Herbicide effects on freshwater benthic diatoms: induction of nucleus alterations and silica cell wall abnormalities.
Benthic diatoms are well known bio-indicators of river pollution by nutrients (nitrogen and phosphorus). Biological indexes, based on diatom sensitivity for non-toxic pollution, have been developed to assess the water quality. Nevertheless, they are not reliable tools to detect pollution by pesticides. Many authors have suggested that toxic agents, like pesticides, induce abnormalities of the diatom cell wall (frustule). High abnormal frustule abundances have been reported in natural diatom communities sampled in streams contaminated by pesticides. However, no direct link was found between the abundances of abnormal frustules in these communities and the pesticide concentrations in stream water. In the present study, a freshwater benthic diatom community, isolated from natural biofilm and cultured under controlled conditions, was treated with a known genotoxic herbicide, maleic hydrazide (MH). Cells were exposed to three concentrations of MH (5x10(-6), 10(-6), 10(-7)M) for 6h followed by a 24h-recovery time. After MH treatments, nucleus alterations were observed: abnormal nucleus location, micronucleus, multinuclear cell or disruption of the nuclear membrane. A dose-dependent increase of nuclear alterations was observed. The difference between the control (9.65 nuclear alterations per 1000 cells observed (9.65 per thousand), S.D.=4.23) and the highest concentrations (29.40 per thousand, S.D.=8.49 for 10(-6)M and 35.96 per thousand, S.D.=3.71 for 5x10(-6)M) was statistically significant (Tukey test, P<0.05). Diatoms also exhibited frustules with deformed morphology and abnormal ornamentation. Significantly increased abundances of abnormal frustules were observed for the highest concentrations (10(-6) and 5x10(-6)M; Tukey test, P<0.05). These two parameters tended to increase together (Pearson correlation=0.702, P<0.05). The results suggest that the induction of abnormal frustules could be associated with the genotoxic effects of MH. The alterations observed could be related to the effects of MH on the synthesis of the proteins involved in frustule formation or in the regulation of the cytoskeleton of the diatom cells.


An improved hollow fiber solvent-stir bar microextraction for the preconcentration of anabolic steroids in biological matrix with determination by gas chromatography-mass spectrometry.
In this paper, a convenient and self-assembled hollow fiber solvent-stir bar microextraction (HF-SSBME) device was developed, which could stir by itself. In the extraction process, the proposed device made the solvent "bar" not floating at the sample solution and exposing to air while organic solvents outside hollow fiber always wrapped with donor phase solvent, which reduced the vaporization of organic solvents. This design could improve the precisions and recoveries of experiments. For evaluating the device, seven anabolic steroids (prasterone, 5α-androstane-3α, 17β-diol, methandriol, 19-norandrostenediol, androstenediol, methyltestosterone and methandienone) were used as model analytes and extraction conditions such as type and volume of organic solvents, agitation speed, extraction time, extraction temperature and salt addition were studied in detail. Under the optimum conditions (15 μL toluene, 40 °C, stirring at 750 rpm for 30 min with 1.5 g sodium chloride addition in 20.0 mL donor phase), the linear ranges of anabolic steroids were 0.25-200 ng mL(-1) with gas chromatography-mass spectrometry. The limits of detection were lower than 0.10 ng mL(-1). The recoveries and precisions in spiked urine and hair samples were between 73.97-93.56% and 2.18-4.47% (n=5). HF-SSBME method combined the intrinsical merits of hollow fiber with the superiority of the proposed self-stirring device which can be developed to two-phase, three-phase and in situ derivatization modes with wide prospect of application. Besides, the pedestal of this proposed device can be converted to fix stir bar in stir bar sorptive extraction (SBSE) method.


No efficacy of processed Fabuless (Olibra) in suppressing appetite or food intake.
To investigate the feasibility of Fabuless (previously called Olibra and Reducal) as a food ingredient for food intake and appetite reduction, by assessing the effects of food processing on efficacy. In total, 24 healthy volunteers (16 female, 8 male; age: 18-43 years; body mass index: 18-37 kg/m(2)) took part in a randomized, placebo-controlled, double-blinded, cross-over trial. Yoghurt-based meal replacement drinks (containing processed or unprocessed Fabuless, or a control fat) were followed by an ad libitum lunch and evening meal (dinner). Key outcome measures were energy intake and self-reported appetite ratings. Compared with control, only unprocessed Fabuless reduced subsequent energy intake, although only during dinner (P < 0.01; control, processed and unprocessed: 4.3, 3.9 and 4.2 MJ, respectively) and not during lunch (3.6, 3.7 and 3.6 MJ). Self-reported appetite scores did not differ between treatments. Although modest effects of unprocessed Fabuless were seen on food intake, but not on appetite, the ingredient was not robust to common food-manufacturing processes (thermal and shear processing). Claims on reduced food intake and appetite relating to this ingredient in food products are, therefore, only valid if functionality has been demonstrated after all relevant processing and storage steps.


Diffuse glioma manifesting as normal pressure hydrocephalus: A potential pitfall in diagnosis-a case report.
•Hydrocephalus is rarely reported in patients with diffuse glioma.•We describe a patient with a low-grade glioma presenting a complex phenotype initially masquerading as hydrocephalus of unknown etiology.•The exact pathophysiological mechanism underlying hydrocephalus in the setting of diffuse glioma remains to be elucidated.•Caution is advised regarding hydrocephalus of unknown etiology, reevaluation is necessary.


Astragaloside IV as a novel CXCR4 antagonist alleviates osteoarthritis in the knee of monosodium iodoacetate-induced rats.
C-X-C chemokine receptor type 4 (CXCR4) inhibition protects cartilage in osteoarthritis (OA) animal models. Therefore, CXCR4 has becoming a novel target for OA drug development. Since dietary and herbal supplements have been widely used for joint health, we hypothesized that some supplements exhibit protective effects on OA cartilage through inhibiting CXCR4 signaling. The single-cell RNA sequencing data of OA patients (GSE152805) was re-analyzed by Scanpy 1.9.0. The docking screening of CXCR4 antagonists was conducted by Autodock Vina 1.2.0. The CXCR4 antagonistic activity was evaluated by calcium response in THP-1 cells. Signaling pathway study was conducted by bulk RNA sequencing and western blot analysis in human C28/I2 chondrocytes. The anti-OA activity was evaluated in monosodium iodoacetate (MIA)-induced rats. Astragaloside IV (ASN IV), the predominate phytochemical in Astragalus membranaceus, has been identified as a novel CXCR4 antagonist. ASN IV reduced CXCL12-induced ADAMTS4,5 overexpression in chondrocytes through blocking Akt signaling pathway. Furthermore, ASN IV administration significantly repaired the damaged cartilage and subchondral bone in MIA-induced rats. The blockade of CXCR4 signaling by ASN IV could explain anti-OA activities of Astragalus membranaceus by protection of cartilage degradation in OA patients. Since ASN IV as an antiviral has been approved by China National Medical Products Administration for testing in people, repurposing of ASN IV as a joint protective agent might be a promising strategy for OA drug development.


Ultrasonic reduction of excess sludge from activated sludge system II: urban sewage treatment.
Previous study showed that sonication was effective to reduce waste activated sludge (WAS) using artificial wastewater. This paper confirms the viability and evaluates the performance of this method in practical wastewater treatment using urban sewage without temperature control. The results showed that sonication significantly lowered the WAS and biomass synthesis, and greatly enhanced the mineralization of sewage organics. The optimal specific energy for sludge lysis was 20.0k Wh/kg DS. Further energy-increase had little benefit on WAS reduction. When the specific energy was 20.0kWh/kgDS and the sludge recycle ratio was 0.007, the WAS decreased by 54%, the biomass synthesis abated by 59%, and the sewage mineralization ratio increased from 31% to 58%. The effluent COD and nitrogen were stable but phosphorus was higher than that of the control bioreactor. The COD removal was lower but the WAS reduction was higher for urban sewage than for artificial wastewater. The accumulation pattern of heavy metals in sludge was greatly alternated by the sonication-cryptic growth; and different metals behaved differently. The sludge Ni concentration increased by 141% while As decreased by 53%.


Lamellar solid-liquid mesophase nucleated by Josephson vortices at the melting of the vortex lattice in Bi2Sr2CaCu2O(8+δ) superconductor.
The local effect of the Josephson vortices on the vortex lattice melting process in Bi2Sr2CaCu2O(8+δ) crystals in the presence of an in-plane field H(ab) is studied by differential magneto-optical imaging. The melting process is found to commence along the Josephson vortex stacks, forming a mesomorphic phase of periodic liquid and solid lamellas, the direction and spacing of which are controlled by H(ab). The reduction of the local melting field H(m) along the Josephson vortex stacks is more than an order of magnitude larger than the reduction of the average bulk H(m) by HH(ab).


Endothelin-1 response to mental stress in early ischemic lesions of the extremities due to systemic sclerosis.
We studied circulating levels of endothelin-1, catecholamines and nitric oxide after a mental arithmetic test in 14 patients with early ischemic lesions of the extremities due to systemic sclerosis and slightly impaired peripheral vascular flow. The test induced an increase (P<0.01) in blood pressure, heart rate, endothelin-1 and catecholamine levels, whereas it did not change the low basal levels of nitric oxide. In healthy subjects (n=20) the test significantly (P<0.01) decreased endothelin-1 without affecting nitric oxide. The low basal levels of nitric oxide and the high plasma concentration of endothelin-1 after psychological stress cannot be explained by an impaired release from the limited ischemic lesions alone. This suggests a diffuse microvascular derangement that aggravates the course of peripheral microvascular ischemic lesions.


Straightforward Access to Multifunctional π-Conjugated P-Heterocycles Featuring an Internal Ylidic Bond.
We report the straightforward one-pot synthesis of novel 5- or 6-membered P-heterocycles featuring an internal ylidic bond: P-containing acenaphthylenes and phenanthrenes. The stability of the compounds tolerates post-functionalization through direct arylation to introduce electron-rich/poor substituents and the synthetic strategy is also compatible with the preparation of more elaborate polyaromatic scaffolds such as acenes and helicenes. Using a joint experimental (X-ray analysis, optical and redox properties) and theoretical approach, we perform a full structure-property relationships study on these new platforms. In particular, we show that molecular engineering allows not only tuning their absorption/emission across the entire visible range but also endowing them with chiroptical or non-linear optical properties, making them valuable dyes for a large panel of photonic or opto-electronic applications.


Target screening method for the quantitative determination of 118 pyrrolizidine alkaloids in food supplements, herbal infusions, honey and teas by liquid chromatography coupled to quadrupole orbitrap mass spectrometry.
An analytical procedure for the screening of 118 pyrrolizidine alkaloids (PAs) was successfully validated and applied to their quantitative determination in food supplements, herbal infusions, honey, and teas. It provides the reliable analyte identification by high-resolution tandem mass spectrometry (HRMS/MS), the accurate determination of 21 regulated PAs, and broad contamination profiles. 10% of 281 analyzed samples resulted contaminated at levels above the maximum levels (MLs) of European legislation. The contamination of herbal infusions of mixed plants can represent a possible health concern (23%; mean of PA sum above ML). A high number of PAs not included in the regulation was detected in honey and herbal food supplements, but their contribution was only relevant to the overall level in honey. The results indicate the need to continue collecting contamination data in food supplements and infusions of mixed herbs and to expand the PA-pool to be monitored in honey and related products.


Lost in hospital: a qualitative interview study that explores the perceptions of NHS inpatients who spent time on clinically inappropriate hospital wards.
Prior research suggests that the placement of patients on clinically inappropriate hospital wards may increase the risk of experiencing patient safety issues. To explore patients' perspectives of the quality and safety of the care received during their inpatient stay on a clinically inappropriate hospital ward. Qualitative study using semi-structured interviews. Nineteen patients who had spent time on at least one clinically inappropriate ward during their hospital stay at a large NHS teaching hospital in England. Patients would prefer to be treated on the correct specialty ward, but it is generally accepted that this may not be possible. When patients are placed on inappropriate wards, they may lack a sense of belonging. Participants commented on potential failings in communication, medical staff availability, nurses' knowledge and the resources available, each of which may contribute to unsafe care. Patients generally acknowledge the need for placement on inappropriate wards due to demand for inpatient beds, but may report dissatisfaction in terms of preference and belonging. Importantly, patients recount issues resulting from this placement that may compromise their safety. Hospital managers should be encouraged to appreciate this insight and potential threat to safe practice and where possible avoid inappropriate ward transfers and admissions. Where such admissions are unavoidable, staff should take action to address the gaps in safety of care that have been identified.


Truncating mutations in C-terminal titin may cause more severe tibial muscular dystrophy (TMD).
Mutations in C-terminal titin cause autosomal dominant tibial muscular dystrophy (TMD) as reported previously. Samples from 25 new families and 25 sporadic new distal myopathy cases were screened for titin mutations. Three novel mutations were discovered in two families from Spain and two families from France. Two mutations, g.292998delT and g.293376delA lead to frameshift and premature stop codons in the second last and the last titin gene (TTN) exons, Mex5 and Mex6, respectively. The third was a nonsense mutation g.293379C>T (p.Q33396X) in Mex6. Patients with the upstream Mex5 mutation showed a more severe phenotype with earlier onset implying a genotype-phenotype correlation.


The effect of gastric Helicobacter pylori eradication on recurrent aphthous stomatitis.
Helicobacter pylori (H. pylori) has been suggested to be associated with recurrent aphthous stomatitis (RAS) as well as many other diseases. We conducted a prospective study on a total of 23 patients with RAS to investigate the relationship between H. pylori and RAS as well as the effect of eradication therapy on the recurrence. All patients underwent endoscopic examination and gastric biopsy. The biopsy materials were examined histopathologically whether they contained H. pylori or not. The density of H. pylori was also noted. The patients with H. pylori infection were followed up for up to 1 year after starting the eradication therapy. Gastric mucosal H. pylori colonization was + in 39%, ++ in 39%, +++ in 9%, and - in 13% of the patients, respectively. There were statistically significant decreases in the recurrence rate and amelioration time of RAS by eradication therapy. There were no significant correlations among the intensity of H. pylori with the recurrence rate, number, diameter, and amelioration time of the lesions in 1-year follow-up. We concluded that eradication of H. pylori may have reducing effects on the recurrence and amelioration period of the RAS.


Patient-controlled regional analgesia (PCRA) with ropivacaine after arthroscopic subacromial decompression.
The aim of the study was to evaluate postoperative analgesia and safety of wound instillation of ropivacaine either by a single dose or a patient-controlled regional anaesthesia (PCRA) technique. In 40 patients undergoing arthroscopic subacromial decompression the surgeon placed a catheter into the subacromial space at the end of the operation. In Phase I (10 patients), ropivacaine 250 mg was injected twice within 1 h. In Phase II, 30 patients were randomised into three groups: group prilocaine-ropivacaine (PR) = 20 ml of 1% prilocaine-epinephrine injected preoperatively into the subacromial bursa + 20 ml of 0.5% ropivacaine infused in the catheter postoperatively; group saline-ropivacaine (SR) = saline-epinephrine (20 ml) preoperatively + 0.5% ropivacaine as in group PR; group saline-saline (SS) = saline-epinephrine (20 ml) preoperatively + saline postoperatively. The PCRA pump was filled with local anaesthetic or saline to allow boluses of 10-ml each, maximum one bolus/h, via the catheter. Pain relief, side-effects and venous plasma concentration of ropivacaine were evaluated during a 24-h-test period. The free plasma concentration of ropivacaine was 0.12 + 0.041 mg l-1 in Phase I. No adverse effects were seen. In Phase II pain at rest and on movement was lower in group PR than in group SS during the first 30 min postoperatively (P < 0.05). Group PR had the lowest morphine consumption (P < 0.05). Five to seven boluses were administered via the PCRA-pump, and 20 min after administration of the study solution, pain was lower in groups PR and SR compared with group SS (P < 0.001). Preoperative intrabursal prilocaine with epinephrine + postoperative subacromial administration of ropivacaine by PCRA-technique provided the most effective analgesia with no major side-effects. The free plasma concentrations of ropivacaine were far below toxic concentrations.


Long-term Health Care Utilization and Associated Costs After Dialysis-Treated Acute Kidney Injury in Children.
Acute kidney injury (AKI) is common among hospitalized children and is associated with increased hospital length of stay and costs. However, there are limited data on postdischarge health care utilization after AKI hospitalization. Our objectives were to evaluate health care utilization and physician follow-up patterns after dialysis-treated AKI in a pediatric population. Retrospective cohort study, using provincial health administrative databases. All children (0-18 years) hospitalized between 1996 and 2017 in Ontario, Canada. Excluded individuals comprised non-Ontario residents; those with metabolic disorders or poisoning; and those who received dialysis or kidney transplant before admission, a kidney transplant by 104 days after discharge, or were receiving dialysis 76-104 days from dialysis start date. Episodes of dialysis-treated AKI, identified using validated health administrative codes. AKI survivors were matched to 4 hospitalized controls without dialysis-treated AKI by age, sex, and admission year. Our primary outcome was postdischarge hospitalizations, emergency department visits, and outpatient physician visits. Secondary outcomes included outpatient visits by physician type and composite health care costs. Proportions with≥1 event and rates (per 1,000 person-years). Total and median composite health care costs. Adjusted rate ratios using negative binomial regression models. We included 1,688 pediatric dialysis-treated AKI survivors and 6,752 matched controls. Dialysis-treated AKI survivors had higher rehospitalization and emergency department visit rates during the analyzed follow-up periods (0-1, 0-5, and 0-10 years postdischarge, and throughout follow-up), and higher outpatient visit rates in the 0-1-year follow-up period. The overall adjusted rate ratio for rehospitalization was 1.46 (95% CI, 1.25-1.69; P<0.0001) and for outpatient visits was 1.16 (95% CI, 1.09-1.23; P=0.01). Dialysis-treated AKI survivors also had higher health care costs. Nephrologist follow-up was infrequent among dialysis-treated AKI survivors (18.6% by 1 year postdischarge). Potential miscoding of study exposures or outcomes. Residual uncontrolled confounding. Data for health care costs and emergency department visits was unavailable before 2006 and 2001, respectively. Dialysis-treated AKI survivors had greater postdischarge health care utilization and costs versus hospitalized controls. Strategies are needed to improve follow-up care for children after dialysis-treated AKI to prevent long-term complications.


Methylenetetrahydrofolate reductase genotypes do not play a role in acute lymphoblastic leukemia pathogenesis in the Italian population.
Methylenetetrahydrofolate reductase (MTHFR) is one of the enzymes involved in folate metabolism and DNA methylation and synthesis. Some genotypes of this highly polymorphic enzyme are associated with decreased activity. Previous studies have suggested that individuals with the MTHFR 677TT, 1298AC and 1298CC have a lower risk of adult acute lymphoblastic leukemia (ALL). In order to test this association we studied the presence of the C677T and A1298C mutant alleles in 174 patients with acute lymphoblastic leukemia and in 110 controls from central Italy. We did not find any association between the different polymorphisms and susceptibility to ALL. In multivariate analysis different genotypes did not show any correlation with the risk of ALL. The adjusted odds ratios and 95% confidence intervals for MTHFR C677T were 0.69 (0.4-1.19) for 677CT versus 677CC wild type, and 0.99 (0.50-1.97) for 677TT versus 677CC. The corresponding values for MTHFR A1298C were 0.93 (0.56-1.53) for 1298AC versus 1298AA wild type and 1.14 (0.36-3.61) for 1298CC versus 1298AA. These results do not support the suggestion that populations carrying different genotypes of the two MTHFR polymorphisms, C677T and A1298C, have a different susceptibility to ALL, at least in the Mediterranean area.


Methylxanthines, inflammation, and cancer: fundamental mechanisms.
Methylxanthines are an integral part of everyday food and drink consumption even though the majority of humans do not identify them by their chemical name. The breakthrough in understanding the action(s) of methylxanthines was in large part due to the understanding that methylxanthines can function as antagonists of adenosine receptors. This represented an example of scientific search and was instructive in view of both new therapeutic options and alarming realizations. It was the subsequent demonstration of the in vivo critical role of A2A adenosine receptors in controlling excessive collateral inflammatory damage that attracted the attention of immunologists to the A2A-adenosine-receptor-antagonizing methylxanthines. We summarize here data showing that caffeine is capable of preventing the inhibition of antitumor T cells in a hypoxic tumor microenvironment. On the other hand, caffeine may exacerbate liver damage by weakening the tissue-protecting A2A adenosine receptor signaling during episodes of acute liver inflammation. However, methylxanthines may also prevent the excessive hepatic connective tissue deposition that is associated with the progression of chronic hepatitis to cirrhosis, which is one of the common causes of mortality.


Into the unknown: A review and synthesis of contemporary models involving uncertainty.
The current review and synthesis serves to define and contextualize fear of the unknown relative to related constructs, such as intolerance of uncertainty, and contemporary models of emotion, attachment, and neuroticism. The contemporary models appear to share a common core in underscoring the importance of responses to unknowns. A recent surge in published research has explored the transdiagnostic impact of not knowing on anxiety and related pathologies; as such, there appears to be mounting evidence for fear of the unknown as an important core transdiagnostic construct. The result is a robust foundation for transdiagnostic theoretical and empirical explorations into fearing the unknown and intolerance of uncertainty.


[Significance of primary radical surgery for survival following treatment of breast cancer. Problems of interpretation of treatment results of prospective, nonrandomized studies exemplified by the Southwest Germany Breast Cancer Study].
In a prospective non-randomised trial 1642 patients were included. After a mean time of 10 years a follow-up analysis was performed. The importance of the radicality of the primary operative therapy of breast cancer should be evaluated. The mean 5 years survival rate was 67.3%, the 10 year survival rate 51.6%. Tumor stage and age had a highly significant influence on the survival rate. Patients with simple mastectomy had a lower survival rate as patients with radical mastectomy. This apparent difference was caused by a different age distribution in the therapy groups. Accordingly the mean life deficiency was the lowest in the simple mastectomy group. In a multiple hazard statistical analysis tumor stage and age showed a highly significant influence on the survival rate. The intraoperative radicality classification showed a significant correlation to the prognoses of the patients. The operative therapy itself had no significant influence on the survival rate of the patients.


Delivery Systems to Enhance Bioaccessibility and Bioavailability of Bioactive Factors: Structure, Property, and Food Applications.
Incorporating bioactive factors to strengthen food nutrition is important for functional food development [...].


Heterozygosity, inbreeding and neonatal traits in Soay sheep on St Kilda.
We investigated whether birth weight and neonatal survival, a period within which 24% of all mortalities occur, were correlated with levels of inbreeding in St Kilda Soay sheep, using pedigree inbreeding coefficients and four marker-based estimators of inbreeding. None of the inbreeding estimators, either of the offspring, or of their mothers, explained significant variation in a lamb's birth weight or probability of surviving the neonatal period, suggesting low inbreeding depression for these traits. We evaluated the correlation between the marker-based measures of inbreeding and inbreeding coefficients obtained from the Soay pedigree, where paternal links were inferred using the same panel of microsatellite markers. Even when using a relatively complete portion of the pedigree, in which all individuals had known maternal and paternal grandparents, the correlation was found to be weak (r = -0.207, where mean f = 0.0168). These results add support to the recent prediction that when the mean and variance in inbreeding are low in a population, heterozygosity-fitness correlations can be very weak or even undetectable. The pursuit of more detailed pedigrees offers the best prospect for identifying inbreeding depression within this study population.


2-[3-(2-Acetoxyphenyl)quinoxa-lin-2-yl]phenyl acetate.
The title compound, C24H18N2O4, crystallizes as a syn-conformer, with dihedral angles between the quinoxaline moiety and the acet-oxy-substituted benzene rings of 53.46 (3)° and 54.78 (3)°. In the crystal, the mol-ecules form chains along [100] via C-H⋯O inter-actions.


Managing chronic kidney disease in type 2 diabetes in family practice.
Diabetic nephropathy is the leading cause of stage 5 chronic kidney disease (CKD) and occurs in 1 in 9 persons with newly diagnosed type 2 diabetes. Screening should begin at the time of type 2 diabetes diagnosis to detect the presence of a decreased estimated glomerular filtration rate (GFR) and/or an elevated albumin excretion rate. The estimated GFR can be used to stage CKD, assess cardiovascular risk, and develop treatment strategies. A multifaceted treatment plan delivered using a collaborative care approach that fosters person self-management is important. Glucose-lowering agents should be selected based on renal function and titrated to achieve an A1c less than 7.0%. Lipid-lowering therapy with a statin should be utilized to achieve a low-density lipoprotein cholesterol less than 100 mg/dL, possibly less than 70 mg/dL. An angiotensin-converting enzyme inhibitor, angiotensin receptor blocker, or direct renin inhibitor, typically in combination with other antihypertensive therapies, is recommended for persons with hypertension, microalbuminuria/macroalbuminuria, and type 2 diabetes, as this approach has been shown to be renoprotective. Angiotensin-converting inhibitors have an additional benefit of improving cardiovascular outcomes in CKD.


Rice versus Xanthomonas oryzae pv. oryzae: a unique pathosystem.
Bacterial blight, caused by Xanthomonas oryzae pv. oryzae (Xoo), is a devastating disease of rice worldwide. The qualitative or pathogen race-specific resistance to this pathogen conferred by major disease resistance (MR) genes has been widely used in rice improvement. Accumulating genetic and molecular data have revealed that the molecular mechanisms of rice qualitative resistance to Xoo are largely different from those of qualitative resistance in other plant-pathogen pathosystems. In this review, we focus on the unique features of rice qualitative resistance to Xoo based on MR genes that have been identified and characterized. The distinctiveness of the rice-Xoo interaction provides a unique pathosystem to elucidate the diverse molecular mechanisms in plant qualitative resistance.


The tumor suppressors Brat and Numb regulate transit-amplifying neuroblast lineages in Drosophila.
In both vertebrates and insects, neurons typically arise from neural stem cells or terminally dividing intermediate progenitors. Here, we describe another mode of neurogenesis where neural stem cells generate secondary precursors that undergo multiple rounds of self-renewing transit-amplifying divisions. We identify the Posterior Asense-Negative (PAN) neuroblasts, which do not express the transcription factors Asense or Prospero. PAN neuroblasts rely on the segregating determinants Numb and Brat to generate smaller, secondary neuroblasts that in turn give rise to ganglion mother cells (GMCs) and neurons throughout larval development. In brat or numb mutants, misspecified secondary neuroblasts are unable to produce differentiated progeny and initiate tumor-like overgrowth. In prospero mutants, however, tumors arise from GMCs while secondary neuroblasts are correctly specified. Our data describe a transit-amplifying lineage in the Drosophila nervous system and suggest that different vulnerabilities in intermediate cell types can affect the outcome of tumor suppressor loss in stem cell lineages.


In silico comparison of whole pelvis intensity-modulated photon versus proton therapy for the postoperative management of prostate cancer.
Limited data exist comparing intensity-modulated photon (IMRT) and proton (IMPT) radiation therapy when treating the prostate bed and pelvic lymph nodes in the postoperative setting for prostate cancer. The aim of this study was to evaluate dosimetric differences between IMRT and IMPT when treating with whole pelvis radiation therapy (WPRT) postoperatively. IMRT and IMPT plans were generated for 10 post-prostatectomy patients treated between July and August 2020. The prescription was 50 Gy radiobiologic equivalent (GyE) (proton radiobiological effective dose 1.1) to the pelvis and 70 GyE to the prostate bed in 2 GyE per fraction. Paired 2-sided Wilcoxon signed-rank tests were used to compare clinical target volume (CTV) coverage and dose to organs at risk (OARs). CTV coverage was met for all plans with 99% of CTVs receiving ≥99% of prescription doses. Dose to OARs was significantly higher with IMRT than IMPT for the following endpoints: bladder V5-V65; bowel V5-V45; sigmoid V5-V50; rectum V5-V70; femoral head V40 and maximum dose; bone V5-V65. Select endpoints with significant differences included bladder V30 (63.5 vs. 44.4%, p < .001), bowel V15 (949 vs. 191 cc, p = .001) and V30 (386 vs. 121 cc, p < .001), rectum V40 (81.8 vs. 32.1%, p < .001) and V50 (47.6 vs. 24.9%, p < .001), femoral head maximum doses (46.4-47.1 vs. 38.3-38.6GyE, p < .001), and bone V10 (93.3 vs. 85.4%, p < . 001). Mean doses for all OARs were significantly higher with IMRT, including bladder (41.9 vs. 29.7GyE, p < .001), bowel (21.2 vs. 5.5GyE, p < .001), and rectum (50.8 vs. 27.3GyE, p < .001). Integral dose to 'Body - CTV' was significantly higher with IMRT (32.8 vs. 18.4 J, p < .001). IMPT provides comparable target coverage to IMRT when treating prostate cancer with WPRT in the postoperative setting while significantly reducing dose to OARs. These data can inform the future clinical management and delivery of post-prostatectomy irradiation for prostate cancer.


Probing cytoskeletal modulation of passive and active intracellular dynamics using nanobody-functionalized quantum dots.
The cytoplasm is a highly complex and heterogeneous medium that is structured by the cytoskeleton. How local transport depends on the heterogeneous organization and dynamics of F-actin and microtubules is poorly understood. Here we use a novel delivery and functionalization strategy to utilize quantum dots (QDs) as probes for active and passive intracellular transport. Rapid imaging of non-functionalized QDs reveals two populations with a 100-fold difference in diffusion constant, with the faster fraction increasing upon actin depolymerization. When nanobody-functionalized QDs are targeted to different kinesin motor proteins, their trajectories do not display strong actin-induced transverse displacements, as suggested previously. Only kinesin-1 displays subtle directional fluctuations, because the subset of microtubules used by this motor undergoes prominent undulations. Using actin-targeting agents reveals that F-actin suppresses most microtubule shape remodelling, rather than promoting it. These results demonstrate how the spatial heterogeneity of the cytoskeleton imposes large variations in non-equilibrium intracellular dynamics.


Cross attention guided multi-scale feature fusion for false-positive reduction in pulmonary nodule detection.
False-positive reduction is a crucial step of computer-aided diagnosis (CAD) system for pulmonary nodules detection and it plays an important role in lung cancer diagnosis. In this paper, we propose a novel cross attention guided multi-scale feature fusion method for false-positive reduction in pulmonary nodule detection. Specifically, a 3D SENet50 fed with a candidate nodule cube is applied as the backbone to acquire multi-scale coarse features. Then, the coarse features are refined and fused by the multi-scale fusion part to achieve a better feature extraction result. Finally, a 3D spatial pyramid pooling module is used to enhance receptive field and a distributed aligned linear classifier is applied to get the confidence score. In addition, each of the five nodule cubes with different sizes centering on every testing nodule position is fed into the proposed framework to obtain a confidence score separately and a weighted fusion method is used to improve the generalization performance of the model. Extensive experiments are conducted to demonstrate the effectiveness of the classification performance of the proposed model. The data used in our work is from the LUNA16 pulmonary nodule detection challenge. In this data set, the number of true-positive pulmonary nodules is 1,557, while the number of false-positive ones is 753,418. The new method is evaluated on the LUNA16 dataset and achieves the score of the competitive performance metric (CPM) 84.8%.


Psychological impacts of coronavirus disease 2019 on people with asthma, allergic rhinitis, and food allergy.
To summarize the current literature of the psychological impacts of coronavirus disease 2019 (COVID-19) on people with allergic diseases and to identify gaps in need of future research. Ovid MEDLINE(R) and Embase Classics + Embase from 1947 to present (October 18, 2021) were searched using a search strategy that included the following keywords: allergic diseases, covid*, and psychological disorders. Primary manuscripts and abstracts using online and telephone surveys, mixed-method studies capturing patient and caregiver experiences, case studies, and published guidelines from allergic disease-specific expert groups were included. People with asthma and other chronic respiratory conditions are at higher risk of negative psychological outcomes, and risk factors include asthma severity, female sex, and previous history of anxiety and depression, likely owing to the perceived risk of severe disease from COVID-19. One study identified that people with allergic rhinitis had significantly high anxiety and depression scores compared with healthy controls (both, P < .001). The psychological impacts of food allergy during COVID-19 were most strongly felt by parents and caregivers. Similarly, parents of children with asthma experienced substantial psychological burden. COVID-19 had a considerable psychological impact on patients with asthma. Limited data have been published on the mental health impacts of COVID-19 on patients with allergic rhinitis and food allergy. As COVID-19 research continues to evolve and the literature captures later stages of the pandemic, it is important that physicians be aware of the potential coincidence of mental illness and chronic allergic diseases and refer these patients, and their caregivers, to appropriate resources while also continuing to manage their allergic disease(s).


Microbial patterns in rumen are associated with gain of weight in beef cattle.
Ruminal microorganisms play a pivotal role in cattle nutrition. The discovery of the main microbes or of a microbial community responsible for enhancing the gain of weight in beef cattle might be used in therapeutic approaches to increase animal performance and cause less environmental damages. Here, we examined the differences in bacterial and fungal composition of rumen samples of Braford heifers raised in natural grassland of the Pampa Biome in Brazil. We aimed to detect microbial patterns in the rumen that could be correlated with the gain of weight. We hypothesized that microorganisms important to digestion process are increased in animals with a higher gain of weight. The gain of weight of seventeen healthy animals was monitored for 60 days. Ruminal samples were obtained and the 16S and ITS1 genes were amplified and sequenced to identify the closest microbial relatives within the microbial communities. A predictive model based on microbes responsible for the gain of weight was build and further tested using the entire dataset., The main differential abundant microbes between groups included the bacterial taxa RFN20, Prevotella, Anaeroplasma and RF16 and the fungal taxa Aureobasidium, Cryptococcus, Sarocladium, Pleosporales and Tremellales. The predictive model detected some of these taxa associated with animals with the high gain of weight group, most of them being organisms that have been correlated to the production of substances that improve the ruminal digestion process. These findings provide new insights about cattle nutrition and suggest the use of these microbes to improve beef cattle breeding.


Modelling molecular stability in the RNA world.
RNA secondary structure, stability and melting curves are calculated for a model of a possible ribozyme corresponding to the RNA directed RNA polymerase (ribopolymerase) required in the RNA world. From these calculations, rates of folding and hybridisation are estimated and used in a stochastic simulation of the dynamics of a population of ribopolymerase molecules. Two models are considered: one synthesising a conventional antiparallel reverse complementary transcript and one synthesising a parallel complementary transcript. It was found that the latter system can operate much more effective in the higher temperatures thought to prevail during the RNA world.


Cognitive Performance and Cerebrospinal Fluid Markers in Preclinical Alzheimer's Disease: Results from the Gothenburg H70 Birth Cohort Studies.
We have previously shown that older adults with preclinical Alzheimer's disease (AD) pathology in cerebrospinal fluid (CSF) had slightly worse performance in Mini-Mental State Examination (MMSE) than participants without preclinical AD pathology. We therefore aimed to compare performance on neurocognitive tests in a population-based sample of 70-year-olds with and without CSF AD pathology. The sample was derived from the population-based Gothenburg H70 Birth Cohort Studies in Sweden. Participants (n = 316, 70 years old) underwent comprehensive cognitive examinations, and CSF Aβ-42, Aβ-40, T-tau, and P-tau concentrations were measured. Participants were classified according to the ATN system, and according to their Clinical Dementia Rating (CDR) score. Cognitive performance was examined in the CSF amyloid, tau, and neurodegeneration (ATN) categories. Among participants with CDR 0 (n = 259), those with amyloid (A+) and/or tau pathology (T+, N+) showed similar performance on most cognitive tests compared to participants with A-T-N-. Participants with A-T-N+ performed worse in memory (Supra span (p = 0.003), object Delayed (p = 0.042) and Immediate recall (p = 0.033)). Among participants with CDR 0.5 (n = 57), those with amyloid pathology (A+) scored worse in category fluency (p = 0.003). Cognitively normal participants with amyloid and/or tau pathology performed similarly to those without any biomarker evidence of preclinical AD in most cognitive domains, with the exception of slightly poorer memory performance in A-T-N+. Our study suggests that preclinical AD biomarkers are altered before cognitive decline.


Performance and selectivity of amphiphilic pillar[5]arene as stationary phase for capillary gas chromatography.
Pillar[n]arenes possess highly symmetrical and rigid pillar-shaped architecture with π-electron rich cavity that afford their reliable host-guest recognition interactions towards matched guests. In this work, a novel amphiphilic pillar[5]arene (P5A-C10-2NH2) was designed, synthesized and employed as the stationary phase for capillary gas chromatography. To date, they have not been reported in the field of chromatography. The P5A-C10-2NH2 capillary column (10 m × 0.25 mm i.d.) was prepared by static coating method. Its capillary column exhibited moderate polarity and column efficiency of 2265 plates/m determined by naphthalene at 120 °C. As evidenced, the P5A-C10-2NH2 column achieved advantageous separation performance for a mixture of 24 analytes of diverse types and exhibited different chromatographic selectivity from two pillar[5]arene derivatives columns and commercial HP-35 column with 35%-phenyl-methylpolysiloxane. Moreover, the P5A-C10-2NH2 column baseline resolved more than a dozen positional and cis-trans isomers. Furthermore, the separation mechanism of P5A-C10-2NH2 column was discussed by quantum chemical calculations. In addition, the P5A-C10-2NH2 column had high thermal stability and excellent separation repeatability 0.01-0.04% for run-to-run, 0.03-0.17% for day-to-day and 3.2-3.9% for column-to-column. The special amphiphilic structure and high resolution for various analytes reveal the good potential of pillararenes as a new class of stationary phases for chromatographic analyses. Moreover, the TPG column achieved improved thermal stability over the GIL column and excellent repeatability.


The prosecutor's fallacy--a pitfall in interpreting probabilities in forensic evidence.
Forensic evidence is often given in terms of a mathematical probability. However, it is easy to make a particular type of error, 'the prosecutor's fallacy', in the interpretation of such probability. This paper highlights the source of this error and briefly introduces Bayes Theorem as the correct theoretical basis for interpreting such evidence. The first Californian legal case in which this error was committed is discussed, followed by all cases in the UK in which this error was highlighted and rectified by the Court of Appeal. It is important for all parties concerned--expert witnesses, lawyers and judges--to understand these principles correctly. Furthermore, the criminal courts face dilemmas when juries are involved. This paper concludes by discussing recent guidance from the Court of Appeal on how such evidence should be presented to the jury and the implications of this guidance.


Comparison between phenylpropanolamine and structurally related compounds on gastric transit in the rat.
Our laboratory previously reported several pharmacological differences between phenylpropanolamine [PPA; (+/-)-norephedrine] and its structurally related compounds in regard to their activity on cardiovascular and appetite-suppressant parameters. The present study investigates the pharmacological differences between PPA, [1R,2R]-(-)-norephedrine [(-)-NOR], [1S,2S]-(+)-norephedrine [(+)-NOR], [1R,2S]-(-)-ephedrine [(-)-EPH], [1S,2R]-(+)-ephedrine [(+)-EPH], [1R,2S]-(-)-norpseudoephedrine [(-)-NORP], [1S,2R]-(+)-norpseudoephedrine [(+)-NORP], [1R,2R]-(-)-pseudoephedrine [(-)-PSE], and [1S,2S]-(+)-pseudoephedrine [(+)-PSE], as determined by their ability to inhibit gastric transit in the rat. (-)-Norephedrine was approximately three times more potent in inhibiting gastric transit than (+)-NOR (p < 0.01). As anticipated, the racemic mixture, PPA, demonstrated an ED50 (25.1 mg/kg) of approximately the mean of the ED50s from the component enantiomers (14.7 and 47.0 mg/kg, respectively). Similarly, administration of 20 mg/kg of either (-)-EPH, (+)-EPH, (-)-PSE, or (+)-PSE significantly decreased gastric transit by 26% (p < 0.001), 12% (p < 0.01), 10% (p < 0.01), and 11% (p < 0.01), respectively. Administration of (-)-NORP and (+)-NORP were without effect. These data confirm and extend previous findings demonstrating pharmacological differences between PPA and its structurally related compounds.


Excessive intra- and supragranular mossy fibers in the dentate gyrus of tottering (tg/tg) mice.
In Timm's sulfide silver preparations, intragranular and supragranular mossy fiber staining is found to be much more prevalent in the temporal dentate gyrus of the spontaneous epileptic mouse, tottering, than at matching levels in unaffected littermate controls. This aberrant distribution of mossy fibers may be due to the spontaneous seizures affecting this mutant.


The global prevalence of HFE and non-HFE hemochromatosis estimated from analysis of next-generation sequencing data.
The prevalence of HFE-related hereditary hemochromatosis (HH) among European populations has been well studied. There are no prevalence data for atypical forms of HH caused by mutations in HFE2, HAMP, TFR2, or SLC40A1. The purpose of this study was to estimate the population prevalence of these non-HFE forms of HH. A list of HH pathogenic variants in publically available next-generation sequence (NGS) databases was compiled and allele frequencies were determined. Of 161 variants previously associated with HH, 43 were represented among the NGS data sets; an additional 40 unreported functional variants also were identified. The predicted prevalence of HFE HH and the p.Cys282Tyr mutation closely matched previous estimates from similar populations. Of the non-HFE forms of iron overload, TFR2-, HFE2-, and HAMP-related forms are predicted to be rare, with pathogenic allele frequencies in the range of 0.00007 to 0.0005. Significantly, SLC40A1 variants that have been previously associated with autosomal-dominant ferroportin disease were identified in several populations (pathogenic allele frequency 0.0004), being most prevalent among Africans. We have, for the first time, estimated the population prevalence of non-HFE HH. This methodology could be applied to estimate the population prevalence of a wide variety of genetic disorders.Genet Med 18 6, 618-626.


Left ventricular function during haemofiltration and haemodialysis: a comparative study.
The relationship between systemic haemodynamics and left ventricular performance during HF and HD was evaluated by M-mode echocardiography. In patients with normal cardiac function and similar rates of fluid removal, special attention was paid to the effects of solute transport and buffer. Convective transport, independent of the replacement buffer, produces an increase in systemic vascular resistance with no changes in ventricular function. In contrast, a diffusive transport induces different effects depending on the dialysate buffer: acetate decreases vascular resistance and bicarbonate significantly improves myocardial contractility shifting the cardiac function curve to the left.


Determination of reducing and non-reducing carbohydrates in food products by liquid chromatography with post-column catalytic hydrolysis and derivatization. Comparison with refractive index detection.
Post-column catalytic hydrolysis combined with 4-aminobenzoic acid hydrazide derivatization is employed for the determination of both reducing and non-reducing carbohydrates in a variety of complex sample matrices such as dairy products, processed foods and tobaccos. Comparison with refractive index detection shows the post-column method to be superior from the standpoint of selectivity, sensitivity and simplicity of sample preparation. Limits of detection are in the low-nanogram range. Quantitative results are presented for the determination of sugars in potato extracts. The method is also applicable for the separation and detection of carbohydrate oligomers.


Synthesis of O2'-methyluridine, O2'-methylcytidine, N4,O2'-dimethylcytidine and N4,N4,O2'-trimethylcytidine from a common intermediate.
A facile synthesis of the title compounds from a readily accessible precursor, 3',5'-O-bis-protected O4-(2-nitrophenyl)uridine, is described.


Virulence of Mycobacterium avium complex strains from acquired immune deficiency syndrome patients: relationship with characteristics of the parasite and host.
The virulence of 24 strains of Mycobacterium avium complex (MAC) isolated from patients with acquired immune deficiency syndrome (AIDS) was assessed using the beige mouse model. Most changes in colony forming unit (cfu) counts in spleen and lungs, and spleen weights occurred between days 1 and 14, with comparatively smaller changes 14-28 days postinfection. The virulence was assessed by a score formulated from the four most useful parameters: mortality, spleen cfu, lung cfu and spleen weights at 28 days. The scores of the 24 strains showed a normal distribution; four strains falling above one standard deviation from the mean were classified as high virulent, those four falling below one standard deviation as low virulent, and the remaining 16 as of intermediate virulence. Virulence was associated with the total number of plasmids and the occurrence of large plasmids (greater than 100 MDa) in the MAC strains. There was an inverse correlation between virulence and the organism's capacity to trigger the release of oxygen metabolites from peritoneal macrophages. Macrophages from mice infected with the MAC strains of different degrees of virulence released superoxide anion (O2-) with a peak at two weeks, the peak levels bearing an inverse correlation to virulence. No association was seen between virulence and source of specimens, biochemical characteristics, drug susceptibility, serotypes or phage types.


The immune system as a sensor of the metabolic state.
Mammals possess a remarkable ability to maintain and defend a constant internal milieu against diverse environmental threats. Unsurprisingly, the two systems tasked with these duties, metabolism and immunity, have evolved to share a common modular architecture that allows extensive bidirectional communication and coordination. Indeed, recent observations have highlighted numerous functionally critical immune regulatory modules located within diverse metabolic circuits. In this review, we discuss the architectural commonality between immunity and metabolism and highlight how these two primordially disparate systems leverage shared regulatory axes to coordinate metabolic physiology under conditions of normality and chronic overnutrition. Such an integrated perspective both advances our understanding of basic physiology and highlights potential opportunities for therapeutic intervention in metabolic dysfunction.


Targeted design of a cubic boron imidazolate cage with sensing and reducing functions.
A cubic cationic cage is rationally designed by using tridentate boron-imidazolate ligands to link tetrahedral metal Zn(ii) centers, which displays excellent properties in the Cr2O7(2-) exchange and can reduce Au(3+) ions into Au nanoparticles directly.


Haematemesis during oral aminophylline treatment.
Two cases of gastrointestinal bleeding in patients being treated with continuous-release aminophylline tablets are reported.


Towards a new science of secondary metabolism.
Secondary metabolites are a reliable and very important source of medicinal compounds. While these molecules have been mined extensively, genome sequencing has suggested that there is a great deal of chemical diversity and bioactivity that remains to be discovered and characterized. A central challenge to the field is that many of the novel or poorly understood molecules are expressed at low levels in the laboratory-such molecules are often described as the 'cryptic' secondary metabolites. In this review, we will discuss evidence that research in this field has provided us with sufficient knowledge and tools to express and purify any secondary metabolite of interest. We will describe 'unselective' strategies that bring about global changes in secondary metabolite output as well as 'selective' strategies where a specific biosynthetic gene cluster of interest is manipulated to enhance the yield of a single product.


[Histological and electron microscopic study of rotator cuff tear].
To understand the changes of rotator cuff during tear and observe the pathologic and ultramicroscopic structure of rotator cuff. Histological and ultra thin slides of samples of 36 cases of rotator cuff were made. The degeneration of rotator cuff happened in synovium side, and then extended to the middle and deep sides of tendon. The deep side of cuff tendon could degenerate without synovium. The repair of tendon could be achieved with two types of healing. It would be difficult to achieve full repair when complete tear and deep side tear occurred to the rotator cuff.


Hepatitis B virus testing by minipool nucleic acid testing: does it improve blood safety?
Hepatitis B virus (HBV) DNA-positive yield since nucleic acid testing (NAT) implementation (minipools of 16 [MP16]) was reported for the first year. We have updated those figures, evaluated the current value of all HBV tests, calculated the HBV residual risk before and after the introduction of MP-NAT, and estimated residual risks with further improvements in HBV screening for US blood donations. All donations were screened by US-required serologic HBV tests and for HBV DNA by MP-NAT (Novartis/Gen-Probe). Further testing by individual-donation polymerase chain reaction (ID-PCR) confirmed various classes of MP-NAT-reactive or -nonreactive donations. The hepatitis B surface antigen (HBsAg)-yield method was used to calculate incidence and the incidence-window-period model used to define residual risk. Of approximately 12.8 million donations screened during 2009 to 2011, a total of 1368 HBV confirmed positives including 941 by MP-NAT were observed (combined 4.32% positive predictive value) of which five were seronegative NAT-yield donations (1:2.6 million) and 25 HBsAg-yield (anti-HBc-nonreactive) donations from which an incidence of 1.62/100,000 person-years (vs. 3.43 during 2006-2008) and residual risk of 1:592,000 to 1:754,000 were calculated. With the addition of MP-NAT, and resulting 8.8-day window-period reduction, residual risks decreased to 1:765,000 to 1:1,006,000. Of the 1368 positives, 99.6% were detected by serology and 68.8% by MP-NAT; ID-PCR detected 427 more infected donors than MP-NAT. HBV MP-NAT and decreases in HBV incidence (likely vaccine-related) in the United States have reduced residual risks to levels comparable to those of human immunodeficiency virus and hepatitis C virus and raise the question of the continued need for all three HBV markers for blood donation screening. Further reductions in residual risk will require the implementation of more sensitive HBV-NAT methods including ID-NAT.


Synthesis of new pyrazolothiazole derivatives from 4-thiazolidinones.
The synthesis of new 2,3,5,6-aryl substituted tetrahydro-2H-pyrazolo[3,4-d]- thiazoles 4a-j as potential biologically active compounds by the cyclocondensation of phenyl hydrazine with new 5-arylidene derivatives 2a-j of 2,3-disubstituted-1,3- thiazolidin-4-ones 1a-e is reported.


Regulation of c-fos and c-jun expression in the rat supraoptic nucleus.
1. We have investigated induction of the nuclear proto-oncogenes c-fos and c-jun in the rat supraoptic nucleus (SON) during physiological stimulation. 2. Dehydration (0-24 hr) was associated with modest, but significant increases in both c-fos and c-jun mRNA at 8 hr and 16 hr as determined by Northern analysis of total RNA extracted from microdissected SON. Prior to 8 hr, and beyond 24 hr, no consistent changes in c-fos and c-jun mRNA were found. Levels of c-fos and c-jun mRNA in the hippocampus were not altered over 24 hr of dehydration. 3. Acute stimulation with hypertonic saline (1.5 M, i.p.) resulted in a marked increase in SON c-fos mRNA at 1 hr (6-fold) and 2 hr (3.5-fold). Small increases in SON c-jun mRNA were observed at these time points. Treatment with a similar volume of 0.9% saline did not elevate SON c-fos and c-jun mRNA levels. 4. Analysis of transcriptional activity with a nuclear run-on assay showed that activation of transcription appears to mediate the induction of c-fos and c-jun mRNA following acute hypertonic saline treatment. During dehydration transcriptional activation is apparent for c-jun but is not well defined for c-fos. 5. The results are discussed with reference to the hypothesis that products of c-fos and c-jun may mediate adaptive changes in hypothalamic gene expression.


Influence of initial water content on the subsequent water sorption and solubility behavior in restorative polymers.
To evaluate the water sorption characteristics and solubility behavior of two resin-based composites, an ormocer, a compomer and a resin-modified glass-ionomer, according to ISO 4049 specifications and also without the initial desiccation cycle. After polymerization, five disks (15 x 1 mm) of each material [Filtek P60 (P60), Solitaire 2 (SOL2), Admira (ADM), Compoglass F (COF) and Fuji II LC (FLC)] were desiccated until a constant mass (ml) was obtained. They were immersed in distilled water for 7 days and immediately weighed after that period (mass m2). Then disks were again desiccated and weighed every day for 35 days (mass m3). Sorption and solubility values were deduced from these different measures. Without initial desiccation mass m1 was obtained just after polymerization. Without initial desiccation, all the materials absorbed less water and solubility was 1.5 to 8 times greater than in standard experiment. For the two protocols, water sorption and solubility were significantly greater in FLC, and ADM showed the least weight loss of all the materials tested.


Correction: Ultrasensitive recognition of AP sites in DNA at the single-cell level: one molecular rotor sequentially self-regulated to form multiple different stable conformations.
[This corrects the article DOI: 10.1039/C9SC04140K.].


A Capuchin monkey (Cebus apella) recognizes when people do and do not know the location of food.
In a previous study, Kuroshima and colleagues demonstrated that capuchin monkeys (Cebus apella) learned to discriminate between a "knower" who inspected a box for food, and a "guesser" who did not. The aim of the present study was to specify whether the subjects learned a simple conditional discrimination or a causal relationship that seeing leads to knowing. In experiment 1, we introduced five types of novel containers to two subjects. Each container was of different shape and color. The subjects gradually learned to reach toward the container the knower suggested. In experiment 2, we diversified the behavior of the knower and the guesser. In experiment 3, in order to eliminate the possibility of discrimination based on differences in the magnitude and the complexity of two trainers, we equated their behaviors. One subject adapted to the novel behaviors of the knower and the guesser, successfully discriminating the two trainers. Thus this monkey clearly learned to use the inspecting action of the knower and the non-inspecting action of the guesser as a discriminative cue to recognize the baited container. This result suggests that one capuchin monkey learned to recognize the relationship between seeing and knowing.


Effect of Strict and Soft Policy Interventions on Laboratory Diagnostic Testing in Ontario, Canada: A Bayesian Structural Time Series Analysis.
Applications of behavioral economics targeted at optimizing laboratory utilization among physicians have been implemented in Ontario through different types of nonfinancial interventions. Strict policy interventions restrict Ontario Health Insurance Plan (OHIP) payment for tests to patients with specific conditions or limit ordering to particular physician specialties, while soft policy interventions involve modifications to the laboratory requisition form. This study evaluates the effectiveness of these interventions in terms of changing physician ordering behavior for eight tests that were subject to a strict or soft policy intervention during the study period. We use a Bayesian structural time series model applied to Ontario laboratory claims data for FY2006 through FY2017. Results show a 16-75% reduction in laboratory services with a strict policy intervention and an 8-36% reduction in laboratory services with a soft policy intervention. Although the overall magnitude of change was smaller for soft policy interventions, interventions designed with soft or strict policy mechanisms addressing laboratory utilization management are effective at influencing physicians' test ordering behavior.


Adjuncts to reduce the incidence of embolic brain injury during operations on the aortic arch.
Two adjunctive techniques for operations involving the aortic arch, retrograde perfusion of cold oxygenated blood through the superior vena cava and establishment of antegrade flow after hypothermic circulatory arrest, are described. These techniques should reduce or possibly eliminate the embolization of air and particulate matter into the cerebral circulation and may reduce the incidence of brain injury.


An Update of Efficacy and Safety of Cetuximab in Metastatic Colorectal Cancer: A Narrative Review.
Colorectal cancer is the second most common cancer, representing 13% of all diagnosed cancers. Cetuximab is a recombinant chimeric monoclonal IgG1 antibody and epidermal growth factor receptor (EGFR) inhibitor. Cetuximab is approved for the first-line treatment in combination with chemotherapy or as a single agent in patients who have failed or are intolerant to chemotherapy in patients with EGFR-expressing, RAS wild-type metastatic colorectal cancer. Cetuximab efficacy emerged from studies that were conducted to approve the drug. Cetuximab is well tolerated; its toxicities are caused by its mechanism of action and the most common adverse reaction is skin toxicity. The main purpose of this manuscript is to present an update on the evidence-based summary of efficacy and safety and on the cost-effectiveness of cetuximab. Furthermore, it suggests a management of adverse drug reactions to improve the tolerability of the drug.


Calcium content in some organs of rats treated with a toxic calciol dosis.
Administration of 100,000 IU of calciol for 3 consecutive days to female rats increased calcium levels in serum, kidney, duodenum and cardiac muscle, but was without effect on calcium content in skeletal muscle, liver and brain.


The phenotype of ex vivo generated cytokine-induced killer cells is associated with overall survival in patients with cancer.
Cytokine-induced killer (CIK) cells are ex vivo generated heterogeneous NK-like T lymphocytes. It is not very clear whether the phenotype of CIK cells is associated with their therapeutic efficacy to cancer patients. Thus, in this study, the association of phenotype of CIK cells and the overall survival of 121 patients with hepatocellular carcinoma (HCC), 74 patients with lung cancer and 42 patients with colorectal cancer, all of whom underwent surgical resection and received autogenous CIK cell therapy, was analyzed. We found that high ratio of the CD3+CD4+ subset was associated with poorer overall survival in colorectal cancer, but not HCC or lung cancer. A high ratio of the CD3+CD8+ subset was associated with improved overall survival in all three types of cancer. A high ratio of the CD3+CD56+ NK-like subset was associated with improved overall survival in lung and colorectal cancer, but not HCC. A high ratio of the CD3-CD56+ NK subset was associated with poorer overall survival in lung and colorectal cancer, but not HCC. In conclusion, the CD3+CD8+ and CD3+CD56+ subsets, especially the CD3+CD8+ subset, may be the major phenotypes responsible for anti-tumor immunity in vivo after autogenous CIK cell therapy.


Do optimal dipoles obtained by the dipole tracing method always suggest true source locations?
Scalp potentials generated by a concentrated electric source in the brain are very similar to potentials generated by an electric dipole at the source position. In this sense a concentrated source in the brain is modelled as an electric dipole. When the source is diffuse such a dipole which best approximates the scalp potential is called an optimal dipole. Its position is calculated by the Dipole Tracing Method based on a realistic head model with homogeneous electric conductivity. There are 2 major difficulties inherent in this method: (1) The low electric conductivity of the skull causes systematic shifts of the optimal dipole positions from the true positions of concentrated sources; (2) the optimal dipoles cannot specify diffuse source positions. The first difficulty is overcome by using the numerical correction obtained by comparing the known dipole positions generated within a human head with their optimal ones. The second difficulty is removed to a certain extent by comparing the optimal dipole positions obtained with the 1-dipole and 2-dipole models together with their dipolarity. We have obtained criteria for the validity of the dipole approximation and source concentration.


Management of infants with intra-uterine growth restriction.
Intra-uterine growth restriction (IUGR) and prematurity are the two causes for delivery of low birth weight infants. In India, IUGR contributes to almost two-thirds of infants in this category. Poor nutritional status and frequent pregnancies are common pre-disposing conditions in addition to obstetric and medical problems during pregnancy. Growth restriction may be symmetrical or asymmetrical depending on the time of insult during pregnancy. The pathological insult in an asymmetrical IUGR occurs during the later part of the pregnancy and has a brain-sparing effect. Common morbidities are more frequent in <3rd percentile group as compared to 3rd-10th percentile group. Guidelines for management of IUGR neonates in these two groups have provided in the protocols.


Idiopathıc pulmonary artery aneurysm.
Pulmonary artery aneurysms are rare pathologic conditions of the thoracic cavity. The ıdiopathic form of the disease is reported very rarely. We report the case of a 16-year-old girl with idiopathic pulmonary artery aneurysm with surface rendered 3-dimensional images of 64-slice computed tomography. A right-sided aortic arch with normal aortic branching was seen. The main pulmonary artery was moderately dilated, and there was aneurysmal dilatation of the right pulmonary artery from its origin to the level of the right descending pulmonary artery. The maximal diameter of the main pulmonary artery was 38 mm; that of the right pulmonary artery was 31 to 34 mm. The left pulmonary artery was of normal diameter (18.5 mm). There was no other accompanying abnormality. Because the patient had no severe symptoms and there were no signs of aneurysmic compression or a shunt, she was scheduled for elective aneurysmectomy.


The sensitivity of gentamicin-resistant gram-negative bacilli to cefotaxime, other cephalosporins and aminoglycosides.
The sensitivities of 80 gentamicin-resistant gram-negative bacilli to cefotaxime, cefuroxime, cefoxitin, cefamandole, cefazolin, tobramycin, netilmicin and amikacin were determined. Amikacin was the most active amino-glycoside. However, the percentage sensitivity to cefotaxime of most of the species was higher than, or equal to any of the other antibiotics tested. Cefotaxime was particulary active against Providencia spp., Serratia spp., Klebsiella spp., and Pseudomonas maltophilia, being 16 to 256 times more active than the next best cephalosporin or cephamycin. Clinical trials of cefotaxime are now required.


Tarsal and metatarsal bone mineral density measurement using volumetric quantitative computed tomography.
A new method for measuring bone mineral density (BMD) of the tarsal and metatarsals is described using volumetric quantitative computed tomography (VQCT) in subjects with diabetes mellitus and peripheral neuropathy. VQCT images of a single foot were acquired twice from eight subjects (mean age 51 [11 SD], seven males, one female). The cortical shells of the seven tarsal and five metatarsal bones were identified and semiautomatically segmented from adjacent bones. Volume and BMD of each bone were measured separately from the two acquired scans for each subject. Whole-bone semiautomatic segmentation measurement errors were determined as the root mean square coefficient of variation for the volume and BMD of 0.8% and 0.9%, respectively. In addition to the whole-bone segmentation methods, we performed atlas-based partitioning of subregions within the second metatarsal for all subjects, from which the volumes and BMDs were obtained for each subregion. The subregion measurement BMD errors (root mean square coefficient of variation) within the shaft, proximal end, and distal end were shown to vary by approximately 1% between the two scans of each subject. The new methods demonstrated large variations in BMDs between the 12 bones of the foot within a subject and between subjects, and between subregions within the second metatarsal. These methods can provide an important outcome measure for clinical research trials investigating the effects of interventions, aging, or disease progression on bone loss, or gain, in individual foot bones.


On latches in biological systems: a comparative morphological and functional study of the retinaculum and the dens lock in Collembola.
Springtails have the ability to jump using morphological structures consisting of a catapult, the furca, and a latching system constructed with interaction of the retinaculum and the dens lock. The retinaculum engages in the furca at the dens lock in order to form a spring mechanism. They exhibit diversified morphological traits that serve as adaptations to a variety of terrestrial strata and aquatic surface environments. This comparative morphofunctional study centered on the retinaculum and the furcular region of the dens lock aims to describe the morphological variation between taxa and provide insights into the functional dynamics of the latching mechanism at work in the jumping apparatus. Using SEM, µCT and cLSM, we compared representatives of Collembola taxa, Poduromorpha (Neanura muscorum and Podura aquatica), Symphypleona (Dicyrtomina ornata) and Neelipleona (Megalothorax minimus), and examined extracts of the environment in which they were collected. A retinaculum is absent in N. muscorum, although vestigial muscles were found. Abdominal musculature varies significantly, being more abundant in springtails with clear segmentation (N. muscorum and P. aquatica), and reduced in springtails with fused segmentation (D. ornata and M. minimus). The M.a-ret varies as regards architecture and point of connection with the ramus, which is lateral in P. aquatica and median in the other species studied. The number of teeth in the retinaculum ramus also varies between three in M. minimus and four in the other species. The dens lock of all species studied has two locks and two furrows. The retinaculum and dens lock interact in a key-lock relationship. The latching and unlatching mechanism from the retinaculum and dens lock appear to be similar in all the taxa examined, occurring by muscle force. This leads us to question the hypothesis that hemolymph pressure may be a force generator in jumping. We offer a reconstruction of the ground pattern of the retinaculum and dens lock and, in addition, an explanation of their functioning and the interaction between them. Finally, we frame the interaction between the retinaculum and the dens lock as a latch in a biological system, a mechanism which functions by force of physical contact.


Indirect determination of captopril by AAS.
An indirect method is described for the determination of captopril (KPL) in pharmaceutical preparations by atomic absorption spectrometry (AAS). The procedure is based on the complexation of KPL with an excess of Pd(II) ion. The unreacted Pd(II) was resoluted on a cationic ion-exchanger resin, while Pd(II)-KPL sequestrate was not retained. The effluent Pd(II) sequestrade was measured by AAS. The absorbance is found to increase linearly with increasing KPL concentration, because the amount of Pd(II) is related to the concentration of KPL, which is corroborate by the calculated correlation coefficient value of 0.9939. The system obeys Beer's law for 1-40 microg ml(-1), S.D. was found to be 0.039 (n = 5). The Pd(II)-KPL complex was obtained in the solid phase. Characterization of the complex was performed by elemental analysis, TG, conductance measurements and IR, 1H-NMR spectroscopy.


Isolation and characterization of heat stable proteinases from Pseudomonas isolate AFT 21.
Pseudomonas strain AFT 21 produced three heat stable extracellular proteinases in milk and nutrient broth at 7 or 21 degrees C, but the proportions depended on medium and cultivation temperature. The three proteinases were EDTA- and o-phenanthroline-sensitive metalloenzymes and were not inhibited by N-ethylmaleimide or phosphoramidon. Proteinases I and II showed maximum activity at pH 7-7.5 and proteinase III at pH 8.5. All three enzymes showed maximum activity at 45-47.5 degrees C, but had relatively high (19-27% of maximum) activity at 4 degrees C. They were unstable at 55 degrees C in phosphate buffer, pH 6.6, or synthetic milk ultrafiltrate (SMUF) containing 12 mmol Ca2+, but were stabilized by short preheating at 100 degrees C. They were extremely heat stable in both phosphate buffer and SMUF, pH 6.6, at 70-150 degrees C. Their D-values at 140 degrees C were 69, 54 and 80 s respectively. The Z-values for Pseudomonas AFT 21 proteinase III in phosphate buffer and SMUF were 29.7 and 30.3 degrees C respectively; the corresponding activation energies for inactivation were 8.7 x 10(4) J mol-1 and 9.2 X 10(4) J mol-1.


Simple Monovalent Metal Ion Logical Order to Regulate the Secondary Conformation of G-Quadruplex.
Based on the reactions of different sequences with single ions K+, Na, NH4 +, double ions high + low, low + high, and triple ions with different addition orders, the best stable ion combinations of 12 quadruplexes with different DNA sequences were reported. From the fluorescence spectrum, except for HT-V15 and PW17 and AS1411 and HT-V18, the structural stability of G-quadrangle formed basically follows a certain rule. In terms of this experiment, according to circular dichroism, the antiparallel quadrupole structure has the largest proportion among quadrupole structures, and 12 optimal DNA addition schemes and sequences have been obtained through exploration. It is worth mentioning that, on the whole, the best addition scheme of AS1411 and HT-V18 is a three-ion scheme, which provides an effective reference for similar experiments in the future.


Cell-Mediated Glomerulonephritis Without Immune Complexes in Native Kidney Biopsies: A Report of 7 Cases.
We report 7 native kidney biopsies with diffuse endocapillary hypercellularity without immune deposits, affecting 5 women and 2 men aged 52-85 years. All patients had acute kidney injury, and 4 had nephrotic-range proteinuria. Comorbidities included breast cancer in 2, pancreatitis in 1, and para-aortic lymphadenopathy and bilateral carpal tunnel syndrome in 1. Kidney biopsies were characterized by predominant T-cell and CD68-positive macrophage infiltration in glomerular capillaries without deposits. Coexisting lesions included small cellular crescents in 5, mild peritubular capillaritis in 1, mononuclear cell intimal arteritis in 1, acute tubulointerstitial nephritis in 4, and mild arteriolosclerosis in 1. During the mean follow-up duration of 24.8 months, 4 patients showed partial or complete initial remission in response to immunosuppression. However, 2 deteriorated when prednisone was rapidly tapered (1 of them achieved subsequent remission with increased prednisone). Three patients developed kidney failure. We propose that this unusual pattern of injury is mediated by abnormal cell-mediated immune response. The underlying causes and pathogenesis of this cell-mediated glomerulonephritis will require further study.


High urinary excretion of nitrate and N-nitrosoproline in opisthorchiasis subjects.
About 50% of the population in some provinces of north-east Thailand are infested with liver fluke (Opisthorchis viverrini), and many develop cholangiocarcinoma subsequently. This study was designed to demonstrate possible endogenous formation of N-nitrosoproline (NPRO) in this population. Diet samples, saliva and urine were taken from subjects with and without liver fluke and analysed for nitrate and nitrite; urine was also analysed for NPRO. Nitrate and nitrite levels in saliva were higher in subjects with liver fluke than in those without; total nitrate and NPRO excretion was also higher in this group. Subjects with liver fluke may therefore be more heavily exposed to N-nitroso compounds than others, and may be at higher risk for cholangiocarcinoma.


Characterization of adsorption on the stationary phase using high-performance immunoaffinity chromatography.
Low-level adsorption on the stationary phase has been studied using immunochemical reagents. An immunoaffinity column has been evaluated using affinity-purified radioisotope-labeled monoclonal antibodies. Recovery experiments including continuous immunosorbent monitoring have been performed. Proper characterization of an immunoaffinity separation can result in the recovery of immunologically active material in high yield.


Non-immunogenic, low-toxicity and effective glioma targeting MTI-31 liposomes.
Liposomes with peptide motifs have been successfully used in glioma-targeted delivery of various general chemotherapy agents. However, their use for the encapsulation of low-toxicity molecularly targeted anticancer agents has been limited. In the present study, we aimed to assess the efficacy and safety of a novel low-toxicity mTORC1/mTORC2 inhibitor (MTI-31) as a treatment for glioma when encapsulated in appropriate liposomes. Since some of the peptide-modified liposomes have been determined to be immunogenic and may have life-threatening consequences in mice, an immunogenicity-based investigation with candidate liposomal carriers was conducted. Following this study, DVAP (DPDADVDRDTDNDS) modified liposomes (DVAP-liposomes) were identified as an immunologically safe carrier and therefore utilized for MTI-31 encapsulation. DVAP is a tumor homing peptide exhibiting high binding affinity to glucose regulated protein 78 (GRP78) overexpressed in glioma, glioma stem cells, vasculogenic mimicry and neovasculature. Modification of liposomes with DVAP imparts a glioma-directing property. In vitro, the developed DVAP-liposomes/MTI-31 were efficiently internalized by U87 cells and consequently showed a potent antiproliferation effect. In vivo, the safety and anti-glioma efficiency of DVAP-liposomes/MTI-31 were validated in intracranial glioma bearing BALB/c nude mice. While showing both systemic and immunological safety, DVAP-liposome/MTI-31 treatment resulted in a significant improvement in the median survival time (24.5 days for saline, 26 days for free MTI-31, 25 days for liposomes/MTI-31 and 36 days for DVAP-liposome/MTI-31). The results highlight MTI-31 as an effective anti-glioma agent when encapsulated in non-immunogenic glioma-targeted liposomes, which may contribute to the development of better anti-glioma treatment.


[Prescription of non-steroidal anti-inflammatory agents and risk of iatrogenic adverse effects: a survey of 1072 French general practitioners].
As a group, non-steroidal anti-inflammatory drugs (NSAIDs) rank first among commonly prescribed drugs for serious adverse reactions. We conducted a cross-sectional survey in which 1072 French general practitioners (GPs) were evaluated for their basic pharmacological knowledge and practice of NSAIDs prescription. Results suggest that GPs have insufficient pharmacological knowledge and provide inadequate management of adverse reaction risk. Well-established risk factors for serious adverse reactions, such as age, are not taken enough into account, and tolerance is not correctly monitored. Drugs allegedly protecting against peptic ulcers are frequently associated but, most of the time, without any relevant justification, such as the patient's risk level or drug's efficacy. Our findings demonstrate a need for greater information among GPs about prescription and tolerance monitoring of NSAIDs.


Spasm of the near reflex associated with organic disease.
Spasm of the near reflex is characterized by transient attacks of convergence, accommodation, and miosis. It is usually observed in young individuals and considered functional. We studied seven patients with spasm of the near reflex who had associated neurologic disorders or head trauma. Two patients had posterior fossa abnormalities (cerebellar tumor, Arnold-Chiari malformation), two patients had pituitary tumors, one patient had a vestibulopathy, and two patients had a history of antecedent head trauma.


5-demethylubiquinone-9-methyltransferase from rat liver mitochondria. Characterization, localization, and solubilization.
The methyltransferase responsible for the conversion of 5-demethylubiquinone-9 to ubiquinone-9 in rat liver mitochondria has been shown to be localized in the inner membrane of rat liver mitochondria. NADH was required to generate the hydroquinone, which was the immediate substrate for methylation. The Km for 5-demethylubiquinone-9 was estimated to be in the range of 60 to 80 nM and the Km for S-adenosylmethionine was found to be 22 micronM. The methyl-transferase was solubilized by Triton X-100, a procedure which inactivated the 5-demethylubiquinone-9 reductase. Dithionite was found to partially substitute for NADH in both membranous and soluble systems. Inhibitors of catechol-O-methyltransferase were not effective inhibitors of 5-demethylubiquinone-9-methyltransferase. In addition, catechol-O-methyltransferase and 5-demethylubiquinone-9-methyltransferase were found to have reciprocal subcellular localizations. It is likely that the hydrophobic side chain of ubiquinone, added to p-hydroxybenzoate in the first biosynthetic step, is required for attachment to the lipid bilayer. This permits subsequent metabolism of the ring system by membrane-bound enzymes, including the final methylation to form ubiquinone-9.


Changes in brain activity after weight loss.
The importance of the regulatory role of the brain in directing glucose homeostasis, energy homeostasis, eating behaviour, weight control and obesity is increasingly recognized. Brain activity in (sub)cortical neuronal networks involved in homeostatic control and hedonic responses is generally increased in persons with obesity. Currently, it is not known if these functional changes can be affected by dieting. The aim of the current study was to investigate whether prolonged fasting and/or weight loss influences neuronal brain activity in obese persons. Fourteen participants with obesity were included (two male participants and 12 female participants, body mass index 35.2 ± 1.2 kg m-2). Whole-brain resting-state functional magnetic resonance imaging was performed after an overnight fast, after a prolonged 48-h fast and after an 8-week weight loss intervention. An 8-week weight loss intervention decreased BOLD signal in areas of the brain involved in salience, sensory motor and executive control. BOLD signal in these areas correlated with leptin levels and body mass index. Weight loss decreased activity in brain areas involved in feeding behaviour and reward processing. These results indicate that these obesity-associated alterations in neuronal activity are related to excessive body weight and might change after weight loss.


The use of karyotyping in the systematics of yeasts.
The use of electrophoretic karyotyping in systematics of yeasts is discussed. New data are provided on the karyotypes of the medically important fungi Hortaea werneckii, Filobasidiella (= Cryptococcus) neoformans, and Malassezia species. Hortaea werneckii has twelve to eighteen bands of chromosomal DNA, ranging in size between 500 and 2300 kb. The karyotypes of Filobasidiella neoformans consist of seven to fourteen bands of chromosomal DNA. The varieties neoformans and bacillispora cannot be separated by their karyotypes, and no obvious correlation was found with serotypes, geography or habitat. All strains of Malassezia pachydermatis studied have similar karyotypes consisting of five bands, whereas in M. furfur, four different karyotypes are prevalent. However, each of these karyotypes is stable.


Overexpression of the type II transforming growth factor-beta receptor inhibits fibroblasts proliferation and activates extracellular signal regulated kinase and c-Jun N-terminal kinase.
Transforming growth factor-beta (TGF-beta) is a bimodal regulator of cellular growth. The cellular effects of TGF-beta depend on the intensity of signals emanating from TGF-beta receptors. Low levels of receptor activity are sufficient to stimulate cell proliferation, while higher degrees of receptor activation are associated with growth inhibition. To study the mechanisms of these effects, a tetracycline-inducible expression system was used to overexpress type II TGF-beta receptors in NIH 3T3 fibroblasts. Overexpressed type II TGF-beta receptors suppressed fibroblast proliferation elicited by TGF-beta1, fibroblast growth factor (FGF) or platelet-derived growth factor (PDGF). Accompanying these anti-proliferative effects, increases in extracellular-signal regulated kinase (ERK) and c-Jun N-terminal kinase (JNK) activity were detected. Furthermore, PDGF alpha-, but not PDGF beta-receptor protein levels were reduced by type II TGF-beta receptor overexpression. In conclusion, our system is an excellent tool to study the molecular mechanisms of growth inhibition by TGF-beta in fibroblasts. Activation of JNK and ERK, or modulation of PDGF receptor expression may be involved in this process.


Establishment, characterization, and transfection potential of a new continuous fish cell line (CAM) derived from the muscle tissue of grass goldfish (Carassius auratus).
A new continuous fish cell line (CAM) has been successfully derived from the muscle tissues of grass goldfish, Carassius auratus. The primary cell cultures were initiated by incomplete trypsinization first and then explant culture in a Leibovitz-15 medium supplemented with 15% fetal bovine serum and 10% fish muscle extract. It was found that the CAM cells were very sensitive to trypsinization and needed to be sub-cultured at a low trypsin concentration of 0.0625% to be able to go through the crisis of spontaneous immortalization transformation, and afterward a total of five derivative cell strains were isolated from the original CAM cell line. This spontaneous immortalization transformation event was recorded successively at passages 44-47, beginning with a large-scale apoptosis and senescence and followed by mitosis arrest and re-activation, thus designated as cell strain CAM-44A, 44B, 45A, 44B, and 47A. Now both the CAM cell line and strains had been sub-cultured for more than 89 times and could be well cryopreserved in the growth medium containing 5% dimethylsulfoxide. Chromosome analysis and COI gene analysis had confirmed the grass goldfish origin of these CAM cells. Transfection potential analysis indicated that Lipofectamine LTX and Xfect were two suitable transfection reagents to be used in the gene delivery of CAM cells with a transfection efficiencies up to 11±6% and 8±3% in the CAM cell lines, respectively. Among the five cell strains, CAM-47A showed the highest transfection potential with a transfection efficiency up to 28 ± 5%. This work will provide a useful cell source for works on the cell-based artificial fish meat production and functional studies of fish myogenesis-related genes.


Nonlinear rheology of glass-forming colloidal dispersions: transient stress-strain relations from anisotropic mode coupling theory and thermosensitive microgels.
Transient stress-strain relations close to the colloidal glass transition are obtained within the integration through transients framework generalizing mode coupling theory to flow driven systems. Results from large-scale numerical calculations are quantitatively compared to experiments on thermosensitive microgels, which reveals that theory captures the magnitudes of stresses semi-quantitatively even in the nonlinear regime, but overestimates the characteristic strain where plastic events set in. The former conclusion can also be drawn from flow curves, while the latter conclusion is supported by a comparison to single particle motion measured by confocal microscopy. The qualitative picture, as previously obtained from simplifications of the theory in schematic models, is recovered by the quantitative solutions of the theory for Brownian hard spheres.


Relationship between the distribution of plasma HDL subclasses and the polymorphisms of APOA5 in hypertriglyceridemia.
This study aims to examine the possible associations between high density lipoprotein (HDL) subclass distribution and APOA5-1131T>C polymorphism in hypertriglyceridemia. The distribution of HDL subclasses was quantified by 2-dimensional electrophoresis in conjunction with immunodetection method. The APOA5-1131T>C polymorphism was identified in 95 hypertriglyceridemic (HTG) patients and 102 healthy subjects by polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP). The APOA5-1131C (C) allele frequency was higher in the HTG group than in the control group. Plasma triglycerides (TG) were significantly higher and apoA5 was significantly lower in patients with the C allele when compared to patients with the APOA5-1131T (T) allele, even more dramatically so in the APOA5-1131CC homozygote. In both the HTG group and the control group, the frequency of the C allele was positively correlated with levels of TG, total cholesterol (TC), low density lipoprotein cholesterol (LDL-C) and apolipoprotein B100 (apoB100), and negatively correlated with levels of high density lipoprotein cholesterol (HDL-C), apolipoprotein A1 (apoA1) and apolipoprotein A5 (apoA5) (P<0.001). In all subjects, the frequency of the C allele was positively correlated with the level of small-sized HDL (preβ(1)-HDL and HDL(3a)), and negatively correlated with levels of HDL(2a) and HDL(2b). Changes in HDL subclass distributions in HTG may be related to the APOA5-1131T>C polymorphism. This polymorphism leads to a general shift towards smaller-sized HDL.


Initial effects of low-level laser therapy on growth and differentiation of human osteoblast-like cells.
Low-level laser therapy is a clinically well established tool for enhancement of wound healing. In vitro studies have also shown that low level laser therapy has a biostimulatory effect on cells of different origin. The aim of this in vitro study was to investigate the initial effect of low-level laser therapy on growth and differentiation of human osteoblast-like cells. SaOS-2 cells were irradiated with laser doses of 1 J/cm2 and 2 J/cm2 using a diode laser with 670 nm wave length and an output power of 400 mW. Untreated cells were used as controls. At 24 h, 48 h and 72 h post irradiation, cells were collected and assayed for viability of attached cells and alkaline phosphatase specific activity. In addition, mRNA expression levels of osteopontin and collagen type I were assessed using semi-quantitative RT-PCR. Over the observation period, cell viability, alkaline phosphatase activity and the expression of osteopontin and collagen type I mRNA were slightly enhanced in cells irradiated with 1 J/cm2 compared with untreated control cells. Increasing the laser dose to 2 J/cm2 reduced cell viability during the first 48 h and resulted in persistently lower alkaline phosphatase activity compared with the other two groups. The expression of osteopontin and collagen type I mRNA slightly decreased with time in untreated controls and cells irradiated with 1 J/cm2, but their expression was increased by treatment with 2 J/cm2 after 72 h. These results indicate that low-level laser therapy has a biostimulatory effect on human osteoblast-like cells during the first 72 h after irradiation. Further studies are needed to determine the potential of low-level laser therapy as new treatment concept in bone regeneration.


MiR-494 acts as a tumor promoter by targeting CASP2 in non-small cell lung cancer.
MiR-494 plays an important role in several types of human cancers, including non-small cell lung cancer (NSCLC). Although the role of miR-494 has been investigated in several studies, the expression profile and underlying mechanism are still poorly understood. In this study, we found that overexpression of miR-494 promoted the proliferation and colony formation of NSCLC cells and reduced their sensitivity to cisplatin-induced apoptosis. By using microarray and Dual luciferase reporter assays, we further showed that caspase-2 (CASP2) is a functional target of miR-494, and the expression of CASP2 is inversely associated with miR-494 in vitro. In addition, miR-494 promoted the proliferation and colony formation of NSCLC cells and reduced their sensitivity to cisplatin-induced apoptosis by targeting CASP2. Therefore, our results suggest that miR-494 plays an oncomiR role in NSCLC cells and may be a candidate biomarker for malignant transformation and a therapeutic target of NSCLC.


Polystyrene nanospheres-induced hepatotoxicity in swamp eel (Monopterus albus): From biochemical, pathological and transcriptomic perspectives.
As ubiquitous emerging pollutants, microplastics (MPs) in aquatic environments have aroused critical global concerns. Despite the occurrence and characteristics of MPs in freshwater agroecosystems well-described by our previous study, their ecotoxicological implications in Monopterus albus remains unfathomed. Herein, we dissected toxic effects and mechanisms of PS-NPs exposure against M. albus hepatic tissues at concentrations of 0.5 (L), 5 (M), 10 (H) mg/L for 28 days using physiochemical measurements, histopathological analysis and transcriptomic sequencing. Results showed that upon PS-NPs treatments, levels of ROS, MDA, 8-OHdG and MFO activity were significantly enhanced relative to the control (C) group, while SP content and T-AOC activity were dramatically suppressed, suggesting ROS burst, lipid peroxidation and DNA damage may occur in liver tissues. This oxidative damage further triggered impaired hepatic function and histopathology, disordered lipid metabolism and hepatocyte apoptosis, as reflected by significantly diminished activities of GPT, GOT, ACP, AKP and LDH, paralleled with augmented levels of TG, TC and HSI as well as Cytc and Caspase-3,8,9 activities. Noticeably, concentration-dependent rises of apoptotic rate, vacuolar degeneration and lipid deposition were manifest in TUNEL, H&E and ORO staining. In addition, a total of 375/475/981 up-regulated as well as 260/611/1422 down-regulated DEGs in C vs L, C vs M and C vs H categories were identified based on RNA-seq, respectively. These DEGs were significantly annotated and enriched into GO terms (membrane, cytoplasm, response to stimuli, oxidation-reduction process) as well as KEGG pathways (ether lipid metabolism, apoptosis, chemical carcinogenesis-reactive oxygen species, non-alcoholic fatty liver disease). Moreover, signaling cascades Keap1-Nrf2, p53 and PPAR were either substantially initiated or dysregulated to orchestrate PS-NPs hepatotoxicity featuring oxidative damage, hepatocyte apoptosis and lipid steatosis. Collectively, this study not only expounded on toxicological mechanisms whereby PS-MPs exerted deleterious effects on M. albus, but also pointed to ecological risks of PS-MPs-induced hepatoxicity and lipid steatosis in this commercially-important species.