Whole-genome duplication in the Multicellularity Long Term Evolution Experiment.

Whole-genome duplication (WGD) is widespread across eukaryotes and can promote adaptive evolution1-4. However, given the instability of newly-formed polyploid genomes5-7, understanding how WGDs arise in a population, persist, and underpin adaptations remains a challenge. Using our ongoing Multicellularity Long Term Evolution Experiment (MuLTEE)8, we show that diploid snowflake yeast (Saccharomyces cerevisiae) under selection for larger multicellular size rapidly undergo spontaneous WGD. From its origin within the first 50 days of the experiment, tetraploids persist for the next 950 days (nearly 5,000 generations, the current leading edge of our experiment) in ten replicate populations, despite being genomically unstable. Using synthetic reconstruction, biophysical modeling, and counter-selection experiments, we found that tetraploidy evolved because it confers immediate fitness benefits in this environment, by producing larger, longer cells that yield larger clusters. The same selective benefit also maintained tetraploidy over long evolutionary timescales, inhibiting the reversion to diploidy that is typically seen in laboratory evolution experiments. Once established, tetraploidy facilitated novel genetic routes for adaptation, playing a key role in the evolution of macroscopic multicellular size via the origin of evolutionarily conserved aneuploidy. These results provide unique empirical insights into the evolutionary dynamics and impacts of WGD, showing how it can initially arise due to its immediate adaptive benefits, be maintained by selection, and fuel long-term innovations by creating additional dimensions of heritable genetic variation.

The effects of a real-time temperature monitoring non-ablative monopolar radiofrequency technology on vulvovaginal atrophy symptoms in postmenopausal Chinese women.

BACKGROUND: Vulvovaginal atrophy (VVA) includes a wide range of conditions affecting the reproductive and urinary systems, often requiring careful evaluation and management for optimal health. AIMS: This study aims to evaluate the symptom management effects of a real time temperature-monitored non-ablative RF device for the treatment of postmenopausal Chinese women with VVA symptoms. METHODS: This pilot study involved 24 postmenopausal Chinese women with one or more VVA symptoms, who wished to remain sexually active. VHIS, VAS, and FSFI were used to track and evaluate various aspects of the patient's condition. Analyses were conducted at the end of the study to verify the statistical significance of the treatment's results. RESULTS: All patients reported substantial, statistically significant, improvements on every VVA symptom tracked. Approximately 80% of the patients reported total symptom reversal at 12-week post-treatment follow-up. CONCLUSION: This pilot study demonstrated that non-ablative, monopolar RF technology equipped with real time temperature monitoring is feasible and safe in the treatment of postmenopausal women with VVA symptoms, and efficacious at up to 12 weeks post-treatment.

Relationships between psychopathological symptoms, pandemic-related stress, perceived social support, and COVID-19 infection history: a network analysis in Chinese college students.

Introduction: Previous coronavirus, 2019 (COVID-19) research has applied network analysis to examine relationships between psychopathological symptoms but rarely extended to potential risk and protective factors or the influence of COVID-19 infection history. This study examined complex inter-relationships between psychopathological symptoms, COVID-19-related stressors, perceived social support, and COVID-19 infection history among Chinese university/college students during the peak of fifth pandemic wave using a network analysis approach. Methods: A Least Absolute Shrinkage and Selection Operator-regularized partial correlation network using Gaussian graphical model was constructed in 1,395 Chinese university/college students in Hong Kong who completed a survey between 15 March and 3 April, 2022. Depressive, anxiety, and acute/traumatic stress symptoms were measured by Patient Health Questionnaire-9, Generalized Anxiety Disorder-7, and Impact of Event Scale-6, respectively. COVID-19-related stressors and perceived social support were measured. Network differences by COVID-19 infection history (COVID-network vs. no_COVID-network) and network communities were examined. Results: Our results showed that the most influential nodes were depressed mood, uncontrollable worries, and uncontrollable thoughts about COVID-19. The main bridging symptoms were concentration problems and psychomotor problems. The COVID-network, comprising participants with a history of COVID-19 infection only, was significantly stronger than the no_COVID-network. Perceived social support and stress from conflicts with family/friends formed a unique community with negative cognition and suicidal idea in the COVID-network only. Conclusion: Our findings indicate that specific interventions targeting interpersonal conflicts and concentration problems as well as facilitating stress buffering effects of social support may represent effective strategies to reduce psychological distress in university/college students during COVID-19 and should be considered for future pandemic preparedness.

Does vaginal estrogen use increase the risk for adverse cardiovascular outcomes?

NO. In general, nonoral estrogen use for menopausal symptoms is associated with a lower cardiovascular (CV) risk profile than oral estrogen use (strength of recommendation [SOR], B; meta-analysis of cohort studies). Vaginal estrogen use is associated with lower risk for coronary heart disease (CHD) and similar risk for myocardial infarction (MI), stroke, and deep vein thrombosis/pulmonary embolism (DVT/ PE) compared with nonuse (SOR, B; cohort studies). Vaginal estrogen therapy also is associated with lower CV-related mortality for 3 to 5 years compared withnonuse (SOR, B; cohort study). No high-quality randomized trials address this topic.

Dysregulated metabolism of the late herpes simplex virus 1 transcriptome through the vhs-VP22 axis uncouples virus cytopathic effect and virus production.

Herpes simplex virus 1 (HSV1) expresses its genes in a classical cascade culminating in the production of large amounts of structural proteins to facilitate virus assembly. HSV1 lacking the virus protein VP22 (Δ22) exhibits late translational shutoff, a phenotype that has been attributed to the unrestrained activity of the virion host shutoff (vhs) protein, a virus-encoded endoribonuclease which induces mRNA degradation during infection. We have previously shown that vhs is also involved in regulating the nuclear-cytoplasmic compartmentalisation of the virus transcriptome, and in the absence of VP22 a number of virus transcripts are sequestered in the nucleus late in infection. Here we show that despite expressing minimal amounts of structural proteins and failing to plaque on human fibroblasts, the strain 17 Δ22 virus replicates and spreads as efficiently as Wt virus, but without causing cytopathic effect (CPE). Nonetheless, CPE-causing virus spontaneously appeared on Δ22-infected human fibroblasts, and four viruses isolated in this way had all acquired point mutations in vhs which rescued late protein translation. However, unlike a virus deleted for vhs, these viruses still induced the degradation of both cellular and viral mRNA suggesting that vhs mutation in the absence of VP22 is necessary to overcome a more complex disturbance in mRNA metabolism than mRNA degradation alone. The ultimate outcome of secondary mutations in vhs is therefore the rescue of virus-induced CPE caused by late protein synthesis, and while there is a clear selective pressure on HSV1 to mutate vhs for optimal production of late structural proteins, the purpose of this is over and above that of virus production.

Gaps in Prenatal Hepatitis B Screening and Management of HBsAg Positive Pregnant Persons in the U.S., 2015-2020.

BACKGROUND: The Advisory Committee for Immunization Practices (ACIP) recommends testing all pregnant women for hepatitis B surface antigen (HBsAg) and testing HBsAg-positive pregnant women for hepatitis B virus deoxyribonucleic acid (HBV DNA). HBsAg-positive pregnant persons are recommended by the American Association for the Study of Liver Diseases to receive regular monitoring, including alanine transaminase (ALT) and HBV DNA and antiviral therapy for active hepatitis and to prevent perinatal HBV transmission if HBV DNA level is >200,000 IU/mL. METHODS: Using Optum Clinformatics Data Mart Database claims data, pregnant women who received HBsAg testing and HBsAg-positive pregnant persons who received HBV DNA and alt testing and antiviral therapy during pregnancy and after delivery during January 1, 2015-December 31, 2020 were analyzed. RESULTS: Among 506,794 pregnancies, 14.6% did not receive HBsAg testing. Pregnant women more likely to receive testing for HBsAg (p<0.01) were persons aged ≥20 years, were Asian, had >1 child, or received education beyond high school. Among the 0.28% (1,437) pregnant women who tested positive for hepatitis B surface antigen, 46% were Asian. The proportion of HBsAg-positive pregnant women who received HBV DNA testing during pregnancy and in the 12 months after delivery was 44.3% and 28.6%, respectively; the proportion that received hepatitis B e antigen was 31.6% and 12.7%, respectively; the proportion that received ALT testing was 67.4% and 47%, respectively; and the proportion that received HBV antiviral therapy was 7% and 6.2%, respectively. CONCLUSIONS: This study suggests that as many as half a million (∼14%) pregnant persons who gave birth each year were not tested for HBsAg to prevent perinatal transmission. More than 50% of HBsAg-positive persons did not receive the recommended HBV-directed monitoring tests during pregnancy and after delivery.

Initiating Primary Care Services when the World Is Paused: Lessons for Pharmacists in the Post-COVID-19 Era.

The COVID-19 pandemic impacted primary care and required pharmacists to adapt when implementing primary care services. Many lessons learned through this process are applicable in the post-pandemic era. First, primary care pharmacists must prepare for an ever-changing role and communicate with stakeholders to align with shifting institutional priorities. Additionally, designing a workflow given limited staffing and in-person communication require flexibility for scheduling and referral processes. Proactive outreach and communication via virtual platforms may be used to build trust in place of in-office interactions with providers. Lastly, fostering relationships with patients is essential to the success of the service and often requires creation of patient-centered goals to account for personal barriers. Many pandemic obstacles are transient; however, telehealth, virtual communication, and the subsequent lessons learned in adaptability, creativity, and flexibility when building a clinic practice are everlasting.

The unvirtuous cycle of discrimination affecting people with hepatitis B: a multi-country qualitative assessment of key-informant perspectives.

BACKGROUND: An estimated 296 million individuals live with chronic hepatitis B worldwide, most have not been diagnosed and remain at risk of liver disease and cancer. People with hepatitis B often face discrimination that denies them employment or education opportunities, results in unfair treatment at work or in school, limits their ability to emigrate to certain countries, and in some cases prohibits them from serving in the military. Discrimination specific to hepatitis B has not been widely documented within the literature. This study aims to investigate and describe hepatitis B related discrimination, document discrimination occurring around the globe, and provide initial recommendations for addressing discrimination using key informant interviews. METHODS: Purposive and snowball sampling were used to identify potential key informants for qualitative interview. Key informants identified as community health leaders, public health scientists, doctors, and researchers, many of whom were also living with hepatitis B. Using a semi-structured guide, participants were asked to describe their experience and any challenges for people living with hepatitis B including marginalization and its' consequences. A codebook was used to guide the organization of data for analysis, and all transcripts N = 17 were double coded. RESULTS: The overarching themes identified from interviews demonstrate explicit experiences with discrimination of those directly affected, the psychological responses, and the negative health outcomes associated with the unvirtuous cycle of discrimination. All key informants reported on the substantial quality of life implications and often poorer health outcomes resulting from hepatitis B discrimination. Participants also identified the significant impact of hepatitis B discrimination occurring within a range of education-based services across several countries as well as military exclusion or removal if individuals are found to have hepatitis B. CONCLUSION: Our data demonstrate that hepatitis B discrimination has a significant impact. Discrimination can occur at various points in life from education, to seeking employment, to marriage, to restrictions on entry, travel and stay in other countries. This study demonstrates the impact of discrimination and the need for future research that can lead to policy change and protections for people living with and impacted by hepatitis B.

Genotypes of Pain and Analgesia in a Randomized Trial of Irritable Bowel Syndrome.

Background: Irritable bowel syndrome (IBS) is a highly prevalent chronic pain disorder with multiple underlying mechanisms and few treatments that have been demonstrated to be effective in placebo controlled trials. One potential reason may be the use of composite outcomes, such as the IBS Symptom Severity Scale (IBS-SSS) which includes descriptive items related to pain frequency and pain intensity as well as bowel dysfunction and bloating. We investigated if different features of IBS pain have distinct genetic associations and if these may be moderated by sex hormones. Participants and Setting: Adult outpatients with moderately severe IBS (>175 on IBS-SSS) enrolled in a clinical trial reported IBS-SSS at baseline and after 6 weeks of therapy. Methods: Fixed effects modeling was used to test the effect of COMT rs4680 genotype to change in pain severity (rated 0-100) and pain frequency (defined as number of days with pain in the past 10 days) from baseline to week 6 with IBS treatment. Parallel exploratory genome-wide association studies (GWAS) were also performed to identify single nucleotide polymorphisms (SNPs) associated with change in pain severity or pain frequency across all participants. Results: A total of 212 participants (74% female) were included. The COMT rs4680 met allele was associated with decreased pain severity over the course of the trial in gene dosage models [beta(SE) -5.9 (2.6), P = 0.028]. Exploratory GWAS for change in pain frequency identified 5 SNPs in close proximity on chromosome 18 near L3MBTL4 which reached genome-wide significance (all P < 5.0E-8). This effect was not mediated by changing estradiol levels. There was also a region of chromosome 7 with 24 SNPs of genome-wide suggestive significance for change in pain severity (all P < 1.0E-5). Conclusions: Previously reported association between COMT rs4680 genotype and treatment response as measured by IBS-SSS is related to pain severity, but not pain frequency. We also identified new candidate genes associated with changes in IBS pain severity (SNX13) and pain frequency (L3MBTL4) in response to treatment. Further studies are needed to understand these associations and genetic determinants of different components of IBS-SSS. ClinicalTrials.gov, Identifier: NCT0280224.

Psychological Predictors of Response to Open-Label Versus Double-Blind Placebo in a Randomized Controlled Trial in Irritable Bowel Syndrome.

OBJECTIVE: There is growing evidence that open-label placebo (OLP) may be an efficacious treatment of chronic and functional conditions. However, patient-level predictors of response to OLP have not been clearly identified. The aim of this study is to evaluate the psychological predictors of response to OLP and to compare this to double-blind placebo (DBP) and no-pill control (NPC). METHODS: This study is a secondary analysis of data collected in a 6-week randomized controlled trial evaluating placebo effects in irritable bowel syndrome (IBS). The primary outcome was change in IBS severity. Hierarchical linear regression identified predictors of placebo response in general and compared them between those randomized to OLP, DBP, and NPC. Predictor variables included personality traits, generalized anxiety, depression, visceral sensitivity (a measure of symptom-specific anxiety), and pain catastrophizing. RESULTS: A total of 210 participants (mean age = 42.3 years, 73.3% female) were included. Regression models revealed that visceral sensitivity was a predictor of response to OLP and NPC but not DBP. Interestingly, the effects were opposite, with high visceral sensitivity predicting less improvement in NPC and more improvement in OLP. Pain catastrophizing was a negative predictor of response to OLP (i.e., high pain catastrophizing was associated with less improvement in OLP). Neither visceral sensitivity nor pain catastrophizing played a significant role for response to DBP. CONCLUSIONS: IBS participants who score low on the Pain Catastrophizing Scale but high on the Visceral Sensitivity Index seem to benefit particularly from OLP. Our study suggests that different psychological mechanisms may be involved in DBP and OLP interventions.

Are They Side Effects? Extraintestinal Symptoms Reported During Clinical Trials of Irritable Bowel Syndrome May Be More Severe at Baseline.

BACKGROUND & AIMS: Many of the reported adverse events in clinical trials of irritable bowel syndrome are extraintestinal symptoms, which typically are assessed by open-ended questions during the trial and not at baseline. This may lead to misattribution of some pre-existing symptoms as side effects to the treatment. METHODS: The current study analyzed data from a 6-week clinical trial of irritable bowel syndrome. Participants were randomized to receive double-blind peppermint oil, double-blind placebo, or treatment as usual. Extraintestinal symptoms were assessed at baseline and at the end of the study. RESULTS: This analysis included 173 participants (30 received double-blind peppermint oil, 72 received treatment as usual, and 71 received double-blind placebo). At baseline, each group reported approximately 5 extraintestinal symptoms per participant. The number of symptoms per participant decreased to an average of 3 by the end-of-study visit, and this change was statistically significant in all groups (P < .001 for each group). When evaluating individual extraintestinal symptoms, the majority of participants did not report new/worse symptoms. In fact, between the baseline assessment and the final assessment, the average symptom severity decreased significantly in all 3 groups (P < .001). CONCLUSIONS: Our study suggests that participants with irritable bowel syndrome often experience extraintestinal symptoms at baseline and that these symptoms generally improve in severity over the course of a clinical trial, regardless of the treatment arm. Systematic assessment of extraintestinal symptoms at the beginning of a clinical trial is necessary to determine more definitively whether these symptoms may be considered an adverse event attributable to a study medication.

Effect of antibiotic pretreatment on bacterial engraftment after Fecal Microbiota Transplant (FMT) in IBS-D.

Fecal microbiota transplantation (FMT) is an attractive strategy to correct microbial dysbiosis in diarrhea-predominant irritable bowel syndrome (IBS-D). Although the mechanism of FMT is thought to be bacterial engraftment, the best approach to achieve engraftment after FMT in IBS-D (and other diseases) is not clear. We evaluated the effect of FMT (with or without pretreatment with antibiotics) on gut microbiome and symptoms in patients with IBS-D. In this randomized, placebo-controlled, single-center study, 44 patients with IBS-D with a least moderate severity (IBS severity scoring system, i.e., IBS-SSS, ≥175) were randomly assigned to one of four groups: single-dose oral FMT alone, single-dose oral FMT following a 7-day pretreatment course of Ciprofloxacin and Metronidazole (CM-FMT) or Rifaximin (R-FMT), or Placebo FMT. Primary endpoint was engraftment post-FMT and secondary endpoints were changes in IBS-SSS, and IBS-quality of life (IBS-QOL) at week 10. Median engraftment was significantly different among the three FMT groups (P = .013). Engraftment post-FMT was significantly higher in the FMT alone arm (15.5%) compared to that in R-FMT group (5%, P = .04) and CM-FMT group (2.4%, P = .002). The mean change in IBS-SSS and IBS-QOL from baseline were not significantly different among the four groups or between the three FMT groups combined vs. placebo at week 10. In summary, antibiotic pretreatment significantly reduced bacterial engraftment after FMT in patients with IBS-D.

Improving Medication Tolerance: A Pilot Study in Disorders of Gut-brain Interaction Treated With Tricyclic Antidepressants.

OBJECTIVES: Tricyclic antidepressants (TCAs) are commonly used to treat disorders of gut-brain interaction (DGBI). However, these medications are often associated with side effects that lead to early treatment discontinuation. Research in other chronic medical conditions suggests that many TCA side effects may be caused by nocebo (negative placebo) effects. The current study tests a brief, verbal intervention aimed at improving tolerance of TCAs in DGBI by providing education about nocebo effects. MATERIALS AND METHODS: This pilot randomized controlled trial was performed in a tertiary care gastroenterology clinic. Participants with DGBI were randomized "standard information," describing the benefits and risks of TCAs, or "augmented information," which included an additional <30-second education about nocebo effects. Two weeks after their visit, participants were emailed a survey evaluating the number and bothersomeness of side effects, adequate relief, global improvement, and treatment satisfaction. RESULTS: Thirty-one patients were randomized and 22 responded to the survey. The average age was 40% and 59% were women. Although not statistically significant, the augmented group attributed nominally fewer symptoms to TCAs than the standard group, with a medium effect size (1.5 vs. 4.2, effect size d=0.56, P=0.212) and reported being significantly less bothered by those symptoms (13.4 vs. 38.1, P=0.037). A nominally larger percentage of the augmented group reported adequate relief of symptoms after 2 weeks of treatment compared with the standard group (55% vs. 27%, respectively). CONCLUSIONS: This pilot study demonstrates that a brief (≈30 s) clinical intervention addressing nocebo effects may improve tolerance of TCAs. These findings provide support for future, fully powered studies to evaluate the impact of framing on clinical outcomes, especially in chronic conditions.

Emerging Microfluidic Approaches for Platelet Mechanobiology and Interplay With Circulatory Systems.

Understanding how platelets can sense and respond to hemodynamic forces in disturbed blood flow and complexed vasculature is crucial to the development of more effective and safer antithrombotic therapeutics. By incorporating diverse structural and functional designs, microfluidic technologies have emerged to mimic microvascular anatomies and hemodynamic microenvironments, which open the floodgates for fascinating platelet mechanobiology investigations. The latest endothelialized microfluidics can even recapitulate the crosstalk between platelets and the circulatory system, including the vessel walls and plasma proteins such as von Willebrand factor. Hereby, we highlight these exciting microfluidic applications to platelet mechanobiology and platelet-circulatory system interplay as implicated in thrombosis. Last but not least, we discuss the need for microfluidic standardization and summarize the commercially available microfluidic platforms for researchers to obtain reproducible and consistent results in the field.

Peppermint Oil Treatment for Irritable Bowel Syndrome: A Randomized Placebo-Controlled Trial.

INTRODUCTION: Peppermint oil is often used to treat irritable bowel syndrome (IBS); however, the overall quality of previous studies is low, and findings have been heterogeneous. This study aimed to compare the effects of peppermint oil vs placebo in relieving IBS symptoms. METHODS: In a 6-week, randomized, double-blind, placebo-controlled trial at a single academic center in the United States, individuals diagnosed with IBS (Rome IV criteria), with moderate to severe symptoms based on the IBS Severity Scoring System (IBS-SSS score ≥175), were randomized to enteric-coated peppermint oil 180 mg 3 times daily vs placebo in a 1:2 ratio. The primary outcome was mean change in IBS-SSS scores from baseline to 6-week endpoint. RESULTS: A modified intent-to-treat analysis revealed that there were substantial mean improvements from baseline to 6-week endpoint in the main outcome measure (IBS-SSS) for both peppermint oil (90.8, SD = 75.3) and placebo (100.3, SD = 99.6). Although the peppermint oil group reported numerically lower improvement than the placebo group, the effect size was small (d = -0.11), and the difference between the groups was not statistically significant (P = 0.97). Similarly, both groups reported substantial improvements on the secondary endpoints; but again, there were no statistically significant differences between the groups on any of the secondary measures. Sensitivity analyses using multiple imputation to replace missing data produced similar results and revealed no significant differences between peppermint oil and placebo on any outcome measure. DISCUSSION: Peppermint oil and placebo both showed clinically meaningful improvement in IBS symptoms. However, there were no significant differences between the groups. Further large, rigorous trials are needed to evaluate the role of peppermint oil for the treatment of IBS.

Open-label placebo vs double-blind placebo for irritable bowel syndrome: a randomized clinical trial.

ABSTRACT: It is commonly believed that blinding to treatment assignment is necessary for placebos to have an effect. However, placebos administered without concealment (ie, open-label placebos [OLPs]) have recently been shown to be effective in some conditions. This study had 2 objectives: first, to determine whether OLP treatment is superior to no-pill control (NPC) in irritable bowel syndrome (IBS) and, second, to compare the efficacy of OLP against double-blind placebo (DBP). In a 6-week, 3-arm, randomized clinical trial, participants were randomized in equal proportions to 3 arms: OLP, DBP, or NPC. Two hundred sixty-two adults (72.9% women), with a mean age of 42.0 (SD = 18.1) years, participated in the primary study. The mean improvement on the IBS Severity Scoring System from baseline to the 6-week end point was significantly greater in OLP compared with that in NPC (90.6 vs 52.3, P = 0.038). Open-label placebo and DBP did not differ significantly on IBS Severity Scoring System improvement (100.3 vs 90.6, P = 0.485). Standardized effect sizes were moderate for OLP vs NPC (d = 0.43) and small for OLP vs DBP (d = 0.10). Participants treated with OLP reported clinically meaningful improvements in IBS symptoms that were significantly greater than those on NPC. Open-label placebo and DBP had similar effects that did not differ significantly, suggesting that blinding may not be necessary for placebos to be effective and that OLP could play a role in the management of patients with refractory IBS.

Genomic Effects Associated With Response to Placebo Treatment in a Randomized Trial of Irritable Bowel Syndrome.

Background and Aims: Irritable bowel syndrome (IBS), a functional pain disorder of gut-brain interactions, is characterized by a high placebo response in randomized clinical trials (RCTs). Catechol-O-methyltransferase (COMT) rs4680, which encodes high-activity (val) or low-activity (met) enzyme variants, was previously associated with placebo response to sham-acupuncture in an IBS RCT. Examining COMT effects and identifying novel genomic factors that influence response to placebo pills is critical to identifying underlying mechanisms and predicting and managing placebos in RCTs. Methods: Participants with IBS (N = 188) were randomized to three placebo-related interventions, namely, double-blind placebo (DBP), open-label placebo (OLP), or simply trial enrollment without placebo treatment [no placebo (i.e., no pill) treatment control (NPC)], for 6 weeks. COMT rs4680, gene-set, and genome-wide suggestive (p < 10-5) loci effects on irritable bowel symptom severity score (IBS-SSS) across all participants were examined. Results: Participants with IBS homozygous for rs4680 met (met/met) had the greatest improvement across all arms, with significantly greater improvement compared to val/val in DBP (beta (SE), -89.4 (42.3); p = 0.04). Twelve genome-wide suggestive loci formed a gene regulatory network highly connected to EGR1, a transcription factor involved in placebo-related processes of learning, memory, and response to stress and reward. EGR1 gene expression in peripheral blood mononuclear cells (PBMC) was significantly reduced at the endpoint across all treatment arms (log fold-change, -0.15; p = 0.02). Gene-set enrichment analysis returned three genome-wide significant ontology terms (GO:0032968, GO:0070934, and GO:0070937) linked to transcription regulation and GO:0003918 associated with DNA topoisomerase regulation. Conclusion: These results suggest common molecular mechanisms in response to varying forms of placebo that may inform personalized IBS treatment and placebo response prediction. Clinical Trial Registration: ClinicalTrials.gov, Identifier: NCT0280224.

Prescribing practices of migraine-specific pharmacotherapy associated with emergency department use for migraine.

OBJECTIVE: This study compared migraine medication prescribing between patients with a migraine diagnosis who used versus did not use the emergency department (ED) for migraine. BACKGROUND: Headache is the fifth most common chief complaint for ED visits nationwide and the third most common potentially avoidable ED diagnosis in the University of Colorado Health system. The reasons some patients use the ED for migraine management while others do not and whether some ED admissions might be preventable remain unclear. METHODS: This retrospective cohort study identified adults with migraine-related diagnoses within 1 year before the index date of July 1, 2018 and compared patient characteristics and migraine medication prescribing patterns between those who did or did not have a subsequent migraine-related ED encounter the following year. ED admission notes were manually reviewed to identify potentially preventable circumstances that led to the ED visit. The primary outcome was the proportion of patients with an active triptan prescription at the index date. RESULTS: Of the 3843 patients identified, 35 patients (0.9%) had a migraine-related ED encounter. Of these, 17/35 (49%) had an active triptan prescription compared to 1360/3808 (36%) of non-ED utilizers (p = 0.114), OR 1.22 (95% CI 0.61-2.45). More ED utilizers had an active prescription for opioids (11/35 [31%] vs. 663/3808 [17%], p = 0.030) and migraine preventive therapy (19/35 [54%] vs. 1149/3808 [30%], p = 0.002), and neurology referrals (20/35 [57%] vs. 654/3808 [17%], p < 0.001) compared to non-ED utilizers. The most common circumstance for migraine-related ED visits was nonresponse to migraine abortive medications administered at home. CONCLUSIONS: Triptan prescribing did not differ between ED utilizers and non-ED utilizers for migraine. Overall, less than half of the total patient population had a triptan prescribed. More ED utilizers had neurology referrals, prescriptions for opioids and preventive therapies, and a history of previous ED visit for any reason, which may be markers for higher disease severity or behavior patterns. Future research and interventions to reduce migraine-related ED use could target high-risk patients such as those with previous ED visits for any indication and neurology referrals.

Effects of a Combination of Three-Dimensional Virtual Reality and Hands-on Horticultural Therapy on Institutionalized Older Adults' Physical and Mental Health: Quasi-Experimental Design.

BACKGROUND: Institutionalized older adults have limited ability to engage in horticultural activities that can improve their physical and mental health. OBJECTIVE: This study explored the effects of a combination of 3D virtual reality and horticultural therapy on institutionalized older adults' physical and mental health. METHODS: The study used a quasi-experimental design. A total of 106 older adults from 2 long-term care facilities were recruited and assigned to the experimental (n=59) or control (n=47) group. The experimental participants received a 9-week intervention. Both groups completed 3 assessments: at baseline, after the intervention, and 2 months later. The outcome variables included health status, meaning in life, perceived mattering, loneliness, and depression. RESULTS: The experimental group demonstrated significantly improved health status (P<.001), meaning in life (P<.001), and perceived mattering (P<.001) as well as significantly reduced depression (P<.001) and loneliness (P<.001) compared to the control group immediately after the intervention; these effects persisted for up to 2 months. CONCLUSIONS: This study verified the beneficial effects of a combination of 3D virtual reality and hands-on horticultural therapy on older adults' health. These results could support the future successful implementation of similar programs for institutionalized older adults on a larger scale.

Combination of 3-Dimensional Virtual Reality and Hands-On Aromatherapy in Improving Institutionalized Older Adults' Psychological Health: Quasi-Experimental Study.

BACKGROUND: In Taiwan, which has one of the most rapidly aging populations in the world, it is becoming increasingly critical to promote successful aging strategies that are effective, easily usable, and acceptable to institutionalized older adults. Although many practitioners and professionals have explored aromatherapy and identified its psychological benefits, the effectiveness of combining 3-dimensional (3D) virtual reality and hands-on aromatherapy remains unknown. OBJECTIVE: A quasi-experimental trial was designed to evaluate the effectiveness of this combination in lowering perceived stress and promoting happiness, sleep quality, meditation experience, and life satisfaction among institutionalized older adults in Taiwan. METHODS: A total of 60 institutionalized elderly participants either received the combined intervention or were in a control group. Weekly 2-hour sessions were implemented over 9 weeks. The outcome variables were happiness, perceived stress, sleep quality, meditation experience, and life satisfaction, which were assessed at baseline and after the intervention. RESULTS: Generalized estimating equation (GEE) analyses indicated that the experimental group showed significant post-intervention improvements in terms of scores for happiness, perceived stress, sleep quality, meditation experience, and life satisfaction (n=48; all P<.001). Another GEE analysis showed that the significant improvements in the 5 outcome variables persisted in participants aged 80 years and older (n=35; all P<.001). CONCLUSIONS: This is the first trial to explore the effectiveness of a combination of 3D virtual reality and hands-on aromatherapy in improving older adults' psychological health. The results are promising for the promotion of psychological health in institutionalized older adults. TRIAL REGISTRATION: ClinicalTrials.gov NCT04324216; https://clinicaltrials.gov/ct2/show/NCT04324216.