000-0.038) mmol glucose/min, P < 0.06). CONCLUSION: Tai Chi had no significant effect on any measure compared to the controls, whereas resistance training improved the insulin sensitivity index in this 12-month study.