The genetic architecture of the human cerebral cortex

The cerebral cortex underlies our complex cognitive capabilities, yet little is known about the specific genetic loci that influence human cortical structure. To identify genetic variants that affect cortical structure, we conducted a genome-wide association meta-analysis of brain magnetic resonance imaging data from 51,665 individuals. We analyzed the surface area and average thickness of the whole cortex and 34 regions with known functional specializations. We identified 199 significant loci and found significant enrichment for loci influencing total surface area within regulatory elements that are active during prenatal cortical development, supporting the radial unit hypothesis. Loci that affect regional surface area cluster near genes in Wnt signaling pathways, which influence progenitor expansion and areal identity. Variation in cortical structure is genetically correlated with cognitive function, Parkinson's disease, insomnia, depression, neuroticism, and attention deficit hyperactivity disorder

Sneddon-Wilkinson disease following COVID-19 vaccination

Sneddon-Wilkinson disease, also known as subcorneal pustular dermatosis (SPD), is a rare disease characterized by vesicles or pustules that may rapidly expand and coalesce. Idiopathic in nature, SPD's clinical presentation of "half-half" blisters, with half of each blister containing pus and half containing clear fluid, is characteristic of this disease. We describe a previously healthy 21-year-old man who developed acute pustular vesicular eruptions consistent with SPD eight days following the Moderna COVID-19 vaccination

Systematic review and estimated cost-efficacy of biologics compared with narrowband ultraviolet B light for the treatment of moderate to severe psoriasis and atopic dermatitis.

Psoriasis and atopic dermatitis are chronic inflammatory skin conditions, each affecting about 2-3% of the United States adult population. Phototherapy, such as narrowband ultraviolet-B (NB-UVB) therapy have been employed for the treatment of both psoriasis and atopic dermatitis for decades. More recently, systemic biologics have been approved by the Food and Drug Administration (FDA), representing a great advancement in dermatology. No comprehensive study to date has compared the cost efficacy of phototherapy compared to FDA-approved biologics for the treatment of psoriasis and atopic dermatitis. We pursued a systematic review of the literature for studies assessing efficacy of NB-UVB or biologics with endpoints including the Psoriasis Area and Severity Index (PASI) and the Eczema Area and Severity Index (EASI). Thirty-four studies including 55 treatment regimens and 5,123 patients were included in the analysis. Phototherapy costs were estimated with Medicare fee schedules for phototherapy-related current procedural terminology code (CPT), and biologic costs were estimated with wholesale acquisition cost (WAC). Total costs to achieve PASI 75 or EASI 75 in each study were standardized to a single month, the adjusted cost, and exploited to a year, the effective yearly cost, allowing direct cost-efficacy comparison despite different durations of treatment described in studies. The psoriasis analysis found NB-UVB to be the most cost-effective therapy, with an adjusted monthly cost of $1714.00 per PASI 75. Infliximab was the least expensive biologic, with an adjusted monthly cost of$2076.00 to $2502.00 per PASI 75. For atopic dermatitis, no NB-UVB studies utilized EASI 75 as their outcome measure, hindering the ability to directly compare cost effectiveness for the treatment of atopic dermatitis. However, all NB-UVB studies depicted a reduced treatment cost per treatment period compared to studies assessing biologics, although this comparison does not account for efficacy. The results depict NB-UVB to be the most cost effective for the treatment of psoriasis and the least expensive per treatment period for the treatment of atopic dermatitis. However, certain factors need to be taken into account. Biologics may be more effective for more severe disease, do not require multiple weekly clinic visits, and the ease for patient compliance may lead some to favor biologic therapy. This study is necessary to allow physicians, patients, and health systems to make informed decisions regarding cost-efficacy for a variety of treatment options

Novel in vivo mouse model of shoulder implant infection.

BACKGROUND:Animal models are used to guide management of periprosthetic implant infections. No adequate model exists for periprosthetic shoulder infections, and clinicians thus have no preclinical tools to assess potential therapeutics. We hypothesize that it is possible to establish a mouse model of shoulder implant infection (SII) that allows noninvasive, longitudinal tracking of biofilm and host response through in vivo optical imaging. The model may then be employed to validate a targeting probe (1D9-680) with clinical translation potential for diagnosing infection and image-guided débridement. METHODS:A surgical implant was press-fit into the proximal humerus of c57BL/6J mice and inoculated with 2 μL of 1 × 103 (e3), or 1 × 104 (e4), colony-forming units (CFUs) of bioluminescent Staphylococcus aureus Xen-36. The control group received 2 μL sterile saline. Bacterial activity was monitored in vivo over 42 days, directly (bioluminescence) and indirectly (targeting probe). Weekly radiographs assessed implant loosening. CFU harvests, confocal microscopy, and histology were performed. RESULTS:Both inoculated groups established chronic infections. CFUs on postoperative day (POD) 42 were increased in the infected groups compared with the sterile group (P < .001). By POD 14, osteolysis was visualized in both infected groups. The e4 group developed catastrophic bone destruction by POD 42. The e3 group maintained a congruent shoulder joint. Targeting probes helped to visualize low-grade infections via fluorescence. DISCUSSION:Given bone destruction in the e4 group, a longitudinal, noninvasive mouse model of SII and chronic osteolysis was produced using e3 of S aureus Xen-36, mimicking clinical presentations of chronic SII. CONCLUSION:The development of this model provides a foundation to study new therapeutics, interventions, and host modifications

Novel in vivo mouse model of shoulder implant infection

Background: Animal models are used to guide management of periprosthetic implant infections. No adequate model exists for periprosthetic shoulder infections, and clinicians thus have no preclinical tools to assess potential therapeutics. We hypothesize that it is possible to establish a mouse model of shoulder implant infection (SII) that allows noninvasive, longitudinal tracking of biofilm and host response through in vivo optical imaging. The model may then be employed to validate a targeting probe (1D9-680) with clinical translation potential for diagnosing infection and image-guided debridement. Methods: A surgical implant was press-fit into the proximal humerus of c57BL/6J mice and inoculated with 2 mu L of 1 x 10(3) (e3), or 1 x 10(4) (e4), colony-forming units (CFUs) of bioluminescent Staphylococcus aureus Xen-36. The control group received 2 mu L sterile saline. Bacterial activity was monitored in vivo over 42 days, directly (bioluminescence) and indirectly (targeting probe). Weekly radiographs assessed implant loosening. CFU harvests, confocal microscopy, and histology were performed. Results: Both inoculated groups established chronic infections. CFUs on postoperative day (POD) 42 were increased in the infected groups compared with the sterile group (P <.001). By POD 14, osteolysis was visualized in both infected groups. The e4 group developed catastrophic bone destruction by POD 42. The e3 group maintained a congruent shoulder joint. Targeting probes helped to visualize low-grade infections via fluorescence. Discussion: Given bone destruction in the e4 group, a longitudinal, noninvasive mouse model of SII and chronic osteolysis was produced using e3 of S aureus Xen-36, mimicking clinical presentations of chronic SII. Conclusion: The development of this model provides a foundation to study new therapeutics, interventions, and host modifications. (C) 2019 Journal of Shoulder and Elbow Surgery Board of Trustees. All rights reserved

The Taf14 YEATS domain is a reader of histone crotonylation

The discovery of new histone modifications is unfolding at startling rates, however, the identification of effectors capable of interpreting these modifications has lagged behind. Here we report the YEATS domain as an effective reader of histone lysine crotonylation – an epigenetic signature associated with active transcription. We show that the Taf14 YEATS domain engages crotonyllysine via a unique π-π-π-stacking mechanism and that other YEATS domains have crotonyllysine binding activity

Trust predicts COVID-19 prescribed and discretionary behavioral intentions in 23 countries

The worldwide spread of a new coronavirus (SARS-CoV-2) since December 2019 has posed a severe threat to individuals' well-being. While the world at large is waiting that the released vaccines immunize most citizens, public health experts suggest that, in the meantime, it is only through behavior change that the spread of COVID-19 can be controlled. Importantly, the required behaviors are aimed not only at safeguarding one's own health. Instead, individuals are asked to adapt their behaviors to protect the community at large. This raises the question of which social concerns and moral principles make people willing to do so. We considered in 23 countries (N = 6948) individuals' willingness to engage in prescribed and discretionary behaviors, as well as country-level and individual-level factors that might drive such behavioral intentions. Results from multilevel multiple regressions, with country as the nesting variable, showed that publicized number of infections were not significantly related to individual intentions to comply with the prescribed measures and intentions to engage in discretionary prosocial behaviors. Instead, psychological differences in terms of trust in government, citizens, and in particular toward science predicted individuals' behavioral intentions across countries. The more people endorsed moral principles of fairness and care (vs. loyalty and authority), the more they were inclined to report trust in science, which, in turn, statistically predicted prescribed and discretionary behavioral intentions. Results have implications for the type of intervention and public communication strategies that should be most effective to induce the behavioral changes that are needed to control the COVID-19 outbreak

Trust predicts COVID-19 prescribed and discretionary behavioral intentions in 23 countries

The worldwide spread of a new coronavirus (SARS-CoV-2) since December 2019 has posed a severe threat to individuals’ well-being. While the world at large is waiting that the released vaccines immunize most citizens, public health experts suggest that, in the mean time, it is only through behavior change that the spread of COVID-19 can be controlled. Importantly, the required behaviors are aimed not only at safeguarding one’s own health. Instead, individuals are asked to adapt their behaviors to protect the community at large. This raises the question of which social concerns and moral principles make people willing to do so. We considered in 23 countries (N = 6948) individuals’ willingness to engage in prescribed and discretionary behaviors, as well as country-level and individual-level factors that might drive such behavioral intentions. Results from multilevel multiple regressions, with country as the nesting variable, showed that publicized number of infections were not significantly related to individual intentions to comply with the prescribed measures and intentions to engage in discretionary prosocial behaviors. Instead, psychological differences in terms of trust in government, citizens, and in particular toward science predicted individuals’ behavioral intentions across countries. The more people endorsed moral principles of fairness and care (vs. loyalty and authority), the more they were inclined to report trust in science, which, in turn, statistically predicted prescribed and discretionary behavioral intentions. Results have implications for the type of intervention and public communication strategies that should be most effective to induce the behavioral changes that are needed to control the COVID-19 outbreak