Prehabilitation sessions can be provided more frequently in a shortened regimen with similar or better efficacy in people with non-small cell lung cancer: a randomised trial.
In people with non-small cell lung cancer, what is the effect of condensing 15 prehabilitation sessions into a 3-week regimen compared with a 5-week regimen? Randomised controlled trial with concealed allocation, intention-to-treat analysis and blinded assessment of the primary outcome. People with diagnosed or suspected non-small cell lung cancer and moderate-to-high risk of postoperative complications. Fifteen supervised prehabilitation sessions delivered with either a dense regimen of five sessions/week for 3 weeks (experimental group) or a non-dense regimen of three sessions/week for 5 weeks (control group). The primary outcome was the change in cardiorespiratory fitness measured by the V̇O2peak in ml/kg/min. The secondary outcomes were the change in other variables of interest measured during cardiopulmonary exercise testing, non-invasive nutritional markers, quadriceps maximal voluntary isometric contractions, maximal inspiratory pressure, quality of life, adherence and postoperative complications. Changes with the experimental regimen were similar to or better than changes with the control regimen for: V̇O2peak (MD 1.2 ml/kg/min, 95% CI -0.1 to 2.6); V̇E/V̇CO2 slope (MD -3.6 points, 95% CI -8.7 to 1.5); and work rate at ventilatory threshold (MD 3.7 W, 95% CI -5.6 to 13.0). The two regimens had similar effects on: peak work rate (MD 1.3 W, 95% CI -6.4 to 9.0), V̇O2 at ventilatory threshold (MD 0.0 ml/kg/min, 95% CI -1.4 to 1.4); body mass index (MD -0.2 kg/m2, 95% CI -0.5 to 0.1); and maximal inspiratory pressure (MD -0.7 cmH2O, 95% CI -9.8 to 8.4). The relative effect was uncertain for quadriceps maximal voluntary isometric contractions, quality of life and complications. Condensing prehabilitation sessions led to similar or better improvement in cardiorespiratory fitness and did not decrease adherence or increase adverse events. This could increase the number of patients who can be referred for prehabilitation, despite short presurgical periods. NCT03936764.


In vivo evaluation of sunscreen application by multispectral imaging: A new tool for educating sunscreen users.
The sun protection factor (SPF) of sunscreens is evaluated using standardized protocols based on the application of 2 mg/cm2 of product. However, the amount of product applied by sunscreen users in real life is likely to be much lower. To evaluate a new multispectral imaging approach for determining the actual quantity of sunscreen applied by users and to assess the benefits of an application guide for the use of an SPF 50+ sunscreen. Analyses of the reflectance spectra obtained from multispectral images were used to determine the actual dose of sunscreen that 26 healthy volunteers applied to their face following three application modalities: a single application, reapplication after 30 min, and application according to an instruction guide. Without the application guide, volunteers applied an average of 1.04 mg/cm2 of sunscreen during the single application and 1.23 mg/cm2 during the repeated application. With the application guide, the amount of sunscreen applied was 1.45 mg/cm2 : around 40% higher than during the single application. Spreading of the sunscreen was also less uniform with the unguided single application than with the other application modalities. This study showed that the multispectral imaging approach can be used to measure the amount of sunscreen applied in vivo. Our findings confirmed that the standard dose used for SPF measurements and other sunscreen tests is far higher than that applied by users in practice. Providing users with precise guidelines could increase the amount of sunscreen applied, resulting in more adequate photoprotection.


Prevalence of patients receiving renal replacement therapy in El Salvador in 2014.
El Salvador has the highest renal failure mortality rate in the Americas. Five healthcare providers offer renal replacement therapy (RRT) in the country. The national RRT prevalence has never been reported. To determine the RRT prevalence in El Salvador and some basic characteristics. The association of nephrology coordinated a nationwide cross-sectional survey during the third quarter of 2014. 31 renal centres participated in the survey, covering 99.5% of patients. National RRT prevalence: 595 per million population (pmp), N=3807, average age 50.4 years, 67.5% male. By modality: peritoneal dialysis (PD) 289 pmp, haemodialysis (HD) 233 pmp, with functioning kidney transplantation 74 pmp (living donor only). Social security covers 25% of the population but treats 49.7% of RRT patients. Generally, higher prevalence was observed in municipalities with renal centres or located on the coast or lowlands. Ninety-five percent of HD patients receive fewer than 3 weekly sessions. Of PD patients, 59% do not belong to a continuous outpatient or automated programme, and 25% still use rigid catheter. Aetiology of chronic kidney disease: unavailable/undetermined 50%, hypertension 21.1%, diabetes 18.9%, glomerulonephritis 6.7%, obstructive causes 1.2%, tubulointerstitial 0.9%, polycystic 0.4% and other 0.7%. Despite the increase in RRT services, the prevalence is lower than the Latin American average (660 pmp). Three quarters of HD and PD patients are under-dialysed. Obsolete RRT techniques are still used. The presence of Mesoamerican nephropathy influences the demographic characteristics (many young patients, two-thirds male, high prevalence in lowlands and coastlands).


Role of respiratory characteristics in treatment adherence with noninvasive home mechanical ventilation in myotonic dystrophy type 1, a retrospective study.
Chronic respiratory insufficiency is common in patients with myotonic dystrophy type 1 (DM1) and can be treated with noninvasive home mechanical ventilation (HMV). HMV is not always tolerated well resulting in low treatment adherence. We aimed to analyze if baseline respiratory characteristics such as pulmonary function, level of pCO2 and presence of sleep apnea are associated with HMV treatment adherence in DM1 patients. Pulmonary function testing, polysomnography and blood gas measurement data of DM1 patients were retrospectively collected. Initiation of HMV and treatment adherence after one year was documented. Patients with low treatment adherence (average daily use of HMV <5 h) were grouped with patients that discontinued HMV and compared with patients with high treatment adherence (average daily use of HMV >5 h). HMV was initiated in 101 patients. After one year, 58 patients had low treatment adherence. There were no differences between the low and high treatment adherence group regarding the respiratory characteristics. None of the included predictors (gender, age, body mass index, cytosine-thymine-guanine repeat length, FVC, daytime pCO2, bicarbonate, nighttime pCO2, nighttime base excess, apnea-hypopnea index and mean saturation during sleep) was able to significantly predict high treatment adherence. In conclusion, the respiratory characteristics are not associated with treatment adherence with HMV in DM1 patients and cannot be used to identify patients at risk for low HMV treatment adherence.


Hydrolyzed Yeast Supplementation to Newly Weaned Piglets: Growth Performance, Gut Health, and Microbial Fermentation.
Hydrolyzed yeast (HY)-derived protein from Saccharomyces cerevisiae has a high digestible protein content and nucleotides and is a sweetener immunostimulatory substance. This could be used in nursery diets to minimize diarrhea and improve the growth rate and gut health of early-weaned piglets. This research was conducted with the objective of examining the effect of the inclusion level of HY as a potential protein ingredient for early-weaned piglets. A total of 72 crossbred weaned piglets [(Landrace × Large White) × Duroc] were assigned to three dietary treatments in six replicates with four pigs per pen. Dietary treatments were: (i) control (CON), piglets weaned at 18 days; (ii) CON diet with 5% HY inclusion (HY5); and (iii) CON diet with 10% HY inclusion (HY10) in a corn-soybean meal-based basal diet. Increasing HY levels positively improved body weight, average daily gain, and average daily feed intake (linear effect, p < 0.05). Furthermore, there was a linear increase in N-retention, albumin, jejunal villus height, villus height-to-crypt depth ratio, immunoglobulin A, acetate and propionate production, and Lactobacillus spp. count proportional to the dose of the HY-supplemented diet (p < 0.05). It also observed a decrease in diarrheal rate, jejunal crypt depth, blood urea nitrogen, pro-inflammatory cytokines, branched amino acids, and E. coli corresponding to the HY-supplemented levels (p < 0.05). However, the changes in the apparent total tract digestibility (dry matter, crude ash, and crude fat), blood glucose, butyrate, and Salmonella spp. were unaffected by the dietary HY level. Therefore, the supplementation of HY in the diet for early-weaned pigs not only supported the growth rate and immune function but also activated the beneficial bacterial growth of the early-weaned piglets.


Morphological observations in the nervous system of prenatal mucopolysaccharidosis II (M. Hunter).
Light and electron microscopic finding in the nervous system of a 23-week-old fetus are reported, in which MPS II was diagnosed prenatally. The degrees of myelination and neuronal differentiation were similar as in a normal fetus of the same age. A storage of mucopolysaccharides in typical vacuolar inclusion bodies was present throughout the peripheral and central nervous system, mainly in cells of mesenchymal origin. "Zebra" bodies and granulo-membranous bodies, which are thought to represent secondard ganglioside accumulation were only found in the well developed neurons of the spinal cord and spinal ganglia, but not in the poorly developed neurons of the cerebellar and cerebral cortex. Mucopolysaccharide storage in endothelial cells of cerebral bood vessels precedes the appearance of lipid storgae in cerebral neurons.


FabQ, a dual-function dehydratase/isomerase, circumvents the last step of the classical fatty acid synthesis cycle.
In the classical anaerobic pathway of unsaturated fatty acid biosynthesis, that of Escherichia coli, the double bond is introduced into the growing acyl chain by the FabA dehydratase/isomerase. Another dehydratase, FabZ, functions in the chain elongation cycle. In contrast, Aerococcus viridans has only a single FabA/FabZ homolog we designate FabQ. FabQ can not only replace the function of E. coli FabZ in vivo, but it also catalyzes the isomerization required for unsaturated fatty acid biosynthesis. Most strikingly, FabQ in combination with E. coli FabB imparts the surprising ability to bypass reduction of the trans-2-acyl-ACP intermediates of classical fatty acid synthesis. FabQ allows elongation by progressive isomerization reactions to form the polyunsaturated fatty acid, 3-hydroxy-cis-5, 7-hexadecadienoic acid, both in vitro and in vivo. FabQ therefore provides a potential pathway for bacterial synthesis of polyunsaturated fatty acids.


pp42/44MAP kinase is a component of the neurogenic pathway utilized by nerve growth factor in PC12 cells.
Nerve growth factor-stimulated mitogen-activated protein kinase (pp42/44MAP) kinase was characterized by sequential column chromatography on DEAE-Sephacel, phenyl-Sepharose CL4B, and S-200. The kinase displayed an apparent molecular mass of 42 kDa and reacted with an antiphosphotyrosine antibody. Peptide mapping of myelin basic protein revealed the presence of one phosphopeptide that was phosphorylated on Thr-97. pp42/44MAP kinase activity was dependent on Mg2+ and inhibited by K252a both in vitro and in vivo. Nerve growth factor-stimulated kinase activation was diminished by down-regulation of protein kinase C with 200 nM 12-phorbol 13-myristate acetate or with staurosporine (1 nM), a protein kinase C inhibitor. Genistein, a protein tyrosine kinase inhibitor, blocked nerve growth factor-mediated neurite extension as well as diminished activation of pp42/44MAP kinase. Our data demonstrate that activation of this kinase system by nerve growth factor displays a requirement for both protein kinase C as well as protein tyrosine kinase. In addition, other agents that are capable of promoting neurite outgrowth in PC12 cells, such as fibroblast growth factor or dibutyryl cyclic AMP, do so independently of activating this kinase system.


[Short-term evaluation of risk factor control and therapeutic prescription in secondary prevention of cardiovascular diseases].
Quantify risk factor control and compliance of present therapeutic recommendations in the two months following an acute myocardial infarction (AMI) or ischemic stroke. Cross-sectional, descriptive study of risk factors and treatments prescribed on discharge after AMI or stroke. A total of 68% of 122 patients (65.6% AMI; 22.1% women; mean age: 64.9), had controlled BP; 70.1% BMI < 30 kg/m2; 54.1% LDL-cholesterol < 100 mg/dl. Controlled BP (78.7% versus 50%) and adequate LDL-cholesterol (62.3% versus 20.5%) were greater after AMI than after stroke (p < 0.001). ACEI/ARA II prescribed after AMI: 30% (p < 0.001). After AMI, 26.2% without beta blocker (only 8.8% contraindicated). HbA1c < 7% in 55.5% of diabetics; BP control inferior to non-diabetics (p < 0.001). Short term control of the risk factors after cardiovascular episode and prescription on hospital discharge are improvable, above all after a stroke.


The contamination of microplastics in China's aquatic environment: Occurrence, detection and implications for ecological risk.
The widespread occurrence of microplastics in aquatic ecosystems that resulted in environmental contamination has attracted worldwide attention. Microplastics pose a potential threat to the growth and health of aquatic organisms, thereby affecting the function of the ecosystems. As one of the top ten countries producing and consuming plastic products globally, China's aquatic ecosystems have been profoundly affected by microplastics. In this review, we have summarized the microplastics contamination in three typical water environments (marine environment, freshwater environment, and wastewater treatment plants) in China, elaborated on the adverse impacts of microplastics on the ecological environment, and evaluated the potential ecological risks exposed to the ecosystem. In addition, the progress of microplastics extraction methods, as the important basis of microplastics related research, in aquatic ecosystems was introduced, especially the difference between the extraction of microplastics from wastewater and sludge samples. At present, most of the research on microplastics focuses on "one point", such as a certain river or wastewater treatment plant. Research on the mitigation and transfer of microplastics among different connected water environments is still lacking. Also, the microscale ecotoxicity caused by microplastics is poorly understood. In the end, we proposed suggestions and perspectives for future research regarding microplastics in the aquatic ecosystems in China.


The uses of 3D human brain organoids for neurotoxicity evaluations: A review.
Neurotoxicity studies aim at understanding the toxic effects and mechanisms of toxicants to human central nervous systems (CNS). However, human brains are the most complex organs, whereas the most commonly used models, such as 2D cell cultures and animal brains, are probably too simple to predict the responses of human brains. Embryonic stem cells (ESCs) or induced pluripotent stem cells (iPSCs)-based 3D human brain organoids hold unprecedented promise for the understanding of neurodevelopment and brain disease development. This review summarizes recent advances of using 3D human brain organoids for neurotoxicity studies. Comparative studies showed that 3D human brain organoids could support the findings obtained by animal or cohort studies, indicating that 3D human brain organoids are reliable models to evaluate the developmental neurotoxicity. 3D human brain organoids have been used to understand the toxicological mechanisms by using both conventional toxicological methods to investigate the signaling pathway changes as well as single cell RNA-sequencing to understand the neuron diversity. Some studies also used brain organoids carrying gene mutations or with virus infections to understand the toxicological responses of brains under diseased conditions. Although there are still limitations associated, 3D human brain organoids are promising tools for future neurotoxicity studies.


Spontaneous extrusion of Hulka-Clemens spring-loaded clips after vaginal hysterectomy: two case reports.
Two patients had previously been sterilized by the application of Hulka-Clemens spring-loaded clips to the Fallopian tubes, had a vaginal hysterectomy. In each patient a clip that was left attached to its tubal remnant was spontaneously extruded through the vaginal vault during the postoperative period.


Interferon-gamma enhances mRNA and surface expression of class I antigen on human extravillous trophoblast.
Human trophoblast cells with immunocytochemical characteristics of the extravillous population have been isolated from 1st trimester placentae. Treatment of these cells with IFN-gamma increases the expression of Class I antigens at both the cell surface and mRNA level. A similar increase in Class I antigens is also found in JEG-3 choriocarcinoma cells after treatment with IFN-gamma. The possibility that aberrant production of IFN-gamma may upset the fetal-maternal equilibrium in vivo is discussed.


Surface modified single molecules free-diffusion evidenced by fluorescence correlation spectroscopy.
We report on the free diffusion of single molecule near an interface studied using fluorescence correlation spectroscopy. In particular, we show that the chemical nature of the substrate may modify the free diffusion of a widely used molecule (rhodamine 6G), thus inducing unexpected effects in fluorescence correlation spectroscopy measurements. Our results show a strong influence, up to a few micrometer from the interface, of the surface polarity. This effect is assessed through the relative weight of the two dimensions diffusion process observed close to the surface. Our results are discussed in terms of competition between surface-solvent, solvent-molecule and molecule-surface specific interactions.


Anomalies associated with gastroschisis and omphalocele: analysis of 2825 cases from the Texas Birth Defects Registry.
The increasing prevalence of abdominal wall defects prompted analysis of anomalies associated with gastroschisis and omphalocele in the Texas Birth Defects Registry (TDBR). Cases of gastroschisis (ICD9 code 756.71), omphalocele (756.70), and/or unspecified anomalies of the abdominal wall (756.79) were obtained from the TDBR after IRB approval and analyzed using Microsoft Access© and Excel© databases. Analysis began with 2825 cases including 1831 of gastroschisis, 814 of omphalocele, and 180 of unspecified abdominal wall defects plus 9680 associated anomalies that were classified according to system. The overall prevalence of abdominal wall defects among 3,806,299 Texas births from 1999 to 2008 was 7.4 per 10,000 with 4.8 per 10,000 for gastroschisis and 2.1 for omphalocele. After excluding ambiguous cases (8.5% possibly misclassified), anomaly spectra were similar for the two AWD with musculoskeletal (limb contractures or defects), cardiovascular, gastrointestinal, urogenital, and central nervous system defects being most common. Of 1831 cases with gastroschisis, 594 (32%) had associated anomalies compared to 654 (80%) of 814 omphalocele cases. Gastroschisis as well as omphalocele has significant associated anomalies that are important to appreciate during pre- and postnatal management.


Torsades de pointes associated with fluoroquinolones: importance of concomitant risk factors.
The fluoroquinolone antibiotics sparfloxacin, grepafloxacin, gatifloxacin, and levofloxacin have been reported to cause torsades de pointes. Pre-existing risk factors increase vulnerability to this life-threatening arrhythmia. In a 65-year-old woman with a history of hypertension, coronary artery disease, systemic lupus erythematosus, and osteomyelitis, QTc interval prolongation (605 ms) and torsades de pointes developed after the initiation of levofloxacin, 250 mg intravenously once daily. The patient was hypokalemic and mildly hypomagnesemic before the initiation of levofloxacin and at the time of occurrence of torsades de pointes. The QTc interval decreased to 399 ms within hours of discontinuation of the levofloxacin, after which she had no further arrhythmias. In this and the majority of other published cases of fluoroquinolone-associated torsades de pointes, patients had at least 1 risk factor for the arrhythmia, and most had multiple risk factors. Fluoroquinolone antibiotics should be avoided whenever possible in patients with pre-existing risk factors for torsades de pointes.


IMRT for breast. a planning study.
To evaluate the performance of ten different treatment-planning systems when intensity modulated (IMRT) plans are designed for breast treatments that include the irradiation of the internal mammary chain. A dataset of five patients (CT images and volumes of interest) was distributed to design IMRT plans on the ten systems. To minimise biases, the same geometry and clinical planning aims were imposed on the individual plans. Results were analysed in terms of dose distributions and dose volume histograms. For target coverage, the volume receiving more than 95% of the prescribed dose ranged from 77% (OTP) to 91% (Eclipse and Pinnacle), the volume receiving more than 107% ranged from 3.3% (Hyperion) to 23.2% (OTP). The mean dose to ipsilateral lung ranged from 13 Gy (Eclipse) to 18 Gy (OTP). The volume of the contralateral breast receiving more than 10 Gy ranged from 3% (Pinnacle) to 26% (Precise). The volume of heart receiving more than 20 Gy ranged from 7% (Eclipse) to 47% (Precise), the maximum significant dose to heart ranged from approximately 27 Gy (XiO) to approximately 49 Gy (Precise). The maximum significant dose to healthy tissue ranged from approximately 51 Gy (Eclipse) to approximately 62 Gy (OTP). It was also possible to show that the treatment geometry proposed here enables to minimise contralateral breast irradiation while keeping minimal ipsilateral lung (or heart) involvement and satisfactory target coverage.


[Bone and neurological complications in a patient undergoing prolonged hemodialysis].
A case observed by chance and thereafter examined and treated is reported. It involved a vertebral fracture which failed to be recognized in a patient undergoing prolonged haemodialysis.


A Leydig cell tumour: a model for the study of lutropin action.
The properties of cells isolated from a Leydig cell tumour have been compared with normal rat testis Leydig cells. These cells were found to be similar in the following respects: 1. Lutropin-stimulated cyclic AMP and testosterone production. 2. Lutropin-activated protein kinase activity followed by phosphorylation of endogenous proteins of mol. wts. 57,000and 14,000. 3. Parallel lutropin dose vs. response curves for phosphorylation of the endogenous proteins and for testosterone production. 4. Two forms of isoenzyme, cyclic AMP dependent protein kinase, present. They differed mainly with respect to the lutropin-stimulated testosterone production, which was much lower in the tumour cells compared with the normal adult testis Leydig cells (4.6 +/- 1.1 and 114 +/- 16 ng testosterone/10(6) cells per 2 h, respectively). However, the lutropin-stimulated steroid production in the tumour cells was quantitatively comparable with the normal rat Leydig cell when the metabolism of pregnenolone in intact cells and mitochondria was inhibited by addition of SU-10603 and/or cyanoketone. It is concluded that the Leydig cell tumour used in this study can be used to investigate certain aspects of lutropin action where large quantities of cells are required.


Soil-transmitted helminth infections and leprosy: a cross-sectional study of the association between two major neglected tropical diseases in Indonesia.
The clinical spectrum of leprosy is dependent on the host immune response against Mycobacterium leprae or the newly discovered Mycobacterium lepromatosis antigen. Helminth infections have been shown to affect the development of several diseases through immune regulation and thus may play a role in the clinical manifestations of leprosy and leprosy reactions. The purpose of this study is to determine the proportion of helminth infections in leprosy and its association with the type of leprosy and type 2 leprosy reaction (T2R). History or episode of T2R was obtained and direct smear, formalin-ether sedimentation technique, and Kato-Katz smear were performed on 20 paucibacillary (PB) and 61 multibacillary (MB) leprosy participants. There are more helminth-positive participants in MB leprosy compared to PB (11/61 versus 0/20, p = 0.034) and in T2R participants compared to non-T2R (8/31 versus 3/50, p = 0.018). Our results suggest that soil-transmitted helminth infections may have a role in the progression to a more severe type of leprosy, as well as the occurrence of T2R. These findings could serve as a fundamental base for clinicians to perform parasitological feces examination in patients who have MB leprosy and severe recurrent reactions to rule out the possibility of helminth infection. Further secondary confirmation of findings are needed to support these conclusions.


High-resolution structure of HLA-A*1101 in complex with SARS nucleocapsid peptide.
The structure of the human MHC-I molecule HLA-A*1101 in complex with a nonameric peptide (KTFPPTEPK) has been determined by X-ray crystallography to 1.45 A resolution. The peptide is derived from the SARS-CoV nucleocapsid protein positions 362-370 (SNP362-370). It is conserved in all known isolates of SARS-CoV and has been verified by in vitro peptide-binding studies to be a good to intermediate binder to HLA-A*0301 and HLA-A*1101, with IC50 values of 70 and 186 nM, respectively [Sylvester-Hvid et al. (2004), Tissue Antigens, 63, 395-400]. In terms of the residues lining the peptide-binding groove, the HLA-A*1101-SNP362-370 complex is very similar to other known structures of HLA-A*1101 and HLA-A*6801. The SNP362-370 peptide is held in place by 17 hydrogen bonds to the alpha-chain residues and by nine water molecules which are also tightly bound in the peptide-binding groove. Thr6 of the peptide (Thr6p) does not make efficient use of the middle (E) pocket. For vaccine development, there seems to be a potential for optimization targeted at this position. All residues except Thr2p and Lys9p are accessible for T-cell recognition.


A G-quadruplex ligand 3,3'-diethyloxadicarbocyanine iodide induces mitochondrion-mediated apoptosis but not decrease of telomerase activity in nasopharyngeal carcinoma NPC-TW01 cells.
The G-quadruplex ligand 3,3'-diethyloxadicarbocyanine iodide (DODC) was reported to enhance the apoptotic potency of pheochromocytoma PC-12 and leukemia HL-60 cells through the inhibition of telomerase activity. In this study, a mitochondrion-mediated apoptotic pathway was demonstrated as another cytotoxic mechanism for DODC action. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and DNA laddering assays were performed to exhibit the cytotoxicity and apoptosis-inducing activity of DODC. Telomeric repeat amplification protocol (TRAP) assay was used to evaluate the effect of DODC on cellular telomerase. The mitochondrial uptake of probe 3,3'-dihexyloxacarbocyanine iodide was measured by flow cytometry. The mitochondrial proteomes were analyzed by two-dimensional gel electrophoresis and matrix-assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF MS). Western blot analyses were adopted to demonstrate the change of the distribution of mitochondrial proteins. DODC alone was able to induce apoptotic cell death but not decrease of telomerase activity in nasopharyngeal carcinoma NPC-TW01 cells. Instead, we found evidence that DODC significantly affected cellular mitochondria. DODC inhibited the uptake of another mitochondrial probe 3,3'-dihexyloxacarbocyanine iodide. By proteomic comparative analysis, we found that DODC induced the increase of prohibitin level in the mitochondria, indicating the occurrence of mitochondrial perturbation. Moreover, DODC was found to induce the levels of p53 and an 18-kDa truncated Bax on mitochondria, which in turn potentiated the release of cytochrome c for activation of caspases. DODC induces NPC-TW01 cell apoptosis via a mitochondrion-mediated mechanism. This paper demonstrates another cytotoxic mechanism of DODC other than inhibition of telomerase.


Inhibition of type A monoamine oxidase by methylquinolines and structurally related compounds.
A series of methylquinolines (MQ) were found to inhibit markedly type A monoamine oxidase (MAO) in human brain synaptosomal mitochondria. 4-MQ and 6-MQ inhibited type A MAO (MAO-A) competitively and 7- and 8-MQ inhibited MAO-A noncompetitively. Among these four isomers of MQ, 6-MQ was the most potent inhibitor; the Ki value toward MAO-A was 23.4 +/- 1.8 microM, which was smaller than the Km value toward kynuramine, an amine substrate, 46.2 +/- 2.8 microM. On the other hand, MQ were very weak inhibitors of type B MAO (MAO-B) and 8-MQ did not inhibit MAO-B in brain synaptosomal mitochondria. The inhibition of MAO-A proved to be reversible; by dialysis the inhibition of MQ was completely reversible. The affinity of these isomers of MQ toward MAO-A or -B was confirmed further with human liver mitochondria as sources of MAO-A and -B and with human placental mitochondria and rat pheochromocytoma PC12h cell line as sources of MAO-A. The relationship of the chemical structure of structurally related quinoline and isoquinoline derivatives to inhibition of the activity of type A or B MAO was examined.


Antibody isotype produced by pregnant mice immunised with fetal allogeneic lymphocytes is mainly IgG1.
Virgin and Pregnant BALB/c mice were immunized three times with (BALB/c X CBA)F1 fetal or adult lymphocytes. An enzyme linked immunosorbent assay (ELISA) was developed for analysing the isotypes and specificities of the alloantibody produced. Pregnant mice immunized with fetal lymphocytes showed an immunodeviation towards IgG1 production compared with other groups.


Factor structure of the Schalock and Keith Quality of Life Questionnaire (QOL-Q): validation on Mexican and Spanish samples.
The Quality of Life Questionnaire (QOL-Q) is used widely to evaluate the quality of life of persons with intellectual disability (ID). Its validity for use with Spanish-speaking cultures has been demonstrated for individuals with visual disabilities, but not for those with physical or intellectual disabilities. Such was the purpose of the present study. Two samples were administered the QOL-Q under standardized procedures. The first sample was composed of 209 Mexican participants with physical disabilities; the second was composed of 424 Spanish participants with ID. The hypothesis tested was: the applicability (i.e. etic properties) of the measure across countries and respondents would be demonstrated if reliability data and if factor composition were similar to the original measure. Cronbach's alpha was used to test reliability and exploratory factor analyses were used to test validity (i.e. factor structure). Data indicated that the reliability and factor structure was similar to that reported in the questionnaire's standardization manual and consistent with that reported in a number of Anglo-Saxon countries. The present study offers additional support for the valid use of the QOL-Q with Spanish-speaking populations.


Nonspecific cytotoxic cells in fish (Ictalurus punctatus). II. Parameters of target cell lysis and specificity.
Fish nonspecific cytotoxic cells (NCC) lyse various transformed human B-cells (NC-37, P3HR-1) and erythroblastoid cells (K562) as well as mouse YAC-1 and P815 cells. Highest NCC activity was found in the anterior (head) kidney, but spleen cells and peripheral blood leucocytes (PBL) also demonstrated cytolytic abilities. Lysis of chromium-51 labeled target cells occurred rapidly and optimum cytolysis developed at either 16 degrees C or 26 degrees C incubation temperatures. Preincubation at temperatures of 4 degrees C or 37 degrees C for 4 hours reduced NCC cytotoxicity. Although catfish (Ictalurus punctatus) are extensively outbred, interfish NCC activities did not significantly vary at the optimum E:T ratios (160). The NCC target antigen specificities were partially determined by cold target inhibition (CTI) studies. YAC-1 and K562 did not produce significant CTI, however. These studies demonstrated the presence of a highly active cytotoxic cell which is widely distributed in fish lymphoreticular tissue. NCC kill divergent kinds of transformed cell types, and the target cell specificity for human transformed B-cells is different from the NCC target cell antigens on other human (K562) and on mouse (YAC-1 and P815) cells.


Catalysis by ionic liquid. A green protocol for the stereoselective debromination of vicinal-dibromides by [pmIm]BF4 under microwave irradiation.
An easily accessible ionic liquid, 1-methyl-3-pentylimidazolium fluoroborate, [pmIm]BF4, has been demonstrated to be an efficient catalyst as well as reaction medium for the stereoselective debromination of a variety of structurally diverse vicinal-dibromides to the corresponding (E)-alkenes in high yields under microwave irradiation. This reaction does not require any organic solvent and any metal or any conventional reducing agent, and the ionic liquid is recycled without any appreciable loss of its catalytic efficiency.


Influence of intrahepatic vessels on volume and shape of percutaneous thermal ablation zones: in vivo evaluation in a porcine model.
Aim of the study was to evaluate the precise influence of different intrahepatic vessels, vessel sizes, and distances from the applicator on volume and shape of hepatic laser ablation zones in an in vivo porcine model. The study was approved by the institutional animal care and use committee. Eighteen computed tomography-guided Nd:YAG laser ablations were performed in the livers of 10 pigs at varying distances from hepatic veins and portal fields. After hepatectomy the livers were cut into 2-mm slices perpendicular to the laser applicator axes. For each ablation zone the maximum achievable (ideal) volume, the segmented (real) volume, the maximum radius, and the radius at the position of adjacent hepatic vessels were determined. The shapes of the ablation zones were evaluated qualitatively. Comparative statistics using the unpaired t test and a multiple linear regression analysis were performed. Ideal and real ablation zone volumes differed by 27.3% (8.6 +/- 1.5 mL vs. 6.4 +/- 1.1 mL; P < 0.0001). Thirty-eight of 60 (63%) hepatic veins versus 28 of 31 (90%) portal veins within the central slices of the 18 ablation zones led to a reduction of the ablation zone's radius, depending on the distance between the vessel and the applicator and the vessel type. Portal fields revealed stronger effects than hepatic veins. The vessel diameter showed no independent effect (P > 0.05). When influencing, all hepatic veins showed a focal indentation whereas portal fields always showed broad flattening of the ablation zone. Portal fields lead to more heat sink than hepatic veins. The effects decreased with the distance between vessel and applicator tip, but less so for portal fields. The 2 vessel types induced considerably different shape alterations of the ablation zones. These results were not dependent on vessel size. This should be considered in the planning of thermal tumor ablations.


Residential addiction treatment providers: Identifying the role of social context in worker health and turnover.
Increased lethality and availability of addictive substances has strained US addiction treatment services, further exacerbating workforce shortages in these settings. The emotional and physical health toll of providing treatment may contribute to shortages. This community-initiated qualitative study aimed to identify conditions that affect provider health and turnover in residential addiction treatment from a Total Worker Health® perspective. Providers (direct service, supervisors, leaders) working in nonprofit residential treatment facilities in Massachusetts were recruited by role and geography to participate in interviews and focus groups. NVivo12 facilitated coding and analysis. 25% of transcripts were double coded to assess interrater reliability and coding consistency (mean Kappa = 0.82). Providers (N = 49) participated in 33 interviews and 4 focus groups. Many participants reported personal addiction histories. Analysis revealed how socio-contextual factors originating outside of residential facilities were dominant influences on "downstream" working conditions, worker health, staff turnover, and by extension, client care. Four primary socio-contextual themes surfaced:1) Changes in type and potency of substances and client need not reliably accompanied by shifts in treatment practices; 2) challenges balancing state requirements and state-provided resources; 3) influence of structural discrimination and addiction stigma on pay and professional advancement; and 4) geographic location of facilities shape work and quality of life. Results were used to develop a conceptual model for residential addiction treatment to illustrate pathways by which ecological factors interact to affect provider health and turnover. Findings indicate that protecting health and wellbeing of providers-many of whom are in addiction recovery themselves- is integral to improving addiction treatment. From this workforce's perspective, recent changes in socio-contextual factors have intensified already challenging working conditions (job demands, pay, advancement), negatively impacting worker health, turnover, and client care. Any interventions to improve treatment outcomes or working conditions in nonprofit addiction facilities must consider larger socio-contextual factors influencing these organizations.


Bovine serum albumin nanospheres carrying progesterone inclusion complexes.
Bovine serum albumin nanospheres carrying cyclodextrin complexes for the delivery of progesterone were produced. Inclusion complexes composed of progesterone and hydroxypropyl-beta-cyclodextrin or dimethyl-beta-cyclodextrin were prepared by spray-drying or freeze-drying methods. Prog alone and its inclusion complexes were incorporated into bovine serum albumin nanospheres using a coacervation method and cross-linking with heating. The nanosphere suspensions were essicated by spray-drying or freeze-drying. The inclusion complexes and the nanospheres were characterized by Fourier Transform-Infrared Spectroscopy (FT-IR) and Differential Scanning Calorimetry (DSC). Phase-solubility diagrams and stability constants were determined in distilled water at different temperatures (10, 25, and 37 degrees C). Size of nanospheres, their drug loading capacity and swelling ability were evaluated, as well as the in vitro controlled release profiles at pH 5.5 and 7.4.


Diabetic foot osteomyelitis: bone markers and treatment outcomes.
Novel bone turnover markers could help with the diagnosis and monitoring of osteomyelitis patients. We compared levels of two bone turnover markers, serum amino-terminal telopeptides (NTx) and bone alkaline phosphatase (BAP), in diabetic patients with and without osteomyelitis. Matched case-control study was conducted with diabetic patients with and without osteomyelitis. Cases not undergoing immediate amputation were followed with repeat measurements after osteomyelitis treatment and for outcome determination. Analysis included 54 subjects, 27 cases and 27 controls. Median BAP levels were similar between cases and controls at enrollment (p=.55) as were median NTx levels (p=.43). Cases with follow-up data (n=18) had similar bone marker levels at enrollment and 6 weeks. No significant differences in BAP or NTx levels at enrollment or follow-up were seen between cases with poor versus favorable outcomes. No differences in NTx or BAP levels were seen between cases and controls. Cases with follow-up data had similar levels at enrollment and 6 weeks. Lack of difference may be due to small sample size, small areas of bone involved in foot osteomyelitis, or limitations of these specific markers. More research is needed.


Class II restriction in mice to the malaria candidate vaccine ring infected erythrocyte surface antigen (RESA) as synthetic peptides or as expressed in recombinant vaccinia.
The immune response to three peptides corresponding to the repeat regions of the malaria candidate vaccine ring infected E surface Ag (RESA) were studied. Both antibody responses and lymphocyte stimulation in mice injected with these peptides without carrier were found to be restricted to certain MHC class II haplotypes. Mice bearing IAk were strong responders to all three peptides. Mice bearing IAd were strong responders only to the 3' repeat peptides, the octamer and tetramer. Mice bearing Is or Iq did not respond to any repeat peptides. Remarkably, the pattern of genetic restriction of the antibody response to the entire RESA as expressed in vaccinia indicated that there were no other epitopes besides the three repeats. Because only one class II haplotype (i.e., k) out of five tested responded strongly to this peptide and only two out of five (i.e., k and d) responded to the octamer or tetramer, it may be difficult to achieve a good immune response against RESA in most or all humans.


Immunosuppression Exposure and Risk of Infection-Related Acute Care Events in Patients With Glomerular Disease: An Observational Cohort Study.
Infections cause morbidity and mortality in patients with glomerular disease. The relative contributions from immunosuppression exposure and glomerular disease activity to infection risk are not well characterized. To address this unmet need, we characterized the relationship between time-varying combinations of immunosuppressant exposure and infection-related acute care events while controlling for disease activity, among individuals with glomerular disease. Prospective, multicenter, observational cohort study. Adults and children with biopsy-proven minimal change disease, focal segmental glomerulosclerosis, membranous nephropathy, or immunoglobulin A nephropathy/vasculitis were enrolled at 71 clinical sites in North America and Europe. A total of 2,388 Cure Glomerulonephropathy Network participants (36% aged <18 years) had at least 1 follow-up visit and were included in the analysis. Immunosuppression exposure modeled on a weekly basis. Infections leading to an emergency department visit or hospitalization. Marginal structural models were used to estimate the effect of time-varying immunosuppression exposure on hazard of first infection-related acute care event while accounting for baseline sociodemographic and clinical factors, and time-varying disease activity. A total of 2,388 participants were followed for a median of 3.2 years (interquartile range, 1.6-4.6), and 15% experienced at least 1 infection-related emergency department visit or hospitalization. Compared to no immunosuppression exposure, steroid exposure, steroid with any other immunosuppressant, and nonsteroid immunosuppressant exposure were associated with a 2.65-fold (95% CI, 1.83-3.86), 2.68-fold (95% CI, 1.95-3.68), and 1.7-fold (95% CI, 1.29-2.24) higher risk of first infection, respectively. Absence of medication dosing data, lack of a control group, and potential bias in ascertainment of outcome events secondary to the coronavirus 2 pandemic. Corticosteroids with or without concomitant additional immunosuppression significantly increased risk of infection leading to acute care utilization in adults and children with glomerular disease.


Bridging primary care practices and communities to promote healthy behaviors.
Primary care practices able to create linkages with community resources may be more successful at helping patients to make and sustain health behavior changes. Health behavior-change interventions in eight practice-based research networks were examined. Data were collected July 2005-October 2007. A comparative analysis of the data was conducted to identify and understand strategies used for linking primary care practices with community resources. Intervention practices developed three strategies to initiate and/or implement linkages with community resources: pre-identified resource options, referral guides, and people external to the practice who offered support and connection to resources. To initiate linkages, practices required the capacity to identify patients, make referrals, and know area resources. Linkage implementation could still be defeated if resources were not available, accessible, affordable, and perceived as valuable. Linkages were facilitated by boundary-spanning strategies that compensated for the lack of infrastructure between practices and resources, and by brokering strategies that identified interested community partners and aided mutually beneficial connections with them. Linkages were stronger when they incorporated practice or resource abilities to motivate the patient, such as brief counseling or postreferral outreach. Further, data suggested that sustaining linkages requires continuous attention and ongoing communication between practices and resources. Creating linkages between primary care practices and community resources has the potential to benefit both patients and clinicians and to lessen the burden on the U.S. healthcare system resulting from poor health behaviors. Infrastructure support and communication systems must be developed to foster sustainable linkages between practices and local resources.


The regional distribution of selenium in Greek cereals.
The selenium content of hard and soft wheat, barley, oats, rye and corn grown in approximately 100 different locations of Greece has been determined fluorimetrically. The mean values +/- SD for these cereal types were 0.29 +/- 0.19, 0.21 +/- 0.12, 0.16 +/- 0.10, 0.14 +/- 0.10, 0.19 +/- 0.10 and 0.12 +/- 0.08 ppm Se (dry weight basis), respectively. Based on data for selenium in corn from 96 different locations, a geobotanic map of Greece for the selenium in soil available for uptake by plants was prepared. Macedonia, West Epirus, south-east Thessaly, north-east Sterea Hellas and the Aegean Islands produce corn deficient or low in selenium, but only sporadic selenium-deficiency diseases in animals have been observed in many of these areas, probably because the farm animals are given mixed food or they are free to graze. No areas with toxic levels of selenium in soil were found.


Molecular techniques for detecting and typing of bacteria, advantages and application to foodborne pathogens isolated from ducks.
In recent times, several foodborne pathogens have become important and a threat to public health. Surveillance studies have provided data and a better understanding into the existence and spread of foodborne pathogens. The application of molecular techniques for detecting and typing of foodborne pathogens in surveillance studies provide reliable epidemiological data for tracing the source of human infections. A wide range of molecular techniques (including pulsed field gel electrophoresis, multilocus sequence typing, random amplified polymorphism deoxyribonucleic acid, repetitive extragenic palindromic, deoxyribonucleic acid sequencing, multiplex polymerase chain reaction and many more) have been used for detecting, speciating, typing, classifying and/or characterizing foodborne pathogens of great significance to humans. Farm animals including chickens, cattle, sheep, goats and pigs, and others (such as domestic and wild animals) have been reported to be primary reservoirs for foodborne pathogens. The consumption of contaminated poultry meats or products has been considered to be the leading source of human foodborne infections. Ducks like other farm animals are important source of foodborne pathogens and have been implicated in some human foodborne illnesses and deaths. Nonetheless, few studies have been conducted to explore the potential of ducks in causing foodborne outbreaks, diseases and its consequences. This review highlights some common molecular techniques, their advantages and those that have been applied to pathogens isolated from ducks and their related sources.


The influence of storage and leukocyte depletion on the antigen densities of FY1, FY2, MNS3 and MNS4 measured by flow cytometry.
Red blood cell (RBC) antigens may present changes in density during storage and leukocyte reduction. We evaluated the influence of these variables on FY1, FY2, MNS3 and MNS4 antigens using quantitative flow cytometry (FCM). Forty-eight RBC units were divided into two sub-units each immediately after collection. One of them was leukocyte reduced before storage. Antigen expression was analyzed on days 1 and 35 of storage by gel-centrifugation and FCM. Three RBC samples were submitted to papain and bromelin treatment. The gel-centrifugation test could not detect any influence of storage or leukocyte reduction. However, by FCM, a wide variation of antigen density among the donors was found. Leukocyte depletion did not change the antigen density but after storage, expression of FY1 and MNS4 showed a slight decrease. Median antigenic density of FY1 was 11,332 in FY1,2 and 23,436 in FY1,-2 donors. FY2 presented 7204 and 7868, respectively. MNS4 had 100,589 and 214,340 sites in donors MNS3,4 and MNS-3,4, respectively, and MNS3 had 10,389 and 21,122 sites, respectively. After enzyme treatments none of the antigens could be detected. FCM was a reproducible technique, suitable for the quantification of the antigens studied in RBC concentrates stored and leukocyte reduced in conditions normally used for blood transfusion.


Possible key role of granzyme B in keratoacanthoma regression.
It is still controversial whether keratoacanthoma is to be considered as a well differentiated variant of squamous cell-carcinoma or a separate entity. As opposed to malignant potential of squamous cell-carcinoma, keratoacanthoma is characterized by a spontaneous regression. However, in some cases, otherwise typical keratoacanthoma can behave aggressively showing the signs of perineural and perivascular invasion and metastases in regional lymph nodes. The most important feature that separates these two closely related entities is a tendency of keratoacanthoma to regress. Causes and detailed mechanism of this regression are still not completely elucidated. Within the past few years, it has become evident that the molecular events regulating cell survival and apoptosis are important contributors to the overall kinetics of benign and malignant cell growth. Immunological mechanisms have been implicated in a phenomenon of spontaneous tumor regression. Recent studies suggested that the tumor regression is dependent mainly on the immune response mediated by cytotoxic T lymphocytes (CD8+), together with helper T cells (CD4+). Cytotoxic T lymphocytes can kill tumor cells and mediate tumor regression in vivo through two distinct molecular mechanisms: Fas/Fas ligand and granzyme B/perforin mediated pathways. Tumor cells are capable of developing different escape mechanisms in order to overcome their sensitivity to apoptotic signals. However, granzyme B, contained in cytolytic granules released upon target cell recognition, can also cause tumor cell death and consequently tumor regression by direct damage to non-nuclear structures through a caspase-independent pathway. Therefore, we propose a key role of plasticity in the granzyme B mediated cell death pathway in the killing of changed tumor cells, resulting in keratoacanthoma regression through apoptosis or direct damage of tumor cells. On the other hand, insufficient activation of cytotoxic T lymphocytes and decreased release or activity of granzyme B could be responsible for squamous cell-carcinoma progression and occasional aggressive behavior in keratoacanthomas. As a first step in confirming or refuting our hypothesis, we suggest a thorough immunohistochemical study of the presence of granzyme B and its activity in keratoacanthoma and squamous cell-carcinoma samples. To our knowledge, no such study has been performed so far.


Melanoma cells can be eliminated by sialylated CD43 × CD3 bispecific T cell engager formats in vitro and in vivo.
Targeted cancer therapy with monoclonal antibodies has proven successful for different cancer types but is limited by the availability of suitable antibody targets. CD43s, a unique sialylated form of CD43 expressed by hematologic malignancies, is a recently identified target and antibodies interacting with CD43s may have therapeutic potential against acute myeloid leukemia (AML) and myelodysplastic syndrome. CD43s is recognized by the human antibody AT1413, that was derived from a high-risk AML patient who successfully cleared leukemia after allogeneic stem cell transplantation. Here we observed that AT1413 binds also to certain non-hematopoietic tumor cells, particularly melanoma and breast cancer. AT1413 immune precipitated CD43s from melanoma cells confirming that it recognizes the same target on melanoma as on AML. AT1413 induced antibody-dependent cellular cytotoxicity against short-term cultured patient-derived melanoma samples. However, AT1413 was unable to affect the growth of melanoma cells in vivo. To increase the efficacy of AT1413 as a therapeutic antibody, we generated two different formats of bispecific T-cell engaging antibodies (TCEs): one binding bivalently (bTCE) and the other monovalently (knob-in-hole; KiH) to both CD43s and CD3ε. In vitro, these TCEs redirected T-cell cytotoxicity against melanoma cells with differences in potencies. To investigate their effects in vivo, we grafted mice that harbor a human immune system with the melanoma cell line A375. Treatment with both AT1413 bTCE and AT1413 KiH significantly reduced tumor outgrowth in these mice. These data indicate a broad therapeutic potential of AT1413 that includes AML and CD43s-expressing solid tumors that originate from CD43-negative tissues.


Fortification of polysaccharide-based packaging films and coatings with essential oils: A review of their preparation and use in meat preservation.
As the demand for botanical food additives and eco-friendly food packaging materials grows, the use of essential oils, edible biodegradable films and coatings are becoming more popular in packaging. In this review, we discussed the recent research trends in the use of natural essential oils, as well as polysaccharide-based coatings and films: from the composition of the substrates to preparing formulations for the production of film-forming technologies. Our review emphasized the functional properties of polysaccharide-based edible films that contain plant essential oils. The interactions between essential oils and other ingredients in edible films and coatings including polysaccharides, lipids, and proteins were discussed along with effects on film physical properties, essential oil release, their active role in meat preservation. We presented the opportunities and challenges related to edible films and coatings including essential oils to increase their industrial value and inform the development of edible biodegradable packaging, bio-based functional materials, and innovative food preservation technologies.


Recent developments in bioreactor scale production of bacterial polyhydroxyalkanoates.
Polyhydroxyalkanoates (PHAs) are biological plastics that are sustainable alternative to synthetic ones. Numerous microorganisms have been identified as PHAs producers. They store PHAs as cellular inclusions to use as an energy source backup. They can be produced in shake flasks and in bioreactors under defined fermentation and physiological culture conditions using suitable nutrients. Their production at bioreactor scale depends on various factors such as carbon source, nutrients supply, temperature, dissolved oxygen level, pH, and production modes. Once produced, PHAs find diverse applications in multiple fields of science and technology particularly in the medical sector. The present review covers some recent developments in sustainable bioreactor scale production of PHAs and identifies some areas in which future research in this field might be focused.


Pre-linguistic social communication skills and post implant language outcomes in deaf children with cochlear implants.
This study investigates the relationship between pre-linguistic social communication skills and age of cochlear implant for future language outcomes in a large sample of deaf children. A retrospective cohort study of records from 75 children. Pre-implant data included Age at Implant, pre-linguistic communication (social, symbolic and speech) skills, and non-verbal ability. Receptive and expressive language development data at 1 year, 2 years and 4 years post implant were analysed to investigate the relationships between pre-implant factors and language outcomes, in particular pre-linguistic social communication skills in early and late implanted children. Age at Implant was the strongest correlate of post implant expressive and receptive language outcomes. The sample was divided into early implanted (<18 month) and late implanted (>18 months) children. In the early implanted group, pre-linguistic social communication skills were the strongest pre-implant correlate of language outcomes four years post-implant. In the late implanted group, there were no significant pre-implant correlates of language outcomes. Long term language outcomes after cochlear implantation are the product of a set of communicative, cognitive and environmental factors. Early pre-implant social communication skills are an important consideration for clinicians who guide parents as to likely long-term outcomes post cochlear implantation. Social communication skills are particularly important for children who receive implants before the age of 18 months.


Prevention of anastomotic stricture with a purse-string suture technique on the gastric side during esophageal carcinoma operations: retrospective study of 463 consecutive cases.
The objective of this study was to investigate the effect of a gastric side purse-string technique on anastomotic strictures during esophageal carcinoma operations. From 1996 to 2005, esophageal carcinoma operations were performed on 1128 consecutive patients. Among them, 463 underwent esophagogastric anastomosis with purse-string sutures on the gastric side (purse group) and the other 665 did not (nonpurse group). Anastomotic strictures, reflux, and leakage were analyzed and compared between the two groups after the operations. Complete follow-up was conducted on all 1128 patients within 6 months after the operation. In contrast to the nonpurse group with a postoperative anastomotic stricture rate of 5.4% (36/665), the purse group demonstrated a significantly lower rate (0.2%, 1/463). The occurrence rates of anastomotic leakage in the nonpurse and purse groups were 0.9% (6/665) and 0.4% (2/463), respectively. Of the 17 cases of gastroesophageal reflux, 15 (15/665, 1.8%) were found in the nonpurse group and 2 (2/463, 1.1%) in the purse group. Thus, a purse-string suture technique on the gastric side might be an effective method for preventing the occurrence of anastomotic strictures after esophageal resection.


[Effect of removal of superior spermatic nerve on spermatogenesis].
To evaluate the role of superior spermatic nerve in the regulation of spermatogenesis. Mature SD rats (350-375 g) received bilateral surgical removal of the superior spermatic nerve(SSN). The animals were killed 1 and 2 months after operation and were studied in comparison with the SD rats of the sham operation group. H. E. staining was employed in observing spermatogenesis, and transmission electron microscopy and terminal deoxynuleotidyl tansferase-mediated dUTP nick end-labeling (TUNEL) were used to detect apoptosis. No pathological changes were observed 1 month after operation. Two months after SSN denervation, spermatogenesis arrest was seen in the seminiferous tubules in which only Sertoli cells or Sertoli cells and a few spermatogonia remained. Chromosome condensation and breakage in germ cells were observed under transmission electron microscope in denervated testes. TUNEL showed that SSN denervation induced apoptosis of spermatogonia and Leydig cells significantly. The superior spermatic nerve seems to be involved in the regulation of spermatogenesis. Further study is worth doing to clarify the possible mechanism of action.


[Molecular characterization of thalassemias in the Valencia community and its relationship with the hematological phenotype].
The aim of the study is to present the first results of molecular characterization of thalassaemias in Valencian Community and their relationship with the haematological parameters. The study includes 87 thalassemic patients: 30 alpha-thalassaemias, 40 beta-thalassaemias and 17 delta beta-thalassaemias. The molecular alterations were studied in white cell blood DNA, either following different PCR methods or by testing the digestion of the amplified PCR products with selective restriction enzymes. The molecular characterization of beta-thalassaemias was achieved in 94% of the subjects, being the transition C-->T in CD-39 the most frequent (44%) of the mutations studied. 94% of the delta beta-thalassaemias studied corresponded to the delta beta-Spanish type. All the alpha thalassaemias characterized (64%) corresponded to the -alpha 3.7 deletion. The reamining 36% were negative for the alpha 0 deletions --MED, --20.5, or the non deletional mutations Hph I and NocI. In the Valencian Community, like what has been described for the beta-thalassaemias in other Mediterranean regions of Spain (Barcelona, Granada and Mallorca), a high incidence in C-->T transition in CD-39 was observed, in contrast with central and south-western regions of Spain, where the G-->A IVS-I-1 is the most frequent mutation. Our study supports that the IVS-I-6 mutations is the one with lower repercussions on the haematological parameters. Our study confirms the Spanish type of delta beta-thalassaemia as the most frequent in the Valencian Community, and that the 3.7 kb alpha deletion is the most frequent mutation for the alpha-thalassaemia, although alpha thalassaemia is also the poorly characterized form of thalassaemia.


The effects of the stress response on immune function in invertebrates: an evolutionary perspective on an ancient connection.
Stress-induced changes in immune function occur in animals across phyla, and these effects are usually immunosuppressive. The function of this immunomodulation remains elusive; however, the existence of specialized receptors on immune cells suggests that it is adaptive. A comparative approach may provide a useful perspective. Although invertebrates have simpler endocrine/neuroendocrine systems and immune systems than vertebrates, they have robust stress responses that include the release of stress hormones/neurohormones. Stress hormones modify immune function in mollusks, insects, and crustaceans. As in vertebrates, the effects of stress hormones/neurohormones on invertebrate immune function are complex, and are not always immunosuppressive. They are context-, stressor-, time- and concentration-dependent. Stress hormone effects on invertebrate immune function may help to re-align resources during fight-or-flight behavior. The data are consistent with the hypothesis that stress hormones induce a reconfiguration of networks at molecular, cellular and physiological levels that allow the animal to maintain optimal immunity as the internal environment changes. This reconfiguration enhances some immune functions while suppressing others. Knowing the molecular details of these shifts will be critical for understanding the adaptive function of stress hormones on immune function.


Comparing prognostic factors of Glut-1 expression and maximum standardized uptake value by FDG-PET in patients with resectable pancreatic cancer.
This study aimed to assess the prognostic values of preoperative maximum standardized uptake value (SUVmax) of primary pancreatic tumors and Glut-1 expression in patients with resectable pancreatic ductal adenocarcinoma (R-PDAC), and to investigate whether Glut-1 expression is more effective than SUVmax in predicting survival in patients with R-PDAC. We investigated 101 R-PDAC patients who underwent pancreatectomy for pancreatic cancer treatment. SUVmax analyzed through 18F-fluoro-2-deoxyglucose positron emission tomography/computed tomography (18F-FDG-PET/CT), and Glut-1 expression, were assessed for predicting the prognosis of patients with R-PDAC. In patients with R-PDAC, the high SUVmax group (≥4.25) had significantly shorter overall survival (OS) and disease-free survival (DFS) than the low SUVmax group (<4.25). Surprisingly, Glut-1 expression was not significantly correlated with SUVmax. Moreover, the high Glut-1 expression group, which was related to higher levels of CA 19-9, had significantly shorter OS and DFS than the low Glut-1 expression group. Furthermore, among the high SUVmax group, OS and DFS were significantly shorter in the high Glut-1 expression group. Multivariate analyses revealed that Glut-1 overexpression was an independent prognostic factor in patients with R-PDAC. Glut-1 knockdown also induced cell cycle arrest in PDAC cells in vitro. The study determined that Glut-1 overexpression is a more powerful prognostic factor than SUVmax for predicting OS and higher risk of recurrence in R-PDAC patients. Glut-1 overexpression is also more likely to be associated with malignant activity in PDAC patients.


SILVA tree viewer: interactive web browsing of the SILVA phylogenetic guide trees.
Phylogenetic trees are an important tool to study the evolutionary relationships among organisms. The huge amount of available taxa poses difficulties in their interactive visualization. This hampers the interaction with the users to provide feedback for the further improvement of the taxonomic framework. The SILVA Tree Viewer is a web application designed for visualizing large phylogenetic trees without requiring the download of any software tool or data files. The SILVA Tree Viewer is based on Web Geographic Information Systems (Web-GIS) technology with a PostgreSQL backend. It enables zoom and pan functionalities similar to Google Maps. The SILVA Tree Viewer enables access to two phylogenetic (guide) trees provided by the SILVA database: the SSU Ref NR99 inferred from high-quality, full-length small subunit sequences, clustered at 99% sequence identity and the LSU Ref inferred from high-quality, full-length large subunit sequences. The Tree Viewer provides tree navigation, search and browse tools as well as an interactive feedback system to collect any kinds of requests ranging from taxonomy to data curation and improving the tool itself.


Performance study on touch-pens size in three screen tasks.
Experiments were aimed at investigating the performance of various sizes of touch-pens. The touch-pens were of three different lengths (80, 110 and 140 mm) and four different diameters (5.5, 8, 11 and 15 mm). Three screen tasks were used for determining a reference of ideal dimensions of a pen-based product. Sixteen subjects used 12 touch-pens to perform pointing-and-clicking, writing and drawing tasks. The subjects were asked to rank their preference after each task in the test. The results showed that the length of touch-pens should be designed to extend beyond the handbreadth when gripped. A touch-pen that facilitates natural pointing-and-clicking, writing and drawing tasks each requires a suitable diameter size. However, these tasks are typically performed together, in particular, the pointing-and-clicking and writing tasks. The recommended diameter for all three combined tasks is 8 mm. This finding indicates that selecting a touch-pen with a diameter of 8 mm and a length of 100 mm or longer is suitable for all pen-based devices.


Detection of 10 variants of biliverdin reductase in rat liver by two-dimensional gel electrophoresis.
We have identified and characterized multiple forms of biliverdin reductase (BVR) in control rat liver cytosol. Two-dimensional electrophoresis of the purified BVR resolved a minimum of 10 discrete protein zones. All 10 proteins were BVR as judged by immunological cross-reactivity toward rabbit anti-rat BVR. Based on the isoelectric focusing pattern of separation, the BVR variants could be organized into five net-charge groups designated as BVR-IEF1 to BVR-IEF5 and three molecular mass groups designated as BVR-MW1-BVR-MW3, respectively. The pI values of the net-charge groups were: BVR-IEF1, 6.23; IEF2, 5.91; IEF3, 5.76; IEF4, 5.61; IEF5, 5.48. The Mr values of the molecular mass groups were: BVR-MW1, 30,400; MW2, 30,700; MW3, 31,400. Single dimension slab gel isoelectric focusing offered greater resolution of the net charge variants, and BVR-IEF3 was further resolved into two variants, IEF3a and IEF3b, with pIs of 5.77 and 5.75, respectively. The six net-charge variants also resolved on a preparative chromatofocusing column and were designated as BVR-CF1-BVR-CF6. The pH values of the peak fractions were: BVR-CF1, 6.91; CF2, 6.33; CF3, 6.03; CF4, 5.82; CF5, 5.45; CF6, 5.27. Correspondence between the isoelectric focusing net-charge variants and the chromatofocusing net-charge variants was established. The Mr and net-charge variants did not represent partially degraded forms of biliverdin reductase produced during purification since the pattern of resolution of variants on slab gel isoelectric focusing or two-dimensional electrophoresis did not change by purifying the proteins in the presence of protease inhibitors and 5 mM EDTA. BVR-CF2 and BVR-CF4 were purified and examined for pH-dependent cofactor requirements for activity. Both net-charge variants and two pH optima that were cofactor-dependent; maximum activity with NADPH, however, was at pH 8.5 and with NADH at pH 6.7. With both variants, however, a higher catalytic rate was observed with NADH than with NADPH at their respective pH optima. Furthermore, BVR-CF2 exhibited a higher catalytic rate than did BVR-CF4 with either cofactor throughout the pH range of 5-9.


Professional accountability and industrial action: contradictory or compatible?
The decision of the RCN to jettison its rule forbidding industrial action has generated a great deal of debate, much of which is fairly ill-informed. This article examines the industrial action issue against the background of the UKCC's Code of Professional Conduct, explores the arguments for and against and draws some conclusions.


Distribution of arginine-vasopressin and vasoactive intestinal peptide messenger RNA in the suprachiasmatic nucleus of the sheep.
The distribution of mRNAs for vasoactive intestinal peptide (VIP) and arginine-vasopressin (VP) was studied in the hypothalamus of the sheep by in situ hybridization. VIP mRNA was detected in the supraoptic nucleus (SON) and in the median part of the suprachiasmatic nucleus (SCN). VP mRNA was observed in the magnocellular system of the hypothalamus and in the dorso-lateral part of the SCN. These results confirm that the SCN is a site of synthesis of both peptides. Therefore, VIP and VP may be involved in diverse physiological functions including the functioning of the biological clock constituted by the SCN.


Gene therapy: Myth or reality?
Gene therapy has become a reality, although still a fragile one. Clinical benefit has been achieved over the last 17years in a limited number of medical conditions for which pathophysiological studies determined that they were favorable settings. They include inherited disorders of the immune system, leukodystrophies, possibly hemoglobinopathies, hemophilia B, and retinal dystrophies. Advances in the treatment of B-cell leukemias and lymphomas have also been achieved. Advances in vector development and possible usage of gene editing may lead to significant advances over the next years.


The use of RT-PCR in the diagnosis and differentiation of vaccine strains of chicken infectious bronchitis and Newcastle disease.
Infectious diseases of young and adult birds with respiratory syndrome are a significant deterrent to the development of industrial poultry farming due to decreased productivity and significant mortality. The only effective method of combating viral diseases is timely and targeted vaccination, which largely depends on laboratory diagnostic results. This article aims to study the real-time reverse transcription polymerase chain reaction, (RT-PCR) which has the prospect of more effective diagnosis of vaccine strains of chicken infectious bronchitis and Newcastle disease. The fastest and most accurate method for the differential diagnosis of pathogens in an associative viral infection is RT-PCR. The method proposed in the article for selecting primers for amplification made it possible to use this method for the simultaneous interspecies differential diagnosis of two or more viral agents, significantly accelerating their diagnosis. The correlation of the nucleotide sequence obtained from sequencing to a specific virus strain is complicated by the lack of a single nomenclature mechanism for separating genetic groups. The results of this study will allow easy and fast typing of sequences into known and databased virus strains and avoid further confusion in the nomenclature of genetic groups in the future.


Body fat measurement in adolescents: comparison of skinfold thickness equations with dual-energy X-ray absorptiometry.
To compare the most commonly used equations to predict body fatness from skinfold thickness, in male and female adolescents, with dual-energy X-ray absorptiometry (DXA) as a reference method of fatness measurement. Cross-sectional nutrition survey. General adolescent population from Zaragoza (Spain). A total of 238 Caucasian adolescents (167 females and 113 males), aged 13.0-17.9 y, were recruited from 15 school groups in 11 public and private schools. The percentage fat mass (%FM) was calculated by using skinfold-thickness equations. Predicted %FM was compared with the reference %FM values, measured by DXA. The lack of agreement between methods was assessed by calculating the bias and its 95% limits of agreement. Most equations did not demonstrate good agreement compared with DXA. However, in male adolescents, Slaughter et al equations showed relative biases that were not dependent on body fatness and the limits of agreement were narrower than those obtained from the rest of equations. In females, Brook's equation showed nonsignificant differences against DXA and the narrowest 95% limits of agreement. Only biases from Brook and Slaughter et al equations were not dependent on body fatness in female adolescents. Accuracy of most of the skinfold-thickness equations for assessment of %FM in adolescents was poor at the individual level. Nevertheless, to predict %FM when a relative index of fatness is required in field or clinical studies, Slaughter et al equations may be used in adolescents from both sexes and the Brook equation in female adolescents.


Angiolipoma of the neck: a case report.
Angiolipomas of the neck are extremely rare; to our knowledge, only 2 cases have been previously reported. We report a new case, which occurred in a 28-year-old woman. The mass was totally resected, and the patient showed no recurrence at the 18-month follow-up.


Imaging how thermal capillary waves and anisotropic interfacial stiffness shape nanoparticle supracrystals.
Development of the surface morphology and shape of crystalline nanostructures governs the functionality of various materials, ranging from phonon transport to biocompatibility. However, the kinetic pathways, following which such development occurs, have been largely unexplored due to the lack of real-space imaging at single particle resolution. Here, we use colloidal nanoparticles assembling into supracrystals as a model system, and pinpoint the key role of surface fluctuation in shaping supracrystals. Utilizing liquid-phase transmission electron microscopy, we map the spatiotemporal surface profiles of supracrystals, which follow a capillary wave theory. Based on this theory, we measure otherwise elusive interfacial properties such as interfacial stiffness and mobility, the former of which demonstrates a remarkable dependence on the exposed facet of the supracrystal. The facet of lower surface energy is favored, consistent with the Wulff construction rule. Our imaging-analysis framework can be applicable to other phenomena, such as electrodeposition, nucleation, and membrane deformation.


Definition of subchromosomal intervals around the myotonic dystrophy gene region at 19q.
The localization to 19q of the gene causing myotonic dystrophy (DM) has been defined more precisely by refinement of the physical location of several linked markers. A somatic cell hybrid mapping panel from cells with t(1;19), t(12;19), and t(X;19) translocation products was constructed to define five different intervals across 19q. In addition, we have derived a series of cell hybrids by irradiation of a der(19)-only hybrid to further subdivide the cen-q13.1 region. Using an array of 36 cloned genes, anonymous DNAs, and enzyme markers, we have tested the location of the panel breakpoints and refined the regional assignment of several of these markers. All markers tightly linked to DM are localized mainly within 19q13.2, thus suggesting that the DM gene is also close to this region.


Molecular interaction between methicillin-resistant Staphylococcus aureus (MRSA) and chicken breast reveals enhancement of pathogenesis and toxicity for food-borne outbreak.
To study pathogenesis and toxicity of Staphylococcus aureus in foods, FORC_062 was isolated from a human blood sample and complete genome sequence has a type II SCCmec gene cluster and a type II toxin-antitoxin system, indicating an MRSA strain. Its mobile gene elements has many pathogenic genes involved in host infection, biofilm formation, and various enterotoxin and hemolysin genes. Clinical MRSA is often found in animal foods and ingestion of MRSA-contaminated foods causes human infection. Therefore, it is very important to understand the role of contaminated foods. To elucidate the interaction between clinical MRSA FORC_062 and raw chicken breast, transcriptome analysis was conducted, showing that gene expressions of amino acid biosynthesis and metabolism were specifically down-regulated, suggesting that the strain may import and utilize amino acids from the chicken breast, but not able to synthesize them. However, toxin gene expressions were up-regulated, suggesting that human infection of S. aureus via contaminated food may be more fatal. In addition, the contaminated foods enhance multiple-antibiotic resistance activities and virulence factors in this clinical MRSA. Consequently, MRSA-contaminated food may play a role as a nutritional reservoir as well as in enhancing factor for pathogenesis and toxicity of clinical MRSA for severe food-borne outbreaks.


Neurulation in the mouse. I. The ontogenesis of neural segments and the determination of topographical regions in a central nervous system.
Ontogenesis of neural segments and positional relationships between the segments and other organs during neurulation were studied in 1,423 ICR mouse embryos by binocular dissecting, light, and scanning electron microscopy. Late in the presomite stage, two transverse sulci, preotic and otic, were seen on the prospective luminal surface of the neural folds. By somite stage 19, the former subdivided into five neuromeres, and by somite stage 21, the latter subdivided into four neuromeres. From the rostral, preotic sulcus, moreover, five other neuromeres were formed by somite stage 20, and between the otic sulcus and the first somite, two neuromeres were formed by somite stage 28. In the caudal part, from the level of the first somite, a total of 39 neuromeres were formed one after another by somite stage 39, and their positions almost correlated with each corresponding somite. Furthermore, the isthmus grew in the boundary between the fifth and sixth neuromere. The most protruding zone in the preotic sulcus formed the eighth neuromere and was located adjacent to the first branchial arch and the trigeminal ganglion. The most protruding zone in the otic sulcus also formed the 11th neuromere and was located adjacent to the second branchial arch. The 12th and 13th neuromeres were situated adjacent to the otic vesicle; the 23rd to 28th neuromeres, adjacent to the forelimb bud; and the 40th to 46th neuromeres, adjacent to the hindlimb bud.


The causal association between iron status and the risk of autism: A Mendelian randomization study.
Emerging evidence indicates a connection between serum iron levels and autism, but the underlying causal association is yet unclear. Thus, we performed two-sample Mendelian randomization (MR) analysis to evaluate the causal link between iron status on autism, using genetic instruments (p < 5E-08) strongly associated with iron status (N = 48,972), including serum iron, ferritin, transferrin levels, and transferrin saturation. Summary statistics of autism was obtained from two independent studies conducted by Psychiatric Genomics Consortium (PGC, Ncases = 5,305, Ncontrols = 5,305) and FinnGen Consortium (FC, Round six, Ncases = 344, Ncontrols = 258,095), respectively. Using the inverse-variance weighted (IVW) method, the combined results of PGC and FC demonstrated that genetically determined serum transferrin level was significantly associated with an increased risk of autism [odds ratio (OR) = 1.16, 95% CI: 1.03-1.30, p = 0.013]. There was no significant causal effect of serum iron (OR = 0.99, 95% CI: 0.72-1.37, p = 0.951), ferritin (OR = 0.88, 95% CI: 0.47-1.64, p = 0.676), and transferrin saturation (OR = 0.89, 95% CI: 0.72-1.09, p = 0.252) on autism. No obvious pleiotropy was found in this MR study. Taken together, our findings highlight that elevation of serum transferrin level might be associated with a high risk of autism, suggesting a potential role of iron deficiency in autism development. Future studies are warranted to clarify the underlying mechanism, which will pave a new path for the prevention and treatment of autism.


Thermodynamic parameters of the interaction between Co(II) bovine carbonic anhydrase and anionic inhibitors.
The pH dependence of the apparent affinity constants of perchlorate for cobalt(II)bovine carbonic anhydrase II has been measured by electronic absorption spectroscopy. The obtained data have been analyzed in terms of the ionization of two acidic groups of CoBCAII, and the affinity of perchlorate for the two water-containing species of the enzyme have been estimated. Furthermore, the affinity constants of nitrate, perchlorate, and azide for CoBCAII in the temperature range 5 degrees C-30 degrees C have been determined by spectrophotometric titrations at pH 7. The affinity constants for these ligands decrease with increasing temperatures. The temperature dependence of binding was used to estimate the enthalpy and entropy parameters for the formation of the corresponding 1:1 adducts. The obtained results indicate that binding of these anions to the cobalt enzyme is an enthalpy driven process which is opposed by a moderate entropy change.


Potential of Curcumin nanoemulsion as antimicrobial and wound healing agent in burn wound infection.
The review article concentrates on the potential uses of curcumin nanoemulsion in treatment and management of burn wound. Poor solubility and low bioavailability of curcumin limits the efficient and effective use of curcumin in management of bacterial infection related to burn wound. Nano particle based drug delivery system can be of great aid to solve this problem. Among this nanoemulsion is most favourable system due to its simplicity and low manufacturing cost. Nanoemulsion also enhances the skin permeation ability of curcumin and thus enhances its pharmacological efficacy specially as a potential antimicrobial agent, which can have applicability as a topical therapeutic agent in burn wound infection.


Neurotoxicity of phenylalanine on human iPSC-derived cerebral organoids.
Phenylketonuria (PKU) is a common genetic metabolic disorder that causes phenylalanine accumulation in the blood. The most serious symptoms are related to the brain, as intellectual disability, seizure, and microcephaly are commonly found in poorly treated PKU patients and the babies of maternal PKU. However, the mechanism of hyperphenylalaninemia on human neurodevelopment is still unclear. Here we utilized human induced pluripotent stem cell (iPSC)-derived cerebral organoids to investigate the neurotoxicity of hyperphenylalaninemia. Cerebral organoids at days 40 or 100 were treated with different concentrations of phenylalanine for 5 days. After phenylalanine treatments, the cerebral organoids displayed alterations in organoid size, induction of apoptosis, and depletion of neural progenitor cells. However, phenylalanine did not have an impact on neurons and glia, including astrocytes, immature oligodendrocytes, and mature oligodendrocytes. Remarkably, a reduction in the thickness of the cortical rosettes and a decrease in myelination at the intermediate zone were inspected with the elevated phenylalanine concentrations. RNA-seq of phenylalanine-treated organoids revealed that gene sets related to apoptosis, p53 signaling pathway, and TNF signaling pathway via NF-kB were enriched in upregulated genes, while those related to cell cycle and amino acid metabolism were enriched in downregulated genes. In addition, there were several microcephaly disease genes, such as ASPM, LMNB1, and CENPE, ranked at the top of the downregulated genes. These findings indicate that phenylalanine exposure may contribute to microcephaly, abnormal cortical expansion, and myelination lesions in the developing human brain.


Matrix metalloproteinases and tissue inhibitors of metalloproteinases in hamster aortic atherosclerosis: correlation with in-situ zymography.
Atherogenesis requires extracellular matrix (ECM) alterations, a process possibly mediated by matrix-degrading metalloproteinases (MMPs) and their endogenous tissue inhibitors (TIMPs). The objective of this study was to examine the immunohistochemical expression patterns of MMPs-1, -2, -3 and -9 and their tissue inhibitors, TIMPs-1, -2, -3 and -4 during the three major stages of atherosclerotic lesion development in hypercholesterolemic Syrian Golden hamsters. Aortic atherosclerotic lesions (fatty streak, fibro-fatty and advanced) were histologically characterized in treated hamsters at 12, 24, and 49 weeks. The immunochemistry expression of these MMPs and TIMPs were examined in treated aortic sections with lesions and control aortic sections without lesions. MMP activity in control aortas and atherosclerotic lesions was characterized by in-situ zymography. Positive immunoreactivity for MMPs-2, -3, -9 and TIMPs-1, -2,-3, and -4 was observed in both control and atherosclerotic aortic arch segments, while MMP-1 was only observed in atherosclerotic lesions. Using in-situ zymography, we identified casein and gelatin degradation in fatty streak, fibro-fatty and advanced lesions. The immunohistochemical expression of these MMPs and TIMPs were examined in treated aortic sections with lesions and control aortic sections without lesions. In all lesion stages, substrate degradation was inhibited with 1,10-phenanthroline. Degradation of these substrates was not observed in control aortas. In addition, substrate degradation was inhibited with 1,10-phenanthroline. These findings suggested that in control segments, the net proteolytic balance was shifted in favor of MMP inhibition. Alternatively, despite the colocalization of MMPs and TIMPs in the treated segments, net proteolytic balance favored the catalytic MMPs.


The clinical application value of salivary pepsin in the diagnosis of gastroesophageal reflux diseases.
Peptest is a noninvasive and convenient diagnostic kit for gastroesophageal reflux disease (GERD). We aimed to explore the application value of Peptest in the diagnosis of GERD. Patients suspected of GERD all completed 24 h pH-impedance monitoring (24 h MII-pH) and then took proton pump inhibitor (PPI) 2 weeks. The postprandial, post-symptom and random salivary samples were taken. Receiver operating characteristic analysis was used to identify the best cutoff value of Peptest, to differentiate GERD patients from non-GERD patients and the optimal sampling time of Peptest was analyzed. Reflux characteristics and esophageal motility between Peptest (+) group and Peptest (-) group were compared in negative 24 h MII-pH patients. Peptest concentration were compared among non-reflux, distal reflux, and proximal reflux groups according to 24 h MII-pH curve. The area under the curve of post-symptom Peptest was highest in three time points and the diagnostic specificity was 81.0% and sensitivity was 53.3% with the diagnostic value of 86 ng/mL. Compared with negative Peptest group, distal mean nocturnal baseline impedance was significantly lower, gastroesophageal junction contractile integral was substantially lower in positive Peptest group in negative 24 h MII-pH patients. The concentration of post-symptom and postprandial Peptest increased gradually in the non-reflux, distal reflux, and proximal reflux groups. Peptest has a relatively low diagnostic value for GERD. Post-symptom Peptset is the best sampling time with the optimal value of 86 ng/mL and may have auxiliary diagnostic value for negative 24 h MII-pH patients. Peptest may assist 24 h MII-pH in monitoring proximal reflux.


Persistence and Adherence of Anticholinergics and Beta-3 Agonist for the Treatment of Overactive Bladder: Systematic Review and Meta-Analysis, and Network Meta-Analysis.
We aimed to investigate the persistence and adherence rate of overactive bladder medications and factors that affect these rates. We conducted electronic English-language literature searches of the PubMed®, Cochrane Library, and EMBASE® databases from the earliest available date of indexing through May 21, 2019 using the Medical Subject Headings (MeSH) terms and EMBASE subject headings (Emtree). Primary measurement outcomes were overall persistence and adherence rate at 6, 12, 24, and 36 months in anticholinergics and mirabegron. Secondary outcomes were individual effect of each medication on persistence and adherence rate at 12 months, and moderating factors affecting the overall persistence and adherence rate at 12 months. Pooled overall persistence rate at 12 months of overactive bladder medications of anticholinergics and mirabegron was 0.218 (95% CI: 0.197-0.240). The pooled overall persistence rate at 12 months was 0.402 (95% CI: 0.277-0.528) in mirabegron, 0.249 (95% CI: 0.182-0.316) in solifenacin, and 0.220 (95% CI: 0.078-0.361) in fesoterodine. Overall adherence rate of overactive bladder medications of anticholinergics and mirabegron was 0.589 (95% CI: 0.507-0.670). The pooled overall adherence rate at 12 months was 0.654 (95% CI: 0.528-0.781) in mirabegron, 0.784 (95% CI: 0.588-0.980) in solifenacin, 0.782 (95% CI: 0.652-0.911) in fesoterodine, and 0.679 (95% CI: 0.651-0.707) in imidafenacin. Persistence and adherence rates were associated with age, gender, anticholinergic exposure history, type of medication, study type, and study year. Persistence and adherence rates were lower than previously reported and were associated with certain clinical and demographic factors.


Synthesis of asymmetric 1,4-disubstituted piperazines and their psychotropic and cardiovascular actions. Part I.
New asymmetric piperazines 1-6 were obtained by condensation of 1-acylpiperazines with 1,2-epoxy-3-chloropropane, 1,2-epoxypropane, arylacid chlorides and secondary amines. The compounds displayed a biological activity: they depressed the central nervous system, altered the blood pressure, and one of them increased the coronary flow.


Draft Genome Sequences of Five Diverse Klebsiella Species Isolates from Intensive Care Unit Patients.
We have examined the draft genomes of five isolates from two different Klebsiella species obtained from intensive care unit patients at two geographically distributed hospitals to examine the genomic diversity of hospital-acquired organisms in this understudied population.


Sodium oxalate corrects calcium interference in Lowry protein assay.
We have previously noted that high levels (10 mM) of calcium interfere with protein determination in the Lowry assay. While there are numerous reports in the literature of substances interfering with the Lowry assay, none of these interfering substances are as ubiquitous as calcium. We hypothesized that physiologic levels of calcium may interfere with the protein determination as measured by the Lowry assay. To test this hypothesis, bovine serum albumin standards from 12.5 to 1600 micrograms/ml were tested in the Lowry assay in the presence of calcium chloride concentrations from 0 to 5 mM. In low protein concentrations (12.5-50 micrograms/ml) 1 to 2 mM calcium induced errors of up to 384%. In samples containing 100 to 400 micrograms/ml protein, 1 to 2 mM calcium induced errors of up to 40%. The addition of sodium oxalate to calcium-spiked protein samples significantly reduced the errors in protein determination at all calcium concentrations tested. This effect also is seen throughout the range of protein concentrations tested (50-1600 micrograms/ml). In most cases sodium oxalate pretreatment of samples used in the Lowry assay reduces errors by 70-95%. Physiologic levels of calcium induce significant errors in the estimation of protein concentration using the Lowry method. Routine pretreatment of Lowry samples with sodium oxalate will provide a more accurate estimation of the protein concentration in biological systems.


Tool Use for Early Detection of Cerebral Palsy: A Survey of Spanish Pediatric Physical Therapists.
The purpose of this study was to assess the use of diagnostic assessment tools in pediatric physical therapy practice in Spain. Best practice recommendations indicate the timely use of key assessment tools to reduce the age of diagnosis of cerebral palsy (CP). Pediatric physical therapists currently working in Spain in early intervention were recruited through targeted physical therapy entities. They were invited to complete the purpose-developed electronic survey, consisting of 45 multiple-choice questions, with 5 thematic blocks. Results from 140 anonymous respondents were analyzed. The average reported age when CP was suspected was 12.6 months. Most used the child's clinical history (88.1%), the Alberta Infant Motor Scale (41.3%), and Vojta Assessment Procedure (32.1%) to assess and detect CP. General Movements Assessment (25.7%) and Hammersmith Infant Neurological Examination (28.4%) were used infrequently. Currently, pediatric physical therapists in Spain rely on clinical history and outdated tools to identify children with CP.Digital Abstract available at: http://links.lww.com/PPT/A361 (English).Digital Abstract available at: http://links.lww.com/PPT/A362 (Spanish).


Lateral preoptic area glutamate neurons relay nociceptive information to the ventral tegmental area.
The ventral tegmental area (VTA) has been proposed to play a role in pain, but the brain structures modulating VTA activity in response to nociceptive stimuli remain unclear. Here, we demonstrate that the lateral preoptic area (LPO) glutamate neurons relay nociceptive information to the VTA. These LPO glutamatergic neurons synapsing on VTA neurons respond to nociceptive stimulation and conditioned stimuli predicting nociceptive stimulation and also mediate aversion. In contrast, LPO GABA neurons synapsing in the VTA mediate reward. By ultrastructural quantitative synaptic analysis, ex vivo electrophysiology, and functional neuroanatomy we identify a complex circuitry between LPO glutamatergic and GABAergic neurons and VTA dopaminergic, GABAergic, and glutamatergic neurons. We conclude that LPO glutamatergic neurons play a causal role in the processing of nociceptive stimuli and in relaying information about nociceptive stimuli. The pathway from LPO glutamatergic neurons to the VTA represents an unpredicted interface between peripheral nociceptive information and the limbic system.


Transcription factor E3, a major regulator of mast cell-mediated allergic response.
Microphthalmia transcription factor, an MiT transcription family member closely related to transcription factor E3 (TFE3), is essential for mast cell development and survival. TFE3 was previously reported to play a role in the functions of B and T cells; however, its role in mast cells has not yet been explored. We sought to explore the role played by TFE3 in mast cell function. Mast cell numbers were evaluated by using toluidine blue staining. FACS analysis was used to determine percentages of Kit and FcεRI double-positive cells in the peritoneum of wild-type (WT) and TFE3 knockout (TFE3(-/-)) mice. Cytokine and inflammatory mediator secretion were measured in immunologically activated cultured mast cells derived from either knockout or WT mice. In vivo plasma histamine levels were measured after immunologic triggering of these mice. No significant differences in mast cell numbers between WT and TFE3(-/-) mice were observed in the peritoneum, lung, and skin. However, TFE3(-/-) mice showed a marked decrease in the number of Kit(+) and FcεRI(+) peritoneal and cultured mast cells. Surface expression levels of FcεRI in TFE3(-/-) peritoneal mast cells was significantly lower than in control cells. Cultured mast cells derived from TFE3(-/-) mice showed a marked decrease in degranulation and mediator secretion. In vivo experiments showed that the level of plasma histamine in TFE3(-/-) mice after an allergic trigger was substantially less than that seen in WT mice. TFE3 is a novel regulator of mast cell functions and as such could emerge as a new target for the manipulation of allergic diseases.