Metabolomic profiles of ovariectomized mice and their associations with body composition and frailty-related parameters in postmenopausal women.

BACKGROUND: Menopause, a dramatical estrogen-deficient condition, is considered the most significant milestone in women's health. PURPOSE: To investigate the metabolite changes attributed to estrogen deficiency using random forest (RF)-based machine learning (ML) modeling strategy in ovariectomized (OVX) mice as well as determine the clinical relevance of selected metabolites in older women. METHODS AND RESULTS: Untargeted and targeted metabolomic analyses revealed that metabolites related to TCA cycle, sphingolipids, phospholipids, fatty acids, and amino acids, were significantly changed in the plasma and/or muscle of OVX mice. Subsequent ML classifiers based on RF algorithm selected alpha-ketoglutarate (AKG), arginine, carnosine, ceramide C24, phosphatidylcholine (PC) aa C36:6, and PC ae C42:3 in plasma as well as PC aa 34:1, PC aa C34:3, PC aa C36:5, PC aa C32:1, PC aa C36:2, and sphingosine in muscle as top featured metabolites that differentiate the OVX mice from the sham-operated group. When circulating levels of AKG, arginine, and carnosine, which showed the most significant changes in OVX mice blood, were measured in postmenopausal women, higher plasma AKG levels were associated with lower bone mass, weak grip strength, poor physical performance, and increased frailty risk. CONCLUSIONS: Metabolomics- and ML-based methods identified the key metabolites of blood and muscle that were significantly changed after ovariectomy in mice, and the clinical implication of several metabolites was investigated by looking at their correlation with body composition and frailty-related parameters in postmenopausal women. These findings provide crucial context for understanding the diverse physiological alterations caused by estrogen deficiency in women.

Inefficient Magnetic-Field Amplification in Supersonic Laser-Plasma Turbulence.

We report a laser-plasma experiment that was carried out at the LMJ-PETAL facility and realized the first magnetized, turbulent, supersonic (Ma_{turb}≈2.5) plasma with a large magnetic Reynolds number (Rm≈45) in the laboratory. Initial seed magnetic fields were amplified, but only moderately so, and did not become dynamically significant. A notable absence of magnetic energy at scales smaller than the outer scale of the turbulent cascade was also observed. Our results support the notion that moderately supersonic, low-magnetic-Prandtl-number plasma turbulence is inefficient at amplifying magnetic fields compared to its subsonic, incompressible counterpart.

Vertebral fracture is associated with myocardial infarction in incident hemodialysis patients: a Korean nationwide population-based study.

Chronic kidney disease (CKD)-mineral and bone disorder suggests that fragile bone and vascular disorder might be connected closely in CKD patients. In this study, fracture event was significantly associated with myocardial infarction (MI) in end-stage renal disease patients on hemodialysis (HD), especially for vertebral fractures. INTRODUCTION: CKD-mineral and bone disorder is characterized by biochemical abnormalities, bone disorders, and vascular calcification. We aimed to verify the association between fracture and MI in CKD patients. METHODS: Records for incident CKD stage 3 to 5 patients and patients who initiated HD between July 2014 and June 2018 were retrieved from the Korean Health Insurance Review & Assessment Service Database. Fractures were defined using diagnostic codes and were classified into vertebral, femoral, and other site fractures. MI was defined using a combination of MI diagnostic codes and related procedure codes. Multiple logistic regressions and 1:1 propensity score matching analysis were conducted. RESULTS: A total of 38,935 patients (HD, 11,379; pre-dialysis CKD, 27,556) were included in this study. A total of 5,057 (13.0%) patients experienced fracture, and 1,431 (3.7%) patients had MI. Multiple logistic regression analysis showed that fracture was significantly associated with MI in the HD group (odds ratio (OR) 1.34, P = 0.024), but not in the pre-dialysis CKD group (OR 1.04, P = 0.701). After propensity score matching for age, gender, and diabetes mellitus between patients with and without fracture, fracture still significantly correlated with MI in HD patients (OR 1.47, P = 0.034) but not in patients with pre-dialysis CKD (OR 1.04, P = 0.751). Subgroup analysis by fracture site found that vertebral fracture was associated with MI in HD patients (OR 2.11, P = 0.024), but femoral or other site fractures were not. CONCLUSION: In HD patients, fracture was significantly associated with MI, especially for vertebral fractures patients.

Magnetic resonance imaging assessment of the substrate for hyposmia in patients with Parkinson's disease.

AIM: To assess whether multimodal magnetic resonance imaging (MRI) could detect neuroanatomical substrates that are distinctive to hyposmic Parkinson's disease (PD). MATERIALS AND METHODS: Among 102 PD patients, 62 were hyposmic and 40 were normosmic. For each patient, a sagittal structural three-dimensional (3D) T1-weighted image was obtained with the magnetisation-prepared rapid acquisition of the gradient-echo sequence to generate subcortical grey matter masking templates and to perform a voxel-based morphometry analysis of the subcortical grey matter volumes. A 3D multi-echo gradient sequence was run to obtain axial magnitude and phase images to produce a quantitative susceptibility map (QSM), and a diffusion-weighted image was acquired to generate an apparent diffusion coefficient (ADC) map. The volumes and average QSM and ADC values of the 15 subcortical grey matter structures were calculated, and the group differences were evaluated using a one-way analysis of covariance with age and gender as covariates. RESULTS: The QSM of the left thalamus significantly increased, while that of the right thalamus significantly decreased in hyposmia. No effects on the cortical volume changes were found other than aging. CONCLUSION: The present results suggest that accumulation of disease-related substances in the left and right thalamus and the increasing asymmetry between the two sides are associated with hyposmia in PD.

Extracorporeal cardiopulmonary resuscitation in refractory intra-operative cardiac arrest: an observational study of 12-year outcomes in a single tertiary hospital.

Refractory intra-operative cardiac arrest is a challenging issue for anaesthetists. In this study, we analysed the outcomes of adult patients who received extracorporeal cardiopulmonary resuscitation for refractory intra-operative cardiac arrest between 2005 and 2016, using data from our institutional extracorporeal membrane oxygenation registry. We defined refractory intra-operative cardiac arrest as the failure of a return of spontaneous circulation after 30 min of cardiopulmonary resuscitation. The primary outcome measure was neurologically intact survival with a cerebral performance category score of 1 or 2 at hospital discharge. Between 2005 and 2016, extracorporeal cardiopulmonary resuscitation was used to treat 23 patients who experienced refractory cardiac arrest in the operating room. The survival rates of neurologically-intact subjects were 9/23 (39%) and 6/23 (26%) at 24 h postoperatively and at hospital discharge, respectively. The main cause of refractory-intra-operative cardiac arrest was haemorrhagic shock in 13 out of 23 (57%) patients, and the neurologically-intact survival rate in these patients was 3/13 (23%) at discharge. Our study showed that approximately a quarter of patients with refractory intra-operative cardiac arrest caused by haemorrhage would receive survival benefit from extracorporeal cardiopulmonary resuscitation. Therefore, extracorporeal cardiopulmonary resuscitation may be a possible option in this clinically-challenging situation.

Normal 'heart' in Parkinson's disease: is this a distinct clinical phenotype?

BACKGROUND AND PURPOSE: Reduction of metaiodobenzylguanidine (MIBG) uptake has been observed in almost all patients with Parkinson's disease (PD), associated with hyposmia, orthostatic hypotension and rapid eye movement sleep behavioral disorder (RBD). In contrast, a subgroup of patients with PD with normal MIBG uptake have been reported to have milder disease and preserved cognition compared with those with lower MIBG. The aim of this study was to investigate whether non-motor manifestations of PD differ between patients with normal and abnormal myocardial MIBG uptake. METHODS: Among 160 de-novo cases of PD, 44 had normal MIBG uptake. Twelve candidate non-motor features were evaluated using questionnaires and laboratory tests. RESULTS: Patients with decreased MIBG uptake had more constipation, RBD, cognitive impairment, hyposmia and orthostatic hypotension than did those with normal MIBG uptake. On linear regression analysis, orthostatic hypotension, olfactory function and probable RBD were significantly associated with MIBG uptake in PD. The principal component analysis showed that the group with normal MIBG was not associated with non-motor impairments. CONCLUSIONS: These results suggest that patients with PD with normal MIBG scans have a relatively low disease burden compared with those with abnormal MIBG. Fewer synuclein pathologies in the myocardia and sympathetic ganglia in PD with preserved MIBG uptake might be associated with lower threshold patterns of Braak synuclein pathology for non-motor manifestations compared with PD with decreased MIBG.

Predictor of fluid responsiveness in the 'grey zone': augmented pulse pressure variation through a temporary increase in tidal volume.

BACKGROUND: Pulse pressure variation (PPV) is widely used as a predictor of fluid responsiveness. However, a previous study has suggested a 'grey zone' between 9 and 13% in which PPV would be inconclusive to predict fluid responsiveness. Considering PPV is based on cardiopulmonary interactions, we evaluated whether an augmented PPV using a temporary increase in tidal volume (V T ) from 8 to 12 ml kg -1 has the predictability for fluid responsiveness in patients within the grey zone. METHODS: Adult patients requiring general anaesthesia were enrolled. During the period when PPV was within the range of 9-13%, haemodynamic variables such as stroke volume index (SVI) and PPV with an 8 ml kg -1 tidal volume ventilation (PPV8) were obtained before and after volume expansion (6 ml kg -1 ) under mechanical ventilation. Augmented PPV induced by 2-min ventilation with a V T of 12 ml kg -1 (PPV12) was also recorded immediately before volume loading. The patients whose SVI increased ≥10% after volume expansion were considered responders. RESULTS: In 38 enrolled patients, 20 were responders. Receiver operating characteristic curve analysis showed PPV12 had an excellent predictability for fluid responsiveness {area under the curve [AUC]=0.935 [95% confidence interval (CI) 0.805-0.989]; sensitivity 95%; specificity 72%; P <0.0001}. The optimal threshold for PPV12 was >17%. However, PPV8 failed to show significant predictability [AUC=0.668 (95% CI 0.497-0.812); sensitivity 65%; specificity 61%; P =0.06]. CONCLUSION: In mechanically ventilated patients, our augmented PPV successfully predicted fluid responsiveness in the previously suggested grey zone. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, NCT02653469.

Bayesian framework for parametric bivariate accelerated lifetime modeling and its application to hospital acquired infections.

Infectious diseases that can be spread directly or indirectly from one person to another are caused by pathogenic microorganisms such as bacteria, viruses, parasites, or fungi. Infectious diseases remain one of the greatest threats to human health and the analysis of infectious disease data is among the most important application of statistics. In this article, we develop Bayesian methodology using parametric bivariate accelerated lifetime model to study dependency between the colonization and infection times for Acinetobacter baumannii bacteria which is leading cause of infection among the hospital infection agents. We also study their associations with covariates such as age, gender, apache score, antibiotics use 3 months before admission and invasive mechanical ventilation use. To account for singularity, we use Singular Bivariate Extreme Value distribution to model residuals in Bivariate Accelerated lifetime model under the fully Bayesian framework. We analyze a censored data related to the colonization and infection collected in five major hospitals in Turkey using our methodology. The data analysis done in this article is for illustration of our proposed method and can be applied to any situation that our model can be used.

Serum metabolomics reveals pathways and biomarkers associated with asthma pathogenesis.

BACKGROUND: Asthma is a chronic inflammatory disease caused by complex interactions of genetic, epigenetic, and environmental factors. For this reason, new approaches are required to clarify the pathogenesis of asthma by systemic review. OBJECTIVE: We applied a (1)H-NMR metabolomics approach to investigate the altered metabolic pattern in sera from patients with asthma and sought to identify the mechanism underlying asthma and potential biomarkers. METHOD: A global profile of sera from patients with asthma (n = 39) and controls (n = 26) was generated using (1)H-NMR spectroscopy coupled with multivariate statistical analysis. Endogenous metabolites in serum were rapidly measured using the target-profiling procedure. RESULTS: Multivariate statistical analysis showed a clear distinction between patients with asthma and healthy subjects. Sera of asthma patients were characterized by increased levels of methionine, glutamine, and histidine and by decreased levels of formate, methanol, acetate, choline, O-phosphocholine, arginine, and glucose. The metabolites detected in the sera of patients with asthma are involved in hypermethylation, response to hypoxia, and immune reaction. Furthermore, the levels of serum metabolites from patients with asthma correlated with asthma severity; in particular, lipid metabolism was altered in patients with lower forced expiratory volume in 1 s percentage (FEV(1)%) predicted values. In addition, potential biomarkers showed strong predictive power in ROC analysis, and the presence of asthma in external validation models was predicted with high accuracy (90.9% for asthma and 100% for control subjects). CONCLUSION & CLINICAL RELEVANCE: These data showed that (1)H-NMR-based metabolite profiling of serum may be useful for the effective diagnosis of asthma and a further understanding of its pathogenesis.

Management of gastric epithelial neoplasia in patients requiring esophagectomy for esophageal cancer.

Esophageal squamous cell carcinoma is occasionally associated with malignancies located in other regions of the alimentary tract, as well as in the head, neck, and upper respiratory tract. The stomach is most commonly used for reconstruction of the alimentary tract after esophagectomy for esophageal cancer. When synchronous tumors are located in the stomach, it is often unsuitable for use in esophageal reconstruction. In such cases, an invasive procedure involving anastomosis between the esophagus and the colon must be performed. However, this procedure is associated with a high incidence of mortality and morbidity. Seven patients with synchronous esophageal cancer and gastric epithelial neoplasia were encountered. First, endoscopic submucosal dissection (ESD) was performed for the gastric epithelial neoplasia. Then, following successful ESD, Ivor-Lewis esophagectomy for esophageal cancer was planned 1 to 2 weeks later. A total of 11 gastric epithelial lesions were found in seven patients. En bloc resection by ESD was possible in all 11 lesions and histologically complete resection was achieved in all 11 lesions. Follow-up endoscopy was done 1-2 weeks after ESD; six patients with well-healing ulcers underwent esophagectomy the next day (8 or 15 days after ESD). In one patient with a poorly healed ulcer, a second follow-up endoscopy was done 1 week later and then esophagectomy was performed the next day (22 days after ESD). Post-surgical complications related to ESD, such as bleeding or mediastinal leak, were not seen in any of the seven patients. In patients with synchronous esophageal cancer and gastric epithelial neoplasia, ESD for gastric epithelial neoplasia followed by Ivor-Lewis esophagectomy 1 to 2 weeks later is an effective choice of treatment.

A new species of Hoya R.Br. (Apocynaceae, Asclepiadoideae) from the Philippines.

Hoyamedusa M.D.De Leon, Cabactulan, Cuerdo & Rodda, sp. nov. (Apocynaceae, Asclepiadoideae) is described from the Philippines. Even though numerous taxa with a shrubby habit from this area are known, it can be immediately separated because of its urceolate corolla and prominent elongated corona lobes. No other species in the genus possesses such a combination of characters.

Mechanically and structurally robust sulfonated block copolymer membranes for water purification applications.

The effective removal of ionic pollutants from contaminated water using negatively charged nanofiltration membranes is demonstrated. Block copolymers comprising polystyrene (PS) and partially hydrogenated polyisoprene (hPI) were synthesized by varying chain architectures. A one step procedure of cross-linking (hPI blocks) and sulfonation reactions (PS chains) was then carried out, which was revealed as an effective method to enhance mechanical integrity of membranes while hydrophilic sulfonated chains remain intact. In particular, the control of chain architecture allows us to create a synergetic effect on optimizing charge densities of the membrane, water permeability, and mechanical integrity under water purification conditions. The best performing membrane can almost completely (>99%) reject various divalent cations and also show NO(3)(-) rejection > 85% and Na(+) rejection > 87%. Well defined nanostructures (tens of nanometers) as well as the periodically arranged water domains (a few nanometers) within hydrophilic phases of the hydrated membranes were confirmed by in situ neutron scattering experiments.

Peroxiredoxin 4 directly affects the male fertility outcome in porcine.

Peroxiredoxins (Prdxs) are known to play a critical role in regulating male fertility as antioxidant enzymes. Although several studies have suggested a close association between Prdxs and male fertility, few studies have explored the efficacy of Prdxs to predict male fertility. Therefore, the current study was designed to discover the most efficient biomarkers among the Prdxs with six isoforms. Our study showed a significant positive correlation between the litter size and the levels of PRDX 4 among all isoforms in spermatozoa. Subsequently, a regression analysis using a combination of markers was conducted to increase efficacy for fertility prediction. Nevertheless, PRDX4 had the highest efficacy compared to other combination models to predict litter size. The prediction accuracy of male fertility was further evaluated through receiver operating characteristic curve analysis, which showed that PRDX 4 could predict the litter size with high overall accuracy of 95%. Moreover, litter size was increased by 1.55 piglets after predicting high litter size using PRDX 4. This is the first study to comprehensively elucidate the role of all isoforms of PRDXs on male fertility to the best of our knowledge. PRDX 4 was tested and evaluated up to a practical level. Data here reported suggesting PRDX 4 marker allowed the highest accuracy for male fertility prediction and diagnosis, leading to a measurable improvement in the male fertility outcome.

Supersonic plasma turbulence in the laboratory.

The properties of supersonic, compressible plasma turbulence determine the behavior of many terrestrial and astrophysical systems. In the interstellar medium and molecular clouds, compressible turbulence plays a vital role in star formation and the evolution of our galaxy. Observations of the density and velocity power spectra in the Orion B and Perseus molecular clouds show large deviations from those predicted for incompressible turbulence. Hydrodynamic simulations attribute this to the high Mach number in the interstellar medium (ISM), although the exact details of this dependence are not well understood. Here we investigate experimentally the statistical behavior of boundary-free supersonic turbulence created by the collision of two laser-driven high-velocity turbulent plasma jets. The Mach number dependence of the slopes of the density and velocity power spectra agree with astrophysical observations, and supports the notion that the turbulence transitions from being Kolmogorov-like at low Mach number to being more Burgers-like at higher Mach numbers.

Characterisation of spatial variability in water quality in the Great Barrier Reef catchments using multivariate statistical analysis.

Water quality monitoring is important to assess changes in inland and coastal water quality. The focus of this study was to improve understanding of the spatial component of spatial-temporal water quality dynamics, particularly the spatial variability in water quality and the association between this spatial variability and catchment characteristics. A dataset of nine water quality constituents collected from 32 monitoring sites over a 11-year period (2006-2016), across the Great Barrier Reef catchments (Queensland, Australia), were evaluated by multivariate techniques. Two clusters were identified, which were strongly associated with catchment characteristics. A two-step Principal Component Analysis/Factor Analysis revealed four groupings of constituents with similar spatial pattern and allowed the key catchment characteristics affecting water quality to be determined. These findings provide a more nuanced view of spatial variations in water quality compared with previous understanding and an improved basis for water quality management to protect nearshore marine ecosystem.

Laboratory evidence of dynamo amplification of magnetic fields in a turbulent plasma.

Magnetic fields are ubiquitous in the Universe. The energy density of these fields is typically comparable to the energy density of the fluid motions of the plasma in which they are embedded, making magnetic fields essential players in the dynamics of the luminous matter. The standard theoretical model for the origin of these strong magnetic fields is through the amplification of tiny seed fields via turbulent dynamo to the level consistent with current observations. However, experimental demonstration of the turbulent dynamo mechanism has remained elusive, since it requires plasma conditions that are extremely hard to re-create in terrestrial laboratories. Here we demonstrate, using laser-produced colliding plasma flows, that turbulence is indeed capable of rapidly amplifying seed fields to near equipartition with the turbulent fluid motions. These results support the notion that turbulent dynamo is a viable mechanism responsible for the observed present-day magnetization.

Podocyte biology in diabetic nephropathy.

Glomerular visceral epithelial cells, namely podocytes, are highly specialized cells and give rise to primary processes, secondary processes, and finally foot processes. The foot processes of neighboring podocytes interdigitate, leaving between them filtration slits. These are bridged by an extracellular substance, known as the slit diaphragm, which plays a major role in establishing size-selective barrier to protein loss. Furthermore, podocytes are known to synthesize matrix molecules to the glomerular basement membrane (GBM), including type IV collagen, laminin, entactin, and agrin. Because diabetic nephropathy is clinically characterized by proteinuria and pathologically by glomerular hypertrophy and GBM thickening with foot process effacement, podocytes have been the focus in the field of research on diabetic nephropathy. As a result, many investigations have demonstrated that the diabetic milieu per se, hemodynamic changes, and local growth factors such as transforming growth factor-beta and angiotensin II, which are considered mediators in the pathogenesis of diabetic nephropathy, induce directly and/or indirectly hypertrophy, apoptosis, and structural changes, and increase type IV collagen synthesis in podocytes. This review explores some of the structural and functional changes of podocytes under diabetic conditions and their role in the development and progression of diabetic nephropathy.

Probabilistic dietary exposure to ethyl carbamate from fermented foods and alcoholic beverages in the Korean population.

The occurrence of ethyl carbamate was investigated in fermented foods and alcoholic beverages of the Korean total diet study. The concentrations of ethyl carbamate ranged from not detected to 166.5 µg kg-1. Dietary exposure to ethyl carbamate was estimated by the probabilistic method. Estimated intakes of ethyl carbamate from foods and alcoholic beverages were 4.12 ng kg-1 body weight (bw) per day for average consumers and 12.37 ng kg-1 bw/day for 95th percentile high consumers. The major foods contributing to ethyl carbamate exposure were soy sauce (63%), followed by maesilju (plum liqueur, 30%), whisky (5%), and bokbunjaju (black raspberry wine, 2%). On the basis of the benchmark dose lower confidence limit 10% (BMDL10) of 0.3 mg kg-1 bw/day, margins of exposure were 128,000 for mean exposure and 40,000 for 95th percentile exposure. This indicates that the exposure of the Korean general population for ethyl carbamate is of low concern. However, careful vigilance should be continued for high consumers of fermented foods and alcoholic beverages.

Comparison of markers predicting litter size in different pig breeds.

To overcome the limitations of conventional analysis of male fertility in animals and humans, proteomic studies have been performed to develop fertility-related biomarkers for prognosis and diagnosis of male fertility. However, the studies were focused on specific species or breeds. Therefore, a study is required to validate whether fertility-related markers would apply to other breeds in pigs. In this study, previously developed fertility-related biomarkers from Landrace were validated to use for prognosis of male fertility in commercially available breeds. Expression level of eight biomarkers in non-capacitated and capacitated (C) spermatozoa from Yorkshire and Duroc boars was analyzed. And then, to explore the validity of these markers for prognosis of male fertility, i.e. litter size, artificial insemination was performed. Among them, RAB2A (NC) and UQCRC1 (NC) turned out to be highest efficient markers for Yorkshire. RAB2A (C) was most efficient marker for Duroc. Average litter size has increased as much as 1.41 live born after prediction using eight fertility-related biomarkers in Yorkshire. In addition, average 2.52 litter size was increased after prediction using eight fertility-related biomarkers in Duroc. Average litter sizes were especially highly increased after prediction of fertility using RAB2A (NC) in Yorkshire (1.57 piglets) and TPI (NC) in Duroc (3.14 piglets), respectively. As a result, all biomarkers were significantly correlated with litter size. However, overall accuracy to predict litter size in three breeds was different in response with each marker. Average litter size after artificial insemination was also significantly affected by marker selection. Therefore, this study suggests that developed fertility-related markers may be used for prognosis and diagnosis of male fertility irrespective of breed. However, selection of efficient markers for breeds should be considered to obtain more accurate and efficient outcomes.