Study Time Points Research Articles

SARS-CoV-2 and Oral Manifestation: An Observational, Human Study.

The correlation between SARS-CoV-2 and oral manifestations is still controversial. The aim of this observational study was to determine the oral manifestation of the hospitalized patients for COVID-19. A total of 20 patients met the inclusion criteria and gave their signed informed consent. A questionnaire of 32 questions regarding the oral and systemic health condition was administrated to these patients during the convalescence. A descriptive statistic was performed. Data were analysed through the use of χ2 test, to assess the statistical significance. A statistically significant increase of about 30% of reporting xerostomia during hospitalization was observed (p = 0.02). Meanwhile, a decrease of oral hygiene was observed during the hospitalization, even if a non-statistically significant difference was shown between the two study time points (before and after hospitalization). During the hospitalization period, 25% of patients reported impaired taste, 15% burning sensation, and 20% difficulty in swallowing. An interesting result was that among the systemic conditions, hypertension was observed in 39% of patients and mostly in female patients (62.5%). Further studies are necessary to better understand the symptoms of this new virus in order to faster detect its presence in humans. Probably, a multidisciplinary team following the COVID-19 patients could be of key importance in treating this disease.

Peri-implantation cytokine profile differs between singleton and twin IVF pregnancies.

It is unknown whether maternal cytokine production differs between twin and singleton gestations in the implantation phase. A difference in maternal serum cytokine concentrations in twins would imply a dose-response to the invading embryos, as opposed to a general immune reaction. A prospective longitudinal cohort of women aged 18-45 at an academic fertility center undergoing in vitro fertilization and embryo transfer (IVF-ET) underwent routine collection of serial serum samples starting 9days after ET and then approximately every 48hours thereafter. Cryopreserved aliquots of these samples were assayed for interleukin-10 (IL-10), tumor necrosis factor-alpha (TNF-α), and C-X-C motif chemokine ligand 10 (CXCL10) using the SimplePlex immunoassay platform. Pregnancies were followed until delivery. Serial measures of serum concentrations of IL-10, CXCL10, and TNF-α in singleton or di-di twin pregnancies from 9 to 15days after IVF-ET were compared. Maternal serum levels of CXCL10 are significantly lower in women with di-di twin pregnancies in early implantation compared to those with singleton gestation (day 9-11, P=.02). Serum levels of TNF-α and IL-10 were comparable at all studied time points (P>.05). Maternal serum levels of CXCL10 are significantly lower in the earliest implantation phase in di-di twins compared to singleton conceptions. Given the known anti-angiogenic role of CXCL10, we hypothesize that lower CXCL10 levels in twin implantations allow an environment that is conducive for the greater vascularization required for the establishment of dual placentation in di-di twins.

Identification and analysis of transepithelial transport properties of casein peptides with anticoagulant and ACE inhibitory activities

Casein is an excellent source for producing anticoagulant and angiotensin I-converting enzyme inhibitory (ACEI) peptides. Here, the anticoagulant and ACEI activities of the casein hydrolysate produced by in vitro simulated gastrointestinal (GI) digestion were evaluated. The casein hydrolysate showed potent anticoagulant activity by prolonging the thrombin time (TT) and activated partial thromboplastin time (APTT), and also presenting great ACEI activity, with an IC50 value of 0.52 mg mL−1. Subsequently, the transepithelial transport properties of the casein hydrolysate were analyzed by using the Caco-2 cell monolayer model. The peptides profile of the casein hydrolysate before and after it passed across the Caco-2 cell monolayer were identified by NanoLC-Q-TOF-MS/MS. The results showed that a total of 121 and 184 peptides were identified before and after casein hydrolysate moved through the Caco-2 cell monolayer, respectively. Eighty peptides were presented at both time points of the transport study. Among the 80 peptides, 26 of them were screened with a high possibility of exerting physiological roles after they were absorbed into the blood by in silico methods, and the physicochemical characteristics, e.g., hydrophobicity, net charge, and toxicity of the peptides also be evaluated. Our results provided a new prospect and approach for producing bioactive peptides from casein with anticoagulant and ACEI activities.

Screening and functional identification of salt tolerance HMG genes in Betula platyphylla

High mobility group (HMG) proteins play an important role in plant responses to abiotic stresses. However, to date, few studies have focused on the functional characterization of HMG genes in woody plants. In this study, 11 BpHMG genes named BpHMG1-BpHMG11 were cloned and characterized from Betula platyphylla. The expression patterns of BpHMG genes under two types of abiotic stress (osmotic and salt stress) and ABA (abscisic acid) treatments were detected by qRT-PCR. The results showed that the expression of 11 BpHMG genes in birch roots, stems and leaves changed in at least one stress treatment time point under all three treatments, suggesting that 11 BpHMG genes could respond to salt, osmotic stress and ABA treatment. In particular, the expression of BpHMG6 in birch stems was significantly upregulated at all studied time points under NaCl stress. The highest level was increased up to 118-fold compared with the control, indicating that this gene may be involved in salt stress responses. To further study the salt tolerance function of BpHMG6, the overexpression vector pROKII-BpHMG6 and silencing expression vector pFGC-BpHMG6 were constructed and transiently transformed into birch. The empty vector pROKII was also transformed as a control. POD activity, H2O2 and MDA levels, relative electrolyte and NBT, DAB and Evans blue staining were analysed and compared between transgenic and control plants under salt stress. The results indicated that the overexpression of BpHMG6 in birch not only increased the activity of protective enzymes under salt stress but also enhanced the ROS scavenging capacity to reduce cell damage and death caused by salt stress. Conversely, the silenced transiently transformed plants displayed the opposite physiological changes. Therefore, BpHMG6 potentially plays a role in salt stress tolerance in transgenic birch plants.

Clinical and Laboratory Associations with Methotrexate Metabolism Gene Polymorphisms in Rheumatoid Arthritis.

Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease that causes loss of joint function and significantly reduces quality of life. Plasma metabolite concentrations of disease-modifying anti-rheumatic drugs (DMARDs) can influence treatment efficacy and toxicity. This study explored the relationship between DMARD-metabolising gene variants and plasma metabolite levels in RA patients. DMARD metabolite concentrations were determined by tandem mass-spectrometry in plasma samples from 100 RA patients with actively flaring disease collected at two intervals. Taqman probes were used to discriminate single-nucleotide polymorphism (SNP) genotypes in cohort genomic DNA: rs246240 (ABCC1), rs1476413 (MTHFR), rs2231142 (ABCG2), rs3740065 (ABCC2), rs4149081 (SLCO1B1), rs4846051 (MTHFR), rs10280623 (ABCB1), rs16853826 (ATIC), rs17421511 (MTHFR) and rs717620 (ABCC2). Mean plasma concentrations of methotrexate (MTX) and MTX-7-OH metabolites were higher (p < 0.05) at baseline in rs4149081 GA genotype patients. Patients with rs1476413 SNP TT or CT alleles have significantly higher (p < 0.001) plasma poly-glutamate metabolites at both study time points and correspondingly elevated disease activity scores. Patients with the rs17421511 SNP AA allele reported significantly lower pain scores (p < 0.05) at both study intervals. Genotyping strategies could help prioritise treatments to RA patients most likely to gain clinical benefit whilst minimizing toxicity.

Development and Evaluation of an Accelerometer-Based Protocol for Measuring Physical Activity Levels in Cancer Survivors: Development and Usability Study.

BackgroundThe collection of self-reported physical activity using validated questionnaires has known bias and measurement error.ObjectiveAccelerometry, an objective measure of daily activity, increases the rigor and accuracy of physical activity measurements. Here, we describe the methodology and related protocols for accelerometry data collection and quality assurance using the Actigraph GT9X accelerometer data collection in a convenience sample of ovarian cancer survivors enrolled in GOG/NRG 0225, a 24-month randomized controlled trial of diet and physical activity intervention versus attention control.MethodsFrom July 2015 to December 2019, accelerometers were mailed on 1337 separate occasions to 580 study participants to wear at 4 time points (baseline, 6, 12, and 24 months) for 7 consecutive days. Study staff contacted participants via telephone to confirm their availability to wear the accelerometers and reviewed instructions and procedures regarding the return of the accelerometers and assisted with any technology concerns.ResultsWe evaluated factors associated with wear compliance, including activity tracking, use of a mobile app, and demographic characteristics with chi-square tests and logistic regression. Compliant data, defined as ≥4 consecutive days with ≥10 hours daily wear time, exceeded 90% at all study time points. Activity tracking, but no other characteristics, was significantly associated with compliant data at all time points (P<.001). This implementation of data collection through accelerometry provided highly compliant and usable activity data in women who recently completed treatment for ovarian cancer.ConclusionsThe high compliance and data quality associated with this protocol suggest that it could be disseminated to support researchers who seek to collect robust objective activity data in cancer survivors residing in a wide geographic area.

Problematic internet use: A scoping review - longitudinal research on a contemporary social problem, 2006-2017.

Background and aims:Problematic internet use (PIU), and kindred concepts such as internet addiction (IA), make up a growing research field, partly due to the suggested inclusion of internet gaming disorder in a future DSM-6 as well as the fact that gaming disorder is on its way to being included in the ICD-11. Conclusions from research are far from unified. This study aims to synthesise the research field of problematic internet use/internet addiction/gaming disorder, with a focus on the reporting of prevalence and change.Methods:Longitudinal studies of PIU/IA formed the basis for a scoping review. Systematic searches of Web of Science, Scopus and Proquest, for peer-reviewed and published articles based on empirical data collected at a minimum of two time points for studies, and with an end point set at 2017, led to the inclusion of 97 studies. Endnote X7 was used to organise the results and NVivo 11 was used for synthesising the results.Results:Analyses focused on prevalence and change. Findings show variation among measures and prevalence as well as in reported outcomes relating to social life and other problems. Most studies reported relations between PIU/IA and other problems in life, but no specific time order could be established. Furthermore, many studies did not present data on prevalence or change even though using a longitudinal survey design.Discussion and conclusions:In summary, the research field is plagued by a lack of consensus and common understanding, regarding both measures, perceptions of the problem, and findings.

A “handy” reminder

Because of the long-term risk of neurodevelopmental impairments, many neonatal intensive care unit (NICU) graduates receive developmental surveillance in high risk infant follow up programs. There are no national recommendations for the duration of follow up but a survey published in 2014 (J Perinatol 2014;34:71-74) showed that programs rarely extend through 5 years of age. A longitudinal study of extremely preterm children published this month in The Journal of Pediatrics reminds us that longer follow up may be necessary for many children. Duncan et al showed that toddlers who had difficulties with bimanual hand function at 18-22 months of corrected age continued to have both fine and gross motor difficulties at 6-7 years of age, independent of whether they had participated in occupational or physical therapy at 18-22 months. Duncan et al did not study whether the children in their study were monitored between study timepoints or if therapy services were continued between 18-22 months and 6-7 years. However, 35% of the cohort had fine motor impairments at 6-7 years suggesting they may have benefited from ongoing developmental monitoring and timely therapy services. We need more studies that help us understand the path between early impairments and school function and studies that help us to prepare high risk infants for school and ameliorate the impact of preschool impairments. Although this study focused on motor difficulties, we know that NICU graduates also are at risk for cognitive, social, and behavioral difficulties. This study therefore serves as a “handy” reminder to maintain developmental vigilance during the toddler years. Article page 51 ▸ Hand Function at 18-22 Months Is Associated with School-Age Manual Dexterity and Motor Performance in Children Born Extremely PretermThe Journal of PediatricsVol. 225PreviewTo determine associations between hand function at age 18-22 months (early) and scores on the Movement Assessment Battery for Children, 2nd edition (MABC) at 6-7 years of age (school age) in extremely preterm children. Full-Text PDF

Quaternary Structure Changes for PrPSc Predate PrPC Downregulation and Neuronal Death During Progression of Experimental Scrapie Disease

Prion diseases are fatal neurodegenerative diseases in mammals with the unique characteristics of misfolding and aggregation of the cellular prion protein (PrPC) to the scrapie prion (PrPSc). Although neuroinflammation and neuronal loss feature within the disease process, the details of PrPC/PrPSc molecular transition to generate different aggregated species, and the correlation between each species and sequence of cellular events in disease pathogenesis are not fully understood. In this study, using mice inoculated with the RML isolate of mouse-adapted scrapie as a model, we applied asymmetric flow field-flow fractionation to monitor PrPC and PrPSc particle sizes and we also measured seeding activity and resistance to proteases. For cellular analysis in brain tissue, we measured inflammatory markers and synaptic damage, and used the isotropic fractionator to measure neuronal loss; these techniques were applied at different timepoints in a cross-sectional study of disease progression. Our analyses align with previous reports defining significant decreases in PrPC levels at pre-clinical stages of the disease and demonstrate that these decreases become significant before neuronal loss. We also identified the earliest PrPSc assemblies at a timepoint equivalent to 40% elapsed time for the disease incubation period; we propose that these assemblies, mostly composed of proteinase K (PK)–sensitive species, play an important role in triggering disease pathogenesis. Lastly, we show that the PK-resistant assemblies of PrPSc that appear at timepoints close to the terminal stage have similar biophysical characteristics, and hence that preparative use of PK-digestion selects for this specific subpopulation. In sum, our data argue that qualitative, as well as quantitative, changes in PrP conformers occur at the midpoint of subclinical phase; these changes affect quaternary structure and may occur at the threshold where adaptive responses become inadequate to deal with pathogenic processes.

P49. Physical activity measures in lumbar laminectomy patients: a prospective comparison of fitness tracker measures versus patient-reported outcome measures

BACKGROUND CONTEXT Assessing spine surgery patients' disability and mobility levels allows clinicians to evaluate the efficacy of surgical procedures and track postoperative recovery. While the current standard, patient-reported outcome measures (PROMs), provides a cross-sectional subjective assessment of functional levels, wearable fitness trackers can continuously and objectively track physical activity even outside of the clinic. PURPOSE The present study aims to assess how a wearable fitness tracker and two PROMs compare in tracking patients' recoveries from lumbar laminectomy. STUDY DESIGN/SETTING This is a prospective observational clinical study conducted within an urban academic health system. PATIENT SAMPLE The sample is composed of patients with lumbar stenosis who have undergone non-revision lumbar laminectomy with or without single level fusion. Patients who have had spine surgery within the past 5 years or have medical conditions that significantly inhibit mobility (including cardiovascular conditions and other orthopedic conditions) were excluded. OUTCOME MEASURES Patient median steps taken per day were continuously collected using the Fitbit Flex 2 fitness tracker. The Oswestry Disability Index (ODI) and Physical and Mental Components of the 12-Item Short Form Health Survey (SF-12 PCS/MCS) PROMs were assessed using standardized questionnaires throughout the study period. METHODS Each patient was provided with a fitness tracker at least 2 weeks prior to surgery until 6 months postoperatively to record median steps taken per day during the preoperative (baseline) and 2 week, 1, 3, and 6 month postoperative intervals. ODI and SF-12 PCS/MCS scores were calculated at enrollment and at the end of each interval. Two-tailed Student's t-tests were used to evaluate changes from baseline. Associations between the change in median steps per day and PROMs throughout the study were evaluated using Pearson's correlation coefficient. RESULTS Twelve of 18 enrolled subjects have thus far completed the study. Average compliance for wearing the fitness tracker, which was defined as the percentage of days the device was worn relative to the number of days the subject was enrolled in the study, was 91%. Average median steps per day and PROM scores normalized to preoperative levels decline immediately after surgery but recover after 1-3 months. Median steps per day were not significantly different from baseline at 6 months postoperatively (2.45% increase; p = 0.60). Average SF-12 PCS and ODI scores surpassed baseline scores by 1 month postoperatively and improved from baseline by 38% and 45% respectively at 6 months postoperatively (p = 0.004 and 0.05). No significant correlations were found between the change in median steps per day and corresponding change in PROM scores at any study time points. CONCLUSIONS Though enrollment is still ongoing, we can conclude that lumbar laminectomy patients had significantly improved SF-12 PCS and ODI scores by 6 months postoperatively while median steps per day only returned to baseline. Patients therefore perceive that their conditions have improved after lumbar laminectomy more quickly than their mobilities objectively increase. The lack of significant correlations between the change in median steps per day and corresponding change in PROM scores throughout the study also suggests that these outcome measurements describe distinct patient experiences. Though patients' self-reported pain-free mobility increases, lifestyle and other factors may be important in explaining the lack of difference between preoperative and 6-month postoperative median steps taken per day. FDA DEVICE/DRUG STATUS This abstract does not discuss or include any applicable devices or drugs.

The effect of umbilical cord milking on cerebral blood flow in very preterm infants: a randomized controlled study.

To compare the effect of umbilical cord milking (UCM) vs. early cord clamping (ECC) on cerebral blood flow (CBF). Preterm infants <31 weeks' gestation were randomized to receive UCM or ECC at birth. Blood flow velocities and resistive & pulsatility indices of middle and anterior cerebral arteries were measured at 4-6 and 10-12 h after birth as an estimate of CBF. Randomization allocated 37 infants to UCM and 36 to ECC. Maternal and antenatal variables were similar. There were no significant differences between groups in middle or anterior CBF velocities and resistive indices at either study time point. CBF variables were not correlated with mean blood pressure, systemic blood flow, or intraventricular hemorrhage. In very preterm infants, UCM compared with ECC was not shown to change CBF indices during the first 12 h of age or correlate with other hemodynamic measures or with intraventricular hemorrhage. ClinicalTrials.gov: NCT01487187.

Association of mitochondrial DNA content and displacement loop region sequence variations with cancer-related fatigue in breast cancer survivors receiving chemotherapy

Cancer-related fatigue (CRF) is characterized by a lack of energy, and mitochondrial dysfunction is postulated to contribute to its etiology. This prospective cohort study assesses the self-reported fatigue levels of early-stage breast cancer patients using the validated Multi-Dimensional Fatigue Symptom Inventory–Short Form (MFSI-SF) and blood samples drawn at three time points: before treatment, approximately 6 weeks, and 12 weeks after the initiation of chemotherapy. The aim of this study is to evaluate mitochondrial measures with CRF, over the course of chemotherapy using mitochondrial DNA (mtDNA content) and displacement loop (D-loop) region sequence variations at nucleotide positions 303, 489 and 514. The relative mtDNA copy number was determined via real-time quantitative polymerase chain reaction and compared between study time points and D-loop sequence variants. The association of mtDNA content with MFSI-SF total and sub-domain scores was analyzed in a sample of 155 patients (mean age ± SD: 51.7 ± 8.8 years). The median mtDNA content decreased over 12 weeks after the initiation of chemotherapy (p < 0.001). Baseline mtDNA content was lower for nucleotide position 303 in sequence variations than for the reference sequence (67.2 copies vs 79.1 copies, p = 0.03). Physical fatigue negatively correlated with mtDNA content in both unadjusted (β = −0.0075, p = 0.048) and adjusted models (β = −0.0062, p = 0.042), accounting for age, anxiety, insomnia, haemoglobin levels and body mass index. Our findings add to the literature indicating that mitochondrial function serves as an important target for mitigating CRF.

Low-level laser therapy effectiveness in reducing initial orthodontic archwire placement pain in premolars extraction cases: a single-blind, placebo-controlled, randomized clinical trial

BackgroundThe objective of this randomized clinical trial was to evaluate Low-Level Laser Therapy (LLLT) effectiveness in spontaneous and chewing pain reduction following initial orthodontic archwire placement.Methods26 patients (mean age 20.07 ± 3.13 years) with maxillary Little’s Irregularity Index (LII) of 7 mm or more that indicates first maxillary premolars extraction and no medications intake were eligible for this trial. Patients were randomly assigned with 1:1 ratio using simple randomization technique to receive either LLL or placebo treatment. Blinding was applicable for patients only. In the laser group, patients received a single LLL dose (wavelength 830 nm, energy 2 J/point) in four points (2 buccal, 2 palatal) for each maxillary anterior tooth root. Patients in the placebo group had the same laser application procedure without emitting the laser beam. Patients were asked to score spontaneous and chewing pain intensity by filling out a questionnaire with a 100-mm Visual Analogue Scale (VAS) after 1, 6, 24, 48, and 72 h of treatment application. Independent t-test was used to compare the mean pain scores between the laser and placebo groups for both spontaneous and chewing pain at each studied time point.ResultsNo dropout occurred so the results of the 26 patients were statistically analyzed. Despite some clinical differences observed between the two groups, no statistical significance was found for each studied time point (p > 0.05) for both spontaneous and chewing pain except after 72 h for chewing pain with a VAS score of (18.84 ± 13.44) mm for the laser group compared to (38.15 ± 27.06) mm for the placebo group.ConclusionsLLLT, with the suggested parameters, is not effective in pain reduction following initial orthodontic archwire placement.Trial registrationName of the registry:Clinicaltrials.govTrial registration number:NCT02568436.Date of registration: 26 September 2015 ‘Retrospectively registered’.

Artificial Saliva in Diabetic Xerostomia (ASDIX): Double Blind Trial of Aldiamed® Versus Placebo.

Xerostomia is a symptom frequently present in patients with type 1 (T1DM) and type 2 diabetes mellitus (T2DM). In the present trial, the activity of an artificial saliva (aldiamed® spray) in comparison to a placebo spray were used to evaluate the xerostomia and the saliva antioxidant capacity (SAT). Sixty patients of both genders with T1DM or T2DM were randomized into two groups of 30 subjects each. The experiment was a double-blind study approved by the Ethics Committee of the “G. d’Annunzio University” of Chieti and Pescara. Moreover, measurements of the stimulated saliva flow rate and the ultrasonography of the submandibular and parotid glands were performed at both the study time points. The results demonstrated statistically significant differences between the treatments in terms of the xerostomia average score. Specifically, the values were at baseline and after 30 days 2.9 ± 1.31 and 3.0 ± 1.44 and 1.4 ± 1.48 and 2.4 ± 0.99 for aldiamed® spray and the placebo, respectively. Meanwhile, no statistically significant differences were shown between the two groups for the other variables, such as the salivary flow rate, the antioxidant capacity of the saliva, and the ultrasonography of the major salivary glands.

Effects of COVID‐19 Lockdown on Lifestyle Behaviors in Children with Obesity Living in Verona, Italy: A Longitudinal Study

ObjectiveThe aim of this study was to test the hypothesis that youths with obesity, when removed from structured school activities and confined to their homes during the coronavirus disease 2019 pandemic, will display unfavorable trends in lifestyle behaviors.MethodsThe sample included 41 children and adolescents with obesity participating in a longitudinal observational study located in Verona, Italy. Lifestyle information including diet, activity, and sleep behaviors was collected at baseline and 3 weeks into the national lockdown during which home confinement was mandatory. Changes in outcomes over the two study time points were evaluated for significance using paired t tests.ResultsThere were no changes in reported vegetable intake; fruit intake increased (P = 0.055) during the lockdown. By contrast, potato chip, red meat, and sugary drink intakes increased significantly during the lockdown (P value range, 0.005 to < 0.001). Time spent in sports activities decreased by 2.30 (SD 4.60) h/wk (P = 0.003), and sleep time increased by 0.65 (SD 1.29) h/d (P = 0.003). Screen time increased by 4.85 (SD 2.40) h/d (P < 0.001).ConclusionsRecognizing these adverse collateral effects of the coronavirus disease 2019 pandemic lockdown is critical in avoiding depreciation of weight control efforts among youths afflicted with excess adiposity. Depending on duration, these untoward lockdown effects may have a lasting impact on a child’s or adolescent’s adult adiposity level.

Efficacy of a Multimodal Online Lifestyle Intervention for Depressive Symptoms and Quality of Life in Individuals With a History of Major Depressive Disorder.

BackgroundMajor depressive disorder (MDD) is a complex bio-psycho-social syndrome that affects millions of individuals and is one of the leading causes of impaired quality of life (QOL). In addition to the symptoms of depression and low mood, many individuals with MDD also suffer from isolation without the sense of a supportive, surrounding community. Given the challenges of treating individuals with MDD, social isolation and a lack of communal connection, this randomized controlled trial was designed to determine the efficacy of a multimodal, online and community-based lifestyle intervention for improving depressive symptoms and QOL in individuals with a history of MDD.Materials and methodsThe study enrolled 71 female or male participants between the ages of 20 and 64 with a self-reported BMI between 18.4 and 34.9 kg/m2 and a history of MDD. Individuals were randomized to either participate in a 44-day multimodal, online, community-based lifestyle intervention or placed on a wait list where they would complete the intervention at a later date. The multimodal intervention involved a self-directed learning program where individuals were guided to make lifestyle changes including adopting a whole-foods diet, increasing movement, and adopting stress management and mindfulness practices. All participants completed the 36-Item Short Form Health Survey (SF-36), the Cleveland Clinic Center for Functional Medicine's Medical Symptoms Questionnaire (MSQ), and the Patient Health Questionnaire-9 (PHQ-9) before and after the online program to assess health-related QOL, overall symptom burden, and depressive symptom burden, respectively. ResultsA total of 37 participants were randomized to participate in the multimodal intervention with 26 completing all three study questionnaires at both study time points; 34 participants were randomized to the wait list control group with 27 completing all three study questionnaires at both study time points. There were no clinically or statistically significant differences between the control group or the intervention group at baseline. The control group showed no clinically nor statistically significant changes in the MSQ, PHQ-9 or any of the eight subdomains of the SF-36 from the beginning to the end of the 10-week study period. When compared to the control group, the intervention group showed statistically and clinically significant improvements in median (M) scores of the SF-36 subdomains of vitality and mental health, and clinically but not statistically significant improvements in the subdomain of emotional role functioning. There were additional statistically and clinically significant improvements in the mean score of the MSQ and M scores of the PHQ-9 (treatment pre-intervention M = 10.5, inter-quartile range [IQR] = 14, to treatment post-intervention M = 5, IQR = 8.25; control pre-intervention M = 15, IQR = 8, to control post-intervention M = 13.5, IQR = 12.5).Conclusions Our randomized controlled study provides evidence for the role of a multimodal, online and community-based lifestyle intervention to improve depressive symptoms, QOL, and total symptom burden in individuals with a history of MDD. Given the growing challenges of effectively supporting individuals suffering with MDD, it appears critical to further explore the utilization of novel, multimodal and self-directed lifestyle interventions.

Assessing changes in microstructural integrity of white matter tracts in children with leukaemia following exposure to chemotherapy.

Intrathecal and intravenous chemotherapy, specifically methotrexate, might contribute to neural microstructural damage. To assess, by diffusion tensor imaging, microstructural integrity of white matter in paediatric patients with acute lymphoblastic leukaemia (ALL) following intrathecal and intravenous chemotherapy. Eleven children diagnosed with de novo ALL underwent MRI scans of the brain with diffusion tensor imaging (DTI) prior to commencement of chemotherapy and at 12months after diagnosis, using a 3-tesla (T) MRI scanner. We investigated the changes in DTI parameters in white matter tracts before and after chemotherapy using tract-based spatial statistics overlaid on the International Consortium of Brain Mapping DTI-81 atlas. All of the children underwent formal neurodevelopmental assessment at the two study time points. Whole-brain DTI analysis showed significant changes between the two time points, affecting several white matter tracts. The tracts demonstrated longitudinal changes of decreasing mean and radial diffusivity. The neurodevelopment of the children was near compatible for age at the end of ALL treatment. The quantification of white matter tracts changes in children undergoing chemotherapy showed improving longitudinal values in DTI metrics (stable fractional anisotropy, decreasing mean and radial diffusivity), which are incompatible with deterioration of microstructural integrity in these children.

Oral preexposure prophylaxis continuation, measurement and reporting

Objective:The aim of this study was to appropriately plan for rollout and monitor impact of oral preexposure prophylaxis (PrEP). It is important to understand PrEP continuation and come to a consensus on how best to measure PrEP continuation. This study reviews data on PrEP continuation to document how it is reported, and to compare continuation over time and across populations.Design:A systematic review and meta-analysis.Methods:We searched MEDLINE, Embase and Global Health and reviewed abstracts from HIV conferences from 2017 to 2018 for studies reporting primary data on PrEP continuation. Findings were summarized along a PrEP cascade and continuation was presented by population at months 1, 6 and 12, with random-effects meta-analysis.Results:Of 2578 articles and 596 abstracts identified, 41 studies were eligible covering 22 034 individuals. Continuation data were measured and reported inconsistently. Results showed high discontinuation at month 1 and persistent discontinuation at later time points in many studies. Pooled continuation estimates were 66% at month 1 [n = 5348; 95% confidence interval (95% CI): 48–82], 63% at month 6 (n = 13 629; 95% CI: 48–77) and 71% at month 12 (n = 14 933; 95% CI: 60–81; higher estimate than previous timepoints due to inclusion of different studies). Adequate data were not available to reliably compare estimates across populations.Conclusion:This review found that discontinuation at one month was high, suggesting PrEP initiations may be a poor measure of effectiveness. Continuation declined further over time in many studies, indicating existing cross-sectional indicators may not be adequate to understand PrEP use patterns. Studies do not measure continuation consistently, and consensus is needed.

Magnetic Resonance-guided Stereotactic Radiotherapy for Localized Prostate Cancer: Final Results on Patient-reported Outcomes of a Prospective Phase 2 Study

BackgroundThe recent introduction of magnetic resonance-guided radiation therapy (MRgRT) has allowed improved treatment planning and delivery of stereotactic body radiotherapy (SBRT) in prostate cancer (PC). The health-related quality of life (HRQoL) outcomes using this novel approach are important in shared decision making for patients. ObjectiveTo report HRQoL using both patient- and clinician-reported outcomes at 1 yr following stereotactic MRgRT for patients with localized PC. Design, setting, and participantsA prospective phase 2 trial included 101 patients with localized PC. InterventionAll patients received 36.25Gy in five fractions of MRgRT delivered within 2 wk. Outcome measurements and statistical analysisHRQoL was prospectively assessed at baseline, at the last fraction, at 6 wk, and at 3, 6, 9, and 12 mo after treatment, by patient-reported outcome measures using European Organization for Research and Treatment of Cancer QLQ-C30 and QLQ-PR25 questionnaires, and International Prostate Symptom Score. At the same time points, clinicians reported on symptomatic adverse events (AEs). Effect sizes for changes in HRQoL were calculated with repeated measures analysis of variance. Results and limitationsAvailability of HRQoL data exceeded 95% at all study time points. From both questionnaires and the recorded AEs, the largest treatment effects on urinary and bowel symptoms were recorded in the first 6 wk of follow-up. Thereafter, all symptoms decreased and returned to baseline values at 12 mo. No grade ≥3 toxicity was reported. No patient reported any relevant limitation due to urinary symptoms, and only 2.2% of patients reported a relevant impact on daily activities due to bowel problems at 1 yr. The majority of patients had intermediate- or high-risk PC for which androgen deprivation therapy (83.2%) was prescribed, thereby precluding study of MRgRT on sexual function. Longer follow-up is awaited in order to evaluate the oncological outcome. ConclusionsDelivery of MRgRT for SBRT resulted in low toxicity at 1 yr. Patient summaryAll patients completed magnetic resonance-guided radiation therapy, which was well tolerated with only transient early urinary and bowel symptoms, which resolved 1 yr after treatment, as confirmed by patient-reported outcome measures.

A Guide to Diet-Microbiome Study Design.

Intense recent interest in understanding how the human gut microbiome influences health has kindled a concomitant interest in linking dietary choices to microbiome variation. Diet is known to be a driver of microbiome variation, and yet the precise mechanisms by which certain dietary components modulate the microbiome, and by which the microbiome produces byproducts and secondary metabolites from dietary components, are not well-understood. Interestingly, despite the influence of diet on the gut microbiome, the majority of microbiome studies published to date contain little or no analysis of dietary intake. Although an increasing number of microbiome studies are now collecting some form of dietary data or even performing diet interventions, there are no clear standards in the microbiome field for how to collect diet data or how to design a diet-microbiome study. In this article, we review the current practices in diet-microbiome analysis and study design and make several recommendations for best practices to provoke broader discussion in the field. We recommend that microbiome studies include multiple consecutive microbiome samples per study timepoint or phase and multiple days of dietary history prior to each microbiome sample whenever feasible. We find evidence that direct effects of diet on the microbiome are likely to be observable within days, while the length of an intervention required for observing microbiome-mediated effects on the host phenotype or host biomarkers, depending on the outcome, may be much longer, on the order of weeks or months. Finally, recent studies demonstrating that diet-microbiome interactions are personalized suggest that diet-microbiome studies should either include longitudinal sampling within individuals to identify personalized responses, or should include an adequate number of participants spanning a range of microbiome types to identify generalized responses.