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

Assessment of Hypertension Control Among Adults Participating in a Mobile Technology Blood Pressure Self-management Program.

ImportanceIt is unclear whether mobile technology hypertension self-management programs are associated with blood pressure (BP) control.ObjectiveTo examine whether engagement with a hypertension self-management program with a BP monitor and connected smartphone application with clinically based digital coaching was associated with BP control during a follow-up period of as long as 3 years.Design, setting, and participantsThis cohort study enrolled US adults with elevated BP or hypertension between January 1, 2015, and July 1, 2020. The hypertension self-management program was provided through the participant's (or their spouse's) employer health plan.ExposuresProgram engagement, defined by average number of application sessions.Main outcomes and measuresSystolic and diastolic BP measured by a US Food and Drug Administration-cleared BP monitor, with categories defined as normal (systolic BP, <120 mm Hg), elevated (systolic BP, 120-129 mm Hg), stage 1 hypertension (systolic BP, 130-139 mm Hg), and stage 2 hypertension (systolic BP ≥140 mm Hg). Other measures included age, gender, depression, anxiety, diabetes, high cholesterol, smoking, geographic region, area deprivation index, self-reported weight, and device-measured physical activity (steps per day).ResultsAmong 28 189 participants (median [IQR] age, 51 [43-58] years; 9424 women [40.4%]; 13 902 men [59.6%]), median (IQR) baseline systolic BP was 129.5 mm Hg (120.5-139.6 mm Hg) and diastolic BP was 81.7 mm Hg (75.7-88.4 mm Hg). Median systolic BP at 1 year improved at least 1 category for 495 of 934 participants (53.0%) with baseline elevated BP, 673 of 966 (69.7%) with baseline stage 1 hypertension, and 920 of 1075 (85.7%) with baseline stage 2 hypertension. Participants in the program for 3 years had a mean (SEM) systolic BP reduction of 7.2 (0.4), 12.2 (0.7), and 20.9 (1.7) mm Hg compared with baseline for those starting with elevated, stage 1 hypertension, and stage 2 hypertension, respectively. Greater engagement was associated with lower systolic BP over time (high-engagement group: 131.2 mm Hg; 95% CI, 115.5-155.8 mm Hg; medium-engagement group: 133.4 mm Hg; 95% CI 116.3-159.5 mm Hg; low-engagement group: 135.5 mm Hg; 95% CI, 117.3-164.8 mm Hg; P < .001); these results persisted after adjusting for age, gender, depression, anxiety, diabetes, high cholesterol, smoking, area deprivation index rank, and US region, which was partially mediated by greater physical activity. A very high BP (systolic BP >180 mm Hg) was observed 11 637 times from 3778 participants. Greater engagement was associated with lower risk of very high BP; the estimated probability of a very high BP was greater in the low-engagement group (1.42%; 95% CI, 1.26%-1.59%) compared with the medium-engagement group (0.79%; 95% CI, 0.71%-0.87%; P < .001) and the high-engagement group (0.53%; 95% CI, 0.45%-0.60%; P < .001 for comparison with both groups).Conclusions and relevanceThe findings of this study suggest that a mobile technology hypertension self-management program can support long-term BP control and very high BP detection. Such programs may improve real-world BP monitoring and control

Place-value and physical size converge in automatic processing of multi-digit numbers

Previous research has shown that multi-digit number processing is modulated by both place-value and physical size of the digits. By pitting place-value against physical size, the present study examined if one of the attributes had a greater impact on the automatic processing of multi-digit numbers. In three experiments, participants were presented with two-digit number pairs that appeared in frames. They were instructed to select the larger frame while ignoring the numbers within the frames. Importantly, we manipulated the physical size of the digits’ (i.e., both decade/unit digits were physically larger) within the frames, the unit-decade compatibility (i.e., the relationship between the numerical values of both decade and unit digits was consistent or inconsistent), and the congruity between the numerical values of the decade digits and the frames’ physical size (i.e., decade value-frame size congruity). In Experiment 1, where all pairs were unit-decade compatible, a decade value-frame size congruity effect emerged for pairs with physically larger decade, but not unit, digits. However, when adding unit-decade incompatible pairs (Experiments 2–3), in unit-decade compatible pairs, there was a decade value-frame size congruity effect regardless of the digits’ physical size. In contrast, in unit-decade incompatible pairs, there was no decade value-frame size congruity effect, even when the physically larger digit (i.e., unit) contradicted the place-value information, presumably due to the cancellation of the opposing influences of the digits’ physical sizes their place-values. Overall, these findings suggest that place-value and physical size are intertwined in the Hindu-Arabic numerical system and are processed as one

Killing Mechanism of Stable <i>N</i>‑Halamine Cross-Linked Polymethacrylamide Nanoparticles That Selectively Target Bacteria

Increased resistance of bacteria to disinfection and antimicrobial treatment poses a serious public health threat worldwide. This has prompted the search for agents that can inhibit both bacterial growth and withstand harsh conditions (<i>e.g.</i>, high organic loads). In the current study, <i>N</i>-halamine-derivatized cross-linked polymethacrylamide nanoparticles (NPs) were synthesized by copolymerization of the monomer methacrylamide (MAA) and the cross-linker monomer <i>N</i>,<i>N</i>-methylenebis(acrylamide) (MBAA) and were subsequently loaded with oxidative chlorine using sodium hypochlorite (NaOCl). The chlorinated NPs demonstrated remarkable stability and durability to organic reagents and to repetitive bacterial loading cycles as compared with the common disinfectant NaOCl (bleach), which was extremely labile under these conditions. The antibacterial mechanism of the cross-linked P(MAA-MBAA)-Cl NPs was found to involve generation of reactive oxygen species (ROS) only upon exposure to organic media. Importantly, ROS were not generated upon suspension in water, revealing that the mode of action is target-specific. Further, a unique and specific interaction of the chlorinated NPs with Staphylococcus aureus was discovered, whereby these microorganisms were all specifically targeted and marked for destruction. This bacterial encircling was achieved without using a targeting module (<i>e.g.</i>, an antibody or a ligand) and represents a highly beneficial, natural property of the P(MAA-MBAA)-Cl nanostructures. Our findings provide insights into the mechanism of action of P(MAA-MBAA)-Cl NPs and demonstrate the superior efficacy of the NPs over bleach (<i>i.e.</i>, stability, specificity, and targeting). This work underscores the potential of developing sustainable P(MAA-MBAA)-Cl NP-based devices for inhibiting bacterial colonization and growth