PTEN over-expression by resveratrol in acute lymphoblastic leukemia cells along with suppression of AKT/PKB and ERK1/2 in genotoxic stress.
The bioactive components of dietary phytochemicals are in the spotlight of research institutes, due to their significant antioxidant activities and health-promoting properties. Resveratrol is a polyphenol which is found abundantly in grapes and berries and has long been known as a chemo-preventive agent. The main purpose of this study was to provide a new mechanistic insight into the growth inhibition of acute lymphoblastic leukemia cells by resveratrol along with a DNA damage agent. It was found that the treatment of pre-B ALL cells by resveratrol in the presence or absence of doxorubicin resulted in decreased cell viability and a synergistic increase in cytotoxicity. Cell death was accompanied by a significant increase in phosphorylated p53 at serine 15 and accumulation of PTEN. In addition, resveratrol inhibited the over-expression of p-AKT and p-ERK1/2. These findings clearly demonstrated that resveratrol and doxorubicin synergistically increase the cytotoxicity of pre-B ALL cells via the hyper-activation of two important tumor suppressor proteins and two major signal transduction pathways.


A removable ocular microdialysis system for measuring vitreous biogenic amines.
A microdialysis system with a removable probe and a fixed scleral entry port is presented. The probe can be inserted several times with minimal trauma, permitting repeated sampling in one animal. The functioning of the setup is illustrated by the measurement of dopamine, dihydroxyphenyl acetic acid, and noradrenaline in the vitreous of healthy rabbits under physiological conditions.


Assessment of Aortic Characteristic Impedance and Arterial Compliance from Non-invasive Carotid Pressure Waveform in The Framingham Heart Study.
The primary goal of this study was to test the hypothesis that a hybrid intrinsic frequency-machine learning (IF-ML) approach can accurately evaluate total arterial compliance (TAC) and aortic characteristic impedance (Zao) from a single noninvasive carotid pressure waveform in both women and men with heart failure (HF). TAC and Zao are cardiovascular biomarkers with established clinical significance. TAC is lower and Zao is higher in women than in men, so women are more susceptible to the consequent deleterious effects of them. Although the principles of TAC and Zao are pertinent to a multitude of cardiovascular diseases, including HF, their routine clinical use is limited because of the requirement for simultaneous measurements of flow and pressure waveforms. For this study, the data were obtained from the Framingham Heart Study (n = 6,201, 53% women). The reference values of Zao and TAC were computed from carotid pressure and aortic flow waveforms. IF parameters of carotid pressure waveform were used in ML models. IF models were developed on n = 5,168 of randomly selected data and blindly tested the remaining data (n = 1,033). The final models were evaluated in patients with HF. Correlations between IF-ML and reference values in all HF and HF with preserved ejection fraction for TAC were 0.88 and 0.90, and for Zao were 0.82 and 0.80, respectively. The classification accuracy in all HF and HF with preserved ejection fraction for TAC were 0.9 and 0.93, and for Zao were 0.81 and 0.89, respectively. In conclusion, the IF-ML method provides an accurate estimation of TAC and Zao in all subjects with HF and in the general population.


A three-channel fluorescent probe for selective detection of ONOO- and its application to cell imaging.
The fluorescent probe, GXY-ADP-2, with xanthene structure as the fluorescent core was designed and prepared for the selective detection of peroxynitrite (ONOO-). ONOO- can be produced endogenously and exogenously and is a strong oxidant with a short half-life. Oxidative modifications of biomolecules, that can be attributed to the formation of ONOO-, occur in the reactions of biomolecules with secondary ONOO--derived radical oxidants. Therefore, it is very important to develop a specific fluorescent probe for detecting ONOO- to monitor oxidative stress state. The excitation wavelength and emission wavelength of the probe are 689 nm and 739 nm respectively. In the process of co-incubation with ONOO-, generate a new substance with two internal conjugated structures through a special reaction mechanism, one giving the fluorescence with the excitation wavelength of 347 nm and the emission wavelength of 484 nm with the detection limit of 0.12 μM, and the other that with the excitation wavelength of 433 nm and the emission wavelength of 583 nm with the detection limit of 0.077 μM. The linear dynamic range of the probe is 0-5 μM. Its response is not affected by the other reactive oxygen species, thus can sensitively detect ONOO-. In bioimaging experiments with HepG2 cells, the green and blue cell fluorescence signals (583 nm and 433 nm, respectively) were increased, while the red one (739 nm) was significantly reduced, under lipopolysaccharide (LPS) induced oxidative stress, proving that the probe could sensitively detect ONOO- in living cells. This work provides a new tool for the dynamic changes of ONOO- and oxidative stress processes in biological systems.


Quality control methodology and implementation of X-radiation standards beams, mammography level, following the standard IEC 61267.
This study presents the results of the establishment of a quality control program developed and applied for the X-ray system of the Calibration Laboratory of IPEN. The X-ray standard beams, mammography level, using molybdenum and aluminum as additional filtration were established after the application of this quality control and the spectrometry of these qualities was made. The reference ionization chamber has traceability to the PTB. The radiation qualities RQR-M, RQA-M, RQN-M and RQB-M, following the recommendations of the IEC 61267 and the IAEA TRS 457 were established.


Insecticidal compound isolated from Syzygium lineare Wall. (Myrtaceae) against Spodoptera litura (Lepidoptera: Noctuidae).
A new crystal compound 2,5-diacetoxy-2-benzyl-4,4,6,6-tetramethyl-1,3-cyclohexanedione was isolated from the leaves of Syzygium lineare. The insecticidal activity of the compound was assessed against fourth instar larvae of Spodoptera litura. Its activity was better than the positive control azadirachtin. The compound was responsible for growth inhibition on S. litura. It induced larval, pupal and adult deformities even at low concentration. The compound may be useful as a botanical pesticide.


Magnetic resonance imaging and diffusion-weighted images of cystic meningioma: correlating with histopathology.
Cystic meningiomas are quite rare, accounting for between 2% and 4% of all intracranial meningiomas. To better understand all the types of cystic meningiomas with magnetic resonance imaging (MRI), diffusion-weighted imaging (DWI) and histopathology, we attempted to correlate the MRI and DWI features of cystic meningiomas with the histopathological findings. We collected 15 cases of cystic meningiomas diagnosed between 1993 and 2000 (5 men and 10 women, 41-80 years old). Fifteen patients had conventional MRI and 14 patients had CT scan. DWI was also performed in three patients. Apparent diffusion coefficient (ADC) images were also done. In the classification of cystic meningiomas, we adopted Worthington's classification, which divides cystic meningiomas into five groups. Tumor resection was performed in all patients. Tumor locations were as follows: convexity (10), falx (2), pterion (2) and lateral ventricle (1). Regarding the types of cystic lesion, type I (3), type II (3), type III (3), type IV (1) and type V (5) were found. Histopathologically, there were six atypical, four meningothelial, two malignant, one fibroblastic, one angiomatous and one transitional. Intratumoral cystic meningiomas were more common in atypical types. Peritumoral cystic meningiomas were more common in meningothelial and atypical types. The cystic portion of the three cystic meningiomas was hypointense or mildly hyperintense on DWI. ADC ratio (ADCR) of DWI for cyst part of two type I cystic meningiomas was 1.25 and 0.82; for cyst part of one type III was 4.04. It is important to recognize the neuroimaging features of the cystic meningiomas. Conventional MRI and DWI may play an important role in the preoperative radiological evaluation and the recognition of these types of cysts for proper surgical treatment.


The toxic benthic dinoflagellate Prorocentrum maculosum Faust is a synonym of Prorocentrum hoffmannianum Faust.
Three strains of the toxic benthic dinoflagellate Prorocentrum hoffmannianum were isolated in the Canary Islands (north-east Atlantic Ocean, Spain). The identity of the strains was determined by phylogenetic analyses of partial LSU rDNA (D1-D2 regions) but their morphology based on SEM images corresponded to P. maculosum. Their toxin profiles were analyzed by liquid chromatography and high resolution mass spectrometry analysis (LC-HRMS) on cell extracts and culture media. Okadaic acid and three analogs were detected in all strains. Rather, in culture media the detected compounds were variable among strains, two of them being okadaic acid analogs not found on cell extracts. As a result, the taxonomy of the species was revised and P. maculosum is proposed as a junior synonym of P. hoffmannianum whose description is emended.


A preliminary comparison of flat affect schizophrenics and brain-damaged patients on measures of affective processing.
Flat affect is a major component of schizophrenia and is often also seen in neurological disorders. A preliminary set of comparisons were conducted to delineate neuropsychological mechanisms underlying flat affect in schizophrenia, and new measures are described for the assessment of affective deficits in clinical populations. Subjects were schizophrenic with flat affect (SZs), right brain-damaged (RBD), Parkinson's Disease (PDs), and normal control (NC) right-handed adults. Subjects were administered affective measures of expression and perception in both facial and vocal channels. For both perceptual and expressive tasks the SZs performed significantly less accurately than the NCs and the PDs but did not differ from the RBDs. This was the case for both face and voice. This finding lends support to the speculation that right hemisphere mechanisms, especially cortical ones, may be compromised among schizophrenics with flat affect.


Rhodium-Catalyzed Diastereoselective [3 + 2] Cycloaddition of Carbonyl Ylide: An Access to the Core Ring System of Cordigol and Lophirone H.
This paper describes a new synthetic strategy for the construction of tricyclic chromeno/quinolino furan frameworks via creation of two new rings and three contiguous stereogenic centers with high diastereoselectivity through a rhodium-catalyzed intramolecular carbonyl ylide cycloaddition reaction for the first time. This protocol allows the synthesis of the core ring system of natural products such as cordigol and lophirone H.


NERF2, a member of the Ets family of transcription factors, is increased in response to hypoxia and angiopoietin-1: a potential mechanism for Tie2 regulation during hypoxia.
Vascular endothelial growth factor (VEGF) and angiopoietins regulate endothelial cell survival and migration and are essential for angiogenesis. Considerable progress has been made towards understanding hypoxia-mediated regulation of VEGF and its receptors. In contrast, little is known about the regulation of angiopoietins and their receptors in hypoxic cells. Using RT-PCR, RNAase protection assay, and Western blotting, we found that Tie1 and Tie2 mRNA and protein levels increased in response to hypoxia in human umbilical vein endothelial cells. Previously, we have shown that NERF2, a member of Ets family of transcription factors that is specifically expressed in endothelial cells, binds to the promoter region of Tie2 and transactivates Tie2 expression. In this study, we show that expression of NERF2 was increased under hypoxia and that this increase temporally correlated with the increase in Tie2 expression. Hypoxia-induced expression of NERF2 and Tie2 was blocked by angiopoietin-2, a competitive inhibitor of angiopoietin-1, and by recombinant soluble extracellular domain of Tie2 but not by VEGF-neutralizing antibodies. In addition, angiopoietin-1 directly induced expression of NERF2 in quiescent cells. These novel findings suggest that angiopoietin-1 regulates expression of NERF2 and its own receptor in hypoxic cells.


Simulations of accidental coal immersion.
Coal is currently becoming an increasingly interesting fossil energy resource and that is the reason why its maritime transport, and hence the risk of collier accidents, increase. In this work, the environmental impact of an accidental coal immersion at sea is studied: the physicochemical effects are estimated using innovative experimental setups--a laboratory seawater canal called "polludrome" is used to evaluate the behaviour of coal particles submitted to a seawater flow, and a specifically designed tub is used to study the physicochemical consequences induced when coal is introduced into continuously renewed seawater. When coal is introduced into seawater, the most easily visible consequences are physical: fine coal particles reduce the daylight penetration up to 100% and move along with the flow, and coal chunks accumulate on the floor. Chemical effects are also measured: humic matters are dissolved from coal into seawater (up to 2 mg L(-1)), but no release of polycyclic aromatic hydrocarbons is evidenced. Some inorganic compounds are dissolved, among which manganese, whose concentrations can reach 1 microg L(-1). Fortunately, the results show that the environmental impact of this type of accident would remain limited.


Heterogeneous irradiation system: enhanced degradation of methylene blue by electron beam irradiation combined with graphite carbon nitride/carbon nanodots.
In the present work, the degradation of methylene blue (MB) was investigated by electron beam irradiation combined with graphite carbon nitride/carbon nanodots (EBI&g-C3N4/CDs). In comparison with EBI alone, the EBI&g-C3N4/CDs method showed a higher removal efficiency of high concentrations of MB (500 mg L-1) from aqueous solution. Investigation on the effect of the synthesized g-C3N4/CDs revealed that CDs and g-C3N4 were both contributing factors, while the latter could enhance the degradation of MB through surface reactions that occurred after adsorption. Experiments on the existence of hydrogen peroxide revealed the synergistic effect between g-C3N4/CDs and hydrogen peroxide. An excellent degradation effect was obtained at natural pH, and the total organic carbon was significantly reduced. Regeneration experiments revealed that the g-C3N4/CDs material has good stability and reusability. The studies in the presence of assorted radical scavengers suggested that ·OH played a vital role in the degradation process and a total of 17 intermediates were detected using liquid chromatograph-mass spectrometer (LC-MS) analysis. The possible degradation mechanisms of MB were proposed.


The pathogenesis of cerebrovascular lesions in hypertensive rats.
In this study we investigated the pathogenesis of hypertensive cerebrovascular lesions by light microscopy, immunohistochemistry, scanning electron microscopy, and transmission electron microscopy. The brains of rats with experimentally induced hypertension exhibited severe edema and intracerebral hemorrhage. Light microscopy of the arteries showed severe medial lesions and the deposition of fibrinoid substance in the intima. Immunohistochemistry showed that intercellular adhesion molecule (ICAM)-1, platelet-endothelial cell adhesion molecule (PECAM)-1, interleukin (IL)-1alpha, IL-6, IL-8, and tumor necrosis factor (TNF)-alpha endothelial cell expression was upregulated. Scanning electron microscopy of these arteries revealed the adhesion of neutrophils, monocytes, and a few platelets to endothelial cells, and their invasion of endothelial cell junctions and opened junctions. Transmission electron microscopy showed neutrophil and monocyte adhesion to the endothelial cells and neutrophil and monocyte invasion of endothelial cell junctions, intimal deposition of fibrinoid substance, and severe medial cell injury. Intravenously injected horseradish peroxidase insulated from endothelial cell junctions and, via pinocytotic vesicles, into the subendothelial space. These findings suggest that hypertension activates endothelial cells to increase the expression of adhesion molecules and cytokines, and induces neutrophil and monocyte adhesion and migration, resulting in endothelial cell injury and increased permeability of endothelial cells, which results in hypertensive arterial disease.


An approach to the problem of heterogeneity of human tumour-cell populations.
1. Successive sampling of ovarian cancers during cytostatic treatment showed several cases of notable changes in their ploidy distribution and one change in model chromosome number, indicating selection of a resistant tumour-cell population. 2. Studies of cell suspensions from human tumour specimens incubated with [3H]-TdR after exposure in vitro to various cytostatic agents have shown variation in labelling between different parts of the same tumour, as well as between the primary tumour and its metastases or ascitic tumour-cell population, which may be accounted for by variation in sensitivity of the tumour-cell population. 3. Studies of nuclear morphology in 20 endometrial cancers before and after progesterone therapy demonstrate considerable variation in the proportion of cells undergoing secretory conversion within the same tumour, indicating primary heterogeneity of the tumour-cell population in response to progesterone.


Selective sensitivity to carboxyamidotriazole by human tumor cell lines with DNA mismatch repair deficiency.
We have previously reported that high-dose nifedipine had a selective antiproliferative effect on colon cancer cell lines deficient in DNA mismatch repair (MMR). We hypothesized that carboxyamidotriazole (CAI), a calcium channel blocker, would also have a selective inhibitory effect on colon cancer cell lines with DNA MMR deficiency. In addition, we speculated that this effect may also be seen in cell lines deficient in DNA MMR derived from other tumor types. Fourteen human cancer cell lines with and without DNA MMR derived from carcinomas of the colon, bladder, ovary and prostate were treated with CAI, vehicle or control drugs (nifedipine and 5-flurouracil). The effect of treatment on growth inhibition, invasion, apoptosis and cell cycle progression was assessed. Selective sensitivity to CAI was observed in all cancer cell lines deficient in MMR. Compared with the MMR-proficient cells, the matched deficient cells were significantly more sensitive to the growth inhibitory effect of CAI and nifedipine, but less sensitive to 5-flurouracil. CAI significantly inhibited the invasive ability of MMR-deficient cancer cells compared to 5-flurouracil. CAI induced more apoptosis but similar level of G(2)/M arrest in MMR (hMLH1- or hMSH6-)-deficient colon cancer cells than MMR-proficient counterparts. CAI selectively inhibits proliferation and invasion in MMR-deficient human cancer cell lines. The antitumor effect is at least partly explained by G2/M cell cycle arrest and induction of apoptosis. These findings may have clinical implications directing clinical trials in selectively targeted patients with DNA MMR tumors.


Echocardiogram done early in neonatal sepsis: what does it add?
One of the major organs affected in neonatal sepsis is the heart. Echocardiogram provides real-time information on the cardiovascular performance rather than dependence on the clinical signs alone, which might lead to misjudgment. To assess left ventricular (LV) functions in septic neonates early after admission using transthoracic color Doppler Echocardiography. Echocardiography was done to 30 septic and 30 nonseptic newborns who were divided among 4 groups (septic full-term, 14; septic preterm, 16; nonseptic full-term, 21; and nonseptic preterm, 9). Comparisons were made among the 4 groups using analysis of variance and post hoc test regarding the systolic function (using ejection fraction and fractional shortening), the diastolic function (using the early patrial peak/atrial peak flow velocity ratio), and the global LV function (using myocardial performance index). The E-wave and the early peak flow velocity/atrial peak flow velocity ratio were significantly lower in the septic neonates, whether full-term or premature, compared to their corresponding age groups in the nonseptic newborns, suggesting LV diastolic dysfunction (P < 0.001 and P < 0.014, respectively). No difference was found in the diastolic function between the full-term and the preterm neonates whether lying within the septic group or in the nonseptic group. Myocardial performance index was significantly higher in the septic neonates who died than in the survivors (P < 0.001). Neonatal sepsis is associated with LV diastolic dysfunction.


Falls, Fear of Falling, and Preventive Measures in Huntington's Disease: The Perspectives of Individuals with Huntington's Disease and Caregivers in Long-Term Care.
Falls are common in Huntington's disease (HD), which can have serious consequences and may therefore lead to fear of falling (FoF). There is little knowledge about falls or FoF in individuals with HD or about formal and informal caregivers' fear about falls in individuals with HD. To explore prevalence of falls, FoF and fall preventive measures both those applied and those not included in managing falls in individuals with HD and their formal and informal caregivers, and to identify the relationship between FoF and, anxiety, awareness and cognitive functioning respectively. In a multi-center observational cross-sectional study, care-independent and -dependent individuals with HD and their formal and informal caregivers were recruited from six Dutch nursing homes specialized in HD. The participants were assessed by means of questionnaires enquiring about falls, FoF, awareness of fall risk, cognition, anxiety and fall preventive measures. For all included 158 individuals with HD, the fall prevalence over the last 30 days was 28.8%. The prevalence of FoF in individuals with HD, formal caregivers and informal caregivers was 47.6%, 25.6%, and 63.5%, respectively, for care-independent individuals with HD and 46.9%, 26.3%, and 62.0%, respectively, for care-dependent individuals with HD. Anticipatory awareness of fall risks and gender are predictors of FoF in care-independent individuals with HD, though not in the care-dependent group. A combination of fall preventive measures is used in most individuals with HD. Fall prevalence is high and FoF is common in individuals with HD and their caregivers. Gender and anticipatory awareness are risk factors for FoF. In addition to the use of individual multifactorial fall prevention strategies, it is important to support both formal and informal caregivers in coping with falls.


The relationship between extracellular calcium concentrations and the induction of hippocampal long-term potentiation.
The effect of varying calcium and magnesium concentrations was observed on the development of long-term potentiation (LTP) in the CA1 region of the rat hippocampus maintained in vitro. Treatments which would be expected to lower the depolarization-induced influx of calcium into neuronal elements (i.e. lowering Ca2+ or raising Mg2+ in the perfusion medium) selectively antagonized LTP, while synaptic transmission, paired-pulse and frequency facilitation, as well as short-term (or post-tetanic) potentiation were all maintained. This suggests that LTP is unrelated to these short-term forms of plasticity, but is either a calcium-dependent process itself, or is dependent upon some other calcium-related phenomenon (such as transmitter release).


Comparative Transcriptome Analysis of Mink (Neovison vison) Skin Reveals the Key Genes Involved in the Melanogenesis of Black and White Coat Colour.
Farmed mink (Neovison vison) is one of the most important fur-bearing species worldwide, and coat colour is a crucial qualitative characteristic that contributes to the economic value of the fur. To identify additional genes that may play important roles in coat colour regulation, Illumina/Solexa high-throughput sequencing technology was used to catalogue the global gene expression profiles in mink skin with two different coat colours (black and white). RNA-seq analysis indicated that a total of 12,557 genes were differentially expressed in black versus white minks, with 3,530 genes up-regulated and 9,027 genes down-regulated in black minks. Significant differences were not observed in the expression of MC1R and TYR between the two different coat colours, and the expression of ASIP was not detected in the mink skin of either coat colour. The expression levels of KITLG, LEF1, DCT, TYRP1, PMEL, Myo5a, Rab27a and SLC7A11 were validated by qRT-PCR, and the results were consistent with RNA-seq analysis. This study provides several candidate genes that may be associated with the development of two coat colours in mink skin. These results will expand our understanding of the complex molecular mechanisms underlying skin physiology and melanogenesis in mink and will provide a foundation for future studies.


IL-4 induces allergic-like inflammatory disease and alters T cell development in transgenic mice.
We have assessed the biologic role of IL-4 by fusing its gene to an immunoglobulin promoter/enhancer and introducing it into transgenic mice. By attenuating the transgene promoter through the insertion of E. coli lac operator sequences, we have created a series of animals that constitutively express varying amounts of IL-4. Overexpression of IL-4 results in a marked increase in serum IgE levels and the appearance of an inflammatory ocular lesion (blepharitis) with characteristic histopathologic features seen in allergic reactions. In addition, expression of the IL-4 transgene in the thymus perturbs T cell maturation, reducing the population of immature CD4+CD8+ thymocytes and peripheral T cells while increasing the population of mature CD8+ thymocytes. These results demonstrate that deregulation of a single cytokine gene in vivo can induce a complex inflammatory reaction resembling that observed in human allergic disease.


RhoA activation-mediated vascular permeability in capillary malformation-arteriovenous malformation syndrome: a hypothesis.
Capillary malformation-arteriovenous malformation (CM-AVM) syndrome is a class of capillary anomalies that are associated with arteriovenous malformations and arteriovenous fistulas, which carry a risk of hemorrhages. There are no broadly effective pharmacological therapies currently available. Most CM-AVMs are associated with a loss of RASA1, resulting in constitutive activation of RAS signaling. However, protein interaction analysis revealed that RASA1 forms a complex with Rho GTPase-activating protein (RhoGAP), a negative regulator of RhoA signaling. Herein, we propose that loss of RASA1 function results in constitutive activation of RhoA signaling in endothelial cells, resulting in enhanced vascular permeability. Therefore, strategies aimed at curtailing RhoA activity should be tested as an adjunctive therapeutic approach in cell culture studies and animal models of RASA1 deficiency.


A Five-Year Comparative Functional and Clinical Evaluation of Two Contemporary Cruciate-Retaining Knee Implants.
The purpose of our study was to compare 2 commonly used highly successful cruciate-retaining knee designs on the basis of patient-reported outcome measures (PROMs), range of motion (ROM), and anterior knee pain (AKP) at a minimum follow-up of 5 years. A cohort of 65 patients underwent unilateral total knee arthroplasty, from January 2013 to December 2013, using NexGen Cruciate Retaining (Zimmer Biomet, Warsaw, IN), a nonmorphogenic knee (NMK) system. They were subsequently operated upon for the contralateral knee using Persona Cruciate Retaining (Zimmer Biomet, Warsaw, IN), a morphogenic knee (MK) system between January 2014 and June 2014. Of the 65 patients, 63 participated in this study. All the patients were compared preoperatively and postoperatively on the basis of PROMs, ROM, and AKP. On the basis of PROMs, ROM, and AKP, there was a statistically significant difference between the 2 groups favoring the MK group, with an ROM of 126.14° in the MK group as compared with 120.76° in the NMK group and P value of <.01. PROMs, ROM, and AKP improved significantly over time after total knee arthroplasty using both MK and NMK implants; however, the outcomes of the former were better than those of the latter, although this difference was not clinically significant.


Effects of single-wall carbon nanotubes in human cells of the oral cavity: geno-cytotoxic risk.
Single-wall carbon nanotubes (SWCNTs) are one of the most extensively produced carbon materials and the environmental, public and professional exposure is therefore dramatically increasing. Consequently the studies on bio-effects and safety of SWCNTs are highly needed. The goal of this study was investigate the effects in vitro of SWCNTs in cells of the oral cavity, never employed in this research field. We exposed human gingival fibroblasts to 50, 75, 100, 125, 150 μg/ml SWCNTs for 24 h and we investigated genotoxicity (Comet assay and micronucleus test), cytotoxicity, oxidative stress, as reactive oxygen species (ROS) generation, and stress response, as Heat shock protein 70 (Hsp70) expression. SWCNTs produced genotoxic effects at all doses, even if detected with different sensitiveness by the two tests, and at the two highest doses induced a strong decrease of the cell proliferation and cell survival, causing apoptosis too. Furthermore, we proved the ability of these nanomaterials to induce oxidative stress and Hsp70 expression. Finally, by inhibition of Hsp70 expression, we demonstrated that this heat shock protein conferred protection against SWCNT geno-cytotoxicity.


A case of aortoduodenal fistula presenting with postoperative lymphatic leakage.
Secondary aortoduodenal fistula (sADF) is a complication of prosthetic graft replacement of the abdominal aorta which often follows a fatal course. This report details our experience with a case of lymphatic fistula that developed after sADF repair. The fistula was refractory to conservative treatment but ultimately responded to lipiodol lymphangiography. A 75-year-old man had undergone prosthetic graft replacement to treat an abdominal aortic aneurysm in 2012 and a thoracic aortic aneurysm in 2015. Upper gastrointestinal endoscopy was performed in 2020, and examination for worsening anemia revealed that the abdominal aortic graft had eroded into the horizontal duodenum. The patient was treated with prosthetic graft replacement and duodenectomy. A refractory lymphatic fistula was noted after surgery, which made ascites accumulation difficult to control, but the patient's condition rapidly improved following therapeutic lymphangiography. Surgery is the first-line therapy for sADF, but clinicians must stay vigilant for infection recurrence and aortoenteric fistulae after a repair, and this requires patient-specific postoperative management. Our modifications, intended to minimize contamination of the operative field in the present case, also facilitated our ability to subsequently treat a refractory lymphatic fistula, which is a rare postoperative complication of the procedure. Procedural modifications to sADF repair aimed at minimizing perioperative contamination are crucial for preventing infection recurrence. Given the extent of invasion, the surgery can cause various postoperative complications, requiring individualized strategies for management and treatment. Therapeutic lymphangiography is one such approach, which holds promise as a first-line treatment for refractory lymphatic fistula.


Enhancement of mechanical strength of TCP-alginate based bioprinted constructs.
To overcome the mechanical drawback of bioink, we proposed a supporter model to enhance the mechanical strength of bioprinted 3D constructs, in which a unit-assembly idea was involved. Based on Computed Tomography images of critical-sized rabbit bone defect, the 3D re-construction was accomplished by a sequenced process using Mimics 17.0, BioCAM and BioCAD software. 3D constructs were bioprinted using polycaprolactone (PCL) ink for the outer supporter under extrusion mode, and cell-laden tricalcium phosphate (TCP)/alginate bioink for the inner filler under air pressure dispensing mode. The relationship of viscosity of bioinks, 3D bioprinting pressure, TCP/alginate ratio and cell survival were investigated by the shear viscosities analysis, live/dead cell test and cell-counting kit 8 measurement. The viscosity of bioinks at 1.0 s-1-shear rate could be adjusted within the range of 1.75 ± 0.29 Pa·s to 155.65 ± 10.86 Pa·s by changing alginate concentration, corresponding to 10 kPa-130 kPa of printing pressure. This design with PCL supporter could significantly enhance the compressive strength and compressive modulus of standardized 3D mechanical testing specimens up to 2.15 ± 0.14 MPa to 2.58 ± 0.09 MPa, and 42.83 ± 4.75 MPa to 53.12 ± 1.19 MPa, respectively. Cells could maintain the high viability (over 80%) under the given printing pressure but cell viability declined with the increase of TCP content. Cell survival after experiencing 7 days of cell culture could be achieved when the ratio of TCP/alginate was 1 : 4. All data supported the feasibility of the supporter and unit-assembly model to enhance mechanical properties of bioprinted 3D constructs.


Competitive inhibition of phosphoinositide hydrolysis by the muscarinic receptor antagonist AF-DX 116 is of low affinity in mouse cerebral cortex.
Carbamylcholine stimulated [3H]inositol phosphate accumulation in mouse cerebral cortical slices with an ED50 value of approximately 70 microM. Increasing concentrations of the M2 selective muscarinic cholinergic receptor antagonist, AF-DX 116 (0.3-3.0 microM). produced parallel shifts to the right for concentration-response curves to carbamylcholine. A pA2 value for AF-DX 116 of 6.5 (low affinity) was obtained from Schild plot analysis. It is concluded that the M2 muscarinic receptor subtype, as defined by high affinity [3H]AF-DX 116 radioligand binding, is not appreciably coupled to polyphosphoinositide hydrolysis in the mouse cerebral cortex.


On the difficulties of being rigorous in environmental geochemistry studies: some recommendations for designing an impactful paper.
There have been numerous environmental geochemistry studies using chemical, geological, ecological, and toxicological methods but each of these fields requires more subject specialist rigour than has generally been applied so far. Field-specific terminology has been misused and the resulting interpretations rendered inaccurate. In this paper, we propose a series of suggestions, based on our experience as teachers, researchers, reviewers, and editorial board members, to help authors to avoid pitfalls. Many scientific inaccuracies continue to be unchecked and are repeatedly republished by the scientific community. These recommendations should help our colleagues and editorial board members, as well as reviewers, to avoid the numerous inaccuracies and misconceptions currently in circulation and establish a trend towards greater rigour in scientific writing.


Role of cAMP-response element-binding protein phosphorylation in hepatic apoptosis under protein kinase C alpha suppression during sepsis.
Previous studies have shown that a decrease in protein kinase C (PKC) alpha levels contributes to hepatic failure and/or apoptosis during sepsis, and suppression of PKCalpha plays a critical role in triggering caspase-dependent apoptosis, which can modulate expression of Bcl-xL. However, the underlying molecular mechanism remains uncertain. In the present study, we examined whether a decrease in the nuclear PKCalpha levels causes hepatic apoptosis via modulation of cAMP-response element-binding protein (CREB) or nuclear factor-kappaB (NFkappaB), the crucial factors regulating the expression of prosurvival Bcl-xL. For polymicrobial sepsis induction, a cecal ligation and puncture model was used; at 9 or 18 h after CLP, experiments were terminated, referring as early or late sepsis, respectively. Additionally, PKCalpha was suppressed by stable transfection of antisense PKCalpha plasmid into a Clone-9 rat hepatic epithelial cell. The results showed that the nuclear PKCalpha was significantly decreased in the liver during sepsis, which was accompanied by decreases in phospho-CREB content, DNA-binding activity of CREB, and Bcl-xL expression. Likewise, the binding activity of NFkappaB increased significantly, which was associated with a decrease in cytosolic inhibitory-kappaBalpha content. The in vitro suppression of PKCalpha also resulted in decreases in the phospho-CREB content and DNA-binding activity, which were accompanied by down-regulation of Bcl-xL and apoptosis, but no significant alteration in NFkappaB-binding activity. The in vivo and in vitro results suggest that the suppression of PKCalpha results in a decreased CREB phosphorylation and subsequent down-regulation of Bcl-xL, which may contribute to the hepatic apoptosis during sepsis.


Subclinical atherosclerosis in multiple vascular beds: an index of atherosclerotic burden evaluated in postmenopausal women.
The Healthy Women Study has evaluated risk factor changes as women go through the menopause. In 274 women, measures of atherosclerosis in the coronary, aorta and carotid arteries were obtained at 8 years postmenopause using electron beam tomography and carotid ultrasound. The purpose of this study was to evaluate the association between baseline premenopausal risk factors and subclinical disease in various vascular beds and with an aggregate atherosclerosis index based on all subclinical measures. The prevalence of measurable disease for the coronaries, carotids and aorta was 45, 55 and 72%, respectively. Disease measures across these three locations were significantly correlated (P<0.001). Premenopausal LDL, triglycerides, blood pressure (BP) and smoking were associated with each measure of subclinical atherosclerosis, and were strikingly associated with the number of elevated disease measures. Among 126 women taking hormone replacement therapy (HRT), there was a strong positive association between systolic BP and subclinical atherosclerosis (P<0.001). No such relationship was seen among women not on HRT and this interaction was significant (P=0.048). An index of subclinical atherosclerosis rather than measurement at a single arterial site may be the best estimate of disease risk. Such a measure should be evaluated for its prognostic value along with individual measures of subclinical disease. Women with lower premenopausal risk factors did not develop high levels of subclinical atherosclerosis, suggesting that atherosclerosis is a preventable disease in women.


Using the intrinsic chirality of a molecule as a label-free probe to detect molecular adsorption to a surface by second harmonic generation.
Chiral second harmonic generation (C-SHG) has been used for the label-free detection of (R)-(+)-1,1'-bi-2-naphthol (RBN) and (S)-(+)-1,1'-bi-2-naphthol (SBN) binding to planar-supported lipid bilayers of 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphotidylcholine (POPC) based on the intrinsic chirality of the molecules. C-SHG adsorption isotherms of RBN and SBN reveal Langmuir adsorption behavior with binding constants of 2.7 +/- 0.2 x 10(5) M(-1) and 3.0 +/- 0.1 x 10(5) M(-1), respectively. The kinetics of RBN binding to a POPC bilayer was also measured. It was determined that the adsorption rate for RBN was 5.7 +/- 0.4 x 10(3) s(-1)M(-1) and the desorption rate was 2.1 +/- 0.8 x 10(-2) s(-1). From the kinetic data a binding constant of 2.7 +/- 1.0 x 10(5) M(-1) was calculated, which agrees well with the thermodynamic measurement. The C-SHG technique was correlated with surface tension measurements in order to determine the RBN surface excess within the POPC membrane. The maximum surface excess of RBN in a monolayer of POPC was 4.3 +/- 0.5 x 10(-11) mol cm2. Using the maximum surface excess in conjunction with the C-SHG binding data a lower limit of detection of 1.5 +/- 0.1 x 10(-13) mols cm(-2) was calculated. The results of these studies show that C-SHG is a powerful tool for the study of chiral molecular interactions at surfaces.


A cluster of Friedreich's ataxia in Rimouski, Québec.
We described a cluster of 8 independent sibships of Friedreich's ataxia in the St-Fabien parish of Rimouski and have shown that they are all related within 6 generations. The study of this geographic and genetic isolate permitted the investigation of certain unusual features of the disease such as constant myopia, delayed reaction times to pain, flexor spasms, and a rapid evolution.


Investigations on possible genotoxic effects ofFusarium toxins in boars.
For several weeks, boars were fed feedstuff containing mycotoxins (zearalenone, nivalenol, and deoxynivalenol). To determine a possible mutagenic effect of this feedstuff, the boars were examinated for structural chromosome aberrations in the lymphocytes. The investigations indicate a genotoxic effect on the boars' lymphocytes.


Do corticosteroids prevent oesophageal stricture after corrosive ingestion?
The most serious complication of corrosive damage to the oesophagus besides perforation is stricture formation. The role of corticosteroids in preventing corrosive-induced strictures is controversial. This review evaluates the usefulness of corticosteroid treatment by critically assessing clinical reports published between 1991 and 2004 in the English, German, French and Spanish literature. Inclusion criteria were the presence of second- or third-degree oesophageal injuries documented by endoscopy and management involving either at least an 8-day course of corticosteroids or no steroid therapy. Ten studies with a total of 572 patients fulfilled the inclusion criteria: six studies employed corticosteroids, two studies did not use corticosteroids, and two studies compared the outcome with and without corticosteroid treatment. In those patients with second-degree burns, the incidence of stricture in the corticosteroid-treated patients was 13.8% and in the non-corticosteroid-treated patients was 6.3%. In those patients with third-degree burns, significantly worse results were found in the corticosteroid-treated group (71.0%) than in the non-corticosteroid-treated group (23.1%). As all studies did not separate second- and third-degree burns, re-analysis of the outcome was undertaken. In the 305 patients treated with corticosteroids, 35.1% developed strictures, whereas 33.3% of the 267 non-corticosteroid-treated patients developed strictures. These data suggest that systemic corticosteroids are not beneficial for second- and third-degree corrosive oesophageal burns. Therefore, the use of corticosteroids in the management of corrosive ingestions should be abandoned as they do not prevent the development of strictures and may lead to the development of serious adverse effects.


Inhibition of glioma cell proliferation by neural stem cell factor.
Neural stem cells (NSC) have unique differentiation-, proliferation-, and motility properties. To investigate whether they secrete factors that interfere with the proliferation of glioma cells, we grew glioma cells in conditioned medium (CM) obtained from cultures of neurospheres including neural stem / progenitor cells (NSPC) isolated from embryonic (E14)- or adult mouse brain or fetal human brain. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and BrdU-labeling assays showed that CM from NSPC (NSPC/CM) contained factor(s) that inhibited the proliferation of glioma cells by 28-87%. Filter-fractionation of NSPC/CM revealed that the 50,000-100,000 nominal molecular weight limit (NMWL) fraction contained the inhibitory activity. On the basis of these observations we transplanted 203G glioma cells and/or NSPC into the intrathecal space of the cisterna magna of mice to investigate whether NSPC interfere with the proliferation of glioma cells in vivo. Mice transplanted with both 203G and NSPC survived significantly longer than did mice transplanted only with 203G. We concluded that NSPC secrete factor(s) that may control glioma cell proliferation.


Gender-based violence attitudes and dating violence experiences of students in nursing and other health sciences: A multicentre cross-sectional study.
Gender-based violence is a major public health problem. Healthcare providers' ability to identify this type of violence and support victims may be influenced by their knowledge, attitudes, and beliefs, which requires solid education. To identify the gender-based violence attitudes and dating violence experiences of students in nursing and other health sciences. A multicentre cross-sectional study was performed. This study was conducted in three faculties of the University of A Coruña, Spain. Participants were undergraduate students of nursing, podiatry, occupational therapy, and physiotherapy. The Attitudes towards Gender and Violence Questionnaire and the Dating Violence Questionnaire were used from October 2019 to March 2020. Descriptive and inferential statistics were calculated to determine associated factors and identify differences in gender-based violence attitudes and dating violence experiences between sexes and degrees. Data from 459 students were analysed, of whom 180 (39.2 %) studied nursing. The mean age was 20.9 (SD = 3.6) and 76.0 % were women. Statistically significant differences were obtained in attitudes towards gender-based violence according to sex where men displayed more sexist attitudes and violence justification. Results showed a significant difference in attitudes regarding the biological usefulness of sexism and violence between students of nursing and other health sciences. 61.9 % of students had experienced one or more abusive behaviours in relationships; no significant differences were detected according to the degree. However, male students experienced dating violence more often than females. It was observed that students who had suffered dating violence showed greater agreement with sexist attitudes that justify violence. Students of health sciences, particularly males and nursing students, show sexist attitudes that justify gender-based violence. They also frequently experience dating violence, especially psychological violence. It is necessary to intensify or include education on these types of violence in the curricula of degrees in health sciences.


Knockout of pgdS and ggt genes improves γ-PGA yield in B. subtilis.
One of the emerging biopolymers that are currently under active investigation is bacterial poly(γ-glutamic acid) (γ-PGA). However, before its full industrial exploitation, a substantial increase in microbial productivity is required. γ-PGA obtained from the Bacillus subtilis laboratory strain 168 offers the advantage of a producer characterized by a well defined genetic framework and simple manipulation techniques. In this strain, the knockout of genes for the major γ-PGA degrading enzymes, pgdS and ggt, leads to a considerable improvement in polymer yield, which attains levels analogous to the top wild γ-PGA producer strains. This study highlights the convenience of using the laboratory strain of B. subtilis over wild isolates in designing strain improvement strategies aimed at increasing γ-PGA productivity.


Modifying a bacterial tyrosinase zymogen for use in protease activity assays.
Current clinical laboratory assays are not sufficient for determining the activity of many specific human proteases yet. In this study, we developed a general approach that enables the determination of activities of caspase-3 based on the proteolytic activation of the engineered zymogen of the recombinant tyrosinase from Verrucomicrobium spinosum (Vs-tyrosinase) by detecting the diphenolase activity in an increase in absorbance at 475 nm. Here, we designed three different zymogen constructs of Vs-tyrosinase, including RSL-pre-pro-TYR, Pre-pro-TYR, and Pro-TYR. The active domain was fused to the reactive site loop (RSL) of α1-proteinase inhibitor and/or its own signal peptide (pre) and/or its own C-terminal domain (pro) via a linker containing a specific caspase-3 cleavage site. Further studies revealed that both RSL peptide and TAT signal peptide were able to inhibit tyrosinase diphenolase activity, in which RSL-pre-pro-TYR had the lowest background signals. Therefore, a specific protease activity such as caspase-3 could be detected when a suitable zymogen was established. Our results could provide a new way to directly detect the activities of key human proteases, for instance, to monitor the efficacy and safety of tumor therapy by determining the activity of apoptosis-related caspase-3 in patients. KEY POINTS: • RSL inhibited the activity of Verrucomicrobium spinosum tyrosinase. • N-pre and C-terminal domain exerted stronger dual inhibition on the Vs-tyrosinase. • The activity of caspase-3 could be measured by the zymogen activation system.


Effects of melatonin and undernutrition on the viability of ovine embryos during anestrus and the breeding season.
This study examined the effects of melatonin and level of nutrition on embryo yield during anestrous and breeding season. Adult Rasa Aragonesa ewes were assigned randomly to one of the four treatment groups in two experiments using a 2x2x2 factorial design. Individuals were treated (+MEL) or not treated (-MEL) with a subcutaneous implant of melatonin for 42d (Melovine, CEVA) and fed 1.5 (control, C) or 0.5 (low, L) times the daily maintenance requirements for 20d. Ewes were mated at oestrus (Day=0) and embryos were recovered on Day 5. Level of nutrition and melatonin supplements did not have a significant effect on ovulation rate or the number of recovered ova per ewe in the Reproductive Season (RS) and the Anestrous Season (AS). During the RS, undernutrition reduced the number of viable embryos per ewe (C: 1.1+/-0.2; L: 0.6+/-0.2; P<0.05); however, the number of viable embryos per ewe in the L+MEL group (0.2+/-0.15) was significantly lower than it was in the L, C+MEL and C groups (0.9+/-0.3, 1.2+/-0.3, 1.0+/-0.4, respectively; P<0.05). In the AS, nutrition did not have a significant effect on the number of viable embryos per ewe, although melatonin supplements might have improved rates slightly. Embryo viability rate (% viable embryos/embryos recovered) was unaffected by melatonin supplements or level of nutrition in the RS and the AS. Season had a strong effect on the number of viable embryos per functional corpus luteum among ewes in the L+MEL group, only (RS: 0.2+/-0.1; AS: 0.6+/-0.2; P<0.05). In conclusion, undernutrition impaired the viability of sheep embryos in the RS, particularly among ewes that were given melatonin supplements subcutaneously, but melatonin appeared to improve embryo quality in the AS, which suggests that the mechanisms involved in the interactive effects of melatonin and nutrition on embryo development are influenced by season.


Novel approaches to the prediction, diagnosis and treatment of cardiac late effects in survivors of childhood cancer: a multi-centre observational study.
Anthracycline-induced cardiac toxicity is a cause of significant morbidity and early mortality in survivors of childhood cancer. Current strategies for predicting which children are at greatest risk for toxicity are imperfect and diagnosis of cardiac injury is usually made relatively late in the natural history of the disease. This study aims to identify genomic, biomarker and imaging parameters that can be used as predictors of risk or aid in the early diagnosis of cardiotoxicity. This is a prospective longitudinal cohort study that recruited two cohorts of pediatric cancer patients at six participating centres: (1) an Acute Cohort of children newly diagnosed with cancer prior to starting anthracycline therapy (n = 307); and (2) a Survivor Cohort of long-term survivors of childhood cancer with past exposure to anthracycline (n = 818). The study team consists of three collaborative cores. The Genomics Core is identifying genomic variations in anthracycline metabolism and in myocardial response to injury that predispose children to treatment-related cardiac toxicity. The Biomarker Core is identifying existing and novel biomarkers that allow for early diagnosis and prognosis of anthracycline-induced cardiac toxicity. The Imaging Core is identifying echocardiographic and cardiac magnetic resonance (CMR) imaging parameters that correspond to early signs of cardiac dysfunction and remodeling and precede global dysfunction and clinical symptoms. The data generated by the cores will be combined to create an integrated risk-prediction model aimed at more accurate identification of children who are most susceptible to anthracycline toxicity. We aim to identify genomic risk factors that predict risk for anthracycline cardiotoxicity pre-exposure and imaging and biomarkers that facilitate early diagnosis of cardiac injury. This will facilitate a personalized approach to identifying at-risk children with cancer who may benefit from cardio- protective strategies during therapy, and closer surveillance and earlier initiation of medications to preserve heart function after cancer therapy. NCT01805778 . Registered 28 February 2013; retrospectively registered.


The anterior costal margin mass in patients with thalassaemia major.
In thalassaemia major, extramedullary haematopoiesis in the form of tumour-like masses, usually occurs in the posterior mediastinum. We present three cases in which such masses were found at the anterior part of the ribs. The radiological signs of this latter location, which is the second most common after the mediastinum, are described.


Second lung malignancy and Richter syndrome in chronic lymphocytic leukemia: case report and literature review.
Chronic lymphocytic leukemia (CLL) is the most frequent lymphoproliferative disease. Transformation into Richter disease and occurrence of second malignancies involving the lungs are rare complications. The hallmarks of any thoracic involvement are still unknown. We report a case of a 56-year-old male patient, with history of tobacco smoking, who presented with recurrent hemoptysis, fatigue and weight loss. Physical examination was normal except a slightly enlarged supraclavicular lymph node. Chest x-ray revealed a mediastinal widening due to enlarged paratracheal nodes and a left parahilar infiltrate. Blood tests showed a hyperlymphocytosis and a biological inflammatory syndrome. CT scan showed bilateral mediastinal and axillary lymphadenopathy, as well as left supraclavicular lymphadenopathy, with a left upper lobe alveolar attenuation and a solitary contralateral pulmonary nodule. Examination of Virchow's node and bone marrow biopsies confirmed metastasis of a pulmonary adenocarcinoma, as well as chronic lymphocytic leukemia with Richter's transformation. The clinical course was unfavorable since the first days of therapy as the patient passed away in a matter of a few days. Steady surveillance of CLL patients and systematic screening for second solid tumors, particularly lung cancer, and Richter's transformation seem to be relevant more than ever. Early diagnosis might help us understand the pathways leading to these complications and adapt therapy.


Maintaining complete virological suppression by reduced doses of nucleos(t)ide analogue in patients with chronic hepatitis B.
In patients with chronic hepatitis B (CHB), withdrawal of nucleos(t)ide analogues (NAs) can put patients at risk of hepatitis relapses. Here, we examined a dose-reducing strategy. From March 2008 to September 2016, 48 patients with CHB who had received full-dose NA (35 entecavir; 13 tenofovir) and achieved complete virological response (lasting for >1 year), were placed on a reduced dose of antivirals (twice a week) subsequently. In a median follow-up period of 33.2 months, only one patient experienced a virological but not biochemical breakthrough. No deterioration of estimated glomerular filtration rate was found. This strategy could be used in areas where full dose, lifelong treatment is unachievable.


Thermal biology of the common garter snake Thamnophis sirtalis (L.) : I. Temporal variation, environmental effects and sex differences.
This paper describes the thermal biology of the common garter snake, Thamnophis sirtalis, a diurnal, viviparous colubrid. The body temperatures of snakes caught in the field are cooler and more variable early and late in the day, and early and late in the active season. On sunny days in midsummer, females average about 1 C° warmer than males. The frequency distribution of body tempratures for females is skewed to the left, whereas that for males is nearly symmetrical. Under cloudy skies, body temperatures are lower and more variable than under sunny skies, and the difference between males and females disappears. This and related considerations suggest to us that males are less determined, or less precise, thermoregulators than are females. Air and ground-surface temperatures, and snout-vent length, are poor predictors of body temperature. In contrast with other studies, we found no indication that the body temperatures of gravid and nongravid females differ either in mean or variance. We discuss our conclusions in light of previous studies and identify in the latter, analytical shortcomings which we believe hinder interpretation and synthesis.


Development of an analytical method for chlorophyll pigments separation by reversed-phase supercritical fluid chromatography.
Chlorophyll pigments give the green colour to plants, which is a quality attribute of food and vegetables. However, the chemical structure of native chlorophyll can change during varied processes (drying, freezing, extraction) applied to plants, which produce degradation compounds that could have a brown and unwanted colour. Systematic experiments have been conducted in supercritical fluid chromatography with a C18 stationary phase to understand and model the chromatographic behaviour of the compounds with respect to the nature of the modifier (MeOH, ACN, and MeOH/ACN 50/50) and its percentage, from 10% to 100%. Specific retention changes were observed, which provide numerous analytical conditions to achieve compound separation. The chromatographic profile of the extract containing native chlorophyll a, b and numerous phytylated chlorophyll derivatives (pheophytin a, a', b, b'; hydroxypheophytin a, a', b, b'; pyropheophytin and lactone derivatives) is strongly impacted by the nature of the modifier and, because of the complexity of the extract, the optimal conditions obtained are unusual for supercritical fluid chromatography. An original method development using an optimization criterion was discussed for the analyses of samples, leading to a fast analytical method with a very low backpressure and a flow rate gradient, but a simplest and rapid method is also suggested for samples displaying fewer derivatives.


Trophic effects of cardiotrophin-1 and interleukin-11 on rat dorsal root ganglion neurons in vitro.
Cardiotrophin-1 (CT-1) was originally isolated for its hypertrophy inducing effects on cardiac myocytes whereas interleukin-11 (IL-11) was identified due to its ability to stimulate an interleukin-6 (IL-6) dependent plasmocytoma cell line. Both cytokines are structurally and functionally related to a group of factors called neuropoietic cytokines, which also includes IL-6, ciliary neurotrophic factor (CNTF), leukemia inhibitory factor (LIF), and oncostatin M. These factors have trophic effects on subsets of neurons. In the present study we examined the influence of CT-1 and IL-11 on newborn rat dorsal root ganglion neuron survival in vitro. Mouse CT-1 showed prominent trophic effects that were comparable to those of CNTF and LIF. Mouse IL-11 alone did not enhance neuronal survival, but soluble mouse IL-11 receptor alpha rendered neurons sensitive to IL-11. Surprisingly, soluble IL-11 receptor alpha even had slight neurotrophic effects by itself. These results suggest that CT-1 and IL-11 might also be involved in the physiological regulation of sensory neuron survival. Thus, they might, like CNTF, become tools for the therapeutic intervention in neurodegeneration due to disease, toxicity, and trauma.


Profiling psychomotor and cognitive aging in four-way cross mice.
In part due to their genetic uniformity and stable characteristics, inbred rodents or their F1 progeny are frequently used to study brain aging. However, it is recognized that focus on a single genotype could lead to generalizations about brain aging that might not apply to the species as a whole, or to the human population. As a potential alternative to uniform genotypes, genetically heterogeneous (HET) mice, produced by a four-way cross, were tested in the current study to determine if they exhibit age-related declines in cognitive and psychomotor function similar to other rodent models of brain aging. Young (4 months) and older (23 months) CB6F1 × C3D2F1 mice were administered a variety of tests for cognitive, psychomotor, and sensory/reflexive capacities. Spontaneous locomotion, rearing, and ability to turn in an alley all decreased with age, as did behavioral measures sensitive to muscle strength, balance, and motor coordination. Although no effect of age was found for either startle response amplitude or reaction time to shock stimuli, the old mice reacted with less force to low intensity auditory stimuli. When tested on a spatial swim maze task, the old mice learned less efficiently, exhibited poorer retention after a 66-h delay, and demonstrated greater difficulty learning a new spatial location. In addition, the older mice were less able to learn the platform location when it was identified by a local visual cue. Because there was a significant correlation between spatial and cued discrimination performance in the old mice, it is possible that age-related spatial maze learning deficits could involve visual or motor impairments. Variation among individuals increased with age for most tests of psychomotor function, as well as for spatial swim performance, suggesting that four-way cross mice may be appropriate models of individualized brain aging. However, the analysis of spatial maze learning deficits in older CB6F1 × C3D2F1 mice may have limited applicability in the study of brain aging, because of a confounding with visually cued performance deficits.


Using Baseline Transcriptional Connectomes in Rat to Identify Genetic Pathways Associated with Predisposition to Complex Traits.
Although rat is a critical model organism in preclinical medications development, its use in systems genetics studies remains sparse. The PhenoGen database and website contain detailed information on the qualitative and quantitative aspects of the rat brain, liver, heart, and brown adipose transcriptome. This database has been generated using the HXB/BXH recombinant inbred panel and is being expanded to a hybrid rat diversity panel that includes many common inbred strains as well. By using such a panel, the PhenoGen project has created a renewable and cumulative resource for the rat genomics community. The database has been used to reconstruct the brain transcriptome identifying both annotated and unannotated transcribed elements that range in size from 20 nucleotides to over 30,000 nucleotides and elements that have a wide variety of roles in the cell including generation of proteins and regulation of the transcription and translation processes. In all 4 tissues, baseline transcriptional connectomes have been generated to model the relationships among transcripts. These connectomes can be used to identify genetic pathways associated with complex traits and to gain insight into biological function of individual transcripts. The PhenoGen website contains tools that allow the user to explore qualitative features of individual genes and to see how the gene relates to other genes within a tissue. The PhenoGen database and website continue to grow and to make use of the latest statistical methods for systems genetics creating a national resource for the rat genomics community.


A Hybrid Conformal Planning Technique with Solitary Dynamic Portal for Postmastectomy Radiotherapy with Regional Nodes.
This study focuses on incorporation of a solitary dynamic portal (SDP) in conformal planning for postmastectomy radiotherapy (PMRT) with nodal regions with an intention to overcome the treatment planning limitations imposed by conventional techniques. Twenty-four patients who underwent surgical mastectomy followed by PMRT were included in this study. Initially, a treatment plan comprising tangential beams fitted to beam's-eye-view (BEV) of chest wall (CW) and a direct anterior field fitted to BEV of nodal region, both sharing a single isocenter was generated using Eclipse treatment planning system. Multiple field-in-fields with optimum beam weights (5% per field) were added primarily from the medial tangent, fitted to BEV of entire target volume, and finally converted into a dynamic portal. Dosimetric analysis for the treatment plans and fluence verification for the dynamic portals were performed. Conformal plans with SDP showed excellent dose coverage (V95%>95%), higher degree of tumor dose conformity (≤1.25) and homogeneity (≤0.12) without compromising the organ at risk sparing for PMRT with nodal region. Treatment plans with SDP considerably reduced the lower isodose spread to the ipsilateral lung, heart, and healthy tissue without affecting the dose homogeneity. Further, gamma evaluation showed more than 96% pixel pass rate for standard 3%/3 mm dose difference and distance-to-agreement criteria. Moreover, this plan offers less probability of "geometrical miss" at the highly irregular CW with regional nodal radiotherapy. Hybrid conformal plans with SDP would facilitate improved dose distribution and reduced uncertainty in delivery and promises to be a suitable treatment option for complex postmastectomy CW with regional nodal irradiation.


PD-L1 Expression and Survival among Patients with Advanced Non-Small Cell Lung Cancer Treated with Chemotherapy.
Recent clinical trial results have suggested that programmed cell death ligand 1 (PD-L1) expression measured by immunohistochemistry may predict response to anti-programmed cell death 1 (PD-1) therapy. Results on the association between PD-L1 expression and survival among patients with advanced non-small cell lung cancer (NSCLC) treated with chemotherapy are inconsistent. We evaluated the relationship between PD-L1 expression and overall survival (OS) among 204 patients with advanced NSCLC treated at Aarhus University Hospital, Aarhus, Denmark, from 2007 to 2012. PD-L1 expression was measured using a prototype immunohistochemistry assay with the anti-PD-L1 22C3 antibody (Merck). PD-L1 strong positivity and weak positivity were defined to be traceable to the clinical trial version of the assay. Twenty-five percent of patients had PD-L1 strong-positive tumors, and 50% had PD-L1 weak-positive tumors. No statistically significant association was found between PD-L1 expression and survival; adjusted hazard ratio of 1.34 (95% confidence interval, 0.88-2.03; median OS, 9.0 months) for the PD-L1 strong-positive group and 1.07 (0.74-1.55; median OS, 9.8 months) for the PD-L1 weak-positive group compared with the PD-L1-negative group (median OS, 7.5 months). No association was seen between PD-L1 expression and OS when PD-L1 expression levels were stratified by median or tertiles. In concordance with previous studies, we found PD-L1 measured by immunohistochemistry to be frequently expressed in patients with advanced NSCLC. However, PD-L1 expression is not a strong prognostic marker in patients with advanced NSCLC treated with chemotherapy.


[Free small intestine transplantation with microvascular anastomosis for complete replacement of the hypopharynx and cervical esophagus].
12 patients were operated on due to a cancer of the hypopharynx (T2-T4, N2-3). After resection, the reconstruction was performed with a free jejunal segment. Intraoperatively the venous anastomosis had to be renewed in 2 cases. One of these patients developed postoperatively a partial necrosis of the transplant. A further patient developed an insufficiency of the proximal anastomosis. One patient died on the 12th postoperative day due to a myocardial infarction. The median survival time was 17 months.


Acoustic Reflex Screening of Conductive Hearing Loss for Third Window Disorders.
This study examines the effectiveness of acoustic reflexes in screening for third window disorders (eg, superior semicircular canal dehiscence) prior to middle ear exploration for conductive hearing loss. Case series with chart review. Outpatient tertiary otology center. A review was performed of 212 ears with acoustic reflexes, performed as part of the evaluation of conductive hearing loss in patients without evidence of chronic otitis media. The etiology of hearing loss was determined from intraoperative findings and computed tomography imaging. The relationship between acoustic reflexes and conductive hearing loss etiology was assessed. Eighty-eight percent of ears (166 of 189) demonstrating absence of all acoustic reflexes had an ossicular etiology of conductive hearing loss. Fifty-two percent of ears (12 of 23) with at least 1 detectable acoustic reflex had a nonossicular etiology. The positive and negative predictive values for an ossicular etiology were 89% and 57% when acoustic reflexes were used alone for screening, 89% and 39% when third window symptoms were used alone, and 94% and 71% when reflexes and symptoms were used together, respectively. Acoustic reflex testing is an effective means of screening for third window disorders in patients with a conductive hearing loss. Questioning for third window symptoms should complement screening. The detection of even 1 acoustic reflex or third window symptom (regardless of reflex status) should prompt further workup prior to middle ear exploration.


Covalent and noncovalent intermediates of an NAD utilizing enzyme, human CD38.
Enzymatic utilization of nicotinamide adenine dinucleotide (NAD) has increasingly been shown to have fundamental roles in gene regulation, signal transduction, and protein modification. Many of the processes require the cleavage of the nicotinamide moiety from the substrate and the formation of a reactive intermediate. Using X-ray crystallography, we show that human CD38, an NAD-utilizing enzyme, is capable of catalyzing the cleavage reactions through both covalent and noncovalent intermediates, depending on the substrate used. The covalent intermediate is resistant to further attack by nucleophiles, resulting in mechanism-based enzyme inactivation. The noncovalent intermediate is stabilized mainly through H-bond interactions, but appears to remain reactive. Our structural results favor the proposal of a noncovalent intermediate during normal enzymatic utilization of NAD by human CD38 and provide structural insights into the design of covalent and noncovalent inhibitors targeting NAD-utilization pathways.


Generating Tonal Distinctions in Mandarin Chinese Using an Electrolarynx with Preprogrammed Tone Patterns.
An electrolarynx (EL) is a valuable rehabilitative option for individuals who have undergone laryngectomy, but current monotone ELs do not support controlled variations in fundamental frequency for producing tonal languages. The present study examined the production and perception of Mandarin Chinese using a customized hand-held EL driven by computer software to generate tonal distinctions (tonal EL). Four native Mandarin speakers were trained to articulate their speech coincidentally with preprogrammed tonal patterns in order to produce mono- and di-syllabic words with a monotone EL and tonal EL. Three native Mandarin speakers later transcribed and rated the speech samples for intelligibility and acceptability. Results indicated that words produced using the tonal EL were significantly more intelligible and acceptable than those produced using the monotone EL.


Diagnostics for Lassa Fever: Detecting Host Antibody Responses.
There are two types of viral diagnostics: (1) those that detect components of the pathogen (like viral RNA or proteins) and (2) those that detect host molecules that rise or fall as a consequence of pathogen infection (like anti-viral antibodies or virus-induced inflammatory cytokines). Quantitative PCR to detect Lassa RNA, and clinical chemistry to detect high liver enzymes (AST/ALT) are commonly used to diagnose Lassa fever. Here, we discuss the various types of diagnostics for Lassa fever and the urgent need for early diagnosis. We also describe a protocol for using the attenuated Lassa vaccine candidate, ML29 , as an antigen for detecting Lassa-specific antibodies. Since antibodies are developed late in the progression of Lassa fever disease, this is not an early diagnostic, but is more useful in surveillance of the population to determine the sero-prevalence of antibodies to Lassa virus (LASV ), and to define treatment options for people in close contact with a Lassa-infected person.


Does emergency medical dispatch priority predict delphi process-derived levels of prehospital intervention?
The Medical Priority Dispatch System (MPDS) is an emergency medical dispatch system widely used to prioritize 9-1-1 calls and optimize resource allocation. This study evaluates whether the assigned priority predicts a Delphi process-derived level of prehospital intervention in each emergency medical dispatch category. All patients given a MPDS priority in a suburban California county from 2004-2006 were included. A Delphi process of emergency medical services (EMS) professionals in another system developed the following categories of prehospital treatment representing increasing acuity, which were adapted for this study: advanced life support (ALS) intervention, ALS-Stat, and ALS-Critical. The sensitivities and specificities of MPDS priority for level of prehospital intervention were determined for each MPDS category. Likelihood ratios of low and high priority dispatch codes for the level of prehospital intervention also were calculated for each MPDS category. A total of 65,268 patients met inclusion criteria, representing 61% of EMS calls during the study period. The overall sensitivities of high-priority dispatch codes for ALS, ALS-Stat, and ALS-Critical interventions were 83% (95% confidence interval 83-84%), 83% (82-84%), and 94% (92-96%). Overall specificities were: ALS, 32% (31-32%); ALS-Stat, 31% (30-31%); and ALS-Critical 28% (28-29%). Compared to calls assigned to a low priority, calls with high-priority dispatch codes were more likely to receive ALS interventions by 22%, ALS-Stat by 20%, and ALS-Critical by 32%. A low priority dispatch code decreased the likelihood of ALS interventions by 48%, ALS-Stat by 45%, and ALS-Critical by 80%. Among high-priority dispatch codes, the rates of interventions were: ALS 26%, ALS-Stat 22%, and ALS-Critical 1.5%, all of which were significantly greater than low-priority calls (p<0.05) [ALS 13%, ALS-Stat 11%, and ALS-Critical 0.2%]. Major MPDS were categories with high sensitivities (>95%) for ALS interventions included breathing problems, cardiac or respiratory arrest/death, chest pain, stroke, and unconscious/fainting; these categories had an average specificity of 3%. Medical Priority Dispatch System categories such as back pain, unknown problem, and traumatic injury had sensitivities for ALS interventions<15%. The MPDS is moderately sensitive for the Delphi process derived ALS, ALS-Stat, and ALS-Critical intervention levels, but nonspecific. A low MPDS priority is predictive of no prehospital intervention. A high priority, however, is of little predictive value for ALS, ALS-Stat, or ALS-Critical interventions.


Seasonal difference in the occurrence of exercise-induced bronchospasm in asthmatics: dependence on humidity.
Most studies on the effects of temperature and humidity on exercise-induced bronchospasm (EIB) in asthmatics have been carried out under indoor conditions. However, any asthmatic patient is exposed to varying climatic conditions. To investigate whether temperature or relative humidity plays a more important role in determining the degree of EIB in asthmatics under naturally exposed climate conditions. To exclude the effects of pollen on EIB, we enrolled 69 subjects with perennial asthma (mean +/- SD: 20.1 +/- 1.5 years). The subjects performed outdoor free running tests. They were divided into winter (n = 25), spring/autumn (n = 22), and summer (n = 22) groups according to the season when they performed the tests. Initial spirometry and skin prick tests were performed. Methacholine bronchial challenge testing and, one day later, the free running tests were done. There were significant differences in temperature and relative humidity among the three groups: However, the relative humidity in winter did not differ from that in spring/autumn. There were no differences in pulmonary functions, airway responsiveness, and atopy score among the three groups. The percentage of cases of positive EIB --fall in forced expiratory volume in 1s FEV(1) of >15% from baseline --in winter (84%, p < 0.05) or spring/autumn (86.4%, p < 0.05) was higher than that in summer (50%). However, the percentage of subjects with a positive EIB in winter did not differ from that in spring/autumn. The maximal percent fall in FEV(1) after exercise in winter did not differ from that in spring/autumn. The occurrence of EIB is associated with environmental temperature and humidity. Under such climatic conditions as in Korea, relative humidity may be a more important factor than temperature in contributing to EIB in patients with perennial asthma.


Primary pull-through for Hirschsprung's disease.
The first report of a successful primary pull-through for Hirschsprung's disease using the endorectal pull-through (ERPT) was by So et al. (J. Pediatr. Surg. 15 (1980) 470; J. Pediatr. Surg. 33 (1998) 673). Subsequently, because of the simplified nature of this approach and the potential for cost savings, several groups have reported excellent results with this procedure. In addition to the ERPT, both the Duhamel and Swenson procedures have been performed in a one-stage fashion. More recently, primary laparoscopic approaches for each of these techniques have been utilized. The purpose of this review is to discuss the technique of primary pull-through, the peri-operative management and a summary of clinical results.


A prognostic eight-gene expression signature for patients with breast cancer receiving adjuvant chemotherapy.
Breast cancer is a popularly diagnosed malignant tumor. Genomic profiling studies suggest that breast cancer is a disease with heterogeneity. Chemotherapy is one of the chief means to treat breast cancer, while its responses and clinical outcomes vary largely due to the conventional clinicopathological factors and inherent chemosensitivity of breast cancer. Using the least absolute shrinkage and selection operator (LASSO) Cox regression model, our study established a multi-mRNA-based signature model and constructed a relative nomogram in predicting distant-recurrence-free survival for patients receiving surgery and following chemotherapy. We constructed a signature of eight mRNAs (IPCEF1, SYNDIG1, TIGIT, SPESP1, C2CD4A, CLCA2, RLN2, and CCL19) with the LASSO model, which was employed to separate subjects into groups with high- and low-risk scores. Obvious differences of distant-recurrence-free survival were found between these two groups. This eight-mRNA-based signature was independently associated with the prognosis and had better prognostic value than classical clinicopathologic factors according to multivariate Cox regression results. Receiver operating characteristic results demonstrated excellent performance in diagnosing 3-year distant-recurrence by the eight-mRNA signature. A nomogram that combined both the eight-mRNA-based signature and clinicopathological risk factors was constructed. Comparing with an ideal model, the nomograms worked well both in the training and validation sets. Through the results that the eight-mRNA signature effectively classified patients into low- and high-risk of distant recurrence, we concluded that this eight-mRNA-based signature played a promising predictive role in prognosis and could be clinically applied in breast cancer patients receiving adjuvant chemotherapy.


Assessing the built environment using omnidirectional imagery.
Observational audits commonly are used in public health research to collect data on built environment characteristics that affect health-related behaviors and outcomes, including physical activity and weight status. However, implementing in-person field audits can be expensive if observations are needed over large or geographically dispersed areas or at multiple points in time. A reliable and more efficient method for observational audits could facilitate extendibility (i.e., expanded geographic and temporal scope) and lead to more standardized assessment that strengthens the ability to compare results across different regions and studies. The purpose of the current study was to evaluate the degree of agreement between field audits and audits derived from interpretation of three types of omnidirectional imagery. Street segments from St. Louis MO and Indianapolis IN were stratified geographically to ensure representation of neighborhoods with different socioeconomic characteristics in both cities. Audits were conducted in 2008 and 2009 using four methods: field audits, and interpretation of archived imagery, new imagery, and Google Street View™ imagery. Agreement between field audits and image-based audits was assessed using observed agreement and the prevalence-adjusted bias-adjusted kappa statistic (PABAK). Data analysis was conducted in 2010. When measuring the agreement between field audits and audits from the different sources of imagery, the mean PABAK statistic for all items on the instrument was 0.78 (archived); 0.80 (new); and 0.81 (Street View imagery), indicating substantial to nearly perfect agreement among methods. It was determined that image-based audits represent a reliable method that can be used in place of field audits to measure several key characteristics of the built environment important to public health research.


Fully synthetic injectable depots with high drug content and tunable pharmacokinetics for long-acting drug delivery.
Clinical studies have validated that antiretroviral (ARV) drugs can serve as an HIV pre-exposure prophylactic (PrEP) strategy. Dosing adherence remains a crucial factor determining the final efficacy outcomes, and both long-acting implants and injectable depot systems are being developed to improve patient adherence. Here, we describe an injectable depot platform that exploits a new mechanism for both formation and controlled release. The depot is a polymeric prodrug synthesized from monomers that incorporate an ARV drug tenofovir alafenamide (TAF) with degradable linkers that can be designed to control release rates. The prodrug monomers are synthetically incorporated into homopolymer or block designs that exhibit high drug weight percent (wt%) and also are hydrophobized in these prodrug segments to drive depot formation upon injection. Drug release converts those monomers to more hydrophilic pendant groups via linker cleavage, and as this drug release proceeds, the polymer chains losing hydrophobicity are then disassociated from the depot and released over time to provide a depot dissolution mechanism. We show that long-acting TAF depots can be designed as block copolymers or as homopolymers. They can also be designed with different linkers, for example with faster or slower degrading p-hydroxybenzyloxycarbonyl (Benzyl) and ethyloxycarbonyl (Alkyl) linkers, respectively. Diblock designs of p(glycerol monomethacrylate)-b-p(Alkyl-TAF-methacrylate) and p(glycerol monomethacrylate)-b-p(Benzyl-TAF-methacrylate) were first characterized in a mouse subcutaneous injection model. The alkylcarbamate linker design (TAF 51 wt%) showed excellent sustained release profiles of the key metabolite tenofovir (TFV) in skin and plasma over a 50-day period. Next, the homopolymer design with a high TAF drug wt% of 73% was characterized in the same model. The homopolymer depots with p(Alkyl-TAFMA) exhibited sustained TFV and TAF release profiles in skin and blood over 60 days, and TFV-DP concentrations in peripheral blood mononuclear cells (PBMC) were found to be at least 10-fold higher than the clinically suggested minimally EC90 protective concentration of 24 fmol/106 cells. These are the first reports of sustained parent TAF dosing observed in mouse and TFV-DP in mouse PBMC. IVIS imaging of rhodamine labeled homopolymer depots showed that degradation and release of the depot coincided with the sustained TAF release. Finally, these polymers showed excellent stability in accelerated stability studies over a six-month time period, and exceptional solubility of over 700 mg/mL in the DMSO formulation solvent. The homopolymer designs have a drug reservoir potential of well over a year at mg/day dosing and may not require cold chain storage for global health and developed world long-acting drug delivery applications.


Gestational 2,3,7,8-tetrachlorodibenzo-p-dioxin exposure effects on sensory cortex function.
Gestational exposure to environmental contaminants such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) poses a significant threat to normal growth and differentiation of the developing brain. To characterize the impact of gestational TCDD exposure on subsequent cortical function, pregnant Long Evans rats were exposed to a single acute dose (100 or 700ng/kg b.w. via gavage) on gestational day 15. This dosing regimen had no significant effect on birth index. After the TCDD-exposed animals were born and reached maturity, neural activity was recorded under urethane anesthesia from neurons in primary somatic sensory cortex. Spontaneous activity was reduced by approximately 50% in barrel cortex compared to corn oil vehicle controls. The magnitude of neuronal response to sensory (whisker) stimuli also was significantly reduced, and responses did not achieve control levels at any stimulus intensity. The greatest deficit was in the short latency component of the cortical responses. These decrements in cortical responsiveness were present in young F1 generation TCDD-exposed animals and persisted for up to 180 days. Because glutamate receptors are crucial to the evoked responses and show developmental regulation, selected iontotropic glutamate receptor subunits (NMDA NR2A+NR2B and GluR1) were profiled for RNA levels in the cortex of F1 generation rats. The expression of NR2B (NMDA receptor) and GluR1 (AMPA receptor) subunits was significantly reduced in the TCDD-exposed F1 generation animals compared to vehicle controls. The results indicate that gestational TCDD exposure results in cortical deficits that are paralled by diminished expression of certain NMDA and AMPA receptor subunits at a time when synapses are being formed for the first time in cortex.


Measurement of bubble size distribution in protein foam fractionation column using capillary probe with photoelectric sensors.
Bubble size is a key variable for predicting the ability to separate and concentrate proteins in a foam fractionation process. It is used to characterize not only the bubble-specific interfacial area but also coalescence of bubbles in the foam phase. This article describes the development of a photoelectric method for measuring the bubble size distribution in both bubble and foam columns for concentrating proteins. The method uses a vacuum to withdraw a stream of gas-liquid dispersion from the bubble or foam column through a capillary tube with a funnel-shaped inlet. The resulting sample bubble cylinders are detected, and their lengths are calculated by using two pairs of infrared photoelectric sensors that are connected with a high-speed data acquisition system controlled by a microcomputer. The bubble size distributions in the bubble column 12 and 1 cm below the interface and in the foam phase 1 cm above the interface are obtained in a continuous foam fractionation process for concentrating ovalbumin. The effects of certain operating conditions such as the feed protein concentration, superficial gas velocity, liquid flow rate, and solution pH are investigated. The results may prove to be helpful in understanding the mechanisms controlling the foam fractionation of proteins.


N-[(E)-Quinolin-2-yl-methyl-idene]-1,2,4-triazol-4-amine hemihydrate.
The title hemihydrate, C12H9N5·0.5H2O, was isolated from the condensation reaction of quinoline-2-carbaldehyde with 4-amino-4H-1,2,4-triazole. The Schiff base mol-ecule adopts an E configuration about the C=N bond and is approximately planar, with a dihedral angle between the quinoline ring system and the 1,2,4-triazole ring of 12.2 (1)°. In the crystal, one water mol-ecule bridges two Schiff base mol-ecules via O-H⋯N hydrogen bonds. The Schiff base mol-ecules are inter-connected by π-π stacking inter-actions [centroid-centroid distances of 3.7486 (7) and 3.9003 (7) Å] into columns along [10].


Transient increase in the number of cholinergic neurons in the developing rat dentate gyrus.
Using a monoclonal antibody against choline acetyltransferase (ChAT), we have examined the distribution of cholinergic neurons in the rat dentate gyrus during development. ChAT-positive neurons were occasionally detected in the hilus on postnatal day 2 (P2). There was a transient abrupt increase in the number and density of ChAT-positive neurons between P15 and P20 and then a decline to the adult level with few ChAT-immunoreactive neurons. A few ChAT-positive varicose fibers and punctae were first seen at P5. They increased in number and density until P20 when they reached the adult level and distribution. These observations suggest the occurrence of a transient expression of cholinergic markers in the hippocampus.


Controlling the rheological properties of W1/O/W2 multiple emulsions using osmotic swelling: Impact of WPI-pectin gelation in the internal and external aqueous phases.
The purpose of this study was to create W1/O/W2 Multiple Emulsions by controlled osmotic swelling, and gelation of whey protein isolate (WPI) and high methoxy pectin (HMP) microspheres in internal and external acidic aqueous phases. Three different kinds of W1/O/W2 multiple emulsions (ME) were prepared, with 8 wt.% Polyglycerol polyricinoleate (PGPR) in their oil phases, with WPI and HMP in internal and external aqueous phases (250 mM NaCl, pH 3.5): (i) ME1: The inner aqueous phase (W1) contained 40% buffer solution, while W2 consisted of 10% WPI and 2% HMP; (ii) ME2: W1 contained 10% WPI, with 2% HMP (250 mM NaCl) in W2; (iii) ME3: 10% WPI and 2% HMP in W1, while W2 contained 1% Tween 80. The original multiple emulsions were diluted by different factors (1:0 to 1:5 with citrate buffer solution), and subject to thermal treatment from 25 to 90 °C to compare their microstructural and rheological properties. It was observed that the ME1 emulsion had higher viscosity and shear modulus than for other emulsions. After dilution however, the shear viscosity of ME3 was higher than ME1 and ME 2 at intermediate shear rates, which showed that the emulsions were osmotically well controlled in internal aqueous phases. Optical and confocal microscopy also supported our rheological measurements with evidence of WPI-HMP gelation, and osmotic swelling, in original and in swollen multiple emulsions. The results of this work may provide useful information about the encapsulation of bioactive compounds, in internal and external aqueous phases, for the development of healthier reduced-fat products in food industry.


High saturated fat diet in teenage years raises breast cancer risk later.
Consuming a lot of of saturated fat or very little mono and polyunsaturated fat in adolescence raises the risk of breast cancer, researchers say.


Dynamic interrelations between environmental innovations, human capital, and energy security in Vietnam: new evidence from an extended TVP-VAR approach.
This study employs an extended joint connectedness approach, as well as a time-varying parameter vector autoregression technique (ETVP-VAR), to characterize the interrelationships among six factors, namely, renewable energy, environmental innovations (EI), gross domestic product (GDP), human capital, energy consumption, and energy productivity (EP), from 1995 to 2019 in Vietnam. Taking a holistic view, it appears that both energy consumption and GDP are net recipients of contagion shocks. In addition, renewable energy, as well as environmental innovations, is critical net transmitters during our studied period. From 1995 to 2003, human capital constantly acted as a crucial net shock absorber before switching to a crucial net transmitter after that year. With a significant exception around 1997, this variable is mostly a shock transmitter when it comes to energy production. Pairwise connectedness reveals that renewable energy consistently appears as a shock transmitter to GDP, human capital, energy consumption, and energy productivity. That being said, environmental innovations consistently contribute to renewable and green energy volatility by transmitting shocks from other markets.


Postoperative rhabdomyolysis following otoplasty: an autopsy case report.
Postoperative rhabdomyolysis is a significant complication that can arise from prolonged surgery, causing potential harm to the kidneys and leading to acute renal failure. Despite its importance, the incidence of rhabdomyolysis following ear reconstruction surgery remains undocumented in the literature. In this report, we present a case study of a male patient in his forties who underwent otoplasty for ear reconstruction after the amputation of his right ear due to a physical assault. The surgery lasted for 8 h under general anesthesia, and unfortunately, the patient developed postoperative rhabdomyolysis, which resulted in severe renal failure and ultimately an unrecoverable cardiac arrest, leading to his death. The autopsy findings indicated no identifiable lesions except for organ congestion, while histopathology revealed acute tubular necrosis of the kidney and muscle rhabdomyolysis. Previous literature has explored the association between surgical duration, location, and rhabdomyolysis, underscoring that this condition is an infrequent yet preventable consequence of prolonged surgery. The co-occurrence of rhabdomyolysis and acute renal injury in this case suggests the presence of comorbidity, emphasizing the need for prompt action to mitigate the negative consequences of rhabdomyolysis. Awareness and early intervention are crucial in preventing and managing this condition effectively.


The opposed influences of beta-adrenergic stimulation and adenosine on the frequency-force relationship of isolated left atria of guinea-pigs.
The normal frequency-force relationship of left guinea-pig atria can be largely suspended when strong beta-adrenergic stimulation by orciprenaline is antagonized by the negative inotropic effect of adenosine, so that contraction amplitude is nearly equal at an intermediate level over a wide range of stimulation rates. Curves obtained with new method for recording continuous frequency-force loops are presented.


1-Benzoyl-3-(4-n-butyl-phen-yl)thio-urea.
The dihedral angle between the benzoyl and phenyl groups in the title compound, C(18)H(20)N(2)OS, is 30.57 (4)°. The crystal packing is characterized by N-H⋯O hydrogen bonds. In the crysta, pairs of N-H⋯S hydrogen bonds link the molecules into inversion dimers.


Glutamate sensitivity and distribution of receptors along normal and denervated locust muscle fibres.
1. Factors influencing the glutamate sensitivity of extrajunctional regions of innervated and denervated locust muscle fibres have been investigated. Properties of the two types of extrajunctional glutamate receptors, D- and H-receptors, have been studied in regions of high and low sensitivity. 2. The low level of extrajunctional sensitivity which is normally present in innervated fibres was 20-30 times higher at the muscle-tendon junction than at other sites; increased sensitivity extended about 20-40 micron from the tendon. After denervation or localized damage the entire extrajunctional sensitivity was increased approximately 100 times above control levels. 3. Applying L-glutamate (which activates D- and H-receptors) and DL-ibotenate (which activates H-receptors) from multibarrelled micropipettes showed that increased extrajunctional sensitivity resulted from an increase in D-receptors while H-receptors were apparently unchanged. 4. Coulomb dose vs. response relationships for the action of glutamate on D-receptors were similar when obtained at the muscle-tendon junction and nerve-muscle junction of innervated fibres or at extrajunctional regions in denervated fibres. 5. Time course of onset and percentage desensitization of D- and H-receptors in innervated fibres were similar. The percentage desensitization of D-receptors in extrajunctional regions of high sensitivity was greatly reduced. 6. It is suggested that D- and H-receptors are independent and that the trigger for increased receptor sensitivity acts specifically on D-receptors. In all respects so far studied, the D-receptors resemble extrajunctional ACh-receptors in vertebrate muscle.


Endoscopic non-aggressive assessment of oesophageal variceal pressure compared with wedged hepatic venous pressure in alcoholic liver cirrhosis.
Ten alcoholic cirrhotic patients presenting with oesophageal varices underwent simultaneous measurement of wedged hepatic venous pressure and endoscopic variceal pressure. The latter was obtained by means of a pneumatic pressure gauge fixed to the tip of a gastrofibroscope. The correlation between these two parameters was highly significant.


Reye's syndrome: patient serum alters mitochondrial function and morphology in vitro.
A direct relationship between a putative Reye's syndrome "serum factor" and generalized mitochondrial damage has been demonstrated in vitro. The clinical features of Reye's syndrome may be secondary to disrupted mitochondrial structure and a consequent impairment of energy-linked functions involving many organs.