Tissue losses and metabolic adaptations both contribute to the reduction in resting metabolic rate following weight loss

OBJECTIVE: To characterize the contributions of the loss of energy-expending tissues and metabolic adaptations to the reduction in resting metabolic rate (RMR) following weight loss. METHODS: A secondary analysis was conducted on data from the Comprehensive Assessment of Long-term Effects of Reducing Intake of Energy study. Changes in RMR, body composition, and metabolic hormones were examined over 12 months of calorie restriction in 109 individuals. The contribution of tissue losses to the decline in RMR was determined by weighing changes in the size of energy-expending tissues and organs (skeletal muscle, adipose tissue, bone, brain, inner organs, residual mass) assessed by dualenergy X-ray absorptiometry with their tissue-specific metabolic rates. Metabolic adaptations were quantified as the remaining reduction in RMR. RESULTS: RMR was reduced by 101 ± 12 kcal/d as participants lost 7.3 ± 0.2 kg (both p \u3c 0.001). On average, 60% of the total reduction in RMR were explained by energy-expending tissues losses, while 40% were attributed to metabolic adaptations. The loss of skeletal muscle mass (1.0 ± 0.7 kg) was not significantly related to RMR changes (r = 0.14, p = 0.16), whereas adipose tissue losses (7.2 ± 3.0 kg) were positively associated with the reduction in RMR (r = 0.42, p \u3c 0.001) and metabolic adaptations (r = 0.31, p \u3c 0.001). Metabolic adaptations were correlated with declines in leptin (r = 0.27, p \u3c 0.01), triiodothyronine (r = 0.19, p \u3c 0.05), and insulin (r = 0.25, p \u3c 0.05). CONCLUSIONS: During weight loss, tissue loss and metabolic adaptations both contribute to the reduction in RMR, albeit variably. Contrary to popularly belief, it is not skeletal muscle, but rather adipose tissue losses that seem to drive RMR reductions following weight loss. Future research should target personalized strategies addressing the predominant cause of RMR reduction for weight maintenance

Mechanisms of Selective Attention in Generalized Anxiety Disorder

A well-established literature has identified different selective attentional orienting mechanisms underlying anxiety-related attentional bias, such as engagement and disengagement of attention. These mechanisms are thought to contribute to the onset and maintenance of anxiety disorders. However, conclusions to date have relied heavily on experimental work from subclinical samples. We therefore investigated individuals with diagnosed generalized anxiety disorder (GAD), healthy volunteers, and individuals with high trait anxiety (but not meeting GAD diagnostic criteria). Across two experiments we found faster disengagement from negative (angry and fearful) faces in GAD groups, an effect opposite to that expected on the basis of the subclinical literature. Together these data challenge current assumptions that we can generalize, to those with GAD, the pattern of selective attentional orienting to threat found in subclinical groups. We suggest a decisive two-stage experiment identifying stimuli of primary salience in GAD, then using these to reexamine orienting mechanisms across groups. </jats:p

Mapping genomic and transcriptomic alterations spatially in epithelial cells adjacent to human breast carcinoma.

Almost all genomic studies of breast cancer have focused on well-established tumours because it is technically challenging to study the earliest mutational events occurring in human breast epithelial cells. To address this we created a unique dataset of epithelial samples ductoscopically obtained from ducts leading to breast carcinomas and matched samples from ducts on the opposite side of the nipple. Here, we demonstrate that perturbations in mRNA abundance, with increasing proximity to tumour, cannot be explained by copy number aberrations. Rather, we find a possibility of field cancerization surrounding the primary tumour by constructing a classifier that evaluates where epithelial samples were obtained relative to a tumour (cross-validated micro-averaged AUC = 0.74). We implement a spectral co-clustering algorithm to define biclusters. Relating to over-represented bicluster pathways, we further validate two genes with tissue microarrays and in vitro experiments. We highlight evidence suggesting that bicluster perturbation occurs early in tumour development

Tissue Localization and Extracellular Matrix Degradation by PI, PII and PIII Snake Venom Metalloproteinases: Clues on the Mechanisms of Venom-Induced Hemorrhage

20 páginas, 4 figuras, 3 tablas y 7 tablas en material suplementario.Snake venom hemorrhagic metalloproteinases (SVMPs) of the PI, PII and PIII classes were compared in terms of tissue localization and their ability to hydrolyze basement membrane components in vivo, as well as by a proteomics analysis of exudates collected in tissue injected with these enzymes. Immunohistochemical analyses of co-localization of these SVMPs with type IV collagen revealed that PII and PIII enzymes co-localized with type IV collagen in capillaries, arterioles and post-capillary venules to a higher extent than PI SVMP, which showed a more widespread distribution in the tissue. The patterns of hydrolysis by these three SVMPs of laminin, type VI collagen and nidogen in vivo greatly differ, whereas the three enzymes showed a similar pattern of degradation of type IV collagen, supporting the concept that hydrolysis of this component is critical for the destabilization of microvessel structure leading to hemorrhage. Proteomic analysis of wound exudate revealed similarities and differences between the action of the three SVMPs. Higher extent of proteolysis was observed for the PI enzyme regarding several extracellular matrix components and fibrinogen, whereas exudates from mice injected with PII and PIII SVMPs had higher amounts of some intracellular proteins. Our results provide novel clues for understanding the mechanisms by which SVMPs induce damage to the microvasculature and generate hemorrhage.This work was performed in partial fulfillment of the requirements for the PhD degree for Cristina Herrera at Universidad de Costa Rica.Peer reviewe

Case finding for dementia during acute hospital admissions: a mixed-methods study exploring the impacts on patient care after discharge and costs for the English National Health Service

Abstract Objective: Between 2012 and 2017 dementia case-finding was routinely carried out on people aged 75 and over with unplanned admissions to acute hospitals across England. The assumption was that this would lead to better planning of care and treatment for patients with dementia following discharge from hospital. However, little is known about the experiences of patients and carers or the impacts on other health services. This study explored the impact of dementia case-finding on older people and their families and on their use of services. Design: Thematic content analysis was conducted on qualitative interview data and costs associated with service use were estimated. Measures included the Mini-Mental State Examination (MMSE), the EuroQol (EQ-5D-5L) quality of life scale and a modified Client Service Receipt Inventory (CSRI). Setting: Four counties in the East of England. Participants: People aged ≥75-years who had been identified by case-finding during an unplanned hospital admission as warranting further investigation of possible dementia and their family carers. Results: We carried out 28 interviews, including 19 joint patient-carer(s), 5 patient only and 4 family carer interviews. Most patients and carers were unaware that memory assessments had taken place, with many families not being informed or involved in the process. Participants had a variety of views on memory testing in hospital and had concerns about how hospitals carried out assessments and communicated results. Overall, case-finding did not lead to general practitioner (GP) follow up after discharge home or lead to referral for further investigation. Few services were initiated because of dementia case-finding in hospital. Conclusions: This study shows that dementia case-finding may not lead to increased GP follow up or service provision for patients after discharge from hospital. There is a need for a more evidence-based approach to the initiation of mandatory initiatives such as case-finding that inevitably consume stretched human and financial resources

Natural and Induced Environment around the International Space Station (ISS) as Observed during On-Orbit Operations of the Robotic External Leak Locator (RELL)

Final Document is attached. The Robotic External Leak Locator (RELL) was deployed to the International Space Station (ISS) with the goal of detecting and locating on-orbit leaks around the ISS. Three activities to investigate and corroborate the background natural and induced environment of ISS were performed with RELL as part of the on-orbit validation and demonstration conducted in November December 2016. The first demonstration activity pointed RELL directly in the ram and wake directions for one orbit each. The ram facing measurements showed high partial pressure for mass-to-charge ratio 16, corresponding to atomic oxygen (AO), as well as the presence of mass-to-charge ratio 17. RELLs view in the wake-facing direction included more ISS structure and several Environmental Control and Life Support System (ECLSS) on-orbit vents were detected, including the Carbon Dioxide Removal Assembly (CDRA), Russian segment ECLSS, and Sabatier vents. The second demonstration activity pointed RELL at three faces of the P1 Truss segment. Effluents from ECLSS and European Space Agency (ESA) Columbus module on-orbit vents were detected by RELL. The partial pressures of mass-to-charge ratios 17 and 18 remained consistent with the first on-orbit activity of characterizing the natural environment. The third demonstration activity involved RELL scanning an Active Thermal Control System (ATCS) radiator. Three locations along the radiator were scanned and the angular position of RELL with respect to the radiator was varied. Mass-to-charge ratios 16 and 17 both had upward shifts in partial pressure when pointing toward the Radiator Beam Valve Modules (RBVMs), likely corresponding to a known, small ammonia leak

International Space Station (ISS) Environmental Control and Life Support System (ECLSS) Vent Flow Reflection and Detection by Robotic External Leak Locator (RELL)

On-orbit Robotic External Leak Locator (RELL) (i.e., mass spectrometer and ion gauge) measurements on the International Space Station (ISS) are presented to show the detection of recurring Environmental Control and Life Support System (ECLSS) vents at multiple ISS locations and RELL pointing directions. The path of ECLSS effluents to the RELL detectors is not entirely obvious at some locations, but the data indicates that diffuse gas-surface reflection or scattering resulting from plume interaction with vehicle surfaces is responsible. RELL was also able to confirm the ISS ECLSS constituents and distinguish them from the ammonia leak based on the ion mass spectra and known venting times during its operation to locate a leak in the ISS port-side External Active Thermal Control System (EATCS) coolant loop

Clinical impairment in premanifest and early Huntington's disease is associated with regionally specific atrophy.

TRACK-HD is a multicentre longitudinal observational study investigating the use of clinical assessments and 3-Tesla magnetic resonance imaging as potential biomarkers for future therapeutic trials in Huntington's disease (HD). The cross-sectional data from this large well-characterized dataset provide the opportunity to improve our knowledge of how the underlying neuropathology of HD may contribute to the clinical manifestations of the disease across the spectrum of premanifest (PreHD) and early HD. Two hundred and thirty nine gene-positive subjects (120 PreHD and 119 early HD) from the TRACK-HD study were included. Using voxel-based morphometry (VBM), grey and white matter volumes were correlated with performance in four domains: quantitative motor (tongue force, metronome tapping, and gait); oculomotor [anti-saccade error rate (ASE)]; cognition (negative emotion recognition, spot the change and the University of Pennsylvania smell identification test) and neuropsychiatric measures (apathy, affect and irritability). After adjusting for estimated disease severity, regionally specific associations between structural loss and task performance were found (familywise error corrected, P < 0.05); impairment in tongue force, metronome tapping and ASE were all associated with striatal loss. Additionally, tongue force deficits and ASE were associated with volume reduction in the occipital lobe. Impaired recognition of negative emotions was associated with volumetric reductions in the precuneus and cuneus. Our study reveals specific associations between atrophy and decline in a range of clinical modalities, demonstrating the utility of VBM correlation analysis for investigating these relationships in HD

Investigating hyper-vigilance for social threat of lonely children

The hypothesis that lonely children show hypervigilance for social threat was examined in a series of three studies that employed different methods including advanced eye-tracking technology. Hypervigilance for social threat was operationalized as hostility to ambiguously motivated social exclusion in a variation of the hostile attribution paradigm (Study 1), scores on the Children’s Rejection-Sensitivity Questionnaire (Study 2), and visual attention to socially rejecting stimuli (Study 3). The participants were 185 children (11 years-7 months to 12 years-6 months), 248 children (9 years-4 months to 11 years-8 months) and 140 children (8 years-10 months to 12 years-10 months) in the three studies, respectively. Regression analyses showed that, with depressive symptoms covaried, there were quadratic relations between loneliness and these different measures of hypervigilance to social threat. As hypothesized, only children in the upper range of loneliness demonstrated elevated hostility to ambiguously motivated social exclusion, higher scores on the rejection sensitivity questionnaire, and disengagement difficulties when viewing socially rejecting stimuli. We found that very lonely children are hypersensitive to social threat