Empagliflozin inhibits increased Na influx in atrial cardiomyocytes of patients with HFpEF.

AIMS: Heart failure with preserved ejection fraction (HFpEF) causes substantial morbidity and mortality. Importantly, atrial remodeling and atrial fibrillation is frequently observed in HFpEF. Sodium-glucose cotransporter 2 inhibitors (SGLT2i) have recently been shown to improve clinical outcomes in HFpEF, and post-hoc analyses suggest atrial antiarrhythmic effects. We tested if isolated human atrial cardiomyocytes from patients with HFpEF exhibit an increased Na influx, which is known to cause atrial arrhythmias, and if that is responsive to treatment with the SGTL2i empagliflozin. METHODS AND RESULTS: Cardiomyocytes were isolated from atrial biopsies of 124 patients (82 with HFpEF) undergoing elective cardiac surgery. Na influx was measured with the Na-dye Asante Natrium Green-2 AM (ANG-2). Compared to patients without heart failure (NF), Na influx was doubled in HFpEF patients (NF vs HFpEF: 0.21±0.02 vs 0.38±0.04 mmol/L/min (N=7 vs 18); p=0.0078). Moreover, late INa (measured via whole-cell patch clamp) was significantly increased in HFpEF compared to NF. Western blot and HDAC4 pulldown assay indicated a significant increase in CaMKII expression, CaMKII autophosphorylation, CaMKII activity, and CaMKII-dependent NaV1.5 phosphorylation in HFpEF compared to NF, whereas NaV1.5 protein and mRNA abundance remained unchanged. Consistently, increased Na influx was significantly reduced by treatment with the CaMKII inhibitor autocamtide-2 related inhibitory peptide (AIP), late INa inhibitor tetrodotoxin (TTX) but also with NHE1 inhibitor cariporide. Importantly, empagliflozin abolished both increased Na influx and late INa in HFpEF. Multivariate linear regression analysis, adjusting for important clinical confounders, revealed HFpEF to be an independent predictor for changes in Na handling in atrial cardiomyocytes. CONCLUSION: We show for the first time increased Na influx in human atrial cardiomyocytes from HFpEF patients, partly due to increased late INa and enhanced NHE1-mediated Na influx. Empagliflozin inhibits Na influx and late INa, which could contribute to antiarrhythmic effects in patients with HFpEF.

Switching between foods is reliably associated with intake across eating events in children.

Emerging evidence suggests switching between foods during an eating event is positively associated with intake. However, it is unclear whether switching is a stable behavior that predicts consumption across multiple eating events. The current study explored whether switching is consistent within children and reliably associated with intake across varied eating events. We analyzed data from 88 (45 F), 7-8-year-old children without obesity participating in a 7-visit prospective cohort study (ClinicalTrials.gov NCT03341247). Amount consumed and energy intake were measured at 4 separate meals of foods that varied by portion sizes served. Meals included macaroni and cheese, chicken nuggets, broccoli, and grapes (all 0.7-2.5 kcal/g). Children's intake was also assessed during 2 eating in the absence of hunger (EAH) paradigms separated by ≥ 1 year. The EAH paradigm included 9 sweet and savory snack foods (all 1.9-5.7 kcal/g). All eating events were video-recorded and switching was assessed by counting the number of times a child shifted between different food items. Results demonstrated that switching was reliably associated with intake at both the meals and the EAH paradigms (ps < 0.01). Specifically, at meals each additional switch was associated with 11.7 ± 1.3 kcal (7.7 ± 0.8 g) more consumed, and during EAH each additional switch was associated with 8.1 ± 2.1 kcal (2.1 ± 0.5 g) more consumed. Switching behavior was also moderately consistent across meals (ICC = 0.70) and EAH paradigms (ICC = 0.50). However, switching at meals was not related to switching at EAH paradigms. This study demonstrates the consistency of switching behavior and its reliable association with intake across eating events, highlighting its potential to contribute to chronic overconsumption and childhood obesity.

Child eating behaviors are consistently linked to intake across meals that vary in portion size.

Prior studies evaluating a single meal in children characterized an "obesogenic" style of eating marked by larger bites and faster eating. It is unclear if this style is consistent across portion sizes within children so we examined eating behaviors in 91 children (7-8 years, 45 F) without obesity (BMI<90th percentile). Children consumed 4 ad libitum meals in the laboratory consisting of chicken nuggets, macaroni, grapes, and broccoli that varied in portion size (100%, 133%, 166%, 200%) with a maximum of 30 min allotted per meal. Anthropometrics were assessed using age and sex adjusted body mass index (BMI) percentile and dual energy x-ray absorptiometry. Bites, sips, active eating time, and meal duration were coded from meal videos; bite size (kcal and g/bite), proportion of active eating (active eating time/meal duration), and eating rate (kcal and g/meal duration) were computed. Intraclass correlation coefficients (ICC) showed that most eating behaviors were moderately consistent across portions (>0.50). The consistency of associations between eating behaviors and total meal intake and adiposity were assessed with general linear models adjusted for food liking, pre-meal fullness, age, and sex. Across all portions, more bites, faster eating rate, and longer meal duration were associated with greater intake. While higher BMI percentile was associated with faster eating rates across all meals, greater fat mass index was only associated with faster eating at meals with portions typical for children (i.e., 100% and 133%). In a primarily healthy weight sample, an 'obesogenic' style of eating was a consistent predictor of greater intake across meals that varied in portion size. The consistent relationship of these behaviors with intake makes them promising targets to reduce overconsumption.

Etiologies and predictors of mortality in an all-comer population of patients with non-ischemic heart failure.

BACKGROUND: Despite progress in diagnosis and therapy of heart failure (HF), etiology and risk stratification remain elusive in many patients. METHODS: The My Biopsy HF Study (German clinical trials register number: DRKS22178) is a retrospective monocentric study investigating an all-comer population of patients with unexplained HF based on a thorough workup including endomyocardial biopsy (EMB). RESULTS: 655 patients (70.9% men, median age 55 [45/66] years) with non-ischemic, non-valvular HF were included in the analyses. 489 patients were diagnosed with HF with reduced ejection fraction (HFrEF), 52 patients with HF with mildly reduced ejection fraction (HFmrEF) and 114 patients with HF with preserved ejection fraction (HFpEF). After a median follow-up of 4.6 (2.5/6.6) years, 94 deaths were enumerated (HFrEF: 68; HFmrEF: 8; HFpEF: 18), equating to mortality rates of 3.3% and 11.6% for patients with HFrEF, 7.7% and 15.4% for patients with HFmrEF and 5.3% and 11.4% for patients with HFpEF after 1 and 5 years, respectively. In EMB, we detected a variety of putative etiologies of HF, including incidental cardiac amyloidosis (CA, 5.8%). In multivariate logistic regression analysis adjusting for age, sex and comorbidities only CA, age and NYHA functional class III + IV remained independently associated with all-cause mortality (CA: HRperui 3.13, 95% CI 1.5-6.51; p = 0.002). CONCLUSIONS: In an all-comer population of patients presenting with HF of unknown etiology, incidental finding of CA stands out to be independently associated with all-cause mortality. Our findings suggest that prospective trials would be helpful to test the added value of a systematic and holistic work-up of HF of unknown etiology.

Socioeconomic, health-care access and clinical determinants of disease severity in Multiple Sclerosis in Chile.

BACKGROUND: MS severity may be affected by genetic, patient-related, disease-related and environmental factors. Socioeconomic status, including income and healthcare access, amongst others, may also have a role in affecting diagnostic delay or therapy prescription. In Chile, two main healthcare systems exist, public-healthcare and private-healthcare, nonetheless universal care laws (e.g., access to High Efficacy Therapy-HET), including both systems, have been recently enacted for people with MS. OBJECTIVE: To assess the role of Socioeconomic Conditions (SEC), clinical variables and public health policies on the impact of disease severity of MS patients in Chile. METHODS: Multicentric, observational, cross-sectional study including patients from two reference centres (1 national reference centre from the private-health system and 1 regional reference centre from the public-health system). SEC and clinical variables included healthcare insurance (private or public), subclassification of health insurance according to monthly income, sex, age at onset, diagnostic delay, disease duration, diagnosis before HET law (as a proxy of HET delay), and current HET treatment. Progression Index (PI), EDSS ≥6.0 and Progressive MS diagnosis were used as outcome measures. Multivariable binary logistic regression was performed. RESULTS: We included 604 patients (460 private-health, 144 public-health), 67% women, 100% white/mestizo, 88% RRMS, mean age 42±12 years, mean age at onset 32±11 years, mean disease duration 10±6 years, median diagnostic delay 0 (0-34) years, 86% currently receiving any DMT, 55% currently receiving HET, median EDSS at last visit of 2.0 (0-10), and median PI 0.17 (0-4.5). Lower monthly income was associated with higher EDSS and higher PI. In the multivariable analysis, public-healthcare (OR 10.2), being diagnosed before HET-law (OR 4.89), longer diagnostic delay (OR 1.26), and older age at onset (OR 1.05) were associated with a higher risk of PI>0.2, while current HET (OR 0.39) was a protective factor. Diagnosis before HET-law (OR 7.59), public-healthcare (OR 6.49), male sex (OR 2.56), longer disease duration (OR 1.2) and older age at onset (OR 1.1) were associated with a higher risk of Progressive MS. Public-healthcare (OR 5.54), longer disease duration (OR 1.14) and older age at onset (OR 1.08) were associated with a higher risk of EDSS ≥6.0 while current treatment with HET had a trend as being a protective factor (OR 0.44, p = 0.05). CONCLUSION: MS severity is impacted by non-modifiable factors such as sex and age at onset. Interventions focused on shortening diagnostic delay and encouraging early access to high-efficacy therapies, as well as initiatives that may reduce the disparities inherent to lower socioeconomic status, may improve outcomes in people with MS.

Early referral of patients with suspected polymyalgia rheumatica - A systematic review.

INTRODUCTION: Prompt diagnosis and treatment of polymyalgia rheumatica (PMR) is crucial to prevent long-term complications and improve patient outcomes. However, there is currently no standardized approach to referral of suspected PMR patients to rheumatologists, leading to inconsistent management practices. The objective of this systematic review was to clarify the existing evidence regarding the following aspects of early management strategies in patients with suspected PMR: diagnostic strategies, GCA screening, glucocorticoid initiation prior to referral, value of shared care and value of fast track clinic. METHODS: Two authors performed a systematic literature search, data extraction and risk of bias assessment independently. The literature search was conducted in Embase, MEDLINE (PubMed) and Cochrane. Studies were included if they contained cohorts of suspected PMR patients and evaluated the efficacy of different diagnostic strategies for PMR, screening for giant cell arteritis (GCA), starting glucocorticoids before referral to secondary care, shared care, or fast-track clinics. RESULTS: From 2,437 records excluding duplicates, 14 studies met the inclusion criteria. Among these, 10 studies investigated the diagnostic accuracy of various diagnostic strategies with the majority evaluating different clinical approaches, but none of them showed consistently high performance. However, 4 studies on shared care and fast-track clinics showed promising results, including reduced hospitalization rates, lower starting doses of glucocorticoids, and faster PMR diagnosis. CONCLUSION: This review emphasizes the sparse evidence of early management and referral strategies for patients with suspected PMR. Additionally, screening and diagnostic strategies for differentiating PMR from other diseases, including concurrent GCA, require clarification. Fast-track clinics may have potential to aid patients with PMR in the future, but studies will be needed to determine the appropriate pre-referral work-up.

Sub-three-cycle pulses at 2 µm from a degenerate optical parametric amplifier.

In this work we present a compact two-stage optical parametric amplifier (OPA) pumped at degeneracy by the fundamental of a Yb:KGW laser system. The output pulses span from 1.7 to 2.5 µm (120-176 THz) and are compressed to a sub-20 fs duration. This parametric amplifier exploits the broad phase-matching bandwidth at the degeneracy point in bismuth triborate (BiBO) and periodically poled lithium tantalate (PPLT). The result drastically expands the availability of ultrashort pulses with few-microjoule energy from near-infrared (NIR) to even longer wavelengths in the mid-infrared (MIR) spectral region.

Calcified cartilage differs in patients with end-stage primary osteoarthritis and secondary osteoarthritis due to rheumatoid arthritis of the hip joint.

OBJECTIVES: Despite distinct aetiologies, the end-stages of primary osteoarthritis (OA) and secondary OA are described by common radiological features. However, the morphology of the bone-cartilage unit may differ depending on the pathogenesis. In this cross-sectional study, we aimed to investigate the histological differences in the bone-cartilage unit of the femoral head between patients with primary OA and secondary OA due to rheumatoid arthritis (RA). METHOD: Femoral heads were obtained from 12 patients with primary OA, six patients with secondary OA due to RA, and 12 control subjects. The femoral heads were investigated using stereological methods to ensure unbiased quantification. RESULTS: The volume (mean difference [95% confidence interval]) (2.1 [0.5;3.8] cm3, p = 0.016) and thickness (413 [78.9;747] µm, p = 0.029) of the articular cartilage and the thickness of the calcified cartilage (56.4 [0.4;113] µm, p = 0.017) were larger in patients with primary OA than in patients with secondary OA due to RA. Femoral head volume (1.2 [-3.6;6.1] cm3, p = 0.598), bone volume fraction (-1.1 [-2.8;5.1] cm3, p = 0.553), subchondral bone thickness (-2.5 [-212;207] µm, p = 0.980), and osteophyte area (25.3 [-53.6;104] cm2, p = 0.506) did not differ between patients. CONCLUSION: The thicker calcified cartilage in primary OA preceding the loss of articular cartilage can be attributed to endochondral ossification. Patients with secondary OA due to RA had severely thinner calcified cartilage as the pathogenesis is driven by inflammation and is characterized by a generalized and more severe loss of articular cartilage.

Comparison of High Throughput Sequencing to Standard Protocols for Virus Detection in Berry Crops.

We completed a comprehensive study comparing virus detection between high throughput sequencing (HTS) and standard protocols in 30 berry selections (12 Fragaria, 10 Vaccinium, and eight Rubus) with known virus profiles. The study examined temporal detection of viruses at four sampling times encompassing two growing seasons. Within the standard protocols, reverse transcription (RT) PCR proved better than biological indexing. Detection of known viruses by HTS and RT-PCR nearly mirrored each other. HTS provided superior detection compared with RT-PCR on a wide spectrum of variants and discovery of novel viruses. More importantly, in most cases in which the two protocols showed parallel virus detection, 11 viruses in 16 selections were not consistently detected by both methods at all sampling points. Based on these data, we propose a testing requirement of four sampling times over two growing seasons for berry and potentially other crops, to ensure that no virus remains undetected independent of titer, distribution, or other virus-virus or virus-host interactions.

Children's inhibitory control abilities in the presence of rewards are related to weight status and eating in the absence of hunger.

The Reflective-Impulsive Dual Processes Model suggests that overeating occurs when the temptation to consume food overrides inhibitory control processes. However, how rewards interact with inhibitory control and their relation to children's weight status and food intake is not understood. Here, 7-to-11-year-old children (n = 66; 32 overweight/obese) completed two versions (baseline [i.e., non-reward incentivized/control] and reward incentivized [food, money, no reward]) of a Go/Nogo task. Intake of palatable foods in the absence of hunger (i.e., eating in the absence of hunger-EAH) was measured following a standardized meal. A drift diffusion model was used to characterize children's performance parameters on the Go/Nogo. On the baseline Go/Nogo, children with higher weight status responded more cautiously, but on reward trials for food/money children were more cautions and made more false alarms relative to the no reward condition. Energy intake during EAH positively correlated with FA errors for food and money vs. no reward, but sex moderated this effect such that FA positively associated with EAH in girls but not boys. Independent of sex, FA for money vs. no reward and food vs. money were both positively associated with energy consumed during EAH. These results suggest that the presence of food and money rewards impair inhibitory control processing, especially in children with higher weight status. Further, increased inhibitory control impairment in response to food rewards, specifically, may be a risk factor for disinhibited eating in girls. Though preliminary, results may be useful in the development of targeted treatments to help moderate excess consumption in children.

Rectal temperature is a prognostic indicator in client-owned guinea pigs.

OBJECTIVES: To determine whether rectal temperature was associated with patient mortality in client-owned guinea pigs upon presentation to a veterinary hospital. MATERIALS AND METHODS: The medical record database at a veterinary teaching hospital was searched for records of guinea pigs from January 2016 through June 2019. Guinea pigs were included in the study if a rectal temperature was measured at presentation and there was data on survival status 7 days post-presentation. If survivor status was not documented in the medical record, follow-up information was obtained from the client via telephone or email. The data was ultimately collected from 201 client-owned guinea pigs who presented for 388 independent examinations. Univariable, multivariable and sensitivity analyses were performed. RESULTS: Guinea pigs with hypothermia (<37.9°C) at presentation had a relative risk of mortality within 7 days of presentation almost 3 times greater than guinea pigs without hypothermia (relative risk: 2.88; 95% confidence interval: 1.86 to 4.48). For each 0.55°C decrease in rectal temperature, the odds of death increased 1.6 times (odds ratio: 1.64; 95% confidence interval: 1.42 to 2.89). Sensitivity analyses confirmed the robustness of the finding. CLINICAL SIGNIFICANCE: Rectal temperature was a predictor of death for guinea pigs presenting for care at a veterinary hospital. Obtaining a rectal temperature recording should be considered for patient guinea pigs.

Increased C reactive protein, cardiac troponin I and GLS are associated with myocardial inflammation in patients with non-ischemic heart failure.

Inflammatory cardiomyopathy diagnosed by endomyocardial biopsy (EMB) is common in non-ischemic heart failure (HF) and might be associated with adverse outcome. We aimed to identify markers predicting myocardial inflammation in HF. We screened 517 patients with symptomatic non-ischemic HF who underwent EMB; 397 patients (median age 54 [IQR 43/64], 28.7% females) were included in this study. 230 patients were diagnosed with myocardial inflammation, defined as ≥ 7.0 CD3+ lymphocytes/mm2 and/or ≥ 35.0 Mac1 macrophages/mm2 and were compared to 167 inflammation negative patients. Patients with myocardial inflammation were more often smokers (52.4% vs. 39.8%, p = 0.013) and had higher C-reactive protein (CRP) levels (5.4 mg/dl vs. 3.7 mg/dl, p = 0.003). In logistic regression models CRP ≥ 8.15 mg/dl (OR 1.985 [95%CI 1.160-3.397]; p = 0.012) and Troponin I (TnI) ≥ 136.5 pg/ml (OR 3.011 [1.215-7.464]; p = 0.017) were independently associated with myocardial inflammation, whereas no association was found for elevated brain natriuretic peptide (OR 1.811 [0.873-3.757]; p = 0.111). In prognostic performance calculation the highest positive predictive value (90%) was detected for the combination of Global longitudinal strain (GLS) ≥ -13.95% and TnI ≥ 136.5 pg/ml (0.90 (0.74-0.96)). Elevated CRP, TnI and GLS in combination with TnI can be useful to detect myocardial inflammation. Smoking seems to predispose for myocardial inflammation.

Accessing distributions of exchange and dipolar couplings in stiff molecular rulers with Cu(II) centres.

Determining distributed exchange couplings is important for understanding the properties of synthetic magnetic molecules. Such distributions can be determined from pulsed dipolar spectroscopy (PDS) data, but this is challenging due to the similar influence of both exchange and dipolar couplings on such data. In this work we introduce two models that aim to identify these two contributions to the spin-spin couplings from frequency-domain PDS data of shape-persistent molecules having either two Cu(ii) ions, or a Cu(ii) ion and a nitroxide radical as the paramagnetic moieties. The first model assumes correlated Lorentzian or Gaussian exchange and dipole-dipole coupling distributions whose parameters are the model's unknowns. The second model relies on prior knowledge of the distance distribution and by performing Tikhonov regularization along the exchange coupling dimension yields the latter distribution model-free. Both models were able to differentiate between the absence and the presence of exchange interaction, to determine the coupling regime (ferro- or antiferromagnetic) and to estimate the distribution shape. In contrast, calculations within the exchange resilient model of the neural network analysis implemented in DeerAnalysis2018 were not able for our data to identify exchange couplings and return correct distance distributions. However, the generic model was able to identify and separate the strongly curved intermolecular background in the relaxation-induced dipolar modulation enhancement (RIDME) experiments. Our analysis revealed that in such systems exchange coupling may be present up to at least 3.3 nm in π-conjugated systems involving Cu(ii)-PyMTA, while it is negligible for distances r ≥ 4.5 nm between Cu(ii) ions and r ≥ 3.8 nm between a Cu(ii) ion and an unpaired electron of a nitroxide radical. Disruption of the π-conjugation between the ligand of the Cu(ii) complex and the nitroxide leads to negligible exchange coupling at distances r ≥ 2.6 nm in the corresponding [Cu(ii)-TAHA]-nitroxide ruler. Overall, for cases with known distance distributions, the presented analysis techniques allow to determine distributions of exchange couplings from PDS data.

Non-specific rheumatic manifestations in patients with Hashimoto's thyroiditis: a pilot cross-sectional study.

PURPOSE: Hashimoto's thyroiditis (HT) is often associated with rheumatic disorders (arthritis, etc.), but many HT patients report non-specific rheumatic signs and symptoms in the absence of clinically evident rheumatic diseases. Aim of this study was to evaluate the prevalence of non-specific rheumatic manifestations (RMs) in HT subjects without classified autoimmune comorbidities. METHODS: 500 HT patients (467 F, 33 M; median age 41 years, range 14-69) and 310 age- and sex-matched controls, consecutively referred to the Endocrine Unit of Messina University Hospital, were evaluated for non-specific RMs. None took L-thyroxine. EXCLUSION CRITERIA: autoimmune comorbidities, infectious, and/or inflammatory diseases, history of neoplasia, BMI > 30 kg/m2. RESULTS: In our HT cohort, 100 patients (20%) complained of one or more RMs, vs 21 controls (6.8%; P < 0.001). There were minimal differences between the manifestations recorded in the two groups, the most common being polyarthralgias and myalgias/fibromyalgia, but non-specific RMs occurred threefold more in HT patients. Comparing HT patients with RMs (96 F and 4 M) with those affected by HT alone, female sex was prevalent (F:M ratio 24:1 vs 5:1) with higher age at diagnosis (median 43 vs 37 years; P < 0.001). HT patients with RMs (62%) were mostly euthyroid (median TSH 2.0 µIU/L) and only 7% overtly hypothyroid, discouraging a possible causal relationship between thyroid dysfunction per se and RMs. CONCLUSIONS: A significant percentage of HT patients complains of non-specific rheumatic signs and symptoms, in the absence of other diagnosed systemic comorbidities and regardless of thyroid functional status, deserving careful evaluation and prolonged follow-up.

Dry season habitat use of fishes in an Australian tropical river.

The modification of river flow regimes poses a significant threat to the world's freshwater ecosystems. Northern Australia's freshwater resources, particularly dry season river flows, are being increasingly modified to support human development, potentially threatening aquatic ecosystems and biodiversity, including fish. More information is urgently needed on the ecology of fishes in this region, including their habitat requirements, to support water policy and management to ensure future sustainable development. This study used electrofishing and habitat survey methods to quantify the dry season habitat use of 20 common freshwater fish taxa in the Daly River in Australia's wet-dry tropics. Of twenty measured habitat variables, water depth and velocity were the two most important factors discriminating fish habitat use for the majority of taxa. Four distinct fish habitat guilds were identified, largely classified according to depth, velocity and structural complexity. Ontogenetic shifts in habitat use were also observed in three species. This study highlights the need to maintain dry season river flows that support a diversity of riverine mesohabitats for freshwater fishes. In particular, shallow fast-flowing areas provided critical nursery and refuge habitats for some species, but are vulnerable to water level reductions due to water extraction. By highlighting the importance of a diversity of habitats for fishes, this study assists water managers in future decision making on the ecological risks of water extractions from tropical rivers, and especially the need to maintain dry season low flows to protect the habitats of native fish.

Increased brain and behavioural susceptibility to portion size in children with loss of control eating.

BACKGROUND: Portion size influences intake (i.e. the portion size effect [PSE]), yet determinants of susceptibility to the PSE are unclear. OBJECTIVE: We tested whether children who reported an episode of loss of control (LOC) eating over the last 3 months would be more susceptible to the PSE and would show differential brain responses to food cues compared with children with no-LOC. METHODS: Across five sessions, children (n = 47; 7-10 years) consumed four test meals at 100%, 133%, 167% and 200% conditions for portion size and completed a functional magnetic resonance imaging scan while viewing pictures of foods varied by portion size and energy density (ED). Incidence of LOC over the past 3 months was self-reported. Random coefficient models were tested for differences in the shape of the PSE curve by LOC status. A whole-brain analysis was conducted to determine response to food cues during the functional magnetic resonance imaging. RESULTS: Reported LOC (n = 13) compared with no-LOC (n = 34) was associated with increased susceptibility to the PSE, as evidenced by a positive association with the linear slope (P < 0.005), and negative association with the quadratic slope (P < 0.05) of the intake curve. Children who reported LOC compared with no-LOC showed increased activation in the left cerebellum to small relative to large portions (P < 0.01) and right cerebellum to High-ED relative to Low-ED food cues (P < 0.01). CONCLUSION: Children who reported LOC were more susceptible to the PSE and showed alterations in food-cue processing in the cerebellum, a hindbrain region implicated in satiety signalling.

Food or money? Children's brains respond differently to rewards regardless of weight status.

BACKGROUND: Brain responses to both food and monetary rewards have been linked to weight gain and obesity in adults, suggesting that general sensitivity to reward contributes to overeating. However, the relationship between brain reward response and body weight in children is unclear. OBJECTIVE: The objective of this study was to assess the brain's response to multiple rewards and the relationship to body weight in children. METHODS: We tested this by performing functional magnetic resonance imaging while children (7- to 11-years-old; healthy weight [n = 31], overweight/obese [n = 30]) played a modified card-guessing task to assess blood-oxygen-level-dependent (BOLD) response to anticipating and winning food and money rewards. Functional magnetic resonance imaging data were analysed using a region of interest and exploratory whole-brain approach. RESULTS: Region of interest results demonstrated increased BOLD response in the striatum to anticipating food vs. neutral (control) and winning money vs. neutral. Whole-brain data showed that winning money vs. food was associated with increased activation in the striatum, as well as regions associated with cognitive control and emotion. Notably, for both approaches, these effects were independent of child weight status. Additionally, children's reported food responsiveness and emotional overeating were negatively correlated with the BOLD response in the left cingulate gyrus for winning food vs. money. CONCLUSION: Overall, findings from this study show that regions associated with reward, cognitive control and emotion may play a role in the brain's response to food and money rewards, independently of how much the child weighs. These findings provide insight into reward sensitivity in children, which may have implications for understanding overeating and the development of obesity.

Effect of re-ensiling on the quality of sorghum silage.

The commercialization of silage in many countries, including Brazil, has increased in recent years. Re-ensiling of previously ensiled forage occurs when silage is relocated from one farm to another, where it will be compacted and sealed again. During this process, silage is exposed to oxygen before being ensiled, which may affect its quality. We exposed sorghum silage to air during the anaerobic storage phase to simulate the transportation of silages between farms. Experimental treatments included silage exposed to air for 0 or 12 h, with or without the use of an inoculant containing a mixture of Lactobacillus plantarum and the propionic bacteria Propionibacterium acidipropionici (1 × 106 cfu/g of forage; Biomax corn, Lallemand, Saint-Simon, France), totaling 4 treatments: conventional silage, conventional silage with inoculant use, re-ensilage after exposure to air, and re-ensilage after exposure to air with use of an inoculant. The sorghum was stored in experimental silos containing about 9.0 kg of fresh forage per replicate. Treatments were tested in a factorial 2 × 2 design with 5 replicates each. Chemical composition, in vitro dry matter digestibility, fermentative characteristics, losses (due to gas, effluents, and total dry matter), microorganism counts, and aerobic stability of sorghum silage were evaluated. Dry matter content of sorghum before ensiling was 273.12 g/kg. The 12-h re-ensiling process increased the effluent loss of the silage when compared with conventional silage (456.42 vs. 201.19 g/kg of FM, respectively). In addition, re-ensiled silages presented lower concentrations of lactic acid and higher concentrations of propionic acid than the silages that had not been opened during storage. The aerobic stability of silage was not affected by the re-ensiling process and the use of inoculant. The use of inoculant increased the pH and loss of dry matter of the silages (4.23 vs. 3.98 and 14.05 vs. 7.82%, respectively) and therefore did not provide any benefits in this study.

Local bone loss in patients with anti-citrullinated peptide antibody and arthralgia, evaluated with high-resolution peripheral quantitative computed tomography.

OBJECTIVE: To investigate bone changes in the metacarpophalangeal (MCP) joints of anti-citrullinated peptide antibody (ACPA)-positive patients with arthralgia, but not arthritis, compared to healthy controls. METHOD: Using a cross-sectional study design, patients were recruited from hospitals and private care rheumatologists, and controls from a test subject website. All subjects underwent medical history interview, clinical examination, and biochemical screening including ACPA. Patients with positive ACPA, arthralgia, and no rheumatic disease were included. Controls without a history or signs of rheumatological disease or positive ACPA were included. A 2.7-cm-long region around the second and third MCP joints was evaluated using high-resolution peripheral quantitative computed tomography with a voxel size of 82 µm. RESULTS: Twenty-nine ACPA-positive patients and 29 healthy controls were evaluated. Trabecular volumetric bone mineral density and bone volume fraction did not differ between the groups. In addition, the cortical bone was not affected in patients, as we found no difference in average cortical thickness and cortical bone area between the groups. In contrast, the trabeculae were significantly (p < 0.05) thinner in both second and third MCP heads compared with controls, whereas trabecular number and trabecular separation did not differ between the groups. No erosions were demonstrated and the number of non-specific breaks did not differ between the groups. CONCLUSION: Trabecular bone changes were observed in ACPA-positive patients with arthralgia compared with healthy controls. The results may reflect inflammatory up-regulated trabecular bone resorption leading to early bone loss before the onset of clinical arthritis.