Transcriptomics-informed large-scale cortical model captures topography of pharmacological neuroimaging effects of LSD.

Psychoactive drugs can transiently perturb brain physiology while preserving brain structure. The role of physiological state in shaping neural function can therefore be investigated through neuroimaging of pharmacologically induced effects. Previously, using pharmacological neuroimaging, we found that neural and experiential effects of lysergic acid diethylamide (LSD) are attributable to agonism of the serotonin-2A receptor (Preller et al., 2018). Here, we integrate brain-wide transcriptomics with biophysically based circuit modeling to simulate acute neuromodulatory effects of LSD on human cortical large-scale spatiotemporal dynamics. Our model captures the inter-areal topography of LSD-induced changes in cortical blood oxygen level-dependent (BOLD) functional connectivity. These findings suggest that serotonin-2A-mediated modulation of pyramidal-neuronal gain is a circuit mechanism through which LSD alters cortical functional topography. Individual-subject model fitting captures patterns of individual neural differences in pharmacological response related to altered states of consciousness. This work establishes a framework for linking molecular-level manipulations to systems-level functional alterations, with implications for precision medicine.

Balloon Angioplasty Versus Stenting in Patients With ST-Elevated Myocardial Infarction Before Subsequent Coronary Artery By-Pass Grafting.

Decision of ad hoc revascularization strategy in patients who require coronary artery bypass grafting (CABG) following primary percutaneous coronary interventions (PCI) is challenging due to the pros and cons of only-ballooning and stenting. In this study, we aimed to compare the outcomes of only-balloon-angioplasty to stenting in primary PCI in patients with ST elevated myocardial infarction (STEMI) who required a subsequent CABG. We retrospectively analyzed 350 consecutive STEMI patients who needed CABG in addition to primary balloon angioplasty (n = 160) and stenting strategy (n = 190). In-hospital and 5-year outcomes of the patients were compared between the 2 groups. In-hospital mortality rates in the ballooning and stenting groups were not nonsignificantly different (11.2% vs 9.5%, respectively, P = .59); 5-year mortality rates were also similar between the 2 groups (9.2% vs 8.7%, P = .89). Additionally, major bleeding rates (3.8% vs 6.3%, P = .28) did not differ between the 2 groups. In conclusion, our study showed no significant difference in-hospital and long-term mortality rates in patients who require CABG after primary PCI irrespective of the ad hoc revascularization strategy.

An Alternative Technique for Ascending and Arcus Aorta Repair in Case of Vascular Diameter Mismatch.

Complicated Type A intramural hematoma involving the arcus aorta requires emergency correction of the aortic arch. Surgical options include reimplantation of the brachiocephalic vessels as an island to a vascular graft, debranching aortic arch surgery, and Kazui technique. This report describes a modified technique for aortic arch repair in a patient with vascular diameter mismatch between the ascending and descending aorta, as well as an intimal tear between the brachiocephalic vessels.

Hierarchical Heterogeneity across Human Cortex Shapes Large-Scale Neural Dynamics.

The large-scale organization of dynamical neural activity across cortex emerges through long-range interactions among local circuits. We hypothesized that large-scale dynamics are also shaped by heterogeneity of intrinsic local properties across cortical areas. One key axis along which microcircuit properties are specialized relates to hierarchical levels of cortical organization. We developed a large-scale dynamical circuit model of human cortex that incorporates heterogeneity of local synaptic strengths, following a hierarchical axis inferred from magnetic resonance imaging (MRI)-derived T1- to T2-weighted (T1w/T2w) mapping and fit the model using multimodal neuroimaging data. We found that incorporating hierarchical heterogeneity substantially improves the model fit to functional MRI (fMRI)-measured resting-state functional connectivity and captures sensory-association organization of multiple fMRI features. The model predicts hierarchically organized higher-frequency spectral power, which we tested with resting-state magnetoencephalography. These findings suggest circuit-level mechanisms linking spatiotemporal levels of analysis and highlight the importance of local properties and their hierarchical specialization on the large-scale organization of human cortical dynamics.

Distinct modes of functional connectivity induced by movie-watching.

A fundamental question in systems neuroscience is how endogenous neuronal activity self-organizes during particular brain states. Recent neuroimaging studies have demonstrated systematic relationships between resting-state and task-induced functional connectivity (FC). In particular, continuous task studies, such as movie watching, speak to alterations in coupling among cortical regions and enhanced fluctuations in FC compared to the resting-state. This suggests that FC may reflect systematic and large-scale reorganization of functionally integrated responses while subjects are watching movies. In this study, we characterized fluctuations in FC during resting-state and movie-watching conditions. We found that the FC patterns induced systematically by movie-watching can be explained with a single principal component. These condition-specific FC fluctuations overlapped with inter-subject synchronization patterns in occipital and temporal brain regions. However, unlike inter-subject synchronization, condition-specific FC patterns were characterized by increased correlations within frontal brain regions and reduced correlations between frontal-parietal brain regions. We investigated these condition-specific functional variations as a shorter time scale, using time-resolved FC. The time-resolved FC showed condition-specificity over time; notably when subjects watched both the same and different movies. To explain self-organisation of global FC through the alterations in local dynamics, we used a large-scale computational model. We found that condition-specific reorganization of FC could be explained by local changes that engendered changes in FC among higher-order association regions, mainly in frontal and parietal cortices.

Hierarchy of transcriptomic specialization across human cortex captured by structural neuroimaging topography.

Hierarchy provides a unifying principle for the macroscale organization of anatomical and functional properties across primate cortex, yet microscale bases of specialization across human cortex are poorly understood. Anatomical hierarchy is conventionally informed by invasive tract-tracing measurements, creating a need for a principled proxy measure in humans. Moreover, cortex exhibits marked interareal variation in gene expression, yet organizing principles of cortical transcription remain unclear. We hypothesized that specialization of cortical microcircuitry involves hierarchical gradients of gene expression. We found that a noninvasive neuroimaging measure-MRI-derived T1-weighted/T2-weighted (T1w/T2w) mapping-reliably indexes anatomical hierarchy, and it captures the dominant pattern of transcriptional variation across human cortex. We found hierarchical gradients in expression profiles of genes related to microcircuit function, consistent with monkey microanatomy, and implicated in neuropsychiatric disorders. Our findings identify a hierarchical axis linking cortical transcription and anatomy, along which gradients of microscale properties may contribute to the macroscale specialization of cortical function.

Biophysical Modeling of Large-Scale Brain Dynamics and Applications for Computational Psychiatry.

Noninvasive neuroimaging has revolutionized the study of the organization of the human brain and how its structure and function are altered in psychiatric disorders. A critical explanatory gap lies in our mechanistic understanding of how systems-level neuroimaging biomarkers emerge from underlying synaptic-level perturbations associated with a disease state. We describe an emerging computational psychiatry approach leveraging biophysically based computational models of large-scale brain dynamics and their potential integration with clinical and pharmacological neuroimaging. In particular, we focus on neural circuit models, which describe how patterns of functional connectivity observed in resting-state functional magnetic resonance imaging emerge from neural dynamics shaped by inter-areal interactions through underlying structural connectivity defining long-range projections. We highlight the importance of local circuit physiological dynamics, in combination with structural connectivity, in shaping the emergent functional connectivity. Furthermore, heterogeneity of local circuit properties across brain areas, which impacts large-scale dynamics, may be critical for modeling whole-brain phenomena and alterations in psychiatric disorders and pharmacological manipulation. Finally, we discuss important directions for future model development and biophysical extensions, which will expand their utility to link clinical neuroimaging to neurobiological mechanisms.

A whole-brain computational modeling approach to explain the alterations in resting-state functional connectivity during progression of Alzheimer's disease.

Alzheimer's disease (AD) is the most common dementia with dramatic consequences. The research in structural and functional neuroimaging showed altered brain connectivity in AD. In this study, we investigated the whole-brain resting state functional connectivity (FC) of the subjects with preclinical Alzheimer's disease (PAD), mild cognitive impairment due to AD (MCI) and mild dementia due to Alzheimer's disease (AD), the impact of APOE4 carriership, as well as in relation to variations in core AD CSF biomarkers. The synchronization in the whole-brain was monotonously decreasing during the course of the disease progression. Furthermore, in AD patients we found widespread significant decreases in functional connectivity (FC) strengths particularly in the brain regions with high global connectivity. We employed a whole-brain computational modeling approach to study the mechanisms underlying these alterations. To characterize the causal interactions between brain regions, we estimated the effective connectivity (EC) in the model. We found that the significant EC differences in AD were primarily located in left temporal lobe. Then, we systematically manipulated the underlying dynamics of the model to investigate simulated changes in FC based on the healthy control subjects. Furthermore, we found distinct patterns involving CSF biomarkers of amyloid-beta (Aß1 - 42) total tau (t-tau) and phosphorylated tau (p-tau). CSF Aß1 - 42 was associated to the contrast between healthy control subjects and clinical groups. Nevertheless, tau CSF biomarkers were associated to the variability in whole-brain synchronization and sensory integration regions. These associations were robust across clinical groups, unlike the associations that were found for CSF Aß1 - 42. APOE4 carriership showed no significant correlations with the connectivity measures.

Dynamic functional connectivity reveals altered variability in functional connectivity among patients with major depressive disorder.

Resting-state fMRI (RS-fMRI) has become a useful tool to investigate the connectivity structure of mental health disorders. In the case of major depressive disorder (MDD), recent studies regarding the RS-fMRI have found abnormal connectivity in several regions of the brain, particularly in the default mode network (DMN). Thus, the relevance of the DMN to self-referential thoughts and ruminations has made the use of the resting-state approach particularly important for MDD. The majority of such research has relied on the grand averaged functional connectivity measures based on the temporal correlations between the BOLD time series of various brain regions. We, in our study, investigated the variations in the functional connectivity over time at global and local level using RS-fMRI BOLD time series of 27 MDD patients and 27 healthy control subjects. We found that global synchronization and temporal stability were significantly increased in the MDD patients. Furthermore, the participants with MDD showed significantly increased overall average (static) functional connectivity (sFC) but decreased variability of functional connectivity (vFC) within specific networks. Static FC increased to predominance among the regions pertaining to the default mode network (DMN), while the decreased variability of FC was observed in the connections between the DMN and the frontoparietal network. Hum Brain Mapp 37:2918-2930, 2016. © 2016 Wiley Periodicals, Inc.

A comparison of the generation of free radicals in saliva of active and passive smokers.

AIM: To reveal any correlation between cigarette smoke and malondialdehyde (MDA) values in the saliva fluid of subjects who are active smokers or nonsmoking subjects who are exposed to cigarette smoke in their environments. MATERIALS AND METHODS: Saliva samples were taken from 3 groups: a control group (group 1), a group inhaling smoke passively (group 2), and a test group (group 3) smoking 20 cigarettes per day; each group consisted of 20 members, giving a total sample of 60 people, aged 20 to 45 years. MDA, which is an indicator of lipid peroxidation, was measured via the colorimetric method. RESULTS: Salivary MDA levels in smokers were found to be significantly higher compared to the control group and the group of passive smokers (P < 0.05). When compared with the control group, the MDA levels of passive smokers and active smokers were higher; when passive and active smokers were compared, the MDA levels of active smokers were higher. When all 3 groups were compared, the MDA levels in the control group (nonsmokers) were observed to be lower than the MDA level of the other 2 groups. CONCLUSION: It was observed that lipid peroxidation, which is an indicator used to determine oxidative stress, and MDA level, which is a product of this reactive chain, are significantly higher in individuals who are smokers. Such a high level of MDA in passive smokers indicates that smoking also affects nonsmokers negatively.

Ascorbic-acid Treatment for Progressive Bone Metastases After Radiotherapy: A Pilot Study.

Context • Researchers have reported improved survival rates for patients with cancer when 10-75 g of vitamin C (ascorbic acid, or AA) is administered intravenously. AA exhibits a cytotoxic effect upon entering a cancer cell. Objective • The current study examined the benefits of intravenous administration of AA in treatment of bone metastases. Design • The study was a pilot study. Setting • The study was performed at Bezmialem Vakif University Medical Facility (BVUMF) in the Department of Radiation Oncology, from 2010-2012. Participants • Participants were 11 cancer patients with bone metastases who were unresponsive to standard cancer treatments and who experienced the following issues after receiving a total of 3000 cGy of radiotherapy: (1) intensifying pain, (2) an increase in metastatic sites, and/or (3) a deterioration in general health. Intervention • The 11 patients received 2.5 g of AA in a physiological saline solution, within 1 h period with 3-10 applications following at 1-wk intervals. Outcome Measures • The ECOG Performance Scale and Visual Analog Scale were used to assess performance and pain. Results • Among the participants administered AA, the mean reduction in pain was 55%, and the median survival time was 10 mo. Participants experienced a 40% grade-I gastrointestinal toxicity and a 30% urinary toxicity. Conclusions • Given the study's results, the current research team found considerable encouragement in the use of AA after radiotherapy for treatment of patients with bone metastases. Toxicity was in the acceptable range for AA treatment.

Perforation of mitral-aortic intervalvular fibrosa secondary to bicuspid aortic valve endocarditis: Possible relation with diagnostic coronary angiography.

Infective endocarditis (IE) remains a serious and deadly disease despite recent advances in diagnosis and treatment. In all IE cases, the rate of healthcare-associated IE has been reported as 23%. Aortic valve endocarditis may extend to mitral-aortic intervalvular fibrosa (MAIVF), which may cause pseudoaneurysm formation and subsequent perforation. Direct perforation of the MAIVF is a rare clinical finding. In this report, we present a case of bicuspid aortic valve endocarditis which manifested as acute heart failure secondary to perforation of MAIVF and developed after diagnostic coronary angiography. .

[The seasonal distribution and effect of tench fish (Tinca tinca L., 1758) helminthes parasites living in Terkos lake]. / Terkos gölü'nde yasayan kadife baliklarinin (Tinca tinca L. 1758) helmint parazitlerinin mevsimsel dagilimi ve etkileri.

OBJECTIVE: The aim of this study, carried out from August, 2009 to July, 2010, was to determine the seasonal distribution of tench fish (Tinca tinca L. 1758) helminthes inhabiting the Terkos lake. METHODS: Living fish gathered from the study area were brought into the laboratory. The species analysis done by ecto and endo parasites of the fish were investigated. RESULTS: During the study, a total of 165 tenches (T. tinca) were investigated. Endoparasites in tenches were found to be plerocercoids of Ligula intestinalis plerocercoid (Linnaeus, 1758), Caryophyllaeus laticeps (Pallas, 1781), Bothriocephalus acheilognathi (Yamaguti, 1934) and Proteocephalus torulosus (Bats ch, 1786) from Cestoda, Asymphylodora tincae (Modeer, 1790) from Digenea and ectoparasite in tenches were found to be Piscicola geometra (Linnaeus, 1761) from Hirudinea. CONCLUSION: The study shows that among these parasites those which were widespread were: Asymphylodora tincae spreads more in spring, Ligula intestinalis in autumn, Caryophyllaeus laticeps, Bothriocephalus acheilognathi and Protocephalus torulosus in summer and Piscicola geometra in winter.

Emergency management for critical left main coronary artery stenosis.

BACKGROUND: Increased experience and improvements in technology seem to have encouraged the use of percutaneous interventions for left main coronary artery (LMCA) occlusions. There is no consensus, however, and the data are inadequate on whether surgery or percutaneous procedures should be the intervention of choice for critical occlusions. METHODS: From January 2002 to December 2006, 108 patients with unprotected LMCA stenosis >80% were treated at our center. Eighty-three patients (77%) underwent bypass grafting and 20 (18%) underwent percutaneous intervention for the purpose of myocardial revascularization. We analyzed parameters demonstrated as risk factors for myocardial revascularization and their predicted effects on outcome. RESULTS: Five patients (5%) died following emergency cardiopulmonary resuscitation before any intervention was performed. The early survival rate was 84.1% in the coronary bypass group and 63% in the percutaneous intervention group. The mean (±SD) survival time was 55.7 ± 2.6 months in the bypass group and 7.6 ± 1.3 months in the percutaneous group. The late-survival rate was also significantly higher in the bypass group. The mean late-survival time was 44.5 ± 3.6 months in the bypass group and 2.3 ± 0.8 months in the percutaneous group. CONCLUSION: Although emergency percutaneous interventions are lifesaving in some cases, these results clearly demonstrate that coronary bypass grafting should be the intervention of choice for myocardial revascularization in patients with critical LMCA occlusion.

Comparison of minimally invasive direct coronary artery bypass and off-pump coronary artery bypass in single-vessel disease.

BACKGROUND: Off-pump coronary surgery is an established method of less invasive cardiac surgery. We compared our early results in patents with I-vessel disease who underwent surgery with full sternotomy with off-pump coronary artery bypass (OPCAB) or a left anterior minithoracotomy with minimally invasive direct coronary artery bypass grafting (MIDCAB) without cardiopulmonary bypass. METHODS: From July 2003 to June 2006, 54 patients with single-vessel disease of the left anterior descending artery who underwent surgery performed by the same surgical team were included in this prospective study. Of these patients, 27 underwent MIDCAB through an anterolateral minithoracotomy, and 27 had OPCAB through a full sternotomy. Patients were selected for the surgical groups on the basis of general condition, anatomical aspects, type of coronary lesions, comorbidities, and patient preferences. Demographic, operative, and postoperative data were collected prospectively. RESULTS: Demographic data, Canadian Cardiovascular Society Classification, and comorbidities were identical for both groups. There were no cases of operative mortality, early graft insufficiency, myocardial infarction, cerebrovascular accident, or conversion to cardiopulmonary bypass in either group. Durations of mechanical ventilation and total hospital stay were shorter in the MIDCAB group, 6.8+/-3.0 hours vs 8.3+/-1.6 hours and 4.5+/-0.7 days vs 5.2+/-1.4 days (P= .03 and P= .03), respectively. Atrial fibrillation was seen in 2 patients in each group; all were returned to sinus rhythm by medical therapy. CONCLUSION: Although MIDCAB grafting is a challenging technique, it may be safely performed on selected patients with low postoperative mortality and morbidity.

Results of treatment methods in cardiac arrest following coronary artery bypass grafting.

BACKGROUND AND AIM OF THE STUDY: Emergency re-revascularization and invasive/noninvasive interventions in intensive care unit (ICU) are two main treatment methods in cardiac arrest following coronary artery bypass grafting (CABG). We evaluated the short- and long-term consequences of these two methods and discussed the indications for re-revascularization. METHODS: Between 1998 and 2004, a total of 148 CABG patients, who were complicated with cardiac arrest, were treated with emergency re-revascularization (n = 36, group R) and ICU procedures (n = 112, group ICU). Re-revascularizations are mostly blind operations depending on clinical/hemodynamic criteria. These are: no response to resuscitation, recurrent tachycardia/fibrillation, and severe hemodynamic instability after resuscitation. Re-angiography could only be performed in 3.3% of the patients. Event-free survival of the groups was calculated by the Kaplan-Meier method. Events are: death, recurrent angina, myocardial infarction, functional capacity, and reintervention. RESULTS: Seventy percent of patients, who were complicated with cardiac arrest, had perioperative myocardial infarction (PMI). This rate was significantly higher in group R (p = 0.013). The major finding in group R was graft occlusion (91.6%). During in-hospital period, no difference was observed in mortality rates between the two groups. However, hemodynamic stabilization time (p = 0.012), duration of hospitalization (p = 0.00006), and mechanical support use (p = 0.003) significantly decreased by re-revascularization. During the mean 37.1 +/- 25.1 months of follow-up period, long-term mortality (p = 0.03) and event-free survival (p = 0.029) rates were significantly in favor of group R. CONCLUSION: Better short- and long-term results were observed in the re-revascularization group.

The severity of positional mitral regurgitation during off-pump coronary artery bypass grafting.

BACKGROUND: The aims of this study were to elucidate the incidence of mitral regurgitation during off-pump coronary artery bypass (OPCAB) surgery to evaluate the relationship of the changes with ventricular function and possible mitral valve regurgitation caused by positioning. METHODS: Included in the study were 60 consecutive patients who underwent CAB grafting on the beating heart. We monitored several hemodynamic variables (systolic arterial pressure, mean arterial pressure, right atrial pressure, pulmonary capillary wedge pressure, and heart rate) at baseline and after each anastomosis and used transesophageal echocardiography (TEE) routinely after sternotomy, during each anastomosis, and after completion of the operation. Valvular functions, ejection fraction, and wall motion systolic index were recorded during each TEE evaluation. RESULTS: All of the patients underwent complete revascularization. We performed 132 consecutive OPCAB anastomoses in 60 patients (60 left anterior descending artery [LAD], 20 right coronary artery [RCA], 45 left circumflex coronary artery [LCX], and 7 diagonal artery grafts). During LCX anastomosis, 38 (84.4%) of 45 patients developed moderate mitral regurgitation. The wall motion score index (WMSI) significantly increased during CX grafting, as was demonstrated by higher WMSI values than for the RCA, diagonal, and LAD grafts. The ejection fraction was decreased significantly during CX and RCA anastomoses compared with baseline levels. The hemodynamic changes were in accord with these findings. The greatest hemodynamic compromise was seen during CX anastomosis. CONCLUSION: Positional mitral regurgitation occurs frequently and is a major contributor to hemodynamic instability during posterior- and lateral-wall revascularization during the OPCAB procedure.

Neo-chordae length adjustment in mitral valve repair.

Appropriate length adjustment of neo-chordae using PTFE sutures for mitral valve repair in degenerative valve disease has a crucial impact on both early and late outcomes of the repair. Herein we describe an adjuvant approach to facilitate the length adjustment.