Psychogenic Aging: A Novel Prospect to Integrate Psychobiological Hallmarks of Aging.

Psychological factors are amongst the most robust predictors of healthspan and longevity, yet are rarely incorporated into scientific and medical frameworks of aging. The prospect of characterizing and integrating the psychological influences of aging is therefore an unmet step for the advancement of geroscience. Psychogenic Aging research is an emerging branch of biogerontology that aims to address this gap by investigating the impact of psychological factors on human longevity. It is an interdisciplinary field that integrates complex psychological, neurological, and molecular relationships that can be best understood with precision medicine methodologies. This perspective argues that psychogenic aging should be considered an integral component of the Hallmarks of Aging framework, opening the doors for future biopsychosocial integration in longevity research. By providing a unique perspective on frequently overlooked aspects of organismal aging, psychogenic aging offers new insights and targets for anti-aging therapeutics on individual and societal levels that can significantly benefit the scientific and medical communities.

Multi-omics microsampling for the profiling of lifestyle-associated changes in health.

Current healthcare practices are reactive and use limited physiological and clinical information, often collected months or years apart. Moreover, the discovery and profiling of blood biomarkers in clinical and research settings are constrained by geographical barriers, the cost and inconvenience of in-clinic venepuncture, low sampling frequency and the low depth of molecular measurements. Here we describe a strategy for the frequent capture and analysis of thousands of metabolites, lipids, cytokines and proteins in 10 µl of blood alongside physiological information from wearable sensors. We show the advantages of such frequent and dense multi-omics microsampling in two applications: the assessment of the reactions to a complex mixture of dietary interventions, to discover individualized inflammatory and metabolic responses; and deep individualized profiling, to reveal large-scale molecular fluctuations as well as thousands of molecular relationships associated with intra-day physiological variations (in heart rate, for example) and with the levels of clinical biomarkers (specifically, glucose and cortisol) and of physical activity. Combining wearables and multi-omics microsampling for frequent and scalable omics may facilitate dynamic health profiling and biomarker discovery.

Precision Medicine Approaches to Mental Health Care.

Developing a more comprehensive understanding of the physiological underpinnings of mental illness, precision medicine has the potential to revolutionize psychiatric care. With recent breakthroughs in next-generation multi-omics technologies and data analytics, it is becoming more feasible to leverage multimodal biomarkers, from genetic variants to neuroimaging biomarkers, to objectify diagnostics and treatment decisions in psychiatry and improve patient outcomes. Ongoing work in precision psychiatry will parallel progress in precision oncology and cardiology to develop an expanded suite of blood- and neuroimaging-based diagnostic tests, empower monitoring of treatment efficacy over time, and reduce patient exposure to ineffective treatments. The emerging model of precision psychiatry has the potential to mitigate some of psychiatry's most pressing issues, including improving disease classification, lengthy treatment duration, and suboptimal treatment outcomes. This narrative-style review summarizes some of the emerging breakthroughs and recurring challenges in the application of precision medicine approaches to mental health care.

Effects of an immersive psychosocial training program on depression and well-being: A randomized clinical trial.

Psychiatry stands to benefit from brief non-pharmacological treatments that effectively reduce depressive symptoms. To address this need, we conducted a single-blind randomized clinical trial assessing how a 6-day immersive psychosocial training program, followed by 10-min daily psychosocial exercises for 30 days, improves depressive symptoms. Forty-five adults were block-randomized by depression score to two arms: (a) the immersive psychosocial training program and 10-min daily exercise group (36 days total; total n = 23; depressed at baseline n = 14); or (b) a gratitude journaling control group (36 days total; total n = 22; depressed at baseline n = 13). The self-report PHQ-9 was used to assess depression levels in both groups at three time points: baseline, study week one, and study week six. Depression severity improved over time, with a significantly greater reduction in the psychosocial training program group (-82.7%) vs. the control group (-23%), p = 0.02 for baseline vs. week six. The effect size for this reduction in depression symptoms was large for the intervention group (d = -1.3; 95% CI, -2.07, -0.45; p < 0.001) and small for the control group (d = -0.3; 95% CI, -0.68, 0.03; p = 0.22). Seventy-nine percent (11/14) of depressed participants in the intervention condition were in remission (PHQ-9 ≤ 4) by week one and 100% (14/14) were in remission at week six. Secondary measures of anxiety, stress, loneliness, and well-being also improved by 15-80% in the intervention group (vs. 0-34% in the control group), ps < 0.05. Overall, this brief, immersive psychosocial training program rapidly and substantially improved depression levels and several related secondary outcomes, suggesting that immersive interventions may be useful for reducing depressive symptoms and enhancing well-being.

Effect of Inquiry-Based Stress Reduction on Well-being and Views on Risk-Reducing Surgery Among Women With BRCA Variants in Israel: A Randomized Clinical Trial.

Importance: The high risk for breast and ovarian cancers conferred by being a carrier of BRCA1 or BRCA2 germline variant can negatively impact physical and psychological well-being. Novel nonpharmacological interventions on well-being in women with BRCA variants have rarely been reported. Objective: To determine the effect of a 12-week inquiry-based stress reduction (IBSR) program on psychological well-being, sleep quality, psychosocial variables, and attitudes toward risk-reducing surgical procedures among women in Israel who carried BRCA variants. Design, Setting, and Participants: This randomized clinical trial had a 12-week intervention period and a 12-week follow-up period. It was conducted between April 1, 2017, and July 31, 2020. Participants were recruited from the Meirav Breast Center at the Sheba Medical Center, Israel, and the intervention was conducted in Tel Aviv, Israel. The cohort included women with BRCA variants. Data were analyzed from August 1 to December 1, 2020. Interventions: Women were randomly assigned to the 12-week IBSR program or standard care. The IBSR technique is based on the skills of mindfulness, inquiry, and cognitive reframing. The intervention included standardized, weekly group meetings conducted throughout 12 weeks. Standard care included semi-annual breast examinations and breast magnetic resonance imaging (alternating), a gynecological examination, a transvaginal ultrasonographic examination, and CA-125 serum determination. Differences between the groups were tested using mixed-effects models in an intent to treat analysis. Main Outcomes and Measures: The primary outcome was psychological well-being, including 6 parameters: autonomy, personal growth, positive relationships, control of the environment, goals in life, and self-acceptance. Secondary outcomes included sleep quality, attitudes toward risk-reducing surgical procedures, and psychosocial variables. Questionnaires were administered at baseline (T1), at completion of the 12-week intervention (T2), and 12 weeks after completion of the intervention (T3). Results: Overall, 100 women (mean [SD] age, 41.37 [11.06] years) completed the study, with 50 randomized to the intervention group and 50 randomized to the control group. Mean (SD) time from variant discovery was 4.7 (3.3) years. There were no differences between the intervention and control groups in baseline mean (SD) scores of psychological well-being parameters (autonomy: 55.20 [11.12] vs 56.77 [9.90]; environmental control: 56.30 [11.98 vs 58.51 [11.41]; positive relationships: 63.10 [15.91] vs 68.10 [9.86]; goals in life: 60.00 [14.12] vs 64.82 [10.57]; self-acceptance: 55.02 [16.62] vs 60.32 [13.50]) except personal growth (63.70 [14.66] vs 68.85 [8.07]). The IBSR group, compared with the control group, experienced better mean (SD) scores on all psychological well-being parameters at T2 (autonomy: 63.64 [8.35] vs 54.73 [10.41]; environmental control: 63.95 [10.05] vs 57.45 [11.43]; personal growth: 73.00 [8.34] vs 65.76 [10.95]; positive relationships 71.17 [9.99] vs 65.06 [12.58]; goals in life: 67.57 [8.88] vs 61.18 [12.87]; self-acceptance: 66.93 [11.15] vs 58.09 [15.55]) and at T3 (autonomy: 62.68 [9.05] vs 56.12 [10.64]; environmental control: 64.55 [10.28] vs 59.35 [12.98]; personal growth: 72.00 [8.06] vs 67.15 [11.82]; positive relationships: 71.24 [9.78] vs 66.92 [12.37]; goals in life: 68.33 [8.54] vs 62.92 [13.24]; self-acceptance: 66.84 [11.35] vs 58.97 [17.03]). Individuals in the IBSR group also experienced statistically significant improvements in sleep quality (mean [SD]: T1, 7.35 [3.97]; T3, 4.63 [3.21], P < .001), whereas the control group experienced no statistically significant difference. Women in the intervention group had a more favorable consideration of risk-reducing oophorectomy, from 7 women (14%) who refused to consider oophorectomy at T1 to 1 woman (2%) who refused to consider it at T3 (P = .04), and similar change in consideration of mastectomy: from 23 women (46%) who refused to consider mastectomy at T1 to 13 women (29%) who refused to consider it at T3 (P < .001). Conclusions and Relevance: This randomized clinical trial found that IBSR improved psychological well-being and led to a more favorable view on risk-reducing surgical procedures for at least 6 months among women in Israel who carried BRCA variants. These results suggest that IBSR may be implemented as a self-practice tool to enhance the well-being of individuals who carry BRCA variants and support them in their decision-making processes. Trial Registration: ClinicalTrials.gov Identifier: NCT03162276.

Associations of choline intake with hypertension and blood pressure among older adults in cross-sectional 2011-2014 National Health and Nutrition Examination Survey (NHANES) differ by BMI and comorbidity status.

Blood pressure (BP) is a known cardiovascular risk factor that is hypothesised to be inversely related to choline intake. A previous study suggested that this association may be more apparent in older adults and may differ according to demographic and health characteristics. The primary study objectives are to investigate the cross-sectional associations of total choline intake with BP (n 843) and prevalent hypertension (n 2113) among USA adults aged ≥ 65 years using the sample from the 2011 to 2014 National Health and Nutrition Examination Survey. Logistic and multiple linear regression models for complex surveys were employed for hypertension status and BP, respectively. Effect modification by sex, race, BMI and comorbidity status were separately investigated using an interaction term. Choline intake interacted with BMI (P-interaction = 0·04) such that choline intake tended to be associated with lower odds of hypertension among people with BMI < 18·5 kg/m2 (OR (95 % CI): 0·64 (0·4, 1·00); P = 0·052). Choline intake was not associated with systolic BP (mean ± sem change per 100 mg of choline: -1·03 ± 0·74 mmHg; P = 0·16). In contrast, its relation to diastolic BP differed by cardiovascular comorbidity (P-interaction = 0·03) with a non-significant (P = 0·13) negative direction of association observed among those who were free of comorbidities and a non-significant (P = 0·26) positive direction observed among those with comorbidities. Collectively, these results suggested that the associations of choline intake with BP levels and hypertension risk among older adults are dependent on other risk factors.

Inquiry Based Stress Reduction (IBSR) Improves Overall Stuttering Experience among Adults Who Stutter: A Randomized Controlled Trial.

Stuttering is a speech disorder that can cause disturbances in the timing and flow of speech. In addition to being a communication disorder, stuttering is often accompanied by a reduction in the quality of life and has impacts on social status, mental well-being, self-acceptance, and the chances of integration into the labor market. The Inquiry Based Stress Reduction (IBSR) program, developed in the United States by Byron Katie in 1986, is the clinical application of "The Work" method (Thework.com) and represents an emerging mindfulness and cognitive-reframing method. IBSR has been demonstrated to improve mental health and well-being in adults and may alleviate psychological and psychosocial symptoms of stuttering. The purpose of this trial was to examine the effect of a 12-week IBSR intervention on the overall stuttering experience and indicators of anxiety, psychological flexibility, and well-being among adults who stutter (AWS). This study was a randomized controlled clinical trial. Participants were randomized to IBSR (n = 28) and control (n = 28) groups. Validated questionnaires of overall stuttering experience (OASES-A), anxiety (STAI), psychological flexibility (PFQ), and satisfaction with life (SWLS) were completed before, after, and one month after the intervention. An intention-to-treat approach was implemented for analysis. Our results show that participants in the IBSR intervention group exhibited a greater improvement in their overall stuttering experience as compared to the control group, as well as in general information on stuttering awareness and perception, reactions to stuttering, communication in daily situations, and quality of life. In addition, we found a greater reduction in anxiety levels and an increase in satisfaction-with-life scores in the IBSR group. These results indicate that IBSR can improve the overall stuttering experience.

Non-traditional immersive seminar enhances learning by promoting greater physiological and psychological engagement compared to a traditional lecture format.

The purpose of this study was to determine the impact of an immersive seminar, which included moderate intensities of physical activity, on learning when compared to traditional lecture format. Twenty-six healthy participants were randomly divided into an immersive seminar or traditional lecture format group and presented material related to positive psychology and human values/beliefs over the course of two days. Physical activity was collected using a bio-harness while salivary cortisol and perceptual measures of well-being were collected over the two days. Performance on an examination related to course material was used to assess learning. Average time spent over 65% of max heart rate, energy expenditure, total bounds, mechanical and physiological load were significantly greater in the immersive seminar group when compared to traditional lecture group. In addition, cortisol levels and perceptual measures of mood, focus, energy, and well-being were significantly greater in the immersive seminar when compared to the traditional lecture format. Participants in the immersive seminar demonstrated significantly greater memory retention of course material 30-days post lecture when compared to the traditional lecture group. These findings support incorporating more physical activity and increasing arousal in order to enhance learning of lecture material.

Effect of Inquiry-Based Stress Reduction (IBSR) Intervention on Well-Being, Resilience and Burnout of Teachers during the COVID-19 Pandemic.

Objective: The COVID-19 pandemic has had a major impact on teachers professional and personal lives. Our primary aim was to assess the effect of a blended Inquiry-Based Stress Reduction (IBSR), an emerging mindfulness and cognitive reframing intervention on teacher's well-being. Our secondary aims were to assess the effect of IBSR on resilience, burnout, mindfulness, and stress among teachers during the COVID-19 pandemic. Methods: The study was a prospective controlled trial with an intervention group (N = 35) and a comparison control group (N = 32). The intervention took place in the Jerusalem District throughout the school year from November 2019 to May 2020. The sessions were conducted in blended learning that included traditional learning (face-to-face) and online learning. Data was analyzed on an intention-to-treat basis. Results: IBSR blended intervention enhanced the resilience and improved the subjective and psychological well-being of teachers in spite of the breakout of the COVID-19 pandemic and the first lockdown in Israel. Simultaneously the control group suffered from enhanced burnout levels and a decline in psychological and subjective well-being. Conclusions: Implementation of IBSR blended intervention during the school year may benefit teachers' well-being and ability to flourish, even during stressful events such as the COVID-19 pandemic.

Pre-symptomatic detection of COVID-19 from smartwatch data.

Consumer wearable devices that continuously measure vital signs have been used to monitor the onset of infectious disease. Here, we show that data from consumer smartwatches can be used for the pre-symptomatic detection of coronavirus disease 2019 (COVID-19). We analysed physiological and activity data from 32 individuals infected with COVID-19, identified from a cohort of nearly 5,300 participants, and found that 26 of them (81%) had alterations in their heart rate, number of daily steps or time asleep. Of the 25 cases of COVID-19 with detected physiological alterations for which we had symptom information, 22 were detected before (or at) symptom onset, with four cases detected at least nine days earlier. Using retrospective smartwatch data, we show that 63% of the COVID-19 cases could have been detected before symptom onset in real time via a two-tiered warning system based on the occurrence of extreme elevations in resting heart rate relative to the individual baseline. Our findings suggest that activity tracking and health monitoring via consumer wearable devices may be used for the large-scale, real-time detection of respiratory infections, often pre-symptomatically.

The Effect of Inquiry-Based Stress Reduction on Teacher Burnout: A Controlled Trial.

Burnout is a well-known phenomenon with significant social, biological and economic costs. In particular, teacher burnout is associated with unfavorable mental health outcomes and economic costs due to reduced hours and teacher turnover. This study investigated the effect of an Inquiry-Based Stress Reduction (IBSR) cognitive-reframing program on teacher burnout using a quasi-experimental design. Fifty-three teachers participated in a prospective intervention with a passive control group. The intervention group completed a 12-week IBSR program with 4.5 h of weekly engagement. Relative to control, teachers in the intervention group showed greater improvements in emotional exhaustion (18.8 ± 5.2 to 15.9 ± 5.7 vs. 16.0 ± 4.8 to 17.4 ± 4.8; p = 0.01) and personal accomplishment (21.8 ± 5.0 to 24.6 ± 4.3 vs. 21.9 ± 4.5 to 22.8 ± 4.3; p = 0.04). Significant correlations were found between change in emotional exhaustion and negative affect (positive correlation; r = 0.32; p = 0.034) and between personal accomplishment and perceived stress (negative correlation; r = -0.451; p = 0.002). This study demonstrates the potential of IBSR to improve teacher well-being. Future randomized studies are needed to evaluate the causality of IBSR in reducing burnout among teachers and other high-stress workplaces.

A longitudinal big data approach for precision health.

Precision health relies on the ability to assess disease risk at an individual level, detect early preclinical conditions and initiate preventive strategies. Recent technological advances in omics and wearable monitoring enable deep molecular and physiological profiling and may provide important tools for precision health. We explored the ability of deep longitudinal profiling to make health-related discoveries, identify clinically relevant molecular pathways and affect behavior in a prospective longitudinal cohort (n = 109) enriched for risk of type 2 diabetes mellitus. The cohort underwent integrative personalized omics profiling from samples collected quarterly for up to 8 years (median, 2.8 years) using clinical measures and emerging technologies including genome, immunome, transcriptome, proteome, metabolome, microbiome and wearable monitoring. We discovered more than 67 clinically actionable health discoveries and identified multiple molecular pathways associated with metabolic, cardiovascular and oncologic pathophysiology. We developed prediction models for insulin resistance by using omics measurements, illustrating their potential to replace burdensome tests. Finally, study participation led the majority of participants to implement diet and exercise changes. Altogether, we conclude that deep longitudinal profiling can lead to actionable health discoveries and provide relevant information for precision health.

Vitamin D binding protein rs7041 genotype alters vitamin D metabolism in pregnant women.

Research has identified reduced circulating 25-hydroxyvitamin D [25(OH)D] in individuals with the rs7041 (c.1296T>G) T allele in the vitamin D binding protein gene ( GC); however, the effects of the T allele on vitamin D biomarkers during pregnancy and lactation are unknown. Thus, we examined the metabolic effects of GC rs7041 on vitamin D biomarkers among third-trimester pregnant ( n = 26), lactating ( n = 28), and nonpregnant/nonlactating ( n = 21) women consuming a single amount of vitamin D (511 IU/d) and related nutrients for 10-12 wk. T allele carriers had less circulating 25(OH)D, regardless of reproductive state [thymine-thymine (TT): 80% of guanine-guanine (GG), P = 0.05; guanine-thymine (GT): 85% of GG, P = 0.1]. Among pregnant women, the T allele attenuated the expected increase in vitamin D binding protein (DBP). Specifically, although GG pregnant women exhibited greater DBP (216%, P < 0.0001) than did GG nonpregnant women, that difference was lessened among GT women, and TT pregnant women did not exhibit greater DBP than TT nonpregnant women. Furthermore, TT pregnant women had greater placental 25(OH)D3 to 24,25-dihydroxyvitamin D ratios (251% of GG, P = 0.07) and less osteocalcin, a bone formation marker, in the cord blood of their neonates (24% of GT, P = 0.02). Overall, the GC rs7041 genotype modified the effects of pregnancy on maternal and placental vitamin D metabolism, with possible functional consequences for fetal bone development and infant health.-Ganz, A. B., Park, H., Malysheva, O. V., Caudill, M. A. Vitamin D binding protein rs7041 genotype alters vitamin D metabolism in pregnant women.

Common Genetic Variants Alter Metabolism and Influence Dietary Choline Requirements.

Nutrient needs, including those of the essential nutrient choline, are a population wide distribution. Adequate Intake (AI) recommendations for dietary choline (put forth by the National Academies of Medicine to aid individuals and groups in dietary assessment and planning) are grouped to account for the recognized unique needs associated with age, biological sex, and reproductive status (i.e., pregnancy or lactation). Established and emerging evidence supports the notion that common genetic variants are additional factors that substantially influence nutrient requirements. This review summarizes the genetic factors that influence choline requirements and metabolism in conditions of nutrient deprivation, as well as conditions of nutrient adequacy, across biological sexes and reproductive states. Overall, consistent and strong associative evidence demonstrates that common genetic variants in choline and folate pathway enzymes impact the metabolic handling of choline and the risk of nutrient inadequacy across varied dietary contexts. The studies characterized in this review also highlight the substantial promise of incorporating common genetic variants into choline intake recommendations to more precisely target the unique nutrient needs of these subgroups within the broader population. Additional studies are warranted to facilitate the translation of this evidence to nutrigenetics-based dietary approaches.

Genetic Variation in Choline-Metabolizing Enzymes Alters Choline Metabolism in Young Women Consuming Choline Intakes Meeting Current Recommendations.

Single nucleotide polymorphisms (SNPs) in choline metabolizing genes are associated with disease risk and greater susceptibility to organ dysfunction under conditions of dietary choline restriction. However, the underlying metabolic signatures of these variants are not well characterized and it is unknown whether genotypic differences persist at recommended choline intakes. Thus, we sought to determine if common genetic risk factors alter choline dynamics in pregnant, lactating, and non-pregnant women consuming choline intakes meeting and exceeding current recommendations. Women (n = 75) consumed 480 or 930 mg choline/day (22% as a metabolic tracer, choline-d9) for 10-12 weeks in a controlled feeding study. Genotyping was performed for eight variant SNPs and genetic differences in metabolic flux and partitioning of plasma choline metabolites were evaluated using stable isotope methodology. CHKA rs10791957, CHDH rs9001, CHDH rs12676, PEMT rs4646343, PEMT rs7946, FMO3 rs2266782, SLC44A1 rs7873937, and SLC44A1 rs3199966 altered the use of choline as a methyl donor; CHDH rs9001 and BHMT rs3733890 altered the partitioning of dietary choline between betaine and phosphatidylcholine synthesis via the cytidine diphosphate (CDP)-choline pathway; and CHKA rs10791957, CHDH rs12676, PEMT rs4646343, PEMT rs7946 and SLC44A1 rs7873937 altered the distribution of dietary choline between the CDP-choline and phosphatidylethanolamine N-methyltransferase (PEMT) denovo pathway. Such metabolic differences may contribute to disease pathogenesis and prognosis over the long-term.

The initial stages of melting of graphene between 4000 K and 6000 K.

Graphene and its analogues have some of the highest predicted melting points of any materials. Previous work estimated the melting temperature for freestanding graphene to be a remarkable 4510 K. However, this work relied on theoretical methods that do not accurately account for the role of bond breaking or complex bonding configurations in the melting process. Furthermore, experiments to verify these high melting points have been challenging. Practical applications of graphene and carbon nanotubes at high temperatures will require a detailed understanding of the behavior of these materials under these conditions. Therefore, we have used reliable ab initio molecular dynamics calculations to study the initial stages of melting of freestanding graphene monolayers between 4000 and 6000 K. To accommodate large defects, and for improved accuracy, we used a large 10 × 10 periodic unit cell. We find that the system can be heated up to 4500 K for 18 ps without melting, and 3-rings and short lived broken bonds (10-rings) are observed. At 4500 K, the system appears to be in a quasi-2D liquid state. At 5000 K, the system is starting to melt. During the 20 ps simulation, diffusion events are observed, leading to the creation of a 5775 defect. We calculate accurate excitation energies for these configurations, and the pair correlation function is presented. The modified Lindemann criterion was calculated. Graphene and nanotubes together with other proposed high melting point materials would be interesting candidates for experimental tests of melting in the weightless environment of space.

Genetic impairments in folate enzymes increase dependence on dietary choline for phosphatidylcholine production at the expense of betaine synthesis.

Although single nucleotide polymorphisms (SNPs) in folate-mediated pathways predict susceptibility to choline deficiency during severe choline deprivation, it is unknown if effects persist at recommended intakes. Thus, we used stable isotope liquid chromatography-mass spectrometry (LC-MS) methodology to examine the impact of candidate SNPs on choline metabolism in a long-term, randomized, controlled feeding trial among pregnant, lactating, and nonpregnant (NP) women consuming 480 or 930 mg/d choline (22% as choline-d9, with d9 indicating a deuterated trimethyl amine group) and meeting folate-intake recommendations. Variants impairing folate metabolism, methylenetetrahydrofolate reductase (MTHFR) rs1801133, methionine synthase (MTR) rs1805087 [wild-type (WT)], MTR reductase (MTRR) rs1801394, and methylenetetrahydrofolate dehydrogenase-methenyltetrahydrofolate cyclohydrolase-formyltetrahydrofolate synthetase (MTHFD1) rs2236225, influenced choline dynamics, frequently through interactions with reproductive state and choline intake, with fewer genotypic alterations observed among pregnant women. Women with these variants partitioned more dietary choline toward phosphatidylcholine (PC) biosynthesis via the cytidine diphosphate (CDP)-choline pathway at the expense of betaine synthesis even when use of betaine as a methyl donor was increased. Choline intakes of 930 mg/d restored partitioning of dietary choline between betaine and CDP-PC among NP (MTHFR rs1801133 and MTR rs1805087 WT) and lactating (MTHFD1 rs2236225) women with risk genotypes. Overall, our findings indicate that loss-of-function variants in folate-metabolizing enzymes strain cellular PC production, possibly via impaired folate-dependent phosphatidylethanolamine-N-methyltransferase (PEMT)-PC synthesis, and suggest that women with these risk genotypes may benefit from choline intakes exceeding current recommendations.-Ganz, A. B., Shields, K., Fomin, V. G., Lopez, Y. S., Mohan, S., Lovesky, J., Chuang, J. C., Ganti, A., Carrier, B., Yan, J., Taeswuan, S., Cohen, V. V., Swersky, C. C., Stover, J. A., Vitiello, G. A., Malysheva, O. V., Mudrak, E., Caudill, M. A. Genetic impairments in folate enzymes increase dependence on dietary choline for phosphatidylcholine production at the expense of betaine synthesis.

Computational Study of Quasi-2D Liquid State in Free Standing Platinum, Silver, Gold, and Copper Monolayers.

Recently, freestanding atomically thick Fe metal patches up to 10 atoms wide have been fabricated experimentally in tiny pores in graphene. This concept can be extended conceptually to extended freestanding monolayers. We have therefore performed ab initio molecular dynamics simulations to evaluate the early melting stages of platinum, silver, gold, and copper freestanding metal monolayers. Our calculations show that all four freestanding monolayers will form quasi-2D liquid layers with significant out-of-plane motion and diffusion in the plane. Remarkably, we observe a 4% reduction in the Pt most likely bond length as the system enters the liquid state at 2400 K (and a lower effective spring constant), compared to the system at 1200 and 1800 K. We attribute this to the reduced average number of bonds per atom in the Pt liquid state. We used the highly accurate and reliable Density Functional Theory (DFT-D) method that includes dispersion corrections. These liquid states are found at temperatures of 2400 K, 1050 K, 1600 K, and 1400 K for platinum, silver, gold, and copper respectively. The pair correlation function drops in the liquid state, while the bond orientation order parameter is reduced to a lesser degree. Movies of the simulations can be viewed online (see Supplementary Material).