Phytoplankton,not allochthonous carbon,sustains herbivorous zooplankton production

Terrestrial organic matter inputs have long been thought to play an important role in aquatic food web dynamics. Results from recent whole lake ¹³C addition experiments suggest terrestrial particulate organic carbon (t-POC) inputs account for a disproportionate portion of zooplankton production. For example, several studies concluded that although t-POC only represented ≈20% of the flux of particulate carbon available to herbivorous zooplankton, this food source accounted for ≈50% of the C incorporated by zooplankton. We tested the direct dietary impact of t-POC (from the leaves of riparian vegetation) and various phytoplankton on Daphnia magna somatic growth, reproduction, growth efficiency, and lipid composition. By itself, t-POC was a very poor quality resource compared to cryptophytes, diatoms, and chlorophytes, but t-POC had similar food quality compared to cyanobacteria. Small additions of high quality Cryptomonas ozolinii to t-POC-dominated diets greatly increased Daphnia growth and reproduction. When offered alone, t-POC resulted in a Daphnia growth efficiency of 5 ± 1%, whereas 100% Cryptomonas and Scenedesmus obliquus diets resulted in growth efficiencies of 46 ± 8% (± SD) and 36 ± 3%, respectively. When offered in a 50:50 mixed diet with Cryptomonas or Scenedesmus, the t-POC fraction resulted in a partial growth efficiency of 22 ± 9% and 15 ± 6%, respectively. Daphnia that obtained 80% of their available food from t-POC assimilated 84% of their fatty acids from the phytoplankton component of their diet. Overall, our results suggest Daphnia selectively allocate phytoplankton-derived POC and lipids to enhance somatic growth and reproduction, while t-POC makes a minor contribution to zooplankton production.     

Eating behavior traits and sleep as determinants of weight loss in overweight and obese adults

Objective:

To examine the associations between eating behavior traits and weight loss according to sleep quality and duration in adults enrolled in common weight-loss interventions.

Methods:

Participants included overweight and obese men and women (n=150) (mean±s.d. age, 38.8±8.6 years; mean±s.d. body mass index (BMI), 33.3±3.5 kg m⁻²) who were subjected to a dietary intervention over a period of 12–16 weeks. Anthropometric measurements, eating behavior traits (Three-Factor Eating Questionnaire), sleep quality (total Pittsburgh Sleep Quality Index (PSQI) score) and sleep duration (hours per night, self-reported from the PSQI) were assessed at both baseline and post intervention. Linear regression analysis was used to quantify the relationships between eating behavior traits and changes in anthropometric markers for all subjects and by sleep categories (short sleep: <7 h per night vs recommended sleep: ⩾7 h per night; poor sleep quality: ⩾5 PSQI score vs good sleep quality: <5 PSQI score). We adjusted for age, sex and baseline BMI in analyses.

Results:

Baseline eating behavior traits were modest predictors of weight-loss success, but they were all significantly associated with their changes over the weight-loss intervention (P<0.01). The diet intervention induced significant changes in eating behavior traits and even more for those having a non-favorable eating behavior profile at baseline. We observed that changes in flexible control and strategic dieting behavior were constantly negatively associated with changes in body weight and fat mass (P<0.05) for recommended duration sleepers. The change in situational susceptibility to disinhibition was positively associated with the change in fat mass and body weight for those having healthy sleeping habits (P<0.05). For poor quality sleepers, the change in avoidance of fattening foods was negatively associated with changes in adiposity (P<0.05).

Conclusion:

Eating behavior traits and sleep may act together to influence the outcome of weight-loss programs.     

Fluctuating silicate:nitrate ratios and coastal plankton food webs

Marine diatoms require dissolved silicate to form an external shell, and their growth becomes Si-limited when the atomic ratio of silicate to dissolved inorganic nitrogen (Si:DIN) approaches 1:1, also known as the “Redfield ratio.” Fundamental changes in the diatom-to-zooplankton-to-higher trophic level food web should occur when this ratio falls below 1:1 and the proportion of diatoms in the phytoplankton community is reduced. We quantitatively substantiate these predictions by using a variety of data from the Mississippi River continental shelf, a system in which the Si:DIN loading ratio has declined from around 3:1 to 1:1 during this century because of land-use practices in the watershed. We suggest that, on this shelf, when the Si:DIN ratio in the river decreases to less than 1:1, then (i) copepod abundance changes from >75% to <30% of the total mesozooplankton, (ii) zooplankton fecal pellets become a minor component of the in situ primary production consumed, and (iii) bottom-water oxygen consumption rates become less dependent on relatively fast-sinking (diatom-rich) organic matter packaged mostly as zooplankton fecal pellets. This coastal ecosystem appears to be a pelagic food web dynamically poised to be either a food web composed of diatoms and copepods or one with potentially disruptive harmful algal blooms. The system is directed between these two ecosystem states by Mississippi River water quality, which is determined by land-use practices far inland.     

Survey of Grain Boundary Energies in Tungsten and Beta-Titanium at High Temperature

Heat treatment is a necessary means to obtain desired properties for most of the materials. Thus, the grain boundary (GB) phenomena observed in experiments actually reflect the GB behaviors at relatively high temperature to some extent. In this work, 405 different GBs were systematically constructed for body-centered cubic (BCC) metals and the grain boundary energies (GBEs) of these GBs were calculated with molecular dynamics for W at 2400 K and β-Ti at 1300 K and by means of molecular statics for Mo and W at 0 K. It was found that high temperature may result in the GB complexion transitions for some GBs, such as the Σ11{332}{332} of W. Moreover, the relationships between GBEs and sin(θ) can be described by the functions of the same type for different GB sets having the same misorientation axis, where θ is the angle between the misorientation axis and the GB plane. Generally, the GBs tend to have lower GBE when sin(θ) is equal to 0. However, the GB sets with the <110> misorientation axis have the lowest GBE when sin(θ) is close to 1. Another discovery is that the local hexagonal-close packed α phase is more likely to form at the GBs with the lattice misorientations of 38.9°/<110>, 50.5°/<110>, 59.0°/<110> and 60.0°/<111> for β-Ti at 1300 K.     

Stimulated emission depletion (STED) nanoscopy of a fluorescent protein-labeled organelle inside a living cell

We demonstrate far-field optical imaging with subdiffraction resolution of the endoplasmic reticulum (ER) in the interior of a living mammalian cell. The diffraction barrier is overcome by applying stimulated emission depletion (STED) on a yellow fluorescent protein tag. Imaging individual structural elements of the ER revealed a focal plane (x, y) resolution of <50 nm inside the living cell, corresponding to a 4-fold improvement over that of a confocal microscope and a 16-fold reduction in the focal-spot cross-sectional area. A similar gain in resolution is realized with both pulsed- and continuous-wave laser illumination. Images of highly convoluted parts of the ER reveal a similar resolution improvement in 3D optical sectioning by a factor of 3 along the optic axis (z). Time-lapse STED recordings document morphological changes of the ER over time. Thus, nanoscale 3D imaging of organelles in the interior of living cells greatly expands the scope of light microscopy in cell biology.     

Chronic lymphocytic leukemia in the elderly: clinico-biological features,outcomes, and proposal of a prognostic model

We investigated the clinico-biological features, outcomes, and prognosis of 949 patients with chronic lymphocytic leukemia according to age. No biological differences (cytogenetics by fluorescent in situ hybridization, IGHV, ZAP-70, CD38, NOTCH1, SF3B1) were found across age groups. Elderly patients (>70 years; n=367) presented more frequently with advanced disease (Binet C/Rai III-IV: 10/12% versus 5/5%; P<0.001), were treated less frequently (23.8% versus 41.9% at 3 years; P<0.001) and in most cases did not receive highly effective regimens and thus had a lower overall response rate (49% with 14% having complete responses versus 69% with 31% having complete responses; P<0.001). The elderly patients also had a shorter overall survival (6.6 versus 13.3 years; P<0.001) and higher disease-unrelated mortality (34.9% versus 6.9% at 10 years; P<0.001). However, disease-attributable mortality was not significantly different between younger and older patients. A combination of Binet stage, ZAP-70 level, β₂-microglobulin concentration and comorbidity identified two risk groups (low-risk: 0–1 parameters; high-risk: 2–4 parameters) with different overall survivals (median: 6.8 versus 11.4 years, P<0.001). In patients requiring treatment, comorbidity at treatment (Cumulative Illness Rating Scale-T>4; hazard ratio 2.2, P<0.001) and response (treatment failure versus response: hazard ratio 1.60, P<0.04) were the most important prognostic factors for overall survival. In conclusion, in our series, elderly patients with chronic lymphocytic leukemia did not present with any biological features distinct from those of younger patients, but did have a poorer clinical outcome. This study highlights the importance of comprehensive medical care, achieving response to therapy, and specific management strategies for elderly patients with chronic lymphocytic leukemia.     

Association of early repolarization pattern and ventricular fibrillation in patients with vasospastic angina: A systematic review and meta‐analysis

BackgroundAn early repolarization (ER) pattern is a risk factor for ventricular fibrillation (VF) in patients with vasospastic angina (VSA) caused by a coronary artery spasm. However, its detailed characteristics and prognostic value for VF remain unclear. Thus, we investigated the relationship between ER and VF in patients with VSA.HypothesisThe ER pattern is associated with VF in patients with VSA.MethodsIn this systematic review and meta‐analysis, we searched PubMed, Embase, Cochrane Library, and Web of Science databases for eligible studies published between January 2011 and December 2020; 8 studies with 1761 patients were included in the final analysis.ResultsThe ER pattern significantly predicted adverse cardiovascular events (ACEs) and VF (odds ratio [OR] = 5.13, 95% confidence interval [95% CI]: 3.16–8.35, p < .00001 and OR = 5.20, 95% CI: 3.05–8.87, p < .00001). The presence of ER in the inferior leads increased the VF risk (OR = 7.80, 95% CI: 4.04–15.05, p < .00001), regardless of the J‐point morphology or type of ST‐segment elevation in the ER pattern. A horizontal/descending ST‐segment elevation was significantly associated with VF in patients with or without an ER pattern during a coronary spasm (OR = 2.28, 95% CI: 1.07–4.88, p = .03). However, obstructive coronary artery disease was unrelated to the ER pattern (OR = 0.82, 95% CI: 0.27–2.53, p = .73).ConclusionsAn ER pattern is significantly associated with an increased risk of ACE in patients with VSA. An inferior ER pattern with horizontal/descending ST‐segment elevation confers the highest risk for VF during VSA onset. Nevertheless, the ER pattern is not associated with obstructive coronary artery disease.     

Existence of nonarithmetic monodromy groups

In an 1885 paper, E. Picard defined a subgroup Τ(Λ) of PU(2,1) generated by monodromies and depending on parameters Λ = (λ₁,λ₂,λ₃,λ₄), 0 < λ_i < 1, < λ_i < 3, λ_i + λ_j ≥ 1, 1 ≤ i < j ≤ 4. The family Τ(Λ) resembles the family of groups Τ([unk]) defined in 1978 but is a different family. In common with the groups Τ([unk]), (i) Τ(Λ) is discrete for a finite number of Λ, (ii) Τ(Λ) is a nonarithmetic lattice for some Λ, and (iii) for all Λ [unk]⁴, there is a compact complex surface S(Λ) with π₁ [S(Λ)] of finite index in Τ(Λ).     

On a third kind of characteristic numbers of the spheroidal functions

A set of real positive numbers γ_αn(c) was found recently to be associated with the spheroidal functions of real order α > -1 as a consequence of their double orthogonality on (-1, 1) and (- ∞, ∞). In the range -1 < α < 0 these numbers are shown to be determined by the eigenvalues of a new integral equation for the spheroidal functions. Thus they represent a third kind of characteristic numbers. The new equation ceases to be an integral equation above the range -1 < α < 0 but it leads to computational formulas for γ_αn(c) that appear from numerical results to be valid for all real α > -1.     

Almost All Roots of zeta(s) = a Are Arbitrarily Close to sigma = 1/2

Let s = σ + it. For any complex a, all but O(1/log log T) of the roots of ζ(s) = a in T < t < 2T lie in|σ - 1/2| < (log log T)²/log T. The results extend easily to other functions satisfying a functional equation such as the Dirichlet L-functions, the Lerch functions, etc.     

Independent effects of diet and exercise training on fat oxidation in non-alcoholic fatty liver disease

AIM To investigate the independent effects of 6-mo of dietary energy restriction or exercise training on wholebody and hepatic fat oxidation of patients with nonalcoholic fatty liver disease(NAFLD).METHODS Participants were randomised into either circuit exercise training(EX;n = 13;3 h/wk without changes in dietary habits),or dietary energy restriction(ER) without changes in structured physical activity(ER;n = 8).Respiratory quotient(RQ) and whole-body fat oxidation rates(Fatox) were determined by indirect calorimetry under basal,insulin-stimulated and exercise conditions.Severity of disease and steatosis was determined by liver histology;hepatic Fatox was estimated from plasma β-hydroxybutyrate co.ncentrations;cardiorespiratory fitness was expressed as VO2 peak.Complete-case analysis was performed(EX:n = 10;ER:n = 6).RESULTS Hepatic steatosis and NAFLD activity score decreased with ER but not with EX.β-hydroxybutyrate concentrations increased significantly in response to ER(0.08 ± 0.02 mmol/L vs 0.12 ± 0.04 mmol/L,P = 0.03) but remained unchanged in response to EX(0.10 ± 0.03 mmol/L vs 0.11 ± 0.07 mmol/L,P = 0.39).Basal RQ decreased(P = 0.05) in response.to EX,while this change was not significant after ER(P = 0.38).VO_(2peak)(P 0.001) and maximal Fa_(tox) during aerobic exercise(P = 0.03) improved with EX but not with ER(P 0.05).The increase in β-hydroxybutyrate concentrations was correlated with the reduction in hepatic steatosis(r =-0.56,P = 0.04).CONCLUSION ER and EX lead to specific benefits on fat metabolism of patients with NAFLD.Increased hepatic Fat_(ox) in response to ER could be one mechanism through which the ER group achieved reduction in steatosis.     

Validation of methods to assess potential biomarkers in pediatric patients with esophageal eosinophilia

AIM: To validate methods for determining mast cell density, extracellular major basic protein content, and presence of fibrosis in esophageal eosinophilia.METHODS: Twenty specimens with > 20 eosinophils/high-power field (hpf) classified as high eosinophil density (HE) and 20 specimens with < 5 eosinophils/hpf classified as low esophageal density (LE) were identified. All 40 specimens underwent immunohistochemical staining and trichrome staining. Mast cell density, extracellular major basic protein (MBP) density, and presence of subepithelial fibrosis were assessed in a standardized manner. All specimens were evaluated by two separate observers and by a single observer on two separate occasions to evaluate reproducibility of the methods.RESULTS: A strong inter-observer correlation was noted for both peak and mean mast cell counts (r = 0.725, P < 0.0001 and r = 0.823, P < 0.0001). A strong intra-observer correlation also was noted for both peak and mean mast cell counts (r = 0.752, P < 0.0001 and r = 0.878, P < 0.0001). A very strong inter-observer correlation was noted for both peak (τ = 0.867, P < 0.0001) and mean extracellular MBP densities (r = 0.925, P < 0.0001). A very strong intra-observer correlation was noted for both peak (τ = 0.875; P < 0.0001) and mean extracellular MBP densities (r = 0.956, P < 0.0001). Excellent inter-rater reliability was found for fibrosis (κ = 0.887). Mast cell and MBP densities, as well as presence of fibrosis, were significantly increased in HE vs LE. The HE group had significantly higher intraepithelial mast cell peak (29.35 ± 21.61 vs 12.45 ± 8.26, P = 0.002) and mean (19.84 ± 15.81 vs 6.35 ± 4.5, P = 0.001) densities than the LE group. The HE group had significantly higher peak extracellular MBP (2.35 ± 0.67 vs 0.45 ± 0.61, P < 0.001) and mean extracellular MBP (1.95 ± 0.76 vs 0.20 ± 0.29, P < 0.0001) densities than the LE group. Seventy-three percent of patients with HE (11/15) had fibrosis, whereas only 10% of patients with LE (1/10) had fibrosis (P < 0.01). MBP performed the best in predicting classification of HE vs LE, with mean MBP demonstrating 100% sensitivity and 95% specificity at the optimal cut point.CONCLUSION: This study provides methodology and proof-of-concept for future evaluation of these biomarkers for differentiating esophageal eosinophilic diseases such as reflux esophagitis and eosinophilic esophagitis.     

Fat-restricted low-glycemic index diet controls weight and improves blood lipid profile: A pilot study among overweight and obese adults in Southwest China

Evidence from trials demonstrating the benefits and risks of low-glycemic index and fat-restricted diets in weight loss and blood lipid profile changes is unclear. This study aimed to assess the implemented and effects of a fat-restricted low-glycemic index diet on weight control and blood lipid profile changes in in overweight/obese Southwest Chinese individualst.This prospective pilot study enrolled overweight/obese subjects at the People''s Hospital of Sichuan Province between February and July 2019. The daily energy intake was reduced by 300 to 500 kcal according to the participant‘s weight and activity level, with low-glycemic index carbohydrate- and fat-energy ratios < 45% and 25% to 30%, respectively. Participants received guidance for 3 months by telephone follow-up, internet interaction, or WeChat. Changes in weight, body composition, and blood profile were measured.A total of 254 patients were finally analyzed, including 101 males and 153 females. After adjusting for potential confounders, weight (P < .001), body mass index (P < .001), waist circumference (P < .001), waist-hip ratio (P < .001), body fat percentage (P < .001), visceral fat area (P < .001), basal metabolism (P = .002), cholesterol (P < .001), and triglycerides (P < .001) were significantly reduced after the 3-month intervention. The above indexes showed no significant differences between men and women.Regardless of gender, fat-restricted low-glycemic index diet might be helpful for controlling weight and lowering blood cholesterol and triglycerides in overweight/obese individuals in Southwest China.     

Patterns of Growth after Kidney Transplantation among Children with ESRD

Background and objectives

Poor linear growth is a frequent complication of CKD. This study evaluated the effect of kidney transplantation on age-related growth of linear body segments in pediatric renal transplant recipients who were enrolled from May 1998 until August 2013 in the CKD Growth and Development observational cohort study.

Design, setting, participants, & measurements

Linear growth (height, sitting height, arm and leg lengths) was prospectively investigated during 1639 annual visits in a cohort of 389 pediatric renal transplant recipients ages 2–18 years with a median follow-up of 3.4 years (interquartile range, 1.9–5.9 years). Linear mixed-effects models were used to assess age-related changes and predictors of linear body segments.

Results

During early childhood, patients showed lower mean SD scores (SDS) for height (−1.7) and a markedly elevated sitting height index (ratio of sitting height to total body height) compared with healthy children (1.6 SDS), indicating disproportionate stunting (each P<0.001). After early childhood a sustained increase in standardized leg length and a constant decrease in standardized sitting height were noted (each P<0.001), resulting in significant catch-up growth and almost complete normalization of sitting height index by adult age (0.4 SDS; P<0.01 versus age 2–4 years). Time after transplantation, congenital renal disease, bone maturation, steroid exposure, degree of metabolic acidosis and anemia, intrauterine growth restriction, and parental height were significant predictors of linear body dimensions and body proportions (each P<0.05).

Conclusions

Children with ESRD present with disproportionate stunting. In pediatric renal transplant recipients, a sustained increase in standardized leg length and total body height is observed from preschool until adult age, resulting in restoration of body proportions in most patients. Reduction of steroid exposure and optimal metabolic control before and after transplantation are promising measures to further improve growth outcome.     

Impacts of common factors of life style on serum liver enzymes

AIM: To investigate the impacts of gender, age and factors of life style (alcohol, overweight, coffee and smoking) on serum liver enzymes.METHODS: Serum alanine aminotransferase (ALT) and gamma-glutamyltransferase (GGT) were measured from 6269 apparently healthy individuals (2851 men, 3418 women, mean age 45 ± 12 years, range 25-74 years) in a national cross-sectional health survey. All subjects underwent detailed clinical examinations and interviews including the amount and pattern of alcohol use, coffee consumption and smoking habits.RESULTS: In this population with a mean ± SD alcohol consumption of 65 ± 105 g/wk and body mass index (BMI) of 26.1 ± 4.3 kg/m², both ALT and GGT were significantly influenced by alcohol use (P < 0.001) and BMI (P < 0.001), whereas smoking increased only GGT (P < 0.001). A significant effect of age on ALT was seen in men (P < 0.001) whereas not in women. Significant two-factor interactions of alcohol use in men were observed with age (ALT: P < 0.01; GGT: P < 0.001) and BMI (GGT: P < 0.05). For ALT, a significant interaction also occurred between BMI and age (P < 0.005). In contrast, women showed significant interactions of alcohol use with BMI (GGT: P < 0.05), smoking (GGT: P < 0.001), and coffee consumption (GGT: P < 0.001).CONCLUSION: Life-style associated changes in liver enzymes may reflect health risks, which should be considered in the definition of normal limits for liver enzymes.     

Obese Patients With a Binge Eating Disorder Have an Unfavorable Metabolic and Inflammatory Profile

To evaluate whether obese patients with a binge eating disorder (BED) have an altered metabolic and inflammatory profile related to their eating behaviors compared with non-BED obese.A total of 115 White obese patients consecutively recruited underwent biochemical, anthropometrical evaluation, and a 75-g oral glucose tolerance test. Patients answered the Binge Eating Scale and were interviewed by a psychiatrist. The patients were subsequently divided into 2 groups according to diagnosis: non-BED obese (n = 85) and BED obese (n = 30). Structural equation modeling analysis was performed to elucidate the relation between eating behaviors and metabolic and inflammatory profile.BED obese exhibited significantly higher percentages of altered eating behaviors, body mass index (P < 0.001), waist circumference (P < 0.01), fat mass (P < 0.001), and a lower lean mass (P < 0.001) when compared with non-BED obese. Binge eating disorder obese also had a worse metabolic and inflammatory profile, exhibiting significantly lower high-density lipoprotein cholesterol levels (P < 0.05), and higher levels of glycated hemoglobin (P < 0.01), uric acid (P < 0.05), erythrocyte sedimentation rate (P < 0.001), high-sensitive C-reactive protein (P < 0.01), and white blood cell counts (P < 0.01). Higher fasting insulin (P < 0.01) and higher insulin resistance (P < 0.01), assessed by homeostasis model assessment index and visceral adiposity index (P < 0.001), were observed among BED obese. All differences remained significant after adjusting for body mass index. No significant differences in fasting plasma glucose or 2-hour postchallenge plasma glucose were found. Structural equation modeling analysis confirmed the relation between the altered eating behaviors of BED and the metabolic and inflammatory profile.Binge eating disorder obese exhibited an unfavorable metabolic and inflammatory profile, which is related to their characteristic eating habits.     

Molecular cloning and characterization of ligand- and species-specificity of amphibian estrogen receptors

Estrogens are essential for normal reproductive activity in both males and females as well as for ovarian differentiation during a critical developmental stage in most vertebrates. To understand the molecular mechanisms of estrogen action and to evaluate estrogen receptor ligand interactions in amphibians, we isolated cDNAs encoding the estrogen receptors (ERα and ERβ) from the Japanese firebelly newt (Cynops pyrrhogaster), Tokyo salamander (Hynobius tokyoensis), axolotl (Ambystoma mexicanum), and Raucous toad (Bufo rangeri). Full-length amphibian ER cDNAs were obtained using 5′ and 3′ rapid amplification of cDNA ends. The predicted amino acid sequences of these amphibian ERs showed a high degree of amino acid sequence identity (over 70%) to each other. We analyzed the relationships of these amphibian ER sequences to other vertebrate ER sequences by constructing a phylogenetic tree. We verified that these were bona fide estrogen receptors using receptor dependent reporter gene assays. We analyzed the effects of natural estrogens, ethinylestradiol, and DDT and its metabolites on the transactivation of the four amphibian species listed above, and Xenopus tropicalis ERs and found that there were species-specific differences in the sensitivity of these ERs to hormones and environmental chemicals. These findings will expand our knowledge of endocrine-disrupting events in amphibians.     

Impact of body mass index on diastolic function in patients with normal left ventricular ejection fraction

Background:

Obesity is a major public health epidemic and is associated with increased risk of heart failure and mortality. We evaluated the impact of body mass index (BMI) on the prevalence of diastolic dysfunction (DD).

Methods:

We reviewed clinical records and echocardiogram of patients with baseline echocardiogram between 1996 and 2005 that showed normal left ventricular ejection fraction (LVEF). Diastolic function was labeled as normal, stage 1, stage 2 or stage 3/4 dysfunction. Patients were categorized as normal weight (BMI <25 kg m⁻²), overweight (25–29.9 kg m⁻²), obese (30–39.9 kg m⁻²) and morbidly obese (⩾40 kg m⁻²). Multivariable ordinal and ordinary logistic regression were performed to identify factors associated with DD, and evaluate the independent relationship of BMI with DD.

Results:

The cohort included 21 666 patients (mean (s.d.) age, 57.1 (15.1); 55.5% female). There were 7352 (33.9%) overweight, 5995 (27.6%) obese and 1616 (7.4%) morbidly obese patients. Abnormal diastolic function was present in 13 414 (61.9%) patients, with stage 1 being the most common. As BMI increased, the prevalence of normal diastolic function decreased (P<0.0001). Furthermore, there were 1733 patients with age <35 years; 460 (26.5%) and 407 (23.5%) were overweight and obese, respectively, and had higher prevalence of DD (P<0.001). Using multivariable logistic regression, BMI remained significant in both ordinal (all stages of diastolic function) and binary (normal versus abnormal). Also, obesity was associated with increased odds of DD in all patients and those aged <35 years.

Conclusions:

In patients with normal LVEF, higher BMI was independently associated with worsening DD.     

Specific transbilayer translocation of dolichol-linked oligosaccharides by an endoplasmic reticulum flippase

The oligosaccharide donor for protein N-glycosylation, Glc₃Man₉GlcNAc₂-PP-dolichol, is synthesized via a multistep pathway that starts on the cytoplasmic face of the endoplasmic reticulum (ER) and ends in the lumen where the glycosylation reaction occurs. This necessitates transbilayer translocation or flipping of the lipid intermediate Man₅GlcNAc₂-PP-dolichol (M5-DLO) across the ER membrane. The mechanism by which M5-DLO—or any other lipid—is flipped across the ER is unknown, except that specific transport proteins or flippases are required. We recently demonstrated M5-DLO flipping activity in proteoliposomes reconstituted from detergent-solubilized ER membrane proteins and showed that it was ATP-independent and required a trypsin-sensitive protein that sedimented at approximately 4S. By using an activity-enriched fraction devoid of glycerophospholipid flippase activity, we now report that M5-DLO is rapidly flipped in the reconstituted system with a time constant τ <2 min, whereas its triantennary structural isomer is flipped slowly with τ >200 min. DLOs larger than M5-DLO are also poorly translocated, with τ ranging from approximately 10 min to >200 min. We conclude that (i) the number and arrangement of mannoses in the DLO glycan has a profound effect on the ability of the DLO to be translocated by the flippase, (ii) glycan size per se does not dictate whether a DLO will be flipped, and (iii) the flippase is highly specific for M5-DLO. Our results suggest a simple structural model for the interaction between the DLO head group and the flippase.     

The Clinical Relevance of Psammoma Body and Hashimoto Thyroiditis in Papillary Thyroid Carcinoma: A Large Case-control Study

This study aims to investigate the impact of psammoma body (PB) on papillary thyroid carcinoma (PTC), and evaluate the association among PB, Hashimoto thyroiditis (HT), and other clinicopathologic characteristics in PTC patients.We conducted a retrospective case-control study involving 1052 PTC patients who underwent total thyroidectomy or lobectomy with lymph node dissection.Psammoma body was observed in 324 out of 1052 PTC (30.8%) patients. Ultrasonographic (US) calcification (P < 0.001), multifocality of the tumor (P = 0.047), lymph node metastasis (LNM) (P < 0.001), HT (P < 0.001), and Primary tumor (T), Regional lymph nodes (N), Distant metastasis (M) staging (P = 0.001) were significantly related to the presence of PB. The presence of PB was significantly associated with US microcalcification (P < 0.001). In the subgroup with HT, compared with the patients without PB, the patients with PB exhibited a higher frequency of central LNM (54.7% vs 32.1%; P < 0.001) and US microcalcification (94.7% vs 38.8%; P < 0.001), as well as smaller tumors (0.9 ± 0.6 vs 1.3 ± 0.9 cm; P < 0.001). In the subgroup without HT, the patients with PB displayed a higher incidence of lateral LNM (25.8% vs 14.6%; P < 0.001), US microcalcification (87.3% vs 52.5%; P < 0.001), and extrathyroidal extension (47.2% vs 34.8%; P = 0.001), as well as larger tumors (1.3 ± 0.9 vs 1.0 ± 0.8 cm; P < 0.001) than without PB. Moreover, in the subgroup with PB, the PTC patients with HT showed a higher LNM (77.9% vs 57.2%; P < 0.001) and a lower frequency of extrathyroidal extension (20.0% vs 47.2%; P < 0.001) than without HT.Psammoma body is a useful predictor of aggressive tumor behavior in PTC patients. HT with PB shows more aggressive behaviors than non-HT with PB in PTC patients.