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Context: Annual ultrasound screening may detect small, node-negative breast cancers that are not seen on mammography. Magnetic resonance imaging (MRI) may reveal additional breast cancers missed by both mammography and ultrasound screening.Objective: To determine supplemental cancer detection yield of ultrasound and MRI in women at elevated risk for breast cancer.Design, Setting, and Participants: From April 2004-February 2006, 2809 women at 21 sites with elevated cancer risk and dense breasts consented to 3 annual independent screens with mammography and ultrasound in randomized order. After 3 rounds of both screenings, 612 of 703 women who chose to undergo an MRI had complete data. The reference standard was defined as a combination of pathology (biopsy results that showed in situ or infiltrating ductal carcinoma or infiltrating lobular carcinoma in the breast or axillary lymph nodes) and 12-month follow-up.Main Outcome Measures: Cancer detection rate (yield), sensitivity, specificity, positive predictive value (PPV3) of biopsies performed and interval cancer rate.Results: A total of 2662 women underwent 7473 mammogram and ultrasound screenings, 110 of whom had 111 breast cancer events: 33 detected by mammography only, 32 by ultrasound only, 26 by both, and 9 by MRI after mammography plus ultrasound; 11 were not detected by any imaging screen. Among 4814 incidence screens in the second and third years combined, 75 women were diagnosed with cancer. Supplemental incidence-screening ultrasound identified 3.7 cancers per 1000 screens (95% CI, 2.1-5.8; P < .001). Sensitivity for mammography plus ultrasound was 0.76 (95% CI, 0.65-0.85); specificity, 0.84 (95% CI, 0.83-0.85); and PPV3, 0.16 (95% CI, 0.12-0.21). For mammography alone, sensitivity was 0.52 (95% CI, 0.40-0.64); specificity, 0.91 (95% CI, 0.90-0.92); and PPV3, 0.38 (95% CI, 0.28-0.49; P < .001 all comparisons). Of the MRI participants, 16 women (2.6%) had breast cancer diagnosed. The supplemental yield of MRI was 14.7 per 1000 (95% CI, 3.5-25.9; P = .004). Sensitivity for MRI and mammography plus ultrasound was 1.00 (95% CI, 0.79-1.00); specificity, 0.65 (95% CI, 0.61-0.69); and PPV3, 0.19 (95% CI, 0.11-0.29). For mammography and ultrasound, sensitivity was 0.44 (95% CI, 0.20-0.70, P = .004); specificity 0.84 (95% CI, 0.81-0.87; P < .001); and PPV3, 0.18 (95% CI, 0.08 to 0.34; P = .98). The number of screens needed to detect 1 cancer was 127 (95% CI, 99-167) for mammography; 234 (95% CI, 173-345) for supplemental ultrasound; and 68 (95% CI, 39-286) for MRI after negative mammography and ultrasound results.Conclusion: The addition of screening ultrasound or MRI to mammography in women at increased risk of breast cancer resulted in not only a higher cancer detection yield but also an increase in false-positive findings.Trial Registration: clinicaltrials.gov Identifier: NCT00072501. [ABSTRACT FROM AUTHOR]

BACKGROUND: The development of obesity is influenced by both genetic and environmental risk factors. Whereas changes in the environment appear to be responsible for the increasing prevalence of obesity, genetic factors interacting with environmental factors would contribute to explain obesity onset and severity. AIM: To explore epidemiologic genotype-by-nutrient interactions in obesity. METHODS: A total of 42 polymorphisms of 26 candidate genes for obesity were genotyped in 549 adult obese women recruited from eight European centres in a case-only study. The nutritional variables assessed in this study were the dietary fibre intake (grams per day), the ratio of dietary polyunsaturated fat to saturated fat (P:S ratio) and the percentage of energy derived from fat in the diet as calculated from a weighed three-day food record (%E). Under the assumption of genotype-nutrient independence in the population, the odds ratio calculated in a sample of obese women would indicate the existence of genotype-by-nutrient interactions, measured as deviations from the multiplicative effects of the genetic and the nutrient factors separately. RESULTS: No new but confirmaty evidences for genotype-by-nutrient interactions in obesity were detected in this case-only study. The test of interaction between fibre intake and the -514 C > T polymorphism of the hepatic lipase gene (LIPC) yielded P-values of 0.01 across different statistical models. Likewise, the -11377G > C polymorphism of the adiponectin gene (ADIPOQ) and the -681 C > G polymorphism of the PPARG3 gene might interact with the percentage of energy derived from fat in the diet for the development of obesity (P-values in the range of 0.01-0.05 across different statistical models). The P-values were not adjusted for multiple testing, so these results should be considered with caution. CONCLUSIONS: Although the use of obese-only samples is theoretically a useful approach to detect interactions, few genotype-by-nutrient interactions have been suggested in obese European women after the analysis of candidate polymorphisms and the selected nutrient variables. The most remarkable multiplicative interaction found in this study refers to the combination of the hepatic lipase gene polymorphism -514 C > T and fibre intake. [ABSTRACT FROM AUTHOR]

OBJECTIVES: To better understand how immobilization and surgery affect muscle size and function in the elderly and to identify effective training regimes. DESIGN: A prospective randomized, controlled study. SETTING: Bispebjerg University Hospital, Copenhagen, Denmark. PARTICIPANTS: Thirty-six patients (aged 60-86) scheduled for unilateral hip replacement due to primary hip osteoarthrosis. INTERVENTION: Patients were randomized to standard home-based rehabilitation (1 h/d x 12 weeks), unilateral neuromuscular electrical stimulation of the operated side (1 h/d x 12 weeks), or unilateral resistance training of the operated side (3/wk x 12 weeks). MEASUREMENTS: Hospital length of stay (LOS), quadriceps muscle cross-sectional area (CSA), isokinetic muscle strength, and functional performance. Patients were tested presurgery and 5 and 12 weeks postsurgery. RESULTS: Mean+/-standard error LOS was shorter for the resistance training group (10.0+/-2.4 days, P<.05) than for the standard rehabilitation group (16.0+/-7.2 days). Resistance training, but not electrical stimulation or standard rehabilitation, resulted in increased CSA (12%, P<.05) and muscle strength (22-28%, P<.05). Functional muscle performance increased after resistance training (30%, P<.001) and electrical stimulation (15%, P<.05) but not after standard rehabilitation. CONCLUSION: Postoperative resistance training effectively increased maximal muscle strength, muscle mass, and muscle function more than a standard rehabilitation regime. Furthermore, it markedly reduced LOS in elderly postoperative patients. [ABSTRACT FROM AUTHOR]

Background: Although the association of clinical hypothyroidism with cognitive deficits is well known, the cognitive effects of thyroid hormones in euthyroid subjects are less studied and understood. The purpose of this study was to examine thyroid-cognition relationships in healthy, euthyroid older men.Methods: We examined healthy men (N = 44, mean age = 72), excluding clinically hypothyroid/hyperthyroid or diabetic/hyperglycemic subjects and those with dementia, depression, CNS medications, or recent illness. Plasma samples obtained across a 24-hour period were pooled, then assayed for total thyroxine (TT4), total triiodothyronine (TT3), and T3 resin uptake. Free thyroxine index (FT4I) was calculated. A broad cognitive battery (including the Wechsler Adult Intelligence Scale-Revised [WAIS-R], the Dementia Rating Scale [DRS], and the Rivermead Behavioral Profile [PROFILE]) was administered to all subjects.Results: Regression analyses controlling age and education showed TT4 and FT4I to have significant positive relationships with measures of overall cognition; TT4 accounted for 8% to 12% of the variance in omnibus cognitive measures such as WAIS Performance, WAIS Verbal score, and GLOBAL cognitive scores.Conclusions: Our findings suggest that within "normal" range of variation in plasma thyroid hormones, TT4 but not T3 positively associates with general cognition in healthy elderly men. [ABSTRACT FROM AUTHOR]

Background: A breath test for volatile organic compounds has identified biomarkers associated with breast cancer. We evaluated the potential clinical and economic benefits of a breath test to detect women at low risk for breast cancer by comparing its negative predictive value (NPV) to the NPV of screening mammography., Methods: Sensitivity and specificity values for screening mammography were obtained from the Food & Drug Administration Mammography Quality Standards Act; Amendments to Part 900 Regulations Docket No. FDA-2013-N-0134. The high values were sensitivity = 79.0%, specificity = 88.9% and the low values were sensitivity = 66.0%, specificity = 88.9%. In two previous studies of 771 women undergoing mammography, breath testing identified breast cancer with sensitivity=84% and specificity = 68.6% in 178 asymptomatic women, and sensitivity=82% and specificity = 77% in 593 who were symptomatic. These values were projected to a hypothetical screening population of 100,000 asymptomatic women with average breast cancer prevalence of 450/100,000, in order to estimate the NPV and PPV (positive predictive value) for breath testing and screening mammography respectively., Results: Breath test in asymptomatic women: NPV = 99.895% and PPV = 1.19%; in symptomatic women: NPV = 99.895% and PPV = 1.59%. For screening mammography, NPV = 99.83% and PPV = 2.82% (low values), increasing to NPV= 99.89% and PPV = 3.12% (high values). A negative breath test identified 68.3% of the screening population as having low risk of breast cancer, with NPV similar to mammography. Based on Medicare reimbursement rates, elimination of mammography in women with a negative breath test could reduce the annual cost of breast cancer screening by 38.9., Conclusions: In a hypothetical screening population, a negative breath test ruled out breast cancer with the same accuracy as a negative mammogram. A screening breath test could potentially eliminate the need for two thirds of all mammograms and reduce the costs of screening without increasing the risk of false-negative findings. If applied in clinical practice, this approach could potentially reduce the costs and burdens of breast cancer screening services, and benefit women by lessening the discomfort, anxiety, radiation exposure, and costs associated with mammography., Competing Interests: Conflict of Interest: Michael Phillips is President and CEO of Menssana Research, Inc. All other authors declare that they have no conflict of interest.

Previous studies have reported volatile organic compounds (VOCs) in the breath as biomarkers of breast cancer. These biomarkers may be derived from cancer-associated fibroblasts, in which oxidative stress degrades polyunsaturated fatty acids to volatile alkanes and methylated alkane derivatives that are excreted in the breath. We evaluated a rapid point-of-care test for breath VOC biomarkers as predictors of breast cancer and abnormal mammograms. We studied 593 women aged⩾18 yr referred to three sites for mammography for a symptomatic breast-related concern (e.g. breast mass, nipple discharge). A rapid point-of-care breath testing system collected and concentrated alveolar breath VOCs on a sorbent trap and analyzed them with gas chromatography and surface acoustic wave detection in <6 min. Breath VOC chromatograms were randomly assigned to a training set or to a validation set. Monte Carlo analysis identified significant breath VOC biomarkers of breast cancer and abnormal mammograms in the training set, and these biomarkers were incorporated into a multivariate algorithm to predict disease in the validation set. Prediction of breast cancer: 50 women had biopsy-proven breast cancer (invasive cancer 41, ductal non-invasive cancer 9) Unsplit data set: breath VOCs identified breast cancer with 83% accuracy (area under curve of receiver operating characteristic), 82% sensitivity and 77.1% specificity. Split data sets: training set breath VOCs identified breast cancer with 80.3% accuracy, 84% sensitivity and 74.3% specificity. Corresponding values in the validation set were 68%% accuracy, 72.4% sensitivity and 61.5% specificity. Prediction of BIRADS 4 and 5 mammograms (versus BIRADS 1, 2 and 3): unsplit data set: breath VOCs identified abnormal mammograms with 76.2% accuracy. Split data sets: breath VOCs identified abnormal mammograms with 74.2% accuracy, 73.3% sensitivity and 60% specificity. Corresponding values in the validation set were 60.5% accuracy, 64.2% sensitivity and 51% specificity. A rapid point-of-care test for breath VOC biomarkers predicted risk of breast cancer and abnormal mammograms in women with breast-related symptoms., (© 2024 IOP Publishing Ltd. All rights, including for text and data mining, AI training, and similar technologies, are reserved.)

Background: Women with dense breasts benefit from supplemental cancer screening with US, but US has low specificity., Purpose: To evaluate the performance of breast US tomography (UST) combined with full-field digital mammography (FFDM) compared with FFDM alone for breast cancer screening in women with dense breasts., Materials and Methods: This retrospective multireader multicase study included women with dense breasts who underwent FFDM and UST at 10 centers between August 2017 and October 2019 as part of a prospective case collection registry. All patients in the registry with cancer were included; patients with benign biopsy or negative follow-up imaging findings were randomly selected for inclusion. Thirty-two Mammography Quality Standards Act-qualified radiologists independently evaluated FFDM followed immediately by FFDM plus UST for suspicious findings and assigned a Breast Imaging Reporting and Data System (BI-RADS) category. The superiority of FFDM plus UST versus FFDM alone for cancer detection (assessed with area under the receiver operating characteristic curve [AUC]), BI-RADS 4 sensitivity, and BI-RADS 3 sensitivity and specificity were evaluated using the two-sided significance level of α = .05. Noninferiority of BI-RADS 4 specificity was evaluated at the one-sided significance level of α = .025 with a -10% margin., Results: Among 140 women (mean age, 56 years ±10 [SD]; 36 with cancer, 104 without), FFDM plus UST achieved superior performance compared with FFDM alone (AUC, 0.60 [95% CI: 0.51, 0.69] vs 0.54 [95% CI: 0.45, 0.64]; P = .03). For FFDM plus UST versus FFDM alone, BI-RADS 4 mean sensitivity was superior (37% [428 of 1152] vs 30% [343 of 1152]; P = .03) and BI-RADS 4 mean specificity was noninferior (82% [2741 of 3328] vs 88% [2916 of 3328]; P = .004). For FFDM plus UST versus FFDM, no difference in BI-RADS 3 mean sensitivity was observed (40% [461 of 1152] vs 33% [385 of 1152]; P = .08), but BI-RADS 3 mean specificity was superior (75% [2491 of 3328] vs 69% [2299 of 3328]; P = .04)., Conclusion: In women with dense breasts, FFDM plus UST improved cancer detection by radiologists versus FFDM alone. Clinical trial registration nos. NCT03257839 and NCT04260620 Published under a CC BY 4.0 license. Supplemental material is available for this article. See also the editorial by Mann in this issue.

The Dual Process Model of Coping with Bereavement (DPM) proposes that there is an adaptive oscillation between loss-oriented (LO) and restorative-oriented (RO) coping processes. Empirical data supports these processes, but the oscillation process is not well-understood. This study explored the correspondence between the DPM and lived experience of bereaved people, with an additional investigation of perceived changes in grief over time. Using a cooperative inquiry inspired participatory research design, nine bereaved adults and three researchers met nine times to discuss experiences of grief. Knowledge production took place through ongoing sharing, exploration, and reflection upon personal experiences and grief theory. Support was found for the LO and RO processes, but they were perceived to overlap. Support was also found for the oscillation process, which was found to hold learning properties. Time off from grief was not supported. Perspectives on how and why grief experiences change over time emerged, emphasizing the importance of acceptance, learning, time, and contextual factors.

The benefits of expressive writing have been explored since at least the 1980s. The effect of expressive bereavement-related writing has been studied primarily in college students, yielding inconclusive results. Nonetheless, recent effective, integrated psychotherapy protocols, targeting complicated and prolonged grief, include writing assignments, typically in the form of letters. The present paper explores how and why letter writing might be effective and meaningful as a therapeutic tool in the context of grief psychotherapy. It describes how working with letters, addressed to the deceased, might help facilitate self-disclosure, promote exposure to what is avoided, confront unfinished business, encourage continuing bonds, and help achieve a coherent narrative around experiences with the loss. As a therapeutic tool, letter writing has the potential to be helpful to many bereaved people, as it is a simple, effective, and meaningful way to access and work with relevant clinical material in the context of psychotherapy., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

This study examined the effectiveness of an 18-session manualized integrative group psychotherapy intervention for parentally bereaved young adults with grief complications. Participants, 63 young adults aged 20-27 years, completed questionnaires assessing symptoms of prolonged grief, PTSD, depression and anxiety prior to and following treatment. Treatment effectiveness was assessed by comparing outcomes for the intervention group to a waitlist comparison group. Results revealed a statistically significant reduction in symptoms of grief (large effects size), PTSD (medium effect sizes), and depression (medium effect size). The treatment did not result in a significant reduction in anxiety symptoms. The study provided preliminary support for this intervention for parentally bereaved young adults., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Context: Cholesterol carried in lipoprotein(a) adds to measured low-density lipoprotein cholesterol (LDL-C) and may therefore drive some diagnoses of clinical familial hypercholesterolemia (FH)., Objective: We investigated plasma lipoprotein(a) in individuals referred to Danish lipid clinics and evaluated the effect of plasma lipoprotein(a) on a diagnosis of FH., Methods: Individuals referred to 15 Danish lipid clinics who were suspected of having FH according to nationwide referral criteria were recruited between September 1, 2020 and November 30, 2021. All individuals were classified according to the Dutch Lipid Clinical Network criteria for FH before and after LDL-C was adjusted for 30% cholesterol content in lipoprotein(a). We calculated the fraction of individuals fulfilling a clinical diagnosis of FH partly due to elevated lipoprotein(a)., Results: We included a total of 1166 individuals for analysis, of whom 206 fulfilled a clinical diagnosis of FH. Median lipoprotein(a) was 15 mg/dL (29 nmol/L) in those referred and 28% had lipoprotein(a) greater than or equal to 50 mg/dL (105 nmol/L), while 2% had levels greater than or equal to 180 mg/dL (389 nmol/L). We found that in 27% (55/206) of those fulfilling a clinical diagnosis of FH, this was partly due to high lipoprotein(a)., Conclusion: Elevated lipoprotein(a) was common in individuals referred to Danish lipid clinics and in one-quarter of individuals who fulfilled a clinical diagnosis of FH, this was partly due to elevated lipoprotein(a). These findings support the notion that the LPA gene should be considered an important causative gene in patients with clinical FH and further support the importance of measuring lipoprotein(a) when diagnosing FH as well as for stratification of cardiovascular risk., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background Most low- and middle-income countries lack access to organized breast cancer screening, and women with lumps may wait months for diagnostic assessment. Purpose To demonstrate that artificial intelligence (AI) software applied to breast US images obtained with low-cost portable equipment and by minimally trained observers could accurately classify palpable breast masses for triage in a low-resource setting. Materials and Methods This prospective multicenter study evaluated participants with at least one palpable mass who were enrolled in a hospital in Jalisco, Mexico, from December 2017 through May 2021. Orthogonal US images were obtained first with portable US with and without calipers of any findings at the site of lump and adjacent tissue. Then women were imaged with standard-of-care (SOC) US with Breast Imaging Reporting and Data System assessments by a radiologist. After exclusions, 758 masses in 300 women were analyzable by AI, with outputs of benign, probably benign, suspicious, and malignant. Sensitivity, specificity, and area under the receiver operating characteristic curve (AUC) were determined. Results The mean patient age ± SD was 50.0 years ± 12.5 (range, 18-92 years) and mean largest lesion diameter was 13 mm ± 8 (range, 2-54 mm). Of 758 masses, 360 (47.5%) were palpable and 56 (7.4%) malignant, including six ductal carcinoma in situ. AI correctly identified 47 or 48 of 49 women (96%-98%) with cancer with either portable US or SOC US images, with AUCs of 0.91 and 0.95, respectively. One circumscribed invasive ductal carcinoma was classified as probably benign with SOC US, ipsilateral to a spiculated invasive ductal carcinoma. Of 251 women with benign masses, 168 (67%) imaged with SOC US were classified as benign or probably benign by AI, as were 96 of 251 masses (38%, P < .001) with portable US. AI performance with images obtained by a radiologist was significantly better than with images obtained by a minimally trained observer. Conclusion AI applied to portable US images of breast masses can accurately identify malignancies. Moderate specificity, which could triage 38%-67% of women with benign masses without tertiary referral, should further improve with AI and observer training with portable US. © RSNA, 2023 Supplemental material is available for this article. See also the editorial by Slanetz in this issue.

Considerable effort has gone into studying bereavement in children, adults and the elderly, but few studies have investigated the effects of bereavement or grief interventions in young adults. Even fewer studies have reported on the effect of interventions for young adults with grief complications. The present study seeks to help fill this gap by describing a Danish treatment program specially developed for young adults with complicated grief reactions. The dual process model of coping with bereavement, psychodynamic theory, and a narrative approach provide the foundation for the treatment. In addition, it utilizes an eclectic use of techniques and a group treatment modality that involves providing individual therapy within a group context. The core elements of the treatment are discussed and then exemplified in two case studies.

Aims: We evaluated the performance of contrast-enhanced ultrasound (CEUS) based on radiomics analysis to distinguish benign from malignant breast masses., Methods: 131 women with suspicious breast masses (BI-RADS 4a, 4b, or 4c) who underwent CEUS examinations (using intravenous injection of perflutren lipid microsphere or sulfur hexafluoride lipid-type A microspheres) prior to ultrasound-guided biopsies were retrospectively identified. Post biopsy pathology showed 115 benign and 16 malignant masses. From the cine clip of the CEUS exams obtained using the built-in GE scanner software, breast masses and adjacent normal tissue were then manually segmented using the ImageJ software. One frame representing each of the four phases: precontrast, early, peak, and delay enhancement were selected post segmentation from each CEUS clip. 112 radiomic metrics were extracted from each segmented tissue normalized breast mass using custom Matlab ® code. Linear and nonlinear machine learning (ML) methods were used to build the prediction model to distinguish benign from malignant masses. tenfold cross-validation evaluated model performance. Area under the curve (AUC) was used to quantify prediction accuracy., Results: Univariate analysis found 35 (38.5%) radiomic variables with p < 0.05 in differentiating between benign from malignant masses. No feature selection was performed. Predictive models based on AdaBoost reported an AUC = 0.72 95% CI (0.56, 0.89), followed by Random Forest with an AUC = 0.71 95% CI (0.56, 0.87)., Conclusions: CEUS based texture metrics can distinguish between benign and malignant breast masses, which can, in turn, lead to reduced unnecessary breast biopsies., (© 2022. Società Italiana di Ultrasonologia in Medicina e Biologia (SIUMB).)

Background: Modern lifestyle is associated with a high prevalence of physical inactivity., Objective: This study aims to investigate the effect of a wearable tracking device on cardiorespiratory fitness among inactive adults and to explore if personal characteristics and health outcomes can predict adoption of the device., Methods: In total, 62 inactive adults were recruited for this study. A control period (4 weeks) was followed by an intervention period (8 weeks) where participants were instructed to register and follow their physical activity (PA) behavior on a wrist-worn tracking device. Data collected included estimated cardiorespiratory fitness, body composition, blood pressure, perceived stress levels, and self-reported adoption of using the tracking device., Results: In total, 50 participants completed the study (mean age 48, SD 13 years, 84% women). Relative to the control period, participants increased cardiorespiratory fitness by 1.52 mL/kg/minute (95% CI 0.82-2.22; P<.001), self-reported PA by 140 minutes per week (95% CI 93.3-187.1; P<.001), daily step count by 982 (95% CI 492-1471; P<.001), and participants' fat percentage decreased by 0.48% (95% CI -0.84 to -0.13; P=.009). No difference was observed in blood pressure (systolic: 95% CI -2.16 to 3.57, P=.63; diastolic: 95% CI -0.70 to 2.55; P=.27) or perceived stress (95% CI -0.86 to 1.78; P=.49). No associations were found between adoption of the wearable tracking device and age, gender, personality, or education. However, participants with a low perceived stress at baseline were more likely to rate the use of a wearable tracking device highly motivating., Conclusions: Tracking health behavior using a wearable tracking device increases PA resulting in an improved cardiorespiratory fitness among inactive adults., (©Lisbeth Hoejkjaer Larsen, Maja Hedegaard Lauritzen, Mikkel Sinkjaer, Troels W Kjaer. Originally published in JMIR Cardio (https://cardio.jmir.org), 15.03.2022.)

Background: The aim of this prospective study was to assess the diagnostic value of nuclear imaging with 18 F-FDG PET/CT (FDG PET/CT), combined 111 In-WBC/ 99m Tc-Nanocoll, and 99m Tc-HDP SPECT/CT (dual-isotope WBC/bone marrow scan) for patients with chronic problems related to knee or hip prostheses (TKA or THA) scheduled by a structured multidisciplinary algorithm., Materials and Methods: Fifty-five patients underwent imaging with 99m Tc-HDP SPECT/CT (bone scan), dual-isotope WBC/bone marrow scan, and FDG PET/CT. The final diagnosis of prosthetic joint infection (PJI) and/or loosening was based on the intraoperative findings and microbiological culture results and the clinical follow-up., Results: The diagnostic performance of dual-isotope WBC/bone marrow SPECT/CT for PJI showed a sensitivity of 100% (CI 0.74-1.00), a specificity of 97% (CI 0.82-1.00), and an accuracy of 98% (CI 0.88-1.00); for PET/CT, the sensitivity, specificity, and accuracy were 100% (CI 0.74-1.00), 71% (CI 0.56-0.90), and 79% (CI 0.68-0.93), respectively., Conclusions: In a standardized prospectively scheduled patient group, the results showed highly specific performance of combined dual-isotope WBC/bone marrow SPECT/CT in confirming chronic PJI. FDG PET/CT has an appropriate accuracy, but the utility of its use in the clinical diagnostic algorithm of suspected PJI needs further evidence.

Purpose: In neuropathic postural tachycardia syndrome, peripheral sympathetic dysfunction leads to excessive venous blood pooling during orthostasis. Up to 84% of patients report leg pain and weakness in the upright position. To explore possible pathophysiological processes underlying these symptoms, the present study examined muscle excitability depending on body position in patients with neuropathic postural tachycardia syndrome and healthy subjects., Methods: In ten patients with neuropathic postural tachycardia syndrome and ten healthy subjects, muscle excitability measurements were performed repeatedly: in the supine position, during 10 min of head-up tilt and during 6 min thereafter. Additionally, lower leg circumference was measured and subjective leg pain levels were assessed., Results: In patients with neuropathic postural tachycardia syndrome, muscle excitability was increased in the supine position, decreased progressively during tilt, continued to decrease after being returned to the supine position, and did not completely recover to baseline values after 6 min of supine rest. The reduction in muscle excitability during tilt was paralleled by an increase in lower leg circumference as well as leg pain levels. No such changes were observed in healthy subjects., Conclusions: This study provides evidence for the occurrence of orthostatic changes in muscle excitability in patients with neuropathic postural tachycardia syndrome and that these may be associated with inadequate perfusion of the lower extremities. Insufficient perfusion as a consequence of blood stasis may cause misery perfusion of the muscles, which could explain the occurrence of orthostatic leg pain in neuropathic postural tachycardia syndrome., (© 2021. The Author(s).)

Objective: Uremic myopathy is a condition seen in end-stage renal disease (ESRD), characterized by muscle weakness and muscle fatigue, in which the pathophysiology is uncertain. The aim of this study was to assess the role of abnormal serum constituents in ESRD patients by relating them to the excitability properties of the tibialis anterior muscle, at rest and during electrically induced muscle activation, by recording muscle velocity recovery cycles (MVRC) and frequency ramp responses., Methods: Eighteen ESRD patients undergoing hemodialysis were evaluated by blood sample, MVRC, and frequency ramp (before and near the end of dialysis treatment), quantitative electromyography, and nerve conduction studies. Patients were compared to 24 control subjects., Results: In patients, muscle relative refractory period, early supernormality, late supernormality after 5 conditioning stimuli, and latency of the last of 15 and 30 frequency ramp pulses were strongly associated with potassium levels (p < 0.01), showing depolarization before and normalization in the end of hemodialysis., Conclusions: In ESRD patients, the muscle membrane is depolarized, mainly due to hyperkalemia., Significance: Since normal muscle fatigue has been attributed to potassium-induced depolarization, it seems likely that this mechanism is also a major cause of the exaggerated muscle fatigue and weakness in ESRD patients., Competing Interests: Declaration of Competing Interest Professor Hugh Bostock receives royalties from UCL for sales of his Qtrac software used in this study. The other authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 International Federation of Clinical Neurophysiology. All rights reserved.)

We evaluated whole breast stiffness imaging by SoftVue ultrasound tomography (UST), extracted from the bulk modulus, to volumetrically map differences in breast tissues and masses. A total 206 women with either palpable or mammographically/sonographically visible masses underwent UST scanning prior to biopsy as part of a prospective, HIPAA-compliant multicenter cohort study. The volumetric data sets comprised 298 masses (78 cancers, 105 fibroadenomas, 91 cysts and 24 other benign) in 239 breasts. All breast tissues were segmented into six categories, using sound speed to separate fat from fibroglandular tissues, and then subgrouped by stiffness into soft, intermediate and hard components. Ninety percent of women had mammographically dense breasts but only 11.2% of their total breast volume showed hard components while 69% of fibroglandular tissues were softer. All smaller masses (<1.5 cm) showed a greater percentage of hard components than their corresponding larger masses ( p < 0.001). Cancers had significantly greater mean stiffness indices and lower mean homogeneity of stiffness than benign masses ( p < 0.05). SoftVue stiffness imaging demonstrated small stiff masses, mainly due to cancers, amongst predominantly soft breast tissues. Quantitative stiffness mapping of the whole breast and underlying masses may have implications for screening of women with dense breasts, cancer risk evaluations, chemoprevention and treatment monitoring.

Purpose: Racial and ethnic disparities have exacerbated during the COVID-19 pandemic as the healthcare system is overwhelmed. While Hispanics are disproportionately affected by COVID-19, little is known about ethnic disparities in the hospital settings. This study investigates imaging utilization and clinical outcomes between Hispanic and non-Hispanic COVID-19 patients in the Emergency Department (ED) and during hospitalization., Methods: Through retrospective chart review, we included 331 symptomatic COVID-19 patients (mean age 53.2 years) at a metropolitan healthcare system from March to June 2020. Poisson regression was used to compare diagnostic imaging utilization and clinical outcomes between Hispanic and non-Hispanic patients., Results: After adjusting for confounders, no statistically significant difference was found between Hispanic and non-Hispanic patients for the number of weekly chest X-rays. Results were categorized into four clinical outcomes: ED management (0.16 ± 0.05 vs. 0.14 ± 0.8, p:0.79); requiring inpatient management (1.31 ± 0.11 vs. 1.46 ± 0.16, p:0.43); ICU admission without invasive ventilation (1.4 ± 0.17 vs. 1.35 ± 0.26, p:0.86); and ICU admission and ventilator support (3.29 ± 0.22 vs. 3.59 ± 0.37, p:0.38). There were no statistically significant relative differences in adjusted prevalence rate between ethnic groups for all clinical outcomes (p > 0.05). There was a statistically significant longer adjusted length of stay (days) in non-Hispanics for two subcohorts: inpatient management (8.16 ± 0.31 vs. 9.72 ± 0.5, p < 0.01) and ICU admission without invasive ventilation (10.39 ± 0.57 vs. 13.45 ± 1.13, p < 0.01)., Conclusions: For Hispanic and non-Hispanic COVID-19 patients in the ED or hospitalized, there were no statistically significant differences in imaging utilization and clinical outcomes., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Objective: To investigate the sensitivity of muscle velocity recovery cycles (MVRCs) for detecting altered membrane properties in critically ill patients, and to compare this to conventional nerve conduction studies (NCS) and quantitative electromyography (qEMG)., Methods: Twenty-four patients with intensive care unit acquired weakness (ICUAW) and 34 healthy subjects were prospectively recruited. In addition to NCS (median, ulnar, peroneal, tibial and sural nerves) and qEMG (biceps brachii, vastus medialis and anterior tibial muscles), MVRCs with frequency ramp were recorded from anterior tibial muscle., Results: MVRC and frequency ramp parameters showed abnormal muscle fiber membrane properties with up to 100% sensitivity and specificity. qEMG showed myopathy in 15 patients (63%) while polyneuropathy was seen in 3 (13%). Decreased compound muscle action potential (CMAP) amplitude (up to 58%) and absent F-waves (up to 75%) were frequent, but long duration CMAPs were only seen in one patient with severe myopathy., Conclusions: Altered muscle fiber membrane properties can be detected in patients with ICUAW not yet fulfilling diagnostic criteria for critical illness myopathy (CIM). MVRCs may therefore serve as a tool for early detection of evolving CIM., Significance: CIM is often under-recognized by intensivists, and large-scale longitudinal studies are needed to determine its incidence and pathogenesis., Competing Interests: Declaration of Competing Interest Professor Hugh Bostock receives royalties from UCL for sales of his Qtrac software used in this study. The other authors have no conflicts of interest to disclose. All authors have approved the final paper., (Copyright © 2021 International Federation of Clinical Neurophysiology. All rights reserved.)

Background: Modern lifestyle is heavily affected by technology such as smartphones, tablets, and other small computers; yet it remains unclear how our health and well-being are affected by the heavy use of these devices., Objective: This feasibility study aims to test two different interventions of an experimental protocol for a forthcoming large-scale community-based study and get estimates of parameters for sample size calculation. The aim of the large-scale study is to investigate the effect of (1) a wearable tracking device on aerobic capacity (VO 2 max/kg) and the effect of (2) restricting media use on total sleep time., Methods: Twenty healthy participants were included and equipped with a wrist-worn device tracking physical activity and sleep. Participants were allocated to either a physical activity group, which was instructed to use the wrist-worn device to support exercise, or a sleep silent group, which was instructed to remove or switch off all electronic devices in the bedroom (except the wrist-worn tracking device). The intervention lasted approximately 4 weeks. Data collected included blood pressure, submaximal cycle ergometer test, self-reported technology use, and compliance of using the wearable tracking device., Results: All participants wore the wearable tracking device 95.8% (SD 4.4%) of the time. Participants in the physical activity group increased aerobic capacity from 30.38 (SD 8.98) to 32.1 (SD 8.71) mL/kg/min (t=-2.31, P=.046) and decreased their systolic blood pressure from 126.5 (SD 15.8) mm Hg to 121.8 (SD 11.7) mm Hg (t=2.72, P=.02). The sleep silent group prolonged their time offline before bedtime from 18.1 (SD 19.4) minutes to 27.2 (SD 17.3) minutes (t=-2.94, P=.02)., Conclusions: The two interventions are feasible to conduct. Participants were willing to wear the tracking device on their wrist and restrict all media use in their bedroom and thereby reduce bedtime technology use. Our results also suggest that tracking physical activity using a wearable device is accompanied by noteworthy health benefits. We outline necessary adjustments for a forthcoming large-scale study., (©Lisbeth Hoekjaer Larsen, Maja Hedegaard Lauritzen, Sirin Wilhelmsen Gangstad, Troels Wesenberg Kjaer. Originally published in JMIR Formative Research (http://formative.jmir.org), 04.01.2021.)

Scope: Brown and brite adipocytes within the mammalian adipose organ provide non-shivering thermogenesis and thus, have an exceptional capacity to dissipate chemical energy as heat. Polyunsaturated fatty acids (PUFA) of the n3-series, abundant in fish oil, have been repeatedly demonstrated to enhance the recruitment of thermogenic capacity in these cells, consequently affecting body adiposity and glucose tolerance. These effects are scrutinized in mice housed in a thermoneutral environment and in a human dietary intervention trial., Methods and Results: Mice are housed in a thermoneutral environment eliminating the superimposing effect of mild cold-exposure on thermogenic adipocyte recruitment. Dietary fish oil supplementation in two different inbred mouse strains neither affects body mass trajectory nor enhances the recruitment of brown and brite adipocytes, both in the presence and absence of a β3-adrenoreceptor agonist imitating the effect of cold-exposure on adipocytes. In line with these findings, dietary fish oil supplementation of persons with overweight or obesity fails to recruit thermogenic adipocytes in subcutaneous adipose tissue., Conclusion: Thus, the authors' data question the hypothesized potential of n3-PUFA as modulators of adipocyte-based thermogenesis and energy balance regulation., (© 2020 The Authors. Molecular Nutrition & Food Research published by Wiley-VCH GmbH.)

Wearable sleep technology allows for a less intruding sleep assessment than PSG, especially in long-term sleep monitoring. Though such devices are less accurate than PSG, sleep trackers may still provide valuable information. This study aimed to validate a commercial sleep tracker, Garmin Vivosmart 4 (GV4), against polysomnography (PSG) and to evaluate intra-device reliability (GV4 vs. GV4). Eighteen able-bodied adults (13 females, M = 56.1 ± 12.0 years) with no self-reported sleep disorders were simultaneously sleep monitored by GV4 and PSG for one night while intra-device reliability was monitored in one participant for 23 consecutive nights. Intra-device agreement was considered sufficient (observed agreement = 0.85 ± 0.13, Cohen's kappa = 0.68 ± 0.24). GV4 detected sleep with high accuracy (0.90) and sensitivity (0.98) but low specificity (0.28). Cohen's kappa was calculated for sleep/wake detection (0.33) and sleep stage detection (0.20). GV4 significantly underestimated time awake (p = 0.001) including wake after sleep onset (WASO) (p = 0.001), and overestimated light sleep (p = 0.045) and total sleep time (TST) (p = 0.001) (paired t-test). Sleep onset and sleep end differed insignificantly from PSG values. Our results suggest that GV4 is not able to reliably describe sleep architecture but may allow for detection of changes in sleep onset, sleep end, and TST (ICC ≥ 0.825) in longitudinally followed groups. Still, generalizations are difficult due to our sample limitations., Competing Interests: Garmin® kindly borrowed us GV4 watches to perform our experiment. This had no influence on our study design, data analysis, results or conclusions and does not alter our adherence to the PLOS ONE policies on sharing data and materials.

Long-term, continuous datasets of high quality are important for instrumentation, control, and automation efforts of wastewater resources recovery facility (WRRFs). This study presents a methodology to increase the reliability of measurements from ammonium ion-selective electrodes (ISEs). This is done by correcting corrupted ISE data with a data source that often is available at WRRFs (volume-proportional composite samples). A yearlong measurement campaign showed that the existing standard protocols for sensor maintenance might still create corrupted dataset, with poor sensor recalibrations responsible for abrupt and unrealistic jumps in the measurements. The proposed automatic correction methodology removes both recalibration jumps and signal drift by using information from composite samples that already are taken for reporting to legal authorities. Results showed that the developed methodology provided a continuous, high-quality time series without the major data quality issues of the original signal. In fact, the signal was improved for 87% of days when a reference sample was available. The effect of correcting the data before use in a data-driven software sensor was also investigated. The corrected dataset led to noticeably smaller day-to-day variations in estimated NH 4 + loads, and to large improvements on both median estimates and prediction bounds. The long time series allowed for an investigation of how much training data that is required to fit a software sensor, which provides estimates that are representative for the entire study period. The results showed that 8 weeks of data allowed for a good median estimate, while 16 weeks are required for obtaining good 80% prediction bounds. Overall, the proposed method can increase the applicability of relatively cheaper ISE sensors for ICA application within WRRFs., Competing Interests: Declaration of Competing Interest We declare that we do not have any commercial or associative interest that represents a conflict of interest in connection with the work submitted., (Copyright © 2020. Published by Elsevier Ltd.)

Purpose: The objective of this study was to investigate the additive effects of combining energy restriction with dietary fibres on change in body weight and gut microbiota composition., Methods: The study was a 12-week randomised, placebo-controlled, double-blinded, parallel intervention trial. A total of 116 overweight or obese participants were assigned randomly either to 10 g inulin plus 10 g resistant maltodextrin or to 20 g of placebo supplementation through 400 mL of milk a day, while on a - 500 kcal/day energy restricted diet., Results: Altogether, 86 participants completed the intervention. There were no significant differences in weight loss or body composition between the groups. The fibre supplement reduced systolic (5.35 ± 2.4 mmHg, p = 0.043) and diastolic (2.82 ± 1.3 mmHg, p = 0.047) blood pressure to a larger extent than placebo. Furthermore, a larger decrease in serum insulin was observed in the placebo group compared to the fibre group (- 26.0 ± 9.2 pmol/L, p = 0.006). The intake of fibre induced changes in the composition of gut microbiota resulting in higher abundances of Parabacteroides and Bifidobacteria, compared to placebo. The effects on blood pressure and glucose metabolism were mainly observed in women, and could be attributed to a higher gut microbiota diversity after intervention. Finally, the fibre group experienced a higher degree of gastrointestinal symptoms, which attenuated over time., Conclusions: Supplementation of inulin and resistant maltodextrin did not provide an additional weight loss during an energy-restricted diet, but reduced both systolic and diastolic blood pressure. Furthermore, the fibre supplement did stimulate the growth of potentially beneficial bacteria genera., Clinical Trial Registry: The study was registered at http://www.clinicaltrials.gov , NCT03135041.

Objectives: The aim of this study was to compare the acute effects of isometric versus dynamic resistance exercise on pain during a pain-provoking activity, and exercise-induced hypoalgesia in participants with patellar tendinopathy., Design: This study was a pre-registered randomised crossover study. Participants were blinded to the study hypothesis., Methods: Participants (N = 21) performed a single session of high load isometric resistance exercise or dynamic resistance exercise, in a randomised order separated by a 7-day washout period. Outcomes were assessed before, immediately after, and 45 min post-exercise. The primary outcome was pain intensity scored on a numeric pain rating scale (NRS; 0-10) during a pain-provoking single leg decline squat (SLDS). Secondary outcomes were pressure pain thresholds (PPTs) locally, distally and remotely, as well as tendon thickness., Results: There was a significant decrease in pain NRS scores (mean reduction 0.9, NRS 95%CI 0.1-1.7; p = 0.028), and increase in PPTs at the tibialis anterior muscle (mean increase 34 kPa 95%CI 9.5-58.5; p = 0.009) immediately post-exercise. These were not sustained 45 min post-exercise for pain (NRS) or PPTs (p > 0.05). There were no differences between exercise on any outcome., Conclusions: While patients with patellar tendinopathy decreased pain during SLDS in response to resistance training, but the magnitude was small. Contraction mode may not be the most important factor in determining the magnitude of pain relieving effects. Similarly, there were only small increases in PPTs at the tibialis anterior which were not superior for isometric exercise., (Copyright © 2019 Sports Medicine Australia. Published by Elsevier Ltd. All rights reserved.)

Objective: This study investigated whether the levels of specific serum microRNAs (miRNAs) were altered following diet-induced weight loss and whether the serum miRNAs differed in the presence of the metabolic syndrome., Methods: The study was a weight loss intervention trial with a prescribed energy deficit of approximately 500 kcal/d. Levels of 22 miRNAs were determined in serum samples from 85 participants with overweight or obesity. miRNAs were analyzed using TaqMan Array miRNA Cards and normalized to the geometric mean of spiked-in ath-miR-159a and U6 small nuclear RNA using the ΔC T method., Results: The average weight loss was 5.7 kg (P < 0.001). miR-122-5p (-0.18 ± 0.06 log fold relative to initial, P < 0.01) and miR-193a-5p (-0.12 ± 0.04, P < 0.01) levels decreased in response to weight loss. miR-126a-3p (0.11 ± 0.04, P = 0.01) and miR-222-3p (1.51 ± 0.12, P < 0.001) levels increased. Furthermore, a higher level of miR-122-5p was observed at baseline in participants with the metabolic syndrome compared with participants without (0.28 ± 0.08, P < 0.01)., Conclusions: Changes in circulating miR-122-5p, miR-126a-3p, miR-193a-5p, and miR-222-3p in response to diet-induced weight loss are demonstrated. Furthermore, assessment of miR-122-5p could be an indicator of an adverse metabolic health status independent of obesity., (© 2020 The Obesity Society.)

Although conventional nerve conduction studies (NCS) and electromyography (EMG) are suitable for the diagnosis of neuromuscular disorders, they provide limited information about muscle fiber membrane properties and underlying disease mechanisms. Muscle velocity recovery cycles (MVRCs) illustrate how the velocity of a muscle action potential depends on the time after a preceding action potential. MVRCs are closely related to changes in membrane potential that follow an action potential, thereby providing information about muscle fiber membrane properties. MVRCs may be recorded quickly and easily by direct stimulation and recording from multi-fiber bundles in vivo. MVRCs have been helpful in understanding disease mechanisms in several neuromuscular disorders. Studies in patients with channelopathies have demonstrated the different effects of specific ion channel mutations on muscle excitability. MVRCs have been previously tested in patients with neurogenic muscles. In this prior study, muscle relative refraction period (MRRP) was prolonged, and early supernormality (ESN) and late supernormality (LSN) were reduced in patients compared to healthy controls. Thereby, MVRCs can provide in vivo evidence of membrane depolarization in intact human muscle fibers that underlie their reduced excitability. The protocol presented here describes how to record MVRCs and analyze the recordings. MVRCs can serve as a fast, simple, and useful method for revealing disease mechanisms across a broad range of neuromuscular disorders.

The predominant indications for revision surgery after total hip (THA) or knee arthroplasty (TKA) are an aseptic failure (AF) and prosthetic joint infection (PJI). Accurate diagnosis is crucial. Therefore, we evaluated prospectively a multidisciplinary diagnostic algorithm including multi-modal radionucleid imaging (RNI) and extended microbiological diagnostics. If the surgeon suspected PJI or AF, revision surgery was performed with multiple samples obtained in parallel for special culture procedures and later molecular analyses. Alternatively, if the underlying cause was not evident, RNI was scheduled comprising 99 Tc - HDP SPECT/CT, 111 In-labeled white blood cells combined with 99 Tc-nanocoll bone marrow SPECT/CT, and 18 F-FDG PET/CT. A multidisciplinary clinical team made a recommendation on the indication for a diagnostic procedure guided by RNI images or revision surgery. A total of 156 patients with 163 arthroplasties were included. Fifty-five patients underwent RNI. In all, 118 revision surgeries were performed in 112 patients: 71 on the indication of AF and 41 revision of PJI. Thirty-four patients were concluded with chronic pain, and revision surgery refrained. The effective median follow-up period was 13 months. A structured approach offered by the algorithm was useful for the clinician in the evaluation of patients with a failing TKA or THA. Surgical revision was possibly obviated in approximately 20% of patients where an explanation or cause of failure was not found. The algorithm served as an effective tool., Competing Interests: The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.

Background/objectives: Pre-treatment gut microbial Prevotella-to-Bacteroides (P/B) ratio and markers of glucose metabolism (i.e., fasting glucose and insulin) have been suggested as biomarkers for optimal weight management. However, both biomarkers need further validation, and the interactions between them for optimal weight management are largely unknown. To investigate differences in weight loss maintenance between subjects with low and high P/B ratio and the potential interactions with markers of glucose metabolism and dietary fiber intake., Subjects/methods: Following an 8-week weight loss period using meal replacement products, subjects losing ≥ 8% of their initial body weight were randomized to one of three protein supplements or maltodextrin for a 24-week weight maintenance period. Habitual diet was consumed along with the supplements expected to constitute 10-15% of total energy. For this analysis we stratified the participants into low and high strata based on median values of pre-intervention P/B ratio, pre-weight loss Homeostatic model assessment of insulin resistance (HOMA-IR) (<2.33 or > 2.33), and dietary fiber intake during the intervention (< 28.5 or > 28.5 g/10 MJ)., Results: Regardless of weight maintenance regimen, subjects with high P/B ratio (n = 63) regained 1.5 (95% CI 0.4, 2.7) kg body weight (P = 0.007) more than subjects with low P/B ratio (n = 63). The regain among subjects with high P/B ratio was particular evident if HOMA-IR was high and dietary fiber intake was low. Consequently, in the high P/B strata, subjects with high HOMA-IR and low fiber intake (n = 17) regained 5.3 (95% CI 3.3, 7.3) kg (P < 0.001) more body weight compared with participants with low HOMA-IR and high fiber intake (n = 16)., Conclusions: Subjects with high P/B ratio were more susceptible to regain body weight compared with subjects with low P/B ratio, especially when dietary fiber intake was low and glucose metabolism was impaired. These observations underline that both the P/B ratio and markers of glucose metabolism should be considered as important biomarkers within personalized nutrition for optimal weight management.

Background & Aims: Gut microbiota composition is linked to obesity and metabolic syndrome. The nutrients and doses required to modulate the gut microbiota towards beneficially influence components of the metabolic syndrome are unclear. This study aimed to investigate diet-induced effects on the gut microbiota and metabolic markers in overweight individuals with indices of the metabolic syndrome., Methods: A twelve-week randomized cross-over trial was conducted with two intervention periods separated by a washout period. The dietary intakes of interest were wheat bran extract, rich in arabinoxylan oligosaccharides (AXOS) (10.4 g/d AXOS) and polyunsaturated fatty acids (PUFA) (3.6 g/d n-3 PUFA). Dietary records, fecal and blood samples, as well as anthropometric data, were collected before and after intervention. Anthropometry and gastrointestinal symptoms were evaluated weekly. Gut microbiota composition was analyzed by massive sequencing of 16S ribosomal RNA gene V3V4 amplicons., Results: Twenty-seven participants completed the study (90%). Intake of AXOS induced an expected bifidogenic effect on gut microbiota (p < 0.01) and increased butyrate-producing bacterial species as well (p < 0.05). Beta-diversity analysis indicated that the structure of the gut microbiota only changed as a result of the AXOS intervention (Permanova = 1.90, p < 0.02) and no changes in metabolic markers were observed after any of the interventions., Conclusions: AXOS intake has a bifidogenic effect and also increases butyrate producers in the gut microbiota; even though this type of dietary fiber did not modulate lipid or glucose metabolic parameters related to metabolic syndrome. Four-week PUFA intake did not induce any notable effect on the gut microbiota composition or metabolic risk markers., Registration: Registered under ClinicalTrials.gov Identifier no. NCT02215343., Clinical Trial Registration: Registered at https://www.clinicaltrials.gov/ (NCT02215343)., Ethical Committee: H-4-2014-052., The Danish Data Protection Agency: 2013-54-0522., (Copyright © 2019 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

A simple model for online forecasting of ammonium (NH 4 + ) concentrations in sewer systems is proposed. The forecast model utilizes a simple representation of daily NH 4 + profiles and the dilution approach combined with information from online NH 4 + and flow sensors. The method utilizes an ensemble approach based on past observations to create model prediction bounds. The forecast model was tested against observations collected at the inlet of two wastewater treatment plants (WWTPs) over an 11-month period. NH 4 + data were collected with ion-selective sensors. The model performance evaluation focused on applications in relation to online control strategies. The results of the monitoring campaigns highlighted a high variability in daily NH 4 + profiles, stressing the importance of an uncertainty-based modelling approach. The maintenance of the NH 4 + sensors resulted in important variations of the sensor signal, affecting the evaluation of the model structure and its performance. The forecast model succeeded in providing outputs that potentially can be used for integrated control of wastewater systems. This study provides insights on full scale application of online water quality forecasting models in sewer systems. It also highlights several research gaps which - if further investigated - can lead to better forecasts and more effective real-time operations of sewer and WWTP systems.

Circulating BDNF is higher in women than in men and suggested to be affected by changes in food intake, body weight, and exercise. The purpose of this study was to compare BDNF concentrations in women and men during a 12-week weight loss intervention. Using a previously published 12-week randomized study, serum BDNF was assessed at baseline and after 12 weeks using an enzyme-linked immunosorbent assay method. Fifty overweight or obese but healthy individuals (26 women, mean age of 36.4 ± 7.9 years; 24 men, mean age of 38.0 ± 5.9 years) were included and allocated into three groups: exercise-only (EXO; 12 weeks of aerobic exercise and isocaloric diet), diet-only (DIO; 8 weeks of very low energy diet (VLED 600 kcal/day) followed by a 4-week weight maintenance diet), or diet and exercise (DEX; 12 weeks of aerobic exercise in parallel with 8 weeks of VLED (800 kcal/day) followed by a 4-week weight maintenance diet). At baseline, BDNF levels were 25% higher in women compared to men ( p =0.006). Body weight was reduced in all intervention groups ( p < 0.006). Exercise (EXO group) induced a 22% reduction in circulating BDNF in men ( p =0.037) and women ( p =0.080). In the DIO and DEX groups, a significant reduction in BDNF levels (29.9%; p =0.035 and 32.5%; p =0.003, respectively) was observed in women but not in men. In conclusion, circulating BDNF was significantly changed by diet alone or combined with exercise in women and only by exercise alone in men. This suggests that changes in circulating BDNF depend on weight loss methods (diet/exercise) as well as sex., Competing Interests: There are no conflicts of interest to disclose., (Copyright © 2019 M. Glud et al.)

Long-term consumption of dietary fiber is generally considered beneficial for weight management and metabolic health, but the results of interventions vary greatly depending on the type of dietary fibers involved. This study provides a comprehensive evaluation of the effects of a specific dietary fiber consisting of a wheat-bran extract enriched in arabinoxylan-oligosaccharides (AXOS) in a human intervention trial. An integrated multi-omics analysis has been carried out to evaluate the effects of an intervention trial with an AXOS-enriched diet in overweight individuals with indices of metabolic syndrome. Microbiome analyses were performed by shotgun DNA sequencing in feces; in-depth metabolomics using nuclear magnetic resonance in fecal, urine, and plasma samples; and massive lipid profiling using mass spectrometry in fecal and serum/plasma samples. In addition to their bifidogenic effect, we observed that AXOS boost the proportion of Prevotella species. Metagenome analysis showed increases in the presence of bacterial genes involved in vitamin/cofactor production, glycan metabolism, and neurotransmitter biosynthesis as a result of AXOS intake. Furthermore, lipidomics analysis revealed reductions in plasma ceramide levels. Finally, we observed associations between Prevotella abundance and short-chain fatty acids (SCFAs) and succinate concentration in feces and identified a potential protective role of Eubacterium rectale against metabolic disease given that its abundance was positively associated with plasma phosphatidylcholine levels, thus hypothetically reducing bioavailability of choline for methylamine biosynthesis. The metagenomics, lipidomics, and metabolomics data integration indicates that sustained consumption of AXOS orchestrates a wide variety of changes in the gut microbiome and the host metabolism that collectively would impact on glucose homeostasis. (This study has been registered at ClinicalTrials.gov under identifier NCT02215343) IMPORTANCE The use of dietary fiber food supplementation as a strategy to reduce the burden of diet-related diseases is a matter of study given its cost-effectiveness and the positive results demonstrated in clinical trials. This multi-omics assessment, on different biological samples of overweight subjects with signs of metabolic syndrome, sheds light on the early and less evident effects of short-term AXOS intake on intestinal microbiota and host metabolism. We observed a deep influence of AXOS on gut microbiota beyond their recognized bifidogenic effect by boosting concomitantly a wide diversity of butyrate producers and Prevotella copri , a microbial species abundant in non-Westernized populations with traditional lifestyle and diets enriched in fresh unprocessed foods. A comprehensive evaluation of hundreds of metabolites unveiled new benefits of the AXOS intake, such as reducing the plasma ceramide levels. Globally, we observed that multiple effects of AXOS consumption seem to converge in reversing the glucose homeostasis impairment., (Copyright © 2019 Benítez-Páez et al.)

Background/objectives: Individuals with high pre-treatment bacterial Prevotella-to-Bacteroides (P/B) ratio have been reported to lose more body weight on diets high in fiber than subjects with a low P/B ratio. Therefore, the aim of the present study was to examine potential differences in dietary weight loss responses between participants with low and high P/B., Subjects/methods: Eighty overweight participants were randomized (52 completed) to a 500 kcal/d energy deficit diet with a macronutrient composition of 30 energy percentage (E%) fat, 52 E% carbohydrate and 18 E% protein either high (≈1500 mg calcium/day) or low ( ≤ 600 mg calcium/day) in dairy products for 24 weeks. Body weight, body fat, and dietary intake (by 7-day dietary records) were determined. Individuals were dichotomized according to their pre-treatment P/B ratio derived from 16S rRNA gene sequencing of collected fecal samples to test the potential modification of dietary effects using linear mixed models., Results: Independent of the randomized diets, individuals with high P/B lost 3.8 kg (95%CI, 1.8,5.8; P < 0.001) more body weight and 3.8 kg (95% CI, 1.1, 6.5; P = 0.005) more body fat compared to individuals with low P/B. After adjustment for multiple covariates, individuals with high P/B ratio lost 8.3 kg (95% CI, 5.8;10.9, P < 0.001) more body weight when consuming above compared to below 30 g fiber/10MJ whereas this weight loss was 3.2 kg (95% CI, 0.8;5.5, P = 0.008) among individuals with low P/B ratio [Mean difference: 5.1 kg (95% CI, 1.7;8.6, P = 0.003)]. Partial correlation coefficients between fiber intake and weight change was 0.90 (P < 0.001) among individuals with high P/B ratio and 0.25 (P = 0.29) among individuals with low P/B ratio., Conclusions: Individuals with high P/B lost more body weight and body fat compared to individuals with low P/B, confirming that individuals with a high P/B are more susceptible to weight loss on a diet rich in fiber.

Aims: Poor myometrial contractility has been demonstrated in women at term with diabetes and decreased muscular mitochondrial content and/or function has been extensively implicated in the progression of type 2 diabetes. Alterations of the uterine mitochondrial phenotype in pregnant women with diabetes have yet to be investigated as a causal link to decreased myometrial contractility., Methods: Observational study of 18 women with diabetes (type 2 and gestational) scheduled for an elective Caesarean section at term with matching controls. A uterine biopsy and fasting blood samples were taken on the day of delivery., Results: Respiration rates in isolated mitochondria and myometrial mRNA levels of genes related to mitochondrial biogenesis were unaffected by diabetes. Mitochondrial quantity examined by quantification of the complexes of the respiratory chain and histology did not indicate alterations in mitochondrial quantity. Citrate syntase activity was higher (0.31 ± 0.02 vs. 0.24 ± 0.02 U/mg protein, P = 0.008), whereas protein content was lower in women with diabetes compared with the control group (94.6 ± 6.9 vs. 118.6 ± 7.4 mg/g wet wt, P = 0.027). Histological examinations did not support any structural alterations in the myometrium or its mitochondria., Conclusion: No indication of decreased mitochondrial function, content, morphology, or localization in the myometrium at term in women with diabetes compared with controls was observed. The increase in citrate syntase activity in the myometrium could be explained by the lower protein content in the myometrium, which we suggest is due to alterations in tissue or cellular composition.

Low back pain (LBP) patients show reorganized trunk muscle activity but if similar changes are manifest in recurrent LBP (R-LBP) patients during asymptomatic periods remains unknown. In 26 healthy and 27 currently asymptomatic R-LBP participants electromyographic activity (EMG) was recorded from trunk and gluteal muscles during series of stepping up and down on a step bench before and during experimentally intramuscular induced unilateral and bilateral LBP. Pain intensity was assessed using numeric rating scale (NRS) scores. Root mean square EMG (RMS-EMG) normalized to maximal voluntary contraction EMG and pain-evoked differences from baseline (ΔRMS-EMG) were analyzed. Step task duration was calculated from foot sensors. R-LBP compared with controls showed higher baseline RMS-EMG and NRS scores of experimental pain (P < .05). In both groups, bilateral compared with unilateral experimental NRS scores were higher (P < .001) and patients compared with controls reported higher NRS scores during both pain conditions (P < .04). In patients, unilateral pain decreased ΔRMS-EMG in the Iliocostalis muscle and bilateral pain decreased ΔRMS-EMG in all back and gluteal muscles during step tasks (P < .05) compared with controls. In controls, bilateral versus unilateral experimental pain induced increased step task duration and trunk RMS-EMG whereas both pain conditions decreased step task duration and trunk RMS-EMG in R-LBP patients compared with controls (P < .05)., Perspective: Task duration and trunk muscle activity increased in controls and decreased in R-LBP patients during experimental muscle LBP. These results indicate protective strategies in controls during acute pain whereas R-LBP patients showed higher pain intensity and altered strategies that may be caused by the higher pain intensity, but the long-term consequence remains unknown., (Copyright © 2018 The American Pain Society. Published by Elsevier Inc. All rights reserved.)

Prosthetic joint failure is mainly caused by infection, aseptic failure (AF), and mechanical problems. Infection detection has been improved with modified culture methods and molecular diagnostics. However, comparisons between modified and conventional microbiology methods are difficult due to variations in specimen sampling. In this prospective, multidisciplinary study of hip or knee prosthetic failures, we assessed the contributions of different specimen types, extended culture incubations, and 16S rRNA sequencing for diagnosing prosthetic joint infections (PJI). Project specimens included joint fluid (JF), bone biopsy specimens (BB), soft-tissue biopsy specimens (STB), and swabs (SW) from the prosthesis, collected in situ , and sonication fluid collected from prosthetic components (PC). Specimens were cultured for 6 (conventional) or 14 days, and 16S rRNA sequencing was performed at study completion. Of the 156 patients enrolled, 111 underwent 114 surgical revisions (cases) due to indications of either PJI ( n = 43) or AF ( n = 71). Conventional tissue biopsy cultures confirmed PJI in 28/43 (65%) cases and refuted AF in 3/71 (4%) cases; one case was not evaluable. Based on these results, minor diagnostic adjustments were made. Fourteen-day cultures of JF, STB, and PC specimens confirmed PJI in 39/42 (93%) cases, and 16S rRNA sequencing confirmed PJI in 33/42 (83%) cases. One PJI case was confirmed with 16S rRNA sequencing alone and five with cultures of project specimens alone. These findings indicated that JF, STB, and PC specimen cultures qualified as an optimal diagnostic set. The contribution of sequencing to diagnosis of PJI may depend on patient selection; this hypothesis requires further investigation., (Copyright © 2018 Larsen et al.)