Influence of cutting parameters on the depth of subsurface deformed layer in nano-cutting process of single crystal copper.
Large-scale molecular dynamics simulation is performed to study the nano-cutting process of single crystal copper realized by single-point diamond cutting tool in this paper. The centro-symmetry parameter is adopted to characterize the subsurface deformed layers and the distribution and evolution of the subsurface defect structures. Three-dimensional visualization and measurement technology are used to measure the depth of the subsurface deformed layers. The influence of cutting speed, cutting depth, cutting direction, and crystallographic orientation on the depth of subsurface deformed layers is systematically investigated. The results show that a lot of defect structures are formed in the subsurface of workpiece during nano-cutting process, for instance, stair-rod dislocations, stacking fault tetrahedron, atomic clusters, vacancy defects, point defects. In the process of nano-cutting, the depth of subsurface deformed layers increases with the cutting distance at the beginning, then decreases at stable cutting process, and basically remains unchanged when the cutting distance reaches up to 24 nm. The depth of subsurface deformed layers decreases with the increase in cutting speed between 50 and 300 m/s. The depth of subsurface deformed layer increases with cutting depth, proportionally, and basically remains unchanged when the cutting depth reaches over 6 nm.


GABAergic and glycinergic systems regulate ON-OFF electroretinogram by cooperatively modulating cone pathways in the amphibian retina.
The network mechanisms underlying how inhibitory circuits regulate ON- and OFF-responses (the b- and d-waves) in the electroretinogram (ERG) remain unclear. The purpose of this study was to investigate the contribution of inhibitory circuits to the emergence of the b- and d-waves in the full-field ERG in the newt retina. To this end, we investigated the effects of several synaptic transmission blockers on the amplitudes of the b- and d-waves in the ERG obtained from newt eyecup preparations. Our results demonstrated that (a) L-APB blocked the b-wave, indicating that the b-wave arises from the activity of ON-bipolar cells (BCs) expressing type six metabotropic glutamate receptors; (b) the combined administration of UBP310/GYKI 53655 blocked the d-wave, indicating that the d-wave arises from the activity of OFF-BCs expressing kainate-/AMPA-receptors; (c) SR 95531 augmented both the b- and the d-wave, indicating that GABAergic lateral inhibitory circuits inhibit both ON- and OFF-BC pathways; (d) the administration of strychnine in the presence of SR 95531 attenuated the d-wave, and this attenuation was prevented by blocking ON-pathways with L-APB, which indicated that the glycinergic inhibition of OFF-BC pathway is downstream of the GABAergic inhibition of the ON-system; and (e) the glycinergic inhibition from the ON- to the OFF-system widens the response range of OFF-BC pathways, specifically in the absence of GABAergic lateral inhibition. Based on these results, we proposed a circuitry mechanism for the regulation of the d-wave and offered a tentative explanation of the circuitry mechanisms underlying ERG formation.


The role of transforming growth factor β1 /Smad pathway in Alzheimer's disease inflammation pathology.
Alzheimer's disease (AD), a progressive disorder, has become a global health problem and is now the main cause of dementia. The aetiology of AD is complex and remains elusive making effective AD treatment difficult. Current drugs for AD only improve symptoms but do not interfere with pathogenic mechanisms. Three main hypotheses have been brought forward regarding AD aetiology, one of them being the 'inflammation hypothesis'. A number of studies have demonstrated that inflammation plays a critical role in AD. Self-limiting neuroinflammation is considered beneficial to AD, whereas chronic inflammation aggravates brain injury and neuronal death. Transforming growth factor β 1(TGF-β1) is an anti-inflammatory cytokine with neuroprotective properties. Smad proteins are downstream molecules of TGF-β signalling. They are cytoplasmic transcription factors that can regulate targeted gene expression. In AD, impairments of TGF-β1/Smad pathways have been observed. Moreover, microglia, astrocytes, inflammasomes, and insulin resistance also have been implicated in AD pathogenesis. Elucidating the molecular mechanisms underlying AD pathogenesis is a fundamental step toward designing new treatment options. In this review, we detail the changes in TGF-β1/Smad pathways in AD and hope this will facilitate further research on AD treatment.


Sirtuin 1 and 2 inhibitors enhance the inhibitory effect of sorafenib in hepatocellular carcinoma cells.
Multidrug resistance (MDR) counteracts the efficiency of sorafenib, an important first-line therapy for hepatocellular carcinoma (HCC). Sirtuins (SIRTs) 1 and 2 are associated with tumor progression and MDR. We treated 2D and 3D cultures (which mimic the features of in vivo tumors) from HCC cells with sorafenib alone or in the presence of SIRTs 1 and 2 inhibitors (cambinol or EX-527; combined treatments). Cultures subjected to combined treatments showed a greater fall in cellular viability, proliferation (PCNA, cyclin D1 and Ki-67 expression and cell cycle analysis), migration and invasion when compared with cultures treated only with sorafenib. Similarly, combined treatments produced more apoptosis (annexin V/PI, caspase-3/7 activity) than sorafenib alone. Since cell cycle dysregulation and apoptotic blockage are reported mechanisms of MDR, the modulation found in PCNA, cyclin D1, Ki-67 and caspase-3/7 proteins by cambinol and EX-527 are probably playing a role in enhancing the sensitivity of HCC cell lines to sorafenib. EX-527 reduced MRP3 and BCRP expression in sorafenib-treated HCC cells. Since ABC transporters contribute to MDR, MRP3 and BCRP could be also influencing in the response of HCC cells to sorafenib. Overall, 2D and 3D cultures behave similarly except that 3D cultures were less sensitive to treatments, reinforcing the clinical relevance of the current study. Findings presented in this manuscript support a potential application for SIRTs 1 and 2 inhibitors since we demonstrated that these compounds enhance the inhibitory effect of sorafenib upon treatment of hepatocellular carcinoma cells lines.


Genome-wide SNP discovery and core marker sets for assessment of genetic variations in cultivated pumpkin (Cucurbita spp.).
Three pumpkin species Cucurbita maxima, C. moschata, and C. pepo are commonly cultivated worldwide. To identify genome-wide SNPs in these cultivated pumpkin species, we collected 48 F1 cultivars consisting of 40 intraspecific hybrids (15 C. maxima, 18 C. moschata, and 7 C. pepo) and 8 interspecific hybrids (C. maxima x C. moschata). Genotyping by sequencing identified a total of 37,869 confident SNPs in this collection. These SNPs were filtered to generate a subset of 400 SNPs based on polymorphism and genome distribution. Of the 400 SNPs, 288 were used to genotype an additional 188 accessions (94 F1 cultivars, 50 breeding lines, and 44 landraces) with a SNP array-based platform. Reliable polymorphisms were observed in 224 SNPs (78.0%) and were used to assess genetic variations between and within the four predefined populations in 223 cultivated pumpkin accessions. Both principal component analysis and UPGMA clustering found four major clusters representing three pumpkin species and interspecific hybrids. This genetic differentiation was supported by pairwise Fst and Nei's genetic distance. The interspecific hybrids showed a higher level of genetic diversity relative to the other three populations. Of the 224 SNPs, five subsets of 192, 96, 48, 24, and 12 markers were evaluated for variety identification. The 192, 96, and 48 marker sets identified 204 (91.5%), 190 (85.2%), and 141 (63.2%) of the 223 accessions, respectively, while other subsets showed <25% of variety identification rates. These SNP markers provide a molecular tool with many applications for genetics and breeding in cultivated pumpkin.


Parental effects in a filamentous fungus: Phenotype, fitness and mechanism.
In nature, organisms have to cope with constantly changing environments. In certain conditions, it may be advantageous for the parents to pass on information about the environment, or resources to their offspring. Such transfers are known as parental effects, and they are well documented in plants and animals, but not in other eukaryotes, such as fungi. Many fungi disperse through spores, and fungal spores can potentially carry information or resources to the next generation. Understanding parental effects and their evolutionary consequences in fungi is of vital importance as they perform crucial ecosystem functions. In this study, we investigated whether parental effects are present in the filamentous fungus Neurospora crassa, how long do they last, whether the effects are adaptive, and what is their mechanism. We performed a fully factorial match/mismatch experiment for a good and a poor quality environment, in which we measured the initial growth of strains that experienced either a matched or mismatched environment in their previous generation. We found a strong silver-spoon effect in initial mycelium growth, which lasted for one generation, and increased fitness during competition experiments. By using deletion mutants that lacked key genes in epigenetic processes, we show that epigenetic mechanisms are not involved in this effect. Instead, we show that spore glycogen content, glucose availability and a radical transcription shift in spores are the main mechanisms behind this parental effect.


The management of toxicities from immune, targeted and ADCs treatments in patients with urothelial cancer.
Newly approved systemic treatment options for metastatic urothelial cancer (mUC) have diversified treatments and improved responses and survival for chemotherapy refractory disease. These systemic treatments have associated toxicities which need appropriate management for patients to stay on treatment and potentially have longer benefit from treatment. We review the expected toxicities of immune checkpoint inhibitors, FGFR inhibitors such as erdafitinib, and antibody drug conjugates such as enfortumab vedotin and sacituzumab govitecan.


Immunohistochemical expression of Bcl2 is an independent predictor of time-to-biochemical failure in patients with clinically localized prostate cancer following radical prostatectomy.
Whether the immunohistochemical expression (IHCE) of the bcl2, the p53 and of the prostate apoptosis response-4 (PAR4) proteins is associated with pre-operative PSA levels, post-operative parameters of prostate cancer (PC) pathology, surgical staging or biochemical failure (BF) of patients with clinically localized PC who underwent radical prostatectomy (RP) of curative intent, was investigated. A retrospective analysis of clinical data evaluating surgical specimens of 131 patients with PC, consecutively treated with RP for clinically localized disease, was performed. The IHC method of streptavidin biotin peroxidase on paraffin tissue sections was used to detect bcl2 and p53 oncoproteins and PAR4 pro-apoptotic protein expression in surgical specimens. Statistically significant relationships were detected between: (i) p53 IHC expression and infiltration of periprostatic tissue (IPT; p = 0.011); (ii) tumor volume (TV; p = 0.027); and (iii) bcl2 IHCE and absence of prostatic intraepithelial neoplasia (PIN) (p = 0.004). Biochemical failure (BF) was documented in 37% of these patients. Kaplan-Meier survival curves showed that the IHCE of bcl2 and p53 was significantly related to BF. Taking the hazard ratio (HR) estimated from the Cox proportional hazard regression model to be 1.00 for patients with negative bcl2 IHCE, a value of 2.82 was found for patients with positive bcl2 IHCE (p = 0.015, 95% CI = 1.22-6.47). The HR for patients with positive p53 IHCE was 2.05 (p = 0.048, 95% CI = 1.00-4.19). Multivariate analysis showed that only seminal vesicle invasion (SVI), pelvic lymph node metastasis (PLNM) and bcl2 IHCE were independent predictors for BF (HR = 3.06, 3.31 and 3.15; p = 0.048, p = 0.031 and p = 0.031 for SVI, PLNM and bcl2 IHCE, respectively). Bcl2 immunohistochemical overexpression in specimens of RP suggests high risk for BF in clinically localized PC.


The nonarticulating portion of the radial head: anatomic and clinical correlations for internal fixation.
The proximal radioulnar joint was dissected in 24 cadaveric elbows to localize the area of the radial head that did not articulate with the lesser sigmoid notch of the ulna. The nonarticulating portion of the radial head was posterolateral in the anatomic position of full supination. Gross observations of the nonarticulating portion of the radial head revealed a thinner band of yellowish cartilage relative to a wider, white, glistening cartilage of the articular portion of the radial head. The nonarticular portion of the radial head did not contain the angled peak, which is most prominent in the middle of the articular portion. The average arc of the nonarticulating radial head was 113 degrees (range, 106 degrees to 120 degrees; standard deviation, 4 degrees). This nonarticulating portion of the radial head (or safe zone for prominent fixation) consistently encompassed a 90 degrees angle localized by palpation of the radial styloid and Lister's tubercle. Using these palpable distal landmarks to localize the safe zone of the radial head, 24 different cadaveric elbows were internally fixed with a plate and screws through 3 different approaches (anterior, lateral, and posterolateral). Regardless of approach, the internal fixation allowed full forearm rotation in all the specimens. Utilization of this method and anatomic landmarks to localize the nonarticular portion of the radial head may assist the surgeon in open reduction and internal fixation of fractures of the radial head and neck.


Targeting of poly(rI)-poly(rC) by fusogenic (F protein) immunoliposomes.
The aim of this study is to investigate the intracellular delivery of polynucleotides by fusogenic immunoliposomes. We have studied the internalization of poly(rI)-poly(rC) (polyIC) by liposomes into murine L929 cells. The liposomes were prepared by incorporating Sendaï virus fusogenic F protein into the lipid bilayer and targeted by a monoclonal antibody (mAb) bound to the liposomes via protein A (Staphylococcus aureus). The immunoliposomes ensured a sufficient yield of polyIC internalization, which was estimated by its ability to induce antiviral activity. In the absence of RNase treatment free and encapsulated polyIC had the same inducing effect, but in the presence of nuclease only the encapsulated polyIC, and not free polyIC, maintained its antiviral effect. The fusion process making possible the internalization of polyIC was confirmed by the fact that the polyIC effect was mainly inhibited by an anti-F protein mAb which inhibited erythrocyte hemolysis by the virus.


The influence of oxygen deprivation and donor age on the effect of statins on human mesenchymal stromal cells.
To date, no study evaluated the effect of oxygen deprivation together with statins pretreatment on human mesenchymal stromal cells (MSCs). The aim of our study was to establish the influence of atorvastatin and rosuvastatin on MSC proliferation and cytotoxicity in different oxygenic conditions. Human MSCs isolated from the bone marrow (n = 12) were incubated with statins. The proliferation rate and cytotoxic effect were evaluated in normoxic (21 %O2) and hypoxic (2%O2) conditions, also in relation to donor age. The treatment with atorvastatin was associated with significantly higher proliferation rate compared to control, both in hypoxic (19 % median increase) and normoxic conditions (20 %), p = 0.02 and p = 0.04, respectively. Atorvastatin had no significant cytotoxic effect on MSCs. Treatment with rosuvastatin in hypoxia resulted in significantly higher proliferation rate (15 %, p = 0.02) comparing to control with no significant cytotoxicity. In atmospheric oxygen concentration, rosuvastatin was associated with no significant change in proliferation and higher cytotoxicity compared to untreated control (p = 0.042 and p = 0.015, for 0.04 μM and 1 μM solutions respectively). There were no differences in the effect of statins on MSC from young donors vs. aged donors. These results suggest that statins could support MSC-based therapy of acute myocardial infarction.


Risk factors for aortic atherosclerosis determined by transesophageal echocardiography in patients with CRF.
The significance of various risk factors for cardiovascular disease (CVD) in the pathogenesis of atherosclerosis in patients with chronic renal failure (CRF) is, to a great deal, unresolved. The high risk for CVD in patients with CRF may be caused by the high prevalence of recognized risk factors for CVD or by factors characteristic of CRF in these patients. In this prospective cross-sectional study, we examined risk factors for thoracic aortic atherosclerosis in a population of patients with CRF consisting of predialysis and dialysis patients, as well as renal transplant recipients. Of 118 patients, 52 patients had moderate to severe predialysis CRF, 32 patients were on dialysis treatment, and 34 patients were renal transplant recipients. Mean age was 52 +/- 12 years, and 35 patients (30%) had diabetes. Multiplane transesophageal echocardiography (TEE) was performed using local anesthesia. Large aortic plaques (LAPs; > or = 3.0 mm in diameter) were found in 39 patients (33%). In univariate analysis, age, duration of hypertension, pulse pressure, low diastolic blood pressure, elevated fibrinogen level, C-reactive protein level, total cholesterol level, low-density lipoprotein cholesterol level, and duration of dialysis or a functioning renal transplant were significantly associated (P < 0.05) with LAP. In multivariate analysis, age, duration of hypertension, and total cholesterol level were associated with LAP. Results of the present TEE study suggest that in addition to duration of hypertension and renal disease, hypercholesterolemia has a role in the pathogenesis of atherosclerosis in patients with CRF.


A longitudinal study of electronic cigarette use and onset of conventional cigarette smoking and marijuana use among Mexican adolescents.
This study evaluated whether e-cigarette trial among Mexican adolescents increased the likelihood of trial and use of conventional cigarettes or marijuana use at follow-up. A school-based longitudinal survey was conducted in 60 public middle schools from the three largest cities in Mexico. Students (12-13years old) were surveyed in 2015 and followed up 20 months later (n=6574). Generalized estimating equations models were used to evaluate the association between e-cigarette trial at baseline and conventional cigarettes smoking and marijuana use at follow-up. Adolescents who had tried e-cigarettes (but not cigarettes) at baseline were more likely to have tried conventional cigarettes at followup compared to adolescents who had tried neither e-cigarettes nor cigarettes (43% vs. 24%, respectively; RR 1.41, 95% CI 1.18-1.70). We also found that adolescents who had tried both conventional cigarettes and e-cigarettes at baseline were more likely to have tried marijuana at follow-up compared to adolescents who had tried neither tobacco product (20% vs. 4%, respectively; RR 2.67, 95% CI 1.78-4.02). Trial of only e-cigarettes was not independently associated with marijuana use at followup. Adolescents who had tried e-cigarettes were more likely to have tried conventional cigarettes and marijuana 20 months later. Although e-cigarettes have been banned in Mexico, it is likely that additional policies and public health campaigns are needed to reduce adolescent use of e-cigarettes and its consequences.


Molecular cloning, prokaryotic expression and the anti-inflammatory activity of porcine PRDX5.
Peroxiredoxin 5 (PRDX5) is the sole member of the atypical 2-Cys subfamily of mammalian PRDXs, a family of thiol-dependent peroxidases. In addition to its antioxidant effect, PRDX5 has been implicated in modulating the inflammatory response. In this study, the full-length cDNA encoding porcine PRDX5 (pPRDX5) was cloned. Subsequently, using porcine alveolar macrophages (PAMs), the target cells of PRRSV infection in vivo, we found that the recombinant pPRDX5 protein inhibited inflammatory responses induced by tumor necrosis factor alpha (TNF-α) or porcine reproductive and respiratory syndrome virus (PRRSV), a virus causing severe interstitial pneumonia in pigs. By contrast, knockdown of endogenous pPRDX5 with specific siRNA enhanced inflammatory responses induced by TNF-α or PRRSV. We also demonstrated that the involvement of pPRDX5 in inflammation regulation depended on its peroxidase activity. Taken together, these results showed that pPRDX5 is an anti-inflammatory molecule, which may play an important immune-regulation role in the pathogenicity of PRRSV.


Massive Transfusion in Children.
Massive transfusions occur frequently in pediatric trauma patients, among some children undergoing surgery, or in children with critical illness. Over the last years, many authors have studied different aspects of massive transfusions, starting with an operative definition. Some information is available on transfusion strategies and adjunctive treatments. Areas that require additional investigation include: studies to assess which children benefit from transfusion protocols based on fixed ratios of blood components vs transfusion strategies based on biophysical parameters and laboratory tests; whether goal-directed therapies that are personalized to the recipient will improve outcomes; or which laboratory tests best define the risk of bleeding and what clinical indicators should prompt the start and stop of massive transfusion protocols. In addition, critical issues that require further study include transfusion support with whole blood vs reconstituted whole blood prepared from packed red blood cells, plasma, and platelets; and the generation of high quality evidence that would lead to treatments which decrease adverse consequences of transfusion and improve outcomes.


Contribution of land use to the interannual variability of the land carbon cycle.
Understanding the driving mechanisms of the interannual variability (IAV) of the net land carbon balance (Snet) is important to predict future climate-carbon cycle feedbacks. Past studies showed that the IAV of Snet was correlated with tropical climate variation and controlled by semiarid vegetation. But today's land ecosystems are also under extensive human land use and management. Here, we report a previously hidden role of land use in driving the IAV of Snet by using an improved biosphere model. We found that managed land accounted for 30-45% of the IAV of Snet over 1959-2015, while the contribution of intact land is reduced by more than half compared with previous assessments of the global carbon budget. Given the importance of land use in modulating future land climate-carbon cycle feedbacks, climate mitigation efforts should strive to reduce land-use emissions and enhance the climate resilience of carbon sinks over managed land.


What Active Space Adequately Describes Oxygen Activation by a Late Transition Metal? CASPT2 and RASPT2 Applied to Intermediates from the Reaction of O2 with a Cu(I)-α-Ketocarboxylate.
Multiconfigurational second-order perturbation theory calculations based on a complete active space reference wave function (CASPT2), employing active spaces of increasing size, are well converged at the level of 12 electrons in 12 orbitals for the singlet-triplet state-energy splittings of three supported copper-dioxygen and two supported copper-oxo complexes. Corresponding calculations using the restricted active space approach (RASPT2) offer similar accuracy with a significantly reduced computational overhead provided an inner (2,2) complete active space is included in the overall RAS space in order to account for strong biradical character in most of the compounds. The effects of the different active space choices and the outer RAS space excitations are examined, and conclusions are drawn with respect to the general applicability of the RASPT2 protocol.


Predictors of Overall and Progression-Free Survival in Patients with Ocular Melanoma Metastatic to the Liver Undergoing Y90 Radioembolization.
To investigate predictors of overall survival (OS) and progression-free survival (PFS) in patients with ocular melanoma metastatic to the liver undergoing yttrium-90 (Y90) radioembolization, including the effect of concurrent immunotherapy. An IRB-approved retrospective review of 24 patients with ocular melanoma metastatic to the liver who underwent Y-90 treatment between June 2003 and January 2018 was performed. Data regarding patients' performance status at the time of Y90, intra-/extrahepatic tumor burden, and treatment response were evaluated. RECIST was used to determine objective tumor response. Kaplan-Meier analysis was used to calculate OS and PFS from the first Y90 therapy. Log-rank analysis was used to determine predictors of prolonged OS and PFS. Median OS from primary diagnosis and diagnosis of liver metastases was 66 months (mo) and 26.3 mo, respectively. Median OS for those who received immunotherapy within 3 months of undergoing Y90 was prolonged at 26.0 mo versus 9.5 mo for others (p = 0.014). Median OS for patients with an ECOG performance status of 0 was prolonged at 26 mo versus 5.5 mo for others (p = 0.003). Median hepatic PFS was prolonged in patients treated with Y-90 on concurrent immunotherapy at 10.3 mo versus 2.7 mo for TARE only (p = 0.002). Patients with an ECOG performance status of 0 had prolonged PFS (p = 0.002). Concurrent immunotherapy and an ECOG performance status of 0 at the time of Y90 therapy appear to be predictors of prolonged OS and PFS in patients with ocular melanoma metastatic to the liver.


Primary progressive aphasia: a patient with stress assignment impairment in reading aloud.
Surface dyslexia is a pattern of reading impairment which has been seldom described in Italian native speakers. We report the case of a female Italian patient, RM, suffering from primary progressive aphasia (PPA) of the fluent type, who presented stress assignment errors in reading aloud. In Italian these errors are considered to be strongly suggestive of surface dyslexia. We studied RM's reading performance in light of existing cognitive models on reading. Since the first assessment, she presented multi-level impairment involving pre-semantic, lexical-semantic and post-semantic stages. Her stress assignment errors have been interpreted as a generalisation of the most frequent tendency in Italian language: namely to assign stress to the penultimate syllable. In agreement with previous studies, our case suggests that surface dyslexia in PPA is not a monolithic entity but, on the contrary, that it may arise from impairment at various stages of the reading process.


Family dynamics and emotional expression among patients with chronic pain and depression.
Exploration of the relative roles of family dynamics and release of constrained, negative emotion in changing pain and depressive symptoms. Eighteen patients presenting mild to moderate depression and diagnoses of psychogenic pain disorder were randomly assigned to 1 of 2 treatment groups. One group was designed to facilitate the release of constrained and overcontrolled negative affect while the other was designed to provide information about pain and depression. Findings suggest that initial incongruity between patient's and significant other's ratings of family relationships retard changes in pain status and depressive symptoms. No significant differences were noted between patients who were taught to express negative feelings and those who were taught simply to understand those feelings. Results are discussed in terms of theories about family dynamics in the initiation and maintenance of pain conditions and in terms of the role of constrained affect as a precursor to both psychogenic pain and depression.


Angiopoietin like protein 4 expression is decreased in activated macrophages.
Angiopoietin like protein 4 (ANGPTL4) inhibits lipoprotein lipase (LPL) activity. Previous studies have shown that Toll-like Receptor (TLR) activation increases serum levels of ANGPTL4 and expression of ANGPTL4 in liver, heart, muscle, and adipose tissue in mice. ANGPTL4 is expressed in macrophages and is induced by inflammatory saturated fatty acids. The absence of ANGPTL4 leads to the increased uptake of pro-inflammatory saturated fatty acids by macrophages in the mesentery lymph nodes due to the failure of ANGPTL4 to inhibit LPL activity, resulting in peritonitis, intestinal fibrosis, weight loss, and death. Here we determined the effect of TLR activation on the expression of macrophage ANGPTL4. LPS treatment resulted in a 70% decrease in ANGPTL4 expression in mouse spleen, a tissue enriched in macrophages. In mouse peritoneal macrophages, LPS treatment also markedly decreased ANGPTL4 expression. In RAW cells, a macrophage cell line, LPS, zymosan, poly I:C, and imiquimod all inhibited ANGPTL4 expression. In contrast, neither TNF, IL-1, nor IL-6 altered ANGPTL4 expression. Finally, in cholesterol loaded macrophages, LPS treatment still decreased ANGPTL4 expression. Thus, while in most tissues ANGPTL4 expression is stimulated by inflammatory stimuli, in macrophages TLR activators inhibit ANGPTL4 expression, which could lead to a variety of down-stream effects important in host defense and wound repair.


Seasonal occurrence of relapses in inflammatory myopathies: a preliminary study.
The seasonal occurrence of relapses was analysed retrospectively in a group of 53 patients with treated dermatomyositis (DM) or polymyositis (PM). In DM, the incidence of both myositic and cutaneous relapses was highest in summer whereas in the PM group relapses was more evenly distributed throughout the seasons but lowest in summer. The present findings suggest that environmental factors such as intercurrent infections and light exposure may be involved in reactivating the disease process and causing relapses in DM but less so in PM. Further prospective studies are needed to assess the role of environmental factors in the initiation and reactivation of the inflammatory myopathies.


N-heterocyclic carbene-mediated hydroacylation-Sonogashira/Heck/Suzuki coupling in a single pot: a new cascade reaction.
A dually NHC-catalyzed reaction cascade comprising an initial hydroacylation of an activated ketone and subsequent Sonogashira/Heck/Suzuki coupling in the same pot is reported. The reaction mechanism and scope of the methodology is presented.


Pure red cell aplasia associated with parvovirus B19 infection occurring late after allogeneic bone marrow transplantation.
Differential diagnosis for anemia late after allogeneic stem cell transplantation is broad. In this report, we describe a case of severe anemia secondary to pure red cell aplasia associated with human parvovirus B19 infection over 8 years after allogeneic bone marrow transplantation. Characteristics of parvovirus B19 infection and the immunosuppressed state after allogeneic stem cell transplantation are reviewed.


Effect of ionic strength and pH on hydraulic properties and structure of accumulating solid assemblages during microfiltration of montmorillonite suspensions.
The structure and hydraulic behaviour of colloidal montmorillonite assemblages formed during constant-pressure microfiltration of feed suspensions under various pH and ionic strengths have been investigated with flux versus time data analysed using both conventional cake filtration theory and a more rigorous sorptivity-diffusivity approach. Size distribution and fractal dimension analyses revealed a shift in assemblage structure from porous to compact as a result of a step-increase in electrolyte concentrations. The hydraulic conductivity of the filter cakes was dramatically affected by suspension ionic strength with significantly higher hydraulic conductivity observed at the higher ionic strengths compared to that observed at lower ionic strengths. Results obtained using the sorptivity-diffusivity model were consistent with conventional cake filtration theory and provided useful insights into the bulk properties of the filter cakes. Cake moisture ratio profiles of the montmorillonite system showed that high suspension ionic strength resulted in denser or less voluminous filter cakes that retained less water than was the case at the low ionic strength. These results suggest that, under low ionic strength conditions, the clay particles associate in suspension in assemblages of high aspect ratio which subsequently form highly "cross-linked" voluminous honeycomb type structures of low permeability once deposited upon the membrane. However, under sufficiently high ionic strength conditions, the high aspect ratio montmorillonite assemblages form nematic structures on deposition on the membrane that are denser yet more permeable than the structures formed at lower salt concentration. The distinct change in properties of the deposited clay on increase in salt concentration may well be indicative of transition from a gel to a nematically ordered phase.


Ligand-of-Numb protein X is an endocytic scaffold for junctional adhesion molecule 4.
Junctional adhesion molecule 4 (JAM4) is a cell adhesion molecule that interacts with a tight junction protein, membrane-associated guanylate kinase inverted 1 (MAGI-1). Our previous studies suggest that JAM4 is implicated in the regulation of paracellular permeability and the signalings of hepatocyte growth factor. In this study, we performed yeast two-hybrid screening to search for an unidentified JAM4-binding protein and obtained one isoform of Ligand-of-Numb protein X1 (LNX1), LNXp70, that is an interactor of Numb. Ligand-of-Numb protein X1 is expressed in kidney glomeruli and intestinal epithelial cells, where JAM4 is also detected. Immunoprecipitation from kidney lysates supports the in vivo interaction of proteins. Biochemical studies reveal that JAM4 directly binds the second PDZ domain of LNX1 through its carboxyl terminus. Junctional adhesion molecule 4, LNX1 and Numb form a tripartite complex in vitro and are partially colocalized in heterologous cells. Ligand-of-Numb protein X1 facilitates endocytosis of JAM4 and is involved in transforming growth factor beta -induced redistribution of JAM4 in mammary epithelial cells. Experiments using dominant-negative constructs and RNA interference insure that Numb is necessary for the LNX1-mediated endocytosis of JAM4. All these findings indicate that LNX1 provides an endocytic scaffold for JAM4 that is implicated in the reorganization of cell junctions.


[The effect of the blood serum from patients subjected to intravenous laser therapy on the parameters of synaptic transmission].
The effect of serum of patients with myocardial ischemia after low-level laser therapy on parameters of synaptic conductance of rat hippocampal neurons was investigated. The serum from patients with an initially low level of neuronal activity obtained after determination of laser irradiation increased the amplitude and that from patients with high activity. Thus the process of normalization of these parameters was observed. Our results may help to optimize the course of medical treatment, and subsequently give an insight to understanding of the mechanism of therapeutic effect of laser irradiation.


Sustained Complete Remission with Incomplete Hematologic Recovery (CRi) in a Patient with Relapsed AML and Concurrent BCR-ABL1 and CBFB Rearrangement Treated with a Combination of Venetoclax and 5-Azacytidine.
The co-occurrence of BCR-ABL1 fusion and core-binding factor (CBF) rearrangements is uncommonly reported in AML. Although CBF rearrangements carry a favorable prognosis, the coexistence of BCR-ABL1 is associated with aggressive disease suggesting a potential advantage of high-intensity chemotherapy in association with tyrosine kinase inhibitors. Herein, we describe a refractory AML patient harboring BCR-ABL1 fusion and CBFB rearrangement that was successfully treated with a combination of venetoclax and hypomethylating agent.


Convergent extension by intercalation without mediolaterally fixed cell motion.
We construct and implement a stochastic model of convergent extension, using a minimal set of assumptions on cell behavior. In addition to the basic assumptions of volume conservation, random cell motion, and cell-cell and cell-ECM adhesion, and a non-standard assumption that cytoskeletal polymerization generates an internal pressure tending to keep cells convex, we find that we need only two conditions for convergent extension. (1) Each cell type has a particular aspect ratio towards which it regulates its geometry. We do not require that cells align in a specific orientation, e.g. to be oriented mediolaterally. (2) The elongating tissue is composed of cells that prefer to be elongated, and these cells must be accompanied by cells which prefer to be round. The latter effectively provide a boundary to capture. In simulations, our model tissue extends and converges to a stacked arrangement of elongated cells one cell wide, an arrangement which is seen in ascidian notochords, but which has not been observed in other models. This arrangement is achieved without any direct mediolateral bias other than that which is provided by the physical edge of the adjacent tissue.


Combined intervention of static magnetic field and growth rate of Microbacterium maritypicum CB7 for Benzo(a)Pyrene biodegradation.
In this work, we have shown for the first time that Microbacterium maritypicum CB7 bacterium is capable to use Benzo(a)Pyrene as a sole source of carbon and energy. We followed the growth kinetics of M. maritypicum CB7 in minimum medium supplemented with 10 mg/l Benzo(a)Pyrene for 30 days. The results obtained showed that M. maritypicum CB7 strain is able to degrade 69% of the initial amount of BaP. In order to improve the rate of biodegradation, we tested for 5 days the effect of a static magnetic field (SMF) at different inductions (50, 100 and 200 mT) on the degradation kinetics of Benzo(a)Pyrene by M. maritypicum CB7. Indeed, at 200 mT, we observed an increase of the yield by the twice of Benzo(a)Pyrene biodegradation rate compared to the non-induced sample. This study shows the important potential of M. maritypicum CB7 for the bioremediation of Benzo(a)Pyrene in the environment and the importance of the application of a SMF to yield the performance of the process suggesting its potential application in bioremediation of polluted sites with hydrocarbons compounds.


Laparoscopic low anterior resection for early rectal cancer.
Early rectal cancer (ERC) is adenocarcinoma that has invaded into, but not extended beyond, the submucosa. Endoscopic or minimal access surgical procedures, such as laparoscopic resection, have emerged as a useful tool in the surgical treatment of such diseases. The aim of this study is to present and analyze the feasibility, the short- and long-term results of laparoscopic colorectal surgery (LCS) in patients with ERC. Between 2002 and 4/2011, a total of 164 patients with colorectal cancer underwent laparoscopic surgery (LS). Of these, 7 patients (4.2%) had ERC and underwent laparoscopic anterior resection (LAR). The median follow-up was 41 months. The mean operative time was 2.5 h. None of the laparoscopic procedures was converted to open surgery. Liquids and solid food were started on median postoperative days 1 and 3, respectively. The median length of postoperative stay was 5 days. Postoperative complications occurred in 2 patients (28.5%), including wound infection in one patient (14.2%) and atelectasis in one patient (14.2%). None of the patients required an urgent re-operation. There was no mortality related to LS. LS for ERC can be used as a strategy sited between endoscopic mucosal resection and open anterior resection with beneficial long- and short-term results. It appears as a technically and oncologically safe procedure when performed by surgeons with sufficient experience in laparoscopic techniques.


Surgical shortening of lengthened iliac arteries in endurance athletes: Short-term and long-term satisfaction.
Endurance athletes are prone to develop flow limitations in iliac arteries (FLIA). Especially in cyclists and ice speed skaters, excessive hemodynamic loading coupled with hip hyperflexion may cause kinking in lengthened iliac arteries necessitating surgical correction. This study investigated the short-term (≤1.5 years) and long-term (≥5 years) satisfaction of operative shortening of the iliac artery in endurance athletes. All patients who were diagnosed and operated for FLIA owing to lengthened and kinked iliac arteries between 1997 and 2015 in one center were analyzed. Short-term follow-up consisted of an incremental maximal cycling test, ankle-brachial index with flexed hips, echo-Doppler examination with peak systolic velocity measurements and contrast-enhanced magnetic resonance angiography before and 6 to 18 months after surgery. Both short- and long-term satisfaction were assessed using questionnaires. A total of 83 patients (90 operated legs; 96.7% males; median age of 34 years at the time of surgery; interquartile range [IQR], 29-47) were analyzed. In the short-term, 87.5% reported symptom reduction with an 86.4% overall satisfaction rate. Symptom-free cycling improved from 272 ± 84 W to 384 ± 101 W (P < .001), whereas the maximal workload increased from 419 ± 72 W to 428 ± 67 W (P = .01). The ankle-brachial index with flexed hips increased from 0.55 (IQR, 0.45-0.65) to 0.62 (IQR, 0.52-0.74; P = .008), and the peak systolic velocity measured with hips flexed decreased from 2.50 m/s (IQR, 1.77-3.13 m/s) to 1.57 m/s (IQR, 1.20-2.04 m/s; P < .001). After a median of 12 years (IQR, 9.0-15.4 years), symptoms were still decreased in 84.1% of patients with an 81.2% overall satisfaction rate (79.5% response rate). Three patients needed a reintervention (recurrent FLIA, n = 2; failure, n = 1). Operative shortening of a lengthened and kinked iliac artery causing FLIA is successful both in the short- and long-term.


One-year clinical outcomes of percutaneous treatment with drug-eluting balloons: results from a multicenter registry.
Percutaneous coronary intervention (PCI) with paclitaxel drug-eluting balloons (DEBs) is used mainly for treatment of in-stent restenosis (ISR) and small vessel disease. Our objective was to evaluate the clinical efficacy of this strategy in a multicenter registry. Between 2009 and 2010 a prospective registry from two centers enrolled 156 consecutive patients undergoing PCI with at least one DEB. A primary composite endpoint of major adverse cardiac events (MACE) (all-cause death, myocardial infarction [MI] and target lesion revascularization [TLR]) was assessed at one-year follow-up. Stepwise Cox regression was used to determine independent predictors of outcome. DEBs (n=206) were used to treat 184 lesions. Procedural success was obtained in 98% of patients (n=150). At one-year follow-up, 86% (n=134) were free of the primary endpoint (6% death, 6% non-procedure related MI and 5% TLR). The independent predictors of MACE at one year were index PCI in the left anterior descending artery (HR 2.81, 95% CI 1.21-6.51; p=0.02) and a history of MI (HR 3.46, 95% CI 1.35-8.84; p=0.01). ISR and DEB diameter or length were not predictors of events. PCI with DEBs in real-world patients with complex lesions is effective, with a low rate of MACE, including TLR, at one-year follow-up. The results are equally good whether the intervention is for ISR or for native coronary disease.


Nullisomy for the distal portion of Xp in a male child with a X/Y translocation.
An unbalanced X/Y translocation was found in a male child with malformed external genitalia and in his mother, who are respectively nullisomic and monosomic for the distal portion of Xp and have the translocated distal segment of Yq in excess. The loss of the distal portion of Xp is supposed to be the cause of the phenotypic abnormalities present in these subjects. The phenotype of our subjects is compared with those of the other cases of X/Y translocation described in the literature.


Rapid reversed-phase high-performance liquid chromatographic analysis of steroid products.
The optimisation of conditions for the application of reversed-phase high-performance liquid chromatography (HPLC) to the analysis of steroid products is discussed. The influence of temperature and flow-rate on column efficiency are described. At 60 degrees, the reduced velocity required to give maximum efficiency, is approximately twice that found at room temperature, allowing faster through-put. (hv) curves are reported for 5-micron Spherisorb-ODS and Hypersil-ODS material for corticosteroids at 60 degrees. On-column injection techniques are discussed and data presented, showing that for corticosteroids on-column loop injection can be efficient as septum injection using the techniques described.


Trends in obesity and its distribution: data from the Northern Sweden MONICA Survey, 1986-2004.
Obesity, especially abdominal, is a risk factor for many diseases. This study explored trends in the prevalence of general and abdominal obesity, 1986-2004, in northern Sweden. Cross-sectional population surveys were performed in 1986, 1990, 1994, 1999, and 2004; 250 men and 250 women aged 25-34, 35-44, 45-54, and 55-64 years (from 1994, also 65-74 years) were randomly selected; the overall participation rate was 77%. Anthropometric data were used. Weight and BMI increased in all men, most significantly in men aged 25-64 years (P<0.0005). Weight increased in women aged 25-64 years (P<0.005) and BMI in women aged 25-44 years (P<0.005). Prevalence of obesity (BMI>or=30) increased significantly in men aged 25-44 and 55-74 years (P<0.005; for men 65-74 years old, P<0.05) and in women aged 25-44 years (P<0.005). Waist circumference decreased significantly between 1986 and 1990 in all women (P<0.005) and in men aged 55-64 years (P<0.05). After 1990 waist circumference increased, most markedly so in women; by 2004 circumference measurements for women, and for men aged 55-64 years, were equal to those of 1986, while for men aged 25-54 years they were higher. Prevalence of abdominal obesity has increased since 1990, most markedly so in women aged 45-64 years (P<0.0005). The rapid increase in both general and central obesity raises concern for the future; increasing abdominal obesity in women is particularly alarming.


Infection-induced inflammatory response of adipocytes in vitro.
Abdominal obesity plays an important role in the development of insulin resistance, diabetes mellitus and atherosclerosis. The exact pathophysiological mechanisms are unclear but adipocyte dysfunction is thought to be crucial. Infections are associated with the development of atherosclerosis as well as diabetes. In this study we investigated whether adipocytes can be infected and whether this results in production of inflammatory cytokines relevant for the development of atherosclerosis and diabetes. Pre-adipocytes were cultured and differentiated into mature adipocytes in vitro. Adipocytes and pre-adipocytes were incubated with infective and heat-inactivated Chlamydia pneumoniae, cytomegalovirus (CMV), adenovirus (Ad) subtypes 2 and 36, influenza A and respiratory syncitial virus (RSV). After 48 h, adiponectin, interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha) and plasminogen activator inhibitor-1 (PAI-1) were measured in supernatants. Infection of adipocytes with Ad-36, CMV and RSV resulted in increased IL-6 production from 192+/-22 pg ml(-1) (uninfected) to 1030+/-86 pg ml(-1), 838+/-59 pg ml(-1) and 1241+/-191 pg ml(-1), respectively (all P<0.01 vs control). In addition, Ad-36 infection slightly reduced PAI production in adipocytes (285+/-26.8 ng ml(-1) vs uninfected: 477+/-71.2 ng ml(-1); P=0.05) and pre-adipocytes (709+/-43.3 ng ml(-1) vs uninfected: 1071+/-71.8 ng ml(-1); P<0.01). In contrast, human Ad type 2 did not exert any effect on IL-6 or PAI production. None of the microorganisms induced significant changes in adiponectin and/or TNF-alpha production. Adipocytes can be infected with several microorganisms in vitro. Infection of adipocytes with Ad-36, but not Ad-2 leads to increased production of IL-6 which might contribute to chronic low-grade inflammation, a process known to be involved in the development of cardiovascular diseases and type 2 diabetes.


Structural characteristics of mangrove forest in different coastal habitats of Gulf of Khambhat arid region of Gujarat, west coast of India.
Tropical mangroves are most productive and highly sensitive to environmental change and act as good bio-indicators of the environmental quality and health of any coastal ecosystem. The present study initiated to know the current ecological status of mangrove species at four selected study sites namely Bhavnagar (Ghogha coast), Bharuch (Dahej coast), Surat (Dumas beach) and Navsari (Purna estuaries), Gulf of Khambhat, Gujarat, India. Observation for a period of one year from January 2014 to December 2014. Mangroves were evaluated for their community structures at each site by standard quadrant method and different diversity indices were used for characterize the species diversity in a mangrove community. The mangrove forest habitat supports the occurrence of a total 16 species (6 mangrove species and 10 associated plant species), 15 species occurred at Navsari, whereas 7, 6 and 10 species occurred at Bhavnagar, Bharuch and Surat respectively. Out of six mangrove species, Avicennia marina was found to be most dominant and abundant mangroves occurring among all the four study locations. The most abundant and dominant mangrove associates were Suaeda maritima and Sesuvium portulacastrum. Simpson's diversity index was varied at a range of zero to 0.6538, showing the presence of less mangrove diversity. Navsari site presented higher diversity with Shannon and Wiener Species Diversity Index of 1.179 in comparison to other sites. The present study revealed that the species abundance, density and diversity of flora associates depend upon species density and diversity of mangroves. Therefore, mangrove forest habitats need to be protected and regular assess.


Oxidative stress: changes in pregnancy and with gestational diabetes mellitus.
Pregnancy is susceptible to oxidative stress and antioxidant defenses can be altered in response to elevated levels of oxidative stress. Limited data in gestational diabetes mellitus (GDM) suggest that products of lipid peroxidation may be increased and antioxidant enzyme activities decreased, although the results have been inconsistent. As in type 2 diabetes mellitus (T2DM), glycemic levels in patients with GDM correlate with concentrations of lipid peroxides. The effects of supplementation with antioxidants or antioxidant-rich food in T2DM are controversial. Whether or not increased antioxidant intake can reduce the complications of GDM in both mother and fetus has not been explored.


Formation of reentrant circuits in the mid-myocardial infarct border zone.
In this study, the mechanisms for onset and maintenance of mid-myocardial (intramural) reentrant circuits are considered, based upon anatomical structure. A model of electrical activation wavefront curvature in the mid-myocardial postinfarction border zone is developed. Two arrhythmogenic structures are considered: 1. a constrained slab of viable tissue, and 2. a strand of surviving myocardial fibers with distal expansion. Equations are formulated to estimate activation coupling intervals, and ranges in taper and circuit dimensions, that will support functional conduction block during premature stimulation and reentrant ventricular tachycardia. For onset and maintenance of reentry, the arrhythmogenic regions forming both slab and strand circuits are in the range of 50-600µm at their thinnest dimension. For constrained slabs, unidirectional block leading to reentry forms in the thin-to-thick direction during premature stimulation, and functional block at lateral boundaries enable formation of a double-loop circuit. The activation wavefront proceeds around the impediment and then curves in the opposite direction through the slab, reentering the previously excited tissue. For strands, unidirectional block forms at a distal expansion in response to premature stimulation. The strand reentrant circuit is bounded by infarcted tissue causing anatomical block, and can be single-loop or coaxial. For all architectures, circuit dimensions ranging from 1.6×1.6mm to 3.5×3.5mm support functional block when premature stimulus coupling intervals are 117-150ms and ventricular tachycardia cycle lengths are 160-350ms. For slab and strand mid-myocardial arrhythmogenic structures, taper and circuit dimensions govern ranges in premature excitation coupling intervals and tachycardia cycle lengths necessary to support functional block.


Erythropoietin, erythropoesis and iron status in children after major surgical stress.
The aim of our study was to evaluate bone marrow stimulation and bone marrow response to post-operative anaemia in children after open heart surgery. In 16 children (age 5.7 +/- 0.9 years, weight 20.1 +/- 3.2 kg) serum erythropoietin, haematocrit, reticulocyte count, ferritin, transferrin saturation and C-reactive protein were assessed perioperatively after cardiopulmonary bypass for surgical repair of atrial septal defect. Erythropoietin increased seven fold from 14 +/- 6.2 (7-30) to 80 +/- 49 (20-171) mU/ml (P < 0.05) and the reticulocyte count a 1.7-fold from 11.1 +/- 3.1 (6-19) to 18.4 +/- 5.9 (10-31) / 1000 (P < 0.05). Transferrin saturation was inversely correlated to C-reactive protein. These findings suggest adequate bone marrow stimulation but an inadequate bone marrow response during the immediate perioperative period, caused by inhibition of erythropoesis by acute postoperative inflammation in children after open heart surgery.


Histamine release from isolated rat mast cells induced by opiates: effect of sterical configuration and calcium.
The stereospecificity of the action of opiates on rat mast cells was investigated by means of the l- and d-isomers levorphanol and dextrorphan. The dose-response curves for histamine release induced by the 2 drugs were of a similar shape with a maximum at 2 X 10(-3) M and a pronounced minimum at 5 X 10(-3) M. At concentrations below 5 X 10(-3) M the effect of both drugs resembled that of morphine, i.e. the release occurred rapidly and inhibition was observed with naloxone, codeine, and antimycin A. Levorphanol, dextrorphan, and the antagonist levallorphan at concentrations above 5 X 10(-3) M seemed to be toxic to mast cells. The uptake of 45Ca in connection with histamine release induced by pethidine, levorphanol, and dextrorphan was lower than that of control cells, whereas the uptake induced by morphine did not differ from that of controls. The inhibition of compound 48/80-induced histamine release by morphine was paralleled by a reduced 45Ca uptake. The time course for the inhibitory effect of preincubation with morphine was similar for the histamine released induced by morphine and by compound 48/80. Washing of the cells after preincubation with morphine was without effect on the inhibition of morphine-induced histamine release, whereas the inhibition of compound 48/80 was reduced. The present observation with morphine and compound 48/80 support our previous impression of similarities in their mode of action, but a mechanism implying an interference by morphine with the disposition of calcium could also account for the findings. The observed antagonism between morphine and calcium resembles that of opiate receptors, but histamine release induced by opiates does not involve stereospecific opiate receptors.


Gastric volvulus: An uncommon and life threatening cause of acute gastric dilatation in a young male: A case report.
Gastric volvulus leading to acute gastric dilatation is a surgical emergency that should be considered as a differential in patients who present to the emergency department with severe epigastric pain and evidence of gastric outlet obstruction. This condition requires a high index of suspicion that enables early diagnosis and treatment.


High-content screening of Thai medicinal plants reveals Boesenbergia rotunda extract and its component Panduratin A as anti-SARS-CoV-2 agents.
Since December 2019, the emergence of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has caused severe pneumonia, a disease named COVID-19, that became pandemic and created an acute threat to public health. The effective therapeutics are in urgent need. Here, we developed a high-content screening for the antiviral candidates using fluorescence-based SARS-CoV-2 nucleoprotein detection in Vero E6 cells coupled with plaque reduction assay. Among 122 Thai natural products, we found that Boesenbergia rotunda extract and its phytochemical compound, panduratin A, exhibited the potent anti-SARS-CoV-2 activity. Treatment with B. rotunda extract and panduratin A after viral infection drastically suppressed SARS-CoV-2 infectivity in Vero E6 cells with IC50 of 3.62 μg/mL (CC50 = 28.06 µg/mL) and 0.81 μΜ (CC50 = 14.71 µM), respectively. Also, the treatment of panduratin A at the pre-entry phase inhibited SARS-CoV-2 infection with IC50 of 5.30 µM (CC50 = 43.47 µM). Our study demonstrated, for the first time, that panduratin A exerts the inhibitory effect against SARS-CoV-2 infection at both pre-entry and post-infection phases. Apart from Vero E6 cells, treatment with this compound was able to suppress viral infectivity in human airway epithelial cells. This result confirmed the potential of panduratin A as the anti-SARS-CoV-2 agent in the major target cells in human. Since B. rotunda is a culinary herb generally grown in China and Southeast Asia, its extract and the purified panduratin A may serve as the promising candidates for therapeutic purposes with economic advantage during COVID-19 situation.


Synthesis, characterization and antiproliferative activity of 1,2-naphthoquinone and its derivatives.
In the present study substituted 1,2-naphthoquinones were synthesized, purified and characterized by spectroscopic studies (UV, FT-IR, ¹H NMR, ¹³ C NMR and elemental analysis). These compounds were evaluated for cytotoxicity against a panel of human cancer cell lines (Hep-G₂ for liver sarcoma, MG-63 for osteosarcoma and MCF-7 for human breast cancer). The cells were dosed with these ortho-naphthoquinone derivatives at varying concentrations, and cell viability was measured by a 3-(4,5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay with doxorubicin as positive control. Significant anticancer activities were observed in vitro for some members of the series, and compounds 1,2-naphthoquinone 2-thiosemicarbazone, 1,2-naphthoquinone-2-semicarbazone, 4-amino-1,2-naphthoquinone 2-thiosemicarbazone and 4-amino-1,2-naphthoquinone-2-semicarbazone are active cytotoxic agents against different cancer cell lines with IC₅₀ values in the range of 5.73-17.67 μM. The obtained data suggested that better anticancer activity was linked with introduction of thiosemicarbazone and semicarbazone moiety in 1,2-naphthoquinone ring system. Outcomes of experimentation also reveal that incorporation of amino group in 1,2-naphthoquinone moiety contributes positively for cytotoxic action of compounds. Docking experiments showed a good correlation between their calculated interaction energies with the topoisomerase-II and the observed IC₅₀ values of all these compounds.


Protective effects of methane-rich saline on diabetic retinopathy via anti-inflammation in a streptozotocin-induced diabetic rat model.
As the commonest complication of diabetes mellitus (DM), diabetic retinopathy (DR) is a neuro-vascular disease with chronic inflammatory. Methane could exert potential therapeutic interest in inflammatory pathologies in previous studies. Our study aims to evaluate the protective effects of methane-rich saline on DR and investigate the potential role of related MicroRNA (miRNA) in diabetic rats. Streptozotocin-induced diabetic Sprague-Dawley rats were injected intraperitoneally with methane-rich or normal saline (5 ml/kg) daily for eight weeks. Morphology changes and blood-retinal barrier (BRB) permeability were assessed by hematoxylin eosin staining and Evans blue leakage. Retinal inflammatory cytokines levels of tumor necrosis factor-α (TNF-α) and interleukin-1β (IL1-β) were evaluated by immunohistochemistry. Retinal protein expressions of glial fibrillary acidic protein (GFAP) and vascular endothelial growth factor (VEGF) were determined by western blotting. Retinal miRNA expressions were examined by miRNA-specific microarray, verified by quantitative RT-PCR and predicted by GO enrichment and KEGG pathway analysis. There was no significant changes in blood glucose level and body weight of diabetic rats with methane-rich or normal saline treatment, but the decreased retinal thickness, retinal ganglial cell loss and BRB breakdown were all significantly suppressed by methane treatment. DM-induced retinal overexpressions of TNF-α, IL-1β, GFAP and VEGF were also significantly ameliorated. Moreover, the methane treatment significantly up-regulated retinal levels of miR-192-5p (related to apoptosis and tyrosine kinase signaling pathway) and miR-335 (related to proliferation, oxidative stress and leukocyte). Methane exerts protective effect on DR via anti-inflammation, which may be related to the regulatory mechanism of miRNAs.


Sources of organic pollution in particulate matter and soil of Silesian Agglomeration (Poland): evidence from geochemical markers.
The exact input of particular sources to polycyclic aromatic hydrocarbons (PAHs) concentrations in urban and industrial agglomerations is still not well recognized. The major breakthrough is possible using geochemical markers. In the air aerosol and soil samples from areas located in the direct influence of industry/traffic in Silesian Agglomeration (Poland), PAHs and other organic compounds were analyzed, including geochemical markers (biomarkers) and polar compounds from fossil fuels and biomass. Gas chromatography (GC-FID) and gas chromatography-mass spectrometry (GC-MS) were applied to investigate the composition of particulate matter and soil extracts. The results suggest that the predominant source of PAHs is fossil fuel. The presence and distribution of steranes, pentacyclic triterpenoids (i.e., hopanes and moretanes) and alkyl PAHs point to traffic emissions and fossil fuel combustion, mainly bituminous coal for power and heat purposes, as the main source of PAHs in the region. Moreover, the presence of fossil fuel biomarker in particulate matter and soil extracts from a rural site, previously considered to be free of organic pollution, requires a cautious interpretation for PAHs results. Apart from the fossil fuel, also other sources of contamination were identified in particulate matter extracts by their markers: phenols and levoglucosan for biomass and diisopropylnaphthalenes for printing materials combustion. The absence of polar biomass combustion indicators in soil extracts might be related to their higher reactivity.


Effect of butylated hydroxyanisole on the level of DNA adduction by aristolochic acid in the rat forestomach and liver.
Administration of butylated hydroxyanisole (BHA) orally at either 0.5 g or 1 g/kg daily for 14 days to rats did not produce any DNA adducts in the forestomach as measured by the 32P-postlabeling method using (1) limiting concentrations of 32P-ATP; (2) nuclease P1 enhancement; or (3) butanol extraction. Experiments were conducted to establish the effects of BHA administration on aristolochic acid (AA) DNA adduct formation in the forestomach and liver, when BHA was administered prior to, together with or after AA administration. Adduct levels per 10(9) nucleotides in the liver after oral dosing daily for 5 days with 1 mg/kg AA and BHA (1 g/kg) or corn oil (5 ml/kg) for 7 days were as follows: (a) BHA and AA given simultaneously; 235 +/- 71, (b) AA + corn oil; 63 +/- 39, (c) AA followed by BHA; 57 +/- 13, (d) AA followed by corn oil; 91 +/- 38, (e) BHA followed by AA; 90 +/- 12, (f) corn oil followed by AA; 83 +/- 24. For the forestomach the values were: (a) 236 +/- 86, (b) 77 +/- 25, (c) 367 +/- 97, (d) 296 +/- 47, (e) 217 +/- 81, (f) 70 +/- 64. These data suggest that BHA could have an enhancing effect on AA-induced lesions in the forestomach if dosed together with, or prior to, AA as adduct levels are significantly higher than in controls.


Evaluation of three second-generation and three confirmatory assays for antibodies to human immunodeficiency virus.
The second-generation enzyme immunoassays (EIAs) for antibodies against human immunodeficiency virus (HIV) from three manufacturers (Abbott, Organon, Wellcome) and three anti-HIV confirmatory tests, i.e. Western Blot (WB, Biotech, Dupont), radioimmunoprecipitation assay (RIPA, CLB) and a competitive immunoassay (CIA, Abbott) were evaluated on a panel of 6,488 serum samples, which had previously been used for the comparison of seven first-generation EIAs. For the present study the panel was expanded with sequential serum samples from 12 individuals followed at 1- to 3-month intervals during seroconversion for anti-HIV. The second-generation EIAs and confirmatory tests were significantly more sensitive than the first-generation EIAs as was demonstrated by detection of 10- to 100-fold higher endpoint titers in anti-HIV-positive sera as well as by earlier detection of anti-HIV in 7-11 of the 12 subjects, who seroconverted. In all sera obtained during early HIV infection anti-gp 160/120env antibodies (WB, CIA) were found in addition to anti-p24 (WB, RIPA) and in serial twofold dilutions of these 'seroconversion samples' the new Abbott EIA and RIPA were significantly more sensitive than WB (p less than 0.05), whereas CIA and the new Organon EIA were significantly less sensitive than WB (p less than 0.05). The new Wellcome EIA was not statistically less sensitive than WB. The CIA was as sensitive as WB for antibodies to envelope proteins (gp41, gp160, gp120), but considerably less sensitive for core (p24) antibodies, as was shown in sera obtained during early as well as later clinical stages of HIV infection.(ABSTRACT TRUNCATED AT 250 WORDS)


The tendency to sign-track predicts cue-induced reinstatement during nicotine self-administration, and is enhanced by nicotine but not ethanol.
Some individuals are particularly responsive to reward-associated stimuli ("cues"), including the effects of these cues on craving and relapse to drug-seeking behavior. In the cases of nicotine and alcohol, cues may acquire these abilities via the incentive-enhancing properties of the drug. To determine the interaction between cue-responsivity and nicotine reinforcement, we studied the patterns of nicotine self-administration in rats categorized based on their tendency to approach a food-predictive cue ("sign-trackers") or a reward-delivery location ("goal-trackers"). In a second experiment, we determined whether nicotine and ethanol altered the incentive value of a food cue. Rats were classified as sign- or goal-trackers during a Pavlovian conditioned approach paradigm. Rats then self-administered intravenous nicotine (0.03 mg/kg infusions) followed by extinction and cue-induced reinstatement tests. We also tested the effects of nicotine (0.4 mg/kg base s.c.) or ethanol (0.7 g/kg i.p.) on the approach to, and reinforcing efficacy of, a food cue. Sign-trackers showed greater reinstatement in response to a nicotine cue. Further, nicotine enhanced sign-tracking but not goal-tracking to a food cue and also enhanced responding for the food cue during the conditioned reinforcement test. Conversely, ethanol reduced sign-tracking and increased goal-tracking, but had no effect on conditioned reinforcement. Our studies demonstrate that the tendency to attribute incentive value to a food cue predicts enhanced cue-induced reinstatement. Additionally, the incentive value of food cues is differentially modulated by nicotine and ethanol, which may be related to the reinforcing effects of these drugs.


Use of etonogestrel implant beyond approved duration: prolonged contraceptive effectiveness.
The subdermal etonogestrel contraceptive implant has a current approved duration of 3 years. There is, however, recent and strong evidence of its effectiveness for 2 additional years during which no pregnancies were documented. We report a case of a 28-year-old woman who had an etonogestrel implant inserted 4 years earlier and wished to get pregnant. The implant was, however, deep in the triceps muscle and could not easily be removed. Her serum levels of etonogestrel remained positive even 6 years after insertion. As infertility investigation revealed endometriosis and bilateral tubal obstruction she was referred for assisted reproduction. Despite obtaining oocytes during an ovarian stimulation cycle, the endometrium was never above 4 mm, precluding embryo transfer. It was decided to remove the implant in order to improve endometrial conditions, after which the patient achieved pregnancy. This case report suggests that the etonogestrel implant is effective for even longer than the most recent studies have shown.


The decisional balance, attitudes, and practice behaviors, its predicting factors, and related experiences of advance care planning in Taiwanese patients with advanced cancer.
Patients with advanced cancer are prone to experience burdensome physical, psychological, and financial consequences. Healthcare providers may not fully appreciate advanced cancer patients' medical care autonomy, such as at that emboded by Advance Care Planning (ACP), and by doing so may compromise their quality of end-of-life (EOL). Hence, it is essential for healthcare providers to effectively assess and communicate with patients' regarding their medical decisions before their patients are incapacitated by their disease progression. The purpose of this investigation was to describe the decisional balance, attitudes, and practice behaviors of ACP and its predictors of ACP-related experiences in Taiwanese patients with advanced cancer. This cross-sectional, descriptive study employed a mixed-methodsquantitative and qualitative design with a sample of 166 patients that were purposely recruited from in-patient oncology units at a regional teaching hospital in southern Taiwan. Study data consisted of patient replies to a 34-item self-report tool, Decisional Balance, Attitudes, Practice Behaviors of ACP (DAP-ACP) and 4 semi-structured questions. Findings indicated that, in general, study participants exhibited favorable ACP-decisional balance and positive ACP-attitudes & practice behaviors. The results also indicated that gender, educational level, and cancer diagnosis were associated with significant differences on the "ACP-decisional balance" and "ACP-attitudes" scales. In addition, our findings documented that the participants' gender and educational level were significant predictors of both ACP-decisional balance and ACP-attitudes. Furthermore the participants' ACP-practice behaviors were predicted by ACP-decisional balance, but not with their ACP-attitudes. The qualitative analysis of the semi-structured questions identified six themes in responses to current medical decision making (e.g., compliance with physician instructions, family engagement in treatment decision-making); and eight themes pertaining to future ACP-related concerns were identified (e.g., family conflict, effectiveness of time-limited trials). To promote patients' engagement in ACP, the healthcare professional need to assess and advocate patients' concerns or attitudes regarding ACP in a timely manner. In addition, factors or concerns that might influence patients' responses to ACP derived from both the quantitative and qualitative findings of this current study need to be considered especially in initiating the dialogue regarding ACP with patients with advanced cancer. No. CYCH 2,019,072, Date of registration 5 Dec 2019.


Rates of progesterone oxidation by rabbit liver microsomes before and after phenobarbitone treatment.
Liver sections, removed from outbred NZW rabbits under anesthesia, were used to determine the rates of progesterone oxidation prior to assessment of the effects of phenobarbitone(PB)-treatment. Progesterone 21-hydroxylase exhibited the same high affinity, low Km kinetics before and after PB-treatment, whereas the Vmax was significantly reduced. PB-treatment did not affect progesterone 21-hydroxylation by the adrenal microsomes of two groups of PB-treated and untreated rabbits. 21-Hydroxylase activity was detected for the first time with spleen microsomes but the majority of spleens examined lacked activity. 6 beta-Hydroxylation by control liver microsomes showed consistently low affinity, high Km-values and was inhibited to a lesser, inconsistent degree than 21-hydroxylation by PB-treatment.


Population biology of the checkerspot butterfly, Euphydryas chalcedona structure of the Jasper Ridge colony.
Euphydryas chalcedona at Jasper Ridge consists of two independently varying major demographic units, similar in scale but not in structure to those of Euphydryas editha. In contrast, however, Jasper Ridge E. chalcedona represent just a portion of a deme-while E. editha occurs as two partially connected demes. The life history and general ecology of E. chalcedona is described and compared with those of its intensively-studied congener. Various problems of mark-release-recapture estimation of population size are discussed.


Influence of tillage systems and sowing dates on the incidence of leaf spot disease in Telfairia occidentalis caused by Phoma sorghina in Cameroon.
The production and leaf quality of Telfairia occidentalis in Cameroon are gravely threatened by leaf spot disease. A field study was conducted in July 2019 and 2020 to determine the influence of tillage systems and sowing dates on the incidence of Telfairia occidentalis leaf spot caused by Phoma sorghina. A randomized block design with three replications and four planting dates was used. The soil physicochemical properties were also determined. Data for disease incidence were registered once every two weeks and submitted to generalized linear model for statistical analysis. The means were separated by Duncan's multiple range test at a 95% confidence interval. Calculations for disease incidence and statistical analysis were conducted using the Microsoft Excel program and SPSS version 23, respectively. Statistical analysis revealed that the zero tilled field generally registered a lower leaf spot disease incidence than the tilled field, which was highly significant (p ≤ 0.05). In addition, the second sowing date in the zero tilled field proved to be better in terms of low disease incidence than other sowing dates employed in the study. Therefore, to minimize the devastating effects of leaf spot disease, zero tillage coupled with the second sowing date could be exploited.


Association of the MTHFR 677C>T and 1298A>C polymorphisms and male infertility risk: a meta-analysis.
One of the possible male sterility risk factors are polymorphisms of Methylenetetrahydrofolate reductase (MTHFR). However, the epidemiologic investigations described inconsistent results regarding MTHFR polymorphism and the risk of male infertility. For that reason, we carried out a meta-analysis of published case-control studies to re-examine the controversy. Electronic searches of Cochrane, EMBASE, Google Scholar, and PubMed were conducted to select eligible studies for this meta-analysis (updated to May 2019). According to our exclusion and inclusion criteria, only high-quality studies that remarked the association between MTHFR polymorphisms and male infertility risk were included. The Crude odds ratio (OR) with a confidence interval of 95% (CI) was used to assess the relationship between MTHFR polymorphism and male infertility risk. Thirty-four case-control studies with 9662 cases and 9154 controls concerning 677C/T polymorphism and 22 case-control studies with 5893 cases and 6303 controls concerning 1298A/C polymorphism were recruited. Both MTHFR polymorphisms had significant associations with male infertility risk (CT + TT vs. CC: OR = 1.37, 95% CI: 1.21-1.55, P = 0.00, I2 = 41.9%); (CC vs. CA + AA: OR = 0.82, 95% CI: 0.52-1.30, P = 0.04, I2 = 50.1%). Further, when stratified by ethnicity, the significant association results were observed in Asians and Caucasians for 677C/T and just Asians for 1298A/C. Some of MTHFR polymorphisms like MTHFR 677C > T are associated with an elevated male infertility risk. To confirm our conclusion and to provide more accurate and complete gene-environment communication with male infertility risk, more analytical studies are needed.


Role of tissue transglutaminase-2 (TG2)-mediated aminylation in biological processes.
Post-translational modification (PTM) is an important mechanism in modulating a protein's structure and can lead to substantial diversity in biological function. Compared to other forms of PTMs such as phosphorylation, acetylation and glycosylation, the physiological significance of aminylation is limited. Aminylation refers to the covalent incorporation of biogenic/polyamines into target protein by calcium-dependent transglutaminases (TGs). The development of novel and more sensitive techniques has led to more proteins identified as tissue transglutaminase (TG2) substrates and potential targets for aminylation. Many of these substrate proteins play a role in cell signaling, cytoskeleton organization, muscle contraction, and inflammation. TG2 is well studied and widely expressed in a variety of tissues and will be the primary focus of this review on recent advance in transglutaminase-mediated aminylation.


Methodology for Exploring Patterns of Epigenetic Information in Cancer Cells Using Data Mining Technique.
Epigenetic changes are a necessary characteristic of all cancer types. Tumor cells usually target genetic changes and epigenetic alterations as well. It is most beneficial to identify epigenetic similar features among cancer various types to be able to discover the appropriate treatments. The existence of epigenetic alteration profiles can aid in targeting this goal. In this paper, we propose a new technique applying data mining and clustering methodologies for cancer epigenetic changes analysis. The proposed technique aims to detect common patterns of epigenetic changes in various cancer types. We demonstrated the validation of the new technique by detecting epigenetic patterns across seven cancer types and by determining epigenetic similarities among various cancer types. The experimental results demonstrate that common epigenetic patterns do exist across these cancer types. Additionally, epigenetic gene analysis performed on the associated genes found a strong relationship with the development of various types of cancer and proved high risk across the studied cancer types. We utilized the frequent pattern data mining approach to represent cancer types compactly in the promoters for some epigenetic marks. Utilizing the built frequent pattern item set, the most frequent items are identified and yield the group of the bi-clusters of these patterns. Experimental results of the proposed method are shown to have a success rate of 88% in detecting cancer types according to specific epigenetic pattern.


Two cases of congenital arteriovenous fistulae of the lower leg treated by percutaneous arterial embolization.
Massive congenital arteriovenous fistulae of the lower limb is a relatively rare disorder that is difficult to treat surgically and often can be managed by percutaneous embolic occlusion. We report two cases of massive congenital arteriovenous fistulae of the lower limb with refractory leg ulcer treated by superselective arterial catheterization and embolization with metal coils. In both cases, the ulcer disappeared and the pigmentation became paler after embolization.


Binding and Characterization of DNA Origami Nanostructures on Lipid Membranes.
DNA origami is an extremely versatile nanoengineering tool with widespread applicability in various fields of research, including membrane physiology and biophysics. The possibility to easily modify DNA strands with lipophilic moieties enabled the recent development of a variety of membrane-active DNA origami devices. Biological membranes, as the core barriers of the cells, display vital structural and functional roles. Therefore, lipid bilayers are widely popular targets of DNA origami nanotechnology for synthetic biology and biomedical applications. In this chapter, we summarize the typical experimental methods used to investigate the interaction of DNA origami with synthetic membrane models. Herein, we present detailed protocols for the production of lipid model membranes and characterization of membrane-targeted DNA origami nanostructures using different microscopy approaches.


Physicochemical characterization of high- and low-melting phenylephrine oxazolidines.
Phenylephrine oxazolidine is a new prodrug of phenylephrine developed for improving ocular absorption and reducing systemic side effects. In the present study, high- and low-melting phenylephrine oxazolidines (HMP and LMP) were characterized in terms of their stereochemistry and crystal properties. It was found that the molecular configuration of the prodrug in the crystals of either HMP or LMP is identical (5R/2R). The two crystals were shown to have the same IR spectra and X-ray diffraction patterns but different crystal habits, thermal properties, solubilities and intrinsic dissolution rates. Single crystal X-ray structure analysis indicates that crystals of both HMP and LMP are orthorhombic and belong to the P2(1)2(1)2(1) space group with four molecules in a unit cell (a = 20.697 A, b = 7.065 A, and c = 9.304 A). The molecules in the crystal are held together by an intermolecular hydrogen bonding interaction between N(3) and O(13). The different physical properties observed for LMP result from crystal imperfections caused by the presence of trace amounts (often at levels < 0.5%) of an unidentified, structurally related synthetic impurity which can be dispersed in the prodrug. It was observed that both HMP and LMP can sustain thermal and mechanical treatment in the solid state. However, LMP was partially converted to HMP when suspended in certain solvents.


Cell division cycle genes nda2 and nda3 of the fission yeast Schizosaccharomyces pombe control microtubular organization and sensitivity to anti-mitotic benzimidazole compounds.
Two genes, nda2 and nda3, previously defined by cold sensitive nuclear division arrest (nda) mutations in the fission yeast Schizosaccharomyces pombe were studied. A mutant nda2-KM52 was found to be supersensitive (at the permissive temperature) to the tubulin-binding drugs such as thiabendazole, methylbenzimidazol-2yl carbamate and nocodazole. A single mutation in nda2 appears to cause both drug supersensitivity and cold sensitivity. The defective phenotypes of nda2-KM52 with a low concentration of the drugs were characterized by nuclear displacement and anomalously situated spindle pole bodies. The allele of the other mutant, nda3-KM311, was sh216 to be linked closely to the ben1 locus, which determines resistance to the drug. The identity of ben1 and nda3 genes was proved by a newly isolated mutant ben1-TB1005; it manifests ben1 resistance and the cold sensitive nda3 phenotype. At 22 degrees C, ben1-TB1005 showed cell branching and deformation characteristic of nda3-KM311. Eleven mutants supersensitive to thiabendazole were newly isolated by replica plating. Four strains were mapped in nda2, while the other four were in nda3. Most of the isolated mutants were blocked at nuclear division in the presence of a low concentration of the drug. Thus, the products of genes nda2 and nda3 (ben1) interact directly or indirectly with the drugs and control, in different ways, microtubular organization in the cells of S. pombe.


Expression of sialylated MUC1 in prostate cancer: relationship to clinical stage and prognosis.
MUC1 is distributed among a variety of normal epithelial tissues, and overexpression of MUC1 is detected in several human cancers. This study aimed to elucidate whether sialylated MUC1 expression correlated with: (i) clinical stage of prostate cancer; (ii) pathological grade of prostate cancer; (iii) pretreatment serum level of prostate-specific antigen (PSA); or (iv) the disease prognosis in patients with prostate cancer who received endocrine therapy. We collected 57 biopsy specimens from prostate cancer patients treated with only endocrine therapy, and 10 specimens of normal prostates. These specimens were stained immunohistochemically by using a novel monoclonal antibody, MY.1E12, to detect sialylated MUC1. The levels of expression, clinical stages, pathological grades, pretreatment serum level of PSA and the prognoses of the patients were statistically analyzed for correlations. There were statistically significant correlations between the expression of sialylated MUC1 and pathological grades (WHO grade, P<0.01; Gleason score, P<0.05). Expression increased according to the progression of the disease (existence of clinical metastasis, P<0.05; clinical T-stage, P<0.01). Patients with high serum levels of PSA had higher expression than those with low levels (P<0.01). The level of sialylated MUC1 significantly correlated with progression-free survival (P<0.01) and cause-specific survival (P<0.01) according to univariate analyses. Furthermore, the level significantly correlated with progression-free survival according to multivariate analysis. These results suggest that sialylated MUC1 plays an important role in the progression of prostate cancer, and that its expression level in the primary lesion is a useful marker for the prognoses of patients undergoing endocrine therapy.


Phase transformations during processing and in vitro degradation of porous calcium polyphosphates.
A 2-Step sinter/anneal treatment has been reported previously for forming porous CPP as biodegradable bone substitutes [9]. During the 2-Step annealing treatment, the heat treatment used strongly affected the rate of CPP degradation in vitro. In the present study, x-ray diffraction and (31)P solid state nuclear magnetic resonance were used to determine the phases that formed using different heat treating processes. The effect of in vitro degradation (in PBS at 37 °C, pH 7.1 or 4.5) was also studied. During CPP preparation, β-CPP and γ-CPP were identified in powders formed from a calcium monobasic monohydrate precursor after an initial calcining treatment (10 h at 500 °C). Melting of this CPP powder (at 1100 °C), quenching and grinding formed amorphous CPP powders. Annealing powders at 585 °C (Step-1) resulted in rapid sintering to form amorphous porous CPP. Continued annealing to 650 °C resulted in crystallization to form a multi-phase structure of β-CPP primarily plus lesser amounts of α-CPP, calcium ultra-phosphates and retained amorphous CPP. Annealing above 720 °C and up to 950 °C transformed this to β-CPP phase. In vitro degradation of the 585 °C (Step-1 only) and 650 °C Step-2 annealed multi-phase samples occurred significantly faster than the β-CPP samples formed by Step-2 annealing at or above 720 °C. This faster degradation was attributable to preferential degradation of thermodynamically less stable phases that formed in samples annealed at 650 °C (i.e. α-phase, ultra-phosphate and amorphous CPP). Degradation in lower pH solutions significantly increased degradation rates of the 585 and 650 °C annealed samples but had no significant effect on the β-CPP samples.


Factors influencing outcome in Guillain-Barré Syndrome: comparison of plasma adsorption against other treatments.
This study was performed to evaluate which factors influence the outcome of Guillain-Barré Syndrome (GBS), focusing on the choice of treatments. Sixty-three GBS patients were retrospectively studied and the following factors were evaluated: sex, age, days from onset of disease to the start of treatment, severity of symptoms, prior infection, autonomic dysfunction, bulbar palsy, anti-ganglioside antibody, and disease form, as well as the choice of treatment. Plasma adsorption (PA, n=39), plasma exchange (PE, n=14), or immunoglobulin treatment (IVIg, n=10) were performed in this study. Outcomes were evaluated using the functional grading scale (FGS) of Hughes. The number of days needed for one functional grade improvement was significantly longer in the elderly, the severe symptom group, and patients with acute motor axonal form, and days needed for two functional grade improvement was significantly longer in the elderly, patients with autonomic dysfunction, and acute motor axonal form. The choice of treatments (PA, PE, or IVIg) did not significantly influence the outcome as determined by both univariate and multivariate analysis. Although patient age, symptoms, and disease form influenced the outcome, treatment methods did not significantly influence the outcome. Since PA does not result in a risk of unknown infection, choosing a PA treatment may be justified, especially for patients (or doctors) who may be anxious about a possibility of unknown infection.


A biomechanical comparison of EndoButton versus suture anchor repair of distal biceps tendon injuries.
The purpose of this study was to compare suture anchor and EndoButton repair of distal biceps injuries in a human bone-tendon model. Right and left arm repairs were alternately performed with either the EndoButton or 2 single-loaded 5-mm suture anchors. Each construct was cyclically loaded by use of a servohydraulic materials testing machine. Initial and final displacements were recorded. All repairs were then loaded to ultimate failure. Ten millimeters of displacement was designated the clinical failure point. The EndoButton group had more stiffness than the suture anchor group during initial cyclic loading (P = .01). There were no differences in final displacement measured after cyclic loading (2.06 mm for suture anchors and 2.58 mm for EndoButton). The EndoButton group had a 16% greater ultimate tensile load than the suture anchor group (274.77 N vs 230.06 N). The EndoButton group also had a 16% higher load to clinical failure (249.95 N vs 209.56 N). These differences were not statistically significant. The EndoButton and suture anchors provide comparable fixation strength for the repair and rehabilitation of distal biceps tendon ruptures.


Making Space for Midwifery in a Hospital: Exploring the Built Birth Environment of Canada's First Alongside Midwifery Unit.
Canada's first alongside midwifery unit (AMU) was intentionally informed by evidence-based birth environment design principals, building on the growing evidence that the built environment can shape experiences, satisfaction, and birth outcomes. To assess the impact of the built environment of the AMU for both service users and midwives. This study aimed to explore the meanings that individuals attribute to the built environment and how the built environment impacted people's experiences. We conducted a mixed-methods study using a grounded theory methodology for data collection and analysis. Our research question and data collection tools were underpinned by a sociospatial conceptual approach. All midwives and all those who received midwifery care at the unit were eligible to participate. Data were collected through a structured online survey, interviews, and focus group. Fifty-nine participants completed the survey, and interviews or focus group were completed with 28 service users and 14 midwives. Our findings demonstrate high levels of satisfaction with the birth environment. We developed a theoretical model, where "making space" for midwifery in the hospital contributed to positive birth experiences and overall satisfaction with the built environment. The core elements of this model include creating domestic space in an institutional setting, shifting the technological approach, and shared ownership of the unit. Our model for creating, shifting, and sharing as a way to make space for midwifery can serve as a template for how intentional design can be used to promote favorable outcomes and user satisfaction.


Development of canine herpesvirus based antifertility vaccines for foxes using bacterial artificial chromosomes.
Using bacterial artificial chromosome (BAC) technology, a canine herpesvirus (CHV)-based recombinant vaccine vector was produced for the development of an antifertility vaccine for foxes. Infectious viruses were recovered following transfection of canid cells with a BAC plasmid carrying the complete CHV genome. In vitro growth characteristics of BAC-derived viruses were similar to that of wildtype (wt)-CHV. Two recombinant antigens, fox zona pellucida protein subunit 3 (fZPC) and enhanced green fluorescent protein (EGFP) as control antigen, were inserted into thymidine kinase (TK) locus of the CHV genome and shown to be efficiently expressed in vitro. Inoculation of foxes with transgenic CHVs induced CHV specific antibodies, but was innocuous and failed to elicit transgene-specific antibody responses. Infectious virus or viral DNA was not detected in mucosal secretions or tissues of vaccinated foxes. The CHV-BAC system proved to be a quick and reliable method to manipulate the CHV genome. It will help to readily apply changes in the vector design in order to improve virus replication in vivo.


Female sex, high soluble CD163, and low HDL-cholesterol were associated with high galectin-3 binding protein in type 1 diabetes.
Galectin-3 binding protein (Gal3BP), sCD163, galectin-3, and depression have been linked to cardiovascular disease and mortality. In patients with type 1 diabetes, female sex has also been linked to cardiovascular disease and mortality. The aim was to explore whether female sex, sCD163, galectin-3, and depression were associated with Gal3BP in patients with type 1 diabetes. We adjusted for metabolic variables, creatinine, smoking, physical inactivity, and cardiovascular disease. Cross-sectional design. Patients with type 1 diabetes (n = 285, women 44%, age18-59 years, diabetes duration 1-55 years) were consecutively recruited from one diabetes outpatient clinic. Blood samples, anthropometrics, and blood pressure were collected, supplemented with data from electronic medical records. High Gal3BP was defined as ≥3.3 mg/l (≥80th percentile). Depression was assessed by a self-report instrument. Linear and logistic regression models were elaborated for the associations and calibrated and validated for goodness of fit with the data variables. Median (q1, q3) Gal3BP was 2.3 (1.8, 3.1) mg/l. The prevalence of high Gal3BP for women was 30% and 14% for men (p = 0.001). Female sex (adjusted odds ratio (AOR) 3.0), sCD163 (per μg/l) (AOR 6.6), and total cholesterol (per mmol/l) (AOR 1.6) were positively associated with high Gal3BP, and HDL-cholesterol (per mmol/l) (AOR 0.2) was negatively associated with high Gal3BP. High Gal3BP levels were associated with female sex, increasing sCD163 and total cholesterol levels, and decreasing HDL-cholesterol levels in patients with type 1 diabetes. The prevalence of high Gal3BP was more than twice as high in the women as in the men.


Characteristics of antibiotic resistance genes in full-scale anaerobic digesters of food waste and the effects of application of biogas slurry on soil antibiotic resistance genes.
The fate of antibiotic resistance genes (ARGs) in full-scale anaerobic digestion (AD) of food waste (FW) and in the soil applied with biogas slurry has not been fully understood. In this study, 12 targeted ARGs and intI1 in FW, intermediate product, and biogas slurry from three full-scale AD were analyzed. The results showed that subcritical water pretreatment was an effective method for ARG attenuation, by which the absolute abundance of total targeted ARGs was removed by 99.69%. The predominant ARGs (ermB, tetM, and tetW) in FW were removed more than 99% after subcritical water pretreatment. The result of field experiments with biogas slurry as fertilizer showed that the absolute abundance of several ARGs (sul2, tetM, blaOXA-1, blaTEM) and intI1 accumulated significantly compared to the control group (CK) during three consecutive growth stages of the rice. The detected abundance of ARGs in paddy field soil increased from 190.50 (CK) to 8.87 × 104 copies/g (wet weight) (soil) during tillering stage, and increased from 4102.65 (CK) to 4.38 × 104 copies/g (wet weight) (soil) during heading time. Biogas slurry improved the soil nutrients (TN, AN, TP, and AP); meanwhile, the concentrations of total salt and Cl- increased. Network analysis indicated that 28 genera were the possible hosts of ARGs; variation partitioning analysis (VPA) indicated that microbial communities (contribution 59.30%) were the main factors that affected the fate of ARGs and intI1.


Modalities of aging in organisms with different strategies of resource allocation.
Although the progress of aging research relies heavily on a theoretical framework, today there is no consensus on many critical questions in aging biology. I hypothesize that a systematic analysis of the intersection of different evolutionary mechanisms of aging with diverse resource allocation strategies in different organisms may reconcile aging hypotheses. The application of disposable soma, mutation accumulation, antagonistic pleiotropy, and life-history theory is considered across organisms with asexual reproduction, organisms with sexual reproduction and indeterminate growth in different conditions of extrinsic mortality, and organisms with determinate growth, with endotherms/homeotherms as a subgroup. This review demonstrates that different aging mechanisms are complementary to each other, and in organisms with different resource allocation strategies they form aging modalities ranging from immortality to suicidal programs. It also revamps the role of growth arrest in aging. Growth arrest evolved in many different groups of organisms as a result of resource reallocation from growth to reproduction (e.g., semelparous animals, holometabolic insects), or from growth to nutrient storage (endotherms/homeotherms). Growth arrest in different animal lineages has similar molecular mechanisms and similar consequences for longevity due to the conflict between growth-promoting and growth-suppressing programs and suppression of regenerative capacity.