Optical scatter imaging detects mitochondrial swelling in living tissue slices

Mitochondrial swelling is observed in neuronal injury and is a key event in many pathways to cell death. Currently, there is no technique for directly measuring mitochondrial size changes within living tissue slices with a field of view of several millimeters. In this paper, we test our hypothesis that Mie light-scatter theory can be used to study mitochondrial swelling in living tissue sections. Using a unique dual-angle scatter ratio (DASR) optical imaging system previously demonstrated to be sensitive to latex particle size changes and N-methyl-D-aspartate (NMDA) treatment of hippocampal slices, we studied mitochondrial swelling induced by 500 microM NMDA treatment of hippocampal slices. We observed a strong (R(2) = 0.73) and significant (P < 0.000005) correlation between the electron microscopy-determined diameters of swollen, intact mitochondria and the DASR imaging. We examined the robustness of the technique by evaluating the correlation between the dual-angle scatter ratio and the diameter of the dendrites, observed to swell, in NMDA-treated slices and found no correlation (R(2) = 0.06). The advantage of DASR imaging over electron microscopy or other methods of studying mitochondrial swelling is the sensitivity of DASR imaging to mitochondrial swelling over a large field of view (>9 mm(2)) in an intact tissue slice. This novel technique may allow for the study of regional changes in mitochondrial swelling and recovery as sequential events within a single specimen. This technique will eventually be useful in studying the efficacy of stroke and other disease therapies targeting mitochondrial swelling.     

The mechanisms and evidence of efficacy of electrical stimulation for healing of pressure ulcer: A systematic review

The objective of this article is to provide a systematic review of the efficacy of electrical stimulation in healing pressure ulcer and to review its mechanism of action. The Cochrane Library, PubMed, CINAHL, Medline, EMBASE, and NHS EED were searched for relevant interventional studies including randomized controlled trials (RCTs) and observational studies. A best‐evidence synthesis was performed to summarize the results of the included studies. A total of seven RCTs and two observational studies met the inclusion criteria. Moderate level of evidence of efficacy with low risk of bias was shown in all seven RCTs. Although some studies have used continuous direct current, most other investigators opted to use high‐voltage pulsed current to minimize the risk of skin burn and to achieve greater current penetration. Overall, the incidence of adverse effects was very low. Two studies that assessed the economic impacts of electrical stimulation revealed substantial health care cost savings. The mechanisms through which electrical stimulation exerts a positive effect on pressure ulcer healing are reasonably well established. Clinical trials have revealed a moderate level of evidence to support its use as an ancillary treatment modality for healing pressure ulcer. Recommendations regarding the optimal electrical stimulation parameters and dosage of use are provided. Further studies to investigate potential barriers that may impede widespread use in different clinical settings are needed.     

Blood lead and cadmium levels and renal function in Korean adults

Background

The objective of this study was to evaluate the associations of blood lead and cadmium levels with estimated glomerular filtration rate (eGFR) and proteinuria in Korean adults.

Methods

This was a cross-sectional study based on the Korea Nation Health and Nutrition Examination Survey (KNHANES) to analyze the association of blood lead and cadmium levels with renal dysfunction and urine protein excretion. We defined renal dysfunction as eGFR < 60 ml/min/1.73 m², as measured by the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation and proteinuria as positive urine dip-stick result.

Results

Blood lead and cadmium levels were significantly increased in the renal dysfunction group compared with the normal renal function group. Lead levels were significantly higher in the proteinuria group than in the group with no proteinuria. There were no differences in cadmium levels according to the amount of proteinuria. Multivariate logistic regression analysis adjusted for age and sex demonstrated higher lead and cadmium levels in the renal dysfunction group than in the group with normal renal function [odds ratio (OR) 1.344, 95 % confidence interval (CI) 1.157–1.162, P < 0.05; OR 1.467, 95 % CI 1.077–1.999, P < 0.05, respectively]. For proteinuria, the fully adjusted ORs comparing the highest versus the lowest lead and cadmium quartiles were 1.22 (95 % CI 1.00–1.50) and 0.51 (95 % CI 0.24–1.08), respectively, showing no significance. For reduced eGFR, the fully adjusted ORs comparing the highest versus the lowest lead and cadmium quartiles were 1.23 (95 % CI 0.98–1.53) and 1.93 (95 % CI 1.39–2.67), respectively, showing the significant association between lead and cadmium levels and renal function. The risk of having reduced eGFR for individuals in the highest quartiles of both lead and cadmium levels in blood was greater than for those in the highest quartile of blood level of lead or cadmium only.

Conclusion

The CKD-EPI equation showed that blood lead and cadmium levels were associated with renal dysfunction in the Korean adult population. This finding has significant implications for environmental institutional strategies regarding heavy metal exposure.     

Risk factors of delayed surgical evacuation for initially nonoperative acute subdural hematomas following mild head injury

Background

Although the majority of patients with minimal acute subdural hematomas (aSDHs) can be managed conservatively, some require delayed aSDH evacuation due to hematoma enlargement. This study was designed to determine the risk factors associated with delayed hematoma enlargement leading to surgery in patients with aSDHs who did not initially require surgical intervention.

Methods

From 2002 to 2012, 98 patients were treated for nonoperative aSDHs following mild head injury (Glasgow Coma Scale scores of 13–15). The outcome variables were radiographic evidence of SDH enlargement on serially obtained computed tomography (CT) images and later surgical evacuation. Univariate and multivariate analyses were applied to both the demographic and initial radiographic features to identify risk factors for SDH progression and surgery.

Results

Overall, 64 patients (65 %) revealed minimal SDH or spontaneous hematoma resolution (conservative group) with conservative management at their last follow-up CT scan. The remaining 34 patients (35 %) received delayed hematoma evacuation (delayed surgery group) a median of 17 days after the head trauma. There were no significant differences between the two groups for baseline characteristics, including age, injury type, degree of brain atrophy, prior history of antithrombotic drugs, and coagulopathy. The presence of cerebral contusions and subarachnoid hemorrhages was more common in the conservative group (p?=?0.003 and p?=?0.003, respectively). On multivariate analysis, hematoma volume (p?=?0.01, odds ratio [OR]?=?1.094, 95 % confidence interval [CI]?=?1.021–1.173) and degree of midline shift (p?=?0.01, OR?=?1.433, 95 % CI?=?1.088–1.888) on the initial CT scan were independently associated with delayed hematoma evacuation.

Conclusions

A critical proportion of patients with minimal aSDHs occurring after mild head injury can progress over several weeks and require hematoma evacuation. Especially patients with a large initial SDH volume and accompanying midline shift require careful monitoring of hematoma progression.     

Longitudinal changes in seizure outcomes after resection of cerebral cavernous malformations in patients presenting with seizures: a long-term follow-up of 46 patients

Background

Seizure is the most common presentation in patients with cerebral cavernous malformations (CCMs). Although many articles have documented seizure outcomes after resection of CCM, few have conducted long-term follow-ups; thus, the fluctuating seizure outcomes have been neglected. The purpose of this study is to describe long-term postoperative seizure outcomes in patients with CCM and to compare seizure outcomes between patients with sporadic seizures and those with chronic seizures.

Methods

Forty-six patients with CCM presenting with seizures underwent surgery. The male-to-female ratio was 1:1, and the average age at initial seizure onset was 27.6 years. The mean preoperative seizure duration was 42.7 months. Patients were divided into two groups: a chronic group (N?=?20) and a sporadic group (N?=?26) according to seizure frequency and duration. The mean postoperative follow-up duration was 96.3 months, and the postoperative seizure outcomes were checked annually based upon Engel’s classification.

Results

After the first year of follow-up, 80.8 % of the sporadic group and 75.0 % of the chronic group were evaluated as Engel class I. These rates increased to 100.0 % and 90.0 %, respectively, at the eighth year of follow-up. Overall, 29 (63.0 %) of the 46 patients experienced changes in seizure outcomes over the follow-up period. Despite their delayed improvements, the chronic group showed less favorable outcomes throughout follow-up (p?=?0.025).

Conclusions

Long-term follow-up is indispensable for accurately assessing postoperative seizure outcomes because these outcomes change continuously. We recommend earlier surgery to achieve seizure-free status in patients with CCM. However, even in the chronic group, surgery is recommended, considering the overall delayed improvement.