Deep Brain Stimulation of the Subgenual Cingulate Cortex for the Treatment of Chronic Low Back Pain

ObjectivesDespite converging basic scientific and clinical evidence of the link between chronic pain and depression, existing therapies do not often take advantage of this overlap. Here, we provide a critical review of the literature that highlights the intersection in brain networks between chronic low back pain (CLBP) and depression and discuss findings from previous deep brain stimulation (DBS) studies for pain. Based on a multidimensional model of pain processing and the connectivity of the subgenual cingulate cortex (SCC) with areas that are implicated in both CLBP and depression, we propose a novel approach to the treatment of CLBP using DBS of the SCC.Materials and MethodsA narrative review with literature assessment.ResultsCLBP is associated with a shift away from somatosensory representation toward brain regions that mediate emotional processes. There is a high degree of overlap between these regions and those involved in depression, including the anterior cingulate cortex, medial prefrontal cortex, nucleus accumbens, and amygdala. Whereas target sites from previous DBS trials for pain were not anatomically positioned to engage these areas and their associated networks, the SCC is structurally connected to all of these regions as well as others involved in mediating sensory, cognitive, and affective processing in CLBP.ConclusionsCLBP and depression share a common underlying brain network interconnected by the SCC. Current data and novel technology provide an optimal opportunity to develop clinically effective trials of SCC DBS for CLBP.     

Is there a place for virtual reality simulators in assessment of competency in percutaneous renal access?

Objective

To assess competency of urology post-graduate trainees (PGTs) in percutaneous renal access (PCA).

Methods

Upon obtaining ethics approval and informed consents, PGTs between post-graduate years (PGY-3 to PGY-5) from all four urology programs in Québec were recruited. PCA competency of each participant was assessed objectively by performing task 4 on the PERC Mentor? simulator, where they had to correctly access and pop 7 balloons in 7 different renal calyces and subjectively by the validated Percutaneous Nephrolithotomy—Global Rating Scale (PCNL-GRS).

Results

A total of 26 PGTs with a mean age of 29.2 ± 0.7 years participated in this study. When compared with the 21 PGTs without practice, all 5 PGTs who had practiced on the simulator were competent (p = 0.03), performed the task with significantly shorter operative time (13.9 ± 0.7 vs. 4.4 ± 0.4 min; p < 0.001) and fluoroscopy time (9.3 ± 0.6 vs. 3.4 ± 0.4 min; p < 0.001), and had significantly higher PCNL-GRS scores (13 ± 0.6 vs. 20.6 ± 1; p < 0.001) and successful attempts to access renal calyces (23 ± 5 vs. 68.7 ± 11; p = 0.001). According to a pass score of 13/25, thirteen PGTs were competent. Competent PGTs performed the task with significantly shorter fluoroscopy time (9.8 vs. 6.5 min; p = 0.01) and higher percentage of successful attempts to access renal calyces (p < 0.001), higher PCNL-GRS scores (p < 0.001), and lower complications (p = 0.01).

Conclusion

The PCNL-GRS in combination with the PERC Mentor? simulator was able to differentiate between competent and non-competent PGTs.

     

Concentration of glycosaminoglycan in ovariectomized mice uterus after treatment with ovarian steroids

The aim of this study was to evaluate the amount of non- and sulfated glycosaminoglycans in the ovariectomized mice uterus, after treatment with ovarian steroids. For this purpose, 50 adult female mice were divided into five groups with 10 animals/each: control group: CG (ovary intact), and ovariectomized groups: OG (vehicle), EG (estradiol), PG (progesterone) and EPG (estradiol combined to progesterone). The treatments started 30 days after ovariectomy. All the animals were treated for 50 consecutive days. These hormones were administered in a sterile oily solution via gavage. Twenty-four hours after the last treatment, all animals were euthanized, removing the uterine horn for biochemical analyses. To quantify, the hyaluronic acid (HA) used ELISA-like fluorometric assay, and the sulfated glycosaminoglycans (GAGs) used agarose gel electrophoresis. The amount of HA was significantly higher in the group treated with progesterone (PG) compared to the others groups (p?p?p?相似文献   

Aging-associated truncated form of p53 interacts with wild-type p53 and alters p53 stability, localization, and activity

Evidence has accumulated that p53, a prototypical tumor suppressor, may also influence aspects of organismal aging. We have previously described a p53 mutant mouse model, the p53+/m mouse, which is cancer resistant yet exhibits reduced longevity and premature aging phenotypes. p53+/m mice express one full length p53 allele and one truncated p53 allele that is translated into a C-terminal fragment of p53 termed the M protein. The augmented cancer resistance and premature aging phenotypes in the p53+/m mice are consistent with a hyperactive p53 state. To determine how the M protein could increase p53 activity, we examined the M protein in various cellular contexts. Here, we show that embryo fibroblasts from p53+/m mice exhibit reduced proliferation and cell cycle progression compared to embryo fibroblasts from p53+/- mice (with equivalent wild-type p53 dosage). The M protein interacts with wild-type p53, increases its stability, and facilitates its nuclear localization in the absence of stress. Despite increasing p53 stability, the M protein does not disrupt p53-Mdm2 interactions and does not prevent p53 ubiquitination. These results suggest molecular mechanisms by which the M protein could influence the aging and cancer resistance phenotypes in the p53+/m mouse.     

Repurposing niclosamide for intestinal decolonization of vancomycin-resistant enterococci

Enterococci are commensal micro-organisms present in the gastrointestinal tract of humans. Although normally innocuous to the host, strains of enterococcus exhibiting resistance to vancomycin (VRE) have been associated with high rates of infection and mortality in immunocompromised patients. Decolonization of VRE represents a key strategy to curb infection in highly-susceptible patients. However, there is a dearth of decolonizing agents available clinically that are effective against VRE. The present study found that niclosamide, an anthelmintic drug, has potent antibacterial activity against clinical isolates of vancomycin-resistant Enterococcus faecium (minimum inhibitory concentration 1–8?µg/mL). E. faecium mutants exhibiting resistance to niclosamide could not be isolated even after multiple (10) serial passages. Based upon these promising in-vitro results and the limited permeability of niclosamide across the gastrointestinal tract (when administered orally), niclosamide was evaluated in a VRE colonization-reduction murine model. Remarkably, niclosamide outperformed linezolid, an antibiotic used clinically to treat VRE infections. Niclosamide was as effective as ramoplanin in reducing the burden of vancomycin-resistant E. faecium in the faeces, caecal content and ileal content of infected mice after only 8 days of treatment. Linezolid, in contrast, was unable to decrease the burden of VRE in the gastrointestinal tract of mice. The results obtained indicate that niclosamide warrants further evaluation as a novel decolonizing agent to suppress VRE infections.     

Adherence to Canada's Food Guide recommendations among Alberta's multi‐ethnic youths is a major concern: findings from the WHY ACT NOW project

Background

Dietary habits formed during youth may result in the development of obesity and chronic diseases in adulthood. We aimed to determine the frequency of the consumption of foods and beverages and the degree of adherence to Canada's Food Guide recommendations among multi‐ethnic youths.

Methods

Participants were recruited from 12 schools in the Edmonton, Alberta area by use of posters, school newsletters and advertisements. A 30‐item food frequency questionnaire was administered by a trained interviewer to assess dietary intake in a convenience sample of 557 (328 females and 229 males) youths aged 11–23 years; for the purpose of the present study, only the 14–18 years age group was considered in the analysis. Participants were divided by sex and self‐identified ethnicity into four groups [Indigenous, African & Middle Eastern (AME ), Asian, and European]. Statistical analysis of the data was undertaken using t ‐tests, Welch's analysis of variance and Games‐Howell tests. P  < 0.05 was considered statistically significant.

Results

Vegetables and Fruit recommendations were the least likely to be followed, with 90.7–96.8% of participants in all groups not consuming the recommended number of servings day^–1. The mean frequency of fruit consumption was lower among Indigenous youths compared to Asian youths (0.90 versus 1.37 times day^–1). A greater proportion of males than females (55.9% versus 44.3%) did not meet the minimum recommendations for Meat and Alternatives (P  = 0.016). The percentage of youths not adhering to recommendations for Milk and Alternatives was 81.7% for Indigenous, 73.3% for AME , 78.6% for Asian and 63.5% for European youths. Indigenous youths more frequently consumed potato chips and soft drinks compared to other ethnic youths. The most frequently consumed beverage was milk (1.25 times day^–1).

Conclusions

The majority of youths did not consume minimum daily recommended servings of Vegetables and Fruit, Milk and Alternatives, and/or Meat and Alternatives food groups. Evidence‐based dietary interventions and public health strategies are needed.