Emotional states of consciousness, or what are typically called emotional feelings, are traditionally viewed as being innately programmed in subcortical areas of the brain, and are often treated as ...different from cognitive states of consciousness, such as those related to the perception of external stimuli. We argue that conscious experiences, regardless of their content, arise from one system in the brain. In this view, what differs in emotional and nonemotional states are the kinds of inputs that are processed by a general cortical network of cognition, a network essential for conscious experiences. Although subcortical circuits are not directly responsible for conscious feelings, they provide nonconscious inputs that coalesce with other kinds of neural signals in the cognitive assembly of conscious emotional experiences. In building the case for this proposal, we defend a modified version of what is known as the higher-order theory of consciousness.
The higher-order theory (HOT) of consciousness has often been misunderstood by critics. Here, we clarify its position on several issues, and distinguish it from other views, such as the global ...workspace theory (GWT) and early sensory models (e.g., first-order local recurrency theories). For example, HOT has been criticized for overintellectualizing consciousness. We show that, while higher-order states are cognitively assembled, the requirements are in fact considerably less than often presumed. In this sense, HOT may be viewed as an intermediate position between GWT and early sensory views. We also clarify that most proponents of HOT do not stipulate consciousness as equivalent to metacognition or confidence. Furthermore, compared with other existing theories, HOT can arguably account better for complex everyday experiences, such as emotions and episodic memories. This makes HOT particularly useful as a framework for conceptualizing pathological mental states.
Misunderstandings about HOT have marginalized it relative to other approaches.We clarify some of the key misunderstandings, including assumptions about the equivalence between consciousness and metacognition, and the role of introspection and the self.We reply to several objections, including those concerning the nature of perception in the visual periphery and issues raised about the value of so-called ‘no report’ paradigms.We also address issues regarding the involvement of prefrontal cortex, including questions about whether it is necessary, and whether its deactivation during dreams and psychedelic states is incompatible with it contributing to higher-order awareness.We propose a reconceptualization of lower-order states that contribute to higher-order awareness, including states of prefrontal cortex and multimodal and mnemonic states processed in posterior cortical areas.We provide arguments as to why the HOT of consciousness may be superior to both GWT and local recurrency theory regarding its ability to account for subjective experiences, especially of complex states such as memories and emotions that occur in everyday life and that are hallmarks of psychopathological conditions.
Background and aims
Brief alcohol interventions in medical settings are efficacious in improving self‐reported alcohol consumption among those with low‐severity alcohol problems. Screening, Brief ...Intervention and Referral to Treatment initiatives presume that brief interventions are efficacious in linking patients to higher levels of care, but pertinent evidence has not been evaluated. We estimated main and subgroup effects of brief alcohol interventions, regardless of their inclusion of a referral‐specific component, in increasing the utilization of alcohol‐related care.
Methods
A systematic review of English language papers published in electronic databases to 2013. We included randomized controlled trials (RCTs) of brief alcohol interventions in general health‐care settings with adult and adolescent samples. We excluded studies that lacked alcohol services utilization data. Extractions of study characteristics and outcomes were standardized and conducted independently. The primary outcome was post‐treatment alcohol services utilization assessed by self‐report or administrative data, which we compared across intervention and control groups.
Results
Thirteen RCTs met inclusion criteria and nine were meta‐analyzed (n = 993 and n = 937 intervention and control group participants, respectively). In our main analyses the pooled risk ratio (RR) was = 1.08, 95% confidence interval (CI) = 0.92–1.28. Five studies compared referral‐specific interventions with a control condition without such interventions (pooled RR = 1.08, 95% CI = 0.81–1.43). Other subgroup analyses of studies with common characteristics (e.g. age, setting, severity, risk of bias) yielded non‐statistically significant results.
Conclusions
There is a lack of evidence that brief alcohol interventions have any efficacy for increasing the receipt of alcohol‐related services.
Outcome after aortic, axillary, or femoral cannulation for acute type A aortic dissection Kreibich, Maximilian; Chen, Zehang; Rylski, Bartosz ...
Journal of thoracic and cardiovascular surgery/The Journal of thoracic and cardiovascular surgery/The journal of thoracic and cardiovascular surgery,
July 2019, 2019-07-00, 20190701, Letnik:
158, Številka:
1
Journal Article
Recenzirano
Odprti dostop
The optimal method for arterial cannulation in acute aortic dissection type A (ADA) remains controversial. The aim of this study was to compare central ascending aortic, axillary, and femoral ...cannulation in patients who underwent surgery for acute ADA.
Between 2006 and 2017, 584 patients were operated on for acute ADA. Of those, 355 (61%) underwent ascending aortic, 101 (17%) right axillary, and 128 (22%) femoral cannulation for arterial inflow. Clinical features and outcomes were compared after inverse probability weighting.
After inverse probability weighting there were no statistical differences in preoperative characteristics. Operative details differed significantly among the 3 groups: hemiarch replacement was performed more often in the central aortic and the femoral group (P < .001), whereas total arch replacement was performed more often in the axillary group (P < .001). Cardiopulmonary bypass (P = .022) and aortic cross-clamp (P = .021) times were shortest in the aortic cannulation group and longest in the femoral cannulation group. Postoperative morbidities were similar; procedure-related stroke (P = .783) and the need for renal replacement therapy (P = .446). In-hospital mortality (P = .680) and long-term survival were similar (log rank, P = .704). Multilevel multivariate mixed effect logistic regression showed that the cannulation strategy was not associated with in-hospital mortality.
Central ascending aortic cannulation in patients with ADA can be used as safely as axillary or femoral cannulation, providing another option for quick and easy establishment of cardiopulmonary bypass.
Transcatheter aortic-valve replacement (TAVR) is the recommended therapy for patients with severe aortic stenosis who are not suitable candidates for surgery. The outcomes beyond 1 year in such ...patients are not known.
We randomly assigned patients to transfemoral TAVR or to standard therapy (which often included balloon aortic valvuloplasty). Data on 2-year outcomes were analyzed.
A total of 358 patients underwent randomization at 21 centers. The rates of death at 2 years were 43.3% in the TAVR group and 68.0% in the standard-therapy group (P<0.001), and the corresponding rates of cardiac death were 31.0% and 62.4% (P<0.001). The survival advantage associated with TAVR that was seen at 1 year remained significant among patients who survived beyond the first year (hazard ratio, 0.58; 95% confidence interval CI, 0.36 to 0.92; P=0.02 with the use of the log-rank test). The rate of stroke was higher after TAVR than with standard therapy (13.8% vs. 5.5%, P=0.01), owing, in the first 30 days, to the occurrence of more ischemic events in the TAVR group (6.7% vs. 1.7%, P=0.02) and, beyond 30 days, to the occurrence of more hemorrhagic strokes in the TAVR group (2.2% vs. 0.6%, P=0.16). At 2 years, the rate of rehospitalization was 35.0% in the TAVR group and 72.5% in the standard-therapy group (P<0.001). TAVR, as compared with standard therapy, was also associated with improved functional status (P<0.001). The data suggest that the mortality benefit after TAVR may be limited to patients who do not have extensive coexisting conditions. Echocardiographic analysis showed a sustained increase in aortic-valve area and a decrease in aortic-valve gradient, with no worsening of paravalvular aortic regurgitation.
Among appropriately selected patients with severe aortic stenosis who were not suitable candidates for surgery, TAVR reduced the rates of death and hospitalization, with a decrease in symptoms and an improvement in valve hemodynamics that were sustained at 2 years of follow-up. The presence of extensive coexisting conditions may attenuate the survival benefit of TAVR. (Funded by Edwards Lifesciences; ClinicalTrials.gov number, NCT00530894.).
Expression quantitative trait locus detection has become increasingly important for understanding how noncoding variants contribute to disease susceptibility and complex traits. The major challenges ...in expression quantitative trait locus fine-mapping and causal variant discovery relate to the impact of linkage disequilibrium on signals due to one or multiple functional variants that lie within a credible set. We perform expression quantitative trait locus fine-mapping using the all-but-one approach, conditioning each signal on all others detected in an interval, on the Consortium for the Architecture of Gene Expression cohorts of microarray-based peripheral blood gene expression in 2,138 European-ancestry human adults. We contrast these results with traditional forward stepwise conditional analysis and a Bayesian localization method. All-but-one conditioning significantly modifies effect-size estimates for 51% of 2,351 expression quantitative trait locus peaks, but only modestly affects credible set size and location. On the other hand, both conditioning approaches result in unexpectedly low overlap with Bayesian credible sets, with just 57% peak concordance and between 50% and 70% SNP sharing, leading us to caution against the assumption that any one localization method is superior to another. We also cross reference our results with ATAC-seq data, cell-type-specific expression quantitative trait locus, and activity-by-contact-enhancers, leading to the proposal of a 5-tier approach to further reduce credible set sizes and prioritize likely causal variants for all known inflammatory bowel disease risk loci active in immune cells.
Objectives
Ideal long‐term vocal fold augmentation materials should be biocompatible, easily administered, allow tissue integration for long‐term effect, and remain at the site of injection. A novel ...silk protein particle suspended in hyaluronic acid (Silk‐HA) has been developed specifically for vocal fold augmentation to address this unmet need. This article presents the 6‐month, preclinical findings of a canine vocal fold injection trial for Silk‐HA.
Methods
Twelve beagle dogs were injected transorally in the lateral/deep aspect of their right thyroarytenoid muscles with 0.3 cc of Silk‐HA or calcium hydroxylapatite in carboxymethyl cellulose (CaHA‐CMC). The Silk‐HA particle injectable was delivered via a custom catheter, whereas CaHA‐CMC was delivered through a commercially available malleable needle. The six dogs from each material group were sacrificed 6 months from the injection date for the evaluation of implant longevity, immune response, and material migration.
Results
Silk‐HA provides immediate medialization of the right vocal fold, lasting for a minimum of 6 months in a canine model. Silk‐HA and CaHA‐CMC both demonstrate similar inflammatory responses. The Silk‐HA was shown to remain without migration at the site of injection in all six canine subjects, whereas CaHA‐CMC demonstrated migration in four of the six canines. In two canines implanted with CaHA‐CMC, material was discovered to migrate to the retropharyngeal lymph nodes.
Conclusion
In a canine subject model, the Silk‐HA material compares favorably in terms of longevity and immune response to CaHA‐CMC. The lack of migration of the Silk‐HA material demonstrates a promising potential for vocal fold injection in the clinic.
Level of Evidence
NA
Laryngoscope, 129:1856–1862, 2019
Among the caspases that cause regulated cell death, a unique function for caspase-7 has remained elusive. Caspase-3 performs apoptosis, whereas caspase-7 is typically considered an inefficient ...back-up. Caspase-1 activates gasdermin D pores to lyse the cell; however, caspase-1 also activates caspase-7 for unknown reasons
. Caspases can also trigger cell-type-specific death responses; for example, caspase-1 causes the extrusion of intestinal epithelial cell (IECs) in response to infection with Salmonella enterica subsp. enterica serovar Typhimurium (S. Typhimurium)
. Here we show in both organoids and mice that caspase-7-deficient IECs do not complete extrusion. Mechanistically, caspase-7 counteracts gasdermin D pores and preserves cell integrity by cleaving and activating acid sphingomyelinase (ASM), which thereby generates copious amounts of ceramide to enable enhanced membrane repair. This provides time to complete the process of IEC extrusion. In parallel, we also show that caspase-7 and ASM cleavage are required to clear Chromobacterium violaceum and Listeria monocytogenes after perforin-pore-mediated attack by natural killer cells or cytotoxic T lymphocytes, which normally causes apoptosis in infected hepatocytes. Therefore, caspase-7 is not a conventional executioner but instead is a death facilitator that delays pore-driven lysis so that more-specialized processes, such as extrusion or apoptosis, can be completed before cell death. Cells must put their affairs in order before they die.
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