Left Versus Right Destroyed Lung Pneumonectomy: Long Term Prognosis and Key Factors Associated With Poor Treatment Outcomes.

INTRODUCTION: To compare and analyze postoperative short-term and long-term prognosis of destroyed lung (DL) disease patients undergoing left versus right pneumonectomy and to identify potential key factors associated with poor treatment outcomes. METHODS: Retrospective analysis was conducted on clinical data of 128 DL patients who underwent pneumonectomy in the thoracic surgery department of the Beijing Chest Hospital from November 2001 to May 2022. Cases were assigned to two groups according to lesion site: a left pneumonectomy group (104 cases) and right pneumonectomy group (24 cases). Postoperative short-term and long-term DL disease clinical features and prognostic factors were analyzed and compared between groups. RESULTS: As compared with the left pneumonectomy group, the right pneumonectomy group experienced greater rates of preoperative diabetes, chronic pulmonary aspergillosis, intraoperative blood loss, postoperative respiratory failure, rehospitalization, tuberculosis (TB) recurrence, bronchopleural fistula (BPF) and empyema. Binary logistic regression analysis revealed a potential correlation between chronic pulmonary aspergillosis and increased odds of developing secondary respiratory failure (adjusted odds ratio: 5.234, 95% confidence interval [CI]: 1.768-15.498). Results of Cox Proportional Hazards Model regression analysis suggested that right pneumonectomy was correlated with increased odds of TB recurrence (adjusted hazard ratio: 4.017, 95% CI: 1.282-12.933) and BPF/empyema (adjusted hazard ratio: 5.655, 95% CI: 1.254-25.505). CONCLUSIONS: Compared to the group undergoing left pneumonectomy, patients with DL who undergo right-sided pneumonectomy may be at a heightened risk of experiencing secondary postoperative TB recurrence and BPF or edema. It is advised to exercise utmost caution and deliberate consideration of these potential risks when contemplating pneumonectomy, with the intention of proactively preventing adverse events.

Single Stage Hybrid Repair for DeBakey Type I Aortic Dissection in High Risk Patients.

OBJECTIVES: To evaluate the efficacy of the less invasive hybrid zone 0 (Z0) total aortic arch repair (HAR, ascending repair + complete debranching + thoracic endovascular aortic repair [TEVAR]) without deep hypothermic circulatory arrest in management of DeBakey type I aortic dissection (IAD). The adverse outcome was defined as a single composite endpoint comprising peri-operative mortality, permanent neurological deficit, and renal failure necessitating haemodialysis at discharge. METHODS: A retrospective review of prospectively collected data was conducted of 120 consecutive patients (mean EuroSCORE = 11.6%) with IAD undergoing HAR (urgent/emergency, n = 97, 80.8%) involving reconstruction of the ascending aorta (zone 0) and total arch exclusion with TEVAR during a 7.5 year period. Multivariable analysis of 27 potential pre-operative and intra-operative risk factors was performed to examine the early composite endpoint and short and long-term overall mortality. RESULTS: The total early (30 day or in hospital) mortality was 9.2% (n = 11). The incidence of the composite endpoint was 11.7% (n = 14). On multivariable analysis, malperfusion syndromes were predictors of the composite endpoint (odds ratio [OR], 4.789; 95% CI 1.362-16.896; p = .015), and previous cerebrovascular accident (OR, 13.74; 95% CI 2.330-81.039; p = .004) and myocardial ischaemia time (OR, 1.038; 95% CI 1.015-1.061; p = .001) predicted short and long-term overall mortality. The overall survival was 84.7% during a median follow up of 3.4 years. Freedom from late aortic adverse events was 93.1% at 5 years, including secondary aortic intervention and endoleak. The maximum diameters of the true lumen increased significantly in stented thoracic (14.4 ± 6.5 mm to 29.7 ± 5.3 mm, p < .001), lower thoracic (14.2 ± 6 mm to 21.6 ± 7.2 mm, p < .001) and abdominal (11.7 ± 4.8 mm to 17.4 ± 4.1 mm, p < .001) aorta. Complete thrombosis of the peri-stent false lumen was achieved in 88.2% of CT scans (82/93) performed a mean of 12 ± 17 months (median 5 months; 25-75% quartile, 2-12 months) post-operatively. CONCLUSIONS: IAD was treated safely and durably by Z0 HAR, and peri-operative mortality and morbidity were not substantially higher despite the older age and high risk of patients.

Angiotensin II Induces an Increase in Matrix Metalloproteinase 2 Expression in Aortic Smooth Muscle Cells of Ascending Thoracic Aortic Aneurysms Through JNK, ERK1/2, and p38 MAPK Activation.

In this study, we hypothesized that angiotensin II (Ang II) induces matrix metalloproteinase 2 (MMP-2) upregulation in aneurysmal smooth muscle cells (ASMCs) derived from ascending thoracic aortic aneurysms (ATAAs). We compared MMP-2 protein levels in ascending aortic specimens using Western blot and plasma concentrations by enzyme-linked immunosorbent assay between ATAA (n = 40) and coronary heart disease patients (n = 40). Additionally, the protein level of angiotensinogen (AGT) in the ascending aorta and the plasma concentration of Ang II were detected by Western blot and radioimmunoassay, respectively, in ATAA and coronary heart disease patients. In ATAA patients, Ang II and MMP-2 plasma levels were significantly increased (P < 0.05). Additionally, AGT and MMP-2 protein levels in the aorta of ATAA patients were higher (P < 0.01). Enhanced AGT suggested that the amount of Ang II in aneurysmal aorta specimens may be also increased, which was confirmed by immunofluorescent staining for Ang II. Moreover, we investigated the effect of Ang II on MMP-2 upregulation by ASMCs and determined the Ang II receptors and intracellular signaling pathways that are involved. Our results showed that treatment with Ang II significantly increased the expression of MMP-2 through the Ang II type 1 receptor (AT1R) and activated the 3 major mitogen-activated protein kinases (MAPKs), JNK, ERK1/2, and p38 MAPK. In conclusion, these results indicate that Ang II can induce MMP-2 expression elevation through AT1R and MAPK pathways in ASMCs and suggest that there is therapeutic potential for angiotensin receptor blocker drugs and MAPK inhibitors in the prevention and treatment of ATAAs.

Angiotensin II induces an increase in MMP-2 expression in idiopathic ascending aortic aneurysm via AT1 receptor and JNK pathway.

The cellular and molecular mechanisms responsible for human idiopathic ascending aortic aneurysm (IAAA) remain unknown. Matrix metalloproteinase-2 (MMP-2) is a key enzyme for the degradation of extracellular matrix in aneurysmal walls. The aim of this study was to elucidate the role of the angiotensin II (Ang II) pathway in MMP-2 induction in IAAA aortic walls. Quantitative polymerase chain reaction and western blot analysis were used to compare the MMP-2 mRNA and protein levels in ascending aortic specimens with those in IAAA patients (n = 10) and heart transplant donors (n = 5) without any aortopathy. It was found that MMP-2 expression was significantly increased, which was associated with elastic lamellae disruption in IAAA walls. Additionally, the expression levels of angiotensinogen (AGT) and Ang II in the ascending aortic tissues from individuals with and without IAAAs were detected by western blot analysis and radioimmunoassay, respectively. The results demonstrated that the expressions of AGT and Ang II protein were significantly increased in the ascending aortic tissues of IAAA patients. Furthermore, whether Ang II induces MMP-2 expression was investigated using human IAAA walls ex vivo culture. It was found that exogenous Ang II increased the MMP-2 expression in a dose-dependent manner, which was completely inhibited by the Ang II type 1 receptor (AT1R) inhibitor candesartan and was mediated by c-Jun N-terminal kinase (JNK) activation. Taken together, these results indicate that Ang II can induce an increase of MMP-2 expression via AT1R and JNK in ex vivo cultured IAAA aortic walls, and suggest that angiotensin receptor blocker (ARB) drugs and JNK inhibitors have the potential in the prevention or treatment of IAAAs.

Tissue distribution and cancer growth inhibition of magnetic lipoplex-delivered type 1 insulin-like growth factor receptor shRNA in nude mice.

The targeted delivery of therapeutic genes into specific tissues, as well as the determination of the biological fate and potential toxicity of nanoparticles, remains a highly relevant challenge for gene-based therapies. Type 1 insulin-like growth factor receptor (IGF-1R), an important oncogene, is frequently over-expressed in lung cancer and mediates cancer cell proliferation as well as tumor growth. In our previous studies, we have successfully applied gene delivery mediated by commercially available nanoparticles (CombiMAG) under a magnetic field, which suppresses IGF-1R expression in a non-small cell lung cancer cell line (A549) in vitro. In the present study, we aimed to investigate the biological distribution and target tumor suppression of magnetofection, as well as its potential toxicity via CombiMAG-carrying plasmids expressing green fluorescent protein (GFP) and short hairpin RNAs (shRNAs) targeting IGF-1R (pGFPshIGF-1Rs) in tumor-bearing mice. The peak expression in various organs appeared 48 h after transfection. Transgene expression via magnetofection was 3-fold improvement than via lipofection. On the 30th day after injection, the tumor size and weight of the CombiMAG-treated group (789.32 ± 39.43 mm(3), 105.5 ± 6.1 mg) were significantly decreased compared with those of the lipofection group (893.83 ± 31.23 mm(3), 164.5 ± 9.1 mg; P< 0.05), and the suppression rate was ∼36%. After a 30-day observation, the injection of CombiMAG did not cause any apparent toxicity. Therefore, IGF-1R shRNA nanoparticles can be valuable and safe delivery agents for RNA interference therapy to tumors in vivo.

[Magnetic liposome mediated shRNA specifically suppresses the growth of non-small cell lung cancer in vitro and in vivo].

OBJECTIVE: To evaluate the inhibition of shRNA mediated by magnetic liposome in the growth of non-small cell lung cancer (NSCLC) under the interference of magnetic field in vitro and in vivo and explore the effects of magnetic field on the efficiency of magnetofection. METHODS: The plasmid of pGFPshIGF-1R was constructed for expressing GFP and shRNA against IGF-1R. CombiMAG as superparamagnetic iron oxide nanoparticles (SPIONs) and Lipofectamine2000 as cationic liposome comprised the magnetic liposome. pGFPshIGF-1R was transferred into A549 cells by magnetofection under a series of interaction durations and intensity of external magnetic fields. pGFPshIGF-1R was delivered into A549 cells in vitro and injected intravenously into the tumor-bearing mice every 48 h for four doses in vivo by way of lipofection or magnetofection. The magnetofection efficiency was analyzed by cytometry and the potency of IGF-1R knockdown by Western blot. At Week 3 after the 4th injection, the mice were sacrificed and the tumors removed and weighed. The tumor inhibition rate was calculated. RESULTS: The interaction durations and intensity of magnetic field could influence the magnetofection efficiency. In vitro, IGF-1R specific-shRNA transfected by lipofection inhibited IGF-1R protein by 56.1% ± 6.0% and by liposomal magnetofection by 85.1% ± 3.0%. In vivo, pGFPshIGF-1R delivered by both lipofection and magnetofection significantly inhibited the tumor growth by 41.3% (P < 0.01) and 65.2% (P < 0.01). CONCLUSIONS: Based on magnetic liposome as gene vectors, magnetofection may become a promising targeted therapy for lung cancer. And the transfection efficiency is influenced by magnetic field.

Laryngopharyngeal Reflux in Obstructive Sleep Apnea-Hypopnea Syndrome: An Updated Meta-Analysis.

Laryngopharyngeal reflux (LPR) is a common disorder in patients with obstructive sleep apnea-hypopnea syndrome (OSAHS). This meta-analysis was carried out to evaluate the LPR prevalence in individuals with OSAHS and to analyze the correlation of LPR positivity with the clinical features of patients with OSAHS. A detailed review of the English and Chinese literature on the occurrence of LPR in patients with OSAHS was performed by employing online search tools such as PubMed, EMBASE, Web of Science, VIP, CNKI, WanFang, etc. Two researchers analyzed the studies for quality according to the STROBE standard checklist. The acquired data were analyzed using Stata 11.0 and R 3.6.1 software. The effect size was estimated and calculated using weighted mean difference (WMD) and correlation coefficients. Moreover, a combined analysis was performed by employing either a random- or fixed-effects model. Ultimately, 27 studies met our inclusion criteria. Our study revealed that the LPR prevalence in OSAHS patients was 49%. We carried out subgroup analyses as per OSAHS severity, ethnicity, and body mass index (BMI). The results suggested that the probability of LPR in European and American patients with OSAHS was higher, and the prevalence of LPR was higher in obese individuals and patients with severe OSAHS. Moreover, apnea-hypopnea index (AHI) and BMI were higher in LPR-positive OSAHS patients than in LPR-negative OSAHS patients, but no significant variation in age was observed in the two groups. Moreover, the reflux symptom index (RSI) scores and the reflux finding score (RFS) exhibited a positive correlation with AHI. The current literature shows a higher incidence of LPR in individuals with OSAHS (49%). The severity of AHI in individuals with OSAHS is associated with the presence of LPR. Patients with OSAHS accompanied by LPR showed higher BMI and AHI as compared to those patients with LPR-negative OSAHS.

Tumor-targeting magnetic lipoplex delivery of short hairpin RNA suppresses IGF-1R overexpression of lung adenocarcinoma A549 cells in vitro and in vivo.

Liposomal magnetofection potentiates gene transfection by applying a magnetic field to concentrate magnetic lipoplexes onto target cells. Magnetic lipoplexes are self-assembling ternary complexes of cationic lipids with plasmid DNA associated with superparamagnetic iron oxide nanoparticles (SPIONs). Type1 insulin-like growth factor receptor (IGF-1R), an important oncogene, is frequently overexpressed in lung cancer and mediates cancer cell proliferation and tumor growth. In this study, we evaluated the transfection efficiency (percentage of transfected cells) and therapeutic potential (potency of IGF-1R knockdown) of liposomal magnetofection of plasmids expressing GFP and shRNAs targeting IGF-1R (pGFPshIGF-1Rs) in A549 cells and in tumor-bearing mice as compared to lipofection using Lipofectamine 2000. Liposomal magnetofection provided a threefold improvement in transgene expression over lipofection and transfected up to 64.1% of A549 cells in vitro. In vitro, IGF-1R specific-shRNA transfected by lipofection inhibited IGF-1R protein by 56.1±6% and by liposomal magnetofection by 85.1±3%. In vivo delivery efficiency of the pGFPshIGF-1R plasmid into the tumor was significantly higher in the liposomal magnetofection group than in the lipofection group. In vivo IGF-1R specific-shRNA by lipofection inhibited IGF-1R protein by an average of 43.8±5.3%; that by liposomal magnetofection inhibited IGF-1R protein by 43.4±5.7%, 56.3±9.6%, and 72.2±6.8%, at 24, 48, and 72 h, respectively, after pGFPshIGF-1R injection. Our findings indicate that liposomal magnetofection may be a promising method that allows the targeting of gene therapy to lung cancer.

Human entorhinal gamma and theta oscillations selective for remote autobiographical memory.

Current source densities in different layers of the human entorhinal cortex (ER) were recorded using a linear array of 24 microelectrodes during three memory conditions: a remote autobiographical condition eliciting recollections of events that occurred 10 or more years ago in the participant's past, a semantic icon condition invoking the mental image of a well-known object, and a semantic knowledge condition asking about general information. Our data demonstrate theta, gamma, and delta oscillations in left ER particularly for remote autobiographical memory. Gamma is predominant in hippocampally projecting layers during presentation of the memory cue, whereas theta is prolonged and dominant in cortically projecting layers during memory retrieval. Gamma interactions between ER and hippocampal formation (HF) may elicit an HF contribution to recall under influences relayed from the association cortex (AC). This contribution may then be relayed back to AC during retrieval of the memory orchestrated by theta interactions with ER. Accordingly, theta oscillations were recorded simultaneously in frontal and temporal cortices.

Responses of human anterior cingulate cortex microdomains to error detection, conflict monitoring, stimulus-response mapping, familiarity, and orienting.

Human anterior cingulate cortex (ACC) activity modulation has been observed in numerous tasks, consistent with a wide variety of functions. However, previous recordings have not had sufficient spatial resolution to determine whether microdomains (approximately one to two columns) are involved in multiple tasks, how activity is distributed across cortical layers, or indeed whether modulation reflected neuronal excitation, inhibition, or both. In this study, linear arrays of 24 microelectrodes were used to estimate population synaptic currents and neuronal firing in different layers of ACC during simple/choice reaction time, delayed word recognition, rhyming, auditory oddball, and cued conditional letter-discrimination tasks. Responses to all tasks, with differential responses to errors, familiarity, difficulty, and orienting, were recorded in single microdomains. The strongest responses occurred approximately 300-800 ms after stimulus onset and were usually a current source with inhibited firing, strongly suggesting active inhibition in superficial layers during the behavioral response period. This was usually followed by a sink from approximately 800 to 1400 ms, consistent with postresponse rebound activation. Transient phase locking of task-related theta activity in superficial cingulate layers suggested extended interactions with medial and lateral frontal and temporal sites. These data suggest that each anterior cingulate microdomain participates in a multilobar cortical network after behavioral responses in a variety of tasks.

The neural substrate of arithmetic operations and procedure complexity.

Recent functional neuroimaging studies have begun to clarify how the human brain performs the everyday activities that require mental calculation. We used fMRI to test the hypotheses that there are specific neural networks dedicated to performing an arithmetic operation (e.g. + or -) and to performing processes that support more complex calculations. We found that the right inferior parietal lobule, left precuneus and left superior parietal gyrus are relatively specific for performing subtraction; and bilateral medial frontal/cingulate cortex are relatively specific for supporting arithmetic procedure complexity. We also found that greater difficulty level was associated with activation in a brain network including left inferior intraparietal sulcus, left inferior frontal gyrus and bilateral cingulate. Our results suggest that the network activated by the simplest calculation serves as a common basis, to which more regions are recruited for more difficult problems or different arithmetic operations.

Angiotensin II increases matrix metalloproteinase 2 expression in human aortic smooth muscle cells via AT1R and ERK1/2.

Increased levels of angiotensin II (Ang II) and activated matrix metalloproteinase 2 (MMP-2) produced by human aortic smooth muscle cells (human ASMCs) have recently been implicated in the pathogenesis of thoracic aortic aneurysm (TAA). Additionally, angiotensin II type 1 receptor (AT1R)-mediated extracellular signal-regulated kinase (ERK)1/2 activation contributes to TAA development in Marfan Syndrome. However, there is scant data regarding the relationship between Ang II and MMP-2 expression in human ASMCs. Therefore, we investigated the effect of Ang II on MMP-2 expression in human ASMCs and used Western blotting to identify the Ang II receptors and intracellular signaling pathways involved. Reverse transcription polymerase chain reaction (RT-PCR) and immunofluorescence data demonstrated that Ang II receptors were expressed on human ASMCs. Additionally, Ang II increased the expression of Ang II type 2 receptor (AT2R) but not AT1R at both the transcriptional and translational levels. Furthermore, Western blotting showed that Ang II increased MMP-2 expression in human ASMCs in a dose- and time-dependent manner. This response was completely inhibited by the AT1R inhibitor candesartan but not by the AT2R blocker PD123319. In addition, Ang II-induced upregulation of MMP-2 was mediated by the activation of ERK1/2, whereas p38 mitogen-activated protein kinase (p38 MAPK) and c-Jun N-terminal kinase (JNK) had no effect on this process. In conclusion, these results indicate that Ang II can increase the expression of MMP-2 via AT1 receptor and ERK1/2 signaling pathways in human ASMCs and suggest that antagonists of AT1R and ERK1/2 may be useful for treating TAAs.

Association of peroxisome proliferator-activated receptor-gamma gene polymorphisms and gene-gene interaction with asthma risk in a Chinese adults population.

AIMS: To investigate the association between single nucleotide polymorphism (SNP) of peroxisome proliferator-activated receptors γ (PPAR γ) and additional gene-gene interactions on asthma risk. METHODS: A total of 882 subjects (602 males, 280 females), with a mean age of 61.3±14.8 years old, including 430 asthma patients and 452 normal subjects were selected in this study, including the genotyping of polymorphisms. Logistic regression was performed to investigate association between SNP and asthma. Generalized MDR (GMDR) was used to analysis the interaction among four SNP. RESULTS: Asthma risk was significantly lower in carriers of Ala allele of the rs1805192 polymorphism than those with Pro/Pro (Pro/Ala+ Ala/Ala versus Pro/Pro, adjusted OR (95% CI)=0.70 (0.51-0.94). In addition, we also found a significant association between rs10865710 and asthma, asthma risk was significantly lower in carriers of G allele of the rs10865710 polymorphism than those with CC (CG+ GG versus CC, adjusted OR (95% CI)=0.68 (0.55-0.95). There was a significant three-locus model (P=0.0107) involving rs1805192, rs10865710 and rs709158, indicating a potential gene-gene interaction among rs1805192, rs10865710 and rs709158. Overall, the three-locus models had a cross-validation consistency of 10 of 10, and had the testing accuracy of 60.72% after covariates adjustment. CONCLUSIONS: Our results support an important association of rs1805192 and rs10865710 with asthma, and additional interaction among rs1805192, rs10865710 and rs709158.

Laminar profile of spontaneous and evoked theta: Rhythmic modulation of cortical processing during word integration.

Theta may play a central role during language understanding and other extended cognitive processing, providing an envelope for widespread integration of participating cortical areas. We used linear microelectrode arrays in epileptics to define the circuits generating theta in inferotemporal, perirhinal, entorhinal, prefrontal and anterior cingulate cortices. In all locations, theta was generated by excitatory current sinks in middle layers which receive predominantly feedforward inputs, alternating with sinks in superficial layers which receive mainly feedback/associative inputs. Baseline and event-related theta were generated by indistinguishable laminar profiles of transmembrane currents and unit-firing. Word presentation could reset theta phase, permitting theta to contribute to late event-related potentials, even when theta power decreases relative to baseline. Limited recordings during sentence reading are consistent with rhythmic theta activity entrained by a given word modulating the neural background for the following word. These findings show that theta occurs spontaneously, and can be momentarily suppressed, reset and synchronized by words. Theta represents an alternation between feedforward/divergent and associative/convergent processing modes that may temporally organize sustained processing and optimize the timing of memory formation. We suggest that words are initially encoded via a ventral feedforward stream which is lexicosemantic in the anteroventral temporal lobe; its arrival may trigger a widespread theta rhythm which integrates the word within a larger context.

A pilot study of functional magnetic resonance imaging of the brain during manual and electroacupuncture stimulation of acupuncture point (LI-4 Hegu) in normal subjects reveals differential brain activation between methods.

OBJECTIVES: To characterize the brain activation patterns evoked by manual and electroacupuncture on normal human subjects. DESIGN: We used functional magnetic resonance imaging (fMRI) to investigate the brain regions involved in electroacupuncture and manual acupuncture needle stimulation. A block design was adopted for the study. Each functional run consists of 5 minutes, starting with 1-minute baseline and two 1-minute stimulation, the interval between the two stimuli was 1 minute. Four functional runs were performed on each subject, two runs for electroacupuncture and two runs for manual acupuncture. The order of the two modalities was randomized among subjects. During the experiment, acupuncture needle manipulation was performed at Large Intestine 4 (LI4, Hegu) on the left hand. For each subject, before scanning started, the needle was inserted perpendicular to the skin surface to a depth of approximately 1.0 cm. Electroacupuncture stimulation was delivered using a continuous rectangular wave form (pulse width 30 ms) at a frequency of 3 Hz. For manual acupuncture, the needle was rotated manually clockwise and counterclockwise at a rate of about 180 times per minute (3 Hz). SUBJECTS: Eleven right-handed, normal, healthy volunteer adults, 6 male and 5 female, ages 21-64 participated in the experiment. RESULTS: Results showed that electroacupuncture mainly produced fMRI signal increases in precentral gyrus, postcentral gyrus/inferior parietal lobule, and putamen/insula; in contrast, manual needle manipulation produced prominent decreases of fMRI signals in posterior cingulate, superior temporal gyrus, putamen/insula. CONCLUSION: These results indicate that different brain networks are involved during manual and electroacupuncture stimulation. It suggests that different brain mechanisms may be recruited during manual and electroacupuncture.

Anterolateral minithoracotomy versus median sternotomy for the treatment of congenital heart defects: a meta-analysis and systematic review.

BACKGROUND: Anterolateral Minithoracotomy (ALMT) for the radical correction of Congenital Heart Defects is an alternative to Median Sternotomy (MS) due to reduce operative trauma accelerating recovery and yield a better cosmetic outcome after surgery. Our purpose is to conduct whether ALMT would bring more short-term benefits to patients than conventional Median Sternotomy by using a meta-analysis of case-control study in the published English Journal. METHODS: 6 case control studies published in English from 1997 to 2011 were identified and synthesized to compare the short-term postoperative outcomes between ALMT and MS. These outcomes were cardiopulmonary bypass time, aortic cross-clamp time, intubation time, intensive care unit stay time, and postoperative hospital stay time. RESULTS: ALMT had significantly longer cardiopulmonary bypass times (8.00 min more, 95% CI 0.36 to 15.64 min, p = 0.04). Some evidence proved that aortic cross-clamp time of ALMT was longer, yet not significantly (2.38 min more, 95% CI -0.15 to 4.91 min, p = 0.06). In addition, ALMT had significantly shorter intubation time (1.66 hrs less, 95% CI -3.05 to -0.27 hrs, p = 0.02). Postoperative hospital stay time was significantly shorter with ALMT (1.52 days less, 95% CI -2.71 to -0.33 days, p = 0.01). Some evidence suggested a reduction in ICU stay time in the ALMT group. However, this did not prove to be statistically significant (0.88 days less, 95% CI -0.81 to 0.04 days, p = 0.08). CONCLUSION: ALMT can bring more benefits to patients with Congenital Heart Defects by reducing intubation time and postoperative hospital stay time, though ALMT has longer CPB time and aortic cross-clamp time.

Intracranial microprobe for evaluating neuro-hemodynamic coupling in unanesthetized human neocortex.

Measurement of the blood-oxygen-level dependent (BOLD) response with fMRI has revolutionized cognitive neuroscience and is increasingly important in clinical care. The BOLD response reflects changes in deoxy-hemoglobin concentration, blood volume, and blood flow. These hemodynamic changes ultimately result from neuronal firing and synaptic activity, but the linkage between these domains is complex, poorly understood, and may differ across species, cortical areas, diseases, and cognitive states. We describe here a technique that can measure neural and hemodynamic changes simultaneously from cortical microdomains in waking humans. We utilize a "laminar optode," a linear array of microelectrodes for electrophysiological measures paired with a micro-optical device for hemodynamic measurements. Optical measurements include laser Doppler to estimate cerebral blood flow as well as point spectroscopy to estimate oxy- and deoxy-hemoglobin concentrations. The microelectrode array records local field potential gradients (PG) and multi-unit activity (MUA) at 24 locations spanning the cortical depth, permitting estimation of population trans-membrane current flows (Current Source Density, CSD) and population cell firing in each cortical lamina. Comparison of the laminar CSD/MUA profile with the origins and terminations of cortical circuits allows activity in specific neuronal circuits to be inferred and then directly compared to hemodynamics. Access is obtained in epileptic patients during diagnostic evaluation for surgical therapy. Validation tests with relatively well-understood manipulations (EKG, breath-holding, cortical electrical stimulation) demonstrate the expected responses. This device can provide a new and robust means for obtaining detailed, quantitative data for defining neurovascular coupling in awake humans.

The human K-complex represents an isolated cortical down-state.

The electroencephalogram (EEG) is a mainstay of clinical neurology and is tightly correlated with brain function, but the specific currents generating human EEG elements remain poorly specified because of a lack of microphysiological recordings. The largest event in healthy human EEGs is the K-complex (KC), which occurs in slow-wave sleep. Here, we show that KCs are generated in widespread cortical areas by outward dendritic currents in the middle and upper cortical layers, accompanied by decreased broadband EEG power and decreased neuronal firing, which demonstrate a steep decline in network activity. Thus, KCs are isolated "down-states," a fundamental cortico-thalamic processing mode already characterized in animals. This correspondence is compatible with proposed contributions of the KC to sleep preservation and memory consolidation.

Processing stages underlying word recognition in the anteroventral temporal lobe.

The anteroventral temporal lobe integrates visual, lexical, semantic and mnestic aspects of word processing, through its reciprocal connections with the ventral visual stream, language areas, and the hippocampal formation. We used linear microelectrode arrays to probe population synaptic currents and neuronal firing in different cortical layers of the anteroventral temporal lobe, during semantic judgments with implicit priming and overt word recognition. Since different extrinsic and associative inputs preferentially target different cortical layers, this method can help reveal the sequence and nature of local processing stages at a higher resolution than was previously possible. The initial response in inferotemporal and perirhinal cortices is a brief current sink beginning at approximately 120 ms and peaking at approximately 170 ms. Localization of this initial sink to middle layers suggests that it represents feedforward input from lower visual areas, and simultaneously increased firing implies that it represents excitatory synaptic currents. Until approximately 800 ms, the main focus of transmembrane current sinks alternates between middle and superficial layers, with the superficial focus becoming increasingly dominant after approximately 550 ms. Since superficial layers are the target of local and feedback associative inputs, this suggests an alternation in predominant synaptic input between feedforward and feedback modes. Word repetition does not affect the initial perirhinal and inferotemporal middle layer sink but does decrease later activity. Entorhinal activity begins later (approximately 200 ms), with greater apparent excitatory post-synaptic currents and multiunit activity in neocortically projecting than hippocampal-projecting layers. In contrast to perirhinal and entorhinal responses, entorhinal responses are larger to repeated words during memory retrieval. These results identify a sequence of physiological activation, beginning with a sharp activation from lower level visual areas carrying specific information to middle layers. This is followed by feedback and associative interactions involving upper cortical layers, which are abbreviated to repeated words. Following bottom-up and associative stages, top-down recollective processes may be driven by entorhinal cortex. Word processing involves a systematic sequence of fast feedforward information transfer from visual areas to anteroventral temporal cortex followed by prolonged interactions of this feedforward information with local associations and feedback mnestic information from the medial temporal lobe.