Dual Phases of Respiration Chain Defect-Augmented mROS-Mediated mCa 2+

Mitochondrial respiratory chain (RC) deficits, resulting in augmented mitochondrial ROS (mROS) generation, underlie pathogenesis of astrocytes. However, mtDNA-depleted cells (ρ0) lacking RC have been reported to be either sensitive or resistant to apoptosis. In this study, we sought to determine the effects of RC-enhanced mitochondrial stress following oxidative insult. Using noninvasive fluorescence probe-coupled laser scanning imaging microscopy, the ability to resist oxidative stress and levels of mROS formation and mitochondrial calcium (mCa2+) were compared between two different astrocyte cell lines, control and ρ0 astrocytes, over time upon oxidative stress. Our results showed that the cytoplasmic membrane becomes permeated with YO-PRO-1 dye at 150 and 130 minutes in RBA-1 and ρ0 astrocytes, respectively. In contrast to RBA-1, 30 minutes after 20 mM H2O2 exposure, ρ0 astrocytes formed marked plasma membrane blebs, lost the ability to retain Mito-R, and showed condensation of nuclei. Importantly, H2O2-induced ROS and accompanied mCa2+ elevation in control showed higher levels than ρ0 at early time point but vice versa at late time point. Our findings underscore dual phase of RC-defective cells harboring less mitochondrial stress due to low RC activity during short-term oxidative stress but augmented mROS-mediated mCa2+ stress during severe oxidative insult

Simultaneous Cranioplasty and Subdural-Peritoneal Shunting for Contralateral Symptomatic Subdural Hygroma following Decompressive Craniectomy

Background. Contralateral subdural hygroma caused by decompressive craniectomy tends to combine with external cerebral herniation, causing neurological deficits. Material and Methods. Nine patients who underwent one-stage, simultaneous cranioplasty and contralateral subdural-peritoneal shunting were included in this study. Clinical outcome was assessed by Glasgow Outcome Scale as well as Glasgow Coma Scale, muscle power scoring system, and complications. Results. Postoperative computed tomography scans demonstrated completely resolved subdural hygroma and reversed midline shifts, indicating excellent outcome. Among these 9 patients, 4 patients (44%) had improved GOS following the proposed surgery. Four out of 4 patients with lethargy became alert and orientated following surgical intervention. Muscle strength improved significantly 5 months after surgery in 7 out of 7 patients with weakness. Two out of 9 patients presented with drowsiness due to hydrocephalus at an average time of 65 days after surgery. Double gradient shunting is useful to eliminate the respective hydrocephalus and contralateral subdural hygroma. Conclusion. The described surgical technique is effective in treating symptomatic contralateral subdural hygroma following decompressive craniectomy and is associated with an excellent structural and functional outcome. However, subdural-peritoneal shunting plus cranioplasty thoroughly resolves the subdural hygroma collection, which might deteriorate the cerebrospinal fluid circulation, leading to hydrocephalus

Roadmap on energy harvesting materials

Ambient energy harvesting has great potential to contribute to sustainable development and address growing environmental challenges. Converting waste energy from energy-intensive processes and systems (e.g. combustion engines and furnaces) is crucial to reducing their environmental impact and achieving net-zero emissions. Compact energy harvesters will also be key to powering the exponentially growing smart devices ecosystem that is part of the Internet of Things, thus enabling futuristic applications that can improve our quality of life (e.g. smart homes, smart cities, smart manufacturing, and smart healthcare). To achieve these goals, innovative materials are needed to efficiently convert ambient energy into electricity through various physical mechanisms, such as the photovoltaic effect, thermoelectricity, piezoelectricity, triboelectricity, and radiofrequency wireless power transfer. By bringing together the perspectives of experts in various types of energy harvesting materials, this Roadmap provides extensive insights into recent advances and present challenges in the field. Additionally, the Roadmap analyses the key performance metrics of these technologies in relation to their ultimate energy conversion limits. Building on these insights, the Roadmap outlines promising directions for future research to fully harness the potential of energy harvesting materials for green energy anytime, anywhere

Freshwater Clam Extract Mitigates Neuroinflammation and Amplifies Neurotrophic Activity of Glia: Insights from In Vitro Model of Neurodegenerative Pathomechanism

Background. An extensive body of research suggests that brain inflammation and oxidative stress are the underlying causes of Parkinson’s disease (PD), for which no potent therapeutic approach exists to mitigate the degradation of dopamine neurons. Freshwater clams, an ancient health food of Chinese origin, have been documented to exhibit anti-inflammatory and antioxidant effects. We previously reported that freshwater clam extract (FCE) can attenuate astrocytic activation and subsequent proinflammatory cytokine production from substantia nigra in an MPTP-induced PD mouse model. This article provides insight into the potential mechanisms through which FCE regulates neuroinflammation in a glia model of injury. Materials and methods. In total, 1 μg/mL lipopolysaccharide (LPS) and 200 μM rotenone were conducted in primary glial cell cultures to mimic the respective neuroinflammation and oxidative stress during injury-induced glial cell reactivation, which is relevant to the pathological process of PD. Results. FCE markedly reduced LPS-induced neuroinflammation by suppressing NO and TNF-α production and the expression of pro-inflammatory cytokines. In addition, FCE was effective at reducing rotenone-induced toxicity by diminishing ROS production, promoting antioxidant enzymes (SOD, catalase, and GPx) and minimizing the decline in glial-cell-secreted neurotrophic factors (GDNF, BDNF). These impacts ultimately led to a decrease in glial apoptosis. Conclusions. Evidence reveals that FCE is capable of stabilizing reactive glia, as demonstrated by reduced neuroinflammation, oxidative stress, the increased release of neurotrophic factors and the inhibition of apoptosis, which provides therapeutic insight into neurodegenerative diseases, including PD

Subdural Lesions Linking Additional Intracranial Spaces and Chronic Subdural Hematomas: A Narrative Review with Mutual Correlation and Possible Mechanisms behind High Recurrence

The purpose of this study was two-fold. The first was to investigate the pathologic mechanisms underlying the formation of subdural fluid collection, an umbrella term referring to a condition commonly seen in the clinical setting. Accumulation of the cerebrospinal fluid (CSF) in the subdural space can be referred to in this disease category, disregarding the underlying source of the subdural fluid. However, in these two clinical situations, especially after trauma or brain surgery, fluid collection from the subarachnoid space (subdural hygroma) or from the ventricle to the subarachnoid space and infusion into the subdural space (external hydrocephalus), surgical management of critical patients may adopt the strategies of burr-hole, subduroperitoneal shunt, or ventriculoperitoneal shunt, which present distinctly different thoughts. Crucially, the former can be further transformed into chronic subdural hematoma (CSDH). The second significant theme was the pathogenesis of CSDH. Once the potential dural border cell (DBC) layer is separated such as if a wound is formed, the physiological mechanisms that seem to promote wound healing will resume in the subdural space as follows: coagulation, inflammation, fibroblast proliferation, neovascularization, and fibrinolysis. These aptly correspond to several key characteristics of CSDH formation such as the presence of both coagulation and fibrinolysis signals within the clot, neomembrane formation, angiogenesis, and recurrent bleeding, which contribute to CSDH failing to coagulate and absorb easily. Such a complexity of genesis and the possibility of arising from multiple pathological patterns provide a reasonable explanation for the high recurrence rate, even after surgery. Among the various complex and clinically challenging subdural lesions, namely, CSDH (confined to the subdural space alone), subdural hygroma (linked in two spaces), and external hydrocephalus (linked in three spaces), the ability to fully understand the different pathological mechanisms of each, differentiate them clinically, and devote more interventional strategies (including anti-inflammatory, anti-angiogenic, and anti-fibrinolysis) will be important themes in the future

Beneficial Impacts of Alpha-Eleostearic Acid from Wild Bitter Melon and Curcumin on Promotion of CDGSH Iron-Sulfur Domain 2: Therapeutic Roles in CNS Injuries and Diseases

Neuroinflammation and abnormal mitochondrial function are related to the cause of aging, neurodegeneration, and neurotrauma. The activation of nuclear factor κB (NF-κB), exaggerating these two pathologies, underlies the pathogenesis for the aforementioned injuries and diseases in the central nervous system (CNS). CDGSH iron-sulfur domain 2 (CISD2) belongs to the human NEET protein family with the [2Fe-2S] cluster. CISD2 has been verified as an NFκB antagonist through the association with peroxisome proliferator-activated receptor-β (PPAR-β). This protective protein can be attenuated under circumstances of CNS injuries and diseases, thereby causing NFκB activation and exaggerating NFκB-provoked neuroinflammation and abnormal mitochondrial function. Consequently, CISD2-elevating plans of action provide pathways in the management of various disease categories. Various bioactive molecules derived from plants exert protective anti-oxidative and anti-inflammatory effects and serve as natural antioxidants, such as conjugated fatty acids and phenolic compounds. Herein, we have summarized pharmacological characters of the two phytochemicals, namely, alpha-eleostearic acid (α-ESA), an isomer of conjugated linolenic acids derived from wild bitter melon (Momordica charantia L. var. abbreviata Ser.), and curcumin, a polyphenol derived from rhizomes of Curcuma longa L. In this review, the unique function of the CISD2-elevating effect of α-ESA and curcumin are particularly emphasized, and these natural compounds are expected to serve as a potential therapeutic target for CNS injuries and diseases

High risk of medical malpractice and breach of contract - focused on the regime of clinical cases in brain and spine surgery

近年來醫療事故層出不窮，由於社會經濟發展、民眾自我權益意識高漲及醫療科技進步，醫病之間的糾紛爭議也更加複雜。同時，雖然醫療訴訟判決有援引民法第184、185、188、192~195、227條、消保法第7條及醫療法、醫師法等相關條文作為法源依據，但實務上判決的判定標準似乎難有一致之見解。尤其是如心臟及腦脊椎等高風險手術糾紛，更易有分歧的見解。 本研究希望從醫師之醫療行為出發，於相關之法令規定下，探討高風險醫療之各種法律關係，並回顧國內文獻與實務判決，探究高風險醫療行為之債務不履行責任。最後本研究以腦脊椎手術訴訟案例為中心，探討了五個判決先例，發現相關案例的訴訟上主張及攻擊防禦，主要集中在侵權行為及契約履行之判定。同時，經由五個案例的評析之後，本研究發現，在高風險醫療訴訟當中，兩造若能在債務不履行事實認定、可歸責事由及法律效果的判斷過程中，提出更多客觀證據，將可引導法官運用更多客觀判定標準，作成客觀成分更高之主觀心證判斷。而在高風險醫療訴訟中，所謂客觀判定標準，本研究認為是「善良管理人義務」、「醫療法規及技術規定」、「醫審會評鑑報告」及「醫療專業人士證詞」。希望藉由個案探討醫生債務不履行之相對判定標準，俾使執業醫師、病患及法律實務工作者在面臨類似案件時，能有所依循，並為日後同類研究之基礎，擴及性質相近之其他醫療類別，以收觸類旁通之效

Statistical relevance of mean hematoma density and it's internal architecture: Potential clinical application in chronic subdural hematomas

Background: The postoperative recurrence rate of chronic subdural hematomas (CSDHs) ranges from 9% to 20%, which is a serious concern for neurosurgeons. Both qualitative and quantitative assessment methods have been developed to identify the mechanisms involved in postoperative recurrence. These methods include Nakaguchi's clinical classification scheme and the quantification of mean hematoma density (MHD). This is the first study to examine the correlations between the quantification of MHD and Nakaguchi's clinical classification of patients with CSDHs. Materials and Methods: This study investigated 35 consecutive cases of CSDH between July 2010 and July 2013. In accordance with Nakaguchi's clinical classification, CSDH cases were separated into four groups: homogenous, laminar, separated, and trabecular. In addition, we quantified the area of the hematoma according to MHD using a computer-based image analysis of preoperative brain computed tomography scans. Results: The mean age of patients was 72.2 ± 8.05 years (range: 55–86). Mean MHD values were as follows: trabecular (12.45 ± 0.72 HU), homogenous (14.46 ± 4.51 HU), laminar (25.99 ± 0.93 HU), and separated (36.32 ± 3.04 HU). Differences in MHD were statistically significant for all CSDH types (P < 0.001, ANOVA with Student–Newman–Keuls post hoc test), and we observed a significant linear relationship between MHD and the priority order of clinical CSDH types determined according to postoperative recurrence (Spearman's rank correlation coefficient = 0.842, P < 0.001). Conclusions: This study provides statistical evidence that MHD is significantly correlated with Nakaguchi's clinical classification of CSDH. The applications of MHD quantification and hematoma's internal architecture helped to gain better understanding of possible mechanisms underlying CSDH recurrence