Disproportional erosion of the middle-lower Yangtze River following the operation of the Three Gorges Dam.
The operation of the Three Gorges Dam (TGD) modifies downstream flow and sediment regimes, triggering disproportional fluvial responses at different distances downstream. However, our understanding of the downstream geomorphic changes in the middle-lower Yangtze River remains incomplete due to the complexity of the river responses across temporal and spatial scales. Here, we leverage data on discharge, suspended sediment concentration (SSC), riverbed grain size, cross-sectional profiles and high-resolution channel bathymetric maps at different locations downstream of the TGD to investigate geomorphic responses. The results show that the magnitude of fluvial erosion decreases downstream, with the Yichang-Luoshan Reach (the first ~500 km downstream) experiencing the most severe erosion in 2003-2020 (~9.05 × 104 t/km/yr). Local changes in riverbed morphology include channel bar erosion, channel incision (~0.43 m/yr in CS1 near the dam site over 2002-2019), riverbank retreat and bed material coarsening (an increase in D50 from 0.175 to 43.1 mm at Yichang station from 2002 to 2017). Such marked erosion is caused by the sharply reduced SSC in the dominant discharge range (10,000-30,000 m3/s) and the extended duration of this dominant discharge range. The sediment erosive magnitude in the Luoshan-Datong Reach is relatively small (3.85 × 104 t/km/yr) in 2002-2020. The Luoshan-Hukou Reach (~500-1000 km downstream) exhibits moderate channel incision, minor bed material coarsening and moderate mid-channel bar lateral erosion. The Hukou-Datong Reach (below 1000 km downstream) experienced minor geomorphic change without significant evidence of bed material coarsening. The relatively small impact of the TGD on the lower reach from Luoshan to Datong can be mainly attributed to the progressive SSC recovery along the river induced by upstream channel erosion providing sediment replenishment. These findings have significant implications for estimating geomorphic changes in response to upstream damming and thus could inform better river management and ecological assessment in other similar alluvial rivers.


The effect on gastric tone of gastric electrical stimulation with trains of short pulses varies with sites and stimulation conditions.
Gastric electrical stimulation (GES) can improve symptoms in patients with gastroparesis and induce weight loss in obese subjects. To evaluate the effect on gastric tone of GES under different conditions at different sites of the stomach. Eleven dogs were implanted with a gastric cannula and two pairs of stimulation electrodes (in the middle of the lesser curvature and of the greater curvature, 10 cm from the pylorus). Gastric tone was assessed with a barostat. GES was applied using: (1) Enterra conditions (14 Hz, 5 mA, 0.3 ms, 0.1 s on, 5 s off); (2) modified Enterra conditions (40 Hz, 5 mA, 0.3 ms, 0.1 s on, 5 s off); and (3) implantable gastric stimulation (IGS) conditions (40 Hz, 5 mA, 0.3 ms, 2 s on, 3 s off). Six sessions were performed randomly with each animal on six separate days. (1) At the lesser curvature, GES with modified Enterra conditions significantly elevated gastric volume from 96.9 +/- 8.3 ml at baseline to 133.9 +/- 11.7 ml (P = 0.015) and a similar effect was observed with IGS (91.3 +/- 7.1 ml vs. 186.3 +/- 27.1 ml, P = 0.013). GES with Enterra conditions had no such an effect. (2) At the greater curvature, GES with Enterra conditions significantly increased gastric volume from basal 94.1 +/- 4.4 ml to 122.1 +/- 11.3 ml (P = 0.032); modified Enterra conditions had the opposite effect (96.5 +/- 9.0 ml vs. 77.4 +/- 11.7 ml, P = 0.025) and no significant effect was observed with IGS conditions. The effects of GES on gastric tone vary with the conditions and sites of stimulation. These findings may help to explain the distinct effects of GES therapy in patients with gastroparesis and obesity.


A probability prediction method for the classification of surrounding rock quality of tunnels with incomplete data using Bayesian networks.
The classification of surrounding rock quality is critical for the dynamic construction and design of tunnels. However, obtaining complete parameters for predicting the surrounding rock grades is always challenging in complex tunnel geological environment. In this study, a new method based on Bayesian networks is proposed to predict the probability for the classification of surrounding rock quality of tunnel with incomplete data. A database is collected with 286 cases in 10 tunnels, involving nine parameters: rock hardness, weathering degree, rock mass integrity, rock mass structure, structural plane integrity, in-situ stress, groundwater, rock basic quality, and surrounding rock level. Moreover, the Bayesian network structure is built using the collected database and quantitatively verified by strength analysis. Then, the accuracy, precision, recall, F-measure and receiver operating characteristic (ROC) curves are utilized for model evaluation. The average values of accuracy, precision, recall, F-measure, and area under the curve (AUC) are approximately 89.2%, 91%, 92%, 91%, and 0.98, respectively. These results indicate that the established classification model has high accuracy, even with small sample size and imbalanced samples. Ten additional sets of tunnel cases (incomplete data) are also used for verification. The results reveal that compared with the traditional Q-system (Q) and rock mass rating (RMR) classification methods, the proposed classification model has the lowest error rate and is capable of using incomplete data to predict sample results. Finally, sensitivity analysis suggests that the rock hardness and rock mass integrity have the strongest impact on the quality of tunnel surrounding rock. Overall, the findings of this study can serve as a useful reference for future rock mass quality evaluation in tunnels, underground powerhouses, slopes, etc.


[Severe foot deformities in adolescents and adults--techniques after Imhäuser, Lelièvre und Lambrinudi].
Severe contraction deformities of the foot, e.g. after trauma or spasticity, often lead to an inability to walk and can, in part, only be rectified by corrective bone osteotomy of the hind and middle foot. In this article, we discuss hind and middle foot osteotomies in cases of severe foot deformities in adolescents and adults. The surgical techniques of Lambrinudi, Imhäuser and Lelièvre will be considered. The surgical technique of Lambrinudi uses a triple arthrodesis between the talus, calcaneus and navicular bones, and the cuboid bone, in addition to the removal of a bone wedge from the talus for correction of the talipes equinus deformity. Severe contraction talipes calvus can be straightened and capable of loading using Imhäuser's technique with wedge osteotomy and arthrodesis in Chopart's joint. The planigrade position is achieved by the removal of a dorsolaterally based wedge from Chopart's joint. Using Lelièvre technique, severe contraction club foot with hind foot varus can be treated with a wedge from Chopart's joint and the talocalcaneal joint with arthrodesis. For stabilization, a compression clamp system is used. The advantages of the system used by us is that, in comparison with other systems, it can also be used for sclerotic bones as the shank is not hammered in but is introduced after boring. Using the compression clamp system, good stability and a high rate of osseous blood circulation can be achieved using osteotomies and arthrodeses. The aim of surgery is, in all cases, the correction of the deformity, functional improvement and the elimination of pressure points and pain.


New records of Phlaeothripinae from New Caledonia, with the description of a new species of Adraneothrips Hood (Thysanoptera, Phlaeothripidae).
Four species of phlaeothripines are newly recorded and illustrated from New Caledonia: Adraneothrips moundi n. sp., Baenothrips cf. cuneatus Zhao Tong, Leichhardtithrips evanidus Tree Mound and Sophiothrips typicus (Ananthakrishnan). The male of L. evanidus is recorded for the first time.


Congestive cardiomyopathy in patients on continuous ambulatory peritoneal dialysis.
We present a report of cardiac dilatation and symptomatic congestive heart failure in two patients receiving treatment with continuous ambulatory peritoneal dialysis (CAPD). Both patients had previous partial parathyroidectomies and persistent hypocalcemia prior to the development of a congestive cardiomyopathy. The hypocalcemia was unresponsive to treatment with activated vitamin D therapy; however, intravenous replenishment of the ionized serum calcium level was accompanied by improvement in cardiac functional parameters. In one of the two patients, chronic calcium repletion with high dialysate calcium was associated with significant improvement in cardiac symptoms and a decrease in left ventricular dilatation. These observations suggest that partial parathyroidectomy and associated hypocalcemia place patients on CAPD at increased risk of cardiac dysfunction.


Outcomes after single-cycle rituximab monotherapy in patients with anti-MAG polyneuropathy: A bi-center experience with an average follow-up of 11 years.
Rituximab is efficacious in myelin-associated glycoprotein (MAG) polyneuropathy, but the question on timing of retreatments is open. We studied 21 anti-MAG polyneuropathy patients who responded to a first cycle of rituximab, were followed-up for an average of 11.2 years, and were retreated only when relapsing. Baseline serum B-cell-activating factor (BAFF) levels were measured. Clinical improvements lasted on average 6 years, and as many as 71% of the patients resulted long-lasting responders. Severity of disease and high serum BAFF levels (cut-off ≥860 pg/mL for relapse risk) at onset seemed to predict worse prognosis. Measurements of these variables could help deal with the issue of maintenance rituximab therapy in MAG polyneuropathy.


Human prostatic lymphoscintigraphy. A preliminary report.
A simple method for demonstrating prostatic lymphatic drainage by transrectal injection of 99mTc labelled antimony sulphide colloid into the prostatic capsule has been developed. This technique may be readily applied in clinical practice with obvious potential in the assessment and follow-up of patients with carcinoma of the prostate.


Oxytocin stimulates translocation of protein kinase C and induces antiviral state in human amnion cells.
Association of protein kinase C (PKC) activity to the membrane fraction was observed in oxytocin treated human amnion cells (UAC). In addition, oxytocin was shown to induce an antiviral state and to inhibit multiplication of vesicular stomatitis virus (VSV) in UAC. These observations together with earlier findings indicate that activation of inositol phospholipid breakdown with a consecutive activation of PKC is a common signal transduction pathway in interferon action and hormonal stimulation.


Up-regulation of TUG1 can regulate miR-494/PDK4 axis to inhibit LPS-induced acute lung injury caused by sepsis.
Acute lung injury (ALI) caused by sepsis is the most common disease and the leading cause of death in intensive care units. Recent studies have revealed that long non-coding RNAs (LncRNAs) are abnormally expressed in sepsis. This study aimed to clarify the role and mechanism of Taurine up-regulated gene 1 (TUG1) in ALI caused by sepsis. Lipopolysaccharide (LPS) was used to simulate sepsis-induced ALI model. RT-PCR, Dual luciferase reporter (DLR) assay and RNA immunoprecipitation (RIP) were used to detect TUG1 and miR-494. The rat model with sepsis-induced ALI was established by intraperitoneal injection of LPS to verify the results of in vitro experiments. The expressions of TUG1 and PDK4 were down-regulated while the expression of miR-494 was up-regulated in lung tissues and human small airway epithelial cells (HSAECs). TUG1 was indirectly mediated. Overexpression of TUG1 or inhibition of miR-494 could significantly improve the survival rate of HSAECs. Transfection of miR-494 mimics achieved the opposite effect. Enzyme-linked immunosorbent assay (ELISA) showed that the expression of arthritis-related factors in rats was increased after up-regulating TUG1. TUG1 is lowly expressed in sepsis. Up-regulating TUG1 can alleviate the inflammatory response in ALI caused by LPS-induced sepsis, which may be a clinical treatment target.


Anemia.
Abnormalities in the routine blood count alert the physician to hematologic problems. The most common of these are red cell abnormalities as reflected in decreased levels of hemoglobin and hematocrit together with changes in mean corpuscular volume and red cell morphology. When the history and physical examination are not diagnostic, systematic use of laboratory tests can determine the category of anemia present. An approach for the laboratory workup of anemia is discussed. Particular attention is paid to the differential diagnosis of the most common anemias in which iron is the limiting factor in erythropoiesis.


The standardisation of thin-layer chromatographic systems for the identification of basic drugs.
Three thin-layer chromatographic systems have been selected on the basis of their discriminating power on which to standardise for the identification of basic drugs. They are systems of silica gel sprayed with 0.1 N NaOH, dried and run using one of the following solvents: cyclohexane-toluene-diethylamine (75:15:10), chloroform-methanol (90:10) or acetone. They can be used in combination since their correlation coefficients are low. Four reference compounds should be used, equally spaced across the plate. The inter-laboratory variation of measurement of RF values has been ascertained and the use of a graphical RF correction method reduced the mean deviation of measurement to 0.02. The measurement of RF values was found to be less reproducible in the middle of the chromatogram than in regions of very low or very high RF values.


Modified frailty index as an indicator for outcomes after lower extremity endovascular revascularization.
The 5-factor frailty index is associated with adverse outcomes after various procedures. This study aimed to evaluate the performance of the 5-factor frailty index after lower extremity endovascular revascularization. The American College of Surgeons' National Surgical Quality Improvement Program Database as retrospectively analyzed for patients undergoing lower extremity endovascular revascularization between 2015 and 2019. Outcomes were assessed using bivariate analyses and multivariate logistic regression analyses. In the study, 11,947 lower extremity endovascular revascularization performed between 2015 and 2019 were identified from National Surgical Quality Improvement Program Database. Median age was 69 (standard deviation 11.44) years, 4,727 (39.6%) were female, and 7,570 (63.4%) were White. In addition, 7,541 (62.9%) were performed for chronic limb threatening ischemia. Thirty-day mortality was 1.7%. Bivariate analysis demonstrated that a 5-factor frailty index score greater than 0.6 was associated with higher rates of discharge to SNF (28.6% vs 8.2%, P < .001, reference 5-factor frailty index = 0), cardiopulmonary arrest (2.0% vs 0.1%, P < .001), readmission (21.1% vs 10.8%, P < .001), reintubation (2.8% vs 0.3%, P < .001), and 30-day mortality (5.1% vs 0.7%, P < .001). Beta blocker use, higher age, chronic limb threatening ischemia indication, and 5-factor frailty index were all associated with increased 30-day mortality. Multivariate logistic regression showed that 5-factor frailty index >0.6 predicted 3 times higher odds for 30-day mortality (odds ratio, 2.988; P = .013), with physiologic high risk (odds ratio, 2.118; P < .001), chronic limb threatening ischemia indication (odds ratio, 2.157; P < .001), and inpatient procedures (odds ratio, 3.409; P < .001) also showing increased risk for mortality. For patients undergoing lower extremity endovascular revascularization, higher 5-factor frailty index was associated with increased hospital resource utilization and 30-day mortality. The 5-factor frailty index may be useful for preoperative risk stratification and predicting adverse outcomes in patients undergoing lower extremity endovascular revascularization.


Fabrication of glucose biosensor for whole blood based on Au/hyperbranched polyester nanoparticles multilayers by antibiofouling and self-assembly technique.
Acknowledging the benefits of hyperbranched polymers and their nanoparticles, herein we report the design and synthesis of sulfonic acid group functionalized hydroxyl-terminated hyperbranched polyester (H30-SO3H) nanoparticles and their biomedical application. The H30-SO3H nanoparticles were characterized by transmission electron microscopy (TEM), Fourier transform infrared (FTIR) spectroscopy and proton nuclear magnetic resonance spectroscopy ((1)H NMR). The good hemocompatibility of H30-SO3H nanoparticles was also investigated by coagulation tests, complement activation and platelet activation. The novel glucose biosensor was fabricated by immobilizing the positively charged Au nanoparticles, H30-SO3H nanoparticles and glucose oxidase (GOx) onto the surface of glassy carbon electrode (GCE). It can be applied in whole blood directly, which was based on the good hemocompatibility and antibiofouling property of H30-SO3H nanoparticles. The biosensor had good electrocatalytic activity toward glucose with a wide linear range (0.2-20 mM), a low detection limit 1.2×10(-5) M in whole blood and good anti-interference property. The development of materials science will offer a novel platform for application to substance detection in whole blood.


Treatment of Fraleys syndrome by upper-pole nephrectomy.
Fraleys syndrome is characterized by vascular compression on the superior infundibulum with secondary dilatation of the upper pole calyx, mostly located on the right side. We present the case of a 22-year-old woman with vascular compression of the upper-pole infundibulocalyceal system (Fraleys syndrome). The patient had a history of frequent hospitalizations for emergency care due to lumbar pain over the past twelve months. The diagnosis was obtained following renal arteriography. Since the surgical treatment by means of upper-pole nephrectomy, the patient has not had any further symptoms.


Influences of both thyroid and bovine growth hormones on substance P, thyrotropin-releasing hormone, serotonin and 5-hydroxyindoleacetic acid contents in the lumbar spinal cord of developing rats.
Neonatal hypothyroidism was induced by injection of 131I on the first living day whilst neonatal hyperthyroidism was induced by daily administration of high doses of thyroxine (T4). Following decapitation, segments of the lumbar spinal cord were microdissected by a punch technique. We measured serotonin and 5-hydroxyindoleacetic acid (5-HIAA) contents by high performance liquid chromatography and both substance P and thyrotropin-releasing hormone (TRH) levels by radioimmunoassay. We demonstrated that: (1) neonatal hyperthyroidism decreased substance P and TRH levels in the dorsal and ventral horns respectively, without modifying serotonin and 5-HIAA contents; (2) neonatal hypothyroidism increased the concentration of substance P in dorsal horn, of TRH in ventral horn (confirming our previous work), of serotonin in ventral horn, and of 5-HIAA in both ventral and dorsal horns; (3) T4-replacement therapy abolishes hypothyroid effects on substance P, TRH, and 5-HIAA, but not on 5-HT accumulation; and (4) bovine growth hormone-replacement therapy has no therapeutic action on the hypothyroid-induced accumulation of substance P, TRH, serotonin and 5-HIAA.


Cyanate modification of essential lysyl residues of the diphosphopyridine nucleotide-specific isocitrate dehydrogenase of pig heart.
The DPN-specific isocitrate dehydrogenase of pig heart is totally and irreversibly inactivated by 0.05 M potassium cyanate at pH 7.4 A plot of the rate constant versus cyanate concentration is not linear, but rather exhibits saturation kinetics, implying that cyanate may bind to the enzyme to give an enzyme-cyanate complex (K equal 0.125 M) prior to the covalent reaction. In the presence of manganous ion the addition of isocitrate protects the enzyme against cyanate inactivation, indicating that chemical modification occurs in the active site region of the enzyme. The dependence of the decrease of the rate constant for inactivation on the isocitrate concentration yields a dissociation constant for the enzyme-manganese-isocitrate complex which agrees with the Michaelis constant. The allosteric activator ADP, which lowers the Michaelis constant for isocitrate, does not itself significantly affect the cyanate reaction; however, it strikingly enhances the protection by isocitrate. The addition of the chelator EDTA essentially prevents protection by isocitrate and manganous ion, demonstrating the importance of the metal ion in this process. The substrate alpha-ketoglutarate and the coenzymes DPN and DPNH do not significantly affect the rate of modification of the enzymes by cyanate. Incubation of isocitrate dehydrogenase with 14C-labeled potassium cyanate leads to the incorporation of approximately 1 mol of radioactive cyanate per peptide chain concomitant with inactivation. Analysis of acid hydrolysates of the radioactive enzyme reveals that lysyl residues are the sole amino acids modified. These results suggest that cyanate, or isocyanic acid, may bind to the active site of this enzyme as an analogue of carbon dioxide and carbamylate a lysyl residue at the active site.


The characteristics of respiratory function and pulmonary hemodynamics in patients with portal hypertension.
To investigate the respiratory function and pulmonary hemodynamics in patients with portal hypertension (PHT). A total of 148 patients with PHT were divided into three groups according to Child-Pugh classification. Results of blood biochemistry test, lung function test, arterial blood gas analysis, free portal pressure (FPP) and pulmonary hemodynamics measurements of the three Child-Pugh grade groups were compared with those of the control group. The overall incidence of arterial hypoxemia was 27.0% in PHT patients. Arterial oxygen tension (PaO(2) ) had a significant negative correlation with FPP (r=-0.76, P<0.01) and Child-Pugh grade (r=-0.42, P<0.01), as well as a positive correlation with systemic vascular resistance (SVR, r=0.24, P=0.01). Alveolar-arterial oxygen difference (A-aDO(2) ) increased in Child-Pugh grade C group when compared with Child-Pugh grade A and B groups (P<0.05). Restrictive impairment of lung function was seen in Child-Pugh grade C group. Direct measurement of the hemodynamics in PHT patients revealed a hyperdynamic disturbance in both systemic and portal venous systems, and was illustrated in pulmonary circulation as an increase of mean pulmonary arterial pressure (MPAP) and pulmonary arterial wedged pressure (PAWP) as well as a decrease of pulmonary vascular resistance (PVR). High output and low resistance are the key characteristics of pulmonary circulation in PHT patients and the decrease of PVR can be detected even when liver function is still compensated.


Epigenetic regulation of innate immune memory in microglia.
Microglia are the tissue-resident macrophages of the CNS. They originate in the yolk sac, colonize the CNS during embryonic development and form a self-sustaining population with limited turnover. A consequence of their relative slow turnover is that microglia can serve as a long-term memory for inflammatory or neurodegenerative events. Using ATAC-, ChIP- and RNA-sequencing, we characterized the epigenomes and transcriptomes of FACS-purified microglia from mice exposed to different stimuli. A repeated endotoxin challenge (LPS) was used to induce tolerance in microglia, while genotoxic stress (DNA repair deficiency-induced accelerated aging through Ercc1 deficiency) resulted in primed (hypersensitive) microglia. Whereas the enrichment of permissive epigenetic marks at enhancer regions could explain training (hyper-responsiveness) of primed microglia to an LPS challenge, the tolerized response of microglia seems to be regulated by loss of permissive epigenetic marks. We identify that inflammatory stimuli and accelerated aging as a result of genotoxic stress activate distinct gene networks. These gene networks and associated biological processes are partially overlapping, which is likely driven by specific transcription factor networks, resulting in altered epigenetic signatures and distinct functional (desensitized vs. primed) microglia phenotypes. This study provides insight into epigenetic profiles and transcription factor networks associated with transcriptional signatures of tolerized and trained microglia in vivo, leading to a better understanding of innate immune memory of microglia.


Kimura disease of the breast: Case report and literature review of current management.
We report a rare case of Kimura disease in a 50-year old female patient who attended our tertiary level Breast Surgery Clinic.


Uric Acid Is Not Associated With Blood Pressure Phenotypes and Target Organ Damage According to Blood Pressure Phenotypes.
Hypertensive patients with increased serum uric acid (SUA) are at increased cardiovascular (CV) risks. Both the European and American hypertension guidelines endorse the utilization of 24 h-ambulatory blood pressure monitoring (24 h-ABPM) for hypertensive patients with increased CV risk. While there is difference in identifying uric acid as a CV risk factor between the European and American guidelines. Therefore, it is unknown whether 24 h-ABPM should be used routinely in hypertensive patients with increased SUA. To address this knowledge gap, we investigated (i) the correlation between SUA and 24 h-ABP; (ii) the association between SUA and blood pressure (BP) phenotypes (controlled hypertension [CH], white-coat uncontrolled hypertension [WCUH], masked uncontrolled hypertension [MUCH], and sustained uncontrolled hypertension [SUCH]); (iii) the association between SUA and target organ damage (TOD: microalbuminuria, left ventricular hypertrophy [LVH], and arterial stiffness) according to BP phenotypes. In 1,336 treated hypertensive patients (mean age 61.2 and female 55.4%), we found (i) there was no correlation between SUA and 24 h, daytime, and nighttime systolic blood pressure/diastolic blood pressure, respectively; (ii) in reference to CH, SUA increase was not associated WCUH (odds ratio [OR] 0.968, P = 0.609), MUCH (OR 1.026, P = 0.545), and SUCH (OR 1.003, P = 0.943); (iii) the overall prevalence of microalbuminuria, LVH, and arterial stiffness was 2.3%, 16.7%, and 23.2%, respectively. After adjustment for covariates, including age, sex, smoking, body mass index, diabetes mellitus, and estimated glomerular filtration rate, there was no association between SUA and TOD in all BP phenotypes. These preliminary findings did not support routine use of 24 h-ABPM in treated hypertensive patients with increased SUA.


A FTIR microspectroscopy study of the structural and biochemical perturbations induced by natively folded and aggregated transthyretin in HL-1 cardiomyocytes.
Protein misfolding and aggregation are associated with a number of human degenerative diseases. In spite of the enormous research efforts to develop effective strategies aimed at interfering with the pathogenic cascades induced by misfolded/aggregated peptides/proteins, the necessary detailed understanding of the molecular bases of amyloid formation and toxicity is still lacking. To this aim, approaches able to provide a global insight in amyloid-mediated physiological alterations are of importance. In this study, we exploited Fourier transform infrared microspectroscopy, supported by multivariate analysis, to investigate in situ the spectral changes occurring in cultured intact HL-1 cardiomyocytes exposed to wild type (WT) or mutant (L55P) transthyretin (TTR) in native, or amyloid conformation. The presence of extracellular deposits of amyloid aggregates of WT or L55P TTR, respectively, is a key hallmark of two pathological conditions, known as senile systemic amyloidosis and familial amyloid polyneuropathy. We found that the major effects, associated with modifications in lipid properties and in the cell metabolic/phosphorylation status, were observed when natively folded WT or L55P TTR was administered to the cells. The effects induced by aggregates of TTR were milder and in some cases displayed a different timing compared to those elicited by the natively folded protein.


Elucidation of the fucose metabolism of probiotic Lactobacillus rhamnosus GG by metabolomic and flux balance analyses.
Lactobacillus rhamnosus GG (LGG) is one of the most widely used probiotics because of its health benefits and safety. Fucose is among the most abundant hexoses in the human intestine, and LGG consumes fucose to produce energy or proliferate. However, no study has elucidated the metabolism by which LGG metabolizes fucose to produce energy, biomass, and extracellular metabolites. We used metabolomics and flux balance analysis to elucidate these mechanisms and highlight how they might affect the host. We found three different metabolic flux modes by which LGG anaerobically metabolizes fucose to produce energy and biomass. These metabolic flux modes differ from homolactic or heterolactic fermentation and account for the production of lactic acid, 1,2-propanediol, acetic acid, formic acid, and carbon dioxide as a result of fucose metabolism in LGG. We also used gas chromatography/time-of-flight mass spectrometry to identify a variety of short-chain fatty acids and organic acids secreted during fucose metabolism by LGG. Our study is the first to elucidate the unique fucose metabolism of LGG in anaerobic condition.


Unilateral joint inflammation induces bilateral and time-dependent changes in neuropeptide FF binding in the superficial dorsal horn of the rat spinal cord: implication of supraspinal descending systems.
Using quantitative autoradiography, the effects of acute and chronic inflammation on specific 125I-1DMethyl-FLFQPQRFamide binding were investigated in the rat spinal cord dorsal horn superficial layers, at 6 and 24 h and 2, 4, 6 and 12 weeks after induction of monoarthritis produced by injection of killed Mycobacterium butyricum suspended in Freund adjuvant in one tibio-tarsal joint. Six hours after monoarthritis induction, no modification in specific 125I-1DMethyl-FLFQPQRFamide binding was observed, whereas a significant bilateral increase occurred after 24 h and 2 weeks in L4/L5 dorsal horns, with a return to control values at 4, 6 and 12 weeks. Specific 125I-1DMethyl-FLFQPQRFamide binding was also investigated 24 h after monoarthritis induction in rats submitted 4 days before the induction to spinal cord lesions at the thoracic level (T9-T10). Hemisection of the spinal cord contralateral to the affected ankle prevented the transient bilateral increase in specific 125I-1DMethyl-FLFQPQRFamide binding, whereas total spinal cord section induced a significant bilateral decrease. All of these modifications were restricted to the spinal segments receiving afferent input from the arthritic ankle (L4/L5); no modifications were found at the levels L1 or C6-C8. These data suggest that FLFQPQRFamide is involved in spinal nociceptive processing during sustained peripheral nociceptor activation. The effects of spinal cord lesions in monoarthritic rats indicate that the modifications seen in the FLFQPQRFamide system activity, during sustained peripheral inflammation, depend on afferent fiber activation as well as on supraspinal controls.


Female Relatives as Lay Doulas and Birth Outcomes: A Systematic Review.
Continuous labor support provided by professional doulas is associated with improved birth outcomes for pregnant women and their infants. However, there is limited data on the impact of using female relatives as lay doulas. This systematic review included nine published studies that examined the association between use of female relatives as lay doulas with childbirth outcomes. In some study populations, there was a decrease in the number of cesarean births and length of labor, and in all studies, there was improved maternal birth satisfaction. However, the woman's chosen female relative often did not receive education regarding labor support skills before providing continuous support. Educational programs designed to teach labor support skills to female relatives are needed.


Sonographic elastography improves the sensitivity and specificity of axilla sampling in breast cancer: a prospective study.
We describe a study to determine whether elastography of axillary lymph nodes (LNs) combined with B-mode ultrasound (US) is capable of differentiating the benign from the metastatic state in patients with breast cancer. B-mode US, elastography and fine-needle aspiration of 90 axillary lymph nodes from 89 female patients with breast cancer are described in this report. Five elastographic patterns were observed as defined by the percentages of high elasticity according to pattern of distribution and degree of hardness of the target LNs. B-mode US and elastography scores were combined to give the final scores. Sensitivity and specificity were 80% and 88%, respectively, for B-mode US alone, 86% and 90% for elastography alone and 84% and 98% for the combined assessment to differentiate the benign from the malignant state. The combination of B-mode US and elastography is capable of identifying metastatic axillary LNs from benign enlargement in patients with breast cancer.


Co-morbid infections in Hansen's disease patients in the United States: considerations for treatment.
120 patients attending a Hansen's disease public health satellite clinic were evaluated for selected latent co-morbidities, consisting of strongyloidiasis, Chagas disease, hepatitis B, HIV, and tuberculosis, and potential exacerbation by immunosuppressive therapy. Implications for treatment of Hansen's disease are discussed.


A human factors engineering conceptual framework of nursing workload and patient safety in intensive care units.
In this paper, we review the literature on nursing workload in intensive care units (ICUs) and its impact on patient safety and quality of working life of nurses. We then propose a conceptual framework of ICU nursing workload that defines causes, consequences and outcomes of workload. We identified four levels of nursing workload (ICU/unit level, job level, patient level, and situation level), and discuss measures associated with each of the four levels. A micro-level approach to ICU nursing workload at the situation level is proposed and recommended in order to reduce workload and mitigate its negative impact. Performance obstacles are conceptualized as causes of ICU nursing workload at the situation level.


Titanium and titanium alloys in dentistry: current trends, recent developments, and future prospects.
Many implant materials have been used in various dental applications depending on their efficacy and availability. A dental implant must possess the required characteristics, such as biocompatibility, corrosion & wear resistance, adequate mechanical properties, osseointegration, etc., to ensure its safe and optimum use. This review analyzes various aspects of titanium (Ti) and Ti alloys, including properties, manufacturing processes, surface modifications, applications as dental implants, and limitations. In addition, it also presents a perception of recent advances in Ti-based implant materials and the futuristic development of innovative dental implants.


A bovine dander allergen, comparative modeling, and similarities and differences in folding with related proteins.
The most important allergenic protein in cow dander and urine is Bos d 2. It is proposed to belong to the family of lipocalins, which are proteins capable of binding small hydrophobic molecules. The allergenic properties of Bos d 2 indicate an interaction between the accessible regions of the native protein and IgE. In this work, a three-dimensional model was created for Bos d 2 by comparative modeling, and features characteristic of outlier lipocalins were observed. The protruding regions of the surface were characterized and used in predicting the possible B-cell epitopes. There is a pocket inside the core and its size is appropriate for small molecules. The model shows a hydrophilic amino acid side chain of glutamic acid 115 on the inner surface of the hole and a phenylalanine as the "gatekeeper" instead of tyrosine, which is common in experimentally modeled lipocalins.


Safety and quality of some chicken meat products in Al-Ahsa markets-Saudi Arabia.
One hundred samples of 10 poultry meat products were collected from AL-Ahsa markets (Kingdom of Saudi Arabia). The samples were ranked from carcass cuts (chilled, frozen, fillet and thigh) to minced meat or further processed products as burger, nuggets, frankfurter and meat paste loaf. Samples were collected in triplicate for sensory, chemical and microbiological analysis to assure their quality and safety. The obtained results revealed variation in chemical composition; some products with high fat percentage had a high thiobarbituric acid value, which resulted in the appearance of an unacceptable flavor. Bacteriological analysis revealed that the mean total bacterial count was ranged from 2.7 × 10(4) cfu/g for nuggets(A) to 3.3 × 10(7) cfu/g for burger(B) and the other products in the range of 10(5)-10(6) cfu/g. While Staphylococcus aureus mean count ranged from less than 10(2) cfu/g for all samples, accept 10(4) and 10(6) cfu/g for mince(B) and frankfurter samples, respectively. Escherichia coli isolated from 70% of the samples and Salmonella arizona was isolated at once from thigh samples. Thirty percentages of samples not comply with Saudi Standards due to sensory unacceptability and 21% of samples nonconforming with bacteriological specifications.


Is there an association between dental caries and genetics? Systematic review and meta-analysis of studies with twins.
This review aimed to assess the agreement of dental caries experience between monozygotic (MZ) and dizygotic (DZ) twins. This systematic review was performed by reviewers in the databases Embase, MEDLINE-PubMed, Scopus, Web of Science and manual searches and gray literature Google Scholar® and Opengray. Observational studies that evaluated dental caries in twins were included. The risk of bias was analyzed using the Joanna Briggs checklist. Meta-analyses were performed to assess the pooled Odds Ratio to estimate the agreement values of dental caries experience and DMF index between pairs of twins (p < 0.05). To assess the certainty of evidence, the GRADE scale was used. 2533 studies were identified, of which 19 were included in the qualitative analysis, six in the quantitative synthesis, with two meta-analyses being carried out. Association between genetics and the development of the disease was observed in most studies. In the risk of bias analysis, 47.4% had moderate risk. Higher agreement of dental caries experience was observed in MZ twins than DZ in both dentitions (OR: 5.94; 95% CI: 2.00-17.57). However, there was no difference between the MZ and DZ twin groups in the analysis comparing DMF index agreement (OR: 2.86; 95%CI: 0.25-32.79). The certainty of evidence was considered low and very low for all studies included in meta-analyses. With very low certainty of the evidence, the genetic factor seems to influence the agreement of the caries experience. Understanding the genetic influence on the disease has the potential to contribute to the development of studies that may use biotechnologies for prevention and treatment as well as guide future research involving gene therapies aiming to prevent the occurrence of dental caries.


Ambulatory ECG monitoring.
The development and widespread application of 24-hour ambulatory ECG monitoring in the last 15 years represent major advances in cardiology. It is the most sensitive method of detecting arrhythmias and allows objective evaluation of such abnormalities and their response to treatment as the patient continues the activities of daily life. Information on prognosis and early diagnosis in patients with coronary artery disease has been obtained but more data and a greater understanding of their relevance in normal populations are necessary. Until then the significance of the findings in many situations, especially in asymptomatic patients, will remain speculative and decisions on whether or not to institute therapy will continue to be somewhat arbitrary.


Maternal age and lifespan do not influence longevity in the rotifer Asplanchna brightwelli.
An analysis of the mean lifespans among the progeny of the viviparous rotifer Asplanchna brightwelli produced during four generations has revealed that longevity of the offspring is not affected by maternal age of the parent or by the parent's lifespan. The production of viable offspring at any time during the parent's reproductive period may be of importance in assuring the continuity of clones of this short-lived rotifer species.


A case report of Williams syndrome with main clinical manifestation of hypercalcemia and gastrointestinal bleeding as the main clinical manifestations, and with an accompanying literature review.
Williams syndrome is an autosomal dominant multisystem disorder caused by a 1.5-1.8 Mb deletion on chromosome 7q11.23. It is characterized by facial deformations, cardiovascular abnormalities, developmental delays, gastrointestinal manifestations, and endocrine disorders. A 1-year-old child presenting with developmental delays, special facial features, gastrointestinal bleeding, renal calcium deposition, and hypotonia was admitted to the hospital for "hypercalcemia and gastrointestinal bleeding." Genetic testing showed a deletion mutation in the 7q11.23 region. Currently, the child receiving treatment to promote calcium excretion and rehabilitation training, but hypercalcemia has recurred. The clinical phenotype of Williams syndrome is complex, and different severities, characterized by developmental delays, facial deformities, cardiovascular abnormalities, gastrointestinal symptoms and endocrine disorders, should be considered in children. The syndrome may require thorough genetic testing for diagnosis and early intervention treatment to improve patient quality of life.


Effects of art therapy for people with mild or major neurocognitive disorders: A systematic review and meta-analysis.
The aim of this study was to analyze the efficacy of non-pharmacological, interactive, and emotional art therapy interventions for patients with mild neurocognitive disorder (mild NCD) or major neurocognitive disorder (MNCD). A systematic review and meta-analysis assessed English-language literature published from January 1, 2001, to August 22, 2021, and indexed in CINAHL, EMBASE, MEDLINE, PubMed, Web of Science, and PsycINFO. People with mild NCD or MNCD who received art therapy were classified as the intervention group. Study quality was assessed using the Risk of Bias (RoB) 2 and the Joanna Briggs Institute tool. Among nine included studies, depression was significantly reduced as compared with control groups (Cohen's d = -0.52 [95 % CI = -0.99-0.05], p < 0.001, I2 = 62.90 %) but not cognitive function or quality of life. People with mild neurocognitive disorder or MNCD are encouraged to engage in art therapy delivered by art therapists collaborating with healthcare providers. The effects of specific types of art therapy should be explored. Healthcare providers should be encouraged to provide art therapy designed to reduce depression in patients with mild NCD or MNCD.


Sustained release of curcumin from fibrin matrix induces cancer cell death and immunomodulation.
Despite the role of curcumin in controlling inflammation, angiogenesis, and cancer in human cells, its therapeutic use is limited. The reasons are quick metabolic breakdown, low aqueous solubility, and bioavailability. This study describes the advantages of clinical-grade curcumin-incorporated fibrin matrix either in lyophilized off-the-shelf wafer or injectable hydrogel forms, as a biodegradable local delivery system. To produce the curcumin-fibrin wafer, used clinical-grade fibrin sealant in a modified composition. To fabricate wafer, we premixed the curcumin with either fibrinogen or thrombin, before clotting into a hydrogel. Sustained release of active curcumin from fibrin wafer, suspended in culture medium at 37 °C lasted for seven days. Upon premixing albumin with thrombin and subsequently adding curcumin into the mixture improved the loading concentration and stability. Dose- and time-dependent apoptotic function of curcumin on cancer cell lines upon release from fibrin wafer, were demonstrated in vitro. In vivo immuno-modulation and a nontoxic response to curcumin released from fibrin into the peritoneal cavity of mice were established. The cytotoxic effect of released curcumin was demonstrated; showing both a preventive and therapeutic role against tumor growth. In vivo studies used Dalton's Lymphoma Ascites (DLA) mice model. Both implanted fibrin wafer and injected hydrogel can breakdown by a physiological process and get cleared by the fibrinolytic mechanism. The lyophilized fibrin wafer could function as a hemostat, adhere to surgical cancer tissues, and arrest bleeding. The potential of curcumin in preventing solid tumor metastasis may be explored upon the sustained delivery of the molecule from the fibrin wafer.


Transgenic mice that express a myelin basic protein-specific T cell receptor develop spontaneous autoimmunity.
We constructed a transgenic mouse model that mimics the human autoimmune disease multiple sclerosis in its spontaneous induction and pathology. Transgenic mice were constructed expressing genes encoding a rearranged T cell receptor specific for myelin basic protein (MBP). T cell tolerance was not induced in the periphery, and functional, autoreactive T cells were found in the spleen and lymph nodes of these mice. Transgenic mice developed experimental allergic encephalomyelitis (EAE) following immunization with MBP and adjuvant plus pertussis toxin as well as with administration of pertussis toxin alone. Spontaneous EAE can develop in transgenic mice housed in a non-sterile facility but not in those maintained in a sterile, specific pathogen-free facility. This model system affords a unique opportunity to dissect the genetic and environmental variables that may contribute to the development of spontaneous autoimmune disease.


Interaction between eye and body movements to perform visual tasks in upright stance.
Synergistic interactions between visual and postural behaviors were observed in a previous study during a precise visual task (search for a specific target in a picture) performed upright as steady as possible. The goal of the present study was to confirm and extend these novel findings in a more ecological condition with no steadiness requirement. Twelve healthy young adults performed two visual tasks, i.e. a precise task and a control task (free-viewing). Center of pressure, lower back, neck, head and eye movements were recorded during each task. The subjective cognitive workload was assessed after each task (NASA-TLX questionnaire). Pearson correlations and cross-correlations between eyes (time-series, characteristics of fixation) and center of pressure/body movements were used to test the synergistic model. As expected, significant negative Pearson correlations between eye and head-neck movement variables were only observed in searching. They indicated that larger precise gaze shifts were correlated with lower head and neck movements. One cross-correlation coefficient (between COP on the AP axis and eyes in the up/down direction) was also significantly higher, i.e. stronger, in searching than in free-viewing. These synergistic interactions likely required greater cognitive demand as indicated by the greater NASA-TLX score in searching. Moreover, the previous Pearson correlations were no longer significant after controlling for the NASA-TLX global score (thanks to partial correlations). This study provides new evidence of the existence of a synergistic process between visual and postural behaviors during visual search tasks.


Predictors of survival in patients with high-risk neuroblastoma who failed tandem high-dose chemotherapy and autologous stem cell transplantation.
This study aims to explore prognostic factors for high-risk neuroblastoma patients with response failure to tandem high-dose chemotherapy and autologous stem cell transplantation (HDCT/auto-SCT). Survival outcomes were compared according to characteristics at initial diagnosis, at relapse/progression, and after relapse/progression in patients who experienced relapse/progression after tandem HDCT/auto-SCT from 2006 to 2018. Forty-nine patients experienced relapse/progression after tandem HDCT/auto-SCT during the study period: 43 received salvage treatment and 30 underwent allogeneic SCT (allo-SCT) after reinduction treatment. Although all six patients who did not undergo salvage treatment died, 13 of the 43 patients who did remain alive. The 3-year probabilities of event-free survival (EFS) and overall survival (OS) from initial relapse/progression among the 49 patients were 14.4% ± 5.2% and 21.2% ± 6.4%, respectively. A higher neuron-specific enolase (NSE) level (>24 ng/mL) at relapse/progression was an independent prognostic factor for worse OS. Nine of 30 patients who underwent allo-SCT remain alive, and the 3-year probabilities of EFS and OS from allo-SCT were 16.5% ± 7.2% and 21.6% ± 8.3%, respectively. A higher NSE level and no incorporation of high-dose 131 I-metaiodobenzylguanidine (HD-MIBG) treatment into allo-SCT were independent prognostic factors for worse EFS and OS after allo-SCT. The results suggest that a higher serum NSE level at relapse/progression is a predictor of worse prognosis in patients with response failure to tandem HDCT/auto-SCT, and that incorporation of HD-MIBG treatment into allo-SCT may improve outcomes.


Abrupt change in radiation-width distribution for 147Sm neutron resonances.
We obtained the total radiation widths of s-wave resonances through an R-matrix analysis of (147)Sm(n,γ) cross sections. Distributions of these widths differ markedly for resonances below and above E(n)=300 eV, which is in stark contrast to long-established theory. We show that this change, as well as a similar change in the neutron-width distribution reported previously, is reflected in abrupt increases in both the average (147)Sm(n,γ) cross section and fluctuations about the average near 300 eV. Such effects could have important consequences for applications such as nuclear astrophysics and nuclear criticality safety.


Dietary Fiber Is Independently Related to Blood Triglycerides Among Adults with Overweight and Obesity.
Metabolic syndrome (MetS), a cluster of visceral adiposity-related risk factors, affects approximately 35% of the United States population. Although improvement in diet quality is an important approach to reducing MetS risk, the role of particular dietary components remains unclear, especially among younger adults. Individual dietary components have been implicated in ameliorating or exacerbating MetS risk; however, the extent to which these factors contribute to MetS prevention has received little attention. This cross-sectional study aimed to assess relations between diet and individual MetS components in young to middle-aged adults who are overweight and/or obese. Participants aged 25-45 y (N = 117) with overweight and obesity, but no other diagnosed metabolic disease, recorded dietary intake over 7 d. MetS components (waist circumference, blood pressure, glucose, triglycerides [TGs], and high-density lipoprotein cholesterol [HDL]) were measured. Visceral adipose tissue was measured by dual-energy X-ray absorptiometry. Linear regression was used to assess relations between diet and MetS risk factors, adjusting for age, sex, and visceral adipose tissue. MetS prevalence in this sample was 32%. Energy-adjusted total fiber intake (β = -0.21, P = 0.02) was inversely associated with TG concentrations. No significant relations were observed between other dietary factors and MetS components. These findings indicate that among MetS components, TG concentrations are potentially sensitive to fiber consumption. These results provide cross-sectional evidence supporting the protective influence of dietary fiber on MetS components among young to middle-aged adults. Additional, well-designed clinical trials are needed to assess the causal relations between various types of dietary fiber and metabolic disease.


Effect of COVID-19 vaccination on mortality by COVID-19 and on mortality by other causes, the Netherlands, January 2021-January 2022.
We aimed to estimate vaccine effectiveness (VE) against COVID-19 mortality, and to explore whether an increased risk of non-COVID-19 mortality exists in the weeks following a COVID-19 vaccine dose. National registries of causes of death, COVID-19 vaccination, specialized health care and long-term care reimbursements were linked by a unique person identifier using data from 1 January 2021 to 31 January 2022. We used Cox regression with calendar time as underlying time scale to, firstly, estimate VE against COVID-19 mortality after primary and first booster vaccination, per month since vaccination and, secondly, estimate risk of non-COVID-19 mortality in the 5 or 8 weeks following a first, second or first booster dose, adjusting for birth year, sex, medical risk group and country of origin. VE against COVID-19 mortality was > 90 % for all age groups two months after completion of the primary series. VE gradually decreased thereafter, to around 80 % at 7-8 months post-primary series for most groups, and around 60 % for elderly receiving a high level of long-term care and for people aged 90+ years. Following a first booster dose, the VE increased to > 85 % in all groups. The risk of non-COVID-19 mortality was lower or similar in the 5 or 8 weeks following a first dose compared to no vaccination, as well as following a second dose compared to one dose and a booster compared to two doses, for all age and long-term care groups. At the population level, COVID-19 vaccination greatly reduced the risk of COVID-19 mortality and no increased risk of death from other causes was observed.


[Protective effect of "neiguan" (PC 6)-electroacupuncture preconditioning on the myocardium in myocardial ischemia/reperfusion rats].
To investigate the effects of "Neiguan" (PC 6)-electroacupunture (EA) preconditioning on the myocardium and its mast cells in myocardial ischemia/reperfusion (MI/R) rats. Eighteen male SD rats were randomly assigned to sham group, model (IR) group and EA group (n=6/ group). MI/R model was established by occlusion of the descending anterior branch of the coronary artery. Blood samples were taken from the femoral vein before MI (T0), EA for 30 min (T1), 30 min after MI (T2), 30 min after MI/R (T3) and 120 min after MI/R (T4) for assaying serum tumor necrosis factor (TNF)-alpha and histamine contents by using ELISA. Serum lactate dehydrogenase (LDH) and creatinkinase isoenzyme (CK-MB) levels were measured at T0, T3 and T4 by using an automatic biochemistry analyzer. The infarct size was detected by Evan's blue and tetrazolium chloride (TTC) staining. Myocardial TNF-alpha and histamine contents were detected by ELISA. The percentage of mast cell degranulation was determined by toluidine blue staining. Following MI/R, serum LDH and CK-MB levels at phase T3 and T4, serum TNF-alpha and histamine contents at phase T2 and T3, and myocardial mast cell degranulation rate increased significantly, and myocardial TNF-alpha and histamine contents decreased in model group in comparison with pre-MI/R (P < 0.05). Compared with IR model group, serum LDH and CK-MB levels at phase T3 and T4, myocardial TNF-alpha and histamine contents all decreased significantly (P < 0.05), but serum TNF-al infarct size was remarkably smaller in EA group than that in IR model group (P < 0.05). "Neiguan" (PC 6)-EA preconditioning has a cardioprotective effect on the ischemia-reperfusion myocardium by promoting mast cell degranulation.


Characterization of plasminogen activator in human cervical cells.
Plasminogen activator activity was detected in human gynecologic specimens using a synthetic fluorogenic peptide substrate assay and confirmed by an 125I-labeled fibrin plate assay. Epithelial cells in these samples contain enzymatic activity that biochemically resembles both the well-characterized plasminogen activator, urokinase, and the less-specific plasminogen activator, trypsin. Inhibition of the cervical cell activity by diisopropylfluorophosphate and p-nitrophenyl-p'-guanidinobenzoate demonstrates that, like urokinase and trypsin, this plasminogen activator is also a serine protease. Polyacrylamide gel electrophoresis of plasminogen that had been incubated with cervical cells indicated the same mechanism of plasminogen activation as exhibited by urokinase. We attempted to correlate plasminogen activator activity of each sample with cytomorphologic diagnosis. Three of the four dysplastic samples analyzed showed higher plasminogen activator activity than did the normal samples.


The health-related quality of life journey of gynecologic oncology surgical patients: Implications for the incorporation of patient-reported outcomes into surgical quality metrics.
To report the changes in patient-reported quality of life for women undergoing gynecologic oncology surgeries. In a prospective cohort study from 10/2013-10/2014, women were enrolled pre-operatively and completed comprehensive interviews at baseline, 1, 3, and 6months post-operatively. Measures included the disease-specific Functional Assessment of Cancer Therapy-General (FACT-GP), general Patient Reported Outcome Measure Information System (PROMIS) global health and validated measures of anxiety and depression. Bivariate statistics were used to analyze demographic groups and changes in mean scores over time. Of 231 patients completing baseline interviews, 185 (80%) completed 1-month, 170 (74%) 3-month, and 174 (75%) 6-month interviews. Minimally invasive (n=115, 63%) and laparotomy (n=60, 32%) procedures were performed. Functional wellbeing (20 → 17.6, p<0.0001) decreased at 1-month, and recovered by 3 and 6months. Emotional wellbeing increased (16.3 → 20.1, p<0.0001) and anxiety decreased (54.2 → 49.0, p<0.0001) at 1-month, and were stable at 3 and 6months. Physical wellbeing scales were not sensitive to surgery. These patterns were consistent across procedure type, cancer diagnosis, and adjuvant therapy administration. In an exploratory analysis of the interaction of QOL and quality, patients with increased postoperative healthcare resource use were noted to have higher baseline levels of anxiety. For women undergoing gynecologic oncology procedures, temporary declines in functional wellbeing are balanced by improvements in emotional wellbeing and decreased anxiety symptoms after surgery. Not all commonly used QOL surveys are sensitive to changes during the perioperative period and may not be suitable for use in surgical quality metrics.


The role of catalytic and regulatory domains of human PrimPol in DNA binding and synthesis.
Human PrimPol possesses DNA primase and DNA polymerase activities and restarts stalled replication forks protecting cells against DNA damage in nuclei and mitochondria. The zinc-binding motif (ZnFn) of the C-terminal domain (CTD) of PrimPol is required for DNA primase activity but the mechanism is not clear. In this work, we biochemically demonstrate that PrimPol initiates de novo DNA synthesis in cis-orientation, when the N-terminal catalytic domain (NTD) and the CTD of the same molecule cooperate for substrates binding and catalysis. The modeling studies revealed that PrimPol uses a similar mode of initiating NTP coordination as the human primase. The ZnFn motif residue Arg417 is required for binding the 5'-triphosphate group that stabilizes the PrimPol complex with a DNA template-primer. We found that the NTD alone is able to initiate DNA synthesis, and the CTD stimulates the primase activity of NTD. The regulatory role of the RPA-binding motif in the modulation of PrimPol binding to DNA is also demonstrated.


Electrographic analysis of the sleep cycle in young depressed patients.
Electrographic (EEG) patterns of nocturnal sleep were investigated in young psychiatric patients during unipolar depressive episodes. EEG-sleep data was recorded in 20 non-psychotic depressed patients all under 26 years old individually matched with a normal control group. All 20 subjects slept in the laboratory for 1-3 consecutive baseline nights from 12-8:00 a.m. During a subsequent extended condition 14 in each group were allowed to sleep ad-lib. Although the mean total time asleep on baseline nights was about the same between groups (greater than 7.1 hr), the depressives had a statistically significant reduction in REM time, increased transitions into stage 1, but most especially averaged: (a) less stage 4; and (b) more stage 1. Compared with the prior eight-hour night 27/28 subjects among both groups exhibited elevated time asleep during the extended condition, but the patients' mean total 10.3 hr sleep was significantly greater by 1.5 hr than the controls (X = 8.8 hr). Sleep exceeding 9 hr on the ad-lib night was a consistent phenomenon which occurred in significantly more (11/14) young depressed patients contrasted to 4/14 control subjects. These findings indicate that young persons with primary affective disorders do not exhibit nocturnal EEG disturbances of comparable severity to most older depressed patients such as reduced time asleep, increased wakefulness or lowered slow-wave (stages 3 and 4) sleep. Although no direct evidence of symptomatic 'hypersomnia' in these patients was provided, the present results demonstrated that some young persons with clinical depression have the capacity to sleep for sustained periods.


Effects of pimobendan on left atrial transport function in cats.
Arterial thromboembolism is a sequela of hypertrophic cardiomyopathy (HCM) in cats related to left atrial (LA) enlargement and dysfunction. Pimobendan improves LA transport function in cats. Twenty-two client-owned cats with HCM and 11 healthy cats. Prospective, double-blind, randomized, placebo-controlled clinical cohort study. Cats were randomized to receive either pimobendan (0.25 mg/kg PO q12h) or placebo for 4 to 7 days. Nineteen echocardiographic variables of LA size and function were evaluated. Statistical comparisons included t tests, analysis of variance, and multivariable analyses. Peak velocity of left auricular appendage flow (LAapp peak; mean ± SD, 0.85 ± 0.20 vs 0.71 ± 0.22 m/s; P = .01), maximum LA volume (P = .03), LA total emptying volume (P = .03), peak velocity of late diastolic transmitral flow (A peak velocity; 0.77 ± 0.12 vs 0.62 ± 0.17 m/s; P = .05), and A velocity time integral (A VTI; 3.05 ± 0.69 vs 3.37 ± 0.49; P = .05) were increased after pimobendan. Mean change after pimobendan was larger in cats with HCM compared to healthy cats for LA fractional shortening (2.1% vs -2.1%; P = .05), A VTI (0.58 vs 0.01 cm; P = .01), LAapp peak (0.20 vs 0.02 m/s; P = .02), LA kinetic energy (3.51 vs -0.10 kdynes-cm; P = .05), and LA ejection force (1.93 vs -0.07 kdynes; P = .01) in the multivariable model. The stronger effect of pimobendan in cats with HCM was independent of LA size. We identified positive, albeit minor, effects of pimobendan on LA function in cats with HCM. Whether or not treatment with pimobendan decreases the risk of cardiogenic embolism deserves further study.


Crystallization and preliminary X-ray diffraction studies on recombinant isopenicillin N synthase from Aspergillus nidulans.
Recombinant Aspergillus nidulans isopenicillin N synthase was purified from an Escherichia coli expression system. The apoenzyme in the presence of saturating concentrations of MnCl2 could be crystallized by either macro- or microseeding, using the hanging drop vapor diffusion technique with polyethylene glycol 8000 as precipitant. The crystals (0.5-1.0 mm overall dimensions) diffract X-rays to at least 2.0 A resolution at synchrotrons and belong to space group P212121 with unit cell dimensions of a = 59.2 A, b = 127.0 A, and c = 139.6 A. The asymmetric unit contains one dimer, and the solvent content of the crystals is 60%. The crystals are radiation sensitive.


Cluster randomised trial of a targeted multifactorial intervention to prevent falls among older people in hospital.
To determine the efficacy of a targeted multifactorial falls prevention programme in elderly care wards with relatively short lengths of stay. Cluster randomised trial. 24 elderly care wards in 12 hospitals in Sydney, Australia. 3999 patients, mean age 79 years, with a median hospital stay of seven days. A nurse and physiotherapist each worked for 25 hours a week for three months in all intervention wards. They provided a targeted multifactorial intervention that included a risk assessment of falls, staff and patient education, drug review, modification of bedside and ward environments, an exercise programme, and alarms for selected patients. Falls during hospital stay. Intervention and control wards were similar at baseline for previous rates of falls and individual patient characteristics. Overall, 381 falls occurred during the study. No difference was found in fall rates during follow-up between intervention and control wards: respectively, 9.26 falls per 1000 bed days and 9.20 falls per 1000 bed days (P=0.96). The incidence rate ratio adjusted for individual lengths of stay and previous fall rates in the ward was 0.96 (95% confidence interval 0.72 to 1.28). A targeted multifactorial falls prevention programme was not effective among older people in hospital wards with relatively short lengths of stay. Australian New Zealand Clinical Trials Registry ACTRNO 12605000467639.


Design of two electrode system for detection of antioxidant capacity with photoelectrochemical platform.
Recently, a flow photoelectrochemical cell has been first developed and applied to assay global antioxidant capacity in our group. Yet, shortcomings of liquid reference electrode such as sample contaminations from the leaking of the reference solution, mechanically fragile, temperature and light sensitivity, etc. are significant restrictions for integration and miniaturization of photoelectrochemical sensing instruments, which have greatly limited their practical applications. Bearing these problems, in this work a novel two electrode flow photoelectron-chemical system (two-EPCS) has been developed for detection of antioxidant capacity. It is noteworthy that the electrochemical modulation-free mode (detection at the potential of 0.0V) is performed, which has greatly simplified the analysis process and will result in significant simplifications of the instrument integrations. During the sample analysis, both standard antioxidants and commercial beverages were detected. Results evaluated from the two-EPCS are well agreed with those of the traditional three-EPCS at low potentials. By unloading of the reference electrode, it is of great convenience to design a novel photoelectrochemical microfluidic chip based on the two-EPCS, which has also been successfully applied for antioxidant capacity assay. It is satisfactory that comparable detection concentration range and sensitivity were accomplished by applying the microfluidic chip technique. Moreover, the two-EPCS is verified to be a universal platform which does not depend on selected optoelectronic materials but pervasive for general photocatalysts. Such a two-EPCS should be considered as a feasible alternative to the three-EPCS, which will become a promising candidate for industrial and commercial photoelectrochemical sensing instrument integrations in the future.


Intensified glycemic control by HbA1c for patients with coronary heart disease and Type 2 diabetes: a review of findings and conclusions.
The occurrence and development of coronary heart disease (CHD) are closely linked to fluctuations in blood glucose levels. While the efficacy of intensified treatment guided by HbA1c levels remains uncertain for individuals with diabetes and CHD, this review summarizes the findings and conclusions regarding HbA1c in the context of CHD. Our review showed a curvilinear correlation between regulated level of HbA1c and therapeutic effectiveness of intensified glycemic control among patients with type 2 diabetes and coronary heart disease. It is necessary to optimize the dynamic monitoring indicators of HbA1c, combine genetic profiles, haptoglobin phenotypes for example and select more suitable hypoglycemic drugs to establish more appropriate glucose-controlling guideline for patients with CHD at different stage of diabetes.


The relationship of overweight and obesity with subjective health and use of health-care services among Spanish women.
To examine the relationship of overweight and obesity with subjective health and use of health-care services among women in Spain. Data were drawn from the 1993 Spanish National Health Survey, covering a 13 244-woman sample representative of the non-institutionalised Spanish population aged 16 y and over. Information was collected through home-based interviews. Multiple logistic regression models were used to calculate odds ratios for suboptimal health (fair, poor or very poor) and utilisation of health-care services by women with normal weight (BMI 18.5-24.9 kg/m(2)), overweight (BMI 25.0-29.9 kg/m(2)) and obesity (BMI>or=30 kg/m(2)). Analyses were adjusted for age, education level, occupation, civil status, social support, tobacco use, alcohol consumption, physical activity at work and during leisure time, job status and town of residence. Frequency of suboptimal health was higher in women with overweight (OR 1.7; 95% CI 1.5-1.9) and obesity (OR 2.1; 95% CI 1.8-2.5) than in those with normal weight. Overweight and obese women visited the physician, used hospital emergency services and took medication with greater frequency than did women of normal weight. There was a positive dose-response relationship (P<0.05) of BMI>or=18.5 kg/m(2) with suboptimal health and utilisation of health-care services. These associations were not wholly explained by BMI-related risk factors and chronic diseases, since their statistical significance remained unchanged and their magnitude was only slightly reduced after adjustment for those factors. The association of overweight and obesity with the use of health-care services did not vary with age, educational level or presence of chronic disease. Overweight and obese women have worse subjective health and make greater use of health-care services. This finding is an additional argument for implementing weight-control programmes in Spain.


Genetic factors in psoriatic arthritis.
The genetic factors that are associated with psoriatic arthritis (PsA) are intricately linked with those that predispose to psoriasis itself. The strongest association is with human leukocyte antigen-Cw*0602, although true susceptibility may lie with one of the neighboring genes along a disease-associated haplotype. There are a number of interesting candidate genes within the major histocompatibility complex (MHC) region with strong functional relevance that have been investigated in PsA. In addition, several areas outside the MHC complex have been highlighted as a result of genetic linkage studies in psoriasis. PsA is a complex, multifactorial disease where multiple genes are likely to influence disease susceptibility, severity, and clinical phenotype. The current evidence for genetic factors in psoriasis and PsA will be reviewed.


Non-Invasive Techniques for Multimodal Monitoring in Traumatic Brain Injury: Systematic Review and Meta-Analysis.
Monitoring brain oxygenation and intracranial pressure non-invasively and continuously is of paramount importance in traumatic brain injury (TBI). The primary motivation of this study was to identify and provide robust evidence of the most effective techniques for the non-invasive multimodal monitoring for traumatic brain injury. Two reviewers independently searched PubMed, Embase, Scopus, the Cochrane Library, and the Web of Science between January 15, 2010, and January 22, 2020. Cohort studies assessing correlation or accuracy of non-invasive techniques for intracranial pressure (ICP) and/or brain oxygenation monitoring in TBI patients were included. The Newcastle-Ottawa Scale was used to assess the methodological quality of the studies. PROSPERO registration ID is CRD42020164739. Eight out of the 12 studies selected focused on the non-invasive measurement of ICP. Near-Infrared spectroscopy was the main technology for brain oxygenation, whereas ultrasound-based techniques were also used for ICP monitoring. PbtO2 monitoring through near-infrared spectroscopy showed low correlation and limited accuracy in detecting hypoxic events. A meta-analysis on non-invasive ICP monitoring revealed a strong pooled correlation coefficient of 0.725 (95 % confidence interval [CI]: 0.450-0.874; I2 91.31%) between transcranial Doppler and the gold standard ICP monitoring. The current meta-analysis has shown that the two most prominent and widely used technologies for non-invasive monitoring in TBI are near-infrared spectroscopy and transcranial Doppler. Both techniques could be considered for the future development of a single non-invasive and continuous multimodal monitoring device for TBI.


Clinical characteristics of congenital cervical atresia and associated endometriosis among 96 patients.
To describe the anatomic variety of congenital cervical atresia and to explore the relationship between this disorder and pelvic endometriosis. In a retrospective study, records were reviewed for 96 patients with a confirmed diagnosis of congenital cervical atresia treated at a center in Beijing, China, between January 1984 and October 2014. Data on demographic parameters, symptoms, anatomic features, and endometriosis were obtained and analyzed. Of the 96 patients, 54 (56%) had pelvic endometriosis, 23 (24%) had a uterine malformation, 75 (78%) had a vaginal malformation, and 12 (13%) had a urinary malformation. The patients with a delay from first symptoms to surgery of more than 1year had a higher incidence of endometriosis than did those with a delay of 1year or less (45/71 [63%] vs 7/23 [30%]; P=0.006), and this trend was not related to the severity of endometriosis (P=0.658). Among the 31 patients with unilateral endometrial cysts, 20 (65%) had left-sided cysts and 11 (35%) had right-sided cysts (P=0.005). More than half of patients with congenital cervical atresia had pelvic endometriosis. Early diagnosis and surgery seem to be necessary to prevent endometriosis among patients with congenital cervical atresia.


Dry Olive Leaf Extract in Combination with Methotrexate Reduces Cell Damage in Early Rheumatoid Arthritis Patients-A Pilot Study.
The effects of co-administration of dry olive leaf extract (DOLE) with standard methotrexate (MTX) therapy on the parameters of cell damage and inflammation in patients with early and long-term rheumatoid arthritis (RA) were evaluated at baseline, 3 and 6 weeks. Patients were assigned to groups: the early phase RA group on MTX monotherapy (E MTX), and the two RA groups that received co-treatment with DOLE and MTX: early (E MTX + DOLE) and long-term phase patients (L-t MTX+ DOLE). Baseline values indicated increased parameters of cell damage and disruption of redox balance in all groups. After three weeks the E MTX + DOLE group maintained high catalase activity, exhibited decrease of lipid peroxidation and protein damage indicators-thiols and nitrites, while levels of DNA damage and pro-inflammatory interleukin-6 were significantly reduced. In E MTX group catalase activity remained unaltered while significant lipid peroxidation and DNA damage reductions were seen only after six weeks. L-t MTX + DOLE group showed only modest alterations of cell damage parameters during six weeks. Combined administration of DOLE with MTX contributes to faster reduction of cell damage, restores oxidative balance and improves interleukin-6 suppression during high disease activity in early phase RA, but not in long term patients. Copyright © 2016 John Wiley & Sons, Ltd.


Isolation and Analysis of Cell Wall Proteome in Elsholtzia splendens Roots Using ITRAQ with LC-ESI-MS/MS.
Cell wall proteins (CWPs) are a prime site for signal perception and defense responses to environmental stresses. To gain further insights into CWPs and their molecular function, traditional techniques (e.g., two-dimensional gel electrophoresis) may be ineffective for special proteins. Elsholtzia splendens is a copper-tolerant plant species that grow on copper deposits. In this study, a fourplex isobaric tag was used for relative and absolute quantitation with liquid chromatography-tandem mass spectrometry approach to analyze the root CWPs of E. splendens. A total of 479 unique proteins were identified, including 121 novel proteins. Approximately 80.79 % of the proteins were extracted in the CaCl2 fraction, 16.08 % were detected in the NaCl fraction, and 3.13 % were identified in both fractions. The identified proteins have been involved in various processes, including cell wall remodeling, signal transduction, defense, and carbohydrate metabolism, thereby indicating a complex regulatory network in the apoplast of E. splendens roots. This study presents the first large-scale analysis of CWPs in metal-tolerant plants, which may be of paramount importance to understand the molecular functions and metabolic pathways in the root cell wall of copper-tolerant plants.


High-efficiency removal of organic pollutants by visible-light-driven tubular heterogeneous micromotors through a photocatalytic Fenton process.
Light-driven micromotors that can be remotely controlled by irradiation have environmental remediation applications. Herein, we describe a facile one-step hydrothermal method for synthesizing visible-light-driven heterogeneous micromotors by simultaneously depositing photocatalytic g-C3N4 and magnetic Fe3O4 nanoparticles on kapok fiber (KF) templates (g-C3N4-Fe3O4@KF). These microdevices exhibit precisely controlled motion in the presence of hydrogen peroxide (H2O2) under visible light via a bubble recoil mechanism. The present g-C3N4-Fe3O4@KF units display-two simultaneous locomotion modes: linear and self-rotation. The velocity of these micromotors can be controlled by multiple approaches, such as by changing the H2O2 concentration or visible light intensity. The photocatalytic propulsion of these microdevices can be conveniently switched on or off by regulating the incident light. As a proof-of-concept, g-C3N4-Fe3O4@KF micromotors were applied to the degradation of Rhodamine B (RhB). On the basis of a combination of photocatalytic Fenton oxidation and enhanced micro-mixing/mass transfer in the solution induced by self-propulsion and self-rotation, these g-C3N4-Fe3O4@KF micromotors enable much more efficient degradation of RhB compared with stationary systems. The magnetic nature of this material additionally allows convenient collection and recycling of the micromotors. The synthesis process can be easily scaled up and therefore may have the potential to fabricate self-propelled micromotors for practical applications.


Administration of low-dose epoetin-alpha facilitates adherence to ribavirin in triple therapy with pegylated interferon-alpha-2b and telaprevir.
Anemia frequently develops in patients given pegylated interferon, ribavirin (RBV), telaprevir (TVR) triple therapy and restricts treatment by forcing reduction or discontinuation of RBV administration. We investigated whether erythropoietin (EPO) could alleviate RBV-induced anemia to help maintain the RBV dose during the first 12 weeks, the triple therapy phase. Twenty-two patients with hepatitis C virus (HCV) genotype 1 were enrolled. Hemoglobin (Hb) concentration was measured every week. If Hb reduction from the baseline was 2 g/dL or more, 12 000 IU of epoetin-α was administrated. When further reduction (≥3 g/dL) was observed, 24 000 IU of epoetin-α was used. Inosine triphosphatase (ITPA) single nucleotide polymorphism (rs1127354) was genotyped for all patients. Among the 22 patients enrolled in this study, three required RBV dose reduction due to anemia, two had to discontinue or reduce TVR and RBV due to creatinine elevation. The remaining 17 patients completed the treatment during the triple therapy phase without reduction of the RBV dose or adverse events attributable to EPO. Regardless of ITPA genotype, Hb decline was well controlled by EPO administration, whereas the total EPO dose tended to be higher in the CC genotype group. The average adherence to RBV during the triple therapy phase was 97.5%. SVR was achieved in 17 patients; two patients had viral breakthrough and three patients had relapse of HCV RNA. EPO can be a favorable alternative to reduction of RBV to facilitate the adherence of patients on TVR-based triple therapy.


The in vitro interaction of Sporothrix schenckii with human endothelial cells is modulated by cytokines and involves endothelial surface molecules.
Sporothrix schenckii is the etiological agent of sporotrichosis, a subcutaneous mycosis that can evolve to systemic complications in immunocompromised patients. Interactions with endothelium are thought to be essential for systemic infections. In the present work, we studied the interaction between S. schenckii and human umbilical vein endothelial cells (HUVECs). S. schenckii interacts with HUVECs in a time-dependent manner. Morphological analysis showed that yeasts locate to interendothelial junctions. Ultrastructural studies showed that internalized yeasts were found inside endocytic vacuoles as early as 2 h, without causing any detectable damage to HUVECs after 24 h of infection. The viability of infected HUVECs was confirmed by the MTT assay. When HUVECs were treated with different concentrations of Interleukin-1beta or transforming growth factor-beta, a significant dose-dependent increase in cell-associated yeasts was observed. The preliminary analysis of the endothelial surface ligands for S. schenckii cells revealed two major molecules, with Mr of approximately 90 and 135 kDa. The interaction of endothelial cell surface molecules with S. schenckii yeast cells was modulated by divalent cations. This is the first demonstration that S. schenckii is able to adhere and invade endothelial cells without significantly affect cellular integrity. Our results suggest the contribution of cytokine-modulated calcium-dependent molecules to this process.


Metabolism-based cyclophosphamide dosing for hematopoietic cell transplant.
When cyclophosphamide (120 mg/kg) is used for hematopoietic cell transplant, the increased area under the curve of carboxyethylphosphoramide mustard (AUC(CEPM)) is related to liver toxicity and death. We determined the feasibility of dose-adjusting cyclophosphamide to a preset metabolic endpoint (AUC(CEPM), 325 +/- 25 micromol/L.h). In 20 patients blood sampling was done over a 16-hour period after administration of 45 mg/kg cyclophosphamide; AUC(CEPM) from 0 to 16 hours was calculated by noncompartmental analysis. The expected AUC(CEPM) for 0 to 48 hours was estimated, and the second cyclophosphamide dose was determined. The mean second cyclophosphamide dose was 42 mg/kg, and the mean total cyclophosphamide dose was 86 mg/kg (range, 54-120 mg/kg). The mean AUC(CEPM) for the time from 0 to 48 hours was 296 micromol/L.h (95% confidence interval, 275-317 micromol/L.h). A retrospective analysis indicated that AUC(CEPM) could be more accurately predicted by use of a population pharmacokinetic model. We conclude that metabolism-based dosing of cyclophosphamide is feasible and that a lower cyclophosphamide dose does not affect engraftment.


Inference of metabolic fluxes in nutrient-limited continuous cultures: A Maximum Entropy approach with the minimum information.
The study of cellular metabolism is limited by the amount of experimental data available. Formulations able to extract relevant predictions from accessible measurements are needed. Maximum Entropy (ME) inference has been successfully applied to genome-scale models of cellular metabolism, and recent data-driven studies have suggested that in chemostat cultures of Escherichia coli (E. coli), the growth rate and uptake rates of limiting nutrients are the most informative observables. We propose the thesis that this can be explained by the chemostat dynamics, which typically drives nutrient-limited cultures toward observable metabolic states maximally restricted in the dimensions of those fluxes. A practical consequence is that relevant flux observables can now be replaced by culture parameters usually controlled. We test our model by using simulations, and then we apply it to E. coli experimental data where we evaluate the quality of the inference, comparing it to alternative formulations that rest on convex optimization.


Comparator and non-comparator mechanisms of change detection in the context of speech--an ERP study.
Automatic change detection reflects a cognitive memory-based comparison mechanism as well as a sensorial non-comparator mechanism based on differential states of refractoriness. The purpose of this study was to examine whether the comparator mechanism of the mismatch negativity component (MMN) is differentially affected by the lexical status of the deviant. Event-related potential (ERP) data was collected during an "oddball" paradigm designed to elicit the MMN from 15 healthy subjects that were involved in a counting task. Topography pattern analysis and source estimation were utilized to examine the deviance (deviants vs. standards), cognitive (deviants vs. control counterparts) and refractoriness (standards vs. control counterparts) effects elicited by standard-deviant pairs ("deh-day"; "day-deh"; "teh-tay") embedded within "oddball" blocks. Our results showed that when the change was salient regardless of lexical status (i.e., the /e:/ to /eI/ transition) the response tapped the comparator based-mechanism of the MMN which was located in the cuneus/posterior cingulate, reflected sensitivity to the novelty of the auditory object, appeared in the P2 latency range and mainly involved topography modulations. In contrast, when the novelty was low (i.e., the /eI/ to /e:/ transition) an acoustic change complex was elicited which involved strength modulations over the P1/N1 range and implicated the middle temporal gyrus. This result pattern also resembled the one displayed by the non-comparator mechanism. These findings suggest spatially and temporally distinct brain activities of comparator mechanisms of change detection in the context of speech.


Dyslipidemia in renal disease: causes, consequences and treatment.
The prevalence of chronic renal insufficiency and its complications, including dyslipidemia, is increasing. Although the characteristics of dyslipidemia in chronic renal insufficiency and its pathophysiology are well known, its cardiovascular and renal impact and the most effective therapeutic approach are poorly defined.


Dimensional distribution control of elongate mineral particles for their use in biological assays.
The aim of the present method is to reduce the dimensional variability of asbestos, elongate mineral particles, and other asbestiform minerals for use in biological assays. Here, the pristine mineral sample is filtered through two nylon meshes of different sizes to obtain a narrower dimensional distribution following a power law. Furthermore, we show that anoxic preparation, autoclaving and storage of the mineral prior to addition into biological cultures did not affect the mineral's chemical properties. This approach avoids the use of highly reactive chemicals modifying mineralogical characteristics and surface properties, which can affect to a major extent mineral toxicity as well as interactions between minerals and biological matter or biofluids. The method can be combined with additional selective approaches to further refine the dimensional range of the minerals. The advantages of this protocol over previous methods are: •Exclusive use of distilled water and 2-propanol, thus eliminating chemicals that can modify bulk or surface properties of the studied minerals.•Successful sterilization of the resulting mineral particles for use in biological assays without compromising mineralogical characteristics.•Applicability of this method across various types of asbestos, elongate mineral particles and, potentially, other hazardous minerals.


Induction Therapy With ATG Compared With Anti-IL2 Basiliximab in Low-Immunologic Risk Kidney Transplant Recipients.
Practically all kidney allograft recipients require immunosuppressive therapy to prevent rejection and loss of the allograft. The aim of this study was to determine the occurrence of biopsy-proven acute rejection in low-immunologic risk kidney transplant recipients according to the type of induction (basiliximab vs low-dose of rabbit antithymocyte globulin [rATG], 3.5 mg/kg). A total of 125 patients after primary kidney transplant were included in the retrospective analysis with 6-month follow-up. The immunosuppression regimen included tacrolimus, mycophenolic acid, and corticoids. We did not find any significant difference in the occurrence of acute rejection or difference in the occurrence of infection complications. Patients in the rATG group had a significantly longer period of cold ischemia, more frequently received kidney transplants from expanded criteria donors, and had significantly more mismatches in HLA-DR. Delayed graft function (DGF) was identified as an independent risk factor for biopsy-proven acute rejection (hazard ratio, 3.4859; P = .003). There was comparable incidence of DGF between the 2 groups despite that there were several factors that are more commonly associated with DGF in the rATG group. Patients with low immunologic risk and high risk of DGF benefit from the rATG induction in dose of 3.5 mg/kg without the increased risk of infection complications with the assumption of good graft function in long-term post-transplant period.


Engineered arterial models to correlate blood flow to tissue biological response.
This paper reviews how biomedical engineers, in collaboration with physicians, biologists, chemists, physicists, and mathematicians, have developed models to explain how the impact of vascular interventions on blood flow predicts subsequent vascular repair. These models have become increasingly sophisticated and precise, propelling us toward optimization of cardiovascular therapeutics in general and personalizing treatments for patients with cardiovascular disease.


[2,3]sigmatropic rearrangements of propargylic and allenic systems.
[2,3]Sigmatropic rearrangements of propargyl sulfonium ylides along with recent advances in the correspondingsulfenate-sulfoxide and sulfinate-sulfone type rearrangements are reviewed. Some new additionalexamples of these types of transformations, including rearrangements of propargylic dialkoxy disulfidesare also surveyed.


Conversation game: talking bacteria.
The story of autonomous unicellular organisms, bacteria with unimaginable computational and evolutionary capabilities along with collective behavior has been running since the first six decades of the twentieth Century. However, do not consider them to be small and simple, because they possess the generic term quorum sensing adopted to describe the cell communication process which co-ordinate gene expression, when the population has reached a high cell density. Bacteria release diffusible signal molecules known as autoinducers or quorum sensing molecules. In recent research, the direction for activating or deactivating nature of a wave of gene expression is predicted experimentally which control bacterial populations subject to a diffusing autoinducer signal. On the other hand, it has been observed that the accumulation of the quorum sensing molecules leads to a negative diffusion coefficient in the solution of governing differential equation.


Retinal nerve fiber layer thickness in patients with retinitis pigmentosa.
To study retinal nerve fiber layer (RNFL) thickness in patients with retinitis pigmentosa (RP). Cross-sectional observational study. One hundred and thirty-seven eyes of 137 patients with RP were examined. The effect of age, gender, laterality, inheritance trait, spherical equivalent refractive error, visual acuity, and the extent of visual field defect on RNFL thickness measured with optical coherence tomography were analyzed by a multiple linear regression model. The average RNFL thickness was 104.1+/-21.7 microm. The multiple R(2) for the model was 0.349. Among the variables studied, ageing and being male were significant risk factors for thinner RNFL thickness. RNFL thickness was not correlated with inheritance trait, laterality, refractive error, visual acuity, or the extent of visual field defect. RNFL thickness in RP patients was not correlated with visual function but ageing as in the normal subjects. Currently proposed therapies, including photoreceptor rescue/transplantation and visual prosthesis, are based on the premise that the inner retinal structures are relatively retained despite the profound loss of photoreceptors. The present result supports this notion.


Effect of three anorectic drugs on brain GABA levels and synthesis in the Zucker rat.
1. Genetically obese Zucker rats and their lean littermates were submitted to a subchronic treatment with fenfluramine, mazindol and amphetamine. GABA levels and synthesis index were measured in different brain areas. 2. GABA levels, similar in obese and lean controls, were not changed after the three treatments. 3. A higher synthesis index of GABA was found in lean rats, in the striatum after mazindol and in the hypothalamus after amphetamine. 4. The three drugs increased the synthesis index of GABA in the remainder of the brain of both obese and lean rats.


Retroperitoneal seminoma and intratubular germ cell neoplasia.
A 30-year-old man with a 6-month history of flank pain was found to have a large retroperitoneal seminoma. A subsequent ultrasound examination revealed an inhomogeneous echo pattern in the normal-sized right testicle, which on orchiectomy showed extensive intratubular germ cell neoplasia. Level sectioning of the entire testicle revealed no extratubular extension of the tumor cells. The retroperitoneal and testicular lesions could represent double primaries. However, the possibility exists that an apparently intratubular germ cell neoplasm may not actually be an in situ lesion and that the retroperitoneal tumor in our case represents a metastasis from the intratubular germ cell neoplasia of the testicle.


Clinical features and outcomes in 38 dogs with cholelithiasis receiving conservative or surgical management.
Ursodeoxycholic acid is used in human medicine for litholytic management of choleliths, but the efficacy of medical management in dogs with cholelithiasis is unknown. To describe the clinical features and outcomes of dogs with cholelithiasis, focusing on cases that received medical treatment, and to identify patient factors that influenced decision-making for surgical or medical management. Thirty-eight dogs with cholelithiasis identified on abdominal ultrasonography (AUS). Medical records of dogs with cholelithiasis on AUS between 2010 and 2019 were retrospectively reviewed. Cases were classified as symptomatic (n = 18) or incidental (n = 20) and divided into medically treated (n = 13), surgically treated (n = 10), and no treatment (n = 15) groups. Biochemical variables and cholelith location were compared between symptomatic and incidental groups using Mann-Whitney U and chi-squared tests, respectively. Survival times were compared using Kaplan-Meier survival analysis. Symptomatic cases had higher alkaline phosphatase (P = .03), gamma-glutamyl transferase (P = .03), and alanine transferase (P = .02) activities than did incidental cases. A higher proportion of symptomatic cases (44.4%) had choledocholithiasis than did incidental cases (0%; P = .003). Seventy percent of surgically managed dogs, 7.7% of medically managed dogs, and 0% of nontreated dogs had choledocholiths at presentation. Seventeen dogs had follow-up AUS: cholelithiasis completely resolved in 4/8 medically treated, 5/7 of surgically treated, and 1/2 nontreated dogs. Median survival time was 457.4 days, with no significant difference between incidental and symptomatic dogs. Medical treatment can be effective for management of cholelithiasis in dogs, with clinical presentation and cholelith location playing important roles in treatment decision-making.


Prediction of sentinel lymph node positivity by growth rate of cutaneous melanoma.
To determine whether growth rate (GR) of cutaneous melanoma predicts the histological sentinel lymph node (SLN) positivity. Retrospective cohort study. Two tertiary melanoma referral centers. A total of 698 patients with invasive primary cutaneous melanoma in whom the SLN was identified between January 1, 2000, and June 30, 2010. Based on previous studies, a surrogate measure for GR in primary invasive melanoma was calculated as the ratio of Breslow thickness to time to melanoma development. The SLN was positive in 20.2% of patients. Multivariate logistic regression analysis revealed that GR, Breslow thickness, and the presence of microscopic satellitosis were independently associated with SLN positivity. The probability of SLN positivity was 8.2% for slow-growth melanomas (<0.10 mm/mo) compared with 19.8% for intermediate-growth melanomas (0.10-0.50 mm/mo) and 37.7% for fast-growth melanomas (>0.50 mm/mo). Growth rate was not an independent predictive factor for survival. Growth rate of primary cutaneous melanoma, together with Breslow thickness and the presence of microscopic satellitosis, predicts the histological SLN positivity.


"Not an Either/or Situation": The Minimization of Violence Against Women In United Kingdom "Domestic Abuse" Policy.
Proposed new legislation in England and Wales on domestic violence and abuse-the "Domestic Abuse Bill"-is underpinned by changes to criminal law, specifically the introduction of coercive and controlling behavior as set out in the Serious Crime Act 2015. The new Bill commits the British government to four main objectives with, it is claimed, prevention and protection at their heart. What is notable, however, is the rubric shift from "violence" to "abuse" in the proposed new legislation and its subscription to a gender symmetry paradigm that suggests a "watering down" of the government's response to gendered violence.