Curcumin differentially regulates the expression of superoxide dismutase in cerebral cortex and cerebellum of l-thyroxine (T4)-induced hyperthyroid rat brain

The present investigation was aimed to elucidate the effect of curcumin on lipid peroxidation (LPx) and superoxide dismutase (SOD) in l-thyroxine (T₄)-induced oxidative stress in cerebral cortex and cerebellum of rat brain. Elevated level of LPx in cerebral cortex declined to control level on supplementation of curcumin to T₄-treated rats. On the other hand, unaltered LPx level in T₄-treated rats showed a significantly decreased level of LPx on supplementation of curcumin. The increased activity of SOD and translated products of SOD1 and SOD2 in cerebral cortex of T₄-treated rats was ameliorated on supplementation of curcumin. The decreased activity of SOD and protein expression of SOD1 in cerebellum of T₄-treated rats were ameliorated on administration of curcumin. On the other hand, SOD2 expression was not influenced either by T₄-treated or by curcumin supplementation to T₄-treated rats. Results of the present investigation reveal that the regulation of expression of SOD by curcumin in different regions (cerebral cortex and cerebellum) of rat brain is different under hyperthyroidism.     

Comparison of two-dimensional manual and three-dimensional SurgiCase and BLUEPRINT planning software measurements of glenoid version,inclination, and humeral subluxation

IntroductionVirtual planning for shoulder arthroplasty using preoperative computed tomography (CT) has been gaining popularity, and it is imperative for surgeons to recognize any differences in measurements that may exist amongst software platforms. The purpose of this study is to compare measurements of glenoid version, inclination, and humeral head subluxation between a manual approach and two varying automated software platforms using either a best-fit sphere technique (Wright-Medical BLUEPRINT) or an anatomic landmarks technique (Materalise SurgiCase).MethodsA case control study of 289 CT images from patients preoperatively planned for a total shoulder arthroplasty or reverse shoulder arthroplasty using SurgiCase (v3.0.110.5) were also successfully analyzed by BLUEPRINT (v2.1.6). Glenoid version, inclination, and subluxation were measured manually in a blind fashion by two separate investigators using axial and coronal images oriented to the scapular plane; interobserver and intraobserver reliabilities were measured using intraclass correlation coefficients (ICCs). Concordance correlation coefficients (CCCs), mean differences, and clinically relevant agreement in measurements between the software platforms and with the manual technique were compared. The impact of greater glenoid retroversion on the differences in measurements between the software platforms was further studied by correlation analysis.ResultsThe mean differences between SurgiCase and BLUEPRINT were + 0.5° for glenoid inclination (P = .064; CCC = 0.84), -0.9° for glenoid version (P < .001; CCC = 0.92), and -1.4% for humeral subluxation (P = .002; CCC = 0.88). Agreement within 5 units was 78.9% for inclination, 89.3% for version, and 64.1% for subluxation. Glenoid retroversion had no relation with the degree of variation in measured inclination (P = .59) or version (P = .56). There were significant differences between manual and 3D software measurements for glenoid inclination, version, and subluxation (P < .001). Both software measurements were more inferiorly inclined (average difference, SurgiCase -3.2° and BLUEPRINT -3.9°), more retroverted (average difference, SurgiCase -4.0° and BLUEPRINT -3.2°), and more posteriorly subluxated (average difference, SurgiCase + 3.4% and BLUEPRINT + 4.8%).ConclusionThe SurgiCase and BLUEPRINT preoperative planning software yield clinically similar measurements for glenoid version, inclination, and subluxation. The degree of glenoid retroversion does not impact the variability of inclination or version between the landmark and best-fit sphere software techniques. Compared to the 2D manual technique, both 3D software programs reported greater inferior inclination, retroversion, and posterior subluxation.Level of evidenceLevel III; Retrospective Diagnostic Study     

Neural correlates of humor detection and appreciation

Humor is a uniquely human quality whose neural substrates remain enigmatic. The present report combined dynamic, real-life content and event-related functional magnetic resonance imaging (fMRI) to dissociate humor detection ("getting the joke") from humor appreciation (the affective experience of mirth). During scanning, subjects viewed full-length episodes of the television sitcoms Seinfeld or The Simpsons. Brain activity time-locked to humor detection moments revealed increases in left inferior frontal and posterior temporal cortices, whereas brain activity time-locked to moments of humor appreciation revealed increases in bilateral regions of insular cortex and the amygdala. These findings provide evidence that humor depends critically upon extant neural systems important for resolving incongruities (humor detection) and for the expression of affect (humor appreciation).     

Repetition-related reductions in neural activity reveal component processes of mental simulation

In everyday life, people adaptively prepare for the future by simulating dynamic events about impending interactions with people, objects and locations. Previous research has consistently demonstrated that a distributed network of frontal–parietal–temporal brain regions supports this ubiquitous mental activity. Nonetheless, little is known about the manner in which specific regions of this network contribute to component features of future simulation. In two experiments, we used a functional magnetic resonance (fMR)-repetition suppression paradigm to demonstrate that distinct frontal–parietal–temporal regions are sensitive to processing the scenarios or what participants imagined was happening in an event (e.g. medial prefrontal, posterior cingulate, temporal–parietal and middle temporal cortices are sensitive to the scenarios associated with future social events), people (medial prefrontal cortex), objects (inferior frontal and premotor cortices) and locations (posterior cingulate/retrosplenial, parahippocampal and posterior parietal cortices) that typically constitute simulations of personal future events. This pattern of results demonstrates that the neural substrates of these component features of event simulations can be reliably identified in the context of a task that requires participants to simulate complex, everyday future experiences.     

Exosomes secreted by prostate cancer cells under hypoxia promote matrix metalloproteinases activity at pre-metastatic niches

Approximately, 30 000 men die from prostate cancer (PCa) every year in the United States, mainly due to the metastasis. Thus, the key events associated with PCa metastasis are under rigorous investigation, with recent studies showing that preparation of pre-metastatic niches (PMN) in distant organs is an important step. However, the molecular basis for PMN preparation is still unclear. Hypoxia in primary tumors promotes aggressiveness; however, its precise role in metastasis is not clear. We recently reported that exosomes secreted by PCa cells under hypoxia promote stemness and invasiveness in naïve PCa cells; however, whether these extracellular vesicles also influence PMN remains unknown. In the present study, we isolated exosomes from human PCa PC3 cells under normoxic (21% O₂, exosomes secreted under normoxic condition [Exo^Normoxic]) and hypoxic (1% O₂, exosomes secreted under hypoxic condition [Exo^Hypoxic]) conditions, and characterized their effect (10 µg exosomes, intraperitoneal (IP) treatment every 48 hours for 4 weeks) on key biomarkers associated with PMN in nude mice. Whole animal fluorescence imaging showed that Exo^Hypoxic treatment promotes matrix metalloproteinases (MMPs) activity in several putative metastatic sites. Histological studies confirmed that Exo^Hypoxic treatment enhanced the level of MMP2, MMP9, and extracellular matrix proteins (fibronectin and collagen) as well as increased the number of CD11b+ cells at selective PMN sites. Furthermore, proteomic profiling of exosomes by liquid chromatography/mass spectrometry identified cargo proteins in Exo^Normoxic and Exo^Hypoxic as well as distinct canonical pathways targeted by them. These results suggest that exosomes secreted by PCa cells under hypoxia plausibly remodel distant PMN, and thus, could be a potential target to control metastatic PCa.     

Decreased segregation of brain systems across the healthy adult lifespan

Healthy aging has been associated with decreased specialization in brain function. This characterization has focused largely on describing age-accompanied differences in specialization at the level of neurons and brain areas. We expand this work to describe systems-level differences in specialization in a healthy adult lifespan sample (n = 210; 20–89 y). A graph-theoretic framework is used to guide analysis of functional MRI resting-state data and describe systems-level differences in connectivity of individual brain networks. Young adults’ brain systems exhibit a balance of within- and between-system correlations that is characteristic of segregated and specialized organization. Increasing age is accompanied by decreasing segregation of brain systems. Compared with systems involved in the processing of sensory input and motor output, systems mediating “associative” operations exhibit a distinct pattern of reductions in segregation across the adult lifespan. Of particular importance, the magnitude of association system segregation is predictive of long-term memory function, independent of an individual’s age.Healthy adult aging is characterized by a progressive degradation of brain structure and function associated with gradual changes in cognition (see reviews in refs. 1, 2). Among the age-accompanied functional changes, one prominent observation is a reduction in the specificity with which distinct neural structures mediate particular processing roles [i.e., a reduction in functional specialization, or “dedifferentiation” (3)]. A reduction in functional specificity has been observed across multiple spatial scales of brain organization, ranging from the firing patterns of single neurons (e.g., refs. 4, 5) to the evoked activity of individual brain areas (6–10). (For additional discussion see ref. 11.)Despite the compelling evidence for age-accompanied reductions in functional specialization across numerous brain areas, the relationship between neural specialization and cognition generally is weak. This likely is related to the fact that broad cognitive domains such as “long-term memory” and “executive control” are mediated by distributed and interacting brain systems, each consisting of multiple interacting brain areas. Thus, relating functional specialization in a single brain area to general measures of cognition likely will be unsuccessful. Such an argument is consistent with the view that severe impairment in cognitive function due to injury or insult typically is a consequence of damage to multiple brain locations (e.g., refs. 12, 13). Based on these considerations, it seems plausible that the cognitive decline evident even in healthy older adults may be related to decreased functional integrity at a systems level of organization. The present report approaches healthy aging from this systems-level perspective in an effort to relate systems-related functional specialization to age-accompanied differences in cognition.Before proceeding, it is important to clarify the meaning of system. The term “system” often is used in relation to brain organization when referring to any group of areas that subserve common processing roles. For example, the visual system comprises brain areas primarily defined by their role in processing visual stimuli (e.g., ref. 14), and the frontal–parietal task control system consists of brain areas involved mainly in adaptive task control (15). Identifying distinct brain systems and defining their functional roles by examining how their constituent areas are modulated by experimental testing or are impaired by brain damage is not an easy endeavor; systems of brain areas typically mediate processing roles that span multiple stimulus and task demands. This reality makes assessing changes in the functional specialization of systems across cohorts of individuals extremely challenging.An alternative formal and complementary approach to defining a brain system involves understanding how brain areas relate to one another via their patterns of shared functional or anatomical relationships in the context of a large-scale network (16, 17). Like many other complex networks, brain networks may be analyzed as a graph of connected or interacting elements. When a brain network graph represents the interaction of areas, one prominent feature is the presence of subsets of areas that are highly interactive with one another and less interactive with other subsets of areas. This pattern of organization reflects the presence of distinct “modules” or “communities” (e.g., ref. 18). Importantly, numerous connectivity-defined human brain modules have been shown to overlap closely with functional systems as defined by other methods of assessing information processing [e.g., task-evoked activity, lesion-mapping (19, 20)]. The close correspondence between differing methods of system identification provides a basis for using connectivity to understand the organization of brain systems and how they may differ with age.Modular brain networks are characterized by a fine balance of dense within-system relationships among brain areas (nodes) that have highly related processing roles, as well as sparser (but not necessarily absent) relationships between areas in systems with divergent processing roles. This pattern of system segregation facilitates communication among brain areas that may be distributed anatomically but nevertheless are in the service of related sets of processing operations, and simultaneously reinforces the functional specialization of systems that perform different sets of processing operations (21). Importantly, segregated systems can communicate with one another via the presence of the sparser connections between them. As such, any deviation in the patterns of within- and between-system connectivity may be considered evidence for a change in the system’s specialization. Furthermore, if aging is associated with changes in functional specialization at the level of brain systems, this may be revealed by examining the differences in patterns of within- and between-system areal connectivity across age.We use functional connectivity, as measured by blood oxygen-level–dependent (BOLD) functional MRI (fMRI) during rest [resting-state functional correlations (RSFCs), see ref. 22], to assess age-related differences in the organization of brain systems. Changes in RSFC patterns between sets of areas have been observed following extensive directed training (23–25), and differences in RSFC patterns also have been reported in cross-sectional comparisons spanning from childhood to older age (e.g., refs. 26–29). The extant data suggest that RSFCs are malleable and reflect sensitivity to a history of coactivation: changes in the processing roles of areas may be characterized by changes in their RSFCs with other areas (for discussion, see ref. 17). This feature makes RSFCs particularly useful in assessing differences in the organization and specialization of brain systems.In the present study, the age-accompanied differences in the functional specialization of brain systems are revealed by examining patterns of within- and between-system areal RSFCs in a large healthy adult lifespan sample (n = 210; age range, 20–89 y). The inclusion of subjects distributed across each decade of adulthood not only allows us to assess how older and younger adults differ in their organization of brain systems, but also provides insight as to whether there is a critical stage of the adult lifespan when differences in system organization may appear. Previous reports attempted to address related questions by examining end points of the adult aging spectrum, focusing on the organization within specific systems (e.g., refs. 26, 28, 30), or using area nodes that are not representative of functional areas [e.g., structural parcels (31–34)]. The latter feature likely contributes to the inconsistent findings observed in the relationship between summary network measures and age groups (e.g., refs. 31, 35 vs. refs. 30, 36). In addition to examining age-related differences in system organization developed from a biologically plausible cortical parcellation of the human brain network, we also relate systems-level differences in organization to differences in general measures of cognitive ability. To foreshadow the results that follow, we report that aging is associated with differences in patterns of connectivity within and between brain systems, that these differences are not uniform across all systems, and that the segregation of brain systems has a direct relationship to measures of cognitive ability independent of age.     

Pulmonary endarterectomy for saddling pulmonary embolism by Aspergillus fungus in an immunocompetent patient

We present a case of Tricuspid valve Aspergillus endocarditis with saddle shaped massive pulmonary embolism occurring in an immunocompetent host. The patient was managed uniquely by pulmonary endarterectomy (PEA) and combination antifungal chemotherapy with Liposomal amphotericin-B + caspofungin.