Integration of leave-one-out method and real-time live cell reporter array system to assess the toxicity of mixtures.
The ever-increasing number of chemicals and complex mixtures demands a time-saving and cost-effective platform for environmental risk assessment. However, there is limit promising tool for evaluating the contribution of each component to the total toxicity effects of the mixture. Here, four widely distributed environmental pollutants with different mode-of-actions, i.e., cadmium chloride (Cd), nitrofurazone (NFZ), triclosan (TCS), and tris(2-chloroethyl) phosphate (TCEP), were selected as components of artificial mixture. Integration of leave-one-out method and high-dimensional live cell array system was used to explore relative contribution of each component from the mixture. A quaternary mixture (All_4_chems) and four ternary mixtures (Leave_Cd, Leave_NFZ, Leave_TCS and Leave_TCEP) were investigated by Escherichia coli (E. coli) live cell array system with 90 environmental stress genes modified by green fluorescent protein (GFP) expressing reporter vectors. E. coli cytotoxicity tests demonstrated that TCS has antagonism effect with other three chemicals (Cd, NFZ and TCEP), while it was additive effect in other three binary combinations. A total of 26, 23, 13, 31 and 23 genes were significantly altered with fold-change greater than 2 over the 4 h exposure by All_4_chems, Leave_Cd, Leave_NFZ, Leave_TCS and Leave_TCEP, respectively. Clustering analysis based on time-series gene expression patterns and transcriptional effect level index (TELI) showed that Leave_TCEP has similar profiles with All_4_chems, demonstrating TCEP has the least contribution among four components to the quaternary mixture. Leave_NFZ has the least number of significantly altered genes, implying NFZ has the largest toxicity effect contribution to the quaternary mixture. The relative contribution in different pathways indicated that Cd has the most contribution to the mixture in redox stress, while TCS has the least contribution in DNA stress pathway. Collectively, our results demonstrated the utility of high-dimensional toxicogenomics data and leave-one-out method in prioritizing the relative contribution of each component in mixture.


Growth at sub-optimal temperatures allows the production of functional, antigen-binding Fab fragments in Escherichia coli.
Expression in Escherichia coli of recombinant genes coding for the kappa-chain and the Fd fragment of an antibody directed against carcinoembryonic antigen gives rise to Fab dimers. These Fab fragments possess antibody activity, as demonstrated by enzyme-linked immunosorbent assay as well as by ligand competition assay. Effective production of soluble Fab in Escherichia coli was achieved by a decrease in the growth temperature. Following a one step purification by anion exchange chromatography, the bacterially-produced Fab retains its activity at 4 degrees C for at least two months. The relatively simple methodology described in this study should be useful for the design and production of antibodies in bacteria.


Hemispheric asymmetry of pentamethylenetetrazol-induced wave-spike discharges and motor imbalance in rats.
An intrinsic asymmetry of nigrostriatal dopamine system postulated to be responsible for motor imbalance in normal rats (Glick et al., 1976) is believed to create asymmetry of arousal-sensitive wave-spike discharges. In the present study, bilaterally recorded pentamethylenetetrazol (PMZ)-activated wave-spike discharges were correlated with circling behavior in intact rats. Thirteen naive rats (10 male, 3 female) were implanted with electrodes symmetrically placed over the visual cortices, and their rotation directionality was assessed in the rotometer subsequent to administration of d-methamphetamine sul-ate, 1.5 mg/kg, i.p. In 9 rats a PMZ injection, 20 mg/kg, i.p., revealed asymmetric wave-spike bursts. All of them reliably rotated in the dirction opposite to the hemisphere with lower amplitude wave-spike discharges. It is believed that the nigrostriatal dopamine system plays a major role in modulating the asymmetry of wave-spike seizures. The findings are discussed as they relate to asymmetric generalized wave-spike dischanges found in certain petit mal patients.


Synthesis and QSPR study on environment-related properties of polychlorinated diphenyl sulfides (PCDPSs).
Twenty-nine congeners of polychlorinated diphenyl sulfide (PCDPS) theoretically possible were synthesized and purified, and their octanol-water partition coefficients (logK(ow)) and high performance liquid chromatography capacity factors (HPLC-logk') were determined. Then the constitutional and structural descriptors were obtained respectively to establish 2D models and comparative molecular similarity indices analysis (CoMSIA) method was used to establish 3D models. All the models were robust and predictive, indicating that the electrostatic effect may be the primary factor influencing the two properties of PCDPS. The logK(ow) and logk' values of all PCDPS congeners were predicted based on these models. The establishment of linear equation on logK(ow) between PCDPS and chlorinated or brominated diphenyl ether (PCDE, PBDE) was attempted, and the hydrophobic differences were considered to relate with the size of the molecules.


Optical and Vibrational Spectra of CsCl-Enriched GeS2-Ga2S3 Glasses.
Optical and FTIR spectroscopy was employed to study the properties of 80GeS2-20Ga2S3-CsCl chalcohalide glasses with CsCl additives in a temperature range of 77-293 K. It is shown that CsCl content results in the shift of fundamental absorption edge in the visible region. Vibrational bands in FTIR spectra of (80GeS2-20Ga2S3)100 - х (СsCl) x (x = 5, 10, and 15) are identified near 2500 cm(-1), 3700 cm(-1),, around 1580 cm(-1), and a feature at 1100 cm(-1). Low energy shifts of vibrational frequencies in glasses with a higher amount of CsCl can be caused by possible thermal expansion of the lattice and nanovoid agglomeration formed by CsCl additives in the inner structure of the Ge-Ga-S glass.


Mycotoxins in foods in Lower Saxony (Germany): results of official control analyses performed in 2009.
In this presentation, the mycotoxin levels-as analysed by the analytical centre for mycotoxin surveillance of the state food laboratory (LAVES Braunschweig)-for approximately 500 food samples are reported. The samples were collected in the year 2009 at retail in the German federal state of Lower Saxony. Aflatoxin and ochratoxin A were analysed in dried fruits, spices, cereals and tree nuts. Ochratoxin A was detected in all samples of dried vine fruits, at levels up to 8.1 μg/kg. Aflatoxins and ochratoxin A were also found in nutmeg and curry powder: the maximum regulatory levels for aflatoxins were exceeded in 25% of the nutmeg samples. Nearly all samples of basmati rice contained aflatoxins, although at levels below the maximum regulatory level in all but one sample. Aflatoxins were also detected in about 50% of hazelnut samples, in 20% of the samples the maximum levels was exceeded (maximum 23.2 μg/kg). In contrast, aflatoxin contents in pistachios were surprisingly low. Fusarium toxins were analysed in cereals and cereal products such as flour, bread, and pasta. Deoxynivalenol (DON) was the predominant toxin found in these samples: DON was found in about 40% of the samples, although the maximum levels were not exceeded (max. 418 μg/kg). Fumonisins (FBs) and zearalenone (ZEA) were specifically analysed in maize products (snacks, flour and oil). Most of these samples (80%) were positive, but at levels not exceeding the maximum levels. Maximum levels were 98 μg/kg (ZEA) and 577 μg/kg (sum of FB1 and FB2). Ergot alkaloids (six major alkaloids) were analysed in rye flour, and approximately 50% were positive. The highest concentration of ergot alkaloids was 1,063 μg/kg; the predominant alkaloids were ergotamine and ergocristine. In conclusion, the results indicate that continuous and efficient control measures for mycotoxins in a wide range of critical foods are necessary to ensure compliance with maximum levels. Although the mycotoxin levels in the vast majority of samples were below maximum levels, year-to-year variation and changes in the production of relevant commodities may result in a different picture in the future.


Effect of polyacetylenic acids from Prunella vulgaris on various plant pathogens.
This study is aiming at characterizing antifungal substances from the methanol extract of Prunella vulgaris and at investigating those substances' antifungal and antioomycete activities against various plant pathogens. Two polyacetylenic acids were isolated from P. vulgaris as active principles and identified as octadeca-9,11,13-triynoic acid and trans-octadec-13-ene-9,11-diynoic acid. These two compounds inhibited the growth of Magnaporthe oryzae, Rhizoctonia solani, Phytophthora infestans, Sclerotinia sclerotiorum, Fusarium oxysporum f. sp. raphani, and Phytophthora capsici. In addition, these two compounds and the wettable powder-type formulation of an n-hexane fraction of P. vulgaris significantly suppressed the development of rice blast, tomato late blight, wheat leaf rust, and red pepper anthracnose. These data show that the extract of P. vulgaris and two polyacetylenic acids possess antifungal and antioomycete activities against a broad spectrum of tested plant pathogens. This is the first report on the occurrence of octadeca-9,11,13-triynoic acid and trans-octadec-13-ene-9,11-diynoic acid in P. vulgaris and their efficacy against plant diseases. The crude extract containing the two polyacetylenic acids can be used as a natural fungicide for the control of various plant diseases.


A calcium message for Niemann-Pick type C.
Calcium is a ubiquitous secondary messenger that is critical for cellular function. In the highlighted article, Tiscione et al. (2019. J. Cell. Biol. https://doi.org/10.1083/jcb.201903018) describe a link between lysosomal cholesterol storage, calcium distribution alterations, and neuronal morphology in the neurodegenerative disorder Niemann-Pick type C.


Milk fermented with Lactobacillus rhamnosus R0011 induces a regulatory cytokine profile in LPS-challenged U937 and THP-1 macrophages.
Fermented dairy products have become attractive functional foods for the delivery of probiotics and their biologically active metabolites. The aim of this study was to examine the immunomodulatory activity of milk fermented with the probiotic lactic acid bacterium Lactobacillus rhamnosus R0011 (LrF) on macrophages challenged with lipopolysaccharide (LPS), a potent pro-inflammatory stimulus. To this end, human THP-1 or U937 monocytes were differentiated into resting macrophages then stimulated with LPS and co-incubated with the LrF or with milk controls. Levels of pro-inflammatory and immunoregulatory cytokines were determined by enzyme-linked immunosorbent assays. Culturing of LPS-stimulated U937 macrophages with either the whole or filtered LrF resulted in an increase in Interleukin (IL)-1Ra production relative to the negative control. THP-1 macrophages cultured with the LrF demonstrated an increase in LPS-induced IL-10 and IL-1β production, while production of LPS-induced IL-6, sCD54, IL-8, IL-1β, TNF-α, IL-12p70 and Transforming Growth Factor-β (TGF-β) was unaffected. Further, the LrF induced the expression of DC-SIGN and CD206, markers of immunoregulatory M2 macrophage polarization, in LPS-challenged THP-1 macrophages. Taken together, milk fermented with L. rhamnosus R0011 increased regulatory cytokine production from LPS-challenged U937 and THP-1 macrophages, while simultaneously up-regulating the production of IL-1β and expression of DC-SIGN and CD206, a profile characteristic of polarization into the immunoregulatory M2 macrophage phenotype.


Dysphagia lusoria: report of a series of six cases.
Dysphagia lusoria is a rare cause of organic dysphagia. This report describes a series of six patients admitted to our university hospital for dysphagia lusoria. Dysphagia was a constant feature in all our patients. Upper gastrointestinal endoscopy and a barium esophagram prompted the diagnosis, which was confirmed by angiography of the aortic arch showing an aberrant right subclavian artery in all cases. Treatment was surgical in all patients with good results.


What is the Role of the Pharmacist in Obesity Management?
Obesity rates have increased over the last two decades. Based on NHANES data, 68.8 % of US adults are classified as overweight or obese. Obesity increases the risk of diseases and can contribute to increased morbidity and mortality. This review examines studies published in which pharmacists have provided weight management services alone or in a team. The electronic databases OVID Medline, International Pharmaceutical Abstracts and EMBASE (1946-2014) were searched. Nine articles were identified in which pharmacists delivered a weight management service either alone or in a team, and eight studies collected outcomes. Six studies evaluated the participant's weight loss or satisfaction with the service, and two studies evaluated weight loss associated with a meal-replacement program. The outcomes from these studies are limited and while positive, have failed to provide significant evidence of the impact of pharmacists providing these services. More randomized, controlled trials are needed to document weight management services.


Clinical experience of capecitabine in metastatic breast cancer.
Results from two phase II studies in metastatic breast cancer have shown that the novel, tumour-selective fluoropyrimidine capecitabine provides an effective and well tolerated therapy in patients with metastatic breast cancer failing or resistant to anthracycline and taxane therapy. Response rates of between 20 and 25% have been observed, with median survival of 12.2-12.6 months. In addition, there was an acceptable incidence of adverse events including diarrhoea and hand-foot syndrome, which can be controlled with a dose reduction. Promising results from two further randomised, phase II studies have indicated that capecitabine may also play a role in first- and second-line treatment of metastatic breast cancer. Capecitabine compared favourably with paclitaxel in anthracycline-resistant patients and with intravenous (i.v.) CMF (cyclophosphamide/methotrexate/5-fluorouracil (5-FU)) in post-menopausal women who had received no prior chemotherapy for metastatic disease, with high efficacy and good tolerability. The results of these four phase II studies demonstrate that capecitabine is active and well tolerated in a range of settings for metastatic breast cancer.


Generating robust human valvular interstitial cell cultures: Protocol and considerations.
Research in heart valve biology is a growing field that has yet to elucidate the fundamentals of valve disease. Human valvular interstitial cells (hVICs) are the best option for studying the cellular mechanisms behind valvular pathologies. However, there is a wide range of isolation procedures for these cells published in the literature. To what extent various isolation methods, patient pathologies, and seeding densities influence the behaviour of hVICs remains unclear. Here, we present an optimised method of hVIC isolation from diseased human valves donated at the time of surgery. We show that two rounds of 1000 U/mL collagenase digestion for not >2 h results in a phenotypically stable cell culture with a near complete absence of endothelial cell contamination. We also suggest that cells should be seeded at 10,000 cells/cm2 for experimentation. We found that patient pathology does not affect the success of the isolation procedure, and that instead, successful cultures are predicted by ensuring >500 mg valve tissue as starting material.


Efficacy of Intra-aortic Balloon Pump before versus after Primary Percutaneous Coronary Intervention in Patients with Cardiogenic Shock from ST-elevation Myocardial Infarction.
Previous studies showed that patients with cardiogenic shock (CS) from ST-elevation acute myocardial infarction (STEMI) supported by intra-aortic balloon pump (IABP) before primary percutaneous coronary intervention (PCI) decreased the risk of in-hospital mortality than patients who received IABP after PCI. However, little evidence is available on the optimal order of IABP insertion and primary PCI. The aim of this study was to investigate the impact of the sequence of IABP support and PCI and its association with major adverse cardiac and cerebrovascular events (MACCEs). Data were obtained from 218 consecutive patients with CS due to STEMI in Beijing Anzhen Hospital between 2008 and 2014, who were treated with IABP and PCI. The patients were divided into two groups: Group A in whom IABP received before PCI (n = 106) and Group B in whom IABP received after PCI (n = 112). We evaluated the myocardial perfusion using myocardial blush grade and resolution of ST-segment elevation. The primary endpoint was 12-month risk of MACCE. Most baseline characteristics were similar in patients between the two groups. However, patients received IABP before PCI were associated with a delay of door-to-balloon time (DBT) and higher troponin I level (P < 0.05). However, myocardial perfusion was significantly improved in patients treated with IABP before PCI (P < 0.05). Overall, IABP support before PCI was not associated with significantly lower risk of MACCE (P > 0.05). In addition, risk of all-cause mortality, bleeding, and acute kidney injury (AKI) was similar between two groups (P > 0.05). Multivariate analysis showed that DBT (odds ratio [OR] 2.5, 95% confidence interval [CI] 1.1-4.8, P = 0.04), IABP support after PCI (OR 5.7, 95% CI 2.7-8.4, P = 0.01), and AKI (OR 7.4, 95% CI 4.9-10.8, P = 0.01) were the independent predictors of mortality at 12-month follow-up. Early IABP insertion before primary PCI is associated with improved myocardial perfusion although DBT increases. IABP support before PCI does not confer a 12-month clinical benefit when used for STEMI with CS.


Different risk factors and prognosis for early and late intrahepatic recurrence after resection of hepatocellular carcinoma.
Recent studies have shown that the prognosis of recurrent hepatocellular carcinoma (HCC) after resection was dependent on the time of recurrence. The current study investigated whether early and late intrahepatic recurrences were associated with different risk factors and prognostic factors. After curative resection of HCC, 246 patients were followed prospectively for recurrence. Intrahepatic recurrences were classified into early (</= 1 year) and late (> 1 year) recurrences. Risk factors for recurrence and prognostic factors for survival after recurrence in each group were analyzed. Early and late intrahepatic recurrences developed in 80 patients and 46 patients, respectively. By multivariate analysis, preoperative tumor rupture (P = 0.022) and venous invasion (P < 0.001) were independent risk factors for early recurrence, whereas cirrhosis (P = 0.018) was the only significant risk factor for late recurrence. By comparing histologic features of resected recurrent and primary tumors, 8 of 9 resected early recurrent tumors (89%) were classified as intrahepatic metastases, whereas all 6 resected late recurrent tumors (100%) were multicentric occurrences. Despite similar treatments, the prognosis for patients with early recurrence was worse than that of patients with late recurrence (median survival of 15.8 months vs. 29.6 months; P = 0.005). Independent prognostic factors for early recurrence were serum albumin level and initial tumor pTNM classification, whereas only serum bilirubin level was found to be an independent prognostic factor for late recurrence. Early and late intrahepatic recurrences after resection of HCC were associated with different risk factors and prognostic factors. Early recurrences appear to arise mainly from intrahepatic metastases, whereas late recurrences are more likely to be multicentric in origin. The current study suggests that different strategies may be needed for the prevention and management of early and late recurrences. Further studies based on genetic analysis of clonal origins of tumors are required to clarify fully the mechanism of early and late recurrences after resection of HCC.


Correction: Non-consensual condom removal, reported by patients at a sexual health clinic in Melbourne, Australia.
[This corrects the article DOI: 10.1371/journal.pone.0209779.].


Small Molecule Regulation of Stem Cells that Generate Bone, Chondrocyte, and Cardiac Cells.
Embryonic stem cells (ESCs) are stem cells (SCs) that can self-renew and differentiate into a myriad of cell types. The process of developing stemness is determined by signaling molecules that drive stem cells to a specific lineage. For example, ESCs can differentiate into mature cells (e.g., cardiomyocytes) and mature cardiomyocytes can be characterized for cell beating, action potential, and ion channel function. A goal of this Perspective is to show how small molecules can be used to differentiate ESCs into cardiomyocytes and how this can reveal novel aspects of SC biology. This approach can also lead to the discovery of new molecules of use in cardiovascular disease. Human induced pluripotent stem cells (hiPSCs) afford the ability to produce unlimited numbers of normal human cells. The creation of patient-specific hiPSCs provides an opportunity to study cell models of human disease. The second goal is to show that small molecules can stimulate hiPSC commitment to cardiomyocytes. How iPSCs can be used in an approach to discover new molecules of use in cardiovascular disease will also be shown in this study. Adult SCs, including mesenchymal stem cells (MSCs), can likewise participate in self-renewal and multilineage differentiation. MSCs are capable of differentiating into osteoblasts, adipocytes or chondrocytes. A third goal of this Perspective is to describe differentiation of MSCs into chondrogenic and osteogenic lineages. Small molecules can stimulate MSCs to specific cell fate both in vitro and in vivo. In this Perspective, some recent examples of applying small molecules for osteogenic and chondrogenic cell fate determination are summarized. Underlying molecular mechanisms and signaling pathways involved are described. Small molecule-based modulation of stem cells shows insight into cell regulation and potential approaches to therapeutic strategies for MSC-related diseases.


Scavenger receptor of class B expressed by osteoblastic cells are implicated in the uptake of cholesteryl ester and estradiol from LDL and HDL3.
Lipoproteins transport many vitamins and hormones that have been shown to be necessary for bone formation. However, the metabolism of LDL and HDL3 by bone-forming osteoblastic cells remains unknown. Here we report that osteoblastic cells express scavenger receptors of class B that are implicated in the uptake of cholesterol and estradiol from LDL and HDL3. The bone tissue is continuously remodeled, and its integrity requires a balance between osteoclastic bone resorption and osteoblastic bone formation. Recent studies have reported the importance of triglyceride-rich lipoproteins for the delivery of lipophilic vitamins necessary for normal bone metabolism. However, the ability of osteoblastic cells to process low- and high-density lipoproteins (LDL and HDL3) and the receptors involved remain unknown. Binding, competition, degradation, and selective uptake assays with LDL and HDL3 radiolabeled in their protein and lipid moieties or with [3H]estradiol were conducted on human osteoblasts (MG-63 cell line and primary cultures of human osteoblasts [hOB cells]) and on mouse osteoblasts (MC3T3-E1 cell line and primary cultures of murine osteoblasts [mOB cells]). The expression of scavenger receptors (SRs) by osteoblastic cells was determined by RT-PCR and Western immunoblotting, and cellular localization was assessed by sucrose gradient fractionation. Osteoblastic cells were able to bind, internalize, and degrade HDL3 and LDL and are capable of selectively taking up cholesteryl esters (CEs) from these lipoproteins. Also, we provide evidence that osteoblastic cells express SR-BI, SR-BII, and CD36 (SR-Bs receptors) and that these receptors are localized in membrane lipid rafts or caveolin-rich membranes. The selective uptake of CE from LDL and HDL3 by osteoblastic cells was strongly inhibited by the known SR-B ligand oxidized LDL, indicating that SR-B receptors are responsible for the selective uptake. Finally, estradiol carried by LDL and HDL3 was selectively transferred to the osteoblastic cells also through SR-B receptors. Overall, our results suggest a novel mechanism for the routing of cholesterol and estradiol to osteoblasts involving the metabolism of LDL and HDL3 by SR-B receptors.


A prospective intervention study of stopping smoking in pregnancy in a routine antenatal care setting.
To evaluate the effect of specific education of midwives on stopping smoking in pregnant women and to determine the effect of this programme on pregnancy outcome. A prospective intervention study. Department of Gynaecology and Obstetrics, Aarhus University Hospital, Denmark. A group of midwives (9 out of 54) was taught the effects of smoking during pregnancy and instructed in various methods of educating women to stop smoking. All pregnant women who attended antenatal care from October 1994 to September 1995 were either in the intervention group (n = 527) or the control group (n = 2629). Pregnant women attending the specifically educated midwives were considered to be the intervention group. They were given individual advice about stopping smoking at the first antenatal visit at about 16 weeks of gestation and a leaflet on smoking and pregnancy. At the first antenatal visit at about 16 weeks of gestation, 22% of the pregnant women smoked. Between the first visit and the routine visit at 30 weeks of gestation 51 (2%) stopped smoking and 56 (2%) started smoking. No differences were found between the intervention group and the control group in the rate of stopping smoking, validated by cotinine measurements. Mean birthweight, mean gestational age and the proportion of preterm birth in the two groups were similar. Education of midwives and integration of advice about smoking cessation at a low cost in routine antenatal care failed to affect smoking habits among pregnant women.


Endocannabinoid regulation of amyloid-induced neuroinflammation.
The modulation of endocannabinoid (EC) levels and the activation of cannabinoid receptors are seen as promising therapeutic strategies in a variety of diseases, including Alzheimer's disease (AD). We aimed to evaluate the effect of the pharmacologic and genetic inhibition of anandamide-degrading enzyme in a mouse model of AD (5xFAD). Pharmacologic inhibition of the fatty acid amide hydrolase (FAAH) had little impact on the expression of key enzymes and cytokines and also on the cognitive impairment, plaque deposition, and gliosis in 5xFAD mice. CB1 blockade exacerbated inflammation in this transgenic mouse model of AD. The genetic inactivation of FAAH led to increases in the expression of inflammatory cytokines. At the same time, FAAH-null 5xFAD mice exhibited a behavioral improvement in spatial memory that was independent of the level of anxiety and was not CB1 mediated. Finally, mice lacking FAAH showed diminished soluble amyloid levels, neuritic plaques, and gliosis. These data reinforce the notion of a role for the EC system in neuroinflammation and open new perspectives on the relevance of modulating EC levels in the inflamed brain.


Is carnosinase 1 gene (CNDP1) polymorphism associated with chronic kidney disease progression in children and young adults? results of a family-based study.
The aim of the study was to investigate the role of the D18S880 microsatellite polymorphism of carnosinase 1 gene (CNDP1), which encodes serum carnosinase, in the development and progression of chronic kidney disease (CKD) of nondiabetic etiology. We applied two different approaches. First, a family-based study was carried out comprising 109 patients with CKD caused by chronic glomerulonephritis (GN) or tubulointerstitial nephritis (IN) and their 218 healthy parents using the transmission/disequilibrium test. CNDP1 polymorphism and serum carnosinase activity were determined in all subjects. Serum carnosinase activity was also measured in 20 healthy controls. Second, we performed a case-control study to determine whether polymorphism in CNDP1 gene and other factors influence the progression of renal impairment. Preferential transmission of the 5 allele of CNDP1 polymorphism from heterozygous parents to their offspring with CKD caused by GN was found. There was no association between that polymorphism and the loss of glomerular filtration rate. Serum carnosinase activity was significantly higher in CKD patients than in controls. This study found no association between the CNDP1 polymorphism and increased risk for development of CKD caused by IN. However, the polymorphism can influence CKD caused by GN. The progression rate of CKD does not depend on this polymorphism. The increased serum carnosinase activity in the CKD patients may suggest its role in the pathomechanism of the disease.


[Development and Effects of Social Learning Theory Based Eye-Health Program for Preschoolers].
The purpose of this study was to develop an eye-health program based on social learning theory (EPST) of preschoolers and evaluate its effectiveness. A nonequivalent control group pre-post test design was utilized and 141 six-year-old preschoolers and their parents participated (experimental group=69, control group=72) in the study. The EPST in this study included eye-health education and eye exercises. Attention, memory, replay, motivation, reinforcement, and self-efficacy were used as interventional strategies. To examine the effectiveness of EPST, proficiency in eye-health activities, refractive power, and visual acuity were measured before and after the intervention. Data were analyzed with SPSS WIN 21.0 using the Shapiro-Wilk test, χ²-test, Mann-Whitney U test and Wilcoxon signed rank test. Following the intervention, eye-health activities, refractive power, and visual acuity significantly improved in the experimental group compared to the control group. The results of this study suggest that EPST is effective in improving eye-health activities, refractive power, and visual acuity in preschoolers, and its wider implementation in educational institutions will promise improved eye-health among preschoolers.


Correlation between delayed-enhancement magnetic resonance and nitrate myocardial Tc-99m tetrofosmin scintigraphy in myocardial infarction: a case report.
Delayed-enhancement magnetic resonance imaging (DE-MRI) has been recently proposed as an alternative tool in identifying myocardial viability and transmural distribution of necrosis in the myocardium. We describe a case of a 71-year-old man admitted for ischemic-like chest pain in which DE-MRI and post-nitrate 99mTc-tetrofosmin myocardial scintigraphy equally contributed to the diagnosis of previous lateral myocardial infarction. In this patient with coronary artery disease, the absence of uptake of tracer at myocardial scintigraphy appeared to be closely correlated to DE-MRI data. Cardiologists can use SPECT or DE-MRI to obtain similar information about myocardial viability.


Brainstem involvement with mycosis fungoides: an unusual central nervous system complication.
Changes in the brainstem were demonstrated with MR imaging in a patient with mycosis fungoides. Previous reports of CNS involvement in this rare disease have not had similar findings.


The Incidence and gastrointestinal infectious risk of functional gastrointestinal disorders in a healthy US adult population.
Functional gastrointestinal disorders (FGDs) are recognized sequelae of infectious gastroenteritis (IGE). Within the active duty military population, a group with known high IGE rates, the population-based incidence, risk factors, and attributable burden of care referable to FGD after IGE are poorly defined. Using electronic medical encounter data (1999-2007) on active duty US military, a matched, case-control study describing the epidemiology and risk determinants of FGD (irritable bowel syndrome (IBS), functional constipation (FC), functional diarrhea (FD), dyspepsia (D)) was conducted. Incidence rates and duration of FGD-related medical care were estimated, and conditional logistic regression was utilized to evaluate FGD risk after IGE. A total of 31,866 cases of FGD identified were distributed as follows: FC 55% (n=17,538), D 21.2% (n=6,750), FD 2.1% (n=674), IBS 28.5% (n=9,091). Previous IGE episodes were distributed as follows: specific bacterial pathogen (n=65, 1.2%), bacterial, with no pathogen specified (n=2155, 38.9%), protozoal (n=38, 0.7%), viral (n=3431, 61.9%). A significant association between IGE and all FGD (odds ratio (OR) 2.64; P<0.001) was seen, with highest risk for FD (OR 6.28, P<0.001) and IBS (OR 3.72, P<0.001), and moderate risk for FC (2.15, P<0.001) and D (OR 2.39, P<0.001). Risk generally increased with temporal proximity to, and bacterial etiology of, exposure. Duration of FGD-related care was prolonged with 22.7% having FGD-associated medical encounters 5 years after diagnosis. FGD are common in this population at high risk for IGE. When considering effective countermeasures and mitigation strategies, attention directed toward prevention as well as the acute and chronic sequelae of these infections is needed.


Natural and antibody-dependent killer cells in the thymus.
Thymocytes contain a small population of light (o = 1.067), large cells with high cytolytic potential against natural killer target as well as against IgG- or IgM-coated erythrocytes and nucleated cells, thus displaying natural killer and antibody-dependent cellular cytotoxicity functions, but not exhibiting T killer cell capacity. As far as characterized, the cells show T cell characteristics: they are nonadherent, nonphagocytic, surface immunoglobulin-negative, C3 receptor-negative, partly Fc gamma receptor-positive, carry the receptor for Helix pomatia A agglutinin, and are, at least partly, cortisone-resistant and Thy-1-positive. The implications of this finding with respect to the lineage of natural killer and killer cells and their interdependence will be discussed briefly.


Evaluation of Endovascular Therapy Combined with Bowel Resection Treatment on Patients with Acute Mesenteric Venous Thrombosis.
This retrospective study aims to investigate the effects of the endovascular and surgical strategy for treating patients with acute mesenteric venous thrombosis (AMVT). We retrospectively studied 68 patients with AMVT who underwent treatment in Jinling Hospital during the period from January 2009 to December 2014. The mean age was 45 ± 12 years (range 20-72 years). All patients were treated by using the combined treatment that included endovascular treatment, damage control surgery, surgical intensive care, and intestinal rehabilitation treatment. Clinical outcomes and complications were compared during the follow-up period. All the 68 cases received anticoagulant treatment. However, only 24 received the endovascular intervention, 19 received surgical resection, and 25 patients received endovascular treatment combined with bowel resection. The overall mortality rate was 2.94% (2 cases). Bowel resection range significantly decreased (92 ± 14 cm vs. 162 ± 27 cm, t = -2.377, P = 0.022) in the combination therapy group, when compared with the surgery group. During the 1-year follow-up period, 4 cases suffered from short bowel syndrome. Our study indicates that AMVT can be successfully treated with the early improvement of intestinal blood circulation. Further, our applied combined approach showed a favorable outcome in mesenteric thrombosis patients and reduced the mortality rate by improving the prognosis significantly.


Study on pulmonary, prostatic and renal (medulla and cortex) distribution of sagamicin at different time intervals.
In order to assess the therapeutic activity of an antibiotic, not only its serum kinetics but also its kinetics in the peripheral tissues must be determined, thus evaluating the specific power of penetration of the drug. Sagamicin is an aminoglycosidic basic antibiotic closely related to gentamicin and its penetration rate into lungs, kidney and prostate, together with its serum concentrations time-course, were investigated. The findings obtained showed that this antibiotic attained a good distribution in the peripheral tissues, where it easily reached therapeutic levels.


A Risk Prediction Model for Post-endoscopic Retrograde Cholangiopancreatography Pancreatitis After Stent Insertion for Malignant Biliary Obstruction: Development and Validation.
Pancreatitis is the most common complication of post-endoscopic retrograde cholangiopancreatography (ERCP). There are currently no prediction models, particularly for post-ERCP pancreatitis (PEP) after biliary stent placement due to malignant biliary obstruction (MBO). To that end, we aim to develop and validate a predictive model for PEP. We retrospectively analyzed the data of patients who underwent ERCP for biliary stent placement due to MBO at the Second Affiliated Hospital of Harbin Medical University from January 1, 2014 to August 31, 2021. The eligible patients were randomly allocated to the development and validation cohorts. A prediction model was built using the development cohort, and the model's effect was validated using a validation cohort. A total of 1524 patients were enrolled, including 1016 in the development cohort and 508 in the validation cohort, with an overall PEP rate of 7.1%. The model's predictors included acute pancreatitis history, the absence of pancreatic duct dilation, nonpancreatic cancer, difficult cannulation, and pancreatic injection. The area under the curve (AUC) in the development cohort was 0.810, and the incidence of PEP in the low-risk, medium-risk, and high-risk groups was 1.53%, 9.12%, and 36.36%, respectively. Meanwhile, the AUC of the validation cohort was 0.781, and the incidence of PEP in the low-risk, medium-risk, and high-risk groups was 4.17%, 8.75%, and 41.67%, respectively. This study was the first to build and validate a risk prediction model, especially for PEP after biliary stent placement due to MBO. Moreover, this model might assist clinicians in identifying high-risk patients and help implement preventive measures in a more timely manner.


Evaluation of photocatalytic activities of supported catalysts on NaX zeolite or activated charcoal.
This study aimed to evaluate the photocatalytic activity of ZnO and Nb2O5 catalysts, both supported on NaX zeolite and activated charcoal (AC). The synergistic effect between oxide and support and the influence of solution pH (3, 7 and 9) on photocatalytic degradation of reactive blue 5G (C.I. 222) were analyzed. The catalysts Nb2O5/NaX, Nb2O5/AC and ZnO/NaX, ZnO/AC with 5 and 10% (wt%) were prepared by wet impregnation. The results showed that the catalysts exhibit quite different structural and textural properties. The synergic effect between ZnO and NaX support was higher than that with the activated charcoal, showing that these catalysts were more efficient. The most photoactive catalyst was 10% ZnO/NaX which showed 100% discoloration of the dye solution at pH 3, 7 and 9 after 0.5, 5 and 2h of irradiation, respectively. The hydrolytic nature of zeolite favored the formation of surface hydroxyl radicals, which increased the activity of the photocatalyst. Thus, catalysts supported on NaX zeolite are promising for use in photocatalysis.


Coexisting ions and long-chain per- and polyfluoroalkyl substances (PFAS) inhibit the adsorption of short-chain PFAS by granular activated carbon.
We assessed the competitive adsorption between long-chain and short-chain PFAS and the impact of coexisting ions to understand the mechanisms leading to the early breakthrough of short-chain PFAS from granular activated carbon (GAC) filters. Three pairs of short-chain and long-chain PFAS representing different functional groups were studied using GAC (Filtrasorb 400) in batch systems. In bisolute systems, the presence of long-chain PFAS decreased the adsorption of short-chain PFAS by 30-50% compared to their single solute adsorption capacity (0.22-0.31 mmol/g). In contrast to the partial decrease observed in bisolute systems, the addition of long-chain PFAS to GAC pre-equilibrated with short-chain PFAS completely desorbed all short-chain PFAS from GAC. This suggested that the outermost adsorption sites on GAC were preferentially occupied by short-chain PFAS in the absence of competition but were prone to displacement by long-chain PFAS. The presence of inorganic/organic ions inhibited the adsorption of short-chain PFAS (up to 60%) but had little to no impact on long-chain PFAS, with the inhibitory trend inversely correlated with Kow values. Study results indicated that the displacement of short-chain PFAS by long-chain PFAS and charge neutralization are important mechanisms contributing to the early breakthrough of short-chain PFAS from GAC systems.


Decadal shifts of East Asian summer monsoon in a climate model free of explicit GHGs and aerosols.
The East Asian summer monsoon (EASM) experienced decadal transitions over the past few decades, and the associated "wetter-South-drier-North" shifts in rainfall patterns in China significantly affected the social and economic development in China. Two viewpoints stand out to explain these decadal shifts, regarding the shifts either a result of internal variability of climate system or that of external forcings (e.g. greenhouse gases (GHGs) and anthropogenic aerosols). However, most climate models, for example, the Atmospheric Model Intercomparison Project (AMIP)-type simulations and the Coupled Model Intercomparison Project (CMIP)-type simulations, fail to simulate the variation patterns, leaving the mechanisms responsible for these shifts still open to dispute. In this study, we conducted a successful simulation of these decadal transitions in a coupled model where we applied ocean data assimilation in the model free of explicit aerosols and GHGs forcing. The associated decadal shifts of the three-dimensional spatial structure in the 1990s, including the eastward retreat, the northward shift of the western Pacific subtropical high (WPSH), and the south-cool-north-warm pattern of the upper-level tropospheric temperature, were all well captured. Our simulation supports the argument that the variations of the oceanic fields are the dominant factor responsible for the EASM decadal transitions.


Pre-sliding of femoral neck system improves fixation stability in pauwels type III femoral neck fracture: a finite element analysis.
Femoral neck fractures are a common injury in older adults and their management presents a significant challenge for orthopedic surgeons. The Femoral Neck System (FNS) was recently introduced for the fixation of femur neck fractures. Although neck shortening was reduced with the FNS, the complication rates were not reduced. Thus, improvements to enhance fixation stability should be made for the FNS. We hypothesized that (1) the pre-sliding technique and (2) the use of longer anti-rotation screw would increase fracture stability. This study aimed to determine the change in fracture stability using the pre-sliding technique and long anti-rotation screw in the FNS for fixation of Pauwels type III femoral neck fractures. Finite element models of Pauwels type III femoral neck fracture fixed with pre-sliding FNS and 5-mm longer anti-rotation screw were established. The models were subjected to normal walking load. The material properties of the elements belonging to the bone were mapped by assigning the formulation with the computed tomography Hounsfield unit. Pauwels type III femoral neck fractures fixed with pre-slided FNS showed better fracture stability, decreasing fracture gap and sliding by 14% and 12%, respectively, under normal walking load. No element of cortical bone in any of the models had an absolute value of principal strain that exceeded 1%. The peak von Mises stress (VMS) of the implants ranged from 260 to 289 MPa, and the highest peak VMS value was 50% lower than the yield strength of the titanium alloy (800 MPa). The longer anti-rotation screw did not affect fracture stability. The pre-sliding technique using the FNS showed higher fracture stability than the standard fixation technique for a Pauwels type III femoral neck fracture. The longer anti-rotation screw did not contribute significantly to fixation stability. As this finite element analysis considered the inhomogeneous mechanical property of the bone, it offered equivalent mechanical conditions to investigate the components of interest.


A WRKY transcription factor confers aluminum tolerance via regulation of cell wall modifying genes.
Modification of cell wall properties has been considered as one of the determinants that confer aluminum (Al) tolerance in plants, while how cell wall modifying processes are regulated remains elusive. Here, we present a WRKY transcription factor WRKY47 involved in Al tolerance and root growth. Lack of WRKY47 significantly reduces, while overexpression of it increases Al tolerance. We show that lack of WRKY47 substantially affects subcellular Al distribution in the root, with Al content decreased in apoplast and increased in symplast, which is attributed to the reduced cell wall Al-binding capacity conferred by the decreased content of hemicellulose I in the wrky47-1 mutant. Based on microarray, real time-quantitative polymerase chain reaction and chromatin immunoprecipitation assays, we further show that WRKY47 directly regulates the expression of EXTENSIN-LIKE PROTEIN (ELP) and XYLOGLUCAN ENDOTRANSGLUCOSYLASE-HYDROLASES17 (XTH17) responsible for cell wall modification. Increasing the expression of ELP and XTH17 rescued Al tolerance as well as root growth in wrky47-1 mutant. In summary, our results demonstrate that WRKY47 is required for root growth under both normal and Al stress conditions via direct regulation of cell wall modification genes, and that the balance of Al distribution between root apoplast and symplast conferred by WRKY47 is important for Al tolerance.


Flexibility on the karyotype evolution in bitterlings (Pisces, Cyprinidae).
In bitterlings (Acheilognathinae) C- and Ag-banding karyotypes of 6 species-subspecies collected in China and South Korea were analyzed. The chromosomal constitution of 2n =46 (4 SM + 42 ST) in Rhodeus atremius fangi was quite different from that of 2n = 48 (8 M + 20 SM + 20 ST) in other species-subspecies in Rhodeus. It was concluded from the analysis of banded chromosomes that the increase in number of ST during the karyotype change from 2n = 48 to 2n = 46 was achieved by a series of pericentric inversions from 24 M-SM to 24 ST, and the decrease in the diploid number was caused by an additional tandem fusion of 4 ST chromosomes, forming a new ST pair in the 2n = 46 karyotype. The karyotype of Tanakia koreensis, T. signifer, and Acheilognathus macropterus is 2n = 48 (8 M + 20 SM + 20 ST), 2n = 48 (8 M + 20 SM + 14-16 ST + 4-6 A), 2n = 44 (14M + 16 SM + 14 ST), respectively. In R. ocellatus ocellatus, T. koreensis, T. signifer and A. macropterus, karyotype changes from 2n = 48 to 2n = 44 due to centric fusion and inversion have also been estimated. It was suggested that C-banding heterochromatin was greatly concerned with the karyotype evolution in bitterlings.


Poisoning in children.
Drug-induced poisoning of children represents a serious medical as well as a social problem linked both to the fields of prevention and therapy. This paper analyses the occurrence and the causative agents of poisoning cases of children under the age of 15, hospitalized in a children's hospital over a two-year period (1985-1986). 33 Poisoning cases represented 1.7% of all hospitalizations, and 49% thereof were induced by drugs.


Proteomic and lipidomic analyses of paraoxonase defined high density lipoprotein particles: Association of paraoxonase with the anti-coagulant, protein S.
Characterizing high density lipoprotein (HDL) particles and their relevance to HDL function is a major research objective. One aim is to identify functionally distinct particles. To try to limit both functional and compositional heterogeneity the present study focused on paraoxonase-1 (PON1) as a target for isolation of a minor HDL subfraction. Immunoaffinity techniques were applied to isolate PON1-containing HDL (P-HDL) and total HDL (T-HDL), which were subsequently characterized and compared. Analyses of the lipidomes showed significant differences between the fractions in the relative concentrations of individual lipid subspecies, notably reduced levels of unsaturated lysophosphatidylcholine (p < 0.05) in P-HDL (reflected in a significantly reduced total lysophosphatidylcholine polyunsaturated fatty acid content, p < 0.004). Significant differences were also observed for the proteomes. P-HDL was highly enriched in the anti-coagulant, vitamin K activated protein S (prot S) (p < 0.0001), and alpha2 macroglobulin (p < 0.01), compared to T-HDL. Conversely, procoagulant proteins kininogen 1 and histidine-rich glycoprotein were largely excluded from P-HDL. Immunoabsorption of PON1 from plasma significantly reduced prot S anti-coagulant activity. The P-HDL lipidome and proteome showed significant differences from T-HDL. Enrichment in anti-coagulation proteins indicates complementary functionalities within P-HDL particles and underlines their anti-atherosclerotic potential.


Bone marrow-derived mononuclear cells ameliorate neurological function in chronic cerebral infarction model mice via improvement of cerebral blood flow.
Stroke is a frequently observed neurological disorder that might lead to permanent and severe disability. Recently, various regenerative therapies have been developed, some of which have already been applied clinically. However, their outcomes have not been fully satisfactory. In particular, the development of regenerative therapies for chronic ischemic stroke is greatly needed. Herein intracerebral administration of bone marrow-derived mononuclear cells (BM-MNCs) was assessed as a potential treatment for chronic ischemic stroke using a severe combined immunodeficiency mouse model characterized by minimal vascular variation unrelated to immunodeficiency. A reproducible model of permanent middle cerebral artery occlusion was prepared, and intracerebral BM-MNC transplantation was performed 14 days after stroke induction in the infarcted brain. Sensorimotor behavioral function and cerebral blood flow were significantly improved upon treatment with BM-MNCs compared to control medium injection. The transplanted cells exhibited characteristics of the vascular endothelium and microglia/macrophages. Significant angiogenesis and suppression of astrogliosis and microgliosis were observed in the affected brain. Messenger RNA expression analysis showed significant increases in anti-inflammatory cytokines, A2 astrocyte/anti-inflammatory microglia markers and vascular endothelial markers such as vascular endothelial growth factor and significant decreases in pro-inflammatory cytokines and A1 astrocyte/pro-inflammatory microglia markers following BM-MNC transplantation. These results suggest that intracerebral administration of BM-MNCs should be considered an effective cell therapy for chronic stroke.


Establishing Animal Welfare Rules of Conduct for the Portuguese Veterinary Profession-Results from a Policy Delphi with Vignettes.
Promoting animal welfare is one of the basic tenets of the veterinary profession and, in doing so, veterinarians are expected to abide to the highest legal and professional standards. However, the Portuguese veterinary code of conduct, established in 1994, largely overlooks animal welfare and fails to address issues such as the euthanasia or humane killing of animals. As part of a wider research aiming to revise the Portuguese veterinary code of conduct, a Policy Delphi study was conducted in late 2018, using a pre-validated three-round structure and vignette methodology, to explore the range of opinions and the level of agreement on end-of-life dilemmas and animal welfare rules of conduct of a purposeful sample of forty-one (out of seventy) Portuguese veterinarians. When faced with ethical vignettes involving end-of-life dilemmas, veterinarians were shown to privilege personal moral agency over legal obligations in order to defend the interests of stakeholders, namely of the animals. Most participants agreed that the suggested animal welfare rules of conduct reflected their own views on the subject (88%), in addition to representing a significant improvement in terms of regulatory standards (93%). We expect that this study will support regulation and policy-making by the Portuguese Veterinary Order and by veterinary representative bodies elsewhere.


Epidemiological aspects of equine babesioses in a herd of horses in Brazil.
Epidemiological studies of Babesia equi and B. caballi were undertaken in a herd of 120 pastured horses in Rio de Janeiro, Brazil. The area where the horses were held was shown to be highly endemic for both Babesia spp., i.e. the prevalence of B. equi antibodies in horses aged 6 months or older ranged from 90.6% to 100% as determined by the immunofluorescence antibody (IFA) test, and the prevalence of B. caballi antibodies as determined by Western blot ranged from 59.4% to 65.5%. From the herd, 20 foals and their dams were selected to estimate the degree of tick infestation and the foals were bled at monthly intervals to determine the incidence of antibodies to B. equi and B. caballi. The incidence of B. equi was 100% by about 127 days of age as determined by IFA of B. caballi was 100% by about 150 days of age as determined by Western blot. Tick infestation of the horses estimated by using a semiquantitative key ranged from at least five ticks on every horse to more than 100 ticks on many horses throughout the year. Except for three Boophilus microplus female ticks, they were identified as Amblyomma cajennense and Anocentor nitens. A. cajennense had one generation per year, whereas An. nitens had three. Kinetes of B. caballi were detected in the haemolymph of two of 68 An. nitens female ticks and in the ovary and eggs of one of these, suggesting that this tick is a significant vector of B. caballi.(ABSTRACT TRUNCATED AT 250 WORDS)


Project Impact: a pharmacotherapy pilot trial investigating the abstinence and treatment adherence of Latino light smokers.
Light smoking is particularly prevalent among Latino smokers. Nicotine replacement (NRT) and varenicline are effective medications for smoking cessation for moderate-heavy smokers but have not been tested in light smokers, and thus, there are no treatment guidelines for use with light smokers. This pilot trial tested the efficacy of NRT and varenicline in increasing smoking abstinence among Latino light smokers. A 3-group (NRT, varenicline, and varenicline-placebo) randomized design was used, and Latino light smokers (≤10 cigarettes per day) received 12 weeks of treatment, which included a culturally informed behavioral health session and ongoing medication management visits. At follow-up, there were no abstinent participants in the placebo and NRT groups. However, 30% of participants in the varenicline group were abstinent at the 3-, 4-, and 6-month follow-up. This study represents the only investigation that specifically targets Latino light smokers using these treatments and characterizing their treatment adherence.


Elevated inflammatory mediators and pulmonary hypertension after applying an extracorporeal circuit in a neonatal sepsis model.
We aimed to study the changes in cytokines, oxidative mediators, and pulmonary blood pressure in a neonatal sepsis model when applying an extracorporeal circuit (ECC). Of 28 anesthetized and mechanically ventilated 3-day-old piglets, 14 underwent cecal ligation and perforation (CLP), of which 7 underwent ECC for 3 h from 3 to 6 h after CLP. The remaining 14 were sham, of which 7 underwent ECC. Serum interleukin (IL)-6, IL-10, tumor necrosis factor (TNF), interferon gamma (IFN-γ), total hydroperoxide (TH), nitric oxide metabolites (NOx), and mean pulmonary arterial blood pressure (mPAP)/mean arterial blood pressure (mABP) ratio were measured at pre-CLP and at 3, 6, and 9 h in the CLP groups, and continued in the sham groups at 12, 15, 18, and 24 h. The CLP group with ECCs compared to the CLP group without it showed higher levels of serum IL-6, IL-10, and NOx at 6 h and higher levels of serum TH at 6 and 9 h. The sham group with ECCs compared to the one without it showed higher levels of serum IL-6 and IL-10 at 12, 15, and 18 h, TH at 6 and 9 h, TNF at 6 h, and IFN-γ at 9 h. The mPAP/mABP ratios in the CLP group with ECCs were higher compared to the CLP group without it at 6 and 9 h. Applying ECCs provoked a window of cytokines, free radicals elevation, and pulmonary hypertension which could be hazardous in critically ill newborns.


Curcumin-loaded Butea monosperma gum-based hydrogel: A new excipient for controlled drug delivery and anti-bacterial applications.
The wide spectrum of applications provided by curcumin has attracted researchers worldwide to identify its molecular targets and employ it in various biomedical applications. The present research work focuses on the development of a Butea monosperma gum-based hydrogel encapsulated with curcumin and further employing it for two diverse applications, i.e., drug delivery and anti-bacterial application. A central composite design was utilized for the optimization of significant process variables to achieve maximum swelling. A maximum of 662 % swelling was attained at initiator (0.06 g), monomer (3 ml), crosslinker (0.08 g), solvent (14 ml), and time (60 s). Furthermore, the characterization of the synthesized hydrogel was performed via FTIR, SEM, TGA, H1-NMR, and XRD analysis. Various important properties like swelling rate under different solutions, water retention capacity, re-swelling capability, porosity, and density measurement suggested that the prepared hydrogel exhibited a highly stable crosslinked network with high porosity (0.23) and density (62.5 g/cm3) values. The encapsulation efficiency of curcumin in the hydrogel was reported to be 93 % and 87.3 %, respectively, wherein BM-g-poly(AA) ∼ Cur exhibited excellent sustained pH-responsive site release of curcumin at two different pH values, with the maximum amount of release taking place at pH 7.4 (792 ppm) and a minimum at pH 5 (550 ppm) due to the lesser ionization of the functional groups present in the hydrogel at a lower pH value. Additionally, the results from the pH shock studies indicated our material to be stable and efficient even with fluctuations in pH, resulting in the optimal amount of drug release at each pH range. Furthermore, anti-bacterial studies revealed that the synthesized BM-g-poly(AA) ∼ Cur was effective against both gram-negative and gram-positive bacteria, with maximum values of zones of inhibition of 16 mm in diameter, thereby showing the best results in comparison to the already developed matrices till date. As a result, the newly discovered BM-g-poly(AA) ∼ Cur properties reflect the hydrogel network's suitability for drug release and anti-bacterial applications.


Cisplatin differently affects amino terminal and carboxyl terminal domains of HSP90.
The 90-kDa heat shock protein (HSP90) is a molecular chaperone that assists in the folding and assembly of proteins in the cytosol. We previously demonstrated that the antineoplastic reagent, cisplatin, inhibits the aggregation prevention activity of mammalian HSP90. We now show that cisplatin binds both the amino terminal and carboxyl terminal domains of the human HSP90 and differently affects these two domains. Cisplatin blocks the aggregation prevention activity of HSP90C, but not HSP90N. In contrast, cisplatin induces a conformational change in HSP90N, but not HSP90C. These results indicate that cisplatin modulates the HSP90 activities through two different mechanisms using the two distinct binding sites of the HSP90 molecule.


The effects of smoke-free legislation on acute myocardial infarction: a systematic review and meta-analysis.
Comprehensive smoke-free legislation has been implemented in many countries. The current study quantitatively examined the reduction in risk of acute myocardial infarction (MI) occurrence following the legislations and the relationship with the corresponding smoking prevalence decrease. PubMed, EMBASE, and Google Scholar databases and bibliographies of relevant studies and reviews were searched for potential original studies published from January 1, 2004, through October 31, 2011. Meta-analysis was performed using a random effect model to estimate the overall effects of the smoking-free legislations. Meta-regression was used to investigate possible causes of heterogeneity in risk estimates. A total of 18 eligible studies with 44 estimates of effect size were used in this study. Meta-analysis produced a pooled estimate of the relative risk of 0.87 (95% confidence interval (CI): 0.84 to 0.91). There was significant heterogeneity in the risk estimates (overall I² = 96.03%, p<0.001). In meta-regression analysis, studies with greater smoking prevalence decrease produced larger relative risk (adjusted coefficient -0.027, 95% CI: -0.049 to -0.006, p=0.014). Smoke-free legislations in public and work places were associated with significant reduction in acute MI risk, which might be partly attributable to reduced smoking prevalence.


Major Internal Carotid Artery Injury During Endoscopic Skull Base Surgery: Case Report.
Major vascular structures are always at risk during complex skull base surgery, particularly with use of the endoscopic endonasal approach, and intraoperative damage of the internal carotid artery (ICA) can be a devastating complication. Herein, we report a case of a young patient who had a major injury of the left ICA during endoscopic resection of a recurrent petrous bone chordoma. Massive bleeding was controlled by a Foley balloon inserted and kept in the resection area. Urgent angiography revealed a persistent leak from the petrous segment of the left ICA, and the vessel was sacrificed with coiling, since a balloon occlusion test showed good collateral blood flow. The patient woke up from anesthesia without a neurological deficit. Salvage resection of recurrent skull base neoplasms deserves specific attention because of the possibility of major vascular damage. In cases of intraoperative ICA injury, its management requires immediate decisions, and the available possibilities for endovascular therapy should always be considered.


Reverse micellar extraction of beta-galactosidase from barley (Hordeum vulgare).
The reverse micellar system of sodium bis(2-ethylhexyl)sulfosuccinate (AOT)/isooctane was used for the extraction and primary purification of beta-galactosidase (EC 220.127.116.11) from the aqueous extract of barley (Hordeum vulgare) for the first time. The process parameters such as the concentration of the surfactant, the volume of the sample injected, and its protein concentration, pH, and ionic strength of the initial aqueous phase for forward extraction, buffer pH, and salt concentration for back extraction are varied to optimize the extraction efficiency. Studies carried out with both phase transfer and injection mode of reverse micellar extraction confirmed the injection mode to be more suitable for beta-galactosidase extraction. The extent of reverse micellar solubilization of proteins increased with an increase in protein concentration of the feed sample. However, back extraction efficiency remained almost constant (13-14.4%), which indicates the selectivity of AOT reverse micelles for a particular protein under given experimental conditions. beta-Galactosidase was extracted with an activity recovery of 98.74% and a degree of purification of 7.2-fold.


Molecular detection of Helicobacter pylori and its genotypic antimicrobial resistance patterns in dyspeptic Mozambican patients.
Helicobacter pylori strains show a high level of genotypic diversity and express several genes that contribute to their pathogenicity and resistance. In Mozambique, there is lack of information regarding its resistance pattern to antibiotics. In this study, we aimed to investigate the prevalence of H. pylori and its genotypic resistance to clarithromycin, metronidazole, and fluoroquinolones in Mozambican dyspeptic patients. Since appropriate eradication should be based on the local resistance rate, our data will guide clinicians in choosing the best drugs for the effective treatment of H. pylori-infected patients. This is a cross-sectional descriptive study conducted between June 2017 and June 2020, in which 171 dyspeptic patients were recruited, and through upper gastrointestinal endoscopy, gastric biopsies were collected from those patients. Polymerase chain reaction was performed for the detection of H. pylori and its resistance mechanisms to clarithromycin (23S rRNA), metronidazole (rdxA), and fluoroquinolones (gyrA); mutations conferring resistance to these antibiotics were investigated by sequencing 23S rRNA, rdxA, and gyrA genes. Of the 171 samples tested, H. pylori was detected in 56.1% (96/171). The clarithromycin resistance rate was 10.4% (the responsible mutations were A2142G and A2143G), the metronidazole resistance rate was 55.2% (4 types of mutations responsible for metronidazole resistance were identified which include, D59N, R90K, H97T, and A118T. However, in many cases, they appeared in combination, with D59N + R90K + A118T being the most frequent combination), and the fluoroquinolones resistance rate was 20% (the responsible mutations were N87I and D91G). H. pylori infection remains common in dyspeptic Mozambican patients. High resistance to metronidazole and fluoroquinolones requires continuous monitoring of antibiotic resistance and adaptation of therapy to eradicate this infection.


New approaches for small-cell lung cancer: local treatments.
Limited-disease small-cell lung cancer (LD-SCLC) can be cured with combinations of systemic chemotherapy and local treatments, predominantly radiation therapy. While systemic control inside the brain has been further improved with the inclusion of prophylactic cranial irradiation, long-term local control remains suboptimal, even with newer chemoradiation protocols. The authors review the current management of LD-SCLC and discuss strategies to improve local control. They present their own experience with the inclusion of surgery in an aggressive combined-modality protocol for patients with LD-SCLC. Different approaches to improve local efficacy of treatment have been explored, including concurrent chemoradiation, administration of radiation as early as possible, newer fractionation schemas, and escalation of overall radiation doses. However, even following the currently most active chemoradiation protocols, local and locoregional relapse of LD-SCLC remains a problem. Surgery is feasible within this clinical setting and may add to long-term local control and possible cures. Further investigation into the inclusion of surgery in LD-SCLC within carefully designed prospective clinical trials seems justified, although final evaluation would necessarily include prospective, randomized testing within a more "modernized" study design compared to the "old" and "historical" randomized Lung Cancer Study Group trial.


Administration of edaravone, a free radical scavenger, during t-PA infusion can enhance early recanalization in acute stroke patients--a preliminary study.
The aim of the present study was to investigate whether administration of edaravone during t-PA infusion can enhance early recanalization in acute stroke patients. This trial was undertaken as a multicenter, single blind, randomized, open-labeled study. Acute stroke patients with M1 or M2 occlusion within 3h of onset were studied prospectively. The subjects were randomly allocated to edaravone (Edaravone group: when t-PA was intravenously infused, intravenous edaravone (30 mg) was started at the same time) and no edaravone (Non-Edaravone group). Early recanalization within 1h after t-PA infusion and neurological recovery 24h after t-PA infusion were compared between the two groups. 40 patients (23 men, 17 women; mean age, 76.4 ± 8.2 years, median 79 years) were enrolled; 23 patients were assigned to the Edaravone group and 17 to the Non-Edaravone group. Early recanalization was more frequently observed in the Edaravone group than in the Non-Edaravone group (56.5% vs. 11.8%, P=0.0072). Eight patients who underwent endovascular therapy immediately after t-PA infusion were excluded, and neurological recovery was analyzed. Remarkable and good recoveries were more frequently observed in the Edaravone group than in the Non-Edaravone group (80.1% vs. 45.5%, P=0.0396). Early recanalization and good neurological recovery were more frequently observed in the Edaravone group than in the Non-Edaravone group. These results demonstrate that administration of edaravone during t-PA infusion should enhance early recanalization in acute stroke patients.


Noscapine induces mitochondria-mediated apoptosis in human colon cancer cells in vivo and in vitro.
Noscapine, a phthalide isoquinoline alkaloid derived from opium, has been widely used as a cough suppressant for decades. Noscapine has recently been shown to potentiate the anti-cancer effects of several therapies by inducing apoptosis in various malignant cells without any detectable toxicity in cells or tissues. However, the mechanism by which noscapine induces apoptosis in colon cancer cells remains unclear. The signaling pathways by which noscapine induces apoptosis were investigated in colon cancer cell lines treated with various noscapine concentrations for 72 h, and a dose-dependent inhibition of cell viability was observed. Noscapine effectively inhibited the proliferation of LoVo cells in vitro (IC(50)=75 μM). This cytotoxicity was reflected by cell cycle arrest at G(2)/M and subsequent apoptosis, as indicated by increased chromatin condensation and fragmentation, the upregulation of Bax and cytochrome c (Cyt-c), the downregulation of survivin and Bcl-2, and the activation of caspase-3 and caspase-9. Moreover, in a xenograft tumor model in mice, noscapine injection clearly inhibited tumor growth via the induction of apoptosis, which was demonstrated using a TUNEL assay. These results suggest that noscapine induces apoptosis in colon cancer cells via mitochondrial pathways. Noscapine may be a safe and effective chemotherapeutic agent for the treatment of human colon cancer.


Effects of Welfare Reform on Education Acquisition of Adult Women.
Education beyond traditional ages for schooling is an important source of human capital acquisition among adult women. Welfare reform, which began in the early 1990s and culminated in the passage of the Personal Responsibility and Work Opportunity Reconciliation Act in 1996, promoted work rather than education acquisition for this group. Exploiting variation in welfare reform across states and over time and using relevant comparison groups, we undertake a comprehensive study of the effects of welfare reform on adult women's education acquisition. We first estimate effects of welfare reform on high school drop-out of teenage girls, both to improve upon past research on this issue and to explore compositional changes that may be relevant for our primary analyses of the effects of welfare reform on education acquisition among adult women. We find that welfare reform significantly reduced the probability that teens from disadvantaged families dropped out of high school, by about 15%. We then estimate the effects of welfare reform on adult women's school enrollment and conduct numerous specification checks, investigate compositional selection and policy endogeneity, explore lagged effects, stratify by TANF work incentives and education policies, consider alternative comparison groups, and explore the mediating role of work. We find robust and convincing evidence that welfare reform significantly decreased the probability of college enrollment among adult women at risk of welfare receipt, by at least 20%. It also appears to have decreased the probability of high school enrollment among this group, on the same order of magnitude. Future research is needed to determine the extent to which this behavioral change translates to future economic outcomes.


Malabsorption Syndromes and Food Intolerance.
Feeding intolerance is ubiquitous in neonatal intensive care units with as many signs and symptoms as possible diagnoses. Optimizing nutrition is paramount in both preterm and term infants. Determining the cause of feeding intolerance and adjusting nutrition interventions is an important part of the daily care of newborns. This review discusses the role of malabsorption and food intolerance as possible causes of nutrition difficulties in the newborn.


Myopericytoma in the corpus cavernosum of the penis: A case report of a rare disease.
Myopericytomas usually occur in the extremities of older individuals; however, they also rarely occur in the penis. We report a case of myopericytoma in the corpus cavernosum of the penis and review the relevant literature. A 76-year-old man presented with a slow-growing painless nodule on the left side of the penis. On physical examination, a non-tender, 7-mm mass was palpable. This tumor showed inhomogeneous low signal intensity on T2-weighted magnetic resonance imaging. The mass was excised and a myopericytoma diagnosed by pathological examination of the operative specimen. We here report a rare case of myopericytoma in the corpus cavernosum of the penis. To the best of our knowledge, this is the second reported case of a myopericytoma in the penis and the first in the corpus cavernosum of the penis. Clinicians should keep this rare possibility in mind when investigating a mass in the penis.


Maze model to study spatial learning and memory in freely moving monkeys.
Many types of mazes have been used in cognitive brain research and data obtained from those experiments, especially those from rodents' studies, support the idea that the hippocampus is related to spatial learning and memory. But the results from non-human primates researches regarding the role of the hippocampus in spatial learning and memory are controversial and inconsistent with those obtained in rodents. This might be due to the differences of the methods used in non-human primates and rodents. Several kinds of maze models including two-dimensional computerized visual maze models and three-dimensional maze models have been developed for non-human primates, but they all have some defects. Therefore, development of a maze model for non-human primates that is comparable with those used in rodents is necessary to solve the controversy. This paper describes a large-scale, three-dimensional outdoor maze model for non-human primates which can be used to study spatial learning and memory. Monkeys learn to use the maze quickly compared with two-dimensional computerized visual mazes. It has many advantages which could make up the limits of the existing three-dimensional mazes in non-human primates, and can be comparable with radial arm mazes used in rodents. Based on the results, we believe that the new maze model will be valuable in many research areas, especially in studies involving spatial learning and memory in freely moving monkeys.


Effect of inhaler drug education on fatigue, dyspnea severity, and respiratory function tests in patients with COPD.
This study was conducted to examine the effect of inhaler drug education on fatigue, dyspnea severity, and respiratory function tests in patients with chronic obstructive pulmonary disease (COPD). This randomized controlled study was conducted with a total of 85 patients treated at the chest diseases clinic and outpatient clinic of a state hospital. The data were collected using questionnaires, respiratory function tests, and the COPD and Asthma Fatigue Scale (CAFS) and Visual Analogue Scale (VAS-for dyspnea severity). It was determined that after 4 weeks of inhaler drug education, the CAFS mean score decreased to 35.32 ± 14.36, the dyspnea severity mean score decreased to 4.76 ± 2.50, and the respiratory function tests mean scores increased to forced expiratory volume in 1 s (FEV1) = 58.83 ± 25.48, forced vital capacity (FVC) = 59.04 ± 19.19, and FEV1/FVC = 88.39 ± 21.59 in the intervention group (p < 0.05). No change was observed in the patients in the control group except for FEV1 and FVC mean scores (p > 0.05). These results demonstrate that inhaler drug education can improve fatigue, dyspnea severity, and respiratory function tests of patients with COPD. The training by nurses of every patient hospitalized in the clinic regarding inhaler drug therapy, and the regular checking of patients' way of using the inhaled drugs, will contribute to COPD management.


In vivo phosphorescence imaging of pO2 using planar oxygen sensors.
Oxygen-dependent quenching of luminescence of metal porphyrin complexes has been used to image the pO(2) distribution over tumor and normal tissue. An experimental setup is described using a platinum(II)-octaethyl-porphyrin immobilized in a polystyrene matrix as transparent planar sensor. Sensitivity over a broad range is high at low pO(2) values (+/- 0.2 mm Hg at 0 mm Hg; +/- 1.5 mm Hg at 160 mm Hg pO(2)). Due to intrinsically referencing via lifetime encoding there was no modification of the sensor response in vivo in the dorsal skinfold chamber model with amelanotic melanoma (A-MEL-3) in awake hamsters when compared to the in vitro calibration. pO(2) measurements over normal tissue (25.8 +/- 5.1 mm Hg) and tumor tissue (9.2 +/- 5.1 mm Hg) were in excellent agreement with previous results obtained in this model using a surface multiwire electrode. Using the presented method the surface pO(2) distribution can be mapped with a high temporal resolution of approximately 100 ms and a spatial resolution of at least 25 mu m. Moreover, the transparent sensor allows the simultaneous visualization of the underlying microvasculature.


Sinonasal Malignancies of Anterior Skull Base: Histology-driven Treatment Strategies.
The advances in endoscopy have revolutionized the management of sinonasal and skull base lesions. Many complex cancers that traditionally required open approaches are now amenable to purely endoscopic endonasal resection, providing less invasive surgery with lower morbidity but with comparable oncologic outcomes in terms of survival rates. This article discusses the current evidence for the multimodal management of sinonasal and anterior skull base cancers focusing on the different treatment protocols driven by histologic subtypes.


Validation of the Hebrew version of the Movement Disorder Society-Unified Parkinson's Disease Rating Scale.
The Movement Disorders Society (MDS) published the English new Unified Parkinson's Disease Rating Scale (MDS-UPDRS) as the official benchmark scale for Parkinson's disease (PD) in 2008. We aimed to validate the Hebrew version of the MDS-UPDRS, explore its dimensionality and compare it to the original English one. The MDS-UPDRS questionnaire was translated to Hebrew and was tested on 389 patients with PD, treated at the Movement Disorders Unit at Tel-Aviv Medical Center. The MDS-UPDRS is made up of four sections. The higher the score, the worst the clinical situation of the patient is. Confirmatory and explanatory factor analysis were applied to determine if the factor structure of the English version could be confirmed in the Hebrew version. The Hebrew version of the MDS-UPDRS showed satisfactory clinimetric properties. The internal consistency of the Hebrew-version was satisfactory, with Cronbach's alpha values 0.79, 0.90, 0.93, 0.80, for parts 1 to 4 respectively. In the confirmatory factor analysis, all four parts had high (greater than 0.90) comparative fit index (CFI) in comparison to the original English MDS-UPDRS with high factor structure (0.96, 0.99, 0.94, 1.00, respectively), thus confirming the pre-specified English factor structure. Explanatory factor analysis yielded that the Hebrew responses differed from the English one within an acceptable range: in isolated item differences in factor structure and in the findings of few items having cross loading on multiple factors. The Hebrew version of the MDS-UPDRS meets the requirements to be designated as the Official Hebrew Version of the MDS-UPDRS.


Contrast sensitivity and pattern visual evoked potential in patients with glaucoma.
Contrast sensitivity and pattern visual evoked potential (VEP) were measured in cases of ocular hypertension and primary open-angle glaucoma at various stages. The visual field of each eye was examined quantitatively and the retinal nerve fiber layer and optic disc were precisely assessed with magnified stereoscope fundus photography. This study revealed that contrast sensitivity of the eyes with glaucoma was within the normal range in the very early stage of the disease. As optic nerve damage advanced, high- or low-frequency loss developed. Further optic nerve damage produced a level type of loss. Pattern VEPs also showed increasing abnormalities as glaucomatous optic nerve damage progressed. Measurements of contrast sensitivity and pattern VEP were found not to be as sensitive as quantified precise visual field measurement or color stereoscopic fundus photography for detection of minor optic nerve damage in cases of early glaucoma. These methods may be useful, however, as an objective and subjective monitor of progression of optic nerve damage in glaucoma.


Development and validation of a spina bifida-specific pediatric quality of life questionnaire: the Spina Bifida Pediatric Questionnaire, SBPQ.
Based on existing questionnaires and patient interview, a health-related quality of life (HRQoL) questionnaire in spina bifida (SB) children is created and validated, the Spina Bifida Pediatric Questionnaire (SBPQ). SB patients from the SB reference centre Ghent University Hospital, Belgium, with mental ability between 6 and 18 years old and their parents were asked to participate in the study, together with a control group. Thirty-nine patients and parents answered the questionnaire once, 20 patients and their parents the test-retest. Thirty-five controls answered the questionnaire once, 34 controls and their parents the test-retest. The final questionnaire was retained when 3 consecutive patients approved all items. Visual clues were added for children with a mental ability below 10 years of age. The test-retest showed a good to excellent agreement for child self-report in 5 domains (not for social functioning), for parent proxy report in all domains (6), for control self-report in 4 domains (not for domain home) and for control parent proxy report in all domains (5). Internal consistency reliability was good in child self-report and in parent proxy report, except for physical functioning in child self-report. There was parent-child agreement for 4 out of 6 domains. Regarding social and emotional functioning, QoL was rated lower by parents than by children themselves. A SB HRQoL questionnaire was developed and validated. Because of visual aid, this questionnaire can be used by both young children and adolescents.


Water buffalo (Bubalus bubalus Arnee) allotypes: identification of a multiple allelic system.
This paper describes two allotypes of water buffalo controlled by two codominant allelic genes. The third allele is a null allele and behaves as a recessive one. The two detectable serum antigens are termed A1 and A2 and the third one (as yet undetectable) A0. The A1 antigen was recovered in the third peak and A2 antigen in the first peak following gel filtration through Sephadex G-200. The A1 antigen is common to water buffalo and cattle; the frequency of the corresponding gene (A1) was the same in both species.


Microextraction on a screw for determination of trace amounts of hexanal and heptanal as lung cancer biomarkers.
Solid phase microextraction on a screw was utilized for the extraction of hexanal and heptanal as lung cancer biomarkers from urine samples. Reduced graphene oxide (rGO) was coated on the surface of a stainless-steel set screw by electrophoretic deposition method. The screw was located inside a glass cover, and the created channel acted as the sample solution flow pass. A 5 mL glass syringe was connected to a syringe pump to direct the sample and the eluent through the channel. The extraction procedure was followed by gas chromatography/mass spectrometry (GC/MS) for separation and determination of the extracted aldehydes. The effective parameters on the extraction efficiencies of the analytes were identified and optimized. Under the optimal extraction conditions, the extraction time was as short as 10 min. The calibration curves indicated good linearity (R2 > 0.97) within the concentration range of 1.0-50 μg L-1. The obtained limits of detection (LODs) for hexanal and heptanal were down to 0.4 and 0.3 μg L-1, respectively. Considering the repeatability, simplicity, and eco-friendliness of this simple extraction method, it can be efficiently used for preconcentration of aldehydes in different samples.


Inhibitory effects of peroxisome proliferator-activated receptor γ agonists on collagen IV production in podocytes.
Peroxisome proliferator-activated receptor-γ (PPAR-γ) agonists have beneficial effects on the kidney diseases through preventing microalbuminuria and glomerulosclerosis. However, the mechanisms underlying these effects remain to be fully understood. In this study, we investigate the effects of PPAR-γ agonist, rosiglitazone (Rosi) and pioglitazone (Pio), on collagen IV production in mouse podocytes. The endogenous expression of PPAR-γ was found in the primary podocytes and can be upregulated by Rosi and Pio, respectively, detected by RT-PCR and Western blot. PPAR-γ agonist markedly blunted the increasing of collagen IV expression and extraction in podocytes induced by TGF-β. In contrast, adding PPAR-γ antagonist, GW9662, to podocytes largely prevented the inhibition of collagen IV expression from Pio treatment. Our data also showed that phosphorylation of Smad2/3 enhanced by TGF-β in a time-dependent manner was significantly attenuated by adding Pio. The promoter region of collagen IV gene contains one putative consensus sequence of Smad-binding element (SBE) by promoter analysis, Rosi and Pio significantly ameliorated TGF-β-induced SBE4-luciferase activity. In conclusion, PPAR-γ activation by its agonist, Rosi or Pio, in vitro directly inhibits collagen IV expression and synthesis in primary mouse podocytes. The suppression of collagen IV production was related to the inhibition of TGF-β-driven phosphorylation of Smad2/3 and decreased response activity of SBEs of collagen IV in PPAR-γ agonist-treated mouse podocytes. This represents a novel mechanistic support regarding PPAR-γ agonists as podocyte protective agents.


Many moral buttons or just one? Evidence from emotional facial expressions.
We investigated whether moral violations involving harm selectively elicit anger, whereas purity violations selectively elicit disgust, as predicted by the Moral Foundations Theory (MFT). We analysed participants' spontaneous facial expressions as they listened to scenarios depicting moral violations of harm and purity. As predicted by MFT, anger reactions were elicited more frequently by harmful than by impure actions. However, violations of purity elicited more smiling reactions and expressions of anger than of disgust. This effect was found both in a classic set of scenarios and in a new set in which the different kinds of violations were matched on weirdness. Overall, these findings are at odds with predictions derived from MFT and provide support for "monist" accounts that posit harm at the basis of all moral violations. However, we found that smiles were differentially linked to purity violations, which leaves open the possibility of distinct moral modules.


Tasty rewards for ants: differences in elaiosome and seed metabolite profiles are consistent across species and reflect taxonomic relatedness.
Diaspores of myrmecochorous plants consist of a seed (or fruit) and an attached appendage (elaiosome) which attracts ants. The elaiosome is a food resource for ants, whereas the seed is an energy source for subsequent germination and plant establishment. Although myrmecochory occurs in many phylogenetically unrelated lineages, multiple phylogenetic lineages display similar variation in elaiosome and seed metabolite composition due to convergent evolution. We focused on four families (Amaryllidaceae, Boraginaceae, Papaveraceae and Poaceae) each represented by two species from different genera. Diaspores of three populations per species were sampled and concentrations of 60 metabolites from five groups (amino acids, fatty acids, organic acids, polyols and sugars) were determined for both elaiosomes and seeds. Variability in metabolite composition was decomposed by hierarchical ANOVA and variation partitioning using redundancy analysis (reflecting both species nested within families, crossed with seed vs. elaiosome). Differences in the metabolite composition of elaiosomes and seeds were consistent across multiple phylogenetic origins (with more pronounced differences at the level of individual metabolites than at the level of metabolite groups) and supported the idea of convergent evolution under strong selection pressure. Elaiosomes contained higher amounts of easily digestible metabolites (especially amino acids) than seeds. Fatty acids were not more concentrated in elaiosomes, which contradicts the literal translation of "elaiosome" (= oil body). The differentiation of metabolite composition closely reflected taxonomic relatedness, particularly at the family level. Differences among populations within species were small, so the metabolite composition can thus be considered as a trait with relatively low intraspecific variability.


Blood manganese concentration is elevated in infants with iron deficiency.
The present study was done to determine whether blood Mn concentration is elevated in iron-deficient infants. Thirty-one infants with iron deficiency and thirty-six control subjects (6-24 months of age) were tested for blood Mn concentration, complete blood counts, serum ferritin, and serum iron/transferring iron-binding capacity (Fe/TIBC). All the 31 iron-deficient infants were treated with iron supplement; however, 19 of them underwent blood Mn checkup again in compliance with follow-up schedule when their ferritin levels returned to the normal range. Iron therapies were done for 1-6 months (mean, 2.8; standard deviation, 1.6) using ferric hydroxide-polymaltose complex (6 mg/kg Fe(3+) daily). Infants with iron deficiency had a higher mean blood Mn concentration than controls (2.550 vs. 1.499 μg/dL, respectively). After iron therapy, the blood Mn levels of iron-deficient infants significantly decreased compared to their pre-therapy levels (2.045 vs. 2.971 μg/dL, respectively), and their hemoglobin and ferritin levels significantly increased. After adjustment for covariates (e.g., age and breast-feeding), multiple linear regression models showed that increased blood Mn levels were significantly associated with low serum ferritin and hemoglobin levels, whereas with Fe/TIBC there was only a tendency. Our results indicate that iron deficiency increases blood Mn levels in infants, presumably by increasing Mn absorption.


Influence of the effective lens position, as predicted by axial length and keratometry, on the near add power of multifocal intraocular lenses.
To calculate the near focal distance of different multifocal intraocular lenses (IOLs) as a function of the 2 parameters that are measured before cataract surgery; that is, axial length (AL) and refractive corneal power (keratometry [K]). GB Bietti Foundation IRCCS, Rome, Italy. Noninterventional theoretical study. The IOL power for emmetropia was first calculated in an eye model with the AL ranging from 20 to 30 mm and K from 38 to 48 diopters (D). Then, the predicted myopic refraction for any given IOL add power (from +1.5 to +4.0 D) was calculated, and from this value the near focal distance was obtained. Calculations were also performed for the average eye (K = 43.81 D; AL = 23.65 mm). The near focal distance increased with increasing values of K and AL for each near power add. The near focal distance ranged between 53 cm and 72 cm (21 inches and 28 inches) for a multifocal IOL with +2.50 D, between 44 cm and 60 cm (17 inches and 24 inches) for a multifocal IOL with +3.00 D add, and between 33 cm and 44 cm (13 inches and 18 inches) for a multifocal IOL with +4.00 D add. In the average eye, the near focal distance ranges between 36 cm (near add power = 4.00 D) and 99 cm (near add power = 1.5 D). Longer eyes with steeper corneas showed the longest near focal distance and could experience more difficulties in focusing near objects after surgery. The opposite was true for short hyperopic eyes. Dr. Hoffer receives licensing fees for the commercial use of the registered trademark Hoffer from all biometry manufacturers using the Hoffer Q formula to ensure that it is programmed correctly and book royalties from Slack, Inc., for the textbook IOL Power. None of the authors has a financial or proprietary interest in any material or method mentioned.


Immunohistochemistry in childhood brain tumors: what are the facts?
In the past, contradictory results have been reported concerning the specificity of neuronal or glial cell markers. However, we have investigated this aspect in a large group of more than 550 brain tumors (among them 60 medulloblastomas). These contradictions can easily be explained by considering two basic facts. First, every neoplastic cell population, especially in embryonic tumors, diffusely infiltrates the brain tissue: non-neoplastic cells, intermingled with tumor cells, can therefore give rise to immunohistochemical and histogenetic misinterpretations. Second, different cell markers can be expressed by one and the same cell (e.g., GFAP, NSE, vimentin), making nosological interpretation of the tumor difficult, impossible, or at best rather subjective. Clear-cut marker positivity is mostly found in the differentiated tumors for which the nosological classification is already clear by the usual histological methods. Only synaptophysin seems to be a reliable marker for neurogenic cells. In embryonic brain tumors (so-called PNET), no correlations between the presence of a given cell marker and the biological behavior of the tumor have so far been detected.


Management of the neck in T1 and T2 buccal squamous cell carcinoma.
Buccal squamous cell carcinoma (SCC) appears to behave more aggressively than other oral subsites, in particular with regards to regional disease at presentation and regional recurrence. Adequate management of the neck is of the utmost importance but is still the subject of debate. An international multicentre retrospective review of 101 patients treated for T1-T2 buccal SCC was performed. Twenty-four were staged clinical node positive (cN+) and underwent therapeutic neck dissection, while 77 were node negative (cN0), with 32 undergoing elective neck dissection (END), with an occult nodal metastasis rate of 28.1%. Depth of invasion (DOI) < 4 mm was associated with a significantly lower rate of cervical nodal metastasis (87.5% versus 12.5%; P = 0.033). END demonstrated a non-significantly lower regional recurrence rate compared to observation (6.3% versus 8.9%, P = 0.670). Regional recurrence was more common in pN+ (24%) and undissected cases (8.9%) than in pN0 patients (0%) (P = 0.011) and was associated with DOI > 5 mm (P = 0.002). Regional recurrence resulted in a reduction in survival (24 versus 93 months, P < 0.001). In the pT2cN0 group, END improved survival (123 versus 26 months, P = 0.009). It is suggested that END be performed in cT2N0 buccal SCC, particularly for tumours with DOI > 4 mm.


Noninvasive determination of the valvar area in aortic valve disease by Doppler echocardiography and radionuclide angiography.
To assess the severity of outlfow obstruction in patients with aortic valve disease, the aortic valvar area was noninvasively determined in 22 patients with isolated aortic stenosis or combined stenosis and regurgitation. The ejection time (ET), maximal velocity (Vmax), and systolic velocity integral (SVI) of the aortic flow was obtained by continuous wave Doppler ultrasound. Left ventricular stroke volume (SV) was determined by radionuclide angiography, using a counts-based nongeometric technique with individual attenuation correction. Aortic valve area (AVA) was calculated using a modified Gorlin formula; AVA = SV/(71.2 X ET X Vmax), and also by dividing the stroke volume by the systolic velocity integral; AVA = SV/SVI. The two noninvasive determinations correlated closely with the valve areas obtained by invasive measurements; r = 0.95, SEE = +/- 0.13 cm2 by the modified Gorlin formula, and r = 0.94, SEE = +/- 0.14 cm2 by the integration method. The two noninvasive calculations showed almost uniform results; r = 0.98, SEE = +/- 0.09 cm2. In conclusion, aortic valve area can be determined with reasonable accuracy by combining Doppler echocardiography and radionuclide angiography. This noninvasive approach may reduce the need for invasive measurements in patients with suspected aortic valve disease. In addition, radionuclide angiography provides important information about left ventricular function.