Study Time Points Research Articles

Associations of Low-Inflammatory Dietary Patterns With Psychological Health and Wellbeing During Weight Loss in Military Family Dependents

ObjectivesEmerging evidence suggests that anti-inflammatory dietary patterns may improve depression, stress, and quality of life. Similar benefits are observed during weight loss interventions; however, the effect of combining these dietary patterns with weight loss is not clear. We evaluated the association between dietary inflammation and measures of psychological health in female military dependents with overweight and obesity during a behavioral weight loss intervention. MethodsParticipants (n = 120) received a 6-month intervention recommending dietary patterns with an anti-inflammatory profile. An energy-adjusted dietary inflammatory index (DII) score was calculated from 28 food components collected using 3 interviewer-administered multiple-pass 24-hour recalls at each study time point. A negative score indicates a lower-inflammatory dietary pattern, and a positive score indicates a pro-inflammatory pattern. Self-reported symptoms of depression, stress, general health, vitality, and psychological quality of life were measured by validated questionnaires. Multivariable linear mixed models were used to assess the association between 6-month changes in DII and each outcome and were adjusted for age, ethnicity, military rank of spouse, body weight, and physical activity. ResultsOn average, females were 42.2 ± 11.8 years old with a body mass index of 34.9 ± 6.4 kg/m2. The average DII score was 0.07 (range: –4.3, 3.0) at baseline. Six-month improvements in DII scores (i.e., for a 1-unit reduction) were associated with fewer self-reported symptoms of depression (β: –0.87; 95% confidence interval: –1.43, –0.31; P = 0.003) and stress (–0.85; –1.44, –0.26; P = 0.005), as well as higher general health (0.57; 0.23, 0.91; P = 0.001), vitality (0.45; 0.12, 0.77; P = 0.008), and psychological quality of life (0.33; 0.11, 0.55; P = 0.004). No significant associations between weight loss or physical activity and any outcome were observed in these models that included the DII. ConclusionsAnti-inflammatory dietary patterns are associated with beneficial effects on a range of psychological health and wellbeing measures independent of weight loss. Funding SourcesJean Mayer USDA Human Nutrition Research Center on Aging Doctoral Scholarship; Department of Defense (DoD) grant W81XWH-14–2-0005 (SBR). Author views do not reflect official DoD or Army policy.

Wide range of applications for machine-learning prediction models in orthopedic surgical outcome: a systematic review

Background and purpose — Advancements in software and hardware have enabled the rise of clinical prediction models based on machine learning (ML) in orthopedic surgery. Given their growing popularity and their likely implementation in clinical practice we evaluated which outcomes these new models have focused on and what methodologies are being employed. Material and methods — We performed a systematic search in PubMed, Embase, and Cochrane Library for studies published up to June 18, 2020. Studies reporting on non-ML prediction models or non-orthopedic outcomes were excluded. After screening 7,138 studies, 59 studies reporting on 77 prediction models were included. We extracted data regarding outcome, study design, and reported performance metrics. Results — Of the 77 identified ML prediction models the most commonly reported outcome domain was medical management (17/77). Spinal surgery was the most commonly involved orthopedic subspecialty (28/77). The most frequently employed algorithm was neural networks (42/77). Median size of datasets was 5,507 (IQR 635–26,364). The median area under the curve (AUC) was 0.80 (IQR 0.73–0.86). Calibration was reported for 26 of the models and 14 provided decision-curve analysis. Interpretation — ML prediction models have been developed for a wide variety of topics in orthopedics. Topics regarding medical management were the most commonly studied. Heterogeneity between studies is based on study size, algorithm, and time-point of outcome. Calibration and decision-curve analysis were generally poorly reported.

Milk Intake Enhances Cerebral Antioxidant (Glutathione) Concentration in Older Adults: A Randomized Controlled Intervention Study

ObjectivesThis randomized controlled trial was to confirm the potential benefit of adequate dairy food intake to raise brain antioxidant, glutathione (GSH), in low dairy consumers through a longitudinal dietary intervention. This confirmatory study is based on our previous findings of positive correlations between brain GSH levels and dairy food consumption, particularly milk (P < 0.001), in a cross-sectional study of older adults. MethodsA total of 80 older adults with a low dairy intake (≤1.5 servings/day) were enrolled in a 3-month milk intervention study. Brain GSH levels were measured using multiple quantum chemical shift imaging at 3 T. After baseline MR scans, participants were randomized into either the intervention or control group using a random-sequence algorithm. The control group continued their usual intake of dairy ≤1.5 servings/day (<1 cup of milk/day) while the milk intervention group was provided 1% milk weekly and instructed to consume 3 cups of milk/day for three months. Dietary intake was assessed with 24-hr diet recalls, 7-day food records, and a Diet Screener Questionnaire and was analyzed using NDSR software. Brain GSH levels in each group were compared between baseline and post-intervention using paired t-tests, and longitudinal changes of GSH levels were compared between groups using two sample t-tests. ResultsAmong 80 enrolled participants (60–89 years old), 66 participants (49 intervention; 17 controls) completed the study. The milk intake of the controls was similar at baseline and the end of study timepoints (0.4 ± 0.4 cups/day for both), while that of the intervention group increased from 0.2 ± 0.3 cups/day to 3.0 ± 0.6 cups/day (P < 0.001). The intervention group showed 7.4 ± 11.7% increases in parietal GSH (P < 0.001) and 4.6 ± 8.7% increases in fronto-parietal GSH (P = 0.003) levels after intervention, while the control group showed no changes in brain GSH. The fronto-parietal GSH increase in the intervention group was greater than that of the control group (P < 0.05). ConclusionsDietary milk consumption could modulate brain GSH levels. This study demonstrates the effect of diet on brain antioxidants, which could lead to the development of new strategies in strengthening cerebral antioxidant defenses and thereby improving brain health in the aging population. Funding SourcesNational Dairy Council.

DOP27 The fibre fermentative capacity of the gut microbiota is diminished in children with Crohn’s Disease and it is independent of disease activity or treatment with exclusive enteral nutrition

Abstract Background Induction of clinical remission with exclusive enteral nutrition (EEN), has been associated with accompanying changes in the concentration of short chain fatty acids (SCFA) (a biomarker of fibre fermentation) in faeces of children with Crohn’s disease (CD) 1. Here, we assessed the fibre fermentative capacity of the gut microbiota of children with active CD in vitro, before, during and after EEN and compared with healthy children. Methods 44 faecal samples from 14 children (female, n=7, age, median [Q1, Q3]: 14.1 [11.1, 15.1] years) with active CD were collected before, during (4 weeks) and at the end of EEN (8 weeks) and after food reintroduction (median [Q1, Q3]: 21 [16, 31] days post-EEN). All children had achieved clinical remission at the end of EEN (weighted Paediatric Crohn’s Disease Activity Index &amp;lt;12.5). A single faecal sample was collected from 11 healthy children (female, n=4, age, median [Q1, Q3]: 12.4 [9.6, 13.0] years). 24-hour in vitro batch fermentations were performed using 4 fibre substrates (pectin, high-resistant maize starch, wheat bran and a mixture of the three). Net production of SCFA was measured with gas chromatography. Results Compared to healthy children, the total production of SCFA was significantly lower in children with CD, for all 4 fibre substrates, and regardless of the study timepoint (Figure 1). Net production of SCFA remained unchanged during EEN and at food reintroduction, and for all fibre substrates (Figure 1). No significant association with levels of faecal calprotectin was observed at any of the timepoints. Acetate production was significantly lower in children with CD compared to healthy children for all fibre substrates except for resistant maize starch (Figure 1). Likewise, except for pectin, production of butyrate was significantly lower in children with CD than healthy controls (Figure 1). Production of propionate did not significantly differ between any of the groups. Legend: Production of SCFA after 24-hour in vitro fermentation of faecal samples from CD and healthy children. Asterisks indicate significant differences. A: before EEN, B: 4-week EEN, C: End of EEN, D: Food reintroduction, HC: Healthy children Conclusion Fibre fermentative capacity is independent of disease activity in patients with CD and remains lower compared to healthy controls. It might be unlikely that the mechanism of action of EEN is mediated by modulation of fibre fermenting bacteria. Reference 1. Gerasimidis K, Bertz M, Hanske L, Junick J, Biskou O, Aguilera M, et al. Decline in presumptively protective gut bacterial species and metabolites are paradoxically associated with disease improvement in pediatric Crohn’s disease during enteral nutrition. Inflamm Bowel Dis. 2014;20(5):861–71.

Graphical representations of patient tolerability data: Recommendations from the National Cancer Institute (NCI) Cancer Moonshot Standardization Working Group.

e18612 Background: Effective communication of treatment tolerability data is essential for clinical decision making and improved patient outcomes, yet standardized approaches to the analysis and visualization of tolerability data in cancer clinical trials are currently limited. To address this need, the Standardization Working Group (SWG) was established within the NCI Cancer Moonshot Tolerability Consortium. This abstract describes the SWG’s initiative to develop a publicly accessible online toolkit with a comprehensive set of guidelines, references, and resources for graphical displays of tolerability data. Methods: A multidisciplinary group of PRO researchers including biostatisticians, clinicians, epidemiologists, and representatives from the NCI and FDA convened monthly to discuss toolkit development and content. Considerations for standardization of graphical displays of tolerability data included (1) types of graphical displays, (2) incorporation of missing data, (3) labeling and color schemes, and (4) software to produce graphical displays. For consistency, considerations of tolerability relied on the Patient-Reported Outcomes version of the CTCAE (PRO-CTCAE), which includes 124 items assessing the frequency, severity, interference, and/or presence of 78 symptomatic adverse events. Graphical displays were generated using simulated PRO-CTCAE data and summarized by composite score (range 0-3).Color schemes that were Section 508 compliant and color blindness accessible were created. Surveys were distributed to 68 consortium members to assess preferences and interpretability of the graphical displays. Results: The SWG created graphical displays for PRO-CTCAE data, including bar charts, butterfly plots, and Sankey diagrams and compiled SAS macros and R functions to do so. Graphical displays made available in the toolkit maximize the use of PRO-CTCAE data, incorporate missingness, support between-arm comparisons, and present data longitudinally over treatment cycles or study timepoints. Survey results for labeling and color schemes were summarized and informed a list of short labels for PRO-CTCAE items (e.g., “radiation burns” for “skin burns from radiation”) and standardized color schemes for use in graphical displays. Survey results were also summarized to provide insight into PRO researchers’ ability to accurately interpret the graphical displays. Conclusions: Standardizinggraphical displays is important for improving the communication and interpretation of tolerability data. The type of graphical display used depends on the purpose of the analysis and should be tailored to the intended audience, including patients. This toolkit will provide a comprehensive resource with best practice recommendations.

Hypothalamic-pituitary-adrenal axis attenuation and obesity risk in sexually abused females

BackgroundChildhood sexual abuse (CSA) confers elevated risks for obesity in females. Mechanisms that explain this link remain unclear. This study tracked serum basal cortisol levels with body mass index (BMI) from childhood into adulthood to test whether hypothalamic-pituitary-adrenal (HPA) axis attenuation accounts for elevated obesity risks for sexually abused females. MethodsData drew from six timepoints of a longitudinal study of the impact of CSA on development. Participants were females aged 6–16 years at time of study enrollment with substantiated CSA and demographically matched non-abused peers. Analyses included only participants who did not have obesity at study enrollment. Main outcomes were BMI growth trajectories across ages 6–27 (n = 150; 66 abused, 84 comparisons) and early adulthood obesity status (ages 20–27; n = 133; 62 abused, 71 comparison). HPA axis functioning indicators were intercept and linear slope parameters extracted from multilevel growth trajectories of serum basal cortisol levels across development. Racial-ethnic minority status, parity, steroid medication use, depression history and disordered eating history were covaried. ResultsWhile controlling for covariates, multilevel modeling indicated that high initial serum basal cortisol levels in childhood and attenuated cortisol growth rate over time (i.e., HPA axis attenuation) were associated with accelerated BMI accumulation (p < .01). Attenuated cortisol growth rate mediated the effect of CSA on accelerated BMI accumulation and on elevated adulthood obesity rates (p < .05). ConclusionThis work establishes a mechanistic association between HPA axis attenuation and obesity, suggesting that trauma treatments for abuse survivors should include interventions that reduce health consequences associated with dysregulated stress physiology.

Concentration-QTc analysis with two or more correlated baselines.

The relationship between drug concentration and QTc interval is typically evaluated by applying the standard analysis model proposed in a scientific whitepaper by Garnett et al. ( https://doi.org/10.1007/s10928-017-9558-5 ). The model is a mixed effects model in which a baseline QTc interval is included as a covariate. Two or more baseline QTc intervals are sometimes observed for a study participant, such as time-matched baselines on a baseline day in parallel studies, or pre-dose baselines in each period in crossover studies. In such situations, the baseline adjustments are not straightforward because these baselines correlate with not only the corresponding QTc intervals after drug administration, but also other QTc intervals at different timepoints for parallel studies, or those in different periods for crossover studies. In this study, we compared three analysis models through simulations and clinical study examples in settings in which two or more baselines were observed for a subject. We compared a model without baseline adjustment, a model with baseline adjustment, and a model in which baseline and baseline mean were included as covariates. In the simulations and clinical study examples, the model with baseline and baseline mean as covariates demonstrated higher accuracy and power than the other models. This model assumed a specific covariance structure in QTc intervals, which well approximated the correlations between QTc intervals within and between days. When there are two or more baselines in concentration-QTc analyses, the baseline mean should be included as a covariate in addition to the corresponding baseline.

Clinical and biochemical effect of laser as an adjunct to non-surgical treatment of chronic periodontitis.

ObjectivesTo evaluate the clinical and biochemical efficacy of laser therapy as an adjunct to non‐surgical treatment in chronic periodontitis.MethodsA systematic search was performed through the PubMed, EMBASE, and Cochrane Library for eligible articles published as of May 2, 2020, supplemented by information search in the System for Information on Programme Literature in Europe and a manual literature search. Only randomized controlled trials (RCTs) used to compare the adjunctive use of laser and non‐surgical treatment alone with an observation period of at least 6 months were included.ResultsSixteen RCTs with a total of 525 subjects were included. Meta‐analysis suggested that the additional use of laser to scaling and root planing (SRP) showed significant superiority over SRP alone among most of clinical parameters involved. Regarding the GCF, although volume in the laser group was lower at week 4 and 12, no significant difference was found regarding the cytokines level. Subgroup analysis revealed that the combined therapy produced no significant difference in PD, CAL and PI at most time points for studies in respect to smokers. No treatment‐related adverse events had been reported in the included studies.ConclusionsPooled analysis suggested that laser‐assisted non‐surgical treatment improved clinical outcome to SRP alone in the management of non‐smoking chronic periodontitis patients.

121 Behavioral Attention Relationships Vary Between Demographic Groups Across Sleep Loss and Recovery

Abstract Introduction The Psychomotor Vigilance Test (PVT) is a behavioral attention measure widely used to describe sleep loss deficits. Although there are reported differences in PVT performance for various demographic groups, no study has examined the relationship between measures on the 10-minute PVT (PVT10) and the 3-minute PVT (PVT3) within sex, age, and body mass index (BMI) groups throughout a highly controlled sleep deprivation study. Methods Forty-one healthy adults (mean±SD ages, 33.9±8.9y) participated in a 13-night experiment [2 baseline nights (10h-12h time in bed, TIB) followed by 5 sleep restriction (SR1-5) nights (4h TIB), 4 recovery nights (R1-R4; 12h TIB), and 36h total sleep deprivation (TSD)]. A neurobehavioral test battery, including the PVT10 and PVT3 was completed every 2h during wakefulness. Repeated measures correlation (rmcorr) compared PVT10 and PVT3 lapses (reaction time [RT] &amp;gt;355ms [PVT3] and &amp;gt;500ms [PVT10]) and response speed (1/RT) by examining correlations by day (e.g., baseline day 2) and time point (e.g., 1000h-2000h) within sex groups (18 females), within age groups defined by a median split (median=32, range=21-49y), and within BMI groups defined by a median split (median=25, range=17-31). Results PVT10 and PVT3 1/RT was significantly correlated at all study days and time points excluding at baseline for the younger group and at R2 for the higher BMI group. PVT10 and PVT3 lapses showed overall lower correlations across the study relative to 1/RT. Lapses were not significantly correlated at baseline for any group, for males across recovery (R1-R4), for the high BMI group at R2-R4, for the older group at R2-R3, or for the younger group at SR5 or R3. Conclusion Differentiating participants based on age, sex, or BMI revealed important variation in the relationship between PVT10 and PVT3 measures across the study. Surprisingly, lapses were not significantly correlated at baseline for any demographic group or across recovery for males or the high BMI or older group. Thus, PVT10 and PVT3 lapses may be less comparable in certain populations when well-rested. These findings add to a growing literature suggesting demographic factors may be important factors to consider when evaluating the effects of sleep loss. Support (if any) ONR Award N00014-11-1-0361;NIH UL1TR000003;NASA NNX14AN49G and 80NSSC20K0243; NIHR01DK117488

In Vivo Analysis of the Biocompatibility and Bone Healing Capacity of a Novel Bone Grafting Material Combined with Hyaluronic Acid.

The present in vivo study analyses both the inflammatory tissue reactions and the bone healing capacity of a newly developed bone substitute material (BSM) based on xenogeneic bone substitute granules combined with hyaluronate (HY) as a water-binding molecule. The results of the hyaluronate containing bone substitute material (BSM) were compared to a control xenogeneic BSM of the same chemical composition and a sham operation group up to 16 weeks post implantationem. A major focus of the study was to analyze the residual hyaluronate and its effects on the material-dependent healing behavior and the inflammatory tissue responses. The study included 63 male Wistar rats using the calvaria implantation model for 2, 8, and 16 weeks post implantationem. Established and Good Laboratory Practice (GLP)-conforming histological, histopathological, and histomorphometrical analysis methods were conducted. The results showed that the new hyaluronate containing BSM was gradually integrated within newly formed bone up to the end of the study that ended in a condition of complete bone defect healing. Thereby, no differences to the healing capacity of the control BSM were found. However, the bone formation in both groups was continuously significantly higher compared to the sham operation group. Additionally, no differences in the (inflammatory) tissue response that was analyzed via qualitative and (semi-) quantitative methods were found. Interestingly, no differences were found between the numbers of pro- and anti-inflammatory macrophages between the three study groups over the entire course of the study. No signs of the HY as a water-binding part of the BSM were histologically detectable at any of the study time points, altogether the results of the present study show that HY allows for an optimal material-associated bone tissue healing comparable to the control xenogeneic BSM. The added HY seems to be degraded within a very short time period of less than 2 weeks so that the remaining BSM granules allow for a gradual osteoconductive bone regeneration. Additionally, no differences between the inflammatory tissue reactions in both material groups and the sham operation group were found. Thus, the new hyaluronate containing xenogeneic BSM and also the control BSM have been shown to be fully biocompatible without any differences regarding bone regeneration.

Self-Efficacy and Motivation to Quit of Smokers Seeking to Quit: Quantitative Assessment of Smoking Cessation Mobile Apps.

BackgroundDecreasing trends in the number of individuals accessing face-to-face support are leaving a significant gap in the treatment options for smokers seeking to quit. Face-to-face behavioral support and other interventions attempt to target psychological factors such as the self-efficacy and motivation to quit of smokers, as these factors are associated with an increased likelihood of making quit attempts and successfully quitting. Although digital interventions, such as smoking cessation mobile apps, could provide a promising avenue to bridge the growing treatment gap, little is known about their impact on psychological factors that are vital for smoking cessation.ObjectiveThis study aims to better understand the possible impact of smoking cessation mobile apps on important factors for successful cessation, such as self-efficacy and motivation to quit. Our aim is to assess the self-efficacy and motivation to quit levels of smokers before and after the use of smoking cessation mobile apps.MethodsSmokers seeking to quit were recruited to participate in a 4-week app-based study. After screening, eligible participants were asked to use a mobile app (Kwit or Quit Genius). The smoking self-efficacy questionnaire and the motivation to stop smoking scale were used to measure the self-efficacy and motivation to quit, respectively. Both were assessed at baseline (before app use), midstudy (2 weeks after app use), and end-study (4 weeks after app use). Paired sample two-tailed t tests were used to investigate whether differences in self-efficacy and motivation between study time points were statistically significant. Linear regression models investigated associations between change in self-efficacy and change in motivation to quit before and after app use with age, gender, and nicotine dependence.ResultsA total of 116 participants completed the study, with the majority being male (71/116, 61.2%), employed (76/116, 65.6%), single (77/116, 66.4%), and highly educated (87/116, 75.0%). A large proportion of participants had a low to moderate dependence on nicotine (107/116, 92.2%). A statistically significant increase of 5.09 points (95% CI 1.83-8.34) from 37.38 points at baseline in self-efficacy was found at the end of the study. Statistically significant increases were also found for the subcomponents of self-efficacy (intrinsic and extrinsic self-efficacies). Similarly, a statistically significant increase of 0.38 points (95% CI 0.06-0.70) from 5.94 points at baseline in motivation to quit was found at the end of the study. Gender, age, and nicotine dependence were not statistically significantly associated with changes in self-efficacy and motivation to quit.ConclusionsThe assessed mobile apps positively impacted the self-efficacy and motivation to quit of smokers making quit attempts. This has important implications on the possible future use of digitalized interventions and how they could influence important psychological factors for quitting such as self-efficacy and motivation. However, further research is needed to assess whether digital interventions can supplement or replace traditional forms of therapy.

Changes in community knowledge and attitudes related to female genital fistula following the implementation of a multi-component intervention in Nigeria and Uganda

Background Despite well-documented individual-level barriers to fistula care access including limited awareness, psychosocial deterrents, and contextual factors, less is known about how these factors manifest and operate at community level. Social normative community perspectives – their knowledge, attitudes and actions in relation to women living with fistula – can offer insight into this mechanism. Our study describes changes in fistula knowledge and attitudes toward those living with fistula among community members in Nigeria and Uganda following implementation of a multi-component intervention addressing treatment barriers. Methods This study adopts a pre-post qualitative design with a comparison site and draws on focus group discussions with female and male community members from three sites in Nigeria and Uganda. Transcripts were analyzed for passages presenting community knowledge and attitudes related to fistula and perceptions of women living with fistula. Summary memos were developed and used to compare viewpoints across study sites and time points and between men and women. Results Community members demonstrated basic knowledge of symptoms of fistula and mixed understanding of its causes; prolonged obstructed labor and iatrogenic causes were most known. Myths and misconceptions around fistula causes commonly relate to incorrect biomedical understanding, witchcraft, and promiscuity. To varying degrees, fistula cause knowledge increased, and misinformation decreased among endline intervention groups with less observed change in endline comparison groups. Awareness that fistula can be surgically repaired free of charge at fistula centers varied across study regions, with higher awareness among individuals who personally knew someone who experienced repair at a center. Although community members at baseline and endline perceive shame and stigma as affecting women living with fistula, community attitudes toward these women show an increase in empathy at endline in intervention areas. Conclusions Community empathy and willingness to help women living with fistula, coupled with reduction in misinformation regarding fistula, its cause and how to access treatment, is an incremental outcome associated with the implementation of a multi-component intervention to address treatment barriers. However, findings reveal that social and behavioral change happens slowly and that further programmatic research on society-targeted approaches emphasizing comprehensive community understanding of fistula and stigma reduction is needed.

Urban air pollution induces alterations in redox metabolism and mitochondrial dysfunction in mice brain cortex

Previous reports indicate that the central nervous system (CNS) is a target of air pollution, causing tissue damage and functional alterations. Oxidative stress and neuroinflammation have been pointed out as possible mechanisms mediating these effects. The aim of this work was to study the chronic effects of urban air pollution on mice brain cortex, focusing on oxidative stress markers, and mitochondrial function. Male 8-week-old BALB/c mice were exposed to filtered air (FA, control) or urban air (UA) inside whole-body exposure chambers, located in a highly polluted area of Buenos Aires city, for up to 4 weeks. Glutathione levels, assessed as GSH/GSSG ratio, were decreased after 1 and 2 weeks of exposure to UA (45% and 25% respectively vs. FA; p < 0.05). A 38% increase in lipid peroxidation was found after 1 week of UA exposure (p < 0.05). Regarding protein oxidation, carbonyl content was significantly increased at week 2 in UA-exposed mice, compared to FA-group, and an even higher increment was found after 4 weeks of exposure (week 2: 40% p < 0.05, week 4: 54% p < 0.001). NADPH oxidase (NOX) and glutathione peroxidase (GPx) activities were augmented at all the studied time points, while superoxide dismutase (Cu,Zn-SOD cytosolic isoform) and glutathione reductase (GR) activities were increased only after 4 weeks of UA exposure (p < 0.05). The increased NOX activity was accompanied with higher expression levels of NOX2 regulatory subunit p47phox, and NOX4 (p < 0.05). Also, UA mice showed impaired mitochondrial function due to a 50% reduction in O2 consumption in active state respiration (p < 0.05), a 29% decrease in mitochondrial inner membrane potential (p < 0.05), a 65% decrease in ATP production rate (p < 0.01) and a 30% increase in H2O2 production (p < 0.01). Moreover, respiratory complexes I-III and II-III activities were decreased in UA group (30% and 36% respectively vs. FA; p < 0.05). UA exposed mice showed alterations in mitochondrial function, increased oxidant production evidenced by NOX activation, macromolecules damage and the onset of the enzymatic antioxidant system. These data indicate that oxidative stress and impaired mitochondrial function may play a key role in CNS damage mechanisms triggered by air pollution.

Topical Imiquimod Does Not Provide an Adjuvant Effect When Administered With Inactivated Influenza A/H5N1 Vaccine in Healthy Young Adults.

Safe, effective, and easy to deploy adjuvants are needed for influenza prepandemic preparedness. Based on recent reports, we hypothesized that preapplication of topical imiquimod followed by intradermal (ID) vaccination with monovalent inactivated influenza A/H5N1 vaccine (MIV A/H5N1) results in improved serologic responses. We randomized 50 healthy adults in a 1:1 ratio to receive topical imiquimod (group 1) or control cream (group 2) followed by ID injection of 9 µg of the hemagglutinin MIV A/H5N1 in 2 doses, 21 days apart. Subjects were followed for safety and serologic responses as measured by the hemagglutination inhibition (HAI) and microneutralization (MN) assays. Solicited and unsolicited adverse events were comparable between groups 1 and 2, and were mostly mild to moderate in severity. At 21 days after dose 2, the geometric mean titers (GMTs) of HAI antibodies against the vaccine strain were 16.2 and 24.3 in groups 1 and 2, respectively. The MN antibody GMTs were 9.3 and 10.7 in groups 1 and 2, respectively. There were no significant differences in antibody levels between groups at study time points. Topical imiquimod administration combined with ID MIV A/H5N1 was safe but did not result in improved serologic responses to the vaccine.Clinical Trials Registration. NCT03472976.

Effect of Dexmedetomidine on Blood Pressure in Hypertension Patients after Emergency Laparotomy for Trauma: A Randomized Double-blind Clinical Trial

Background: Patients with a history of hypertension experience higher postoperative complications than healthy individuals. The frequency of such complications is also higher in emergency patients than elective ones; therefore, it seems that preventive measures are essential. Objectives: The present study aimed at determining the effect of dexmedetomidine on blood pressure in patients with hypertension after emergency laparotomy for trauma. Methods: The present study was a randomized, double-blind clinical trial performed from 2019 to 2020 on patients with a history of hypertension undergoing emergency laparotomy. Patients received the intervention 15 minutes before surgery (the intervention group: intravenous (iv) dexmedetomidine and the control group: normal saline), and the intensity of the pain(VAS), agitation(RASS), and blood pressure were measured and compared at different time points. Data were compared using SPSS software (version 21) by t-test and Chi-square tests considering a significance level of <0.05. Results: There were statistically significant differences between the two groups just after the drug infusion and at all studied time points (p <0.05), so that the intervention group had more stable blood pressure. Pain intensity (p <0.05) and the degree of agitation (p <0.05) in the intervention group were significantly lower than that in the control group at all studied time points. Conclusion: Dexmedetomidine infusion leads to a stabilization of blood pressure during surgery and after surgery, pain relief, and agitation in patients with hypertension undergoing emergency laparotomy for trauma.

Probiotic stool secretory immunoglobulin A modulation in children with gastroenteritis: a randomized clinical trial

ABSTRACTBackgroundWe previously conducted the Probiotic Regimen for Outpatient Gastroenteritis Utility of Treatment (PROGUT) study, which identified no improvements in children with acute gastroenteritis (AGE) administered a probiotic. However, the aforementioned study did not evaluate immunomodulatory benefits.ObjectivesThe object of this study was to determine if stool secretory immunoglobulin A (sIgA) concentrations in children with AGE increase more among participants administered a Lactobacillus rhamnosus/helveticus probiotic compared with those administered placebo.MethodsThis a priori planned multicenter, randomized, double-blinded, placebo-controlled ancillary study enrolled children presenting for emergency care who received a 5-d probiotic or placebo course. Participants submitted stool specimens on days 0, 5, and 28. The primary endpoint was the change in stool sIgA concentrations on day 5 compared with baseline.ResultsA total of 133 (n = 66 probiotic, 67 placebo) of 886 PROGUT participants (15.0%) provided all 3 specimens. Median stool sIgA concentrations did not differ between the probiotic and placebo groups at any of the study time points: day 0 median (IQR): 1999 (768, 4071) compared with 2198 (702, 5278) (P = 0.27, Cohen's d = 0.17); day 5: 2505 (1111, 5310) compared with 3207 (982, 7080) (P = 0.19, Cohen's d = 0.16); and day 28: 1377 (697, 2248) compared with 1779 (660, 3977) (P = 0.27, Cohen's d = 0.19), respectively. When comparing measured sIgA concentrations between days 0 and 5, we found no treatment allocation effects [β: −0.24 (−0.65, 0.18); P = 0.26] or interaction between treatment and specimen collection day [β: −0.003 (−0.09, 0.09); P = 0.95]. Although stool sIgA decreased between day 5 and day 28 within both groups (P < 0.001), there were no differences between the probiotic and placebo groups in the median changes in sIgA concentrations when comparing day 0 to day 5 median (IQR) [500 (−1135, 2362) compared with 362 (−1122, 4256); P = 0.77, Cohen's d = 0.075] and day 5 to day 28 [−1035 (−3130, 499) compared with −1260 (−4437, 843); P = 0.70, Cohen's d = 0.067], respectively.ConclusionsWe found no effect of an L. rhamnosus/helveticus probiotic, relative to placebo, on stool IgA concentrations. This trial was registered at clinicaltrials.gov as NCT01853124.

The effect of a performing arts intervention on caregivers of people with mild to moderately severe dementia

Objectives This study aimed to determine the feasibility and acceptability of a multi-modal performing arts intervention (MPAI) for caregivers of people with mild to moderately severe dementia. The secondary objective was to examine how MPAI might change caregiver burden, caregiver resiliency, and perceived quality of life (QoL) for care recipients. Method The study features a mixed-methods design. Caregivers (N = 32) completed the Zarit Burden Interview (caregiver burden) Brief Resilience Scale (resiliency) and Quality of Life-Alzheimer’s disease measure (care recipient QoL) at five study timepoints. Semi-structured interviews (N = 15) documented the intervention’s acceptability and caregivers’ subjective experiences. Feasibility was indexed through withdrawal and attendance analysis. Braun and Clarke (2006) thematic analysis guided the qualitative analysis. Results Caregiver burden significantly declined from baseline through final follow-up. Caregiver resiliency and care recipient QoL were not significantly changed but trended up during the intervention until it dropped at the end of the program. Qualitative data suggests the reversal in resiliency and QoL may be explained by caregivers’ increased anxiety as the program ended. Acceptability data indicated caregivers were unanimously highly satisfied with the intervention, desiring to continue participation. Feasibility findings provide recommendations for intervention improvements. Conclusion MPAI could reduce caregiver burden and increase resilience for informal caregivers of a person with dementia. Effects drop off quickly at the end of the program, indicating the need for ongoing interventions that provide social support, a respite from the pressures of care recipients’ dependency, and the relief that caregivers experience when they perceive benefits to their care recipient’s well-being.

Clarifying the connection between parental conditional regard and contingent self-esteem: An examination of cross-lagged relations in early adolescence.

Relations between parental conditional regard (PCR) and children's motivational and emotional functioning have been demonstrated by past research. However, most available studies relied on cross-sectional correlational data, leaving open the causal direction of these relations. In the present article, we sought to contribute to this topic and examined the longitudinal connection between PCR and adolescents' contingent self-esteem (CSE) over time. Hypotheses were tested in two longitudinal studies with differently gifted samples of German high school students (N=188 and N=202 students, respectively). Data were gathered at three time points in Study 1 and at two time points in Study 2. In both studies, adolescents answered questionnaires regarding positive and negative PCR in the academic domain as well as general CSE (and additionally academic CSE in Study 2). Cross-lagged analyses revealed several significant paths from CSE to PCR, and some paths from PCR to CSE, indicating the presumed reciprocal relationship between these constructs. Our findings suggest that children high in CSE may lead their parents to engage in PCR and that these effects may be more pronounced than vice versa. Possible reasons for these findings and their implications are discussed.

Botulinum Toxin A and Osteosarcopenia in Experimental Animals: A Scoping Review.

We conducted a scoping review to investigate the effects of intramuscular injection of Botulinum Toxin A (BoNT-A) on bone morphology. We investigated if the muscle atrophy associated with Injection of BoNT-A had effects on the neighboring bone. We used the search terms: osteopenia, bone atrophy, Botulinum Toxin A, Micro-CT, mice or rat. The following databases were searched: Medline, Embase, PubMed and the Cochrane Library, between 1990 and 2020. After removal of duplicates, 228 abstracts were identified of which 49 studies satisfied our inclusion and exclusion criteria. The majority of studies (41/49) reported a quantitative reduction in at least one measure of bone architecture based on Micro-CT. The reduction in the ratio of bone volume to tissue volume varied from 11% to 81% (mean 43%) according to the experimental set up and study time points. While longer term studies showed muscle recovery, no study showed complete recovery of all bone properties at the termination of the study. In experimental animals, intramuscular injection of BoNT-A resulted in acute muscle atrophy and acute degradation of the neighboring bone segment. These findings may have implications for clinical protocols in the use of Botulinum Toxin in children with cerebral palsy, with restraint recommended in injection protocols and consideration for monitoring bone density. Clinical studies in children with cerebral palsy receiving injections of Botulinum are indicated.

Perinatal depression and children's developmental outcomes at 2 years postpartum

BackgroundPerinatal depression has been associated with a range of adverse outcomes for children's neurodevelopment. AimsThis study sought to examine the impact of maternal perinatal depression on 2-year-olds' social-emotional, cognitive, language, and adaptive behavioural development, using data collected at the fifth timepoint of a prospective longitudinal study, which followed participants from pregnancy through to toddlerhood. Participants61 women and their children (M age = 26 months, SD = 1.83; 35 boys and 26 girls), of the original cohort of 98, who had been recruited during pregnancy, and stratified into three participant groups: 1. Depressed (those with a clinical diagnosis of Major Depressive Disorder [MDD]); 2. History (currently euthymic with a previous MDD episode); 3. Control (no history of psychiatric disorder). Outcome measuresDepression severity was assessed using the Hamilton Depression Rating Scale (HAM-D), and children's developmental outcomes were measured using the Bayley Scales of Infant and Toddler Development, 3rd Edition (BSID-III). ResultsNo direct associations between mothers' depression and children's social-emotional, cognitive or language development were observed. However, an unexpected positive association between maternal depression and children's social adaptive behaviour was found, which conferred an advantage on children whose mothers had suffered from depression. ConclusionsThe current findings contribute to the literature examining the impact of perinatal depression on early childhood outcomes. The unexpected positive association found between maternal depression and children's adaptive behaviour should prompt further research examining the adaptive resilience of young children exposed to maternal depression. This is discussed in the context of differential-susceptibility theory.