Raman Optical Activity on a Solid Sample: Identification of Atropisomers of Perfluoroalkyl Chains Having a Helical Conformation and No Chiral Center.
Perfluoroalkyl (Rf) chains have a specific helical conformation due to the steric repulsion between the adjacent CF2 units. Although Rf chains have no chiral center, two chiral structures, i.e., the right-handed (R) and left-handed (L) helices, are available as the most stable conformations, which are atropisomers to each other. According to the stratified dipole array (SDA) theory, the helical structure about the chain axis plays a key role in the spontaneous molecular aggregation of Rf chains in a two-dimensional manner, and the Rf chains having the same chirality tend to be aggregated spontaneously to generate molecular domains. This implies that an Rf compound in a solid state should be a mixture of the R and L domains, and each domain should exhibit distinguishable optical activity. To identify molecular domains with different atropisomers, in this study, Raman optical activity (ROA) measurements were performed on a Raman imaging spectrometer. Through the ROA measurements of recrystallized solid samples of an Rf compound, each particle exhibits an apparent optical activity, and the two atropisomers were readily distinguished. As a result, an Rf compound with the same helicity is found to be spontaneously aggregated as expected by the SDA theory.


Differences in the Intestinal Microbiome Associated with Diarrhea during Lenvatinib Treatment for Hepatocellular Carcinoma.
Lenvatinib has been widely used for the treatment of advanced hepatocellular carcinoma (HCC). Some adverse events, including diarrhea, have been reported for lenvatinib. Diarrhea may be associated with the changes in the intestinal microbiome; however, the underlying mechanism has not been elucidated. In this study, we aimed to investigate the relationship between the intestinal microbiome and diarrhea caused by lenvatinib via analysis of fecal samples collected before treatment. A total of 21 patients with advanced HCC who were treated with lenvatinib were enrolled. Fecal samples were collected from patients. The patients were divided into diarrhea (n = 8) and nondiarrhea groups (n = 12). We compared the characteristics of patients, incidence of adverse events, composition of the intestinal microbiome, and enrichment of functional pathways between both groups using QIIME2 and PICRUSt2. The median age of the two groups was 73 years. The nondiarrhea group comprised a relatively higher number of male patients than the diarrhea group; however, there were no significant differences in patient characteristics between both groups. The proportion of the microbiome was similar, and alpha and beta diversities were not significantly different between both groups. The relative abundance of order Bacteroidales, including Parabacteroides and Prevotella, was higher in the diarrhea group than in the nondiarrhea group. PICRUSt2 analysis showed some metabolic pathways, including butanoate (butyrate) metabolism, were enriched in the nondiarrhea group when compared with those in the diarrhea group. Differences in the intestinal microbiomes and their functions may influence the incidence of diarrhea during lenvatinib treatment.


Development of a DNA metabarcoding method for the identification of fifteen mammalian and six poultry species in food.
Meat products are prone to adulteration by the replacement of meat from more expensive animal species with meat from cheaper sources. We present a DNA metabarcoding method allowing the identification and differentiation of 15 mammalian and six poultry species in foodstuffs. The method, developed on the MiSeq® platform, targets a mitochondrial 16S rDNA region recently found to be suitable for the differentiation of 300 mammalian species. We designed a novel primer pair for poultry and applied it in combination with the primer pair for mammalian species in a duplex assay. The applicability of the method was investigated by analysing DNA extracts from muscle, DNA extract mixtures and extracts from model sausages. Our results indicated that the species of interest can be identified, differentiated and detected down to a proportion of 0.1%. Since 96 samples can be sequenced in one run, the method has high potential for application in routine analysis.


[Pharmacokinetic, bacteriological and clinical studies of cefuzonam in the field of obstetrics and gynecology].
Cefuzonam (CZON, L-105), an antibiotic injectable of cephalosporin family, was studied pharmacokinetically, clinically and bacteriologically to examine its distribution to female genital tissues and the activity on infections in the field of obstetrics and gynecology. Maximum concentrations in serum and genital tissues achieved 19-46 minutes after intravenous injection of CZON 1 g were 69.6 micrograms/ml for serum, 63.1 micrograms/g for oviduct, 34.2 micrograms/g for ovary, 22.5 micrograms/g for endometrium, 33.4 micrograms/g for myometrium, 30.7 micrograms/g for cervix uteri, and 37.1 micrograms/g for portio vaginalis. Clinical efficacies on 15 cases of intrauterine infection and adnexitis were proved with 4 cases of 'marked improvement' and 11 cases of 'improvement', thus the efficacy rate was 100%. Of 21 strains of aerobes and anaerobes isolated from infectious lesions, 19 strains were eliminated after administration of the drug. No side effects were observed. From these results of fundamental and clinical studies CZON appeared to be a highly useful drug fro the obstetric and gynecological infections.


Successful implantation of a cochlear implant in a four-yr-old boy after kidney transplantation: a case report.
Sensorineural hearing loss is common in children with chronic renal insufficiency. The implantation of a CI is performed routinely in children with profound sensorineural hearing loss. A feared complication is a local infection with subsequent meningitis. Because of this risk, a successful implantation of a CI in children under immunosuppression after kidney transplantation has yet to be described. A four-yr-old boy with congenital renal dysplasia and posterior urethral valves, who was successfully transplanted with a kidney from his father at the age of two and a half yr, is presented. The boy had profound bilateral hearing loss before transplantation, most likely due to ototoxic antibiotic medication and long-term furosemide use. A hearing aid was insufficient; therefore, a CI was performed 20 months after the transplantation and no complications occurred in the 24 months of follow-up. This is the first report of a successful CI in a child after kidney transplantation.


Multiresidue analysis of avermectins in bovine liver by immunoaffinity column cleanup procedure and liquid chromatography with fluorescence detector.
A multiresidue liquid chromatography (LC) method was developed to detect avermectin, ivermectin, doramectin, and eprinomectin simultaneously in bovine liver. The extracted samples were cleaned up by an immunoaffinity column, which was prepared by coupling anti-avermectin polyclonal antibody with CNBr-activated Sepharose 4B. The dynamic column capacities of avermectin, ivermectin, doramectin, and eprinomectin were 3531, 3542, 3543, and 3284 nglmL gel, respectively. The eluate was evaporated to dryness, and residues were derivatized and determined by LC with fluorescence detector set at 365 nm excitation and 465 nm emission wavelengths. Recoveries ranged from 79.3 to 115.9% with coefficients of variation of 1.1-19.4% when avermectin, ivermectin, doramectin, and eprinomectin were spiked at levels of 5-100 ng/g. The limit of quantitation of the method was 2 ng/g for each drug.


Osteogenesis of electrically stimulated bone cells mediated in part by calcium ions.
Culture selected and expanded osteoblastic cells may be able to be reintroduced into massive skeletal defects to accelerate cell mediated regeneration of skeletal tissues, especially in bone ingrowth in total joint replacement, fracture healing, and osteoporosis. In vitro osteogenic cell culture is a useful model in studying the mechanism of bone metabolism under direct current stimulation. In this study, an osteoblastlike cell line was isolated from newborn rat calvaria. The osteogenic processes of the in vitro cultured cell line were studied by cytochemical, electron microscopic, and energy dispersive x-ray analysis techniques that resembled those observed in membrane bone ossification centers in vivo. Direct current stimulation of 100 microA/cm2 accelerated greatly the proliferation and calcification of the in vitro cultured cells. Intracellular free calcium ion metabolism was measured with an Adherent Cell Analysis and Sorting Machine. Under direct current stimulation, intracellular free calcium ion concentration increased an average of 2.3 times of the original level, which may play a key role in regulating osteogenesis and bone metabolism.


LERK-2, a binding protein for the receptor-tyrosine kinase ELK, is evolutionarily conserved and expressed in a developmentally regulated pattern.
We have isolated and characterized cDNA clones that encode the rat homologue of a binding protein, LERK-2, for the receptor tyrosine kinase, elk. The cDNAs contain an open reading frame of 1527 nucleotides capable of encoding a protein 345 amino acid residues in length. The nucleotide sequence of the present clones is > 90% identical to the previously identified human LERK-2 cDNA, and the predicted proteins encoded by the rat and human clones are identical at 95% of amino acid residues. Recombinant proteins expressed from the rat cDNAs bind to elk with high affinity, similar to recombinant human LERK-2 and an endogenously-expressed rat elk-binding protein. Expression of the rat LERK-2 mRNA was detected in embryonic brain, kidney, lung, skeletal muscle, thymus, liver, and heart, and diminished in the early post-natal period. Significant LERK-2 mRNA expression in the young adult rat was restricted to the lung, kidney, heart and testes.


Acute promyelocytic leukemia and differentiation therapy: molecular mechanisms of differentiation, retinoic acid resistance and novel treatments.
Incorporation of all-trans-retinoic acid (ATRA) into the treatment of acute promyelocytic leukemia (APL), a type of acute myeloid leukemia (AML), revolutionized the therapy of cancer in the last decade and introduced the concept of differentiation therapy. ATRA, a physiological metabolite of vitamin A (retinol), induces complete clinical remissions (CRs) in about 90% of patients with APL. In contrast to the cytotoxic chemotherapeutics, ATRA can selectively induce terminal differentiation of promyelocytic leukemic cells into normal granulocytes without causing bone marrow hypoplasia or exacerbation of the frequently occurring fatal hemorrhagic syndromes in patients with APL. However, remissions induced by ATRA alone are transient and the patients commonly become resistant to the therapy, leading to relapses in most patients and thus limiting the use of ATRA as a single agent. Therefore, ATRA is currently combined with anthracycline-based chemotherapy, and this regimen dramatically improves patient survival compared to chemotherapy alone, curing about 70% of the patients. However, 30% of APL patients still relapse and die in five years. Recently, arsenic trioxide (As2O3) was proven to be highly effective in inducing CRs not only in APL patients relapsed after ATRA treatment and conventional chemotherapy but also in primary APL patients. Despite the well-documented clinical efficacy of ATRA, molecular mechanisms responsible for development of ATRA resistance are not well understood. Based on in vitro and clinical observations, several mechanisms, including induction of accelerated metabolism of ATRA, decreased bioavailability and plasma drug levels, point mutations in the ATRA-binding domain of promyelocytic leukemia (PML)-retinoic acid receptor-alpha (RARα) and other molecular events have been proposed to explain ATRA resistance. In this review, the molecular mechanisms of ATRA-induced myeloid cell differentiation and resistance are discussed, together with novel clinical approaches to overcome ATRA resistance in APL.


Inhibitory effects of an aqueous extract from Cortex Phellodendri on the growth and replication of broad-spectrum of viruses in vitro and in vivo.
Cortex Phellodendri (C. Phellodendri), the dried trunk bark of Phellodendron amurense Ruprecht, has been known as a traditional herbal medicine, showing several bioactivities. However, antiviral activity of C. Phellodendri aqueous extract (CP) not reported in detail, particularly aiming the prophylactic effectiveness. In vitro CP antiviral activity evaluated against Influenza A virus (PR8), Vesicular Stomatitis Virus (VSV), Newcastle Disease Virus (NDV), Herpes Simplex Virus (HSV), Coxsackie Virus (H3-GFP) and Enterovirus-71 (EV-71) infection on immune (RAW264.7) and epithelial (HEK293T/HeLa) cells. Such antiviral effects were explained by the induction of antiviral state which was determined by phosphorylation of signal molecules, secretion of IFNs and cytokines, and cellular antiviral mRNA expression. Furthermore, Compounds present in the aqueous fractions confirmed by HPLC analysis and evaluated their anti-viral activities. Additionally, in vivo protective effect of CP against divergent influenza A subtypes was determined in a BALB/c mouse infection model. An effective dose of CP significantly reduced the virus replication both in immune and epithelial cells. Mechanically, CP induced mRNA expression of anti-viral genes and cytokine secretion in both RAW264.7 and HEK293T cells. Furthermore, the main compound identified was berberine, and shows promising antiviral properties similar to CP. Finally, BALB/c mice treated with CP displayed higher protection levels against lethal doses of highly pathogenic influenza A subtypes (H1N1, H5N2, H7N3 and H9N2). CP including berberine play an immunomodulatory role with broad spectrum antiviral activity, due to induction of antiviral state via type I IFN stimulation mechanism. Consequently, C. Phellodendri could be a potential source for promising natural antivirals or to design other antiviral agents for animal and humans.


Amine coupling versus biotin capture for the assessment of sulfonamide as ligands of hCA isoforms.
This work was dedicated to the development of a reliable SPR method allowing the simultaneous and quick determination of the affinity and selectivity of designed sulfonamide derivatives for hCAIX and hCAXII versus hCAII, in order to provide an efficient tool to discover drugs for anticancer therapy of solid tumors. We performed for the first time a comparison of two immobilization approaches of hCA isoforms. First one relies on the use of an amine coupling strategy, using a CM7 chip to obtain higher immobilization levels than with a CM5 chip and consequently the affinity with an higher precision (CV% < 10%). The second corresponds to a capture of proteins on a streptavidin chip, named CAP chip, after optimization of biotinylation conditions (amine versus carboxyl coupling, biotin to protein ratio). Thanks to the amine coupling approach, only hCAII and hCAXII isoforms were efficiently biotinylated to reach relevant immobilization (3000 RU and 2700 RU, respectively) to perform affinity studies. For hCAIX, despite a successful biotinylation, capture on the CAP chip was a failure. Finally, concordance between affinities obtained for the three derivatives to CAs isozymes on both chips has allowed to valid the approaches for a further screening of new derivatives.


Ceramide structural features required to stimulate ABCA1-mediated cholesterol efflux to apolipoprotein A-I.
Ceramide is a component of the sphingomyelin cycle and a well-established lipid signaling molecule. We recently reported that ceramide specifically increased ABCA1-mediated cholesterol efflux to apolipoprotein A-I (apoA-I), a critical process that leads to the formation of cardioprotective HDL. In this report, we characterize the structural features of ceramide required for this effect. C2 dihydroceramide, which contains a fully saturated acyl chain and is commonly used as a negative control for ceramide apoptotic signaling, stimulated a 2- to 5-fold increase in ABCA1-mediated cholesterol efflux to apoA-I over a 0-60 muM concentration range without the cell toxicity apparent with native C2 ceramide. Compared with C2 ceramide, C6 and C8 ceramides with medium-length N-acyl chains showed a similar extent of efflux stimulation (a 2- to 5-fold increase) but at a higher onset concentration than the less hydrophobic C2 ceramide. In contrast, the reduced and methylated ceramide analogs, N,N-dimethyl sphingosine and N,N,N-trimethyl sphingosine, failed to stimulate cholesterol efflux. We found that changes in the native spatial orientation at either of two chiral carbon centers (or both) resulted in an approximately 50% decrease compared with native ceramide-stimulated cholesterol efflux. These data show that the overall ceramide shape and the amide bond are critical for the cholesterol efflux effect and suggest that ceramide acts through a protein-mediated pathway to affect ABCA1 activity.


Integrating Information Literacy and Evidence-Based Medicine Content within a New School of Medicine Curriculum: Process and Outcome.
This column describes a process for integrating information literacy (IL) and evidence-based medicine (EBM) content within a new school of medicine curriculum. The project was a collaborative effort among health sciences librarians, curriculum deans, directors, and faculty. The health sciences librarians became members of the curriculum committees, developed a successful proposal for IL and EBM content within the curriculum, and were invited to become course instructors for Analytics in Medicine. As course instructors, the librarians worked with the other faculty instructors to design and deliver active learning class sessions based on a flipped classroom approach using a proprietary Information Mastery curriculum. Results of this collaboration may add to the knowledge base of attitudes and skills needed to practice as full faculty partners in curricular design and instruction.


Simple behavioral measures of central alpha-adrenoceptor blocking activity of drugs.
Behavior of mice exposed to open field was investigated after treatment with various alpha-adrenoceptor antagonists. In addition, the interaction with clonidine and exploratory response in rats were tested. Preferential alpha-2 antagonists were found to change characteristically the open-field behavior in mice: they consistently increased grooming and decreased rearing activity. Yohimbine, rauwolscine and piperoxane produced bell-shaped effects on grooming which were compatible with their alpha-1 antagonistic activity at higher doses. Similarly, these drugs antagonized the clonidine-induced hypoactivity at lower dose-ranges and decreased the exploration in rats after higher doses. Selective alpha-1 antagonists showed only depressant effects on various behavioral measures. The results of this study indicate that the selectivity of alpha-1 or alpha-2 receptor blockade in mice and rats can be reliably determined by using behavioral parameters.


[Effect of 5-phosphoribosyl-1-pyrophosphate on the L-glutamate dehydrogenase activity of the bovine liver].
Bovine liver glutamate dehydrogenase (GDH) is a very complex enzyme in its molecular structure and activity regulation. The present paper deals with the effect of PRPP on GDH activity. This phosphate sugar, playing a key role in purine metabolism, behaves as an effector in the L-glutamate oxidation, showing both an activating effect (at low L-glu concentration) and an inhibiting one (as far as 40%), increasing with L-glu and coenzyme (3-acetyl-pyridine adenine dinucleotide) concentration. The inhibition is quite evident at low PRPP concentration, thus suggesting a physiologic role in cellular regulation of GDH activity.


Closed-cycle, low-vibration 4 K cryostat for ion traps and other applications.
In vacuo cryogenic environments are ideal for applications requiring both low temperatures and extremely low particle densities. This enables reaching long storage and coherence times, for example, in ion traps, essential requirements for experiments with highly charged ions, quantum computation, and optical clocks. We have developed a novel cryostat continuously refrigerated with a pulse-tube cryocooler and providing the lowest vibration level reported for such a closed-cycle system with 1 W cooling power for a <5 K experiment. A decoupling system suppresses vibrations from the cryocooler by three orders of magnitude down to a level of 10 nm peak amplitudes in the horizontal plane. Heat loads of about 40 W (at 45 K) and 1 W (at 4 K) are transferred from an experimental chamber, mounted on an optical table, to the cryocooler through a vacuum-insulated massive 120 kg inertial copper pendulum. The 1.4 m long pendulum allows installation of the cryocooler in a separate, acoustically isolated machine room. At the experimental chamber, we measured the residual vibrations using an interferometric setup. The positioning of the 4 K elements is reproduced to better than a few micrometer after a full thermal cycle to room temperature. Extreme high vacuum on the 10-15 mbar level is achieved. In collaboration with the Max-Planck-Institut für Kernphysik, such a setup is now in operation at the Physikalisch-Technische Bundesanstalt for a next-generation optical clock experiment using highly charged ions.


Multicentre Randomised trial of Acute Stroke treatment in the Ambulance with a nitroglycerin Patch (MR ASAP): study protocol for a randomised controlled trial.
Some studies have suggested that transdermal administration of glyceryl trinitrate (GTN; nitroglycerin) in the first few hours after symptom onset increases the chance of a favourable outcome after ischaemic stroke or intracerebral haemorrhage, possibly through an increase in intracranial collateral blood flow and a reduction in blood pressure. The Multicentre Randomised trial of Acute Stroke treatment in the Ambulance with a nitroglycerin Patch (MR ASAP) aims to assess the effect of transdermal GTN, started within 3 h after stroke onset in the prehospital setting, on functional outcome at 90 days in patients with acute ischaemic stroke or intracerebral haemorrhage. MR ASAP is a phase III, multicentre, randomised, open-label clinical trial with a blinded outcome assessment. A total of 1400 adult patients with suspected stroke and a systolic blood pressure ≥ 140 mmHg will be randomised to transdermal GTN (5 mg/day), administered as a transdermal patch by paramedics in the prehospital setting within 3 h of stroke onset and continued for 24 h or to standard care. The primary outcome is the score on the modified Rankin Scale (mRS) at 90 days, analysed with ordinal logistic regression. Secondary outcomes include blood pressure and collateral circulation at hospital admission, neurological deficit measured with the National Institutes of Health Stroke Scale at 24 h, and mortality and poor outcome (mRS score 3 to 6) at 90 days. This trial will be conducted in the Netherlands and will use a deferred consent procedure. The trial is part of the Collaboration for New Treatments of Acute Stroke (CONTRAST) programme. MR ASAP will assess whether very early administration of GTN improves outcome after stroke in a setting where rates of intravenous thrombolysis and endovascular treatment for acute ischaemic stroke are high. The deferred consent procedure facilitates prompt GTN treatment and will prevent delay to revascularisation therapies. If early transdermal GTN treatment proves to be effective, this low-cost treatment can be readily implemented into daily clinical practice. ISRCTN Registry, ISRCTN99503308 . Registered on 2 January 2018.


Acute Effects of Different Blood Flow Restriction Protocols on Bar Velocity During the Squat Exercise.
The main goal of the present study was to evaluate the effects of different blood flow restriction (BFR) protocols (continuous and intermittent) on peak bar velocity (PV) and mean bar velocity (MV) during the squat exercise at progressive loads, from 40 to 90% 1RM. Eleven healthy men (age = 23.4 ± 3.1 years; body mass = 88.5 ± 12.1 kg; squat 1RM = 183.2 ± 30.7 kg; resistance training experience, 5.7 ± 3.6 years) performed experimental sessions once a week for 3 weeks in random and counterbalanced order: without BFR (NO-BFR), with intermittent BFR (I-BFR), and with continuous BFR (C-BFR). During the experimental session, the participants performed six sets of the barbell squat exercise with loads from 40 to 90% 1RM. In each set, they performed two repetitions. During the C-BFR session, the cuffs were maintained throughout the training session. During the I-BFR, the cuffs were used only during the exercise and released for each rest interval. The BFR pressure was set to ∼80% arterial occlusion pressure (AOP). Analyses of variance showed a statistically significant interaction for MV (p < 0.02; η2 = 0.18). However, the post hoc analysis did not show significant differences between particular conditions for particular loads. There was no significant condition × load interaction for PV (p = 0.16; η2 = 0.13). Furthermore, there were no main effects for conditions in MV (p = 0.38; η2 = 0.09) as well as in PV (p = 0.94; η2 = 0.01). The results indicate that the different BFR protocols used during lower body resistance exercises did not reduce peak bar velocity and mean bar velocity during the squat exercise performed with various loads.


METEOROLOGICAL VARIABLES ASSOCIATED WITH SUBARACHNOID HEMORRHAGE: A SINGLE CENTER STUDY.
Spontaneous subarachnoid hemorrhage (SAH) can occur unexpectedly and independently of the classic risk factors. Several different factors could affect intracranial aneurysm (IA) rupture, such as morphological and hemodynamic factors. The aim of this study was to establish the potential association of meteorological data such as temperature, atmospheric pressure, and humidity, and the onset of clinical symptoms preceding hospital admission of patients with acute SAH due to IA rupture. This retrospective study included 130 consecutive patients admitted for non-traumatic SAH with a determinable onset of SAH symptoms. The effects of meteorological parameters of atmospheric pressure, ambient temperature, and relative air humidity on the day of acute SAH onset and 24 hours prior to the onset of symptoms were recorded and analyzed in each patient. Spearman rank correlation analysis was used to assess the risks of incident SAH on the basis of daily meteorological data. Seasonal incidence of acute SAH showed the peak incidence in winter and a trough in summer, with monthly incidence peak in January and December. The circadian rhythm analysis showed the peak incidence of SAH in the forenoon, followed by the evening. Acute SAH incidence showed moderate positive association with daily atmospheric pressure (p<0.05), while no association was found with ambient temperature and relative air humidity. Our results suggested no significant association of changes in ambient temperature and relative humidity with the risk of SAH. Increases in atmospheric pressure were weakly associated with a higher SAH risk. Additional studies are needed to establish in detail both meteorological and morphological factors important to predict IA rupture and SAH.


Chest physiotherapy may be associated with brain damage in extremely premature infants.
To determine whether a characteristic form of brain damage (encephaloclastic porencephaly) was associated with chest physiotherapy treatment in preterm babies. A retrospective case-control study was undertaken among 454 infants of birth weight less than 1500 gm cared for during the 3-year period of 1992 to 1994. Thirteen babies of 24 to 27 weeks of gestation who weighed 680 to 1090 gm at birth had encephaloclastic porencephaly. Twenty-six control subjects were matched for birth weight and gestation. The patients received two to three times as many treatments with chest physiotherapy in the second, third, and fourth weeks of life as did control infants (median 79 vs 19 treatments in the first 4 weeks, p < 0.001). Patients also had more prolonged and severe hypotension in the first week than did control subjects (median duration of hypotension 4 vs 0.5 days, p < 0.01), and were less likely to have a cephalic presentation (31% vs 81%, p < 0.01). Since December 1994 no very low birth weight baby has received chest physiotherapy treatment in the first month of life in our nursery, and no further cases have occurred. Encephaloclastic porencephaly may be a previously unrecognized complication of chest physiotherapy in vulnerable extremely preterm infants.


Numerical simulation of blood flow in femoral perfusion: comparison between side-armed femoral artery perfusion and direct femoral artery perfusion.
Computational numerical analysis was performed to elucidate the flow dynamics of femoral artery perfusion. Numerical simulation of blood flow was performed from the right femoral artery in an aortic model. An incompressible Navier-Stokes equation and continuity equation were solved using computed flow dynamics software. Three different perfusion models were analyzed: a 4.0-mm cannula (outer diameter 15 French size), a 5.2-mm cannula (18 French size) and an 8-mm prosthetic graft. The cannula was inserted parallel to the femoral artery, while the graft was anastomosed perpendicular to the femoral artery. Shear stress was highest with the 4-mm cannula (172 Pa) followed by the graft (127 Pa) and the 5.2-mm cannula (99 Pa). The cannula exit velocity was high, even when the 5.2-mm cannula was used. Although side-armed perfusion with an 8-mm graft generated a high shear stress area near the point of anastomosis, flow velocity at the external iliac artery was decreased. The jet speed decreased due to the Coanda effect caused by the recirculation behind sudden expansion of diameter, and the flow velocity maintains a constant speed after the reattachment length of the flow. This study showed that iliac artery shear stress was lower with the 5.2-mm cannula than with the 4-mm cannula when used for femoral perfusion. Side-armed graft perfusion generates a high shear stress area around the anastomotic site, but flow velocity in the iliac artery is slower in the graft model than in the 5.2-mm cannula model.


ACTL6A suppresses p21Cip1 expression to enhance the epidermal squamous cell carcinoma phenotype.
Epidermal squamous cell carcinoma (SCC) is a common and highly invasive form of cancer. SCC arises due to ultraviolet light exposure and is associated with increased expression of pro-cancer genes and reduced expression of cancer suppressors. Actin-Like Protein 6A (ACTL6A, BAF53a) is an important protein subunit of the SWI/SNF epigenetic chromatin regulatory complex. ACTL6A is elevated in cancer cells and has been implicated as a driver of cancer cell proliferation and tumor growth. In the present study, we show that ACTL6A drives SCC cell proliferation, spheroid formation, invasion and migration, and that these activities are markedly reduced by ACTL6A knockdown. We further show that ACTL6A expression is associated with reduced levels of the p21Cip1 cyclin-dependent kinase inhibitor and tumor suppressor protein. Molecular studies show that ACTL6A interacts with p53 DNA response elements in the p21Cip1 gene promoter to suppress p21Cip1 promoter activity and mRNA and protein level. Additional studies show that an increase in p21Cip1 expression in ACTL6A knockdown cells is required for suppression of the SCC cell phenotype, suggesting that p21Cip1 is a mediator of ACTL6A action. We further show that this regulation is p53 independent. These findings suggest that ACTL6A suppresses p21Cip1 promoter activity to reduce p21Cip1 protein as a mechanism to maintain the aggressive epidermal SCC phenotype.


In situ visualization of a glycoform of transferrin: localization of α2,6-sialylated transferrin in the liver.
We previously found that a lectin, Sambucus sieboldiana agglutinin (SSA), bound to α2,6-sialylated glycan epitopes on transferrin and inhibited anti-transferrin antibody binding to the antigen in ELISA (SSA inhibition). Here we report that SSA inhibition is applicable to immunohistochemistry, localizing α2,6-sialylated transferrin in the liver. Immunohistochemistry using anti-transferrin polyclonal antibody revealed that transferrin was detected in hepatocytes near interlobular veins. Addition of SSA lectin markedly attenuated the staining. Sialidase treatment of a liver section abolished SSA binding and concomitantly cancelled SSA inhibition, suggesting that SSA binding to glycan epitopes on the section was essential for the inhibition. To examine the importance of proximity between antigen epitopes and SSA-binding (glycosylation) sites, we prepared two anti-peptide antibodies against partial amino acid sequences of transferrin. One antibody (Tf-596Ab) is against a peptide sequence, Cys596-Ala614, which is proximal to N-glycosylation sites (Asn-432 and Asn-630). The other (Tf-120Ab) is against a peptide sequence, Val120-Cys137, distal to the sites. The staining signals of Tf-596Ab were reduced by the addition of SSA, whereas those of Tf-120Ab were reduced only a little. This result suggests that proximity of the antigen epitope to SSA binding sites is critical for SSA inhibition in immunohistochemistry.


[Epigenetics 2.0: The multiple faces of the genome].
Epigenetics is the branch of genetics that studies the dynamic relationship between stable genotypes and varying phenotypes. To this end, epigenetics aims to discover the molecular mechanisms that explain how different nutrients and hormones, environmental changes, and emotional, social and cognitive experiences modify gene expression and behaviors, even permanently so. Psychiatry has learned that diseases with strong genetic predisposition, such as schizophrenia, show a concordance of around 50% between monozygotic twins, thus evidencing the importance of the genetic background and the presence of environmental variables that stimulate or block phenotypic development. The interest in epigenetics has increased during the last few years due to fundamental discoveries made in molecular and behavioral genetics, although within this framework factual knowledge coexists with fictional expectations and wrong concepts. Is it possible that epigenetic variants modify temperament and human behavior? May abused or neglected children develop long-lasting epigenetic marks in their DNA? May bipolar states correlate with different epigenetic signatures? Studying these subjects in not an easy task, but experiments performed in lab animals suggest that these conjectures are reasonable, although there is still a long distance between hypotheses and scientifically proven facts.


Aversive functions of response effort: Fact or artifact?
Historically, effort has been viewed as aversive. Most supporting evidence comes from studies demonstrating increased force/effort requirements reduce operant responding. Changes in force/effort requirements, however, are often accompanied by changes in response definition when mechanical devices are used to define the response. As a consequence, responses measured at one point in a study may go unmeasured at other points. In an alternative approach, we used a continuous measurement strategy that provided a means to fix the threshold force defining the response class and simultaneously allowed independent manipulation of the force criteria required to produce reinforcement. Rats pressed a force transducer according to a fixed-ratio 5 schedule of food delivery. The criterion force was systematically increased and decreased; the threshold for response detection was constant. When response rates included only criterion responses, overall rate decreased when force requirements increased. By contrast, when all responses, both those meeting force criteria and those that did not (above the threshold but below the criteria for reinforcement) were included in the rate calculation, increases in force increased response rate. Increases in force criteria also increased the maximum force (g) and time-integral of force (g-s) of operant behavior. Control conditions showed increases in responding could be explained by the emergence of subcriterion responses, irrespective of force. We conclude that prior results showing effort decreases response rates are due to an artifact arising from inadvertent changes in response definitions. Increases in effort may better be understood as changes in the response:reinforcer payoff owing to the emergence of a subcriterion response class.


Development of specialist and advanced practice in North America.
North American literature provides interesting ideas about the nature of specialist and advanced practice which are useful in informing British thinking on these subjects. However, the two roles do not have the same meanings as their British counterparts. Clarification of the terminology used and the roles described are essential if we are to understand the concepts. This article presents an overview of the literature about clinical nurse specialist and advanced practitioner roles within North America and identifies differences and similarities between the two.


Listeria intracellular growth and virulence require host-derived lipoic acid.
Listeria monocytogenes is a Gram-positive intracytosolic pathogen that causes severe disease in pregnant and immunocompromised individuals. We found that L. monocytogenes lacking the lipoate protein ligase LplA1 was defective for growth specifically in the host cytosol and was less virulent in animals by a factor of 300. A major target for LplA1, the E2 subunit of pyruvate dehydrogenase (PDH), lacked a critical lipoyl modification when the DeltalplA1 strain was grown intracellularly, which suggests that abortive growth was due to loss of PDH function. Thus, the use of host-derived lipoic acid may be a critical process for in vivo replication of bacterial pathogens.


Functional Connectivity of the Brain Across Rodents and Humans.
Resting-state functional magnetic resonance imaging (rs-fMRI), which measures the spontaneous fluctuations in the blood oxygen level-dependent (BOLD) signal, is increasingly utilized for the investigation of the brain's physiological and pathological functional activity. Rodents, as a typical animal model in neuroscience, play an important role in the studies that examine the neuronal processes that underpin the spontaneous fluctuations in the BOLD signal and the functional connectivity that results. Translating this knowledge from rodents to humans requires a basic knowledge of the similarities and differences across species in terms of both the BOLD signal fluctuations and the resulting functional connectivity. This review begins by examining similarities and differences in anatomical features, acquisition parameters, and preprocessing techniques, as factors that contribute to functional connectivity. Homologous functional networks are compared across species, and aspects of the BOLD fluctuations such as the topography of the global signal and the relationship between structural and functional connectivity are examined. Time-varying features of functional connectivity, obtained by sliding windowed approaches, quasi-periodic patterns, and coactivation patterns, are compared across species. Applications demonstrating the use of rs-fMRI as a translational tool for cross-species analysis are discussed, with an emphasis on neurological and psychiatric disorders. Finally, open questions are presented to encapsulate the future direction of the field.


Integrative elements for Bacillus subtilis yielding tetracycline-dependent growth phenotypes.
We describe the construction and application of elements for random insertion of promoter containing DNA into the genome of Bacillus subtilis. The outward-facing promoter of these integrative elements termed InsTet(G+) is inducible by tetracycline so that conditional mutants are generated. We constructed three InsTet(G+) variants using different regulatory windows. In the first, the regulator gene tetR is located within the element, allowing one-step mutagenesis. The second contains tetR in the chromosome and yields the best regulation efficiency. The third exploits xylose-dependent tetR expression from a plasmid, enabling induction of TetR synthesis so that distinct expression levels of an affected gene can be adjusted. We have obtained mutant strains with all three variants. For some of them, growth can be modulated by the presence of effectors. Most growth defects occur in the presence of inducers, presumably due to regulated expression of antisense RNA.


Identification and characterization of atypical 2-cysteine peroxiredoxins from mud crab Scylla paramamosain: The first evidence of two peroxiredoxin 5 genes in non-primate species and their involvement in immune defense against pathogen infection.
Peroxiredoxin 5 (Prx5) belongs to a novel family of evolutionarily conserved antioxidant proteins that protect cells against various oxidative stresses. Generally, no more than one Prx5 transcript had been reported in non-primate species. In this study, two Prx5 genes (coined as SpPrx5-1 and SpPrx5-2) were firstly isolated from the mud crab, Scylla paramamosain, through RT-PCR and RACE methods. The open reading frame of SpPrx5-1 and SpPrx5-2 were 561 bp and 429 bp in length, encoding 186 and 142 amino acids polypeptide, respectively. Both the conserved signatures of peroxiredoxin catalytic center and Prx5-specific domain were identified in SpPrx5-1 and SpPrx5-2. Phylogenetic analysis indicated that both SpPrx5 clustered together with other animal Prx proteins and were classified into Prx5 subfamily. Tissue-specific expression analysis revealed that both SpPrx5-1 and SpPrx5-2 were ubiquitously expressed, highest in hepatopancreas, and showed remarkably similar transcription patterns. Quantitative RT-PCR analysis exhibited that both SpPrx5 genes changed dramatically in hepatopancreas, although showing different expression profiles, after virus-analog poly (I:C) or Vibrio alginolyticus challenge. The expression levels of both SpPrx5s were significantly enhanced in hepatopancreas after poly (I:C) stimulation, while SpPrx5-2 exhibited a more prompt response than SpPrx5-1. Nevertheless, the expression levels of both SpPrx5s were significantly reduced in hepatopancreas after Vibrio alginolyticus challenge in which SpPrx5-1 showed a more prompt response than SpPrx5-2. These results suggested the involvement of SpPrx5s in responses against viral and bacterial infections and further highlighted their functional importance in the immune system of Scylla paramamosain.


Variation in Generic Drug Manufacturers' Product Characteristics.
Studies suggest appearance may be an important factor in medication nonadherence. This study was undertaken to characterize the range of appearances and costs of 16 oral solid generic medications in four major chronic diseases/conditions. We identified frequently prescribed medications in four therapeutic classes-antidiabetics, 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors (statins), beta blockers, and heart failure drugs-and verified that each had at least three generic manufacturer sources in 2016. The color, shape, scoring, and size for each formulation were compared. Prices were determined based on manufacturers' self-reported wholesale acquisition costs effective December 31, 2016. We identified 40 unique manufacturers for the antidiabetics, 35 for the statins, 38 for the beta blockers, and 71 for the heart failure agents. For all 16 drugs across all four disease states, there was an average of three colors, two shapes, 11 manufacturers, and four appearances when color and shape together are considered. The cost variance per drug ranged from 2% to more than 62,253%. Substantial appearance variation among generically equivalent products raises the strong possibility that patients may experience product switches that could increase the likelihood of nonadherence. Our data support the need to further study drug appearance changes and interventions as a potential factor affecting chronic disease adherence outcomes.


Molecular characterisation and expression of Atlantic cod (Gadus morhua) myoglobin from two populations held at two different acclimation temperatures.
Much previous research has demonstrated the plasticity of myoglobin concentrations in both cardiac and skeletal myocytes in response to hypoxia and training. No study has yet looked at the effect of thermal acclimation on myoglobin in fish. Atlantic cod (Gadus morhua) from two different populations, i.e. the North Sea and the North East Arctic, were acclimated to 10 and 4 degrees C. Both the myoglobin mRNA and myoglobin protein in cod hearts increased significantly by up to 3.7 and 2.3 fold respectively as a result of acclimation to 4 degrees C. These increments were largest in the Arctic population, which in earlier studies have been shown to possess cold compensated metabolic demands at low temperatures. These metabolic demands associated with higher mitochondrial capacities may have driven the increase in cardiac myoglobin concentrations, in order to support diffusive oxygen supply. At the same time the increase in myoglobin levels may serve further functions during cold acclimation, for example, protection of the cell against reactive oxygen species, and scavenging nitric oxide, thereby contributing to the regulation of mitochondrial volume density.


First measurements of the absolute neutron spectrum using the magnetic recoil spectrometer at OMEGA (invited).
A neutron spectrometer, called a magnetic recoil spectrometer (MRS), has been built and implemented at the OMEGA laser facility [T. R. Boehly et al., Opt. Commun. 133, 495 (1997)] for absolute measurements of the neutron spectrum in the range of 6-30 MeV, from which fuel areal density (rhoR), ion temperature (T(i)), and yield (Y(n)) can be determined. The results from the first MRS measurements of the absolute neutron spectrum are presented. In addition, measuring rhoR at the National Ignition Facility (NIF) [G. H. Miller et al., Nucl. Fusion 44, S228 (2004)] will be essential for assessing implosion performance during all stages of development from surrogate implosions to cryogenic fizzles to ignited implosions. To accomplish this, we are also developing an MRS for the NIF. As much of the research and development and instrument optimization of the MRS at OMEGA are directly applicable to the MRS at the NIF, a description of the design and characterization of the MRS on the NIF is discussed as well.


Volatile organic compounds from arctic bacteria of the Cytophaga-Flavobacterium-Bacteroides group: a retrobiosynthetic approach in chemotaxonomic investigations.
Volatile organic compounds emitted by different marine arctic strains of the Cytophaga-Flavobacterium-Bacteroides group were investigated by using a modified closed-loop stripping apparatus (CLSA). Seven of nine strains emitted volatiles, dominated by methyl ketones, in specific patterns. The methyl ketones were aliphatic saturated, or unsaturated, and comprised 12 to 18 C-atoms, sometimes with terminal Me branches. They were identified by GC/MS, retention-index calculations, derivatization with dimethyl disulfide for C=C bond location, and GC/FTIR to elucidate their uniform (Z)-configuration. The proposed structures of all methyl ketones were subsequently confirmed by synthesis, while the absolute configuration of chiral volatiles was elucidated by stereoselective synthesis. From retrobiosynthetic considerations, it was found that strain ARK10267 uses mainly valine, and strain ARK10063 mainly isoleucine for formation of starters for the ketone biosynthesis, which is correlated to fatty acid biosynthesis. Four strains (ARK10223, ARK10044, ARK10141, and ARK10146) use leucine. These separations are supported by phylogenetic affiliations based on 16S rRNA. Strain ARK10255b, in the course of this study found to be not a member of the Cytophaga-Flavobacterium-Bacteroides phylum, did not emit aliphatic ketones of medium chain length, but methionine-derived 4-(methylsulfanyl)butan-2-one and corresponding 4-(methylsulfanyl)butan-2-ol. Most of the compounds described have not been reported previously from nature.


Bidirectional role of reactive oxygen species during inflammasome activation in acrolein-induced human EAhy926 cells pyroptosis.
Acrolein, a known toxin in tobacco smoke, has been demonstrated to be associated with inflammatory cardiovascular diseases, such as atherosclerosis. However, the definite mechanism of acrolein-induced inflammation remains unclear. Here, we report that acrolein induces reactive oxygen species (ROS) production in EAhy926 cells. Additionally, acrolein induces EAhy926 cells' inflammatory response and pyroptosis by activating NOD-like receptor protein 3 (NLRP3) inflammasome. Also, acrolein-induced cytotoxicity could be attenuated by N-acetyl-L-cysteine (NAC). Furthermore, acrolein upregulates the level of autophagy which can be reversed by NAC. Notably, the present study also indicates that autophagy inhibited by inhibitor 3-methyladenine (3MA) and siAtg7 exacerbate acrolein-induced NLRP3 inflammasome activation and pyroptosis. In summary, acrolein induced cytotoxicity by ROS-mediated NLRP3 inflammasome activation, and ROS upregulates the level of autophagy to inhibit the NLRP3 inflammasome excessive activation, indicating the bidirectional role of ROS in acrolein-induced cellular inflammation. Our results may provide novel mechanistic insights into acrolein-induced cardiovascular toxicity.


Gaps in Parental Understanding of Sleep Disturbances During Maintenance Therapy for Pediatric Acute Lymphoblastic Leukemia.
Background: Acute lymphoblastic leukemia (ALL) is the most common cancer in childhood, with survival rates approaching 90%. Sleep disturbance is common among ALL patients, often developing during the initial stages of chemotherapy treatment. While there have been significant efforts to understand and intervene in this issue during survivorship, there is far less research on children who are actively receiving treatment. In the current study, we sought to better understand the parent's experience in the sleep domain during maintenance therapy, including their perceptions of how their child's medical team had managed sleep disturbances, and recommendations for how to improve sleep management. Method: Fifteen parents of pediatric ALL patients (aged 4-12 years) completed semistructured interviews. Interview content was analyzed using a multistage thematic analysis. Results: Parents consistently expressed feeling unprepared to manage the sleep disruptions that arose during treatment, often reporting that they did not recall being told this would be a side effect. They were enthusiastic about learning how to improve their child's sleep, though they did not want pharmacotherapeutic interventions or additional medical/psychosocial appointments to address this. Conclusion: Despite consistent provider communication on sleep, parents report limited knowledge of the issue. This provides an obvious intervention target to improve treatment-related sleep disturbances. Clear messaging may help direct parents' attention and expectations regarding their child's treatment and potential for disturbed sleep, possibly in the form of a behavioral intervention that empowers parents with information about how to support their child's sleep health while they are undergoing treatment for ALL.


[1,2-Bis-(diisopropyl-phosphan-yl)ethane-κP,P']dichloridonickel(II)-9H-carbazole (1/2).
In the title compound, [NiCl(2)(C(14)H(32)P(2))]·2C(12)H(9)N, the neutral [Ni(dppe)Cl(2)] complex [dppe is 1,2-bis-(diisopropyl-phosphan-yl)ethane] consists of a tetracoordinated Ni(2+) cation and has a crystallographic twofold axis passing through the metal atom and the mid-point of the CH(2)-CH(2) bond of the dppe ligand. The metal atom shows slight tetra-hedral distortion from an ideal square-planar coordination geometry, as reflected in the dihedral angle between NiCl(2) and NiP(2) planes of 15.32 (2)°. The 9H-carbazole ring system is essentially planar (r.m.s. deviation = 0.022 Å). In the crystal packing, there are two symmetry-related 9H-carbazole mol-ecules between two adjacent Ni(II) complexes, with an angle between the carbazole mean planes of ca 77°.


The metalloproteinase ADAMTS1: a comprehensive review of its role in tumorigenic and metastatic pathways.
As it was first characterized in 1997, the ADAMTS (A Disintegrin and Metalloprotease with ThromboSpondin motifs) metalloprotease family has been associated with many physiological and pathological conditions. Of the 19 proteases belonging to this family, considerable attention has been devoted to the role of its first member ADAMTS1 in cancer. Elevated ADAMTS1 promotes pro-tumorigenic changes such as increased tumor cell proliferation, inhibited apoptosis and altered vascularization. Importantly, it facilitates significant peritumoral remodeling of the extracellular matrix environment to promote tumor progression and metastasis. However, discrepancy exists, as several studies also depict ADAMTS1 as a tumor suppressor. This article reviews the current understanding of ADAMTS1 regulation and the consequence of its dysregulation in primary cancer and ADAMTS1-mediated pathways of cancer progression and metastasis.


Single alpha-domain constructs of the Na+/Ca2+ exchanger, NCLX, oligomerize to form a functional exchanger.
Spliced isoforms of the Na+/Ca2+ exchanger, NCLX, truncated at the alpha-repeat region have been identified. The activity and functional organization of such proteins are, however, poorly understood. In the present work, we have studied Na+/Ca2+ exchange mediated by single alpha-repeat constructs (alpha1 and alpha2) of NCLX. Sodium-dependent calcium transport was fluorescently detected in both the reversal and forward modes; calcium-dependent outward currents were also recorded using a whole cell patch configuration in HEK293 cells heterologously expressing either the alpha1 or alpha2 single-domain proteins. In contrast, calcium transport and reversal currents were not detected when cells were transfected with a vector or with an alpha2 mutant (alpha2-S273T). Thus, our data indicate that the single alpha-domain constructs mediate electrogenic Na+/Ca2+ exchange. The alpha1 domain, but not the alpha2, exhibited partial sensitivity to the NCX inhibitor, KB-R7943, while Li+-dependent Ca2+ efflux was detected in cells expressing either the alpha1 or alpha2 construct. The functional organization of the single alpha-domain constructs was assessed using a dominant-negative approach. Coexpression of the alpha1 or alpha2 constructs with the nonfunctional alpha2-S273T mutant had a synergistic inhibitory effect on Na+/Ca2+ transport. Dose-dependence analysis of the inhibition of alpha2 construct activity by the alpha2-S273T mutant indicated that the functional unit is either a dimer or a trimer. Immunoprecipitation analysis indicated that the alpha2 construct indeed interacts with the alpha2-S273T mutant. Taken together, our data indicate that although single alpha1 or alpha2 domain constructs are independently capable of Na+/Ca2+ exchange, oligomerization is required for their activity. Such organization may give rise to transport activity with distinct kinetic parameters and physiological roles.


Reduced lung function in leukaemia patients undergoing bone marrow transplantation.
20 patients with leukaemia in remission or early relapse received an allogeneic bone marrow graft. Patients were conditioned according to Seattle protocol with high dose cyclophosphamide and total body irradiation to a total dose of 8 Gray to the lungs delivered by a 6 MV linear accelerator at a dose rate of approximately 0.06 Gray/min. As prophylaxis against the graft versus host reaction, methotrexate and/or cyclosporin A were given. Lung function was studied prior to treatment and every 3 months thereafter. Before treatment a marked decrease was seen in the CO diffusion capacity when compared to the predicted value, while the flow volume relationships were within normal limits. The cause of this is unknown, but may be due to previous infections and the cytostatic treatment given. After bone marrow transplantation, a further irreversible decrease was seen in the CO diffusion capacity and vital capacity indicating an additive effect of the lung irradiation.


Effects of different rearing systems on meat production traits and meat fiber microstructure of Beijing-you chicken.
Beijing-you is a Chinese local chicken which is raised for both meat and eggs. In the present study, we detected the effects of different rearing systems on growth, slaughtering performances and meat quality of Beijing-you chickens at 26-40 weeks of age. Six hundred Beijing-you hens were randomly allocated into two groups at 16 weeks of age and raised in free range or battery cage systems. The body weight, slaughtering performance and meat quality were measured for each group at the ages of 26, 30, 35 and 40 weeks. Some of the traits were dramatically influenced by the two systems, although most of them did not show significant changes. For the meat fiber microstructure, we found that the diameter of thigh and breast muscle fiber in the free range group were significantly increased than in the cage group (P < 0.05) at 26 weeks of age. The ratio of fast muscle fiber in thigh muscle samples of the free range group was significantly reduced compared to that of cage group at both 35 (P < 0.01) and 40 (P < 0.01) weeks of age, indicating that the free range system could promote the transforming of fast muscle fiber to slow muscle fiber.


Calories and portion sizes in recipes throughout 100 years: an overlooked factor in the development of overweight and obesity?
Large portion sizes have been associated with large energy intake, which can contribute to the development of overweight and obesity. Portion sizes of non-home cooked food have increased in the past 20 years, however, less is known about portion sizes of home-cooked food. The aim of the study was to assess if the portion sizes measured in calories in Danish cookbook recipes have changed throughout the past 100 years. Portion size measured in calories was determined by content-analysis of 21 classic Danish recipes in 13 editions of the famous Danish cookbook "Food" from 1909 to 2009. Calorie content of the recipes was determined in standard nutritional software, and the changes in calories were examined by simple linear regression analyses. Mean portion size in calories increased significantly by 21% (β = 0.63; p < 0.01) over the past 100 years in the analyzed recipes. The mean portion size in calories from a composed homemade meal increased by 77% (β = 2.88; p < 0.01). The mean portion size in calories from meat increased by 27% (β = 0.85; p = 0.03), starchy products increased by 148% (β = 1.28; p < 0.01), vegetables increased by 37% (β = 0.21; p = 0.13) and sauce increased by 47% (β = 0.56; p = 0.02) throughout the years. Portion sizes measured in calories in classical Danish recipes have increased significantly in the past 100 years and can be an important factor in increased energy intake and the risk of developing overweight and obesity.


RELATION OF GUILT, SHAME, BEHAVIORAL AND CHARACTEROLOGICAL SELF-BLAME TO DEPRESSIVE SYMPTOMS IN ADOLESCENTS OVER TIME.
In a two-wave, longitudinal study, 221 nonreferred adolescents completed measures of guilt, shame, Behavioral self-blame (BSB), Characterological self-blame (CSB), depressive symptoms measures, and attributional style. Goals were to examine similarities between Tangney's (1996) conceptualization of guilt and shame and Janoff-Bulman's (1979) conceptualization of BSB and CSB in adolescents. Specific aims were (1) to examine the relation of depressive symptoms and depressive cognitions to shame, guilt, CSB, and BSB, (2) to estimate the longitudinal relations between depressive symptoms and measures of guilt, shame, BSB, and CSB, and (3) to assess the convergent and discriminant validity of shame/CSB measures and guilt/BSB measures. Results suggest that shame and CSB converge into a common construct, significantly related to depressive symptoms and cognitions. Convergence of guilt and BSB, however, was limited to particular pairs of measures.


[Metals, air pollution, and health: mosses to the rescue of epidemiology].
While evidence has accumulated about the links between long-term exposure to air pollution and health, little is known about the health effects of airborne metals. In France, the law makes it mandatory to monitor atmospheric concentrations and deposition of some airborne metals, through measurements or modelling. But the available data are either too scarce or irregular, making them difficult to use in large-scale epidemiology: using mosses in the wild offers a welcome alternative. Mosses belong to the few vegetal organisms able to accumulate airborne metals. As such, they have been used for decades in air quality survey networks in Europe. They provide data to assess population exposure to airborne metals and may complement classical research programmes on air pollution epidemiology. As an example, we estimated associations between exposure to airborne metals of anthropogenic origin and increased mortality in France.


Bioresorbable nanofiber-based systems for wound healing and drug delivery: optimization of fabrication parameters.
Wound healing is a complex process that often requires treatment with antibiotics. This article reports the initial development of a biodegradable polymeric nanofiber-based antibiotic delivery system. The functions of such a system would be (a) to serve as a biodegradable gauze, and (b) to serve as an antibiotic delivery system. The polymer used in this study was poly(lactide-co-glycolide) (PLAGA), and nanofibers of PLAGA were fabricated with the use of the electrospinning process. The objective of this study was to determine the effect of fabrication parameters: orifice diameter (needle gauge), polymer solution concentration, and voltage per unit length, on the morphology and diameter of electrospun nanofibers. The needle gauges studied were 16 (1.19 mm), 18 (0.84 mm), and 20 (0.58 mm), and the range of polymer solution concentration studied was from 0.10 g/mL to 0.30 g/mL. The effect of voltage was determined by varying the voltage per unit electrospinning distance, and the range studied was from 0.375 kV/cm to 1.5 kV/cm. In addition, the mass per unit area of the electrospun nanofibers as a function of time was determined and the feasibility of antibiotic (cefazolin) loading into the nanofibers was also studied. The results indicate that the diameter of nanofibers decreased with an increase in needle gauge (decrease in orifice diameter), and increased with an increase in the concentration of the polymer solution. The voltage study demonstrated that the average diameter of the nanofibers decreased with an increase in voltage. However, the effect of voltage on fiber diameter was less pronounced as compared to polymer solution concentration. The results of the areal density study indicated that the mass per unit area of the electrospun nanofibers increased linearly with time. Feasibility of drug incorporation into the nanofibers was demonstrated with the use of cefazolin, a broad-spectrum antibiotic. Overall, these studies demonstrated that PLAGA nanofibers can be tailored to desired diameters through modifications in processing parameters, and that antibiotics such as cefazolin can be incorporated into these nanofibers. Therefore, PLAGA nanofibers show potential as antibiotic delivery systems for the treatment of wounds.


Collateral benefits of the family check-up in early childhood: primary caregivers' social support and relationship satisfaction.
This research investigated potential collateral benefits of the Family Check-Up (FCU) intervention, namely, primary caregivers' perceived social support and couple relationship satisfaction. A subsample of 435 low-income families with a 2-year-old child was recruited to participate in a randomized controlled trial assessing preventative effects of the FCU. Longitudinal growth models were used to evaluate intention-to-treat effects of the FCU on increases in primary caregivers' ratings of social support satisfaction with perceived social support and significant-other relationships, and indirect effects on primary caregivers through improvements in children's behavior problems. Support was found for a model in which reductions in child problem behavior from ages 2 to 4 predicted positive change in caregiver-rated social support and relationship satisfaction over a 3-year period. This indirect effects model is discussed with respect to implications for early childhood prevention research focused on improving family functioning.


Total synthesis of methyl sarcophytoate, a marine natural biscembranoid.
The total synthesis of methyl sarcophytoate (1), a marine natural biscembranoid, has been achieved by the thermal Diels-Alder reaction between the 14-membered dienophile unit, methyl sarcoate (2), and the 14-membered diene unit 64. Methyl sarcoate (2) was prepared using n-BuLi-Bu(2)Mg-mediated dithiane coupling, Kosugi-Migita-Stille coupling, and Grubbs ring-closing metathesis. The diene unit 64 was prepared using Sharpless asymmetric epoxidation, Grubbs ring-closing metathesis, 6-exo-tet epoxide opening, and n-BuLi-Bu(2)Mg-mediated Ito-Kodama cyclization. The final Diels-Alder reaction between 2 and 64 proceeded with high site, endo/exo, pi-face, and regioselectivities. During this reaction, partial E --> Z isomerization at the C4 position was observed.


Pharmacological mechanism of quercetin in the treatment of colorectal cancer by network pharmacology and molecular simulation.
Colorectal cancer is a serious threat to people's life due to its high incidence and high mortality. Quercetin can effectively treat colorectal carcinoma (CRC), but its exact mechanism of action is still unclear. Then quercetin-related target genes were obtained from Swiss Target Prediction database and Similarity Ensemble Approach (SEA) database, and CRC-related target genes were obtained from GeneCards database, respectively. Common target genes were obtained by FunRich software. String software was used to construct a protein-protein interaction (PPI) network. R package was used for gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. Molecular docking, molecular dynamics (MD) simulation and post-dynamics simulation were used to explore the binding stability of quercetin to key targets. In total, 103 and 141 target information of quercetin were obtained from the Swiss Target Prediction database and SEA database, respectively. 1,649 CRC-related genes were obtained from GeneCards database. FunRich software was used to draw venny map and obtain 36 intersection targets of quercetin and CRC. String software was used to construct the PPI network. The core genes were AKT1, EGFR, MMP9, KDR, MET and PTK2. There were 532 items related to biological processes, 14 items related to cellular components, and 43 items related to molecular functions among the key target GO enrichment items. KEGG enrichment pathways of key targets involved cancer pathways, PI3K-Akt signal pathway, etc. The results of molecular docking, MD simulation and post-dynamics simulation showed they had a good affinity and formed a stable effect. So quercetin may play an important role in the treatment of CRC by acting on AKT1, EGFR, MMP9, KDR, MET and PTK2 to affect the development of CRC.Communicated by Ramaswamy H. Sarma.


Practice patterns of Canadian Ophthalmological Society members in cataract surgery--2009 survey.
To establish the practice patterns of the members of the Canadian Ophthalmological Society (COS) in cataract surgery. A questionnaire consisting of multiple choice questions on cataract surgery practices was sent as an attachment by email to the members of the COS. Seven-hundred and seventy-seven COS members with a valid email address in the Society's database. A 29-item questionnaire pertaining to cataract surgery practices was sent by email. A reminder email with the attached questionnaire was sent 3 weeks later. The survey data were descriptively analyzed with the Statistical Package for the Social Sciences (SPSS) v 16.0 software and the results compared with those from surveys by the American Society of Cataract and Refractive Surgery and the European Society of Cataract and Refractive Surgeons. There were 161 responses. Of these, 30 members did not do any cataract surgery, and a further 8 responses were incomplete, therefore, 123 responses were analyzed. The majority of the respondents (69.1%) were between 40-59 years old. Phacoemulsification was the procedure of choice of all the respondents. Topical anaesthesia with clear corneal incisions was the most popular technique. Only 59.8% of respondents used a NSAID drop while 90.1% used a steroid drop postoperatively. The practice patterns of the members of the COS for cataract surgery have not been reported before. This survey will serve as a baseline for future ones.


[Nuclear RNA turnover. 1. Metabolic heterogeneity].
It is usually necessary to compare the kinetics of labelling of nucleoside triphosphates and nuclear RNAs to determine the turnover rate (half-life, T1/2) of nuclear RNAs. It is shown that the widely adopted correction for non-constant specific radioactivity of precursor pool is not correct in general and could be used only for very stable RNAs. The method for T1/2 determination is described which is suitable for any form of UTP labelling kinetics. Besides, the criterion was found for revelation of metabolic heterogeneity of nuclear RNA population. Rat liver nuclear DNA-like RNA appeared to be heterogeneous and consisted of two subpopulations, one rapidly labelled with T1/2 about 30 min and other, three times larger, with no labelling during the experiment.


Serum immunoreactive trypsin and trypsin inhibitors during acute pancreatitis.
Serum trypsin, total trypsin-inhibitor capacity, alpha-1-antitrypsin and alpha-2-macroglobulin were analyzed daily in ten patients hospitalized as a result of acute pancreatitis. Markedly raised serum trypsin concentrations were found in all patients. Alpha-1-antitrypsin and the trypsin-inhibitor capacity were also significantly increased as compared to post-illness values, but alpha-2-macroglobulin tended to decrease during acute pancreatitis. The post-illness values of all these parameters were in the normal range. It is concluded that a deficiency of alpha-1-antitrypsin, trypsin-inhibitor capacity of alpha-2-macroglobulin is not present in patients with acute pancreatitis which could render the pancreas more vulnerable to its own proteases. During acute pancreatitis trypsin is released into the circulation, but it is effectively inactivated by serum protease inhibitors, mainly alpha-1-antitrypsin, which can be seen as an increased trypsin-inhibitor capacity in these patients. The use of protease inhibitors in the treatment of acute pancreatitis seems to be unnecessary against this background. Increased serum trypsin values can be used when confirming the diagnosis of acute pancreatitis.


MALDI-2 Mass Spectrometry for Synthetic Polymer Analysis.
Synthetic polymers are ubiquitous in daily life, and their properties offer diverse benefits in numerous applications. However, synthetic polymers also present an increasing environmental burden through their improper disposal and subsequent degradation into secondary micro- and nanoparticles (MNPs). These MNPs accumulate in soil and water environments and can ultimately end up in the food chain, resulting in potential health risks. Matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI MSI) has the potential to study localized biological or toxicological changes in organisms exposed to MNPs. Here, we investigate whether MALDI-2 postionization can provide a sensitivity enhancement in polymer analysis that could contribute to the study of MNPs. We evaluated the effect of MALDI-2 by comparing MALDI and MALDI-2 ion yields from polyethyleneglycol (PEG), polypropylene glycol (PPG), polytetrahydrofuran (PTHF), nylon-6, and polystyrene (PS). MALDI-2 caused a signal enhancement of the protonated species for PEG, PPG, PTHF, and nylon-6. PS, by contrast, preferentially formed radical ions, which we attribute to direct resonance-enhanced multiphoton ionization (REMPI). REMPI of PS led to an improvement in sensitivity by several orders of magnitude, even without cationizing salts. The improved sensitivity demonstrated by MALDI-2 for all polymers tested highlights its potential for studying the distribution of certain classes of polymers in biological systems.


The symptom experience of hospitalised Chinese children and adolescents and relationship to pre-hospital factors and behaviour problems.
To describe the symptom experience of hospitalised Chinese children and adolescents and examine the relationship of symptoms to pre-hospital factors and child behaviour. Data were collected at two hospital sites in Hong Kong (HK) and at five hospitals in the Chinese Mainland (CM). A total of 307 hospitalised children and adolescents (ages 2-18) and their primary caregiver (e.g., mother, father or grandparent) participated in the study. Children and adolescents completed an age-appropriate symptom diary on one evening and subsequent morning early in their hospital stay. Parents completed the diary for the children less than 6 years of age. Parents also completed an age-appropriate Chinese version of the Child Behaviour Checklist. Over 50% of the children and adolescents reported some degree of pain, 75% of them reported evening tiredness, and 21% reported gastrointestinal symptoms. The intensity of symptoms varied by age and region and symptoms often co-occurred. Greater symptom burden was predicted by previous surgery, higher level of worst pain prior to hospitalisation, parent report of child behaviour problems, and co-occurrence of other symptoms. Hospitalised Chinese children manifest symptoms of pain, tiredness, and gastrointestinal distress that vary based on pre-hospital factors and are associated with child behaviour problems. Further research is needed to identify causes and treatments for children's symptoms.


Ontogeny of defensive reactions in Norway rats.
Young rats of several ages were presented with stimuli (a caged domestic cat, a footshock, and a suddenly moving object) known to be aversive to adults and disruptive of behavior in mature animals. Twenty-day-old rats were relatively unaffected by these events, while rats aged 30 days and older tended to reduce their locomotion and freeze upon the presentation of these cues. These data are consistent with Bolles' hypothesis that shock-elicited responses are innate defensive reactions. We also suggest that the inefficient passive avoidance learning in juvenile rats may result from their deficit in shock-induced freezing.


The Peripheral Immune System and Amyotrophic Lateral Sclerosis.
Amyotrophic lateral sclerosis (ALS) is a severe neurodegenerative disease that is defined by loss of upper and lower motor neurons, associated with accumulation of protein aggregates in cells. There is also pathology in extra-motor areas of the brain, Possible causes of cell death include failure to deal with the aggregated proteins, glutamate toxicity and mitochondrial failure. ALS also involves abnormalities of metabolism and the immune system, including neuroinflammation in the brain and spinal cord. Strikingly, there are also abnormalities of the peripheral immune system, with alterations of T lymphocytes, monocytes, complement and cytokines in the peripheral blood of patients with ALS. The precise contribution of the peripheral immune system in ALS pathogenesis is an active area of research. Although some trials of immunomodulatory agents have been negative, there is strong preclinical evidence of benefit from immune modulation and further trials are currently underway. Here, we review the emerging evidence implicating peripheral immune alterations contributing to ALS, and their potential as future therapeutic targets for clinical intervention.


The past and future of uncertainty in advanced illness: a systematic scoping review of underlying cognitive processes.
To explain what cognitive capacity shapes uncertainty in advanced illness by identifying the types of evidence, mapping underlying cognitive processes to uncertainty, and outlining future directions for research and interventions. A systematic scoping review of mixed study designs was carried out following the methodological framework of Arksey and O'Malley (2005) and using qualitative content analysis. PubMed, CINAHL, Embase, and PsycINFO were searched for original studies published in full and in English through December 2021 that reported on uncertainty in illness and related cognitions, cognitive science, or cognitive functions. After screening 978, 18 articles met the inclusion criteria for review. We found the cognitive capacity of mental time travel - to relive the past or foresee life in the future - interacted with episodic memory retrieval to inform decision-making, and prospection to imagine, predict or prepare for future outcomes to determine lesser or greater uncertainty in advanced illness. Mental time travel is a fundamental cognitive function when the future is limited by an advanced illness, to review life as a meaningful narrative. The role of mental time travel to construct or make sense of uncertain futures inherent in advanced illness can inform theory and targets for intervention.


[Potential Source Contribution Analysis of the Particulate Matters in Shanghai During the Heavy Haze Episode in Eastern and Middle China in December, 2013].
A heavy haze pollution episode occurred in early December, 2013 in middle and eastern China, which lasted for a long period, and covered a large area. During this episode, the hourly maximum concentrations of PM10 and PM2.5 in Shanghai exceeded 700 µg.m-3 and 600 µg.m-3, respectively. To obtain the major air mass transportation path, trajectories reaching urban Shanghai area were analyzed using HYSPLIT model and cluster analysis. Potential Source Contribution Function (PSCF) and Concentration-Weighted Trajectory (CWT) methods were applied to study the potential source regions and the individual contributions to PM10 in Shanghai in December, 2013. The results showed that the northwest and the north paths were the major air mass transport paths in December, among which 79. 6% of the total trajectories came from mainland, while 20. 4% reached Shanghai through the ocean. These were the main transportation paths causing high PM10 mass concentration in December in Shanghai. The potential regions affecting the heavy haze episode in early December in Shanghai were distributed in the Yangtze River Delta including Jiangsu, Zhejiang and Anhui. Besides, air mass from Shandong, Hebei and Henan also had certain impact. The results showed that regional and even super-regional pollution joint control was of significant importance to reduce the frequent heavy air pollution episodes.


Oral manifestations of juvenile hyaline fibromatosis: a case report.
Hyaline fibromatosis is a rare autosomal recessive disease of connective tissue, characterised by an accumulation of hyaline in the skin as well as various organs. The clinical features include: multiple cutaneous nodules, joint contractures, osteolytic lesions and gingival hypertrophy. This paper reports the case of an 11-year-old boy, who was referred to our dental clinic complaining of pain in his mouth. On examination, the patient had gross maxillary and mandibular gingival hyperplasia, which caused severe feeding difficulties. He also had severe dental decay, mal-positioned teeth and limited mouth opening. Treatment was done under general anesthesia to remove excess gingival tissue and extract the severely decayed teeth. Histological examination confirmed the diagnosis of juvenile hyaline fibromatosis. It was concluded that patients with this condition have special dental needs. Early diagnosis of the affected children is important in order to start early preventive dental therapy.


Activation of Akt through gp130 receptor signaling is required for Kaposi's sarcoma-associated herpesvirus-induced lymphatic reprogramming of endothelial cells.
Kaposi's sarcoma (KS) is the most common tumor of AIDS patients worldwide. KS-associated herpesvirus (KSHV) is the infectious cause of this highly vascularized skin tumor. The main cell type found within a KS lesion, the spindle cell, is latently infected with KSHV and has markers of both blood and lymphatic endothelial cells. During development, lymphatic endothelial cells differentiate from preexisting blood endothelial cells. Interestingly, KSHV infection of blood endothelial cells induces lymphatic endothelial cell differentiation. Here, we show that KSHV gene expression is necessary to maintain the expression of the lymphatic markers vascular endothelial growth factor receptor 3 (VEGFR-3) and podoplanin. KSHV infection activates many cell signaling pathways in endothelial cells and persistently activates STAT3 through the gp130 receptor, the common receptor of the interleukin 6 family of cytokines. We find that KSHV infection also activates the phosphatidylinositol 3-OH-kinase (PI3K)/Akt cell signaling pathway in latently infected endothelial cells and that gp130 receptor signaling is necessary for Akt activation. Using both pharmacological inhibitors and small interfering RNA knockdown, we show that the gp130 receptor-mediated activation of both the JAK2/STAT3 and PI3K/Akt cell signaling pathways is necessary for KSHV-induced lymphatic reprogramming of endothelial cells. The induction of the lymphatic endothelial cell-specific transcription factor Prox1 is also involved in KSHV-induced lymphatic reprogramming. The activation of gp130 receptor signaling is a novel mechanism for the differentiation of blood endothelial cells into lymphatic endothelial cells and may be relevant to the developmental or pathological differentiation of lymphatic endothelial cells as well as to KSHV pathogenesis.


Factors associated with infection amongst paediatric patients with systemic lupus erythematosus treated in the intensive care unit.
To identify determinants and outcomes associated with infection in paediatric systemic lupus erythematosus (SLE) patients at admission and during hospitalization in intensive care units (ICUs). A retrospective cohort study of paediatric SLE patients admitted to two ICUs was conducted. Frequency and risk factors of infection as well as mortality were studied. Seventy-three infection episodes amongst 55 patients were analysed. The median age was 14.4 years (IQR 12.5-16). The median SLEDAI was 16 (IQR 12-20). Twenty-nine episodes were documented at admission; the CRP was higher in these patients (6.58 versus 1.04 mg/dl, p<0.001) than in non-infected patients, even after multivariate adjustment (OR 8.6, 95% CI = 2.1-34.8, p = 0.003). Twenty-five (34.7%) episodes occurred during hospitalization. Lupus activity (OR 1.14, 95% CI = 1.01-1.27, p = 0.029), cyclophosphamide (OR 17.9, 95% CI = 2-156, p = 0.009) and mechanical ventilation (OR 16, 95% CI = 2.1-122, p = 0.008) were associated with infection. Ten episodes (14%) led to death. Admission to the ICU due to infection was strongly associated with mortality (90% versus 31.8%, OR 19.4, 95% CI = 2.3-163, p = 0.006). In paediatric lupus patients admitted to the ICU, elevated CRP should alert clinicians to possible infection. During hospitalization, SLE activity and cyclophosphamide were associated with infection. Infection at admission to the ICU was strongly associated with mortality.


The death of Adolf Hitler--forensic aspects.
The death of Adolf Hitler is one of the unsolved mysteries of the twentieth century. Numerous historians and journalists have attempted to piece together the details, but despite the interest in the forensic literature regarding the identification of the body, there has not been much scientific debate about the alleged cause of death--cyanide poisoning, gunshot injury, or both. The available literature concerning Hitler's cause of death is incomplete because the toxicological analysis has not been performed and because the skull bone fragment with a gunshot wound possibly from Hitler's corpse has not been properly examined. This has given basis for various theories, which are reviewed. We believe that mtDNA analysis of the skull fragments and of Hitler's jaw, now filed in Moscow, and samples from maternal relatives of Hitler are crucial linking the skull fragment with the gunshot wound to Hitler.


Death and Dying in the Emergency Department.
The Research to Practice column is intended to improve the research critique skills of the advanced practice registered nurse (APRN) and to assist with the translation of research into practice. For each column, a topic and a particular research study are selected. The stage is set with a case presentation. The research article is then reviewed and critiqued, and the findings are discussed in relation to the case presented. Our current column discusses factors associated with the quality of the death and dying experience in the emergency department (ED) from the perspective of health care providers with implications for APRN practice and strategies using the following study: . "Exploring the quality of the dying and death experience in the emergency department: An integrative literature review," International Journal of Nursing Studies, 85, 106-117. Our case involves a man with metastatic colon cancer where his oncology nurse practitioner recommends no further treatment and tells him he has approximately 6 months to live.


Early Deterioration, Hematoma Expansion, and Outcomes in Deep Versus Lobar Intracerebral Hemorrhage: The FAST Trial.
In patients with intracerebral hemorrhage (ICH), it is unclear whether early neurological deterioration, hematoma expansion (HE), and outcome vary by supratentorial ICH location (deep versus lobar). Herein, we assessed these relationships in a clinical trial cohort that underwent brain imaging early after symptom onset. We hypothesized that HE would occur more frequently, and outcome would be worse in patients with deep ICH. We performed a post hoc analysis of the FAST (Factor-VII-for-Acute-Hemorrhagic-Stroke-Treatment) trial including all patients with supratentorial hemorrhage. Enrolled patients underwent brain imaging within 3 hours of symptom onset and 24 hours after randomization. Multivariable regression was used to test the association between ICH location and 3 outcomes: HE (increase of ≥33% or 6mL), early neurological deterioration (decrease in Glasgow Coma Scale score ≥2 points or increase in National Institutes of Health Stroke Scale ≥4 points within 24 hours of admission), and 90-day outcome (modified Rankin Scale). Of 841 FAST trial patients, we included 728 (mean age 64 years, 38% women) with supratentorial hemorrhages (deep n=623, lobar n=105). HE (44 versus 27%, P=0.001) and early neurological deterioration (31 versus 17%, P=0.001) were more common in lobar hemorrhages. Deep hemorrhages were smaller than lobar hemorrhages at baseline (12 versus 35mL, P<0.001) and 24 hours (14 versus 38mL, P<0.001). Unadjusted 90-day outcome was worse in lobar compared with deep ICH (median modified Rankin Scale score 5 versus 4, P=0.03). However, when adjusting for variables included in the ICH score including ICH volume, deep location was associated with worse and lobar location with better outcome (odds ratio lobar location, 0.58 [95% CI, 0.38-0.89]; P=0.01). In this secondary analysis of randomized trial patients, lobar ICH location was associated with larger ICH volume, more HE and early neurological deterioration, and worse outcome than deep ICH. After adjustment for prognostic variables, however, deep ICH was associated with worse outcome, likely due to their proximity to eloquent brain structures.


Protein damage and degradation by oxygen radicals. IV. Degradation of denatured protein.
Proteolytic degradation of oxidatively damaged [3H] bovine serum albumin [( 3H]BSA) was studied during incubation with cell-free erythrocyte extracts and a wide variety (14) of purified proteases. [3H]BSA was pretreated by exposure (60Co radiation) to the hydroxyl radical (.OH), the superoxide anion radical (O2-), or the combination of .OH + O2- + oxygen. Treated (and untreated) samples were dialyzed and then incubated with erythrocyte extract or proteases for measurements of proteolytic susceptibility (release of acid-soluble counts). Both .OH and .OH + O2- + caused severalfold increases in proteolytic susceptibility (with extract and proteases), but O2- alone had no effect. Proteolytic susceptibility reached a maximum at 15 nmol of .OH/nmol of BSA and declined thereafter. In contrast, proteolytic susceptibility was still increasing at an .OH + O2-/BSA molar ratio of 100 (50% .OH + 50% O2-). Degradation in erythrocyte extracts was conducted by a novel ATP- and Ca2+-independent pathway, with maximal activity at pH 7.8. Inhibitor profiles indicate that this pathway may involve metalloproteases and serine proteases. Comparisons of proteolytic susceptibility with multiple modifications to BSA primary, secondary, and tertiary structure revealed a high correlation (r = 0.98) with denaturation/increased hydrophobicity by low concentrations of .OH. Covalent aggregation reactions (BSA cross-linking) may explain the declining proteolytic susceptibility observed at .OH/BSA molar ratios greater than 20. Protein denaturation may also have caused the increased proteolytic susceptibility induced by .OH + O2- + O2, but no simple correlation could be obtained. Results with .OH + O2- + O2 appear to have been complicated by direct BSA fragmentation reactions involving (.OH-induced) protein radicals and oxygen. These data indicate a direct and quantitative relationship between protein damage by oxygen radicals and increased proteolytic susceptibility. Oxidative denaturation may exemplify a simple, yet effective inherent mechanism for intracellular proteolysis.


The combined effects of elevated pCO2 and food availability on Tigriopus japonicus Mori larval development, reproduction, and superoxide dismutase activity.
Previous studies have shown that ocean acidification has little effect on adult Tigriopus japonicus copepods, and mainly impairs the early development and reproduction of females. This study investigated the possible interactive effect between CO2-induced seawater acidification and food availability on larval development and reproductive output in T. japonicus. Copepods were exposed to either pH8.1 or pH7.3 under different food concentrations (0.5×104-80.0×104cells/mL). Both the development of nauplii and copepodites was delayed at pH7.3 with a greater effect at lower food concentrations. The reproductive output followed a bell-shaped curve with the highest reproductive output at food concentrations between 30×104 and 40×104cells/mL. As an indicator of oxidative stress, the activity of superoxide dismutase increased at lower pH, with a greater increase at lower food concentrations. Therefore, the effect of elevated pCO2 on T. japonicus was food dependent.


Cows' milk allergy in the syndrome of thrombocytopenia with absent radius.
A girl with the syndrome of thrombocytopenia with absent radius had severe diarrhoea and dehydration relieved by withdrawal of cows' milk and aggravated by its reintroduction on three occasions. Deterioration in gastrointestinal symptoms was associated with haematological relapse with thrombocytopenia, leucocytosis, anaemia, and eosinophilia. There appeared to be a correlation between milk exposure and the haematological and gastrointestinal disturbances. Supporting evidence from published reports for such a correlation is reviewed. Cows' milk protein intolerance may be a factor in precipitating haematological relapse in susceptible infants with radius aplasia. Early withdrawal of cow's milk protein should be tried in thrombocytopenia with absent radius, especially in cases with prominent gastrointestinal upset.


Characterization of Zn(O,S) Buffer Layers for Cu(In,Ga)Se2 Solar Cells.
Zn(O,S) thin films were deposited using a ZnS target under Ar/O2 gases by radio-frequency magnetron sputtering. As the O2 concentration increased, the deposition rates of the Zn(O,S) films decreased due to increase of O-. The crystalline structure of Zn(O,S) was maintained at up to 0.6% O2, while the films became unstable at the condition exceeding 0.8% O2. This was attributed to incomplete nucleation and film growth on the substrate at the room temperature. Additionally, optical emission spectroscopy analysis indicated that an increased O- intensity at high O2 concentration was responsible for the slow deposition rate and increased oxygen concentration of the films. X-ray diffraction and scanning electron microscopy revealed the formation of a Zn(O,S) crystal structure with partial substitution of O for S and uniform and dense grains of the films. X-ray photoelectron spectroscopy showed that the Zn(O,S) films have a uniform composition of each element and consisted of a mixed crystal structure of Zn(O,S) with Zn-O bonding. Overall, the results of this study confirmed that Zn(O,S) films deposited by radio-frequency sputtering using Ar/O2 gas at room temperature can be applied to Cu(In,Ga)Se2 solar cells as a buffer layer.


Optimization of Ultrasonic-Assisted Extraction of Total Phenolics from Citrus aurantium L. Blossoms and Evaluation of Free Radical Scavenging, Anti-HMG-CoA Reductase Activities.
The objective of this study was to develop an ultrasonic-assisted procedure for the extraction of total phenolics from Citrus aurantium L. blossoms (CAB) and evaluate the free radical scavenging activity and anti-HMG-CoA reductase activity of the total phenolics. In this work, a Box- Behnken design based on single-factor experiments was used to explore the optimum extraction process. Under the optimum conditions (extraction solvent 70.31% ethanol, extraction temperature 61.94 °C, extraction time 51.73 min, and liquid-to-solid ratio 35.63 mL/g), the extraction yield of total phenolics was 95.84 mg gallic acid equivalents (GAE)/g dry matter (DM), which was highly consistent with the theoretical value (96.12 mg GAE/g DM). The higher contents of total phenolics and five main phenolic compounds obtained from the optimized ultrasonic-assisted extraction (UAE) proved its efficiency when compared with conventional heat reflux extraction (HRE). The total phenolic extract showed excellent free radical scavenging properties against 1,1-diphenyl-2-picrylhydrazyl radical (DPPH·), 2,2'-azino-bis-(3-ethylbenzthiazoline-6-sulphonic acid) radical (ABTS+·), hydroxyl radical (·OH) and superoxide anion radical (·O2-), with IC50 values of 197.007, 83.878, 218.643, and 158.885 μg/mL, respectively; the extracts also showed good inhibition of β-hydroxy-β-methylglutaryl-CoA reductase (HMG-CoA reductase) activity, with an IC50 value of 117.165 μg/mL. Total phenolics from CAB could be a potential source of natural free radical scavenger and HMG-CoA reductase inhibitor.


Intracranial chondrosarcoma--case report.
The authors report the case of a 54-year-old male who was found to have a large intracranial chondrosarcoma at the site from which chondromas had been partially removed twice, 6 and 10 years previously. On the third admission, the second through tenth and the twelfth cranial nerves on the right side were involved. Computed tomographic scans showed a large mass in the right middle and posterior fossae and the right ethmoid sinus. Angiography demonstrated an extradural mass in the right middle fossa. The tumor in the middle and posterior fossae was subtotally removed, and second, third, and eighth cranial nerve function improved postoperatively. Histological examination of tumor specimens showed active proliferation of poorly differentiated cartilagenous cells, suggestive of sarcomatous transformation of the pre-existing chondroma. It is emphasized that chondromas should be removed as completely as possible and that patients must be followed carefully after surgery.


Sex-specific metabolic profiles of androgens and its main binding protein SHBG in a middle aged population without diabetes.
The role of androgens in metabolism with respect to sex-specific disease associations is poorly understood. Therefore, we aimed to provide molecular signatures in plasma and urine of androgen action in a sex-specific manner using state-of-the-art metabolomics techniques. Our study population consisted of 430 men and 343 women, aged 20-80 years, who were recruited for the cross-sectional population-based Study of Health in Pomerania (SHIP-TREND), Germany. We used linear regression models to identify associations between testosterone, androstenedione and dehydroepiandrosterone-sulfate (DHEAS) as well as sex hormone-binding globulin and plasma or urine metabolites measured by mass spectrometry. The analyses revealed major sex-specific differences in androgen-associated metabolites, particularly for levels of urate, lipids and metabolic surrogates of lifestyle factors, like cotinine or piperine. In women, in particular in the postmenopausal state, androgens showed a greater impact on the metabolome than in men (especially DHEAS and lipids were highly related in women). We observed a novel association of androstenedione on the metabolism of biogenic amines and only a small sex-overlap of associations within steroid metabolism. The present study yields new insights in the interaction between androgens and metabolism, especially about their implication in female metabolism.