Computed Tomography Study of the Retrosigmoid Craniotomy Keyhole Approach Using Surface Landmarks.

Background: Due to a lack of accessibility and individual differences in surgical procedures, many previous studies on keyholes are not practical. Objective: To study the surface landmarks for optimal keyhole placement in the retrosigmoid approach. Methods: The three-dimensional (3D) skull images of 79 patients were reconstructed using workstations, with a total of 149 hemiskull base 3D images then analyzed. Skull-surface landmarks were marked, the lateral-skull surface was observed, and the positional relationships between the asterion and the extension line of the posterior margin of the mastoid process were measured. The position of the superior curvature of the sigmoid sinus groove was located before it was projected onto the lateral surface of the skull and defined as the keypoint. The positional relationship between the keypoint and the skull-surface landmarks was observed in an established coordinate system using spatial proportion relationships. Results: The asterion was located around the extension line of the posterior margin of the mastoid process, and the vertical distance from the extension line was <15 mm. It was found that 93.29% (139/149) of the keypoints were located in a 7 mm radius circle, with the center at (-0.41, -3.01) in the coordinate system in the 3D computed tomography images. Conclusion: When using this method, the spatial proportion relationship of the anatomical marks can accurately locate keyholes, therefore providing technical support when employing the retrosigmoid approach.

Relationship between nosocomial infections and coronavirus disease 2019 in the neurosurgery unit: clinical characteristics and outcomes from a Chinese Tertiary-Care Hospital.

BACKGROUND: The COVID-19 pandemic has raised awareness of infection prevention and control. We found that the incidence of nosocomial infection in neurosurgery has changed. This study aimed to evaluate the impact of "coronavirus disease 2019 (COVID-19) prevention and control measures" on nosocomial infections in neurosurgery. METHODS: To explore changes in nosocomial infections in neurosurgery during the COVID-19 pandemic, the clinical data of inpatients undergoing neurosurgery at Taizhou Hospital of Zhejiang Province between January 1 and April 30, 2020 (COVID-19 era) were first analyzed and then compared with those from same period in 2019 (first pre-COVID-19 era). We also analyzed data between May 1 and December 31, 2020 (post-COVID-19 era) at the same time in 2019 (second pre-COVID-19 era). RESULTS: The nosocomial infection rate was 7.85% (54/688) in the first pre-COVID-19 era and 4.30% (26/605) in the COVID-19 era (P = 0.01). The respiratory system infection rate between the first pre-COVID-19 and COVID-19 eras was 6.1% vs. 2.0% (P < 0.01), while the urinary system infection rate was 1.7% vs. 2.0% (P = 0.84). Between the first pre-COVID-19 and COVID-19 eras, respiratory system and urinary infections accounted for 77.78% (42/54) vs. 46.15% (12/26) and 22.22% (12/54) vs. 46.15% (12/26) of the total nosocomial infections, respectively (P < 0.01). Between the second pre-COVID-19 and post-COVID-19 eras, respiratory system and urinary accounted for 53.66% (44/82) vs. 40.63% (39/96) and 24.39% (20/82) vs. 40.63% (39/96) of the total nosocomial infections, respectively (P = 0.02). CONCLUSIONS: The incidence of nosocomial infections in neurosurgery reduced during the COVID-19 pandemic. The reduction was primarily observed in respiratory infections, while the proportion of urinary infections increased significantly.

Asbestos Detection with Fluorescence Microscopy Images and Deep Learning.

Fluorescent probes can be used to detect various types of asbestos (serpentine and amphibole groups); however, the fiber counting using our previously developed software was not accurate for samples with low fiber concentration. Machine learning-based techniques (e.g., deep learning) for image analysis, particularly Convolutional Neural Networks (CNN), have been widely applied to many areas. The objectives of this study were to (1) create a database of a wide-range asbestos concentration (0-50 fibers/liter) fluorescence microscopy (FM) images in the laboratory; and (2) determine the applicability of the state-of-the-art object detection CNN model, YOLOv4, to accurately detect asbestos. We captured the fluorescence microscopy images containing asbestos and labeled the individual asbestos in the images. We trained the YOLOv4 model with the labeled images using one GTX 1660 Ti Graphics Processing Unit (GPU). Our results demonstrated the exceptional capacity of the YOLOv4 model to learn the fluorescent asbestos morphologies. The mean average precision at a threshold of 0.5 (mAP@0.5) was 96.1% ± 0.4%, using the National Institute for Occupational Safety and Health (NIOSH) fiber counting Method 7400 as a reference method. Compared to our previous counting software (Intec/HU), the YOLOv4 achieved higher accuracy (0.997 vs. 0.979), particularly much higher precision (0.898 vs. 0.418), recall (0.898 vs. 0.780) and F-1 score (0.898 vs. 0.544). In addition, the YOLOv4 performed much better for low fiber concentration samples (<15 fibers/liter) compared to Intec/HU. Therefore, the FM method coupled with YOLOv4 is remarkable in detecting asbestos fibers and differentiating them from other non-asbestos particles.

Reduced carbon use efficiency and increased microbial turnover with soil warming.

Global soil carbon (C) stocks are expected to decline with warming, and changes in microbial processes are key to this projection. However, warming responses of critical microbial parameters such as carbon use efficiency (CUE) and biomass turnover (rB) are not well understood. Here, we determine these parameters using a probabilistic inversion approach that integrates a microbial-enzyme model with 22 years of carbon cycling measurements at Harvard Forest. We find that increasing temperature reduces CUE but increases rB, and that two decades of soil warming increases the temperature sensitivities of CUE and rB. These temperature sensitivities, which are derived from decades-long field observations, contrast with values obtained from short-term laboratory experiments. We also show that long-term soil C flux and pool changes in response to warming are more dependent on the temperature sensitivity of CUE than that of rB. Using the inversion-derived parameters, we project that chronic soil warming at Harvard Forest over six decades will result in soil C gain of <1.0% on average (1st and 3rd quartiles: 3.0% loss and 10.5% gain) in the surface mineral horizon. Our results demonstrate that estimates of temperature sensitivity of microbial CUE and rB can be obtained and evaluated rigorously by integrating multidecadal datasets. This approach can potentially be applied in broader spatiotemporal scales to improve long-term projections of soil C feedbacks to climate warming.

Ki-67 as a prognostic marker in early-stage non-small cell lung cancer in Asian patients: a meta-analysis of published studies involving 32 studies.

BACKGROUND: Despite the large number of published papers analyzing the prognostic role of Ki-67 in NSCLC, it is still not considered an established factor for routine use in clinical practice. The present meta-analysis summarizes and analyses the associations between Ki-67 expression and clinical outcome in NSCLC patients. METHODS: PubMed, Cochrane, and Embase databases were searched systematically using identical search strategies. The impacts of Ki-67 expression on survival in patients with NSCLC and NSCLC subtypes were evaluated. Furthermore, the association between Ki-67 expression and the clinicopathological features of NSCLC were evaluated. RESULTS: In total, 32 studies from 30 articles met the inclusion criteria, involving 5600 patients. Meta-analysis results suggested that high Ki-67 expression was negatively associated with overall survival (OS; HR = 1.59, 95 % CI 1.35-1.88, P < 0.001) and disease-free survival (DFS; HR = 2.21, 95 % CI 1.43-3.42, P < 0.001) in NSCLC patients. Analysis of the different subgroups of NSCLC suggested that the negative association between high Ki-67 expression and OS and DFS in Asian NSCLC patients was stronger than that in non-Asian NSCLC patients, particularly in early-stage (Stage I-II) adenocarcinoma (ADC) patients. Additionally, while high expression was more common in males, smokers, and those with poorer differentiation, there was no correlation between high Ki-67 expression and age or lymph node status. Importantly, significant correlations between high Ki-67 expression and clinicopathological features (males, higher tumor stage, poor differentiation) were seen only in Asian NSCLC patients. CONCLUSIONS: The present meta-analysis indicated that elevated Ki-67 expression was associated with a poorer outcome in NSCLC patients, particularly in early-stage Asian ADC patients. Studies with larger numbers of patients are needed to validate our findings.

Relationships between meteorological parameters and criteria air pollutants in three megacities in China.

Meteorological conditions play a crucial role in ambient air pollution by affecting both directly and indirectly the emissions, transport, formation, and deposition of air pollutants. In this study, the relationships between meteorological parameters and ambient air pollutants concentrations in three megacities in China, Beijing, Shanghai, and Guangzhou were investigated. A systematic analysis of air pollutants including PM2.5, PM10, CO, SO2, NO2, and O3 and meteorological parameters including temperature, wind speed (WS), wind direction (WD) and relative humanity (RH) was conducted for a continuous period of 12 months from March 2013 to February 2014. The results show that all three cities experienced severe air quality problems. Clear seasonal trends were observed for PM2.5, PM10, CO, SO2 and NO2 with the maximum concentrations in the winter and the minimum in the summer, while O3 exhibited an opposite trend. Substantially different correlations between air pollutants and meteorological parameters were observed among these three cities. WS reversely correlated with air pollutants, and temperature positively correlated with O3. Easterly wind led to the highest PM2.5 concentrations in Beijing, westerly wind led to high PM2.5 concentrations in Shanghai, while northern wind blew air parcels with the highest PM2.5 concentrations to Guangzhou. In Beijing, days of top 10% PM2.5, PM10, CO, and NO2 concentrations were with higher RH compared to days of bottom 10% concentrations, and SO2 and O3 showed no distinct RH dependencies. In Guangzhou, days of top 10% PM2.5, PM10, CO, SO2, NO2 and O3 concentrations were with lower RH compared to days of bottom 10% concentrations. Shanghai showed less fluctuation in RH between top and bottom 10%. These results confirm the important role of meteorological parameters in air pollution formation with large variations in different seasons and geological areas. These findings can be utilized to improve the understanding of the mechanisms that produce air pollution, enhance the forecast accuracy of the air pollution under different meteorological conditions, and provide effective measures for mitigating the pollution.

Antenna-specific glutathione S-transferase in male silkmoth Bombyx mori.

Glutathione S-transferases (GSTs) are multifunctional enzymes that are widely distributed in different species. GSTs detoxify exogenous and endogenous substances by conjugation to reduced glutathione. We characterized BmGSTD4, an antenna-specific GST, in male silkmoths. The full-length mRNA of Bmgstd4 was cloned by RACE-PCR and contained an open reading frame of 738 bp encoding a 245 amino acid protein. The antenna specificity of BmGSTD4 was validated at the mRNA and protein levels and BmGSTD4 was shown to localize in the sensillum of male silkmoth antennae. Homology modeling and multi-sequence alignment suggested that BmGSTD4 was a typical GST belonging to the δ class and had a canonical GST fold with a conserved N-terminus, including a glutathione-binding site and a C-terminal domain harboring a hydrophobic substrate-binding site. Restricted expression of BmGSTD4 in silkmoth antennae combined with GST activity suggested that BmGSTD4 was involved in the detoxification of harmful chemicals.

Research progress and challenges in stem cell therapy for diabetic foot: Bibliometric analysis and perspectives.

BACKGROUND: Stem cell therapy has shown great potential for treating diabetic foot (DF). AIM: To conduct a bibliometric analysis of studies on the use of stem cell therapy for DF over the past two decades, with the aim of depicting the current global research landscape, identifying the most influential research hotspots, and providing insights for future research directions. METHODS: We searched the Web of Science Core Collection database for all relevant studies on the use of stem cell therapy in DF. Bibliometric analysis was carried out using CiteSpace, VOSviewer, and R (4.3.1) to identify the most notable studies. RESULTS: A search was conducted to identify publications related to the use of stem cells for DF treatment. A total of 542 articles published from 2000 to 2023 were identified. The United States had published the most papers on this subject. In this field, Iran's Shahid Beheshti University Medical Sciences demonstrated the highest productivity. Furthermore, Dr. Bayat from the same university has been an outstanding researcher in this field. Stem Cell Research & Therapy is the journal with the highest number of publications in this field. The main keywords were "diabetic foot ulcers," "wound healing," and "angiogenesis." CONCLUSION: This study systematically illustrated the advances in the use of stem cell therapy to treat DF over the past 23 years. Current research findings suggested that the hotspots in this field include stem cell dressings, exosomes, wound healing, and adipose-derived stem cells. Future research should also focus on the clinical translation of stem cell therapies for DF.

Targeted mutation of Fas ligand gene attenuates brain inflammation in experimental stroke.

Inflammation is an important contributing mechanism in ischemic brain injury. The current study elucidates a previously unexplored role of Fas ligand (FasL) in post-stroke inflammatory responses that is independent of its well-known effect in triggering apoptosis. Focal cerebral ischemia was induced for 2 h by right middle cerebral artery occlusion (MCAO) in FasL mutant (gld) and wild-type mice. FasL mutation profoundly reduced brain damage and improved neurological performance from 6 to 72 h after ischemic stroke. The production of inflammatory cytokines in the brain was attenuated in gld mice after ischemia in the absence of dramatic change in inflammatory cell apoptosis. FasL mutation attenuated the recruitment of peripheral inflammatory cells (neutrophil) and inhibited the activation of residential glial cells (microglia and astrocyte). FasL mutation reduced CD8(+) T cells and turned the Th1/Th2 balance towards Th2 in the brain and peripheral blood after cerebral ischemia. In contrast to cerebral ischemia, the molecular and cellular inflammatory changes induced by intracerebroventricular injection of lipopolysaccharide (LPS) were also attenuated in gld mice. Moreover, the soluble FasL (sFasL) and phospho-SAPK/JNK were decreased in gld mice, suggesting that the inflammatory role of FasL in experimental stroke might relate to sFasL and the c-Jun N-terminal kinase (JNK) signaling pathway. Taken together, our data suggest a novel role of FasL in the damaging inflammatory responses associated with cerebral ischemia. Neutralization of FasL may be a novel therapeutic strategy to suppress post-stroke inflammation and improve the long-term outcomes of stroke.

Evaluation of burnout among stay-behind healthcare workers during the current Omicron wave of COVID-19 in Taizhou, China.

Background: Since February 2022, a new Omicron wave of COVID-19 emerged in Shanghai, China. Many healthcare workers came to Shanghai from hospitals of other parts of China as aid workers. Hospitals in areas with mild COVID-19 outbreaks will inevitably be understaffed, it is likely to cause job burnout of stay-behind healthcare workers. Stay-behind healthcare workers were those who had not been dispatched to support COVID-19 prevention and control in other regions. This study was designed to evaluate the burnout among stay-behind healthcare workers in the current COVID-19 Omicron wave in Taizhou, China. Methods: A population-based, anonymous, cross-sectional online survey was designed in the Wen-Juan Xing platform. The survey was sent to all stay-behind healthcare workers of the hospital (n = 1739) from April 29 to May 3, 2022. The Maslach Burnout Inventory-General Survey (MBI-GS) was used for the burnout survey. For univariate analysis, the χ2 test and one way ANOVA were used to assess differences in categorical variables and continuous variables, respectively. The effect of independent associated risk factors on each type of burnout was examined using the multinomial logistic regression model. Results: A total of 434 participants completed the survey invitation effectively. A total of 71.2% of stay-behind healthcare workers experienced burnout during COVID-19, including 54.8% experiencing mild to moderate burnout and 16.4% experiencing severe burnout. Night shift, depression, social support, positive coping and number of children appeared to be significantly related to mild to moderate burnout. Night shift, depression, social support, positive coping, number of children, professional title, and anxiety appeared to be significantly related to severe burnout. Conclusion: Job burnout among stay-behind healthcare workers was an important problem during the current Omicron wave of COVID-19. Night shift, depression, social support, positive coping, and number of children were associated with mild to moderate and severe burnout. Anxiety and professional title were associated with severe burnout.

catena-Poly[[tris[silver(I)-µ-4,4'-bi-pyridine-κN:N']] tris-(perchlorate) di-hydrate].

In the title compound, {[Ag(3)(C(10)H(8)N(2))(3)](ClO(4))(3)·2H(2)O}(n), one of the Ag(I) ions, one of the 4,4'-bipyridine (bipy) ligands and one of the perchlorate anions are each situated on a twofold rotation axis. Each Ag(I) ion is coordinated by two N atoms from two bridging bipy ligands, forming chains along [101]. π-π inter-actions between the pyridine rings [centroid-centroid distances = 3.638 (8) and 3.688 (8) Å] connect the chains. Inter-molecular O-H⋯O hydrogen bonds link the uncoord-inated water mol-ecules and the perchlorate anions.

Bis(µ-3-chloro-benzene-1,2-dicarboxyl-ato-κO:O)bis-[diaqua-(5,5'-dimethyl-2,2'-bipyridine-κN,N')copper(II)].

In the centrosymmetric binuclear title compound, [Cu(2)(C(8)H(3)ClO(4))(2)(C(12)H(12)N(2))(2)(H(2)O)(4)], the Cu(II) ion is six-coordinated by two N atoms from a 5,5'-dimethyl-2,2'-bipyridine ligand, two bridging O atoms from two 3-chloro-benzene-1,2-dicarboxyl-ate ligands and two water mol-ecules in a distorted octa-hedral geometry. The binuclear complex mol-ecules are linked together by inter-molecular O-H⋯O hydrogen bonds into a layer parallel to (100). The layers are connected by C-H⋯Cl hydrogen bonds. Intra-molecular O-H⋯O hydrogen bonds and π-π inter-actions [centroid-centroid distance = 3.5958 (16) Å] are also present.

Irradiance uniformity optimization for a photodynamic therapy treatment device with 3D scanner.

SIGNIFICANCE: The light dose in photodynamic therapy (PDT) has a considerable influence on its treatment effect, and irradiance uniformity is an issue of much concern for researchers. However, achieving intelligent and personalized dosimetry adjustments remains a challenge for current PDT instruments. AIM: To meet the requirements of intelligent and personalized dosimetry adjustments for the light dose on an irregular surface, a new PDT device with its optimal control method is proposed. APPROACH: This research introduces a new PDT device that includes a 3D scanner, a light-emitting diode (LED) array, and a computer. The 3D scanner is proposed to generate the point cloud of the lesion and the LED array light source, and obtain the relative position and rotation parameters between them. Then, an image segmentation algorithm is used to segment the lesion point cloud into several cluster regions. Last, the current of each LED unit is adjusted separately to achieve the expected irradiance on each cluster. RESULTS: Compared with the general light source, the optimized light source increases the effective irradiance area by 9% to 15% and improves its uniformity by ∼9 % on a human port-wine stain head model. CONCLUSIONS: The device and its optimal method may be used for optimizing the light dosimetry to realize intelligent and personalized treatment.

Geometry preserving projections algorithm for predicting membrane protein types.

Given a new uncharacterized protein sequence, a biologist may want to know whether it is a membrane protein or not? If it is, which membrane protein type it belongs to? Knowing the type of an uncharacterized membrane protein often provides useful clues for finding the biological function of the query protein, developing the computational methods to address these questions can be really helpful. In this study, a sequence encoding scheme based on combing pseudo position-specific score matrix (PsePSSM) and dipeptide composition (DC) is introduced to represent protein samples. However, this sequence encoding scheme would correspond to a very high dimensional feature vector. A dimensionality reduction algorithm, the so-called geometry preserving projections (GPP) is introduced to extract the key features from the high-dimensional space and reduce the original high-dimensional vector to a lower-dimensional one. Finally, the K-nearest neighbor (K-NN) and support vector machine (SVM) classifiers are employed to identify the types of membrane proteins based on their reduced low-dimensional features. Our jackknife and independent dataset test results thus obtained are quite encouraging, which indicate that the above methods are used effectively to deal with this complicated problem of predicting the membrane protein type.

IL-2mAb reduces demyelination after focal cerebral ischemia by suppressing CD8+ T cells.

AIMS: Demyelination, one of the major pathological changes of white matter injury, is closely related to T-cell-mediated immune responses. Thus, we investigate the role of an IL-2 monoclonal antibody (IL-2mAb, JES6-1) in combatting demyelination during the late phase of stroke. METHODS: IL-2mAb or IgG isotype antibody (0.25 mg/kg) was injected intraperitoneally 2 and 48 hours after middle cerebral artery occlusion (MCAO) surgery. Infarct volume, peripheral immune cell infiltration, microglia activation, and myelin loss were measured by 2,3,5-triphenyte trazoliumchloride staining, immunofluorescence staining, flow cytometry, and Western blot. Intraperitoneal CD8 neutralizing antibody (15 mg/kg) was injected 1 day before MCAO surgery to determine the role of CD8+ T cells on demyelinating lesions. RESULTS: IL-2mAb treatment reduced brain infarct volume, attenuated demyelination, and improved long-term sensorimotor functions up to 28 days after dMCAO. Brain infiltration of CD8+ T cells and peripheral activation of CD8+ T cells were both attenuated in IL-2 mAb-treated mice. The protection of IL-2mAb on demyelination was abolished in mice depleted of CD8+ T cell 1 week after stroke. CONCLUSIONS: IL-2mAb preserved white matter integrity and improved long-term sensorimotor functions following cerebral ischemic injury. The activation and brain infiltration of CD8+ T cells are detrimental for demyelination after stroke and may be the major target of IL-2mAb posttreatment in the protection of white matter integrity after stroke.

[Study on expression of matrix metalloproteinase-2 and matrix metalloproteinase-9 in brain tissue adjacent to hemorrhage after brain hemorrhage in human].

OBJECTIVE: To investigate the expression and significance of matrix metalloproteinase-2 (MMP-2) and MMP-9 in peri-hematoma brain tissues after acute brain hemorrhage in human. METHODS: Forty-two patients with acute brain hemorrhage received surgery, the brain tissues adjacent to hemorrhagic site were obtained during surgery, and positive expressions of MMP-2 and MMP-9 were determined with immunohistochemical staining. Brain tissues from 30 patients with cerebral trauma were obtained to serve as controls. RESULTS: The positive expressions of MMP-2 and MMP-9 in focal brain tissues were significantly elevated in early acute brain hemorrhage. Compared with 28 and 27 cases with MMP-2 and MMP-9 positive expression respectively in control group, there were 39 and 37 cases with MMP-2 and MMP-9 positive expression respectively in acute brain hemorrhage group. There were no significant differences between two groups (both P>0.05). CONCLUSION: MMP-2 and MMP-9 might contribute to brain edema formation in the acute intra-cerebral hemorrhage of human.

Dynamic model of vascular-targeted photodynamic therapy.

Vascular-targeted photodynamic therapy has shown efficiency in treating port wine stains. A dynamic model that incorporates blood flow, kinetic diffusion, oxygen and photosensitizer consumption and reaction, and light modulation is proposed to reveal the interactions among light, photosensitizer, and oxygen. Simulation results show that pulse light modulation synchronized with heartbeats hold the advantage of increased singlet oxygen accumulation, higher oxygen concentration and lower temperature. Meanwhile, constant light treatment is advantageous in terms of higher temperature, lower total oxygen concentration and singlet oxygen accumulation. Therefore, the optimized treatment protocol may involve a balance among the phototoxicity, hypoxia, and photothermolysis.

Effects of dietary oregano essential oil and vitamin E supplementation on meat quality, stress response and intestinal morphology in pigs following transport stress.

This study investigates the effects of dietary oregano essential oil (OEO) and vitamin E (Vit E) supplementation on meat quality, stress response and intestinal morphology in pigs following transport stress. A total of 288 finishing pigs were randomly assigned to three groups: a basal diet or a basal diet supplemented either with 200 mg/kg Vit E or 25 mg/kg OEO. After a 28-day feeding trial, total of 132 finishing pigs according diet and transport stress were assigned to one of four treatment groups: 1) control treatment without transport stress (Control group), 2) control treatment with 5-hr transport stress (Negative group), 3) Vit E treatment with 5-hr transport stress and 4) OEO treatment with 5-hr transport stress. Transport stress pigs had lower muscle 45 min pH (pHi) and higher drip loss than control pigs. Dietary OEO and Vit E supplementation significantly increased 45min pH under transport stress, and the OEO groups produced lower 24-hr drip loss values (P<0.05) than that of pigs from the negative group. The OEO-supplemented pigs showed decreased serum levels of creatine kinase (CK) and cortisol (P<0.05), and decreased Hsp 27 (heat shock protein 27) and Hsp 70 (heat shock protein 70) mRNA expression in the muscle (P<0.05). Additionally, histological analysis revealed intestinal epithelial damage in transport stress pigs that was reversed by dietary supplementation with OEO. In conclusion, supplementation with dietary OEO may be superior to supplementation with dietary Vit E in alleviating the meat quality, stress response and intestinal morphology of pigs after challenge due to transportation stress.

Caspase-3 in serum predicts outcome after aneurysmal subarachnoid hemorrhage.

BACKGROUND: Caspase-3 represents a promising marker of apoptosis. This study was designed to investigate the serial change of serum caspase-3 activities and analyze the relationships between caspase-3 activities and the severity and prognosis of aneurysmal subarachnoid hemorrhage (aSAH). METHODS: We determined serum caspase-3 activities of 118 controls at study entry and 118 patients at admission and at days 1, 2, 3, 5 and 7 after aSAH. Activities were compared with regard to (i) time interval between onset of symptoms and blood sampling, (ii) stroke severity quantified by World Federation of Neurological Surgeons (WFNS) scores and modified Fisher scores and (iii) 6-month outcome. RESULTS: Serum caspase-3 activities were increased after aSAH, peaked at day 3, gradually decreased afterwards, and substantially were higher in patients than in controls. Caspase-3 activities were higher in patients suffering from death or an unfavorable outcome (Glasgow Outcome Scale score of 1-3), had close relation to WFNS scores and modified Fisher scores, and possessed high areas under receiver operating characteristic curve. Moreover, caspase-3 activities at admission and at day 3 predicted poor outcome independently of age, WFNS scores and modified Fisher scores. CONCLUSION: Increased serum caspase-3 activities are highly associated with the severity and prognosis after aSAH.

Remote Ischemic Preconditioning-Mediated Neuroprotection against Stroke is Associated with Significant Alterations in Peripheral Immune Responses.

AIMS: Remote ischemic preconditioning (RIPC) of a limb is a clinically feasible strategy to protect against ischemia-reperfusion injury after stroke. However, the mechanism underlying RIPC remains elusive. METHODS: We generated a rat model of noninvasive RIPC by four repeated cycles of brief blood flow constriction (5 min) in the hindlimbs using a tourniquet. Blood was collected 1 h after preconditioning and 3 days after brain reperfusion. The impact of RIPC on immune cell and cytokine profiles prior to and after transient middle cerebral artery occlusion (MCAO) was assessed. RESULTS: Remote ischemic preconditioning protects against focal ischemia and preserves neurological functions 3 days after stroke. Flow cytometry analysis demonstrated that RIPC ameliorates the post-MCAO reduction of CD3(+)CD8(+) T cells and abolishes the reduction of CD3(+)/CD161a(+) NKT cells in the blood. In addition, RIPC robustly elevates the percentage of B cells in peripheral blood, thereby reversing the reduction in the B-cell population after stroke. RIPC also markedly elevates the percentage of CD43(+)/CD172a(+) noninflammatory resident monocytes, without any impact on the percentage of CD43(-)/CD172a(+) inflammatory monocytes. Finally, RIPC induces IL-6 expression and enhances the elevation of TNF-α after stroke. CONCLUSION: Our results reveal dramatic immune changes during RIPC-afforded neuroprotection against cerebral ischemia.