Rapid whole-brain myelin imaging with selective inversion recovery and compressed SENSE.

PURPOSE: Quantitative magnetization transfer (QMT) using selective inversion recovery (SIR) can quantify the macromolecular-to-free proton pool size ratio (PSR), which has been shown to relate closely with myelin content. Currently clinical applications of SIR have been hampered by long scan times. In this work, the acceleration of SIR-QMT using CS-SENSE (compressed sensing SENSE) was systematically studied. THEORY AND METHODS: Phantoms of varied concentrations of bovine serum albumin and human scans were first conducted to evaluate the SNR, precision of SIR-QMT parameters, and scan time. Based on these results, an optimized CS-SENSE factor of 8 was determined and the test-retest repeatability was further investigated. RESULTS: A whole-brain SIR imaging of 6 min can be achieved. Bland-Altman analyses indicated excellent agreement between the test and retest sessions with a difference in mean PSR of 0.06% (and a difference in mean R1f of -0.001 s-1 ). In addition, the assessment of the intraclass correlation coefficient (ICC) revealed high reliability in nearly all the white matter and gray matter regions. In white matter regions, the ICC was 0.93 (95% confidence interval [CI]: 0.88-0.96, p < 0.001) for PSR, and 0.90 (95% CI: 0.83-0.94, p < 0.001) for R1f . In gray matter, ICC was 0.84 (95% CI: 0.66-0.93, p < 0.001) in PSR, and 0.98 (95% CI: 0.95-0.99, p < 0.001) for R1f . The method also showed excellent capability to detect focal lesions in multiple sclerosis. CONCLUSION: Rapid, reliable, and sensitive whole-brain SIR imaging can be achieved using CS-SENSE, which is expected to significantly promote widespread clinical translation.

Evaluation of two-stage designs of Phase 2 single-arm trials in glioblastoma: a systematic review.

BACKGROUND: Due to economical and ethical reasons, the two-stage designs have been widely used for Phase 2 single-arm trials in oncology because the designs allow us to stop the trial early if the proposed treatment is likely to be ineffective. Nonetheless, none has examined the usage for published articles that had applied the two-stage designs in Phase 2 single-arm trials in brain tumor. A complete systematic review and discussions for overcoming design issues might be important to better understand why oncology trials have shown low success rates in early phase trials. METHODS: We systematically reviewed published single-arm two-stage Phase 2 trials for patients with glioblastoma and high-grade gliomas (including newly diagnosed or recurrent). We also sought to understand how these two-stage trials have been implemented and discussed potential design issues which we hope will be helpful for investigators who work with Phase 2 clinical trials in rare and high-risk cancer studies including Neuro-Oncology. The systematic review was performed based on the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA)-statement. Searches were conducted using the electronic database of PubMed, Google Scholar and ClinicalTrials.gov for potentially eligible publications from inception by two independent researchers up to May 26, 2022. The followings were key words for the literature search as index terms or free-text words: "phase II trials", "glioblastoma", and "two-stage design". We extracted disease type and setting, population, therapeutic drug, primary endpoint, input parameters and sample size results from two-stage designs, and historical control reference, and study termination status. RESULTS: Among examined 29 trials, 12 trials (41%) appropriately provided key input parameters and sample size results from two-stage design implementation. Among appropriately implemented 12 trials, discouragingly only 3 trials (10%) explained the reference information of historical control rates. Most trials (90%) used Simon's two-stage designs. Only three studies have been completed for both stages and two out of the three completed studies had shown the efficacy. CONCLUSIONS: Right implementation for two-stage design and sample size calculation, transparency of historical control and experimental rates, appropriate selection on primary endpoint, potential incorporation of adaptive designs, and utilization of Phase 0 paradigm might help overcoming the challenges on glioblastoma therapeutic trials in Phase 2 trials.

Determinants of adherence to physical activity guidelines among overweight and obese African American breast cancer survivors: implications for an intervention approach.

OBJECTIVE: Public health agencies encourage breast cancer survivors (BCSs) to follow their physical activity guidelines (PAGs). However, adherence to these guidelines is low. African American (AA) BCSs are more often overweight or obese and less likely than women of other races to report adherence to physical activity recommendations. This study examined socioeconomic, clinical, and psychosocial correlates with meeting PAGs. DESIGN: AA women diagnosed and treated for breast cancer and participating in a breast cancer support group (N = 193) completed a lifestyle assessment tool capturing demographic characteristics; breast cancer diagnosis and treatment history; health-related quality of life; weight history, including body mass index and post-diagnosis weight gain; and physical activity. Logistic regressions were used to determine if these covariates were associated with meeting [>8.3 metabolic equivalent task (MET) hr/wk]; partially meeting (4.15-8.3 MET hr/wk); or not meeting (<4.15 MET hr/wk) PAGs. RESULTS: Only 54% of AA BCSs reported meeting current PAGs. Participants reporting weight gain of ≤5 lbs post-diagnosis, and those who received surgical treatment for breast cancer were more likely to complete at least 8.3 MET hr/wk. Better physical functioning and lesser pain intensity were associated with meeting PAGs. CONCLUSION: Several factors influence physical activity behaviors and are likely to be important in developing effective interventions to assist AA survivors manage their weight. It is essential that providers and breast cancer support groups that assist survivors to remain physically active and to manage their weight should be aware of these factors. These findings may help generate hypotheses for future research to undergird efforts to increase physical activity among African American BCSs.

Persons Who Failed to Obtain Colorectal Cancer Screening Despite Participation in an Evidence-Based Intervention.

In a previous report, we demonstrated the efficacy of an educational intervention focused on increasing colorectal cancer screening rates among African Americans. Despite participating in the intervention, however, nearly two-thirds of participants did not seek and receive screening. Participants were African-Americans over age 49 (N = 257) who had not been screened for colorectal cancer according to guidelines. At baseline, participants completed tests measuring fatalism, perceived stress, self-esteem, attitudes/benefits/barriers, social support, and social network diversity. Those who completed the educational intervention were followed up by telephone to learn if they had been screened. We compared the scores on the psychometric tests of the participants who had been screened against the scores of those who had not. Only the mean scores on the attitudes, benefits, and barriers scale distinguished participants who had been screened from those who had not (p = 0.0816 on bivariate testing and p = 0.0276 in the logistic regression model). Social interaction among participants or social cognitive learning may have played a role in determining which participants were screened, but we were not able to demonstrate this. The major factor distinguishing participants who were not screened was their attitude toward screening at baseline. There is a subset of African Americans who are persistently resistant to screening, and their perspective in this regard must be addressed if colorectal cancer disparities are to be reduced.

Advancing breast cancer survivorship among African-American women.

Advances have occurred in breast cancer survivorship but, for many African-American women, challenges and gaps in relevant information remain. This article identifies opportunities to address disparities in breast cancer survival and quality of life, and thereby to increase breast cancer survivorship among African-American women. For breast cancer survivors, common side effects, lasting for long periods after cancer treatment, include fatigue, loss of strength, difficulty sleeping, and sexual dysfunction. For addressing physical and mental health concerns, a variety of interventions have been evaluated, including exercise and weight training, dietary interventions, yoga and mindfulness-based stress reduction, and support groups or group therapy. Obesity has been associated with breast cancer recurrence and poorer survival. Relative to white survivors, African-American breast cancer survivors are more likely to be obese and less likely to engage in physical activity, although exercise improves overall quality of life and cancer-related fatigue. Considerable information exists about the effectiveness of such interventions for alleviating distress and improving quality of life among breast cancer survivors, but few studies have focused specifically on African-American women with a breast cancer diagnosis. Studies have identified a number of personal factors that are associated with resilience, increased quality of life, and positive adaptation to a breast cancer diagnosis. There is a need for a better understanding of breast cancer survivorship among African-American women. Additional evaluations of interventions for improving the quality of life and survival of African-American breast cancer survivors are desirable.

Determining left ventricular hypertrophy in overweight-obese youth using electrocardiogram criteria.

BACKGROUND AND PURPOSE: There is an escalating prevalence of obesity in youth that increases the risk for cardiovascular alterations such as left ventricular hypertrophy (LVH). The purpose of this study is to identify the most effective electrical voltage measurement for determining LVH in youth who are overweight and obese. METHODS: A retrospective chart review was conducted to determine sensitivity, specificity, and the receiver operator characteristic (ROC) curve of 4 popular electrical voltage measures. RESULTS: Our findings indicated the sensitivity and specificity for Cornell product (50.0%; 96.2%), Cornell voltage (52.9%; 98.0%), Romhilt Estes (50.0%; 100.0%), and Sokolow-Lyon index (60.0%; 86.4%) consecutively. CONCLUSION: The Romhilt-Estes and Cornell voltage measures displayed the highest specificity and could prove to be beneficial as a screening method to rule out LVH in overweight and obese youth.

Quisinostat is a brain-penetrant radiosensitizer in glioblastoma.

Histone deacetylase (HDAC) inhibitors have garnered considerable interest for the treatment of adult and pediatric malignant brain tumors. However, owing to their broad-spectrum nature and inability to effectively penetrate the blood-brain barrier, HDAC inhibitors have failed to provide substantial clinical benefit to patients with glioblastoma (GBM) to date. Moreover, global inhibition of HDACs results in widespread toxicity, highlighting the need for selective isoform targeting. Although no isoform-specific HDAC inhibitors are currently available, the second-generation hydroxamic acid-based HDAC inhibitor quisinostat possesses subnanomolar specificity for class I HDAC isoforms, particularly HDAC1 and HDAC2. It has been shown that HDAC1 is the essential HDAC in GBM. This study analyzed the neuropharmacokinetic, pharmacodynamic, and radiation-sensitizing properties of quisinostat in preclinical models of GBM. It was found that quisinostat is a well-tolerated and brain-penetrant molecule that extended survival when administered in combination with radiation in vivo. The pharmacokinetic-pharmacodynamic-efficacy relationship was established by correlating free drug concentrations and evidence of target modulation in the brain with survival benefit. Together, these data provide a strong rationale for clinical development of quisinostat as a radiosensitizer for the treatment of GBM.

A Phase 0 Trial of Ceritinib in Patients with Brain Metastases and Recurrent Glioblastoma.

PURPOSE: Ceritinib is an orally bioavailable, small-molecule inhibitor of anaplastic lympoma kinase (ALK), insulin-like growth factor 1 receptor (IGFR1), and focal adhesion kinase (FAK), which are highly expressed in glioblastoma and many brain metastases. Preclinical and clinical studies indicate that ceritinib has antitumor activity in central nervous system (CNS) malignancies. This phase 0 trial measured the tumor pharmacokinetics (PK) and pharmacodynamics (PD) of ceritinib in patients with brain metastasis or recurrent glioblastoma. PATIENTS AND METHODS: Preoperative patients with brain tumors demonstrating high expression of pSTAT5b/pFAK/pIGFR1 were administered ceritinib for 10 days prior to tumor resection. Plasma, tumor, and cerebrospinal fluid (CSF) samples were collected at predefined timepoints following the final dose. Total and unbound drug concentrations were determined using LC-MS/MS. In treated tumor and matched archival tissues, tumor PD was quantified through IHC analysis of pALK, pSTAT5b, pFAK, pIGFR1, and pIRS1. RESULTS: Ten patients (3 brain metastasis, 7 glioblastoma) were enrolled and no dose-limiting toxicities were observed. Ceritinib was highly bound to human plasma protein [median fraction unbound (Fu), 1.4%] and to brain tumor tissue (median Fu, 0.051% and 0.045% in gadolinium-enhancing and -nonenhancing regions respectively). Median unbound concentrations in enhancing and nonenhancing tumor were 0.048 and 0.006 µmol/L, respectively. Median unbound tumor-to-plasma ratios were 2.86 and 0.33 in enhancing and nonenhancing tumor, respectively. No changes in PD biomarkers were observed in the treated tumor samples as compared to matched archival tumor tissue. CONCLUSIONS: Ceritinib is highly bound to plasma proteins and tumor tissues. Unbound drug concentrations achieved in brain metastases and patients with recurrent glioblastoma were insufficient for target modulation.

Profound cardioprotection with chloramphenicol succinate in the swine model of myocardial ischemia-reperfusion injury.

BACKGROUND: Emerging evidence suggests that "adaptive" induction of autophagy (the cellular process responsible for the degradation and recycling of proteins and organelles) may confer a cardioprotective phenotype and represent a novel strategy to limit ischemia-reperfusion injury. Our aim was to test this paradigm in a clinically relevant, large animal model of acute myocardial infarction. METHODS AND RESULTS: Anesthetized pigs underwent 45 minutes of coronary artery occlusion and 3 hours of reperfusion. In the first component of the study, pigs received chloramphenicol succinate (CAPS) (an agent that purportedly upregulates autophagy; 20 mg/kg) or saline at 10 minutes before ischemia. Infarct size was delineated by tetrazolium staining and expressed as a % of the at-risk myocardium. In separate animals, myocardial samples were harvested at baseline and 10 minutes following CAPS treatment and assayed (by immunoblotting) for 2 proteins involved in autophagosome formation: Beclin-1 and microtubule-associated protein light chain 3-II. To investigate whether the efficacy of CAPS was maintained with "delayed" treatment, additional pigs received CAPS (20 mg/kg) at 30 minutes after occlusion. Expression of Beclin-1 and microtubule-associated protein light chain 3-II, as well as infarct size, were assessed at end-reperfusion. CAPS was cardioprotective: infarct size was 25±5 and 41±4%, respectively, in the CAPS-pretreated and CAPS-delayed treatment groups versus 56±5% in saline controls (P<0.01 and P<0.05 versus control). Moreover, administration of CAPS was associated with increased expression of both proteins. CONCLUSIONS: Our results demonstrate attenuation of ischemia-reperfusion injury with CAPS and are consistent with the concept that induction of autophagy may provide a novel strategy to confer cardioprotection.

Unexplained fetal death has a biological signature of maternal anti-fetal rejection: chronic chorioamnionitis and alloimmune anti-human leucocyte antigen antibodies.

AIMS: Chronic chorioamnionitis is a histological manifestation of maternal anti-fetal cellular rejection. As failure of graft survival is the most catastrophic event in organ transplantation, we hypothesized that fetal death could be a consequence of maternal rejection. The aim of this study was to assess whether there is evidence of cellular and antibody-mediated rejection in fetal death. METHODS AND RESULTS: Placental histology was reviewed for the presence of chronic chorioamnionitis in unexplained preterm fetal death (n=30) and preterm live birth (n=103). Amniotic fluid CXCL10 concentrations were measured with a specific immunoassay. Chronic chorioamnionitis was more frequent in fetal death than in live birth (60.0% versus 37.9%; P<0.05) and fetal death had a higher median amniotic fluid CXCL10 concentration than live birth (2.0 versus 1.8 ng/ml, P<0.05), after adjusting for gestational age at amniocentesis. Maternal anti-human leucocyte antigen class II panel-reactive seropositivity determined by flow cytometry was higher in fetal death compared to live birth (35.7% versus 10.9%; P<0.05). CONCLUSIONS: Chronic chorioamnionitis is a common pathologic feature in unexplained preterm fetal death. This novel finding suggests that cellular and antibody-mediated anti-fetal rejection of the mother is associated with fetal death (graft failure) in human pregnancy.

Human papillomavirus vaccine guideline adherence among Arizona's Medicaid beneficiaries.

Cancers caused by human papillomavirus (HPV) can be prevented with the timely uptake and completion of the HPV vaccine series. Series completion is associated with increased vaccine effectiveness and longevity of protection. Medicaid beneficiaries are among populations with higher HPV vaccine uptake; however, little research describes factors that influence their HPV vaccine series completion. This study reports on a secondary data analysis of Arizona Medicaid data (Arizona Health Care Cost Containment System) from years 2008-2016. We summarized patient data using descriptive statistics and explored relationships between demographic variables and HPV vaccine administration information using bivariate logistic regression. Results of this analysis showed that females were more likely to complete the series as compared to males, and the age group that had the greatest odd of vaccine completion were 13-17-year-olds, the catch-up vaccine population. White Medicaid beneficiaries were most likely to adhere to HPV vaccine guidelines, followed by Hispanic beneficiaries. Patients receiving care in urban settings were more likely to complete the HPV vaccine series than people receiving care in rural areas of the state. Although statistically insignificant, people living with HIV were less likely to complete the 3-dose series. Future work should focus on ensuring that HPV vaccine age-eligible Medicaid, including people living with HIV, adhere to HPV vaccine guidelines. Expanding programs such as Vaccines for Children and scope of practice for dental professionals to offer the vaccine may provide additional options for Medicaid beneficiaries to vaccinate.

Former Foster System Youth: Perspectives on Transitional Supports and Programs.

Youth aging out of the foster care system have well-documented challenges when transitioning to adulthood. Multiple transition services provide support in the transition process; however, limited research is available regarding youth's perceptions of programming. In this pilot study, sixteen youth between ages 18 and 20 participated in semi-structured interviews, support mapping, and resiliency measurements to gather the experiences of the transition from foster care. Comparisons between those who chose initial transition supports and those who did not receive or delayed receiving transition supports were initially explored. Common themes emerged in participants' needs and perceived resiliency regardless of transition support services. All youth reported relationship, trust, and concern for well-being as highly important characteristics in transition team members. A need for earlier transition programming, decision-making opportunities, and life skills courses were important themes in transition programming needs. Implications for policy, research, and practice are presented based upon findings.

The frequency, clinical significance, and pathological features of chronic chorioamnionitis: a lesion associated with spontaneous preterm birth.

Acute chorioamnionitis is a well-established lesion of the placenta in cases with intra-amniotic infection. In contrast, the clinicopathological significance of chronic chorioamnionitis is unclear. This study was conducted to determine the frequency and severity of chronic chorioamnionitis in normal pregnancy and in various pregnancy complications. Placentas from the following patient groups were studied: (1) term not in labor (n=100), (2) term in labor (n=100), (3) preterm labor (n=100), (4) preterm prelabor rupture of membranes (n=100), (5) preeclampsia at term (n=100), (6) preterm preeclampsia (n=100), and (7) small-for-gestational-age at term (n=100). Amniotic fluid CXCL10 concentration was measured in 64 patients. CXCL9, CXCL10, and CXCL11 mRNA expressions in the chorioamniotic membranes were assessed using real-time quantitative reverse transcription-PCR. The frequency of chronic chorioamnionitis in the preterm labor group and the preterm prelabor rupture of membranes group was 34 and 39%, respectively, which was higher than that of normal-term placentas (term not in labor, 19%; term in labor, 8%; P<0.05 each). The frequency of chronic chorioamnionitis in the preeclampsia at term group, preterm preeclampsia group, and small-for-gestational-age group was 23, 16, and 13%, respectively. Concomitant villitis of unknown etiology was found in 38 and 36% of preterm labor cases and preterm prelabor rupture of membranes cases with chronic chorioamnionitis, respectively. Interestingly, the median gestational age of preterm chronic chorioamnionitis cases was higher than that of acute chorioamnionitis cases (P<0.05). The median amniotic fluid CXCL10 concentration was higher in cases with chronic chorioamnionitis than in those without, in both the preterm labor group and preterm prelabor rupture of membranes group (P<0.05 and P<0.01, respectively). CXCL9, CXCL10, and CXCL11 mRNA expression in the chorioamniotic membranes was also higher in cases with chronic chorioamnionitis than in those without chronic chorioamnionitis (P<0.05). We propose that chronic chorioamnionitis defines a common placental pathological lesion among the preterm labor and preterm prelabor rupture of membranes groups, especially in cases of late preterm birth. Its association with villitis of unknown etiology and the chemokine profile in amniotic fluid suggests an immunological origin, akin to transplantation rejection and graft-versus-host disease in the chorioamniotic membranes.

Relationship of vitamin D and parathyroid hormone with obesity and body composition in African Americans.

BACKGROUND: Obesity disproportionately affects African Americans (AA) (especially women), and is linked to depressed 25-hydroxyvitamin D (25-OH D) and elevated parathyroid hormone (PTH). The relationship of 25-OH D and PTH with body composition and size in AA is not well known. OBJECTIVE: To determine the relationship of 25-OH D and PTH levels with body composition and anthropometric measures. DESIGN: A cross-sectional study was conducted in 98 healthy, overweight, adult AA enrolled in an NIH/NIEHS-sponsored weight loss/salt-sensitivity trial. MEASUREMENTS: Multivariable linear regression analyses were used to explore the relationship of 25-OH D and PTH with body composition, determined by dual-energy X-ray absorptiometry, and anthropometric measures. Body composition and size were contrasted across vitamin D/PTH groups using general linear models: (i) normal (25-OH D >50 nmol/l, PTH

Patterns and Disparities in Human Papillomavirus (HPV) Vaccine Uptake for Young Female Adolescents among U.S. States: NIS-Teen (2008-2016).

BACKGROUND: Several studies have reported differential vaccine uptake outcomes that are associated with sociodemographic and socioeconomic characteristics, as well as provider type. However, none has examined a trend over a multiple-year span. In this study, we utilize a longitudinal data-based approach to examine state-level human papillomavirus (HPV) vaccine trends and their influences over time. METHODS: We analyzed National Immunization Survey - Teen data (2008-2016) to estimate HPV vaccine initiation rate in young female adolescent ages 13-17 years old among U.S. States. We identified growth patterns using the latent class growth method and explored state-level characteristics, including socioeconomic and sociodemographic attributes, and health legislation and policy-related programs among patterns. RESULTS: We identified three growth patterns, which showed gradually increasing vaccination trends but different baseline HPV uptake rates (high, moderate, low). States within Pattern 1 (highest HPV vaccination rates) included the lowest percentage of families with incomes below federal poverty level, the highest percentage of bachelor's degree or higher, and the lowest number of uninsured, while states within Pattern 3 (lowest HPV vaccination rates) included families with socioeconomic attributes along the opposite end of the spectrum. CONCLUSIONS: Latent class growth models are an effective tool to be able to capture health disparities in heterogeneity among states in relation to HPV vaccine uptake trajectories. IMPACT: These findings might lead to designing and implementing effective interventions and changes in policies and health care coverage to promote HPV vaccination uptake for states represented under the lowest trajectory pattern.

Tobacco and estrogen metabolic polymorphisms and risk of non-small cell lung cancer in women.

To explore the potential role for estrogen in lung cancer susceptibility, candidate single-nucleotide polymorphism (SNPs) in tobacco and estrogen metabolism genes were evaluated. Population-based cases (n = 504) included women aged 18-74, diagnosed with NSCLC in metropolitan Detroit between November 2001 and October 2005. Population-based controls (n = 527) were identified through random digit dialing and matched on race and age. Eleven SNPs in 10 different genes were examined in relation to risk: CYP1A1 Msp1, CYP1A1 Ile462Val, CYP1B1 Leu432Val, CYP17, CYP19A1, XRCC1 Gln399Arg, COMT Val158Met, NQO1 Pro187Ser, GSTM1, GSTT1 and GSTP1 Ile105Val. Lung cancer risk associated with individual SNPs was seen for GSTP1 [A allele; odds ratio (OR) = 1.85; 95% confidence interval (CI), 1.04-3.27] and XRCC1 (A/A genotype; OR = 1.68; 95% CI, 1.01-2.79) in white women and CYP1B1 (G allele; OR = 11.1; 95% CI, 1.18-104) in black women smokers. White women smokers carrying two risk genotypes at the following loci were at increased risk of lung cancer compared with individuals not carrying risk alleles at these loci: CYP17 and GSTM1, COMT and GSTM1, CYP17 and GSTT1, XRCC1 and GSTP1, CYP1B1 and XRCC1 and COMT and XRCC1. The most parsimonious model of lung cancer risk in white smoking women included age, family history of lung cancer, history of chronic lung disease, pack-years, body mass index, XRCC1 A/A genotype, GSTM1 null and COMT A/G or G/G genotype. These findings support the need for continued study of estrogen in relation to lung cancer risk. Polymorphisms in the tobacco metabolism, estrogen metabolism and DNA repair pathways will be useful in developing more predictive models of individual risk.

Widespread microbial invasion of the chorioamniotic membranes is a consequence and not a cause of intra-amniotic infection.

Acute chorioamnionitis is a response to amniotic fluid (AF) infection. However, it remains unclear whether substantial bacterial propagation in the chorioamniotic membranes (CAMs) precedes microbial invasion of the amniotic cavity (MIAC), which is inconsistent with characteristic 'amniotropic neutrophil migration' in acute chorioamnionitis. This study was performed to determine whether CAMs have widespread bacterial infection during MIAC and whether bacteria normally colonize CAMs. AF pellets and CAMs from the following groups were studied: group 1, patients with positive (n=18) or negative (n=22) AF cultures; group 2, patients with or without acute chorioamnionitis in which the amnion and chorion were studied separately (n=60); and group 3, patients at term who underwent a cesarean delivery (n=30). SYTO 9/propidium iodide fluorescent staining and fluorescent in situ hybridization for 16S rRNA were performed. Real-time quantitative PCR for 16S rDNA and PCR for genital mycoplasmas were also conducted. Bacteria were more frequently detected in AF than in CAMs of patients with positive AF culture (100 vs. 33%; P<0.0001). Bacteria were detected more frequently in CAMs as the severity of chorioamnionitis increased (P<0.01). The median 16S rRNA gene copy number in the amnion was significantly greater than in the chorion (group 2; P<0.0001). Bacteria were not detected in CAMs or AF in women at term before labor (group 3). A fraction of patients with chorioamnionitis or MIAC did not have bacteria in CAMs. Collectively, the findings herein indicate that MIAC does not follow widespread infection of CAMs, but precedes it. We propose a model of MIAC: the initial stage is intra-amniotic bacterial invasion through a discrete region of the CAMs, followed by intra-amniotic proliferation, and bacterial invasion of CAMs primarily extends from the amniotic fluid. This study emphasizes the importance of assessing the intra-amniotic compartment for diagnosis and treatment of preterm birth.

Organized Social Activity, Physical Exercise, and the Risk of Insomnia Symptoms Among Community-Dwelling Older Adults.

Objectives: To compare the risk of insomnia symptoms among community-dwelling older adults who participated and did not participate in organized social activity and physical exercise. Design: Secondary data analysis of a prospective cohort study. Material and Methods: Community-dwelling older adults ≥65 years of age with no insomnia symptoms at baseline were included in the study. Participants were followed up yearly for 3 years. Insomnia symptoms, social activity, and physical exercise status of study participants were assessed at baseline and during follow-up. Results: Study participants who reported engaging in organized social activity and low-intensity physical exercise and organized social activity and high-intensity physical exercise were less likely to report insomnia symptoms during follow-up compared with those who did not engage in any activity. Conclusion: These results suggest beneficial effect of organized social activity and physical exercise in maintaining sleep quality in old age.

Validity of a Food and Fluid Exercise Questionnaire for Macronutrient Intake during Exercise against Observations.

Information about the accuracy of self-reported food and fluid intake during competitions is scarce. The objective of this study was to validate a previously developed food and fluid exercise questionnaire (FFEQ) against direct observations made during competitions in athletes. Fifty-eight recreational endurance athletes participating in four different running events and one cross duathlon in the Netherlands between 2015 and 2017 were recruited. The FFEQ overestimated the median energy and carbohydrate intake by 27.6 kcal/h (20.6%) and 9.25 g/h (30.8%) (p < 0.001), respectively, compared to direct observation. Reporting bias (i.e., correlation between the difference between methods and average of both methods) increased with a higher energy (r: 0.41, p < 0.01) and carbohydrate intake (r: 0.44, p < 0.01). No statistically significant difference was found between FFEQ-reported fluid intake per hour and observations (median difference: -2.93 mL, -1.1%; p = 0.48) and no fluid reporting bias was identified (r: 0.23, p = 0.08). FFEQ-reported energy (r: 0.74), carbohydrate (r: 0.74), and fluid (r: 0.85) intake was strongly correlated with the observed intake (all p-values < 0.001). In conclusion, the FFEQ accurately estimates the fluid intake on a group level during competitions in recreational athletes. Even though FFEQ overestimates the energy and carbohydrate intake, it is still a useful tool for ranking individuals based on their intake.

Smartphone-Based Meditation for Myeloproliferative Neoplasm Patients: Feasibility Study to Inform Future Trials.

BACKGROUND: Myeloproliferative neoplasm (MPN) patients often report high symptom burden that persists despite the best available pharmacologic therapy. Meditation has gained popularity in recent decades as a way to manage cancer patient symptoms. OBJECTIVE: The aim of this study was to examine the feasibility of 2 different consumer-based meditation smartphone apps in MPN patients and to examine the limited efficacy of smartphone-based meditation on symptoms compared with an educational control group. METHODS: Patients (n=128) were recruited nationally through organizational partners and social media. Eligible and consented patients were enrolled into 1 of 4 groups, 2 of which received varying orders of 2 consumer-based apps (10% Happier and Calm) and 2 that received one of the apps alone for the second 4 weeks of the 8-week intervention after an educational control condition. Participants were asked to perform 10 min of meditation per day irrespective of the app and the order in which they received the apps. Feasibility outcomes were measured at weeks 5 and 9 with a Web-based survey. Feasibility outcomes were acceptability, demand, and limited efficacy for depression, anxiety, pain intensity, sleep disturbance, sexual function, quality of life, global health, and total symptom burden. RESULTS: A total of 128 patients were enrolled across all 4 groups, with 73.4% (94/128) patients completing the intervention. Of the participants who completed the 10% Happier app, 61% (46/76) enjoyed it, 66% (50/76) were satisfied with the content, and 77% (59/76) would recommend to others. Of those who completed the Calm app, 83% (56/68) enjoyed it, 84% (57/68) were satisfied with the content, and 97% (66/68) would recommend to others. Of those who completed the educational control, 91% (56/61) read it, 87% (53/61) enjoyed it, and 71% (43/61) learned something. Participants who completed the 10% Happier app averaged 31 (SD 33) min/week; patients completing the Calm app averaged 71 (SD 74) min/week. 10% Happier app participants saw small effects on anxiety (P<.001 d=-0.43), depression (P=.02; d=-0.38), sleep disturbance (P=.01; d=-0.40), total symptom burden (P=.13; d=-0.27), and fatigue (P=.06; d=-0.30), and moderate effects on physical health (P<.001; d=0.52). Calm app participants saw small effects on anxiety (P=.29; d=-0.22), depression (P=.09; d=-0.29), sleep disturbance (P=.002; d=-0.47), physical health (P=.005; d=0.44), total symptom burden (P=.13; d=-0.27), and fatigue (P=.13; d=-0.27). Educational control participants (n=61) did not have effects on any patient-reported outcome except for a moderate effect on physical health (P<.001; d=0.77). CONCLUSIONS: Delivering meditation via the Calm app is feasible and scored higher in terms of feasibility when compared with the 10% Happier app. The Calm app will be used to implement a randomized controlled trial, testing the effects of meditation on symptom burden in MPNs. TRIAL REGISTRATION: ClinicalTrials.gov NCT03726944; https://clinicaltrials.gov/ct2/show/NCT03726944 (Archived by WebCite at http://www.webcitation.org/77MVdFJwM).