The circadian clock is disrupted in pancreatic cancer.

Disruption of the circadian clock is linked to cancer development and progression. Establishing this connection has proven beneficial for understanding cancer pathogenesis, determining prognosis, and uncovering novel therapeutic targets. However, barriers to characterizing the circadian clock in human pancreas and human pancreatic cancer-one of the deadliest malignancies-have hindered an appreciation of its role in this cancer. Here, we employed normalized coefficient of variation (nCV) and clock correlation analysis in human population-level data to determine the functioning of the circadian clock in pancreas cancer and adjacent normal tissue. We found a substantially attenuated clock in the pancreatic cancer tissue. Then we exploited our existing mouse pancreatic transcriptome data to perform an analysis of the human normal and pancreas cancer samples using a machine learning method, cyclic ordering by periodic structure (CYCLOPS). Through CYCLOPS ordering, we confirmed the nCV and clock correlation findings of an intact circadian clock in normal pancreas with robust cycling of several core clock genes. However, in pancreas cancer, there was a loss of rhythmicity of many core clock genes with an inability to effectively order the cancer samples, providing substantive evidence of a dysregulated clock. The implications of clock disruption were further assessed with a Bmal1 knockout pancreas cancer model, which revealed that an arrhythmic clock caused accelerated cancer growth and worse survival, accompanied by chemoresistance and enrichment of key cancer-related pathways. These findings provide strong evidence for clock disruption in human pancreas cancer and demonstrate a link between circadian disruption and pancreas cancer progression.

Impact of OPTN policy 3.7D providing waiting time modification for candidates affected by race-inclusive eGFR calculations: Early results from a single center.

INTRODUCTION: OPTN Policy 3.7D, implemented January 5, 2023, mandates that all kidney transplant programs modify waiting time for candidates affected by race-inclusive eGFR calculations. We report the early impact of this policy change. METHODS: Our transplant program reviewed all listed transplant candidates and identified patients potentially eligible for waiting time modification. Eligible candidates received waiting time modification after submission of supporting evidence to the OPTN. We reviewed the impact on waiting time and transplant activity through October 1, 2023. RESULTS: Forty-six adult patients on our center's active waiting list self-identified as Black/African American. 25 (54.3%) candidates qualified for waiting time modification. A median 451 (321, 1543.5) additional days of waiting time was added for qualifying patients. Of the 25 patients who qualified for waiting time modification, 11 patients received a deceased donor kidney in the early period following waiting time modification, including 5 patients transplanted within 1 month after modification. CONCLUSIONS: Policy 3.7D is one of few national mandates to address specifically structural racism within transplantation. Implementation has yielded near immediate effects with greater than 40% of time-adjusted patients at our center receiving a deceased donor kidney transplant in the initial months after policy enactment. Early assessment demonstrates great potential impact for this policy.

Tailoring cytomegalovirus prophylaxis based on T cell immunity panel assessment in kidney transplant patients at high risk of cytomegalovirus.

BACKGROUND: Valganciclovir prophylaxis against cytomegalovirus (CMV) is recommended for solid organ transplant recipients, but is associated with drawbacks, including expense and leukopenia. Our center adopted a strategy of serial assessment with a CMV-specific T cell immunity panel (CMV-TCIP) and cessation of valganciclovir prophylaxis upon demonstration of adequate CD4+ responses in kidney transplant patients at high risk of CMV disease. METHODS: We retrospectively reviewed adult recipients of a kidney or pancreas transplant between August 2019 and July 2021 undergoing serial CMV-TCIP monitoring. Included patients were considered high risk for CMV, defined by donor positive (D+)/recipient negative (R-) CMV IgG serostatus, or recipient positive (R+) patients who received induction with a lymphocyte-depleting agent. Prophylaxis was discontinued after a patient's first CMV-specific CD4+ T cell value of ≥0.20%. Risk of clinically significant CMV infection (csCMVi) in those who underwent early discontinuation of CMV prophylaxis and predictors of CMV T cell immunity were analyzed. RESULTS: Of 54 included patients, 22 stopped prophylaxis early due to CMV-specific CD4+ T cell immunity at a median of 4.7 (IQR: 3.8-5.4) months after transplant. No instances of csCMVi were observed in the 22 patients who had prophylaxis discontinued early, of whom 19/22 were CMV R+ and 3/22 were CMV D+/R-. Donor/recipient CMV serostatus was predictive of immunity (p <.001). CONCLUSION: Early discontinuation of valganciclovir prophylaxis in patients with CMV CD4+ T cellular immunity appears safe and potentially beneficial in this preliminary series, especially in R+ patients. Further study is warranted, given that truncated prophylaxis may yield patient-level benefits.

Genomic analysis of siderophore ß-hydroxylases reveals divergent stereocontrol and expands the condensation domain family.

Genome mining of biosynthetic pathways streamlines discovery of secondary metabolites but can leave ambiguities in the predicted structures, which must be rectified experimentally. Through coupling the reactivity predicted by biosynthetic gene clusters with verified structures, the origin of the ß-hydroxyaspartic acid diastereomers in siderophores is reported herein. Two functional subtypes of nonheme Fe(II)/α-ketoglutarate-dependent aspartyl ß-hydroxylases are identified in siderophore biosynthetic gene clusters, which differ in genomic organization-existing either as fused domains (IßHAsp) at the carboxyl terminus of a nonribosomal peptide synthetase (NRPS) or as stand-alone enzymes (TßHAsp)-and each directs opposite stereoselectivity of Asp ß-hydroxylation. The predictive power of this subtype delineation is confirmed by the stereochemical characterization of ß-OHAsp residues in pyoverdine GB-1, delftibactin, histicorrugatin, and cupriachelin. The l-threo (2S, 3S) ß-OHAsp residues of alterobactin arise from hydroxylation by the ß-hydroxylase domain integrated into NRPS AltH, while l-erythro (2S, 3R) ß-OHAsp in delftibactin arises from the stand-alone ß-hydroxylase DelD. Cupriachelin contains both l-threo and l-erythro ß-OHAsp, consistent with the presence of both types of ß-hydroxylases in the biosynthetic gene cluster. A third subtype of nonheme Fe(II)/α-ketoglutarate-dependent enzymes (IßHHis) hydroxylates histidyl residues with l-threo stereospecificity. A previously undescribed, noncanonical member of the NRPS condensation domain superfamily is identified, named the interface domain, which is proposed to position the ß-hydroxylase and the NRPS-bound amino acid prior to hydroxylation. Through mapping characterized ß-OHAsp diastereomers to the phylogenetic tree of siderophore ß-hydroxylases, methods to predict ß-OHAsp stereochemistry in silico are realized.

The impact of multi-organ transplant allocation priority on waitlisted kidney transplant candidates.

Kidney-alone transplant (KAT) candidates may be disadvantaged by the allocation priority given to multi-organ transplant (MOT) candidates. This study identified potential KAT candidates not receiving a given kidney offer due to its allocation for MOT. Using the Organ Procurement and Transplant Network (OPTN) database, we identified deceased donors from 2002 to 2017 who had one kidney allocated for MOT and the other kidney allocated for KAT or simultaneous pancreas-kidney transplant (SPK) (n = 7,378). Potential transplant recipient data were used to identify the "next-sequential KAT candidate" who would have received a given kidney offer had it not been allocated to a higher prioritized MOT candidate. In this analysis, next-sequential KAT candidates were younger (p < .001), more likely to be racial/ethnic minorities (p < .001), and more highly sensitized than MOT recipients (p < .001). A total of 2,113 (28.6%) next-sequential KAT candidates subsequently either died or were removed from the waiting list without receiving a transplant. In a multivariable model, despite adjacent position on the kidney match-run, mortality risk was significantly higher for next-sequential KAT candidates compared to KAT/SPK recipients (hazard ratio 1.55, 95% confidence interval 1.44, 1.66). These results highlight implications of MOT allocation prioritization, and potential consequences to KAT candidates prioritized below MOT candidates.

Meditation training modulates brain electric microstates and felt states of awareness.

Meditation practice is believed to foster states of mindful awareness and mental quiescence in everyday life. If so, then the cultivation of these qualities with training ought to leave its imprint on the activity of intrinsic functional brain networks. In an intensive longitudinal study, we investigated associations between meditation practitioners' experiences of felt mindful awareness and changes in the spontaneous electrophysiological dynamics of functional brain networks. Experienced meditators were randomly assigned to complete 3 months of full-time training in focused-attention meditation (during an initial intervention) or to serve as waiting-list controls and receive training second (during a later intervention). We collected broadband electroencephalogram (EEG) during rest at the beginning, middle, and end of the two training periods. Using a data-driven approach, we segmented the EEG into a time series of transient microstate intervals based on clustering of topographic voltage patterns. Participants also provided daily reports of felt mindful awareness and mental quiescence, and reported daily on four experiential qualities of their meditation practice during training. We found that meditation training led to increases in mindful qualities of awareness, which corroborate contemplative accounts of deepening mental calm and attentional focus. We also observed reductions in the strength and duration of EEG microstates across both interventions. Importantly, changes in the dynamic sequencing of microstates were associated with daily increases in felt attentiveness and serenity during training. Our results connect shifts in subjective qualities of meditative experience with the large-scale dynamics of whole brain functional EEG networks at rest.

Using Clustering to Examine Inter-individual Variability in Topography of Auditory Event-Related Potentials in Autism and Typical Development.

Although prior studies have compared sensory event-related potential (ERP) responses between groups of autistic and typically-developing participants, it is unclear how heterogeneity contributes to the results of these studies. The present study used examined individual differences in these responses. 130 autistic children and 81 typically-developing children, aged between 2 and 5 years, listened to tones at four identity levels while 61-channel electroencephalography was recorded. Hierarchical clustering was used to group participants based on rescaled ERP topographies between 51 and 350 ms. The hierarchical clustering analysis revealed substantial heterogeneity. Some of the seven clusters defined in this analysis were characterized by prolonged fronto-central positivities and/or weak or absent N2 negativities. However, many other participants fell into clusters in which N2 responses were present at varying latencies. Atypical response morphologies such as absent N2 responses and/or prolonged positive-going responses found in some autistic participants may account for prior research findings of attenuated N2 amplitudes in autism. However, there was also considerable overlap between groups, with participants of both groups appearing in all clusters. These results emphasize the utility of using clustering to explore individual differences in brain responses, which can expand on and clarify the results of analyses of group mean differences.

Metabolic rescue in pluripotent cells from patients with mtDNA disease.

Mitochondria have a major role in energy production via oxidative phosphorylation, which is dependent on the expression of critical genes encoded by mitochondrial (mt)DNA. Mutations in mtDNA can cause fatal or severely debilitating disorders with limited treatment options. Clinical manifestations vary based on mutation type and heteroplasmy (that is, the relative levels of mutant and wild-type mtDNA within each cell). Here we generated genetically corrected pluripotent stem cells (PSCs) from patients with mtDNA disease. Multiple induced pluripotent stem (iPS) cell lines were derived from patients with common heteroplasmic mutations including 3243A>G, causing mitochondrial encephalomyopathy and stroke-like episodes (MELAS), and 8993T>G and 13513G>A, implicated in Leigh syndrome. Isogenic MELAS and Leigh syndrome iPS cell lines were generated containing exclusively wild-type or mutant mtDNA through spontaneous segregation of heteroplasmic mtDNA in proliferating fibroblasts. Furthermore, somatic cell nuclear transfer (SCNT) enabled replacement of mutant mtDNA from homoplasmic 8993T>G fibroblasts to generate corrected Leigh-NT1 PSCs. Although Leigh-NT1 PSCs contained donor oocyte wild-type mtDNA (human haplotype D4a) that differed from Leigh syndrome patient haplotype (F1a) at a total of 47 nucleotide sites, Leigh-NT1 cells displayed transcriptomic profiles similar to those in embryo-derived PSCs carrying wild-type mtDNA, indicative of normal nuclear-to-mitochondrial interactions. Moreover, genetically rescued patient PSCs displayed normal metabolic function compared to impaired oxygen consumption and ATP production observed in mutant cells. We conclude that both reprogramming approaches offer complementary strategies for derivation of PSCs containing exclusively wild-type mtDNA, through spontaneous segregation of heteroplasmic mtDNA in individual iPS cell lines or mitochondrial replacement by SCNT in homoplasmic mtDNA-based disease.

Within and between-person correlates of the temporal dynamics of resting EEG microstates.

Microstates reflect transient brain states resulting from the synchronous activity of brain networks that predominate in the broadband EEG. There has been increasing interest in how the functional organization of the brain varies across individuals, or the extent to which its spatiotemporal dynamics are state dependent. However, little research has examined within and between-person correlates of microstate temporal parameters in healthy populations. In the present study, neuroelectric activity recorded during eyes-closed rest and during simple visual fixation was segmented into a time series of transient microstate intervals. It was found that five data-driven microstate configurations explained the preponderance of topographic variance in the EEG time series of the 374 recordings (from 187 participants) included in the study. We observed that the temporal dynamics of microstates varied within individuals to a greater degree than they differed between persons, with within-person factors explaining a large portion of the variance in mean microstate duration and occurrence rate. Nevertheless, several individual differences were found to predict the temporal dynamics of microstates. Of these, age and gender were the most reliable. These findings not only suggest that the rich temporal dynamics of whole-brain neuronal networks vary considerably within individuals, but that microstates appear to differentiate persons based on trait individual differences. Rather than focusing exclusively on between-person differences in microstates as measures of brain function, researchers should turn their attention towards understanding the factors contributing to within-person variation.

Deconstructing the effects of concentration meditation practice on interference control: The roles of controlled attention and inflammatory activity.

Prior work has linked meditation practice to improvements in interference control. However, the mechanisms underlying these improvements are relatively unknown. In the context of meditation training, improvements in interference control could result eitherfrom increases in controlled attention to goal-relevant stimuli, or from reductions in automatic capture by goal-irrelevant stimuli. Moreover, few studies have linked training-related changes in attention to physiological processes, such as inflammatory activity, that are thought to influence cognitive function. This study addresses these gaps by examining associations between cognitive performance and cytokines in the context of an intensive meditation retreat. Participants were randomly assigned to complete 3 months of meditation training first, or to serve as waitlist controls. The waitlist-control participants then later completed a separate 3-month training intervention. We assessed participants' interference control with a flanker task and used computational modeling to derive component processes of controlled and automatic attention. We also collected blood samples at the beginning, middle, and end of training to quantify changes in cytokine activity. Participants who completed training evidenced better controlled attention than waitlist controls during the first retreat intervention, and controls showed significant improvements in controlled attention when they completed their own, second retreat. Importantly, inflammatory activity was inversely associated with controlled attention during both interventions. Our results suggest that practice of concentration meditation influences interference control by enhancing controlled attention to goal-relevant task elements, and that inflammatory activity relates to individual differences in controlled attention.

Epistaxis Complicated by Hemolacria: A Case Report.

Hemolacria is a rare complication of epistaxis treated with nasal compression or tamponade. We report the case of a man, aged 81 years, with end-stage renal disease who developed hemolacria after insertion of a "Rhino Rocket" nasal tamponade device to treat persistent epistaxis. The hemolacria resolved after treatment with intranasal oxymetazoline. In the setting of epistaxis with nasal tamponade, hemolacria is thought to be caused by retrograde flow from the inferior nasal turbinates via an anatomic connection with the lacrimal system, with passage through the valves of Hasner and Rosenmüller to the lacrimal ducts. Hemolacria is very rare even in severe cases of epistaxis; we postulate that only patients with either congenital absence or acquired incompetence of the lacrimal valves are predisposed to hemolacria after treatment of epistaxis with a tamponade device. Physicians should be aware that hemolacria in the setting of epistaxis is usually a self-limited condition that can be treated with conservative measures to control nasal hemorrhage.

Modulation of Event-related Potentials of Visual Discrimination by Meditation Training and Sustained Attention.

The ability to discriminate among goal-relevant stimuli tends to diminish when detections must be made continuously over time. Previously, we reported that intensive training in shamatha (focused-attention) meditation can improve perceptual discrimination of difficult-to-detect visual stimuli [MacLean, K. A., Ferrer, E., Aichele, S. R., Bridwell, D. A., Zanesco, A. P., Jacobs, T. L., et al. Intensive meditation training improves perceptual discrimination and sustained attention. Psychological Science, 21, 829-839, 2010]. Here we extend these findings to examine how discrimination difficulty and meditation training interact to modulate event-related potentials of attention and perceptual processing during vigilance. Training and wait-list participants completed a continuous performance task at the beginning, middle, and end of two 3-month meditation interventions. In the first intervention (Retreat 1), the continuous performance task target was adjusted across assessments to match training-related changes in participants' perceptual capacity. In the second intervention (Retreat 2), the target was held constant across training, irrespective of changes in discrimination capacity. No training effects were observed in Retreat 1, whereas Retreat 2 was associated with changes in the onset of early sensory signals and an attenuation of within-task decrements at early latencies. In addition, changes at later stimulus processing stages were directly correlated with improvements in perceptual threshold across the second intervention. Overall, these findings demonstrate that improvements in perceptual discrimination can modulate electrophysiological markers of perceptual processing and attentional control during sustained attention, but likely only under conditions where an individual's discrimination capacity is allowed to exceed the demand imposed by the difficulty of a visual target. These results contribute to basic understanding of the dependence of perceptual processing and attentional control to contextual demands and their susceptibility to directed mental training.

Donor's APOL1 Risk Genotype and "Second Hits" Associated With De Novo Collapsing Glomerulopathy in Deceased Donor Kidney Transplant Recipients: A Report of 5 Cases.

The presence of 2 APOL1 risk variants (G1/G1, G1/G2, or G2/G2) is an important predictor of focal segmental glomerulosclerosis (FSGS) and chronic kidney disease in individuals of African descent. Although recipient APOL1 genotype is not associated with allograft survival, kidneys from deceased African American donors with 2 APOL1 risk variants demonstrate shorter graft survival. We present a series of cases of presumed de novo collapsing FSGS in 5 transplanted kidneys from 3 deceased donors later identified as carrying 2 APOL1 risk alleles, including 2 recipients from the same donor whose kidneys were transplanted in 2 different institutions. Four of these recipients had viremia in the period preceding the diagnosis of collapsing FSGS. Cytomegalovirus and BK virus infection were present in 3 and 1 of our 5 cases, respectively, around the time that collapsing FSGS occurred. We discuss viral infections, including active cytomegalovirus infection, as possible "second hits" that may lead to glomerular injury and allograft failure in these recipients. Further studies to identify additional second hits are necessary to better understand the pathologic mechanisms of donor APOL1-associated kidney disease in the recipient.

Teaching Safe Opioid Prescribing During the Opioid Epidemic: Results of the 2018 Clerkship Directors in Internal Medicine Survey.

BACKGROUND: Educating medical trainees across the continuum is essential to a multifaceted strategy for addressing the opioid epidemic. OBJECTIVE: To assess the current state of internal medicine clerkship content on safe opioid prescribing and opioid use disorder, and barriers to curriculum implementation. DESIGN: National Annual (2018) Clerkship Directors in Internal Medicine (CDIM) cross-sectional survey. PARTICIPANTS: One hundred thirty-four clerkship directors at all Liaison Committee of Medical Education accredited US medical schools with CDIM membership as of October 1, 2018. MAIN MEASURES: The survey section on safe opioid prescribing and opioid use disorder education in the internal medicine clerkship addressed assessment of current curricula, perceived importance of curricula, barriers to implementation, and plans to start or expand curricula. Descriptive statistics were used to summarize responses, and Pearson's chi-square and Fisher's exact tests for statistical comparisons. KEY RESULTS: The survey response rate was 82% (110/134). Overall 54.1% of responding institutions reported covering one or more topics related to safe opioid prescribing or opioid use disorder in the internal medicine clerkship. A preponderance of clerkship directors (range 51-86%) reported that various opioid-related topics were important to cover in the internal medicine clerkship. Safe opioid prescribing topics were covered more frequently than topics related specifically to opioid use disorder. The main barriers identified included time (80.9%) and lack of faculty expertise (65.5%). CONCLUSIONS: Clerkship directors agreed that incorporating safe opioid prescribing and opioid use disorder topics in the internal medicine clerkship is important, despite wide variation in current curricula. Addressing curricular time constraints and lack of faculty expertise in internal medicine clerkships will be key to successfully integrating content to address the opioid epidemic.

Ambiguity of NRPS Structure Predictions: Four Bidentate Chelating Groups in the Siderophore Pacifibactin.

Identified through a bioinformatics approach, a nonribosomal peptide synthetase gene cluster in Alcanivorax pacificus encodes the biosynthesis of the new siderophore pacifibactin. The structure of pacifibactin differs markedly from the bioinformatic prediction and contains four bidentate metal chelation sites, atypical for siderophores. Genome mining and structural characterization of pacifibactin is reported herein, as well as characterization of pacifibactin variants accessible due to a lack of adenylation domain fidelity during biosynthesis. A spectrophotometric titration of pacifibactin with Fe(III) and 13C NMR spectroscopy of the Ga(III)-pacifibactin complex establish 1:1 metal:pacifibactin coordination and reveal which of the bidentate binding groups are coordinated to the metal. The photoreaction of Fe(III)-pacifibactin, resulting from Fe(III) coordination of the ß-hydroxyaspartic acid ligands, is reported.

Energy metabolism in the acquisition and maintenance of stemness.

Energy metabolism is traditionally considered a reactive homeostatic system addressing stage-specific cellular energy needs. There is however growing appreciation of metabolic pathways in the active control of vital cell functions. Case in point, the stem cell lifecycle--from maintenance and acquisition of stemness to lineage commitment and specification--is increasingly recognized as a metabolism-dependent process. Indeed, metabolic reprogramming is an early contributor to the orchestrated departure from or reacquisition of stemness. Recent advances in metabolomics have helped decipher the identity and dynamics of metabolic fluxes implicated in fueling cell fate choices by regulating the epigenetic and transcriptional identity of a cell. Metabolic cues, internal and/or external to the stem cell niche, facilitate progenitor pool restitution, long-term tissue renewal or ensure adoption of cytoprotective behavior. Convergence of energy metabolism with stem cell fate regulation opens a new avenue in understanding primordial developmental biology principles with future applications in regenerative medicine practice.

ß-Hydroxyaspartic acid in siderophores: biosynthesis and reactivity.

A growing number of siderophores are found to contain ß-hydroxyaspartic acid (ß-OH-Asp) as a functional group for Fe(III) coordination, along with the more common catechol and hydroxamic acid groups. This review covers the structures, biosynthesis, and reactions of peptidic ß-OH-Asp siderophores. Hydroxylation of Asp in siderophore biosynthesis is predicted to be carried out either through discrete aspartyl ß-hydroxylating enzymes or through hydroxylating domains within non-ribosomal peptide synthetases, both of which display sequence homology to known non-heme iron(II), α-ketoglutarate-dependent dioxygenases. Ferric complexes of ß-OH-Asp siderophores are photoreactive, resulting in reduction of Fe(III) and oxidative cleavage of the siderophore to yield distinct types of photoproducts. Probing the photoreactivity of synthetic Fe(III)-α-hydroxycarboxylate clusters yields mechanistic insights into the different photoproducts observed for ß-OH-Asp and other α-hydroxycarboxylate siderophore Fe(III) complexes.

Cellularly active N-hydroxyurea FEN1 inhibitors block substrate entry to the active site.

The structure-specific nuclease human flap endonuclease-1 (hFEN1) plays a key role in DNA replication and repair and may be of interest as an oncology target. We present the crystal structure of inhibitor-bound hFEN1, which shows a cyclic N-hydroxyurea bound in the active site coordinated to two magnesium ions. Three such compounds had similar IC50 values but differed subtly in mode of action. One had comparable affinity for protein and protein-substrate complex and prevented reaction by binding to active site catalytic metal ions, blocking the necessary unpairing of substrate DNA. Other compounds were more competitive with substrate. Cellular thermal shift data showed that both inhibitor types engaged with hFEN1 in cells, and activation of the DNA damage response was evident upon treatment with inhibitors. However, cellular EC50 values were significantly higher than in vitro inhibition constants, and the implications of this for exploitation of hFEN1 as a drug target are discussed.

Insight meditation and telomere biology: The effects of intensive retreat and the moderating role of personality.

A growing body of evidence suggests that meditation training may have a range of salubrious effects, including improved telomere regulation. Telomeres and the enzyme telomerase interact with a variety of molecular components to regulate cell-cycle signaling cascades, and are implicated in pathways linking psychological stress to disease. We investigated the effects of intensive meditation practice on these biomarkers by measuring changes in telomere length (TL), telomerase activity (TA), and telomere-related gene (TRG) expression during a 1-month residential Insight meditation retreat. Multilevel analyses revealed an apparent TL increase in the retreat group, compared to a group of experienced meditators, similarly comprised in age and gender, who were not on retreat. Moreover, personality traits predicted changes in TL, such that retreat participants highest in neuroticism and lowest in agreeableness demonstrated the greatest increases in TL. Changes observed in TRGs further suggest retreat-related improvements in telomere maintenance, including increases in Gar1 and HnRNPA1, which encode proteins that bind telomerase RNA and telomeric DNA. Although no group-level changes were observed in TA, retreat participants' TA levels at post-assessment were inversely related to several indices of retreat engagement and prior meditation experience. Neuroticism also predicted variation in TA across retreat. These findings suggest that meditation training in a retreat setting may have positive effects on telomere regulation, which are moderated by individual differences in personality and meditation experience. (ClinicalTrials.gov #NCT03056105).

The effect of movement-focused and breath-focused yoga practice on stress parameters and sustained attention: A randomized controlled pilot study.

Yoga-based practices (YBP) typically involve a combination of movement sequences, conscious regulation of the breath, and techniques to engage attention. However, little is known about whether effects of YBP result from the synergistic combination of these components, or whether a subset may yield similar effects. In this study we compared the effect of a movement-focused practice and a breath-focused practice on stress parameters (perceived stress and salivary cortisol) and sustained attention (response inhibition) in yoga naïve university students. While participants of both programs showed a reduction in perceived stress and salivary cortisol, only the breath-focused group showed improvements in sustained attention. In addition, improvement in sustained attention was correlated with reduction in perceived stress but not with reduction in salivary cortisol. We discuss these findings in the context of a theoretical framework outlining bottom-up neurophysiological and top-down neurocognitive mechanisms hypothesized to be engaged by YBP.