Adenovirus-mediated delivery of relaxin reverses cardiac fibrosis.
We have evaluated the effectiveness of systemic adenovirally delivered mouse relaxin on reversing fibrosis in a transgenic murine model of fibrotic cardiomyopathy due to beta(2)-adrenergic receptor (beta(2)AR) overexpression. Recombinant adenoviruses expressing green fluorescent protein (Ad-GFP), rat relaxin (Ad-rRLN) and mouse relaxin (Ad-mRLN) were generated and Ad-rRLN and Ad-mRLN were demonstrated to direct the expression of bioactive relaxin peptides in vitro. A single systemic injection of Ad-mRLN resulted in transgene expression in the liver and bioactive relaxin peptide in the plasma. Ad-mRLN, but not Ad-GFP, treatment reversed the increased left ventricular collagen content in beta(2)AR mice to control levels without affecting collagen levels in other heart chambers or in the lung and kidney. Hence a single systemic injection of adenovirus producing mouse relaxin reverses cardiac fibrosis without adversely affecting normal collagen levels in other organs and establishes the potential for the use of relaxin gene therapy for the treatment of cardiac fibrosis.


A real-time classification algorithm for EEG-based BCI driven by self-induced emotions.
The aim of this paper is to provide an efficient, parametric, general, and completely automatic real time classification method of electroencephalography (EEG) signals obtained from self-induced emotions. The particular characteristics of the considered low-amplitude signals (a self-induced emotion produces a signal whose amplitude is about 15% of a really experienced emotion) require exploring and adapting strategies like the Wavelet Transform, the Principal Component Analysis (PCA) and the Support Vector Machine (SVM) for signal processing, analysis and classification. Moreover, the method is thought to be used in a multi-emotions based Brain Computer Interface (BCI) and, for this reason, an ad hoc shrewdness is assumed. The peculiarity of the brain activation requires ad-hoc signal processing by wavelet decomposition, and the definition of a set of features for signal characterization in order to discriminate different self-induced emotions. The proposed method is a two stages algorithm, completely parameterized, aiming at a multi-class classification and may be considered in the framework of machine learning. The first stage, the calibration, is off-line and is devoted at the signal processing, the determination of the features and at the training of a classifier. The second stage, the real-time one, is the test on new data. The PCA theory is applied to avoid redundancy in the set of features whereas the classification of the selected features, and therefore of the signals, is obtained by the SVM. Some experimental tests have been conducted on EEG signals proposing a binary BCI, based on the self-induced disgust produced by remembering an unpleasant odor. Since in literature it has been shown that this emotion mainly involves the right hemisphere and in particular the T8 channel, the classification procedure is tested by using just T8, though the average accuracy is calculated and reported also for the whole set of the measured channels. The obtained classification results are encouraging with percentage of success that is, in the average for the whole set of the examined subjects, above 90%. An ongoing work is the application of the proposed procedure to map a large set of emotions with EEG and to establish the EEG headset with the minimal number of channels to allow the recognition of a significant range of emotions both in the field of affective computing and in the development of auxiliary communication tools for subjects affected by severe disabilities.


Transcriptomic analysis of B cells suggests that CD70 and LY9 may be novel features in patients with systemic lupus erythematosus.
Dysfunction of B-cell subsets is critical in the development of systemic lupus erythematosus (SLE). There is a great diversity of B-lineage cells, and their features and functions in SLE need to be clarified. In this study, we analyzed single-cell RNA sequencing (scRNA-seq) data from peripheral blood mononuclear cells (PBMCs) and bulk transcriptomic data of isolated B-cell subsets from patients with SLE and healthy controls (HCs). We preformed scRNA-seq analysis focused on the diversity of B-cell subsets and identified a subset of antigen-presenting B cells in SLE patients that highly expressed ITGAX. A list of marker genes of each B-cell subset in patients with SLE was also identified. Comparison of bulk transcriptomic data of isolated B-cell subpopulations between SLE patients and HCs revealed the upregulated differentially expressed genes (DEGs) for each B-cell subpopulation in SLE. Common genes identified using these two methods were considered to be upregulated marker genes of B cells in SLE. The scRNA-seq data of SLE patients and HCs revealed that CD70 and LY9 were overexpressed in B cells vs. other cell types from SLE patients, and this pattern was validated by RT‒qPCR. Because CD70 is the cellular ligand of CD27, previous studies on CD70 have focused mainly on T cells from SLE patients. LY9 appears to have different functions in mice and humans: its expression is decreased in lupus-prone mice but is increased in T cells and some B-cell subpopulations in SLE patients. Here, we describe the overexpression of two costimulatory molecules, CD70 and LY9, which may be a novel feature of B cells in SLE patients.


Predictors of long-term stenosis in bicuspid aortic valve repair.
The use of modern techniques for bicuspid aortic valve repair has been shown to provide safe and durable results against recurrent regurgitation. However, an emerging body of evidence is indicating that aortic stenosis might be an additional late complication of these procedures. To date, the pathogenesis and clinical impact of aortic stenosis after bicuspid aortic valve repair are poorly understood. A retrospective analysis of 367 patients with bicuspid aortic valve repair was performed to identify predictors of reoperation for stenosis. Bicuspid aortic valve repair was performed using a combination of procedures on the leaflet, annulus, and aortic root. During a median follow-up of 8 years, reoperation for stenosis was required in 33 patients (9.0%). Freedom from reoperation for stenosis was 100%, 99.6%, 91.7%, and 74.9% at 1, 5, 10, and 15 years, respectively. The following factors were independently associated with reoperation for aortic stenosis: Leaflet or raphe resection with shaving was a protective factor (hazard ratio, 0.34; 95% confidence interval, 0.16-0.71; P = .004), whereas the use of expanded polytetrafluoroethylene for free-edge running suture (hazard ratio, 2.55; 95% confidence interval, 1.16-5.57; P = .019), supracoronary replacement of the ascending aorta in combination with valve repair (hazard ratio, 5.41; 95% confidence interval, 2.11-13.85; P = .001), and the need for a second aortic crossclamp (hazard ratio, 10.95; 95% confidence interval, 2.80-42.80; P = .001) were associated with increased risk of reoperation for aortic stenosis. While confirming previous findings, our analysis suggests that the inability to restore leaflet mobility and polytetrafluoroethylene for free-edge running suture are risk factors for stenosis. The so-called ascending phenotypes are probably more prone to stenosis. If the first attempt to repair is unsuccessful, the risk of late reoperation for aortic stenosis is high.


Acute respiratory arrest due to hypokalemia.
An uncommon but treatable etiology of acute respiratory failure is hypokalemia. A 36-year-old woman with previously undiagnosed distal renal tubular acidosis presented with foot and ankle swelling that was being treated with furosemide. She had been seen by three physicians within 24 hours and was diagnosed as having depression or hysterical conversion reaction. Her symptoms progressed to respiratory arrest. Initial treatment consisted of administering 40 mEq of KCl over one hour through a central venous line. The patient recovered rapidly and was weaned off a respirator within 24 hours of admission.


Ketamine reversed short-term memory impairment and depressive-like behavior in animal model of Parkinson's disease.
The most common features of Parkinson's disease (PD) are motor impairments, but many patients also present depression and memory impairment. Ketamine, an N-methyl-d-aspartate (NMDA) receptor antagonist, has been shown to be effective in patients with treatment-resistant major depression. Thus, the present study evaluated the action of ketamine on memory impairment and depressive-like behavior in an animal model of PD. Male Wistar rats received a bilateral infusion of 6 μg/side 6-hydroxydopamine (6-OHDA) into the substantia nigra pars compacta (SNc). Short-term memory was evaluated by the social recognition test, and depressive-like behaviors were evaluated by the sucrose preference and forced swimming tests (FST). Drug treatments included vehicle (i.p., once a week); ketamine (5, 10 and 15 mg/kg, i.p., once a week); and imipramine (20 mg/kg, i.p., daily). The treatments were administered 21 days after the SNc lesion and lasted for 28 days. The SNc lesion impaired short-term social memory, and all ketamine doses reversed the memory impairment and anhedonia (reduction of sucrose preference) induced by 6-OHDA. In the FST, 6-OHDA increased immobility, and all doses of ketamine and imipramine reversed this effect. The anti-immobility effect of ketamine was associated with an increase in swimming but not in climbing, suggesting a serotonergic effect. Ketamine and imipramine did not reverse the 6-OHDA-induced reduction in tyrosine hydroxylase immunohistochemistry in the SNc. In conclusion, ketamine reversed depressive-like behaviors and short-term memory impairment in rats with SNc bilateral lesions, indicating a promising profile for its use in PD patients.


Saddle nasal deformity.
Correction of the saddle nasal deformity requires generous elevation and mobilization of the overlying soft tissue, the restoration of skeletal support, and the provision of nasal mucosa lining ("the forgotten link"). For moderate to severe saddle deformities, calvarial bone grafts serve well to reconstruct the disrupted skeletal framework.


Three-hour collection of committed and multipotent hematopoietic progenitor cells by apheresis.
Although multipotent progenitor cells have been collected from blood in humans by apheresis in 1- to 2-hour collections, longer-term collections of multipotent progenitor cells have not been reported. To determine whether such collections could be sustained, the authors performed six 3-hour collections on five normal volunteers, processing a mean of 8024 ml of blood. Blood samples were taken at 0, 1.5, and 3 hours, and component samples were taken at 1.5 and 3 hours. Cell counts, differentials, and committed myeloid (CFU-GM), erythroid (BFU-E), and multipotent (CFU-MIX or CFU-GEMM) progenitor cell assays were performed. Collection efficiency for progenitor cells, the number of cells collected divided by the number in the blood processed, did not diminish significantly. The number collected in the second 1.5-hour period resembled the number collected during the first. Circulating numbers did not fall significantly during apheresis. Prolongation of apheresis collections may reliably increase the number of progenitor cells available for eventual hematopoietic reconstitution.


Developing a genetic services assessment tool to inform quality improvement efforts in state genetic service delivery.
The Institute of Medicine recommended the utilization of metrics to improve quality in health care, although they have rarely been used in genetics. This study developed and tested a set of metrics for a quality assessment tool for genetic services METHODS: A systematic review of literature, guidelines, and consensus statements identified candidate measures for a possible assessment tool. An expert panel conducted a modified Delphi technique to rank the metrics. Ratings were computed to generate a score for each metric, creating a set of metrics for consensus discussions, pilot testing, and feasibility testing in eight Midwestern states. The panel reduced 61 candidate metrics to 21 for pilot testing in two states, which further limited and refined the set to 16 metrics. These 16 were categorized into five domains: service capacity, access to care, data systems, performance reporting, and workforce. Further feasibility testing in one Regional Genetics Collaborative identified the tool's usefulness and barriers to implementation. These quality metrics for both clinical and public health genetics across the lifespan may help medical professionals and policymakers evaluate quality and cost-effectiveness of genetic services on a statewide basis and stimulate outcome-oriented, health services research in medical genetics and genomics.


Different effects of cyclophosphamide in vivo and phosphamide mustard in vitro on two cell clones of chemically induced mammary carcinoma of the rat.
Two cell clones of a methylnitrosourea-induced rat mammary carcinoma, a hyperdiploid (44 chromosomes, clone A) and a hypertetraploid clone (88 chromosomes, clone B) were cultured and transplanted subcutaneously into three groups of eight rats. Group 1 was treated with 62.6 mg cyclophosphamide/kg, group 2 with 41.8 mg/kg once weekly for 3 weeks. The volume of tumors derived from clone B cells was diminished by the administration of the agent, whereas clone A cell tumors did not respond. Incubation of cells of both clones with phosphamide mustard in vitro showed that cells of clone B are much more sensitive to the activated cyclophosphamide, especially after incubation in low concentrations of 40 microM and 20 microM, than those of clone A. It is concluded that the initial success of cyclophosphamide therapy on chemically induced tumors is due to the different sensitivities of the tumor cell populations.


Pasture is a risk factor for Toxoplasma gondii infection in fattening pigs.
As consumer awareness of animal welfare increases throughout Europe, housing of pigs in more animal-friendly systems is becoming more common. There is concern that these free-range and organic management systems increase the prevalence of zoonotic meat-borne pathogens, such as Toxoplasma gondii. In this study we compared the seroprevalence of T. gondii between commercial fattening pigs raised on conventional and on organic farms in Sweden. Furthermore, potential associations between presence of T. gondii antibodies and type of production, access to pasture, and geographical region were analysed. A significant difference in T. gondii seroprevalence was found between conventional (1%) and organic pigs (8%). The higher odds of seropositivity in organic production was attributed to pasture access specifically (OR=1.8 for a one-month increase in length of pasture exposure). This study shows that the prevalence of T. gondii in Swedish conventional pigs is low. However, as pigs with access to pasture are at higher risk of infection and because the demand for animal-friendly production systems is increasing, there is an obvious need to practically manage the higher T. gondii presence in products from pigs raised in organic systems with outdoor access.


[Epidural intracranial measurement of pressure using conventional pressure transducers. Introduction of a new method].
Today there are no doubts about the great significance of continuous measurement of intracranial pressure in neuromonitoring. Numerous systems of measurement have been evolved and are available. However, they are rather costly because of their minute size that makes them not only expensive to buy but also to maintain on account of their susceptibility to disturbances and their vulnerability. Hence, the author presents as an alternative to the conventional measurement systems a simple measurement method with a low susceptibility to faults and, above all, at a reasonable price. This method works satisfactorily with the conventional pressure sensors that are usually employed in intraarterial blood pressure measurement. In contrast to the normal procedure, however, the sensors are not implanted; the intracranial pressure is transmitted to extracranial via a liquid column and is then led to the measuring element. This method is accurate and permits reliable recording of the cerebral pulse curve or of the mean value for trend analysis.


Multiomics Approach Reveals an Important Role of BNIP3 in Myocardial Remodeling and the Pathogenesis of Heart Failure with Reduced Ejection Fraction.
Previous work showed a role of BNIP3 in myocardial remodeling and progression to HFrEF. We utilized a multiomics approach to unravel BNIP3-related molecular mechanisms in the pathogenesis of HFrEF. BNIP3 knockdown in HFrEF improved glycolysis, pyruvate metabolism, branched-chain amino acid catabolism, and oxidative phosphorylation, and restored endoplasmic reticulum (ER)-mitochondrial (mt) calcium and ion homeostasis. These effects of BNIP3 on cardiac metabolism were related to its interaction and downregulation, and/or phosphorylation, of specific mt-proteins involved in the aforementioned metabolic pathways, including the MICOS and SLC25A families of carrier proteins. BNIP3 affected ER-mt-calcium and ion homeostasis via its interaction-induced VDAC1 dimerization and modulation of VDAC1 phosphorylation at Ser104 and Ser241, and the downregulation of LETM1. At the ER level, BNIP3 interacted with the enzyme SERCA2a and the PKA signaling complex, leading to the downregulation of SERCA2a and PKA-mediated Ser16 phospholamban phosphorylation. Additionally, BNIP3 attenuated AMPK and PRKCE activity by modulating AMPK phosphorylation at Ser485/491 and Ser377 residues, and PRKCE phosphorylation at Thr521 and Thr710 residues. BNIP3 also interacted with sarcomeric, cytoskeletal, and cellular transcription and translation proteins, and affected their expression and/or phosphorylation. In conclusion, BNIP3 modulates multiple pathobiological processes and constitutes an attractive therapeutic target in HFrEF.


Hamiguitan Range: A sanctuary for native flora.
Hamiguitan Range is one of the wildlife sanctuaries in the Philippines having unique biodiversity resources that are at risk due to forest degradation and conversion of forested land to agriculture, shifting cultivation, and over-collection. Thus, it is the main concern of this research to identify and assess the endemic and endangered flora of Hamiguitan Range. Field reconnaissance and transect walk showed five vegetation types namely: agro-ecosystem, dipterocarp, montane, typical mossy and mossy-pygmy forests. Inventory of plant species revealed 163 endemic species, 35 threatened species, and 33 rare species. Assessment of plants also showed seven species as new record in Mindanao and one species as new record in the Philippines. Noteworthy is the discovery of Nepenthes micramphora, a new species of pitcher plant found in the high altitudes of Hamiguitan Range. This species is also considered site endemic, rare, and threatened. The result of the study also showed that the five vegetation types of Mt. Hamiguitan harbor a number of endangered, endemic, and rare species of plants. Thus, the result of this study would serve as basis for the formulation of policies for the protection and conservation of these species and their habitats before these plants become extinct.


Computationally predicting clinical drug combination efficacy with cancer cell line screens and independent drug action.
Evidence has recently emerged that many clinical cancer drug combinations may derive their efficacy from independent drug action (IDA), where patients only receive benefit from the single most effective drug in a drug combination. Here we present IDACombo, an IDA based method to predict the efficacy of drug combinations using monotherapy data from high-throughput cancer cell line screens. We show that IDACombo predictions closely agree with measured drug combination efficacies both in vitro (Pearson's correlation = 0.93 when comparing predicted efficacies to measured efficacies for >5000 combinations) and in a systematically selected set of clinical trials (accuracy > 84% for predicting statistically significant improvements in patient outcomes for 26 first line therapy trials). Finally, we demonstrate how IDACombo can be used to systematically prioritize combinations for development in specific cancer settings, providing a framework for quickly translating existing monotherapy cell line data into clinically meaningful predictions of drug combination efficacy.


Temporal and spatial differentiation characteristics of soil arsenic during the remediation process of Pteris vittata L. and Citrus reticulata Blanco intercropping.
The intercropping of hyperaccumulators and fruit trees has great application prospects owing to its environmental and economic benefits. However, the variation tendency and spatial distribution characteristics of pollutants in soil are unclear. A 19-month pot positioning experiment was conducted to clarify the spatio-temporal characteristics of arsenic (As) during Pteris vittata L.-Citrus reticulata Blanco intercropping process. The results showed that: (1) In the early stage, the solubilization of soil As by P. vittata was dominant. At 3 months, the water-soluble As in P. vittata rhizosphere soil increased by 19.4-55.4% compared with the initial state. In the later stage, the As extraction from soil by P. vittata was dominant. At 19 months, the water-soluble As in P. vittata rhizosphere soil decreased by 24.6-71.2% compared with the initial state. The water-soluble As in C. reticulata rhizosphere soil in intercropping, under the role of P. vittata, reached 1.75-2.35 times that of monoculture at 7 months, and was not significantly different from that of monoculture at 19 months. (2) The spatial distribution characteristics of soil As, affected by As-hyperaccumulation of P. vittata, showed that the As variability of intercropping and P. vittata monoculture was greater than that of C. reticulata monoculture. The area of P. vittata remediating soil was approximately 15 cm horizontally around its planting point and at least 25 cm vertically. (3) P. vittata-C. reticulata intercropping did not affect the phytoremediation efficiency and effectively reduced the risk of As pollution for C. reticulata. The As concentration in C. reticulata leaves of open intercropping decreased by 39.0-64.2% (early-maturity) and 25.6-59.1% (late-maturity) compared with that of monoculture, similar to that in clean soil. This study analyzed the As migration characteristics during P. vittata-C. reticulata intercropping through time and space and provides important theoretical support for the remediation and safe use of As-contaminated farmland.


Low-Pressure Sensitive Piezochromic Fluorescence Switching of Tetraphenylethylene-Anthraquinone.
Sensing of low-pressure signals is of great importance for cutting-edge technologies. Organic piezochromic molecules offer a promising library of pressure sensitive materials which can be tailor-designed toward specific requirements. However, very few examples of low-pressure sensitive piezochromic fluorescent molecules have been obtained till date, and the underlying mechanisms are still in its infancy. Herein, we report highly sensitive piezochromic fluorescent switching under low-pressure regimes (∼60 kPa) of tetraphenylethylene-anthraquinone (TPE-AQ) based on the controlled molecular design and polymorphic phase strategy. The influence of both intramolecular conformation effect and variations of intermolecular stacking modes on the piezochromic property of TPE-AQ is investigated. The underlying mechanism of the low-pressure sensitive piezochromic fluorescence switching is demonstrated to be closely related to the loosely packed molecular orientation, as confirmed by X-ray diffraction measurements combined with simulations. This work provides a way to design highly efficient pressure sensors based on organic molecular systems.


Transcriptome, bioaccumulation and toxicity analyses of earthworms (Eisenia fetida) affected by trifloxystrobin and trifloxystrobin acid.
As a promising fungicide, the potential environmental risk of trifloxystrobin (TFS) and its main metabolism trifloxystrobin acid (TFSA) in soil environment should be given special attention. The present study investigated the potential risks of TFS and TFSA in soil environment to earthworms (Eisenia fetida) through measuring several biomarkers. Residual analysis showed that TFSA was more stable than TFS in artificial soil with half-lives ranging from 138.6 to 231.0 d and 20.4-24.7 d, respectively. Additionally, the accumulation of TFS in earthworms increased in the beginning and then decreased from day 14, while that of TFSA continuously increased. At concentrations of 4.0 mg/kg and 10.0 mg/kg, the weight and lysosomal membrane stability of earthworms were reduced; however, the superoxide dismutase (SOD) activity, glutathione-S-transferase (GST) activity and malondialdehyde (MDA) content in earthworms were enhanced by TFS and TFSA. Moreover, the growth inhibition effect and the oxidative damage level induced by TFSA to earthworms were higher than those induced by TFS. The transcriptome analysis date indicated that the differentially expressed genes (DEGs) in both TFS and TFSA treatments were mainly enriched in ribosome pathway and lysosome pathway, finally affecting the protein synthesis and proteolysis in earthworms. The findings of the present study indicated that TFSA may pose a higher risk in the soil environment than TFS.


Diuretics. Clinical pharmacology and therapeutic use (Part II).
25 years have elapsed since the introduction of the first effective oral diuretic, chlorothiazide. Diuretics are now amongst the most widely prescribed drugs in clinical practice worldwide. Availability of these drugs has not only brought therapeutic benefit to countless numbers of patients but it has at the same time provided valuable research tools with which to investigate the functional behaviour of the kidney and other electrolyte-transporting tissues. Despite many remaining gaps in our knowledge of the biochemical processes involved in diuretic drug action, available compounds can be divided into 5 groups on the basis of their preferential effects on different segments of the nephron involved in tubular reabsorption of sodium chloride and water. Firstly, there is a heterogeneous group of chemicals that share the common property of powerful, short-lived diuretic effects that are complete within 4 to 6 hours. These agents act on the thick ascending limb of Henle's loop and are known as 'high ceiling' or 'loop' diuretics. The second group are the benzothiadiazines and their many related heterocyclic variants, all of which localise their effects to the early portion of the distal tubule. The third group comprises the potassium-sparing diuretics which act exclusively on the Na+-K+/H+ exchange mechanisms in the late distal tubule and cortical collecting duct. The action of drugs in groups 2 and 3 is prolonged to between 12 and 24 hours. The fourth group consists of diuretics that are chemically related to ethacrynic acid but have the unusual property of combining within the same molecule the property of saluresis and uricosuria. These compounds have actions, to different individual extents, in the proximal tubule, thick ascending limb, and early distal tubule and are known as 'polyvalent' diuretics. Finally, there is a mixed group of weak or adjunctive diuretics which includes the vasodilator xanthines such as aminophylline, and the osmotically active compounds such as mannitol. The metabolic consequences of continued diuretic usage are considered along with non-metabolic sequelae such as ototoxicity or interactions with other concurrent treatments. The relationships between the clinical benefits conferred and the potential harms generated by long term diuretic therapy are also discussed.


Prevalence of PD-L1 expression in head and neck squamous precancerous lesions: a systematic review and meta-analysis.
Studies concerning programmed death-ligand 1 (PD-L1) expression in precancerous lesions of head and neck (HN) region have shown variable results. We systematically reviewed the published evidence on PD-L1 expression in HN precancerous lesions. Of 1058 original articles, 14 were included in systematic review and 9 in meta-analysis. The pooled estimate of PD-L1 expression was 48.25% (confidence interval [CI] 21.07-75.98, I2 98%, tau2 0.18). PD-L1 expression appeared to be more frequent in precancerous lesions than in normal mucosa (risk ratio [RR] 1.65, CI 0.65-4.03, I2 91%, tau2 0.82) and less frequent than in invasive squamous cell carcinoma (RR 0.68, CI 0.43-1.08, I2 91%, tau2 0.22). PD-L1 expression could reflect a point of balance between host immune response and cancer escape ability. High heterogeneity and moderate quality suggest that further studies with larger sample size and more rigorous case selection will allow more precise assessment of PD-L1 expression in HN precancerous lesions.


The detection of non-random patterns of distribution of species along a gradient.
A simple method for detecting non-random patterns of distribution of the boundaries of species is described. The method uses transects running across a community, where the number of upper and lower boundaries of species in each quadrat is recorded. The expected number of quadrats containing one or more boundaries can be calculated from the binomial distribution. The mean deviation of observed from expected number of such quadrats, for a set of transects, can be tested for departures from zero. Significant departures greater than zero indicate regular dispersion of boundaries. A mean deviation significantly less than zero indicates clustering of the boundaries. The method is unbiased and thus corrects previously published methods.


Comparison of Hyperemic Impedance Echocardiography with Dobutamine Stress Echocardiography to Detect Inducible Myocardial Ischemia: A Pilot Study.
Stress echocardiography using exercise or pharmacological stressors is either contraindicated or associated with significant side effects in some patients. This pilot study was designed to evaluate a new technique, hyperemic impedance echocardiography (HIE). It is based on reactive coronary hyperemia when transient limb ischemia is induced by tourniquet inflation. We hypothesized that this physiologic coronary hyperemia can identify inducible myocardial ischemia by assessment of regional wall motion abnormalities on echocardiography when compared with dobutamine stress echocardiography (DSE). Twenty consecutive outpatients with suspected stable coronary artery disease (CAD) who underwent clinically indicated DSE were recruited for performance of HIE after informed consent was obtained. Standard graded dobutamine infusion protocol from 5 to 40 μg/kg per min was used for DSE. HIE was performed by inflating tourniquets at a pressure of 10 mmHg below the systolic blood pressure for 1 minute in three of four extremities at a time for total of four cycles. Echocardiography was performed immediately after the last rotating tourniquet deflation. DSE and HIE were classified as abnormal for development of new or worsening wall motion abnormality in at least one myocardial segment. Test characteristics were also determined for a subset of these patients (n = 12) who underwent clinically indicated coronary angiography. Hyperemic impedance echocardiography showed 86% sensitivity, 67% specificity, 86% positive predictive value, and 67% negative predictive value with a test accuracy of 80% to detect inducible myocardial wall motion abnormalities when compared with DSE. HIE also showed 83% sensitivity, 75% negative predictive value with a test accuracy of 66.7% for detection of significant (≥50% diameter stenosis) CAD on coronary angiography. In this pilot study, HIE was a feasible, safe, and promising method for detection of inducible myocardial ischemia by assessment of regional wall motion abnormalities when compared to DSE and coronary angiography. Larger studies are needed to confirm these findings.


Silicone glue coated stainless steel wire for solid phase microextraction.
A new solid phase microextraction (SPME) fiber based on high-temperature silicone glue coated on a stainless steel wire is presented. The fiber coating can be prepared easily in a few minutes, it is mechanically stable and exhibits relatively high thermal stability (up to 260 degrees C). The extraction properties of the fiber to benzene, toluene, ethylbenzene, and xylenes (BTEX) were examined using both direct and headspace SPME modes coupled to gas chromatography-flame ionization detection. The effects of the extraction and desorption parameters including extraction and desorption time, sampling and desorption temperature, and ionic strength on the extraction/desorption efficiency have been studied. For both headspace and direct SPME the calibration graphs were linear in the concentration range from 0.5 microg L(-1) to 10 mg L(-1) (R2>0.996) and detection limits ranged from 0.07 to 0.24 microg L(-1). Single fiber repeatability and fiber-to-fiber reproducibility were less than 6.8 and 21.5%, respectively. Finally, headspace SPME was applied to determine BTEX in petrol station waste waters with spiked recoveries in the range of 89.7-105.2%.


Fibroblast growth factor 21 attenuates hypoxia-induced pulmonary hypertension by upregulating PPARγ expression and suppressing inflammatory cytokine levels.
Hypoxia-induced pulmonary hypertension (HPH) is a progressive disease characterized by a sustained, elevated pulmonary arterial pressure and vascular remodeling. The latter pathogenesis mainly involves overproliferation of pulmonary artery smooth muscle cells (PASMCs). Fibroblast growth factor 21 (FGF21) has recently emerged as a novel regulator that prevents cardiac hypertrophic remodeling. However, its possible role in pulmonary remodeling remains unclear. The activation of peroxisome proliferator activated receptor γ (PPARγ) is reported to attenuate HPH by suppressing proliferative signals. Loss of PPARγ in the lung contributes to abnormal proliferation of PASMCs. FGF21 is a key regulator of PPARγ activity in adipocytes, but its role has not been elucidated in PASMCs. Therefore, we hypothesized that FGF21 may confer therapeutic effects in HPH by upregulating the expression of PPARγ. Sprague-Dawley rats were exposed to hypoxia and treated with FGF21 for 4 weeks. In parallel, hypoxic conditions and FGF21 were administered to rat PASMCs for 48 h. FGF21 attenuated the hypoxia-induced elevation in mean pulmonary arterial pressure (mPAP), right ventricular hypertrophy (RVH), medial thickening and overproliferation of PASMCs. Furthermore, FGF21 abrogated the reductions in PPARγ expression and increases in TNF-α, IL-1 and IL-6 levels in PASMC culture media. Collectively, these results demonstrate that FGF21 could potentially attenuate the pathogenic derangements of HPH by targeting PPARγ and inflammatory cytokines.


Isolation and characterization of a rice cDNA similar to the bovine brain-specific 14-3-3 protein gene.
We isolated a rice cDNA clone which is similar to the bovine brain-specific 14-3-3 protein (an activator protein of tyrosine and tryptophan hydroxylase involved in the synthetic pathway of monoamine) gene. The deduced amino acid sequence of the cDNA indicated a surprising similarity to a potent inhibitor of Ca(2+)-phospholipid-dependent protein kinase C. DNA blot analysis indicated that this gene is located at more than a single locus in rice genome DNA. Expression of this gene is regulated by external stresses.


Bilateral hand-assisted laparoscopic renal surgery in the supine position: the spleen at risk.
We evaluated the safety of simultaneous bilateral renal procedures performed using hand-assisted laparoscopy (HAL) with the patient in the supine position. After securely strapping the patient to the table, a hand-port device is placed via a 7-cm supraumbilical or peri-umbilical incision with two to four 5-mm to 12-mm trocars placed bilaterally. During a 3-year period, 8 bilateral HAL renal operations were initiated (upper pole partial nephrectomies, 3 nephroureterectomies, 3 bilateral nephrectomies, and right nephrectomy with left adrenalectomy). Mean patient age was 41 years. One patient with ADPKD required conversion to open due to failure to progress secondary to excessive perirenal fat and 22-cm kidneys. The other 7 were completed successfully with a mean operative time of 417 minutes and mean EBL of 336cc. Two patients received transfusions. Two small splenic lacerations, managed conservatively, were the only complications. Bilateral hand-assisted laparoscopic renal surgery with the patient in the supine position (rolling the table side to side) is feasible in the majority of patients. However, very large kidneys (eg, ADPKD) may be better approached with the patient in the lateral decubitus position or via an open subcostal incision. Importantly, the spleen appears to be at increased risk for capsular injury due to apparent increased difficulty of left colon mobilization in the "rolled" or "airplaned" supine position.


A novel cyclopentyl methyl ether electrolyte solvent with a unique solvation structure for subzero (-40 °C) lithium-ion batteries.
1 M LiFSI in cyclopentyl methyl ether is shown as a novel electrolyte with a unique solvation structure to form a thin robust multilayer solid electrolyte interface with an inorganic LiF-rich inner layer. Aggregates and contact ion pairs are actively formed in the solvation shell and reduced on the graphite anode during lithiation. This EC-free electrolyte provides 86.9% initial efficiency, and 355 mA h g-1 over 350 cycles with an excellent capacity retention of 84% at a 1C rate. An excellent low-temperature performance of 370, 337, and 330 mA h g-1 at 0, -10, and -20 °C, respectively, at a 0.1C rate is recorded. Furthermore, at -40 °C, the graphite half-cell has a capacity of 274 mA h g-1 without electrolyte freezing.


Y2 receptor proteins for peptide YY and neuropeptide Y. Characterization as N-linked complex glycoproteins.
Affinity labeling using [125I-Tyr36]PYY and homobifunctional affinity crosslinking reagents of the rabbit Y2 receptor for peptide YY(PYY) results in specifically labeled proteins of both M(r) = 50,000 to 60,000 and M(r) = 96,000 to 115,000 [1,2]. In this work the glycoprotein nature of affinity labeled Y2 receptor proteins were investigated by enzymatic deglycosylation using neuraminidase, endoglycosidase F (endo F), N-glycosidase F (PNGase F), and O-glycanase treatment. Only N-glycosidase F and neuraminidase increased the electrophoretic mobility of the radiolabeled receptor bands, whereas all other glycosidases did not. PNGase F treatment of both radiolabeled receptor bands electroeluted from gel slices reduced the apparent molecular mass of by 16-17 kDa units, that is M(r) = 96,000 to 79,000 and M(r) = 60,000 to 44,000, indicating removal of N-linked oligosaccharide chains of similar size from both species. Neuraminidase treatment caused slight increases in the electrophoretic mobilities suggesting the presence of terminal sialic residues. It is concluded that the Y2 binding proteins are N-linked complex (sialo)glycoproteins with a minimal core protein size of M(r) = 44,000. Furthermore, based on this sensitivity pattern of the glycosidases, the Asn-linked carbohydrate may be of the tri- or tetra-antennary complex type containing terminal sialic acid residues.


The treatment of gastric cancer with combined surgical resection and chemotherapy.
A series of 156 patients with gastric cancer during a 15-year period were reviewed retrospectively to determine the effectiveness of combined surgery and adjuvant chemotherapy. The patients were divided into a 9-year prechemotherapy period and a 6-year chemotherapy period. Review of the data revealed an increase in the incidence of distant disease. The utilization of surgery as the only mode of treatment declined. Combination surgery and adjuvant chemotherapy utilization increased. Comparison of survival for surgery vs. adjuvant chemotherapy, expressed as percentage of survivors for each year, revealed an increase at 1 and 2 years with no difference at 3 years for all stages. A similar comparison for patients with regional spread showed an increase at 1,2 and 3 years with no difference therafter. The 5-year survival was 5% for both groups. The data has suggested that surgery and adjuvant chemotherapy increases 1-,2-, and 3-year survival rates but does not affect the longterm results.


Synthesis and biological evaluation of N-(aryl)-2-thiophen-2-ylacetamides series as a new class of antitubercular agents.
The present article describes a series of 21 N-(aryl)-2-thiophen-2-ylacetamides, which were synthesized and evaluated for their in vitro antibacterial activity against Mycobacterium tuberculosis, and the activity expressed as the minimum inhibitory concentration (MIC) in mug/mL. The compounds 2, 3, 7, 8, 11, 12, 15, 16, and 20 exhibited activity between 25 and 100 microg/mL and could be a good start point to find new lead compounds in the fight against multidrug resistant tuberculosis.


Intracellular lipid droplets in functioning transitional parathyroid oxyphil adenomas. A caveat.
Histochemical demonstration of intracellular lipid droplets on frozen section has been used to distinguish normal parathyroid tissue from that of adenoma and chief cell hyperplasia. Differentiation is based on the observation that the cells of adenoma and chief-cell hyperplasia largely lack intracellular lipid, which is present in the suppressed chief cells of normal glands in patients with adenoma. We present two functional transitional oxyphil adenomas that contained abundant intracellular lipid. Failure to recognize that transitional oxyphilic adenomas may contain focal accumulation of intracellular lipid droplets could lead to confusion in histologic interpretation.


Hypomania: a depressive inhibition override defense mechanism.
Evolutionary perspectives on bipolar disorders can further our understanding of the origins of these conditions, and assist clinicians in distinguishing normal from abnormal states. Hypomania is unique amongst bipolar conditions in that it seems to have beneficial aspects and can be difficult to diagnose, in contrast to full-blown mania and depression. A theoretical perspective regarding the evolution of hypomania as a defense mechanism is presented. Literature review focused on the fitness reducing aspects of depression and the fitness enhancing aspects of hypomania/mania. Of all the adversity inherent in depression, inhibition of physical and mental activity-depressive inhibition-has the most detrimental consequences, and throughout our evolution would have significantly reduced fitness. It is proposed that hypomania evolved as a depressive inhibition override defense mechanism, typically operating in a short-term time frame, to restore physical and mental activity to fitness sustaining or enhancing levels. Over-activity and not mood enhancement enabled hypomania to function as a defense mechanism against the fitness reducing state of depressive inhibition. Contributing to depressive inhibition are the Behavioral Activation System (BAS) and the Behavioral Inhibition System (BIS), two basic motivational systems. Depressive inhibition consists to some extent of low BAS and high BIS. As human intelligence evolved cognitions inhibiting BAS and activating BIS became amplified, resulting in intensified depressive inhibition. A theoretical perspective. Given its ability to override depressive inhibition hypomania might be viewed as a natural treatment as opposed to a problem to treat, producing maximal improvement in areas where functioning has suffered the most while typically enhancing social behavior.


Breast cancer vascularity: color Doppler sonography and histopathology study.
In this prospective study, the authors examined 50 patients with breast tumors (malignant, n = 32; benign, n = 18) to investigate the correlation between color Doppler flow mapping and histopathological findings and to evaluate the clinical significance of color Doppler mapping. Among the 32 patients with breast cancer, color Doppler signals were detected in 24 patients (75%). The maximum flow velocities varied from 5 to 34 cm/sec, with 16 (67%) of them above 15 cm/sec. Among the 18 patients with benign tumors, color Doppler signals could be detected in 7 (39%). The maximum flow velocity varied from 3 to 30 cm/sec but was over 15 cm/sec in only two patients (28%). Histological studies revealed that color Doppler signals detected by Doppler sonography correlated with disordered neovascularization penetrating the lesion from its periphery, consisting of thin-walled blood vessels and large arteriovenous shunts. Although large tumors tend to have high Doppler flow, there is no significant correlation between the maximum flow velocity and tumor size. There is also no significant correlation between the detection of high flow color Doppler signals and the age, receptor status, tumor size, lymph node metastases, or clinical stage of patients with breast cancer. However, there is a positive association (p < 0.05) between nodal metastases and higher tumor flow velocity in T1 (< or = 2 cm) breast tumors, but not in larger tumors. It is concluded that color Doppler is useful in the assessment of tumor vascularity but is of limited value in the differentiation of benign from malignant lesions. However, the presence of color Doppler signals in T1 breast cancer suggesting early dissemination of the cancer might be of important clinical significance in detecting those small, apparently early, but aggressive tumors with poor prognosis.


Coding of signals in noise by amphibian auditory nerve fibers.
Rate-level (R-L) functions derived for pure-tones and pure-tones in broadband noise were obtained for auditory nerve fibers in the treefrog, Eleutherodactylus coqui. Normalized R-L functions for low-frequency, low-threshold fibers exhibit a horizontal rightward shift in the presence of broadband background noise. The magnitude of this shift is directly proportional to the noise spectrum level, and inversely proportional to the fiber's threshold. R-L functions for mid- and high-frequency fibers also show a horizontal shift, but to a lesser degree, consistent with their elevated thresholds relative to the low-frequency fibers. The implications of these findings for the processing of biologically significant sounds in the high levels of background noise in the animal's natural habitat are considered.


Chronic obstructive pulmonary disease prevalence among nonsmokers by occupation in the United States.
To examine the prevalence of chronic obstructive pulmonary disease (COPD) among nonsmokers by occupation in the United States. The 1997 to 2004 National Health Interview Survey data for working adults aged 25 years or more were used to estimate the COPD prevalence and to examine change in COPD prevalence between 1997 to 2000 and 2001 to 2004 by occupational groups. During 1997 to 2004, COPD prevalence was 2.8%. The COPD prevalence was highest in financial records processing (4.6%) occupations. There was a slight increase in COPD prevalence during the two survey periods from 2.8% during 1997 to 2000 compared with 2.9% during 2001 to 2004. No significant changes in the COPD prevalence between the two periods were found. Nevertheless, the elevated COPD prevalence in certain occupational groups suggests that other risk factors play a role in developing COPD.


Clinical features of SMARCA2 duplication overlap with Coffin-Siris syndrome.
Coffin-Siris syndrome is a rare congenital malformation and intellectual disability syndrome. Mutations in at least seven genes have been identified. Here, we performed copy number analysis in 37 patients with features of CSS in whom no causative mutations were identified by exome sequencing. We identified a patient with a 9p24.3-p22.2 duplication and another patient with the chromosome der(6)t(6;9)(p25;p21)mat. Both patients share a duplicated 15.8-Mb region containing 46 protein coding genes, including SMARCA2. Dominant negative effects of SMARCA2 mutations may contribute to Nicolaides-Baraitser syndrome. We conclude that their features better resemble Coffin-Siris syndrome, rather than Nicolaides-Baraitser syndrome and that these features likely arise from SMARCA2 over-dosage. Pure 9p duplications (not caused by unbalanced translocations) are rare. Copy number analysis in patients with features that overlap with Coffin-Siris syndrome is recommended to further determine their genetic aspects. © 2016 Wiley Periodicals, Inc.


Paeoniflorin drives the immunomodulatory effects of mesenchymal stem cells by regulating Th1/Th2 cytokines in oral lichen planus.
Lichen planus (LP) is a chronic inflammatory disease. Oral lichen planus (OLP) mainly appears as oral mucosal reticular or ulcerative lesions with an unknown etiology. We aimed to explore the immunomodulatory effect of paeoniflorin (PF) in mesenchymal stem cells (MSCs) and the potential involvement of Th1/Th2 cytokines in OLP. The effects of paeoniflorin on the proliferation and migration of MSCs were detected by Cell Counting Kit-8 (CCK8) and Transwell assays. MSCs were subjected to osteogenic, adipogenic and neurogenic induction followed by Alizarin red, oil red O, real-time PCR and immunofluorescence assays. We found that paeoniflorin promoted the proliferation, migration and multilineage differentiation of MSCs from OLP lesions (OLP-MSCs) in vitro. Paeoniflorin pretreatment increased the inhibitory effect of OLP-MSCs on peripheral blood mononuclear cells. Furthermore, paeoniflorin-pretreated OLP-MSCs simultaneously decreased Th1 cytokine levels and increased Th2 cytokine levels in T lymphocyte cocultures. Finally, paeoniflorin-pretreated OLP-MSCs also promoted the Th1/Th2 balance both in vitro and in the serum of mice that received skin allografts. In conclusion, paeoniflorin enhanced MSC immunomodulation and changed the inflammatory microenvironment via T lymphocytes, suggesting that the improvement of OLP-MSCs is a promising therapeutic approach for OLP.


Regional differences in the control of lipolysis in human adipose tissue.
Omental fat cells were 30% smaller than those in subcutaneous regions. In omental fat cells with a mean diameter of 95 mu, the basal cAMP concentration was 50% lower, but the basal rate of glycerol release was three times as rapid as in subcutaneous (epigastric) fat cells of identical size. Added at maximal effective concentration, noradrenaline increased the level of cAMP and the rate of glycerol release more markedly in the omental than in the subcutaneous adipocytes, whereas the response to isopropyl noradrenaline was similar. Before starvation the lipolytic effects of noradrenaline and isopropyl noradrenaline, respectively, were identical in the two regions of subcutaneous adipose tissue investigated (femoral and hypogastric). The findings were well related to the tissue levels of cAMP induced by the two agents. During starvation noradrenaline and isopropyl noradrenaline increased the cAMP level and the rate of lipolysis in fat cells obtained from the hypogastric region, whereas noradrenaline decreased these parameters in femoral adipocytes. Starvation was associated with a more prominent inhibitory effect of phenylephrine on basal and isopropyl-noradrenaline-induced lipolysis in femoral than in hypogastric adipose tissue. In conclusion, differences exist between different regions of adipose tissue in their lipolytic responsiveness to noradrenaline, which seems related to the balance between alpha- and beta-adrenergic receptor response.


Residual micro-stress distributions in heat-pressed ceramic on zirconia and porcelain-fused to metal systems: Analysis by FIB-DIC ring-core method and correlation with fracture toughness.
The production of fixed partial dentures (FPDs) induces complex residual stress profiles, due to both the thermal expansion coefficient mismatch between the veneering ceramic and the framework and to the thermal gradients occurring during the final cooling. Detailed knowledge of residual stress distributions in the veneering ceramics is important to understand the interface phenomena with the framework and the consequences of the different firing systems. The first objective of this study was to analyse the residual stress distribution in heat-pressed ceramic on zirconia core with micrometer spatial resolution, with also a focus on the stress at the interface versus porcelain-fused-to-metal samples. The second purpose was to correlate the residual stress with the fracture toughness. The micron-scale focused ion beam (FIB) ring-core method was used to map the residual stress over the cross-sections of the veneering ceramics. The methodology is based on FIB micro-milling of annular trenches, combined with high-resolution in situ scanning electron microscope (SEM) imaging, a full field strain analysis by digital image correlation (DIC) and numerical models for residual stress calculation. Fracture toughness was evaluated by using high load Vickers indentation and hardness/modulus were measured by nanoindentation testing also across the interfaces. Both prosthetic systems showed a compressive stress at the ceramic surface on a micron-scale. The stress profile for porcelain fused to metal (PFM) showed a transition to tensile stress at the half of the layer, whilst the stress in proximity of the interface was more compressive in both the cases. Residual stress on a micron scale are higher in magnitude than the corresponding macro-scale values reported in the literature, due to the stress relaxation given, at larger scales, by micro-voids and cracks. The stress field was directly correlated with the indentation fracture toughness, which was higher in those areas where the compressive stress is greater. Stress analysis in correspondence of interfacial porosity for the zirconia sample also showed that micro-defects could induce local modifications of the residual stress field, which may even locally generate a tensile stress state. The interfacial stress in dental systems was analysed on a micron scale and can give further insights into the process/property/performance correlation for this class of materials. In particular, interfacial and/or local modifications of the residual stress are expected to have a significant influence on crack nucleation mechanism in correspondence of micro-defects. A direct correlation between residual stress distribution and fracture toughness was proposed. It is noteworthy that the method can be used to study real crowns and bridges. In fact, complex geometries can be easily analysed by this procedure.


Efficacy of bilateral thoracoscopic sympathectomy in a patient with catecholaminergic polymorphic ventricular tachycardia.
A 27-year-old woman with frequent implantable cardioverter defibrillator (ICD) shocks related to catecholaminergic polymorphic ventricular tachycardia (VT) experienced aborted sudden death due to incessant polymorphic VT despite the administration of beta-blockers, verapamil, and flecainide. Catheter ablation failed to suppress the polymorphic VT. Based on the temporary efficacy of the local anesthetic administered at the left and right cervical sympathetic nerves to suppress VT under an isoproterenol infusion, stepwise, bilateral thoracoscopic sympathectomy was performed. Postoperatively, no further VT or syncopal episodes were documented under ICD telemetry. Bilateral thoracoscopic sympathectomy may be an alternative for patients with drug-refractory catecholaminergic polymorphic VT.


Frequency of cervical smear-tests among patients of general practitioners.
Eight hundred and thirty-eight women who attended 36 general practitioners were asked when they had last undergone a cervical smear-test. Only 6% of women who were between 25 and 54 years of age had never undergone a smear-test, but in women who were younger and older than this age range the proportion was one-third. We estimated from this pattern of use of cervical smear-tests that only 60% of invasive cervical cancer is being prevented, and the major contribution to the remaining risk factors comes from women of over 55 years of age who either have not undergone a smear-test or had undergone one a long time previously. This information suggests that general practitioners and the public-health system should be more active in ensuring that all at-risk women undergo cervical smear-tests.


Peroxidase activity in human alveolar macrophages demonstrated by 3-amino-9-ethyl-carbazol as substrate.
Airdried smears of routine sputa, bronchial secretions, and bronchus lavages were incubated to demonstrate peroxidase activity in the alveolar macrophages, with 3-amino-9-ethyl-carbazol as substrate. In light microscopic examination two deposition patterns of reaction product could be found: Reaction product only to be found on, resp. in the nuclear membrane; Reaction product deposited in granules throughout the cytoplasm, some cells being totally loaded. However, most of the alveolar macrophages did not show any peroxidase activity. Thus the population of alveolar macrophages comprises resident and exudate forms.


Prefascial marsupialization of the pregnant uterus.
A case report is presented of a white woman, gravida 4, para 2, abortus 1, who experienced protrusion of a gravid uterus through the anterior rectus fascia. The uterus subsequently became entrapped and was reduced only after cesarean section at 34 weeks' gestation.


Biology of plasma cells.
Multiple myeloma, the second most common haematopoietic cancer, represents a collection of plasma-cell neoplasms that invariably become fatal when self-renewing myeloma cells begin unrestrained proliferation. Myeloma cells are arrested as intermediates in plasma-cell differentiation as a consequence of transformation. Unlike normal plasma cells, myeloma cells retain the self-renewing potential. Although impaired apoptosis accounts for the accumulation of myeloma cells in the bone marrow during the plateau phase of the disease, cell-cycle deregulation underlies unrestrained proliferation of self-renewing myeloma cells in aggressive myelomas and during relapse. The mechanism that governs deregulated cell-cycle re-entry and progression in multiple myeloma is unknown, and the relationship between myeloma cells and their normal counterparts is undefined. Plasma-cell differentiation is a complex multi-step process. This chapter will address recent advances in the mechanism of normal plasma-cell differentiation and our current understanding of the relationship between plasma-cell differentiation and myeloma pathogenesis.


Soft tissue sarcoma: advances in understanding and management.
Soft tissue sarcomas are a rare group of neoplasms readily dispersed throughout the body with different histopathologies and different outcomes. The present review summarizes advances made in biology, distribution and natural history, and emphasises predictive models for outcome. Complete resection remains the major factor in providing cure, with limited benefits in the control of the local disease by radiation therapy and only minimal benefit of systemic therapy for metastatic disease. Identification of targeted therapy utilising direct specific molecular targets raises hope that future progress in control, if not cure, is realistic.


National trends in ideal cardiovascular health among adults in Bhutan from three cross-sectional surveys in 2007, 2014, and 2019.
The study aimed to estimate the prevalence, distribution, and correlates of ideal cardiovascular health (CVH) among individuals (20-69 years) across three cross-sectional surveys in 2007, 2014 and 2019 in Bhutan. Cross-sectional data were analysed from 9712 individuals (20-69 years, mean age = 37.6 years) who participated in the 2007, 2014 or 2019 Bhutan STEPS surveys, had complete measurement of CVH metrics, and had no history of a cardiovascular disease in 2014 and 2019. Ideal CVH measures included non-smoking, healthy diet, physical activity, body mass index (< 23 kg/m2), blood pressure < 120/ < 80 mmHg, total cholesterol < 200 mg/dL, and fasting blood glucose < 100 mg/dL). The prevalence of five to seven ideal CVH metrics increased from 11.6% in 2007 to 37.9% in 2019. Trend analyses showed that ideal physical activity, ideal total cholesterol, ideal blood pressure, and ideal fasting glucose increased from 2007 to 2019, while ideal fruit and vegetable intake, ideal smoking, and ideal body mass index decreased from 2007 to 2019. Five to seven ideal CVH metrics, 0-7 ideal CVH metrics, and 0-14 poor, intermediate, and ideal CVH metrics increased from 2007 to 2019. In the adjusted logistic regression analysis, older age decreased the odds of having 5-7 ideal CVH metrics in all three study years. Male sex increased the odds, and employment decreased the odds of 5-7 ideal CVH metrics in 2007, and urban residence increased the odds of 5-7 ideal CVH metrics in 2014 and decreased the odds in 2019. The proportion of meeting 5-7 ideal CVH metrics increased in Bhutan. Primary and secondary prevention programmes must be strengthened to improve CVH in Bhutan, considering identified associated factors.


Multidrug-resistant organisms in a community living facility: tracking patient interactions and time spent in common areas.
Contact precautions in community living facilities (CLF) are used to reduce the transmission of multidrug-resistant organisms (MDRO). However, this policy does not address the contamination of shared spaces, devices (eg, wheelchairs), and interactions with other patients. Using a real-time surveillance system, this study examines the time MDRO-positive patients spend interacting with others in communal areas. The findings from this study may be used to tailor MDRO policies and practices to the specific needs of CLF.


Dihydrothiamine-like substances as experimental artefacts.
Experimental controls have shown that the dihydrothiamine-like substance previously reported as isolated from animal tissues was an artefact. In addition, no evidence is found for the reduction of thiamine by NADH.


Motion sickness and postoperative vomiting in children.
Motion sickness is considered an important risk factor for postoperative nausea and vomiting in children. The aim of this study was to verify the impact of motion sickness on the incidence of vomiting after routine surgery in children, and to compare the incidence of vomiting, after combined regional/general anaesthesia, using either halothane or sevoflurane. We prospectively studied 420 children (369 males and 51 females) who received general anaesthesia and inguinal field block for common paediatric surgery. The children were randomly allocated into one of two groups (halothane or sevoflurane). In the 200 children in the first group (H), general anaesthesia was induced and maintained with halothane, whereas in the 220 children in the second group (S), anaesthesia was induced and maintained with sevoflurane. There were 79 children with a prior history of motion sickness (MS+) and 341 without such a history (MS-). In the MS+ population, the incidence of vomiting was similar in both H and S groups, being around 33%. However, repeated episodes of vomiting in MS+ children were more frequent when halothane was used. In the MS- group, the incidence of vomiting was significantly greater in the H group (19%) than in the S group (8%). In the postoperative period, we found that MS+ children vomit more than MS- children, regardless of the inhalation anaesthetic used. However, MS- children displayed a higher incidence of vomiting when halothane was used rather than sevoflurane.


Predischarge postpartum methicillin resistant Staphylococcus aureus infection and group B streptococcus carriage at the individual and hospital levels.
We sought to characterize the relationship between individual group B streptococcus (GBS) colonization and pre-discharge postpartum methicillin resistant Staphylococcus aureus (MRSA) infection in United States women delivering at term. We also sought to examine the association between hospital GBS colonization prevalence and MRSA infection. Data was from the Nationwide Inpatient Sample, a representative sample of United States community hospitals. Hierarchical regression models were used to estimate odds ratios adjusted for patient age, race, expected payer, and prepregnancy diabetes and hospital teaching status, urbanicity, ownership, size, and geographic region. We used multiple imputation for missing covariate data. There were 3,136,595 deliveries and 462 cases of MRSA infection included in this study. The odds ratio for individual GBS colonization was 1.2 (95% confidence interval: 0.9 to 1.5). For a five-percent increase in the hospital prevalence of GBS colonization, the odds ratio was 0.9 (95% CI: 0.1 to 5.6). The odds ratio estimate for the association of hospital GBS prevalence with MRSA infection is too imprecise to make conclusions about its magnitude and direction. Barring major bias in our estimates, individual GBS carriage does not appear to be strongly associated with predischarge postpartum MRSA infection.


Kinetics of lactose hydrolysis and galactooligosaccharides formation in beverages based on goat's milk and its permeate.
The aim of this work was the analysis of galactooligosaccharides (GOS) formation in a model mixture of goat's milk and its permeate from microfiltration and further concentration by ultrafiltration based on the hydrolysis and transgalactosylation of lactose under various temperature and time regimes. These reactions were catalyzed by a β-galactosidase from Kluyveromyces lactis. Simultaneous hydrolysis and transgalactosylation of the milk lactose was carried out at 37, 40, and 43 °C for 6 h. The maximum GOS content in the mixture was obtained at 37 °C after 20 min. It was 6.9% of the total sugars and the degree of lactose hydrolysis was 13.3%. This was about 10% more GOS than in milk. The mixture containing GOS had a faster maximum acidification rate, 33% greater than before transgalactosylation.


p16, p14, p53, cyclin D1, and steroid hormone receptor expression and human papillomaviruses analysis in primary squamous cell carcinoma of the endometrium.
Pathogenetically, endometrioid adenocarcinomas of the endometrium are associated with hyperestrogenism and serous papillary carcinomas with alterations of p53. The etiology of primary endometrial squamous cell carcinoma (ESCC), however, is speculative. The purpose of this study was to evaluate the role of p14, p16, p53, cyclin D1, steroid hormone receptors, and human papillomaviruses (HPV) infection in the pathogenesis of primary endometrial squamous cell carcinoma. The expression of p16, p14, p53, cyclin D1, and steroid hormone receptors (estrogen, progesterone, and androgen) was examined immunohistochemically in 8 primary ESCCs. HPV analysis was performed using general primers and HPV typing. The median age of the patients was 62.1 years. Four cases showed positive nuclear and cytoplasmic p16 staining in an insular pattern, and 1 case nuclear positivity for p53 and estrogen receptors, respectively. Four of 8 cases were positive for progesterone receptor analysis and cyclin D1. All cases were negative for p14 and androgen receptor staining. All but one case were negative for HPV analysis. Five patients were alive with and without evidence of disease after a mean follow-up of 6.1 years. The results of this study suggest that alterations of the p16 pathway may play an etiologic role in at least a proportion of the ESCC, but without any association to HPV infection. Factors known to play a pathogenetic role in types 1 and 2 of endometrial carcinomas are not associated with primary ESCC. However, prognostically, ESCCs are more related to type 1 cancers.


NRF2 drives an oxidative stress response predictive of breast cancer.
Many breast cancer patients are diagnosed with small, well-differentiated, hormone receptor-positive tumors. Risk of relapse is not easily identified in these patients, resulting in overtreatment. To identify metastasis-related gene expression patterns, we compared the transcriptomes of the non-metastatic 67NR and metastatic 66cl4 cell lines from the murine 4T1 mammary tumor model. The transcription factor nuclear factor, erythroid 2-like 2 (NRF2, encoded by NFE2L2) was constitutively activated in the metastatic cells and tumors, and correspondingly a subset of established NRF2-regulated genes was also upregulated. Depletion of NRF2 increased basal levels of reactive oxygen species (ROS) and severely reduced ability to form primary tumors and lung metastases. Consistently, a set of NRF2-controlled genes was elevated in breast cancer biopsies. Sixteen of these were combined into a gene expression signature that significantly improves the PAM50 ROR score, and is an independent, strong predictor of prognosis, even in hormone receptor-positive tumors.


Relations of left ventricular mass and systolic function to endothelial function and coronary flow reserve in healthy, new discovered hypertensive subjects.
Left ventricular hypertrophy (LVH) is prognostically relevant, associated with major cardiovascular risk factors and with atherosclerosis. However, whether LVH is independently associated with impaired coronary flow reserve (CFR) and with endothelial dysfunction is disputed. We assessed the relationship of LV mass and systolic function to CFR and endothelial function in new discovered never treated subjects with essential arterial hypertension, but without coronary artery disease or microalbuminuria. LVH, ejection fraction (EF) and stress-corrected midwall shortening (MWS, a measure of myocardial contractility) were assessed by echocardiography. CFR was assessed by single-photon emission computed tomography and dipyridamole infusion. Endothelial function was evaluated by assessing 1-min postischaemic flow-mediated dilatation of the brachial artery (FMD); nitroglycerine-mediated dilatation (NMD) of the same brachial artery was used as measure of nonendothelium-dependent vasodilatation. In approximately 1 year, we enrolled 21 subjects who met stringent inclusion criteria (47+/-10 years old, 26.6+/-2.8 kg/m2, 78% men). Five patients showed LVH. Multivariate analyses showed a significant negative correlation of LV mass index with FMD (beta=-0.61, P<0.05) but not with NMD, neither with CFR. Stress-corrected MWS showed independent correlation with CFR (beta=0.51, P<0.05). Thus, in clinically healthy, new discovered hypertensive subjects, never treated and mostly in the early stage of arterial hypertension, LVH can be associated with endothelial dysfunction while maximal dipyridamole- dependent CFR may be preserved; nevertheless, a cardiac phenotype presenting with tendency to impaired myocardial contractility, assessed by stress-corrected MWS, showed association with lower CFR in the early stage of arterial hypertension.


Emerging biotechnology applications in natural product and synthetic pharmaceutical analyses.
Pharmaceutical analysis is a discipline based on chemical, physical, biological, and information technologies. At present, biotechnological analysis is a short branch in pharmaceutical analysis; however, bioanalysis is the basis and an important part of medicine. Biotechnological approaches can provide information on biological activity and even clinical efficacy and safety, which are important characteristics of drug quality. Because of their advantages in reflecting the overall biological effects or functions of drugs and providing visual and intuitive results, some biotechnological analysis methods have been gradually applied to pharmaceutical analysis from raw material to manufacturing and final product analysis, including DNA super-barcoding, DNA-based rapid detection, multiplex ligation-dependent probe amplification, hyperspectral imaging combined with artificial intelligence, 3D biologically printed organoids, omics-based artificial intelligence, microfluidic chips, organ-on-a-chip, signal transduction pathway-related reporter gene assays, and the zebrafish thrombosis model. The applications of these emerging biotechniques in pharmaceutical analysis have been discussed in this review.


Improving the physical diagnosis skills of third-year medical students: a controlled trial of a literature-based curriculum.
To determine if a literature-based physical diagnosis curriculum could improve student knowledge, skill, and self-confidence in physical diagnosis. Prospective controlled trial of an educational intervention. Required internal medicine clerkship for third-year medical students at Brown Medical School. Third-year medical students who completed the internal medicine clerkship during the academic year 1999-2000: 32 students at 1 clerkship site received the intervention; a total of 50 students at 3 other clerkship sites served as controls. Physical diagnosis curriculum based on 8 articles from the Journal of the American Medical Association's Rational Clinical Examination series. Intervention students met weekly for 1 hour with a preceptor to review each article, discuss the sensitivity and specificity of the maneuvers and findings, and practice the techniques with an inpatient who agreed to be visited and examined. Physical diagnosis knowledge for the 8 topics was evaluated using a 22-item multiple choice question quiz, skill was evaluated using trained evaluators, and self-confidence was assessed using an end-of-clerkship survey. Intervention students scored significantly higher than the control group on the knowledge quiz (mean correct score 70% vs 63%, P =.002), skills assessment (mean correct score 90% vs 54%, P <.001), and self-confidence score (mean total score 40 vs 35, P =.003), and they expressed greater satisfaction with the physical diagnosis teaching they received in the clerkship. This physical diagnosis curriculum was successful in improving students' knowledge, skill, and self-confidence in physical diagnosis.


Antiinflammatory and antioxidant activity of Hypericum rumeliacum Boiss. subsp. apollinis (Boiss. & Heldr.) Robson & Strid methanol extract.
Plants of the genus Hypericum are widely used in folk medicine for the treatment of gastric ailments (including pectic ulcers), burns, swelling, inflammation, anxiety, as well as for bacterial and viral infections. The aerial parts of Hypericum rumeliacum Boiss. subsp. apollinis (Boiss. & Heldr.) Robson & Strid (Guttiferae), a perennial herb growing wild in Greece, were subjected to biological and phytochemical studies. The H. rumeliacum methanol extract showed, on the DPPH test, antioxidant activity (IC(50) = 23.61 microg/mL). The antiinflammatory activity of the extract (70 mg/kg, i.p.), in the carrageenan-induced paw oedema in rat, was studied. In this experimental model an inhibition of paw oedema, significant from the first to third hour, was observed. The histological examination confirmed resolution of the inflammatory process observed in vivo. Through HPLC analysis of the H. rumeliacum methanol extract, the naphthodianthrones hypericin, pseudohypericin and some polyphenol compounds, such as chlorogenic acid, rutin and isoquercitrin, were identified and quantified. The antioxidant activity of H. rumeliacum could be chiefly related to polyphenol compounds that are well known as the main contributors to the free radical-scavenging effects. The antiinflammatory effect of the methanol extract of the aerial parts could be due to the synergic action both of hypericin and polyphenol compounds.


Calibration of methylene-referenced lipid-dissolved xenon frequency for absolute MR temperature measurements.
Absolute MR temperature measurements are currently difficult because they require precalibration procedures specific for tissue types and conditions. Reference of the lipid-dissolved 129 Xe resonance frequency to temperature-insensitive methylene protons (rLDX) has been proposed to remove the effect of macro- and microscopic susceptibility gradients to obtain absolute temperature information. The scope of this work is to evaluate the rLDX chemical shift (CS) dependence on lipid composition to estimate the precision of absolute temperature measurements in lipids. Neat triglycerides, vegetable oils, and samples of freshly excised human and rodent adipose tissue (AT) are prepared under 129 Xe atmosphere and studied using high-resolution NMR. The rLDX CS is measured as a function of temperature. 1 H spectra are also acquired and the consistency of methylene-referenced water proton and rLDX CS values are compared in human AT. Although rLDX CS shows a dependence on lipid composition, in human and rodent AT samples the rLDX shows consistent CS values with a similar temperature dependence (-0.2058 ± 0.0010) ppm/°C × T (°C) + (200.15 ± 0.03) ppm, enabling absolute temperature measurements with an accuracy of 0.3°C. Methylene-referenced water CS values present variations of up to 4°C, even under well-controlled conditions. The rLDX can be used to obtain accurate absolute temperature measurements in AT, opening new opportunities for hyperpolarized 129 Xe MR to measure tissue absolute temperature.


Disseminated subcutaneous nocardiosis caused by Nocardia farcinica diagnosed by FNA biopsy and 16S ribosomal gene sequencing.
Nocardia is an infrequent but significant cause of infections in the immunocompromised host. Clinical syndromes are varied and ranges from pulmonary, disseminated, cutaneous, and CNS involvement. Here we describe a case of disseminated subcutaneous nodules in a patient with multiple myeloma caused by Nocardia farcinica. The diagnosis was made by FNA biopsy which revealed gram positive filamentous bacilli in background of acute inflammation on smears. This was confirmed by 16S ribosomal gene sequencing. Prompt identification of N. farcinica is important because of its intrinsic resistance to broad spectrum cephalosporins and high risk of dissemination.


[Psychological factors following ankle fractures : A review article].
Ankle fractures have many short and long-term consequences for patients. For this reason, psychosocial factors also play a role in the success of the treatment in addition to the surgical treatment. The aim of this article is to give an overview of the psychological aspects in the context of fractures as well as explanatory models for the different ways of coping. In addition, an overview of the empirical data with respect to psychological influences and outcome factors in lower extremity fractures, specifically ankle fractures, is given. The current research indicates that psychosocial factors have a decisive influence on the physical and psychological outcome.


A new coagglutination test for detecting pneumococcal C-polysaccharide.
A new coagglutination test (PnC-CoA) for detecting pneumococcal C-polysaccharide (PnC) was compared with a commercial kit for detecting capsular polysaccharide using sputum samples from 105 patients with pneumonia. The sensitivity obtained with PnC-CoA was 95.8% and with the commercial kit 83.3%; the specificity was 96.5% and 91.2%, respectively. The PnC-CoA is simple to perform and it is a rapid, sensitive and specific test for detecting Streptococcus pneumoniae in sputa from adult patients with pneumonia.


Inhibitory effects of a water-soluble jujube polysaccharide against biofilm-forming oral pathogenic bacteria.
Oral diseases caused by infectious pathogens raises significant concerns in public health. In the light of side effects of current antibiotics therapy and growing drug resistance of pathogenic bacteria, natural products have become attractive alternatives for antibiotics agents in dental practice. This current study investigated the effects of polysaccharides extracted from Zizyphus jujuba Mill. on three major oral biofilm-forming pathogenic bacteria including caries-inducing Streptococcus mutans, lesions-causing MRSA, and periodontitis-related Porphyromonas gingivalis, as well as general oral microbiota. Our results demonstrated that jujube polysaccharide prepared in this study was mainly composed by galacturonic acid with an average molecular weight 242 kDa, which were further characterized for structural features by FT-IR spectra and NMR spectroscopy analysis. This jujube polysaccharide was shown to exhibit remarkable inhibitory effects against all the tested oral bacterial pathogens through various mechanisms including growth inhibition, biofilm prevention and disruption, intervention of bacterial infection (adhesion and invasion), attenuation of cytotoxicity, modulation of excessive inflammatory response of LPS-stimulated and MRSA-infected macrophages as well as positive regulation of oral microbiota. The present study paves the way to explore jujube polysaccharides for the prevention and treatment of oral infectious diseases. Graphic Abstract.


Vital dyes increase the rigidity of the internal limiting membrane.
To assess the stiffness of the natural human internal limiting membrane (ILM) and evaluate potential changes of the mechanical properties following staining with brilliant blue (BB) and indocyanine green (ICG). Unstained ILM specimens were obtained during ophthalmic surgical procedures. After removal, the specimens were dissected into five parts. Two fragments were stained with BB and ICG, respectively, for 1 min, another two specimens were stained similarly followed by additional subsequent illumination using a standard light source (PENTA LUX x 50, Ophthalmologische Systeme GmbH Fritz Ruck). The fifth part served as an untreated control. All specimens were then analyzed using atomic force microscopy (AFM) in contact mode with a scan rate of 0.6 Hz. Two scan regions of 10 × 10 μm were chosen and stiffness was determined by using AFM in a force spectroscopy mode. The force curves were plotted with a data rate of 5000 Hz. In all specimens both the retinal side and vitreal side were analyzed. Staining resulted in a significant increase in tissue stiffness. An increase was seen both for the vitreal (BB: P<0.001; ICG: P<0.01) and retinal side (BB: P<0.01; ICG: P<0.01), with the retinal side being significantly stiffer in all control and stained samples. Additional illumination after staining did further increase tissue rigidity in most samples but not significantly. Staining significantly increases the stiffness of the human ILM. This might explain the fact that the stained ILM can be removed more easily and in larger fragments during vitreoretinal surgical procedures compared with unstained ILM.


Transvascular protein movement in the intact ischemic hindlimb.
Postischemic limb swelling following reperfusion may be related to microvascular changes associated with ischemia. We used lymph-to-plasma total protein concentration ratios (L/P) and lymph flow (QL) as an index of transvascular exchange in the intact dog hindlimb during steady state (C) (1 hr), ischemia (I) (6 hr), and reperfusion (R) (3 hr). Central pressures, femoral arterial and venous pressures (PA, PV) and QL were recorded every 15 min. Lymph was collected from a femoral lymphatic in the passively flexed leg (50 cycles/min). Three groups of animals were studied: GI, sham-operated (N = 5); GII, moderate ischemia (N = 7, PA = 30-45% C); and GIII, severe ischemia (N = 7, PA = 5-20% C). In GI, QL gradually increased over 10 hr without change in L/P. Moderate ischemia produced a decrease in QL, 3.55 +/- 2.02 mg/hr to 0.92 +/- 0.53 mg/hr (P less than 0.0001), and QL remained below baseline during R with no change in L/P over the 10 hr. Severe ischemia produced a similar decrease in QL, 1.91 +/- 2.05 mg/hr to 0.15 +/- 0.1 mg/hr (P less than 0.01); however, an increase to 2.56 +/- 2.14 mg/hr occurred during R. Severe ischemia increased L/P 0.42 +/- 0.08 to 0.64 +/- 0.23 (P less than 0.001) and remained elevated during R at 0.63 +/- 0.18 (P less than 0.001). An increase in the wet-to-dry weight ratio of ischemic to nonischemic muscle after reperfusion was noted only in GIII, 3.82 +/- 1.17 vs 2.60 +/- 0.45 (P less than 0.04). Severe ischemia produces changes in vascular integrity which augment protein flow. Prevention of these vascular changes may help to minimize the muscle swelling of reperfusion.


Association of Glutathione S-Transferase P-1 (GSTP-1) rs1695 polymorphism with overall survival in glioblastoma patients treated with combined radio-chemotherapy.
Glioblastoma (GBM) is the most frequent malignant primary brain tumor in adults and, despite recent advances, the prognosis for this cancer remains dismal. The aims of this study were to test the influence of XRCC1 rs25487, XRCC3 rs861539, XRCC3 rs1799794, RAD51 rs1801320 and GSTP-1 rs1695 single nucleotide polymorphisms on progression free survival (PFS) and overall survival (OS) in GBM patients treated with radiotherapy (RT) and temozolomide (TMZ). Fifty GBM patients treated with upfront radio-chemotherapy (RT 60 Gy/30 sessions; TMZ 75 mg/m2 during RT and 200 mg/m2 days 1 → 5 every 28 days) were enrolled. Survival curves were calculated using the Kaplan-Meier method, and the log-rank test was used to evaluate differences between curves. A trend to a statistically significant association with PFS in univariate and multivariate COX regression analysis was found with GSTP-1 rs1695 polymorphism (p = 0.087 and p = 0.097 on univariate and multivariate analyses, respectively). Conversely, the same GSTP-1 rs1695 SNP revealed a statistically significant association with OS (p = 0.007 and p = 0.042 on univariate and multivariate analysis, respectively). Our pharmacogenetic prospective study suggests that GSTP-1 rs1695 genotypes can be associated with different OS in GBM patients treated with RT and TMZ.


Comprehensive bioinformatics analysis of acquired progesterone resistance in endometrial cancer cell line.
Progesterone resistance is a problem in endometrial carcinoma, and its underlying molecular mechanisms remain poorly understood. The aim of this study was to elucidate the molecular mechanisms of progesterone resistance and to identify the key genes and pathways mediating progesterone resistance in endometrial cancer using bioinformatics analysis. We developed a stable MPA (medroxyprogesterone acetate)-resistant endometrial cancer cell subline named IshikawaPR. Microarray analysis was used to identify differentially expressed genes (DEGs) from triplicate samples of Ishikawa and IshikawaPR cells. PANTHER, DAVID and Metascape were used to perform gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis, and cBioPortal for progesterone receptor (PGR) coexpression analysis. GEO microarray (GSE17025) was utilized for validation. The protein-protein interaction network (PPI) and modular analyses were performed using Metascape and Cytoscape. Further validation were performed by real-time polymerase chain reaction (RT-PCR). In total, 821 DEGs were found and further analyzed by GO, KEGG pathway enrichment and PPI analyses. We found that lipid metabolism, immune system and inflammation, extracellular environment-related processes and pathways accounted for a significant portion of the enriched terms. PGR coexpression analysis revealed 7 PGR coexpressed genes (ANO1, SOX17, CGNL1, DACH1, RUNDC3B, SH3YL1 and CRISPLD1) that were also dramatically changed in IshikawaPR cells. Kaplan-Meier survival statistics revealed clinical significance for 4 out of 7 target genes. Furthermore, 8 hub genes and 4 molecular complex detections (MCODEs) were identified. Using microarray and bioinformatics analyses, we identified DEGs and determined a comprehensive gene network of progesterone resistance. We offered several possible mechanisms of progesterone resistance and identified therapeutic and prognostic targets of progesterone resistance in endometrial cancer.


Bond strengths and remnant adhesive resin on debonding for orthodontic bonding techniques.
Bond strengths and remnant adhesive resin on the tooth surface after debonding for three bonding techniques used to attach foil mesh orthodontic brackets to 315 freshly extracted bovine incisor teeth were compared in an in vitro study. Each method of bonding used 105 teeth in groups of 15, bonded with seven different (bis-GMA type) two-paste chemically cured resins. The direct method comprised bonding the attachments directly to the incisors with the composite resin. The indirect-1 method comprised securing attachments to die-stone models of the teeth with a water soluble glue, making silicone positioners to transfer the brackets from the models to the teeth, and bonding to the teeth with the use of the two-paste composite resin system. The indirect-2 method comprised bonding the attachments to die-stone models of the teeth with composite resin, making silicone positioners to transfer the brackets from the models to the teeth, and bonding to the teeth with the use of unfilled sealant resin. Significant differences in bond strength existed among the groups evaluated. The direct technique had statistically significant (p < 0.05) higher bond strength as compared with the indirect-1 and indirect-2 techniques in four of the seven groups evaluated. The indirect-1 and indirect-2 techniques were not significantly different (p < 0.05) in bond strength in six of seven groups tested. The indirect-2 technique had significantly lower adhesive remnant index scores (ARI) compared with the direct and indirect-1 techniques.(ABSTRACT TRUNCATED AT 250 WORDS)


Interference screws are more likely to perform better than cortical button and cross-pin fixation for hamstring autograft in ACL reconstruction: a Bayesian network meta-analysis.
Anterior cruciate ligament (ACL) reconstruction is widely accepted as the first choice of treatment for ACL injury, but there is disagreement in the literature regarding the optimal femoral fixation method. This meta-analysis assesses the evidence surrounding three common femoral fixation methods: cortical button (CB), cross-pin (CP) and interference screws (IS). A systematic search was conducted in Medline, EMBASE and the Cochrane Library to identify studies with evidence level I or II that compared at least two femoral fixation methods with hamstring autograft for ACL reconstruction. Ten primary outcomes were collected. Risk of bias was assessed following the Cochrane Handbook for Systematic Reviews of Interventions. Standardized mean differences (SMD) were estimated using random-effects network meta-analysis in a Bayesian framework. Probability of ranking best (ProBest) and surface under the cumulative ranking curve (SUCRA) were used to rank all treatments. Funnel plots were used to identify publication bias and small-study effects. Sixteen clinical trials were included for analysis out of 2536 retrieved studies. Bayesian network meta-analysis showed no significant differences among the three fixation methods for the ten primary outcome measures. Based on the 10 outcome measures, the IS, CB and CP had the highest ProBest in 5, 5 and 0 outcomes, and the highest SUCRA values in 5, 4 and 1 outcomes, respectively. No substantial inconsistency between direct and indirect evidence, or publication bias was detected in the outcomes. There were no statistical differences in performance among the CP, CB and IS femoral fixation methods with hamstring autograft in ACL reconstruction, although the IS was more likely to perform better than CB and CP based on the analysis of outcome measures from the included studies. 1.


Tobacco Use, Dependence, and Age of Initiation among Youths with Cognitive Disability.
To examine the prevalence of tobacco use by product type among youths with cognitive disability; the prevalence of tobacco dependence among youths with cognitive disability; and the relationship between age of tobacco use initiation and cognitive disability. This cross-sectional study analyzed data from the 2019 National Youth Tobacco Survey (NYTS). Participants were a nationally representative sample of 19 018 students in grades 6-12. Estimates were calculated for ever use, current use, age of tobacco use initiation, and tobacco dependence. Associations between use patterns and cognitive disability status were examined using bivariate analyses and multivariable logistic regression. Compared with youths without cognitive disability, youths with cognitive disability had significantly greater odds of ever using any tobacco product (aOR, 1.49; 95% CI, 1.31-1.70), currently using any tobacco product (aOR, 1.41; 95% CI, 1.26-1.58), and currently using electronic cigarettes (e-cigarettes), cigarettes, cigars, hookahs, roll-your-own cigarettes, and heated tobacco products, specifically. They had higher prevalence and odds of reporting younger age of tobacco use initiation (aOR, 1.25; 95% CI, 1.10-1.43). Higher prevalence and odds of tobacco dependence were also observed among youths with cognitive disability compared with youths without cognitive disability (P < .001). These findings reinforce the importance of developing early primary prevention efforts to reduce or delay tobacco use among adolescents with cognitive disability. They also suggest the need to address co-occurring disorders during tobacco cessation programs with this high-risk group.


Electrocardiographic wave form and cardiac arrhythmias.
In addition to its established diagnostic uses, the electrocardiogram may be useful for predicting ventricular fibrillation and other arrhythmias. Non-uniform recovery of excitability, which is a factor in vulnerability, is the determinant of QRST deflection area, and regionally selective sampling by body surface electrocardiographic mapping may permit recognition of the locally disparate recovery related to fibrillation. Preliminary experimental and clinical studies support this possibility and suggest that the multipolar content of QRST area distributions on the body surface is a marker of vulnerability.


The use of urethral, condom, and suprapubic catheters in aged nursing home patients.
In this study of 4,259 aged patients in 53 randomly selected nursing homes in Maryland, we found that 10% of women and 15% of men used a urine collection device. Among bedfast patients, 47% of women and 58% of men and, among patients with decubitus ulcers, 37% of women and 33% of men were using a urine collection device. The indwelling urethral catheter was the most commonly used device. Indeed, for women, few other options were available: 93% of women used this device. In women, multiple logistic regression analysis indicated that presence of a decubitus ulcer and occupation of a long-term care bed were the attributes most strongly associated with the use of the urethral catheter. Of men with urine collection devices, 43% were using the urethral catheter; poor mobility status was the characteristic most strongly associated with its use. Long-term urethral catheterization has been well studied and is associated with universal bacteriuria and with a number of complications. Options need to be further explored, particularly external urine collection devices for women. Furthermore, because urethral catheterization may be used as a management technique for decubitus ulcers, prevention of the latter may diminish the use of urethral catheters and their subsequent complications.


Dose tolerance at helium and nitrogen temperatures for whole cell electron tomography.
Electron tomography is currently the only method that allows the direct three-dimensional visualization of macromolecules in an unperturbed cellular context. In principle, tomography should enable the identification and localization of the major macromolecular complexes within intact bacteria, embedded in amorphous ice. In an effort to optimize conditions for recording data that would bring us close to the theoretical limits, we present here a comparison of the dose tolerance of Caulobacter crescentus cells embedded in amorphous ice at liquid helium versus liquid nitrogen temperature. The inner and outer cell membranes, and the periodic structure of the S-layer of this Gram-negative bacterium provide ideal features to monitor changes in contrast and order as a function of dose. The loss of order in the S-layer occurs at comparable doses at helium and nitrogen temperatures. Macroscopic bubbling within the cell and the plastic support develops at both temperatures, but more slowly at helium temperature. The texture of the bubbles is finer in initial stages at helium temperature, giving an impression of contrast reversal in some parts of the specimen. Bubbles evolve differently in different organelles, presumably a consequence of their different chemical composition and mechanical properties. Finally, the amorphous ice "flows" at helium temperature, causing changes in the relative positions of markers within the specimen and distorting the cells. We conclude that for cryo-electron tomography of whole cells liquid nitrogen temperature provides better overall data quality.


Giant milkweed (Calotropis gigantea): A new plant resource to inhibit protozoa and decrease ammoniagenesis of rumen microbiota in vitro without impairing fermentation.
This study screened six different species of forest plants and then further evaluated the most promising plant, giant milkweed (Calotropis gigantea), for the potential to improve nitrogen utilization efficiency (NUE) through inhibiting rumen protozoa in vitro. Ground leaves of giant milkweed at 1.6 and 3.2 mg/mL decreased the counts of Entodinium cells by 41.30% and 58.89%, respectively, and damaged their cell surface structure. Dasytricha, Isotricha, Epidinium, Ophryoscolex, and Diplodinium were not affected, while total bacterial and archaeal populations did not decrease. Ammonia nitrogen (NH3-N) concentration decreased by 50.64% and 33.33% at 1.6 g/mL and 3.2 mg/mL, respectively. Volatile fatty acid (VFA) production and methane production remained unaffected, but butyrate production increased. The giant milkweed leaves contained (per gram of dry matter) 3636 μg phenolics including 205.9 μg of 3-hydroxybenzoic acid, 2079 μg flavonoids including 1197.5 μg of quercetin and 91.4 μg of myricetin, and 490 μg alkaloids including 219.8 μg of anthraquinone glycosides. The effective inhibition of Entodinium was accompanied by a decrease in NH3-N concentration, and methane production did not increase except for the dose of 1.6 mg/mL. Giant milkweed may be used as a new feed additive or an alternative to chemicals or antibiotics for sustainable animal husbandry enhancing NUE in ruminants.