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Objective: This paper sought to identify the instruments used to measure depression in heart failure (HF) and elucidate the impact of treatment interventions on depression in HF. Methods: The Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines were followed. Studies published from 1988 to 2018 covering depression and HF were identified through the review of the PubMed and PsycINFO databases using the keywords: "depres*" AND "heart failure." Two authors independently conducted a focused analysis, identifying 27 studies that met the specific selection criteria and passed the study quality checks. Results: Patient-reported questionnaires were more commonly adopted than clinician-rated questionnaires, including the Beck Depression Inventory, the Patient Health Questionnaire (PHQ-9), and the Hospital Anxiety and Depression Scale. Six common interventions were observed: antidepressant medications, collaborative care, psychotherapy, exercise, education, and other nonpharmacological interventions. Except for paroxetine, selective serotonin reuptake inhibitors failed to show a significant difference from placebo. However, the collaborative care model including the use of antidepressants showed a significant decrease in PHQ-9 score after one year. All of the psychotherapy studies included a variation of cognitive behavioral therapy and patients showed significant improvements. The evidence was mixed for exercise, education, and other nonpharmacological interventions. Conclusion: This study suggests which types of interventions are more effective in addressing depression in heart failure patients.

In yeast, the formation of Ure2 fibrils underlies the prion state [URE3], in which the yeast loses the ability to distinguish good nitrogen sources from bad ones. The Ure2 prion domain is both necessary and sufficient for the formation of amyloid fibrils. Understanding the structure of Ure2 fibrils is important for understanding the propagation not only of the [URE3] prion but also of other yeast prions whose prion domains share similar features, such as the enrichment of asparagine and glutamine residues. Here, we report a structural study of the amyloid fibrils formed by the Ure2 prion domain using site-directed spin labeling and electron paramagnetic resonance (EPR) spectroscopy. We completed a spin label scanning of all the residue positions between 2 and 80 of the Ure2 prion domain. The EPR data show that the Ure2 fibril core consists of residues 8-68 and adopts a parallel in-register β-sheet structure. Most of the residues show strong spin-exchange interactions, suggesting that there are only short turns and no long loops in the fibril core. Based on the strength of spin-exchange interactions, we determined the likely locations of the β-strands. EPR data also show that the C-terminal region of the Ure2 prion domain is more disordered than the N-terminal region. The roles of hydrophobic and charged residues are analyzed. Overall, the structure of Ure2 fibrils appears to involve a balance of stabilizing interactions, such as asparagine ladders, and destabilizing interactions, such as stacking of charged residues.

Objective: Psychiatric symptoms are frequently comorbid with Cushings syndrome (CS), a relatively rare condition that results from chronic hypercortisolism. Psychiatric manifestations might be present in the prodromal phase, during the course of the illness, and even after the resolution of CS. Our goals are to review the prevalence of psychiatric symptoms in CS; to determine the impact of psychiatric symptoms on morbidity, functioning, and quality of life; and to analyze the impact of treatment of CS on psychiatric symptoms. Methods: A systematic search of the literature database was conducted according to predefined criteria. Two authors independently conducted a focused analysis of the full-text articles and reached a consensus on 17 articles to be included in this review. Results: Overall, studies suggested that psychiatric symptoms-including, most prominently, depression-were present in a significant proportion of patients with CS. They reported lower health-related quality of life, which persisted even following the resolution of hypercortisolism. Though treatment and cure of CS significantly improved psychiatric symptoms, some patients did not achieve complete resolution of psychiatric symptoms and required continued psychiatric treatment. Conclusion: The majority of the literature indicates that psychiatric manifestations are an important part of CS and overall lower health-related quality of life and psychiatric symptoms can persist even after the cure of CS. This emphasizes the significance of early diagnosis for psychiatric management and stresses the importance of monitoring the long-term effects of neurocognitive and psychiatric symptoms and its impact on the quality of life, even after hypercortisolism resolution.

BackgroundThe major published clinical guidelines for the management of hypothyroidism and osteoporosis are not uniformly consistent and may be a significant contributor to variability of clinical care delivered by endocrinologists, in addition to other factors, such as physician experience, physician and patient perceptions, and patient comorbidities. The purpose of this study was to assess practice patterns of hypothyroidism and osteoporosis within an academic endocrine clinic.MethodsA retrospective medical record review of the first 200 adult patients (n = 100 with primary hypothyroidism and n = 100 with osteoporosis or osteopenia) seen by an endocrinologist beginning January 2, 2017at a large U.S. urban tertiary academic medical center was performed. Data were collected regarding patient demographics, clinic visit type, patterns of ordering laboratory tests and imaging, and choice of pharmacologic treatment.ResultsMost patients with hypothyroidism (99%) had a serum thyroid stimulating hormone concentration measured. Other thyroid indices measured included serum total thyroxine (10%), serum free thyroxine [T4] (82%), serum free T4 index (6%), serum total triiodothyronine [T3] (9%), and serum free T3 (12%). Forty-eight percent also had serum thyroid antibodies checked. A variety of thyroid hormone supplements were used to treat hypothyroidism, including levothyroxine (83%), levothyroxine and liothyronine combination (8%), and desiccated thyroid extract (6%). In regards to patients with osteoporosis, mean duration of all pharmacologic therapy combined was 73.4 ± 81.9 months. For those with more than one bone density (DXA) scans (64%), the mean time interval between two consecutive DXA scans was variable (mean 32.0 ± 24.7 [SD] months). Sixty eight percent of the patients had bone turnover markers assessed within 7 months of the visit.ConclusionsThis study reports a real-world experience of endocrinology practice patterns at a large U.S. academic healthcare system. For the common diagnoses of hypothyroidism and osteoporosis, there are opportunities for increased standardization of care, particularly regarding the ordering of laboratory testing and radiologic studies. Identifying areas with significant practice variability may improve the quality and health outcomes and reduce the cost of care for patients with these conditions. Increased understanding regarding the reasons behind ordering various studies may help physician and patients further align their goals.

We combined translating ribosome affinity purification (TRAP) with in utero electroporation (IUE), called iTRAP to identify the molecular profile of specific neuronal populations during neonatal development without the need for viral approaches and FACS sorting. We electroporated a plasmid encoding EGFP-tagged ribosomal protein L10a at embryonic day (E) 14-15 to target layer 2-4 cortical neurons of the somatosensory cortex. At three postnatal (P) ages-P0, P7, and P14-when morphogenesis occurs and synapses are forming, TRAP and molecular profiling was performed from electroporated regions. We found that ribosome bound (Ribo)-mRNAs from ∼7300 genes were significantly altered over time and included classical neuronal genes known to decrease (e.g., Tbr1, Dcx) or increase (e.g., Eno2, Camk2a, Syn1) as neurons mature. This approach led to the identification of specific developmental patterns for Ribo-mRNAs not previously reported to be developmentally regulated in neurons, providing rationale for future examination of their role in selective biological processes. These include upregulation of Lynx1, Nrn1, Cntnap1 over time; downregulation of St8sia2 and Draxin; and bidirectional changes to Fkbp1b. iTRAP is a versatile approach that allows researchers to easily assess the molecular profile of specific neuronal populations in selective brain regions under various conditions, including overexpression and knockdown of target genes, and in disease settings.

Panic attacks and panic disorders are common in the general population. However, the presence of panic attacks associated with primary hyperaldosteronism has been rarely documented. We describe a patient with new-onset hyperaldosteronism secondary to adrenal adenoma who presented with recurrent panic attacks. The patient underwent adenoma resection, which was the definitive cure for the patients hyperaldosteronism and panic attacks. Clinicians should include hyperaldosteronism on the differential for medical etiologies of panic attacks. Further research is needed to elucidate the mechanistic relationship between primary hyperaldosteronism and panic attacks.

ObjectiveThyroid eye disease (TED), an autoimmune inflammatory process involving the orbital tissues around the eye, is the most common extra-thyroidal manifestation of Graves' disease (GD). Due to changes in the patient's appearance, TED is a socially and visually disabling condition with significant impacts on quality of life. The aim of this study is to assess predictors of strabismus, a severe manifestation of TED.DesignSingle-institution retrospective case-control study. Cases of Graves' ophthalmopathy patients with strabismus were matched 1:1 to controls of Graves' ophthalmopathy patients without strabismus by age and sex.PatientsPatients ≥18 years old with severe Graves' ophthalmopathy who received their medical care at UCLA with strabismus between 2012 and 2015.MeasurementsEligibility criteria for cases was a diagnosis of Graves' ophthalmopathy with a subsequent diagnosis of strabismus. Using conditional logistic regression, the odds ratios of developing strabismus following the diagnosis of Graves' disease were assessed. The prognostic indicators assessed include race, ethnicity, cigarette smoking (active), serum thyroid peroxidase (TPO) antibody positivity, serum thyroglobulin (Tg) antibody positivity, antithyroidal medication use, and steroid use.ResultsThe study sample (45 cases 1:1 matched against 45 controls) was comprised primarily of non-Hispanic, non-Latino Caucasian women with TED (mean ± SD age 63.0 ± 13.1 years). There were no significant predictors for the development of strabismus, including cigarette smoking (active), serum thyroid peroxidase (TPO) antibody positivity, serum thyroglobulin (Tg) antibody positivity, antithyroidal medication, and steroid use.ConclusionsNo significant predictors of strabismus, a severe manifestation of Graves' ophthalmopathy, were identified following a diagnosis of TED in this study.

Many professional organizations recommend skin self-examination (SSE) as a tool for early detection of malignancy among melanoma survivors, a growing population that is at increased risk for new or recurrent melanoma. This study examined the frequency and correlates of SSE use among melanoma survivors. Additionally, we assessed skin exam use among children of survivors, who are at elevated lifetime risk for the disease. The California Cancer Registry was used to identify melanoma survivors, who were contacted, screened for eligibility, and invited to participate in a survey. The survey, administered by mail, web, or telephone, assessed a broad range of topics related to melanoma prevention in high-risk families. The present study focuses on skin examination practices of survivors and their children and potential correlates of these practices. Among a sample of 316 melanoma survivors, fewer than one in five participants performed monthly skin self-exams, a lower rate than that observed in previous studies. Although greater family history of melanoma, use of skin protection strategies, and the perceived severity of melanom were associated with more frequent use of skin self-exams, these relationships disappeared in adjusted analyses. Participants reported unexpectedly frequent use of skin examinations for their children despite the lack of professional guidelines for this practice. Interventions are needed to improve skin self-examination practices among melanoma survivors and to counsel parents about optimal melanoma prevention strategies for their children.

ObjectiveAbnormal serum liver function tests are common in patients with untreated thyrotoxicosis, even prior to the initiation of antithyroidal medications that may worsen the severity of the abnormal serum liver biochemistries. There is a wide range of the incidence of these abnormalities in the published literature. The aim of this study was to assess the risks factors and threshold of thyrotoxicosis severity for developing an abnormal liver biochemical test upon the diagnosis of new thyrotoxicosis.DesignSingle-institution retrospective cohort study.PatientsPatients of ≥18 years old receiving medical care at a large, academic, urban US medical centre between 2002-2016.MeasurementsInclusion criteria were a serum thyroid stimulating hormone (TSH) concentration of

Formation of amyloid fibrils underlies a wide range of human disorders, including Alzheimer's and prion diseases. The amyloid fibrils can be readily detected thanks to thioflavin T (ThT), a small molecule that gives strong fluorescence upon binding to amyloids. Using the amyloid fibrils of Aβ40 and Aβ42 involved in Alzheimer's disease, and of yeast prion protein Ure2, here we study three aspects of ThT binding to amyloids: quantification of amyloid fibrils using ThT, the optimal ThT concentration for monitoring amyloid formation and the effect of ThT on aggregation kinetics. We show that ThT fluorescence correlates linearly with amyloid concentration over ThT concentrations ranging from 0.2 to 500 µM. At a given amyloid concentration, the plot of ThT fluorescence versus ThT concentration exhibits a bell-shaped curve. The maximal fluorescence signal depends mostly on the total ThT concentration, rather than amyloid to ThT ratio. For the three proteins investigated, the maximal fluorescence is observed at ThT concentrations of 20-50 µM. Aggregation kinetics experiments in the presence of different ThT concentrations show that ThT has little effect on aggregation at concentrations of 20 µM or lower. ThT at concentrations of 50 µM or more could affect the shape of the aggregation curves, but this effect is protein-dependent and not universal.

In this paper, we describe a novel and simple process for the fabrication of all-transparent and encapsulated polymeric nanofluidic devices using nano-indentation lithography. First, a nanomechanical probe is used to 'scratch' nanoscale channels on polymethylmethacrylate (PMMA) substrates with sufficiently high hardness. Next, polydimethylsiloxane (PDMS) is used twice to duplicate the nanochannels onto PDMS substrates from the 'nano-scratched' PMMA substrates. A number of experiments are conducted to explore the relationships between the nano-indentation parameters and the nanochannel dimensions and to control the aspect ratio of the fabricated nanochannels. In addition, traditional photolithography combined with soft lithography is employed to fabricate microchannels on another PDMS 'cap' substrate. After manually aligning the substrates, all uncovered channels on two separate PDMS substrates are bonded to achieve a sealed and transparent nanofluidic device, which makes the dimensional transition from microscale to nanoscale feasible. The smallest dimensions of the achievable nanochannels that we have demonstrated thus far are of ~20 nm depth and ~800 nm width, with lengths extendable beyond 100 μm. Fluid flow experiments are performed to verify the reliability of the device. Two types of colloidal solution are used to visualize the fluid flow through the nanochannels, that is, ethanol is mixed with gold colloid or fluorescent dye (fluorescein isothiocyanate), and the flow rate and filling time of liquid in the nanochannels are estimated based on time-lapsed image data. The simplicity of the fabrication process, bio-compatibility of the polymer substrates, and optical transparency of the nanochannels for flow visualization are key characteristics of this approach that will be very useful for nanofluidic and biomolecular research applications in the future.

BackgroundFirst-degree relatives of melanoma survivors have a substantially higher lifetime risk for melanoma than individuals with no family history. Exposure to ultraviolet radiation (UVR) is the primary modifiable risk factor for the disease. Reducing UV exposure through sun protection may be particularly important for children with a parental history of melanoma. Nonetheless, limited prior research has investigated sun protection practices and sun exposure among these children.MethodsThe California Cancer Registry was used to identify melanoma survivors eligible to participate in a survey to assess their children's sun protection practices and sun exposure. The survey was administered by mail, telephone, or web to Latino and non-Latino white melanoma survivors with at least one child (0-17 years; N = 324).ResultsSun exposure was high and the rate of sunburn was equivalent to or higher than estimates from average-risk populations. Use of sun protection was suboptimal. Latino children were less likely to wear sunscreen and hats and more likely to wear sunglasses, although these differences disappeared in adjusted analyses. Increasing age of the child was associated with lower sun protection and higher risk for sunburn, whereas higher objective risk for melanoma predicted improved sun protection and a higher risk for sunburns. Perception of high barriers to sun protection was the strongest modifiable correlate of sun protection.ConclusionsInterventions to improve sun protection and reduce sun exposure and sunburns in high-risk children are needed.ImpactIntervening in high-risk populations may help reduce the burden of melanoma in the United States.

The contaminant assessment and management (or “Contam”) research area focuses on developing and implementing embedded networked sensing (ENS) technology to support this new observational strategy in the context of mass and energy distributions and fluxes across a range of temporal and synoptic scales. The specific areas of interest for Contam include soils, groundwater, and riparian systems. The Contam application domain is unique relative to the other three CENS applications in that it is often concerned with enabling adaptive management of environmental problems through engineered responses triggered by ENS observations. Example applications include improving our understanding of river metabolism in relation to adjacent and upstream land management practices, creating closed-loop feedback-control systems for conserving irrigation water and avoiding excessive nitrogen application in agricultural systems, delineating nutrient fluxes between groundwater and surface water, and rapid identification of coastal pollutants.

The presence of arsenic in the groundwater has led to the largest environmental poisoning in history; tens of millions of people in the Ganges Delta continue to drink groundwater that is dangerously contaminated with arsenic (As). Rice fields receive large loads of arsenic with irrigation water and provide recharge to the underlying aquifer. It is currently not known whether rice fields are a sink or source of arsenic in the hydrologic system. In the dry season, as As(III)-containing minerals are oxidized, As(V) is released and will adhere to Fe hydr(oxide) minerals. When sediments are inundated with water, reducing conditions will then drive reduction of Fe hydr(oxides) and release of As. We have been intensively studying a field site in Munshiganj, Bangladesh with extremely high levels of arsenic in groundwater (up to 1.2 mg/L). To better understand geochemical and microbial processes leading to As mobilization in surface sediment, we deployed sensors to take temporally dense measurements across our experimental rice paddy. Data collected in both 2006 and 2007 showed trends in geochemical parameters indicating that diurnal, possibly plant-induced, processes may be important. Over a two month period, nitrate concentrations decrease consistently each day as ammonium levels increase, presumably through temperature driven reductive processes. Nitrate concentrations in the subsurface then increase while ammonium levels decrease, possibly due to root oxygen leakage or rapid infiltration of oxygen rich surface water. Using sediment from the rice paddy and artificial irrigation water, laboratory microcosms were constructed to simulate the diurnal cycles observed at the field site. In carbon-ammended treatments, Fe and As cycling can occur on the order of days. Oscillations in redox conditions on diurnal as well as seasonal time scales may be important in the mobilization of arsenic into aquifers. By elucidating As mobilization mechanisms at an experimental rice paddy, this work could ultimately lead to solutions that minimize As exposure in critical populations.

Shadows, as all other objects that surround us, are incorporated into the body and extend the body mediating perceptual information. The current study investigates the hypothesis according to which the perception of object shadows would predict the perception of body shadows. 38 participants (19 males and 19 females) aged 23 years on average were immersed into a virtual reality environment and instructed to perceive and indicate the coincidence or non coincidence between the movement of a ball shadow with regard to ball movement on the one hand, and between their body shadow and their body position in space on the other. Their brain activity was recording via a 32-channel EEG system, in which beta (13.5-30 Hz) oscillations were analyzed. A series of Multiple Regression Analysis (MRA) revealed that the beta dynamic oscillations patterns of the bilateral occipito-parieto-frontal pathway associated with the perception of ball shadow appeared to be a significant predictor of the increase in beta oscillations across frontal areas related to the body shadow perception and the decrease in beta oscillations across frontal areas connected to the decision making of the body shadow. Taken together, the findings suggest that inferential thinking ability relative to body shadow would be reliably predicted from object shadows and that the bilateral beta oscillatory modulations would be indicative of the formation of predictive neural frontal assemblies, which encode and infer body shadow neural representation, that is, a substitution of the physical body. [ABSTRACT FROM AUTHOR]

Minimally invasive surgery (MIS) has significantly improved the field of surgery, with benefits including shorter operating time, improved recovery time, minimizing stress and pain due to smaller incisions, and even improving mortality. MIS procedures, including their indications, impact, limitations, and possible future evolution in neonates and infants, are discussed in this article.