Clinical characteristics of individuals with Down syndrome deceased with CoVID-19 in Italy-A case series.
Persons with Down syndrome (DS) are presumed to be at high risk of severe CoVID-19, due to immune dysregulation and often compromised cardiopulmonary function. Aim of the present study is to assess epidemiological and clinical characteristics of individuals with DS deceased in Italian hospitals with CoVID-19. We used a nationwide database of 3,438 patients deceased with RT-PCR-confirmed SARS-CoV-2 infection in Italy (10.4% of all deaths with CoVID-19 in the country at the time of analysis). Data on demographics, pre-existing comorbidities and in-hospital complications leading to death were extracted from medical charts obtained from hospitals. Data on individuals with DS deceased with CoVID-19 were obtained from this sample. Sixteen cases of death in individuals with DS (0.5% of all charts analyzed) were identified. Acute respiratory distress syndrome occurred in all 16 cases. Compared with individuals without DS, those with DS deceased with CoVID-19 were younger (52.3 ± 7.3 vs. 78.1 ± 10.6 years, p < .001) and presented a higher incidence of superinfections (31.2 vs. 13.0%, p = .029). Autoimmune diseases (43.8 vs. 4%, p < .001), obesity (37.5 vs. 11%, p = .009), and dementia (37.5 vs. 16.3%, p = .012) were more prevalent in individuals with DS. ICU admissions was similar in both groups (25 vs. 18.8%, p = .129). Individuals with DS deceased with CoVID-19 are younger than individuals without DS. Comorbidity burden and increased risk of complications (i.e., bacterial superinfections) can influence CoVID-19 prognosis in individuals with DS. Specific strategies to prevent and mitigate the effects of CoVID-19 in the population with DS are needed.


Control of ColE1 plasmid replication: enhancement of binding of RNA I to the primer transcript by the Rom protein.
RNA I prevents a transcript (RNA II) from the ColE1 primer promoter to form a hybrid with the template DNA and thereby inhibits formation of primer for DNA replication. Binding of RNA I to RNA II is responsible for the inhibition. The Rom protein, a plasmid-specified 63 amino acid protein, enhances the inhibitory effect of RNA I on primer formation by enhancing the binding of RNA I to RNA II. In vivo, RNA I controls plasmid copy number and incompatibility and inhibits expression of a galK gene fused to the primer promoter. The rom gene modulates these activities of RNA I. These functions of the rom gene can be explained by alteration of the binding of RNA I to RNA II by the Rom protein.


Application of indocyanine green (ICG) fluorescence for endoscopic biopsy of intraventricular tumors.
Many reports have already indicated the benefit of pathological diagnosis of intra- and periventricular tumors with neuroendoscopic biopsy. However, it is also well known that studies can be occasionally inconclusive because of the small and/or inadequate samples for identification of abnormal tissues. The application of indocyanine green (ICG) fluorescence for endoscopical tumor biopsy under the intraventricular surroundings is a new area not previously reported. We attempted visual differentiation of intraventricular lesions from the surrounding structure using ICG fluorescence and considered the most appropriate region for biopsy. Three cases (13–14 year-old boys) with secondary hydrocephalus caused by intra- and periventricular tumors were operated for endoscopic transventricular biopsy combined with endoscopic third ventriculostomy. Final pathological diagnoses were suprasellar malignant lymphoma and germ cell tumors in two patients, both associated with intraventricular dissemination. Enhanced tumor visualization with 12.5 mg of ICG administration was obtained using the D-light P light equipment and ICG telescope 5.8 mm/19 cm. It was possible to identify the tumor mass margins themselves and detect the differences of intratumoral ICG accumulation. The areas of tumor dissemination were identifiable by neuroendoscopy but unable to be visualized by ICG fluorescence. We were able to obtain an ICG fluorescence imaging inside the cerebral ventricles by new D-light P system comprised of a camera head telescope. ICG fluorescence with neuroendoscopy can provide useful information for choosing the point of biopsy of intra- and periventricular tumors. However, we need to assess if the ICG accumulation site is the most appropriate for biopsy.


Breastfeeding Simulation With the Standardized Patient.
Despite an emphasis on lactation and the availability of resources to support and sustain lactation, our community hospital's rates of exclusive breastfeeding remained less than the 50% to 70% benchmark recommended by The Joint Commission and the World Health Organization. Concluding that we had exhausted the majority of evidence-based best practices described in the literature, we sought to find a new way to provide an engaging, useful medium for nursing education and improvement of clinical nurses' skills related to breastfeeding. Here, we describe the simulation program we developed using the standardized patient model. Although our rates of exclusive breastfeeding remained unchanged after introducing the simulation program, the experience enabled us to identify inconsistent practices and knowledge gaps.


Paediatric porto-sinusoidal vascular disease: Two different clinical phenotypes with subtle histological differences.
In paediatrics, porto-sinusoidal vascular disease (PSVD) is relatively unknown and probably underdiagnosed. We aimed to describe clinical phenotypes, histology and outcome of children diagnosed with PSVD. Retrospective multicentre study of children diagnosed with PSVD. Diagnosis of PSVD was based on histopathology reports; liver specimens were re-evaluated by two expert liver pathologists. Sixty two children diagnosed with PSVD (M/F = 36/26, median age 6.6 years, range 3.3-10.6), from 7 centres, were included. Thirty-six presented with non-cirrhotic portal hypertension, PH, (PH-PSVD Group = 58%) while 26 had a liver biopsy because of chronic elevation of transaminases without PH (noPH-PSVD Group = 42%). On histology review, the two groups differed for the prevalence of obliterative portal venopathy (more prevalent in PH-PSVD, p = 0.005), and hypervascularised portal tracts (more common in noPH-PSVD, p = 0.039), the other histological changes were equally distributed. At multivariate analysis, platelet count ≤185 000/mm3 was the only independent determinant of PH (p < 0.001). After a median follow-up of 7 years (range 3.0-11.2), in PH-PSVD group 3/36 (8%) required TIPS placement, 5/36 (14%) developed pulmonary vascular complications of PH, and 7/36 (19%) required liver transplantation. In noPH-PSVD none progressed to PH nor had complications. Paediatric patients with PSVD present with two different clinical phenotypes, one characterised by PH and one by chronic elevation of transaminases without PH. PSVD should be included among the conditions causing isolated hypertransaminasaemia. On histology, the differences between the two groups are subtle. Medium-term outcome is favourable in patients without PH; progression of the disease is observed in those with PH.


Government financial support and financial performance of SMEs: A dual sequential mediator approach.
Government financial support (GFS) is an important factor for firms in developing countries, particularly small and medium enterprises (SMEs), to be competitive and perform better. Nonetheless, studies on the relationship between GFS and firm performance have yielded inconclusive results. Researchers' efforts to resolve the inconclusiveness led to an examination of competitive advantage (CA) as a simple mediator. This study contends that CA should not be the first mediator but rather a resource acquired with GFS, such as cloud ERP, which has CA-enabled qualities, as opposed to GFS, which lacks the ability to offer CA to firms. Hence, using 204 Malaysian manufacturing SMEs as a sample, this study investigates the dual sequential mediation of cloud ERP implementation (CERPI) and CA in the GFS-financial performance (FPER) relationship. PLS-SEM was employed as a data analysis method and for hypotheses assessment. Findings reveal that the GFS is not directly associated with FPER. However, GFS is positively related to CERPI, which subsequently enhances CA positively. CA is also positively associated with FPER, and CERPI and CA sequentially mediate the GFS and FPER relationship positively. This study makes a contribution to the literature by providing a more holistic understanding of the complex relationship between GFS and FPER. This study could assist SMEs and policymakers in gaining a better understanding of the process and requirements for realising valuable benefits from GFS.


Preliminary x-ray investigation of an orthorhombic crystal of hevein.
Hevein, a small protein from the latex of Hevea brasiliensis, has been crystallized by the vapor diffusion method using 2-methyl-2,4-pentanediol and CaCl2 as the precipitant agents. The crystals are orthorhombic space group P21212 with a = 21.88, b = 31.90, and c = 51.24 A and one molecule in the asymmetric unit. The crystals are quite stable to x-rays and suitable for a high resolution three-dimensional structure determination.


O-acylated lysergol and dihydrolysergol-I derivatives as competitive antagonists of 5-HT at 5-HT2 receptors of rat tail artery. Allosteric modulation instead of pseudoirreversible inhibition.
Twelve ergolines (O-acylated lysergol and dihydrolysergol-I derivatives) were synthesized to study their antagonism of 5-HT responses in comparison with methylsergide and LY 53857 [6-methyl-1-(1-methylethyl)-8 beta-ergoline carboxylic acid 2-hydroxy-1-methylpropyl-ester hydrogen maleate] in cylindrical segments of the isolated rat tail artery. With regard to (9.10-didehydro-6-methyl-8 beta-ergoline)methyl R,S-2-methylbutyrate, the most potent new ergoline derivative, we examined the phenomenon of insurmountable antagonism to 5-HT by methylsergide. O-Acylated lysergol and dihydrolysergol-I derivatives competitively antagonized 5-HT-induced contractions with calculated pA2 values of 7.30 +/- 0.42 for the weakest and 8.42 +/- 0.35 for the most potent ergoline derivative in this series. N1-isopropyl substitution did not generally enhance 5-HT2 receptor affinities but lowered affinities for alpha 1 adrenoceptors in rat aorta. Methysergide and LY 53857 were insurmountable antagonists of 5-HT in rat tail artery. Preincubation with (9.10-didehydro-6-methyl-8 beta-ergoline)methyl R,S-2-methylbutyrate (1 mumol/l) partially prevented the depression of 5-HT-induced contractions caused by methysergide (1-10 nmol/l). Methysergide (100 nmol/l) abolished the protective effect of (9.10-didehydro-6-methyl-8 beta-ergoline)methyl R,S-2-methylbutyrate. (9.10-Didehydro-6-methyl-8 beta-ergoline)methyl R,S-2-methylbutyrate (1 mumol/l), concomitantly incubated with methysergide (30 nmol/l), partially restored the maximum response to 5-HT that had been depressed by methysergide (30 nmol/l). Partial restoration could not be mimicked by washout of methysergide.(ABSTRACT TRUNCATED AT 250 WORDS)


[The lymphatic system--terra incognita? Demonstrated by morphological assessment of resorption processes].
The lymphatic system has been demonstrated by means of special microscopic investigations, using morphologically comprehensive resorption procedures. References has been made to the literature which gives an account of the available knowledge about the lymphatic system and the scientific concepts produced in the course of the centuries. After going into the fundamental morphological principles of parenteral resorption and resorption in the bovine uterus, a description is given of the transport of the vital dyes patent blue violet and Japanese ink, which was followed microscopically in the lymphatic system. A further phenomenon emerges with the concept of persorption, where the particles are in the micron range and have also been identified microscopically in the pathways of the lymphatic system.


Object strength--an accurate measure for small objects that is insensitive to partial volume effects.
There are currently four problems in characterising small nonuniform lesions or other objects in Magnetic Resonance images where partial volume effects are significant. Object size is over- or under-estimated; boundaries are often not reproducible; mean object value cannot be measured; and fuzzy borders cannot be accommodated. A new measure, Object Strength, is proposed. This is the sum of all abnormal intensities, above a uniform background value. For a uniform object, this is simply the product of the increase in intensity and the size of the object. Biologically, this could be at least as relevant as existing measures of size or mean intensity. We hypothesise that Object Strength will perform better than traditional area measurements in characterising small objects. In a pilot study, the reproducibility of object strength measurements was investigated using MR images of small multiple sclerosis (MS) lesions. In addition, accuracy was investigated using artificial lesions of known volume (0.3-6.2 ml) and realistic appearance. Reproducibility approached that of area measurements (in 33/90 lesion reports the difference between repeats was less than for area measurements). Total lesion volume was accurate to 0.2%. In conclusion, Object Strength has potential for improved characterisation of small lesions and objects in imaging and possibly spectroscopy.


Triple procedure of penetrating keratoplasty, extra capsular cataract extraction and posterior chamber I.O.L. implantation.
Ten cases of triple procedure of PKP, ECCE with IOL implantation have been presented and there results discussed.


Hemotropic Mycoplasma.
Hemoplasma infections are erythrocytic infections in both cats and dogs but are more common, and more often associated with disease, in cats. Mycoplasma haemofelis is the most pathogenic species in cats, causing hemolytic anemia and fever in immunocompetent hosts, whereas Mycoplasma haemocanis usually only results in hemolytic anemia in splenectomized or immunocompromised dogs. Diagnosis is by polymerase chain reaction on blood samples because cytology is unreliable. Prompt treatment of clinical disease with supportive care and at least 2 weeks of doxycycline is usually successful. Transmission pathways have not been confirmed, but indirect, via vectors, and direct via bites/fights/predation are likely.


Noise and cochlear blood flow.
The effect of noise after unilateral transection of the cervical sympathetic trunk on cochlear blood flow was studied in anesthetized cats. The sound pressure level was 100 dB and the exposure time 6 min. Neither noise nor sympathectomy were found to affect the blood flow.


The role of triglyceride lipases in cancer associated cachexia.
Cancer associated cachexia (CAC) is a complex multiorgan syndrome frequently associated with various forms of cancer. Affected patients suffer from a dramatic loss of skeletal muscle and adipose tissue. Most cases are accompanied by anorexia, and nutritional supplements are not sufficient to stop or reverse its course. CAC impairs many forms of therapeutic interventions and accounts for 15-20% of all deaths of cancer patients. Recently, several studies have recognized the importance of lipid metabolism and triglyceride hydrolysis as a major metabolic pathway involved in the initiation and/or progression of CAC. In this review, we explore the contributions of the triglyceride lipases to CAC and discuss various factors modulating lipase activity.


Rap1A positively regulates T cells via integrin activation rather than inhibiting lymphocyte signaling.
T cell receptor (TCR) stimulation activates the small GTPase Rap1A, which is reported to antagonize Ras signaling and induces T cell anergy. To address its role in vivo, we generated transgenic mice that constitutively expressed active Rap1A within the T cell lineage. We found that active Rap1A did not interfere with the Ras signaling pathway or antagonize T cell activation. Instead of anergy, the T lymphocytes that constitutively expressed active Rap1A showed enhanced TCR-mediated responses, both in thymocytes and mature T cells. In addition, Rap1A activation was sufficient to induce strong activation of the beta1 and beta2 integrins via an avidity-modulation mechanism. This shows that, far from playing an inhibitory role during T cell activation, Rap1A positively influences T cells by augmenting lymphocyte responses and directing integrin activation.


Arteriovenous malformation of the forearm as a result of a persistent median artery.
Most arteriovenous malformations usually arise from pre-existing named vessels. We report an unusual variant of an arteriovenous malformation. An 18-year-old man presented with a painful swelling of the right forearm. Arteriograms suggested branches of the anterior interosseous artery were feeding the malformation. Operative findings however, revealed the presence of a persistent median artery, which was contributing branches to the swelling.


Preparation of fcc-2H-fcc Heterophase Pd@Ir Nanostructures for High-Performance Electrochemical Hydrogen Evolution.
With the development of phase engineering of nanomaterials (PEN), construction of noble-metal heterostructures with unconventional crystal phases, including heterophases, has been proposed as an attractive approach toward the rational design of highly efficient catalysts. However, it still remains challenging to realize the controlled preparation of such unconventional-phase noble-metal heterostructures and explore their crystal-phase-dependent applications. Here, various Pd@Ir core-shell nanostructures are synthesized with unconventional fcc-2H-fcc heterophase (2H: hexagonal close-packed; fcc: face-centered cubic) through a wet-chemical seeded method. As a result, heterophase Pd66 @Ir34 nanoparticles, Pd45 @Ir55 multibranched nanodendrites, and Pd68 @Ir22 Co10 trimetallic nanoparticles are obtained via the phase-selective epitaxial growth of fcc-2H-fcc-heterophase Ir-based nanostructures on 2H-Pd seeds. Importantly, the heterophase Pd45 @Ir55 nanodendrites exhibit excellent catalytic performance toward electrochemical hydrogen evolution reaction (HER) under acidic conditions. An overpotential of only 11.0 mV is required to achieve a current density of 10 mA cm-2 on Pd45 @Ir55 nanodendrites, which is lower than those of the conventional fcc-Pd47 @Ir53 counterparts, commercial Ir/C and Pt/C. This work not only demonstrates an appealing route to synthesize novel heterophase nanomaterials for promising applications in the emerging field of PEN, but also highlights the significant role of the crystal phase in determining their catalytic properties.


C/EBPα-mediated transcriptional activation of miR-134-5p entails KPNA3 inhibition and modulates focal hypoxic-ischemic brain damage in neonatal rats.
Hypoxic-ischemic brain damage (HIBD) is a frequent cause of mortality and neurological handicaps in infants and children worldwide. To understand better the pathogenesis and management of HIBD, we established a HIBD model by common carotid artery ligation followed by systemic hypoxia in neonatal rats, and in other studies induced neuronal death in rat pheochromocytoma (PC12) cells by 12 h of oxygen-glucose deprivation (OGD). The level of KPNA3 declined in rats following experimental HIBD and in PC12 cells following OGD. KPNA3 overexpression protected neonatal rats against HIBD and PC12 cells against OGD-induced cell death. KPNA3 demonstrated to be the target of miR-134-5p could be activated by the transcriptional factor CCAAT/enhancer binding protein alpha (C/EBPα). The expression of miR-134-5p and C/EBPα was elevated in rats following experimental HIBD and in PC12 cells following OGD. In the parallel experiments, C/EBPα knockdown and miR-134 inhibition protected against HIBD pathology in neonatal rats and against OGD-induced neuronal death in PC12 cells. These findings reveal that the C/EBPα/miR-134-5p/KPNA3 axis mediates hypoxic-ischemic brain damage and neuronal death, thus presenting a potential therapeutic target for the treatment of human newborns at risk for HIBD.


Boron deficiency inhibits root cell elongation via an ethylene/auxin/ROS-dependent pathway in Arabidopsis seedlings.
One of the earliest symptoms of boron (B) deficiency is the inhibition of root elongation which can reasonably be attributed to the damaging effects of B deprivation on cell wall integrity. It is shown here that exposure of wild-type Arabidopsis thaliana seedlings to B deficiency for 4h led to a drastic inhibition of root cell length in the transition between the elongation and differentiation zones. To investigate the possible mediation of ethylene, auxin, and reactive oxygen species (ROS) in the effect of B deficiency on root cell elongation, B deficiency was applied together with aminoethoxyvinylglycine (AVG, a chemical inhibitor of ethylene biosynthesis), silver ions (Ag(+), an antagonist of ethylene perception), α-(phenylethyl-2-oxo)-indoleacetic acid (PEO-IAA, a synthetic antagonist of TIR1 receptor function), and diphenylene iodonium (DPI, an inhibitor of ROS production). Interestingly, all these chemicals partially or fully restored cell elongation in B-deficient roots. To further explore the possible role of ethylene and auxin in the inhibition of root cell elongation under B deficiency, a genetic approach was performed by using Arabidopsis mutants defective in the ethylene (ein2-1) or auxin (eir1-4 and aux1-22) response. Root cell elongation in these mutants was less sensitive to B-deficient treatment than that in wild-type plants. Altogether, these results demonstrated that a signalling pathway involving ethylene, auxin, and ROS participates in the reduction of root cell elongation when Arabidopsis seedlings are subjected to B deficiency. A similar signalling process has been described to reduce root elongation rapidly under various types of cell wall stress which supports the idea that this signalling pathway is triggered by the impaired cell wall integrity caused by B deficiency.


Rhesus monkey (macaca mulatta) allotypes. Identification of three low density lipoprotein allotypes controlled by independent genes.
Three rhesus monkey allotypes are described, which are located on distinct low density lipoprotein molecules. These three markers have been detected using double immunodiffusion in agar. They are inherited in a simple Mendelian manner and controlled by three independent genes.


Analysis of organic compounds of water-in-crude oil emulsions separated by microwave heating using comprehensive two-dimensional gas chromatography and time-of-flight mass spectrometry.
In this work the higher peak capacity and resolution of comprehensive two-dimensional gas chromatography (GCxGC) has been successfully applied, for the first time, to tentatively identify several polar organic compounds of organic extracts of aqueous phases resulting from microwave demulsification process of water-in-crude oil emulsions. Results have shown that higher temperatures and longer exposure time to microwave irradiation produced water phases with a wider variety of polar organic compounds. The microwave process showed to be suitable for the extraction of several polar compounds classes of petroleum. The proposed microwave extraction method and GCxGC identification of polar compounds of petroleum samples are of practical interest for the petrochemical industry due to corrosion and related problems associated with these polar compounds in refinery equipments. The GCxGC/time-of-flight MS technique shows to be very important in the total separation of different classes of compounds and allows the identification of many compounds in these classes.


Calculating Transition Energy Barriers and Characterizing Activation States for Steps of Fusion.
We use continuum mechanics to calculate an entire least energy pathway of membrane fusion, from stalk formation, to pore creation, and through fusion pore enlargement. The model assumes that each structure in the pathway is axially symmetric. The static continuum stalk structure agrees quantitatively with experimental stalk architecture. Calculations show that in a stalk, the distal monolayer is stretched and the stored stretching energy is significantly less than the tilt energy of an unstretched distal monolayer. The string method is used to determine the energy of the transition barriers that separate intermediate states and the dynamics of two bilayers as they pass through them. Hemifusion requires a small amount of energy independently of lipid composition, while direct transition from a stalk to a fusion pore without a hemifusion intermediate is highly improbable. Hemifusion diaphragm expansion is spontaneous for distal monolayers containing at least two lipid components, given sufficiently negative diaphragm spontaneous curvature. Conversely, diaphragms formed from single-component distal monolayers do not expand without the continual injection of energy. We identify a diaphragm radius, below which central pore expansion is spontaneous. For larger diaphragms, prior studies have shown that pore expansion is not axisymmetric, and here our calculations supply an upper bound for the energy of the barrier against pore formation. The major energy-requiring deformations in the steps of fusion are: widening of a hydrophobic fissure in bilayers for stalk formation, splay within the expanding hemifusion diaphragm, and fissure widening initiating pore formation in a hemifusion diaphragm.


Tenascin-C induces prolonged constriction of cerebral arteries in rats.
Tenascin-C (TNC), a matricellular protein, is induced in association with cerebral vasospasm after subarachnoid hemorrhage. The aim of this study was to assess the vasoconstrictive effects of TNC and its mechanisms of action on cerebral arteries in vivo. Two dosages (1 and 10μg) of TNC were administered intracisternally to healthy rats, and the effects were evaluated by neurobehavioral tests and India-ink angiography at 24, 48, and 72h after the administration. Western blotting and immunohistochemistry were performed to explore the underlying mechanisms on constricted cerebral arteries after 24h. The effects of toll-like receptor 4 (TLR4) antagonists (LPS-RS), c-Jun N-terminal kinase (JNK), and p38 inhibitors (SP600125 and SB203580) on TNC-induced vasoconstriction were evaluated at 24h. Higher dosages of TNC induced more severe cerebral arterial constriction, which continued for more than 72h. TNC administration also upregulated TLR4, and activated JNK and p38 in the smooth muscle cell layer of the constricted cerebral artery. LPS-RS blocked TNC-induced TLR4 upregulation, JNK and p38 activation, and vasoconstrictive effects. SP600125 and SB203580 abolished TNC-induced TLR4 upregulation and vasoconstrictive effects. TNC may cause prolonged cerebral arterial constriction via TLR4 and activation of JNK and p38, which may upregulate TLR4. These findings suggest that TNC causes cerebral vasospasm and provides a novel therapeutic approach against it.


Partial Obstruction of the Endotracheal Tube by a Part of the Metallic Stylet; Case Report and Review of the Literature.
Endotracheal intubation is common in the emergency department, intensive care units, and operating rooms. It involves the insertion of an endotracheal tube (ETT) through the mouth or nose into the trachea to maintain a patent airway and facilitate mechanical ventilation. Using a stylet during intubation can guide the ETT through the vocal cords. However, complications can arise when the stylet is not removed after successful intubation. Herewith, we reported a patient who was two years old and suffered from respiratory failure. However, in the first 12 hours, we observed a foreign body in the trachea, a small end of a metal stylet immediately removed by bronchoscope. This case demonstrates that multiple uses of a stylet, especially by a single user, can result in impaction of the stylet in the ETT during intubation, requiring force when the stylet is withdrawn after intubation, which can result in breakage, shearing, and retention of the stylet or plastic sheath in the lumen of the ETT.


Characterization of amino acid transport systems in human placental brush-border membrane vesicles.
Brush-border microvillous plasma membrane vesicles were prepared from human full-term placental syncytiotrophoblasts and purified 33-fold from the homogenate with reference to a membrane marker enzyme, alkaline phosphatase (EC 18.104.22.168). Transport of alpha-(methylamino)isobutyrate by the membrane vesicles was stimulated in the presence of an Na+ gradient from the outside to the inside of the vesicles. The initial rate of uptake in a 10-s period was enhanced with increasing concentration of Na+ in the external medium. The level of alpha-(methylamino)isobutyrate transported into the vesicles reached a maximum 1 min after the start of incubation at 37 degrees C, and then decreased with time due to efflux. Extrapolation to infinite medium osmolarity showed no uptake, indicating transport of alpha-(methylamino)isobutyrate into membrane vesicles. The initial rate of uptake was dependent on temperature and pH: the highest rate occurred at 37 degrees C and the optimal pH was 8.0. When the alpha-(methylamino)isobutyrate concentration was varied, the initial rate of uptake dependent on an Na+ gradient (out greater than in) obeyed Michaelis-Menten kinetics with Km and Vmax values of 1.07 mM and 3.23 nmol/10 s per mg of protein, respectively. Cross-inhibition patterns indicated that at least three Na+-dependent and two Na+-independent carrier-mediated pathways existed in the human placental brush border. One Na+-dependent pathway interacted with all substrates tested. Another Na+-dependent route interacted with L-proline, alpha-(methylamino)isobutyrate, and L-methionine, while a third pathway was selective for L-methionine. One Na+-independent pathway was selective for L-cysteine, while the other pathway interacted with all substrates tested.


The cellular fate of cortical progenitors is not maintained in neurosphere cultures.
Neural progenitors of the mouse forebrain can be propagated in vitro as neurospheres in the presence of bFGF and EGF. However, less is understood whether regional characteristics or developmental stage properties of these cells are maintained in neurosphere cultures. Here we show that the original cell fate is lost in neurosphere cultures. We isolated neural progenitors from the dorsal telencephalon of D6-GFP mice and cultured them in vitro. The expression profile was specifically changed in cultured cells in just three passages. Markers of the dorsal forebrain were downregulated and several ventrally-expressed genes were induced. The altered gene expression led to a profound phenotypic change of cultured cells. D6-GFP positive cortical progenitors produce excitatory neurons in the cortex and few astrocytes in vivo but after culture in vitro, these cells differentiate into many astrocytes and also oligodendrocytes and inhibitory neurons. Wnt signaling in cultured neurospheres was downregulated in the same manner as other dorsal markers but dominant active Wnt signaling slowed down the loss of the dorsal identity in neurospheres.


The effect of muscle architecture on the biomechanical failure properties of skeletal muscle under passive extension.
This study investigates the biomechanical failure properties of five architecturally different skeletal muscles and examines the role muscle structure plays in the passive extension characteristics of musculotendinous units. The muscles used in this study fall into four morphologic categories: fusiform, unipennate, bipennate, and multipennate. Each muscle was pulled to failure at three different rates of strain (1, 10, and 100 cm/min). Specimens of fusiform, unipennate, and bipennate muscles were pulled from their proximal as well as distal attachments. The relationship of elongation to failure of the entire musculotendinous unit to resting muscle fiber length was examined to determine the effect of angle of pennation and fiber length on the failure properties. Our results demonstrate that all four muscle types tested show injury and rupture at the musculotendinous junction whether pulled from proximal or distal attachment, regardless of muscle structure and rate of strain. There was a statistically significant difference (P less than 0.005) in the degree of elongation to failure relative to resting muscle fiber length, with a tendency to greater elongation relative to fiber length for muscles with more pennate structure (tibialis anterior, 72.7% +/- 1.0%; extensor digitorum longus, 113.1% +/- 3.5%; rectus femoris, 225.5% +/- 3.7% elongation in percent resting fiber length).


A novel modelling framework to prioritize estimation of non-point source pollution parameters for quantifying pollutant origin and discharge in urban catchments.
Stormwater runoff in urban catchments contains heavy metals (zinc, copper, lead) and suspended solids (TSS) which can substantially degrade urban waterways. To identify these pollutant sources and quantify their loads the MEDUSA (Modelled Estimates of Discharges for Urban Stormwater Assessments) modelling framework was developed. The model quantifies pollutant build-up and wash-off from individual impervious roof, road and car park surfaces for individual rain events, incorporating differences in pollutant dynamics between surface types and rainfall characteristics. This requires delineating all impervious surfaces and their material types, the drainage network, rainfall characteristics and coefficients for the pollutant dynamics equations. An example application of the model to a small urban catchment demonstrates how the model can be used to identify the magnitude of pollutant loads, their spatial origin and the response of the catchment to changes in specific rainfall characteristics. A sensitivity analysis then identifies the key parameters influencing each pollutant load within the stormwater given the catchment characteristics, which allows development of a targeted calibration process that will enhance the certainty of the model outputs, while minimizing the data collection required for effective calibration. A detailed explanation of the modelling framework and pre-calibration sensitivity analysis is presented.


Analyzing the genetic characteristics and function of the swine leukocyte antigen 2 gene in a Chinese inbreed of pigs.
To study the genetic characteristics and function of swine leukocyte antigen (SLA) class I from the Hebao pig, a rare inbreed in China, a pair of primers was designed to amplify the SLA-2 gene (SLA-2-HB) and then the genetic characteristics of the gene were analyzed. The 3D homology modeling was used to analyze the structure and function of SLA-2-HB proteins. After cloning, sequencing and computer analysis, four SLA-2-HB alleles were found, all of 1119 bp. Sites 3-1097 were an open reading frame encoding 364 amino acids with two sets of intra-chain disulfide bonds comprising four cysteines situated in sites 125, 188, 227 and 283. By alignment of SLA-2-HB sequences with other SLA-2 alleles in the IPD database, 11 key variable amino acid sites were found in the extracellular domain of the SLA-2-HB alleles at sites 23(F), 24(I), 43(A), 44(K), 50(Q), 73(N), 95(I), 114(R), 155(G), 156(E) and 216(S), which could be used to differentiate other SLA-2 alleles. The 3D homology modeling demonstrated that the eight of 11 key variable amino acid sites were all in antigenic binding groove of SLA-2-HB proteins. The amino acid identities between SLA-2-HB and other SLA-2, SLA-1 and SLA-3 alleles were 86.2-97.0%, 85.0-93.9% and 83.3-88.6%, respectively. The phylogenetic tree of SLA-2-HB showed that it was relatively independent of the other SLA-2 genes. Furthermore, the SLA-2-HB alleles were similar to HLA-B15 and HLA-A2 functional domains and preserved some functional sites of HLA-A2. It was concluded that SLA-2-HB are novel alleles of SLA-2 and that the Hebao pig might have evolved independently in China.


Monoamine and opioid interactions in spinal analgesia and tolerance.
Noradrenergic and serotonergic neurons, originating in the brainstem and terminating in the dorsal horn, modulate the spinal processing of nociception. The inhibitory effects of norepinephrine (NE) and serotonin (5-HT) on elements of nociceptive transmission may be direct, or secondary to the release of neuromodulators such as opioid peptides. Two major criteria have been used in pharmacological studies of spinal opioid and monoamine interactions: the ability of opioid antagonists to attenuate the antinociceptive effects evoked by stimulating the release of endogenous NE and 5-HT in the lumbar spinal cord, or by the intrathecal injection of exogenous NE and 5-HT; and the development of cross tolerance between opioids and each of NE and 5-HT. Evidence regarding the spinal interaction between opioids and monoamines in mediating behavioural analgesia is reviewed. Recent results from this laboratory indicate that IT (-)naloxone but not (+)naloxone produces dose-dependent antagonism of IT NE-induced antinociception in the rat. This effect was not due to hyperalgesia. In rats made tolerant to spinal morphine using continuous IT infusion, the antinociceptive effect of continuous IT NE was significantly attenuated. However, no cross tolerance was observed between morphine and 5-HT. Observations from a variety of studies support the hypothesis of a spinal opioid link which contributes, in part, to NE-induced antinociception. However, this interaction remains to be conclusively established.


Mutual expression of the transcription factors Runx3 and ThPOK regulates intestinal CD4⁺ T cell immunity.
The gut mucosa hosts large numbers of activated lymphocytes that are exposed to stimuli from the diet, microbiota and pathogens. Although CD4(+) T cells are crucial for defense, intestinal homeostasis precludes exaggerated responses to luminal contents, whether they are harmful or not. We investigated mechanisms used by CD4(+) T cells to avoid excessive activation in the intestine. Using genetic tools to label and interfere with T cell-development transcription factors, we found that CD4(+) T cells acquired the CD8-lineage transcription factor Runx3 and lost the CD4-lineage transcription factor ThPOK and their differentiation into the T(H)17 subset of helper T cells and colitogenic potential, in a manner dependent on transforming growth factor-β (TGF-β) and retinoic acid. Our results demonstrate considerable plasticity in the CD4(+) T cell lineage that allows chronic exposure to luminal antigens without pathological inflammation.


Use of Decision Cases for Building SNAP-Ed Implementers' Capacities to Realize Policy, Systems, and Environmental Strategies.
To develop and validate decision cases as a capacity-building training tool for implementing policy, systems, and environmental (PSE) change strategies. Study phases were: (1) in-depth interviews conducted repeatedly over a year with Supplemental Nutrition Assistance Program Education (SNAP-Ed) partner sites and once with SNAP-Ed implementers to identify dilemmas when implementing PSE change strategies; (2) decision cases developed to highlight dilemmas; and (3) focus groups with SNAP-Ed implementers to determine decision case utility as a capacity-building training tool. A southeastern state. SNAP-Ed partner sites and implementers; Focus group participants. Decision cases. To establish content validity, a thematic analysis of interviews identified common dilemmas when implementing PSE change strategies. SNAP-Ed implementers' focus groups provided feedback to determine the utility and validity of decision cases developed from the analysis. Common dilemmas of implementation of PSE change strategies reported by SNAP-Ed partner sites (n = 20) and implementers (n = 8) were lack of site and educator readiness and capacity; communication breakdowns; and prioritization of nutrition education over PSE implementation. Focus group participants (n = 8) reviewed a case and discussion guide and recommended them as a capacity-building tool for training. Using decision cases could help build SNAP-Ed implementers' capacities to implement nutrition PSE change strategies and strengthen partnerships.


Characterization of springtime airborne particulate matter-bound reactive oxygen species in Beijing.
Epidemiologic studies have suggested that particulate matter (PM)-associated adverse health effects are related to particle composition. To study the toxicological characteristics of dust storm, airborne PM10 was collected at two sites in Beijing from March to May 2012. The production of reactive oxygen species (ROS), quantified by dithiothreitol (DTT), was used to measure the PM-induced oxidative potential. Two dust storm (DS) samples were monitored during the sampling period: one happened on March 28th (DS1) and the other one was on April 28th (DS2). The backward trajectory results showed that both events originated from Inner Mongolia and Mongolia, respectively. The increased trends of ROS activities during the dust storm episode in PM10 were observed for all the dust storms owing to a higher concentration of water-soluble components for all the PM10 samples compared to nondust storm ones. Interestingly, the correlations between DTT consumption with water-soluble species yield interesting results about the spatial variability of redox activity between sites. In particular, a tracer of soil suspension, namely Fe, contributed the most fraction to ROS variability in the urban background site. Water-soluble organic carbon (WSOC) made the highest contribution to ROS variability, suggesting that vehicle emission might be important driving factors of the PM-induced oxidative stress in the urban site.


Sex differences in the antidepressant-like effects of ketamine.
Current medications for major depression suffer from numerous limitations. Once the right drug for treatment has been determined, it still takes several weeks for it to take effect and improve mood. This time lag is a serious concern for the healthcare community when dealing with patients with suicidal thoughts. However, recent clinical studies have shown that a single low-dose injection of ketamine, an N-methyl D-aspartate receptor (NMDAR) antagonist, has rapid antidepressant effects that are observed within hours and are long lasting. Although major depression affects twice as many women as men, all studies examining the rapid antidepressant effects of ketamine have focused on male subjects. Thus, we have investigated the behavioral and molecular effects of ketamine in both male and female rats and demonstrated greater sensitivity in female rats at a low dose of ketamine, a dose does not have antidepressant-like effects in male rats. The antidepressant-like effects of this low dose of ketamine were completely abolished when female rats were ovariectomized (OVX), and restored when physiological levels of estrogen and progesterone were supplemented, suggesting a critical role for gonadal hormones in enhancing the antidepressant-like effects of ketamine in female rats. In preclinical studies, the mammalian target of rapamycin (mTOR) in the medial prefrontal cortex and the eukaryotic elongation factor (eEF2) in the hippocampus have been proposed as critical mediators of ketamine's rapid antidepressant actions. In our hands, the increased sensitivity of female rats to a low dose of ketamine was not mediated through phosphorylation of mTOR or eEF2.


Factors influencing the demand of the service of community based animal health care in Zimbabwe.
This study was done to find out about animal health service providers and factors that determined demand for community based veterinary service delivery in smallholder sector of Zimbabwe. Focus group discussions and a questionnaire was used to collect data on veterinary services providers and socio-economic factors related to animal health from a sample (N=333) smallholder livestock farmers from Gutu district of Masvingo province in Zimbabwe. Analytical techniques used were descriptive statistics, K-mean cluster analysis and Tobit regression model. Results showed that the majority of farmers (45%) obtained services from both Community Based Animal Health Workers (CBAHWs) and Department of Veterinary Service (DVS), 25% DVS only, 20% used CBAHWs while 10% did not seek any services. Further analysis showed that distance to CBAHW, distance to AHMC and employment status were significantly related to demand for CBAHWs with coefficients of -1.5, 0.7 and -10.3, respectively. The study thus concluded that CBAHW is an alternative animal health service delivery approach already practiced in smallholder farming sectors of Zimbabwe. Socio-economic factors significantly influenced the demand for CBAHW services. Given limited resources by state sponsored veterinary services, it is recommended that the CBAHWs approach should be encouraged as supplementary service provider especially in areas further DVS. These community organizations can be empowered by the state to deliver more improved services based on hygiene and modern science at a relatively low cost to farmers.


Are Adrenal Lesions of 6 cm or More in Diameter a Contraindication to Laparoscopic Adrenalectomy? A Case-Control Study.
The aim of this case-control study is to compare the surgical outcomes of laparoscopic adrenalectomy (LA) for lesions measuring ≥6 cm versus ≤5.9 cm in diameter. Eighty-one patients with adrenal gland lesions ≥6 cm in diameter (intervention group) were identified. Patients were matched to 81 patients with adrenal gland ≤5.9 cm in diameter (control group) based on disease (Conn-Cushing syndrome, pheochromocytoma, primary or secondary adrenal cancer or other disease), lesion side (right, left), surgical technique (anterior transperitoneal approach for right and left LA or anterior transperitoneal submesocolic for left LA) and body mass index class (18-24.9, 25-29.9, 30-34.9, 35-39.9, ≥40 kg/m2). Surgical outcomes were compared between the intervention and control groups. Mean operative time was statistically significantly longer in the interventional arm (101.4 ± 52.4 vs. and 85 ± 31.6 min, p = 0.0174). Eight conversions were observed in the intervention group (9.8%) compared to four in the control group (4.9%) (p = 0.3690). Five (6.1%) and three (3.7%) postoperative complications were observed in the intervention and control groups, respectively (p = 0.7196). Mean postoperative hospital stay was 4.6 ± 2.4 and 4.1 ± 2.3 days in the intervention and control groups, respectively (p = 0.1957). Operative time was statistically significantly longer in adrenal gland lesions ≥6 cm in diameter (vs. ≤5.9 cm). Conversion and complication rates were also higher, but the difference was not statistically significant. Based on the present data, adrenal gland lesions ≥6 cm in diameter are not an absolute contraindication to the laparoscopic approach.


Green production of titanium dioxide nanometric particles through electrolytic anodic dissolution of titanium metal.
Nanometric titanium derivatives such as hydroxide and dioxide compounds have a great attention because they are significant industrial material of commercial importance and applications in photocatalyst, semiconductors, and wastewater treatment. The present investigation gives the results of anodic dissolution preparation of titanium hydroxide nanometric particles followed by calcination for complete conversion to nanometric titanium dioxide product. The optimum conditions for the anodic dissolution of titanium metal were pH 4, C.D. 65 mA/cm2, 25 °C, 150 rpm, electrode gap distance 3 cm, and NaCl 3 g/l for electrolysis time 240 min and thermally calcinated at 600 °C for 240 min., to reach complete conversion to anatase titanium dioxide nanopowder of main particles size of 77 nm with major percentage of 70%. Chemical and physical characterizations were carried out for evaluation of the obtained products including transmission electron microscope, EDX, XRD, and the scanning advanced electronic diffraction pattern. Preliminary economic indicators were calculated to show that the capital cost of the plant is $1.613 million, with annual operating cost of $0.915 million which means the required investment is $2.528 million. The operating cost for the production of nanometric anatase TiO2 is $30.5/kg with depreciation excluding the land price.


Inhibition of phagocytosis and glucose metabolism of alveolar macrophages during pulmonary tumour growth.
Alveolar macrophage (AM) phagocytic activity and glucose metabolism were evaluated during lung tumour growth in adult rats challenged i.v. with 10(5) viable Walker 256 tumour cells. Phagocytosis was estimated by the in vitro uptake of (14)C-labelled Pseudomonas aeruginosa and glucose oxidation was evaluated by (14)CO(2) production from 1-(14)C-glucose. AM were harvested by lung lavage from rats prior to and at 7 and 21 days following i.v. tumour-cell challenge. Macroscopic lung tumour nodules were not observed by 7 days after tumour challenge. However, 3 weeks after tumour challenge, tumour nodules were clearly identifiable on the surfaces of the lungs. One week after the i.v. tumour challenge a marked increase in the number of AM was evident. The in vitro phagocytosis of (14)C-labelled Pseudomonas aeruginosa was unaltered at that time, but became progressively depressed thereafter. Three weeks after tumour challenge, this decrease in phagocytic activity was evident when cells were incubated in normal serum, and was furtheri ntensified by serum obtained from tumour-bearing animals. Glucose oxidation by AM in either the resting condition or during bacterial phagocytosis was clearly decreased at both 1 and 3 weeks following i.v. tumour challenge. These findings indicate that the growth of pulmonary metastases is associated with a depression of alveolar macrophage bacterial phagocytic capacity, perturbations in serum opsonic activity and distinct alterations in macrophage energy metabolism. The metabolic dysfunction may impair pulmonary macrophage host defences against lung tumour growth.


Assessing the importance of thermogenic degassing from the Karoo Large Igneous Province (LIP) in driving Toarcian carbon cycle perturbations.
The emplacement of the Karoo Large Igneous Province (LIP) occurred synchronously with the Toarcian crisis (ca. 183 Ma), which is characterized by major carbon cycle perturbations. A marked increase in the atmospheric concentration of CO2 (pCO2) attests to significant input of carbon, while negative carbon isotope excursions (CIEs) in marine and terrestrial records suggest the involvement of a 12C-enriched source. Here we explore the effects of pulsed carbon release from the Karoo LIP on atmospheric pCO2 and δ13C of marine sediments, using the GEOCLIM carbon cycle model. We show that a total of 20,500 Gt C replicates the Toarcian pCO2 and δ13C proxy data, and that thermogenic carbon (δ13C of -36 ‰) represents a plausible source for the observed negative CIEs. Importantly, an extremely isotopically depleted carbon source, such as methane clathrates, is not required in order to replicate the negative CIEs. Although exact values of individual degassing pulses represent estimates, we consider our emission scenario realistic as it incorporates the available geological knowledge of the Karoo LIP and a representative framework for Earth system processes during the Toarcian.


Chromosome evolution in retinoblastoma.
An attempt to reconstruct the chromosome evolution in 19 primary retinoblastoma tumors was made, taking into consideration the frequencies of the rearrangements for each case. The rearrangements were classified as early or late according to their frequency. Early chromosome rearrangements were +1q, +6p, -13/del(13q), -16/del(16q), -17/del(17p), and late rearrangements were (in decreasing order) -8, -17/del(17p), -22, +3/+3q, -4, -19, +1q, +7/+7q, -14, +21. Chromosome evolution was reconstructed by the analysis of parsimony using programs of phylogenetic inference, which belong to the computer package PHYLIP. Results of the reconstruction of chromosome evolution suggest that there are two types of retinoblastoma tumors which can be distinguished based on chromosome imbalance, and correlate with the presence or absence of additional copies of the short arm (p) of chromosome 6. Tumors with additional 6p chromosome had marked heterogeneity, with a high frequency of early as well as late chromosome changes. By contrast, tumors with a normal 6p complement had the fewest chromosome changes and, in particular, a lower frequency of late changes.


1. Caged females of Rhyacionia buoliana attract males only during a limited period in the early evening. Outside this time no flying males could be observed. 2. Even when abdominal extracts of females are offered during a period of 24 hours, flight activity of males occurs only between late afternoon and beginning darkness. 3. Males could be attracted by abdominal extracts before females released scent and before the general male flight started. 4. On clear evenings extracts placed on aisles attracted males later than those in plantations. This difference in timing is explained by differences in light intensity between the two areas.


Cytokine gene polymorphisms and the susceptibility to liver cirrhosis in patients with chronic hepatitis C.
The speed of fibrosis progression varies considerably between patients with chronic hepatitis C. This study analyzed whether cytokine gene polymorphisms are associated with a progressive course of the disease. Leukocyte DNA from 101 patients with chronic hepatitis C, 52 patients with hepatitis C virus (HCV)-induced cirrhosis and 200 Caucasian blood donors was prepared. Using PCR, RFLP and PAGE, gene polymorphism analysis of the interleukin (IL)1alpha( - 889), IL1beta( - 511 and +3954), IL1 receptor agonist (RA)(intron2 VNTR), IL4(intron3 VNTR) and TNFalpha( - 308) loci was performed. Of the polymorphisms analyzed, IL1beta( - 511) and IL1RA(intron2 VNTR) were unevenly distributed between the study groups. The IL1 (- 511)*A2A2 genotype occurred significantly more often in chronic hepatitis C and HCV-induced liver cirrhosis than in the controls (P < 0.01, P < 0.05, respectively). Patients with HCV-induced cirrhosis displayed a significantly higher frequency of the IL1RA(intron2 VNTR)*A2 polymorphism than patients with chronic hepatitis C and controls (P < 0.05). Although the IL1beta( - 511)*A2A2 genotype may increase the susceptibility to acquire chronic hepatitis C and IL1RA(intron2 VNTR)*A2 polymorphism is associated with disease progression to cirrhosis, our results indicate that the analyzed cytokine gene polymorphisms have an overall low impact on the natural course of chronic hepatitis C infection.


Induction of tubulin by docetaxel is associated with p53 status in human non small cell lung cancer cell lines.
Docetaxel (DOC), a member of the taxane family of anticancer drugs, binds to tubulin and produces unnaturally stable microtubules that induce cell death. DOC is used clinically alone or in combination with other compounds to treat advanced stages of cancer. We have treated the human lung cancer cell lines A549 and H1299 and human cervical cancer HeLa cells with low concentrations of DOC to characterize the response of beta-tubulin isotypes and p53 genes. The relationship between p53 function and DOC, acting through a microtubule-based mechanism, was examined. We found that after 18-hr treatment with DOC, beta-tubulin gene transcription was enhanced in p53-null H1299 cells but not in A549 cells. Also, p53 RNA was strongly induced in the A549 cells. In addition, beta-tubulin levels also increased in the H1299 cells after the DOC treatment. Further demonstrating an association of DOC treatment with p53 and beta-tubulin, inhibition of p53 expression by interference RNA in A549 cells showed increasing beta-tubulin gene expression with DOC treatment. We also selected a clone from the H1299 cells that stably expressed p53, examined the beta-tubulin expression after DOC treatment and found an inhibition of beta-tubulin induction in these p53-expressing cells. Our data suggest that the initial response of cells to DOC treatment involves p53; alternatively, in the absence of p53, tubulins may be transactivated. Selection of the DOC-resistant A549 cells showed beta-tubulin expression was increased, in contrast to the initial response to the DOC treatment. From the initial and selection responses of beta-tubulin in cancer cells, it appears that there is a p53-associated beta-tubulin expression as a result of the DOC treatment.


Evaluation of potential human carcinogenicity of the synthetic monomer ethyl acrylate.
Ethyl acrylate (EA) is an acrylic monomer used in the manufacture of a variety of polymers and copolymers as components of many commercially important products. Human exposure to EA occurs primarily in the workplace via inhalation or dermal contact. In F344 rat and B6C3F(1) mouse studies of EA carcinogenicity conducted by the National Toxicology Program [National Toxicology Program, NTP, 1986. Carcinogenesis Studies of Ethyl Acrylate (CAS No. 140-88-5) in F344/N Rats and B6C3F(1) Mice (Gavage Studies) (Tech. Rep. Ser. No. 259; NIH Publication No. 87-2515), Research Triangle Park, NC, USA], the only increased tumor incidences was in squamous cell papillomas and carcinomas of the forestomach, when EA was administered by gavage in corn oil at 100 or 200mg/kg/day (high dose; HD). The neoplasms were preceded by forestomach irritation, inflammation, hyperkeratosis and hyperplasia of the forestomach mucosa. In studies in which rats and mice were exposed at comparable doses to EA in drinking water, by inhalation, or by dermal application, no neoplasms in the forestomach or in any other tissue were reported. EA exhibited clastogenicity and related mutagenicity in vitro, but was non-genotoxic in vivo, including in the forestomach of treated rats. The in vitro clastogenicity response correlates well with cellular toxicity, mediated by non-protein sulfhydryl depletion and mitochondrial impairment. Thus, the carcinogenicity in the forestomach can be ascribed to a non-genotoxic mode of action (MOA). The forestomach mucosal hyperplastic and even dysplastic changes, observed chronically, were reversible, provided the HD exposure was not longer than 6months. This again supports a non-genotoxic MOA. In addition, the route and rate of EA exposure in rodents for forestomach neoplasia are irrelevant to potential human exposure, since humans do not have forestomach and are not exposed to EA by oral bolus. Thus, the weight of evidence indicates that the tumors produced in the rodent carcinogenicity studies arise from conditions that are irrelevant for human risk assessment.


Rab11a regulates MMP2 expression by activating the PI3K/AKT pathway in human hepatocellular carcinoma cells.
As a member of the Rab GTPase family, Rab11a plays an important role in vesicle transport and tumor progression. However, it is not clear whether it can also be used as an oncoprotein in hepatocellular carcinoma (HCC). In this study, database and immunohistochemical analyses showed that Rab11a was highly expressed in HCC tissues, and associated with poor clinical prognosis. Rab11a overexpression promoted the proliferation, migration, invasion, and anti-apoptosis of human HCC cell lines, MHCC-97H and HCC-LM3, whereas the downregulation of Rab11a inhibited these biological tumor activities. Nude mice xenograft demonstrated that Rab11a had a positive effect on the growth of hepatocellular carcinoma cells in vivo. Further studies found that the PI3K/AKT pathway and matrix metalloproteinase 2 (MMP2) upregulation can be activated by over-expression of Rab11a. However, MMP2 upregulation induced by Rab11a can be inhibited by the PI3K/AKT pathway inhibitor, LY294002. Altogether, our study established for the first time that Rab11a can play a pro-cancer role in HCC, as a novel oncoprotein, by activating the PI3K/AKT pathway to regulate MMP2 expression.


The accuracy of acuity scoring tools to predict 24-h mortality in traumatic brain injury patients: A guide to triage criteria.
Prompt identification of traumatic brain injury (TBI) is vital for patients in critical condition; however, it is not clear which acuity scoring tools are associated with short-term mortality. The aim of this study was to determine the accuracy of acuity scoring tools and 24-h mortality among TBI patients in both prehospital and hospital settings. This study was an observational, prospective cohort, in which patients with TBI were followed from the accident scene to the hospital. Vital signs and acuity scoring tools, including the Revised Trauma Score (RTS), Injury Severity Score (ISS), National Early Warning Score (NEWS), Shock Index (SI), Modified Shock Index (MSI) and Trauma and Injury Severity Score (TRISS), were collected both on the scene as well as at the hospital. A logistic regression was performed to ascertain the effects of clinical parameters on the likelihood of survival of patients with TBI regarding 24-h mortality. A total of 185 patients were included in this study. The mortality rate was 14% (25/185). The logistic regression model was statistically significant at χ2=60.8, p=0.001. A hierarchical forward stepwise logistic regression analysis showed that age, hospital RTS and prehospital NEWS significantly improved mortality predictions. The model explained the 51.2% variance in survival of patients with TBI. The NEWS and the RTS may be used to triage TBI patients for prehospital and hospital emergency care, respectively. Therefore, because traditional vital signs criteria may be of limited use for the triage of TBI patients, it is recommended that acuity scoring tools be used in such cases.


Oestradiol-induced hypotension in spontaneously hypertensive rats: putative role for intracellular cations, sodium-potassium flux and prostanoids.
1. The effect of oestradiol alone and in combination with indomethacin on blood pressure, erythrocyte cation concentration and Na(+)-K+ flux has been studied in adult female normotensive and spontaneously hypertensive rats. 2. Oestradiol alone resulted in a significant decrease in blood pressure in spontaneously hypertensive rats (from 165.3 +/- 3.9 to 146.4 +/- 2.7 mmHg, P less than 0.001), whereas it induced a significant increase in normotensive rats (from 111.8 +/- 1.8 to 124.1 +/- 3.6 mmHg, P less than 0.001). When indomethacin and oestradiol were administered simultaneously or when indomethacin was given alone, no change in blood pressure occurred in spontaneously hypertensive rats (158.6 +/- 6.9 and 159.8 +/- 6.2 mmHg, respectively). 3. The fall in blood pressure induced by oestradiol in spontaneously hypertensive rats was associated with significant reductions in erythrocyte K+ concentration (from 127.4 +/- 1.2 to 116.9 +/- 1.7 mmol/l of cells, P less than 0.001), in erythrocyte Na+ concentration (from 14.3 +/- 0.8 to 13.0 +/- 0.6 mmol/l of cells, P less than 0.02), in ouabain-sensitive erythrocyte Na+ flux (from 17.8 +/- 0.3 to 16.0 +/- 0.4 mmol h-1 (l of cells)-1, P less than 0.01) and in ouabain-sensitive erythrocyte K+ flux (from 11.4 +/- 0.2 to 10.4 +/- 0.2 mmol h-1 (l of cells)-1, P less than 0.01). No change in blood pressure, erythrocyte cation concentration or Na(+)-K+ flux occurred when oestradiol and indomethacin were given together or when indomethacin was administered alone.(ABSTRACT TRUNCATED AT 250 WORDS)


Peony root extract upregulates transthyretin and phosphoglycerate mutase in mouse cobalt focus seizure.
Cobalt focus is a seizure focus model in which cerebral neurons exhibit long-lasting severe spike discharges, followed by neuronal death. However, the neuronal death is prevented when peony root extract (PR) is administered prior to cobalt application. We tested the hypothesis that PR modulates the expression of neuroprotective proteins in the cerebrum of mouse cobalt focus by proteomic analysis using two-dimensional polyacrylamide gel electrophoresis and mass spectrometry to screen for differentially expressed proteins. Analyses revealed that transthyretin, a carrier protein for thyroid hormones and retinoids, and the brain form of phosphoglycerate mutase, a glycolytic enzyme, were upregulated in the cobalt-treated mouse cerebrum and further increased by PR administration in association with upregulation of neurogranin/RC3, a target of the transcriptional activation by thyroid hormones and retinoids. These findings suggest that PR-induced protection of mouse cerebral neurons involves neurotrophic events caused by thyroid hormones and/or retinoids and enhanced glycolysis.


Evaluation of SEE-FIM (Sectioning and Extensively Examining the FIMbriated End) Protocol in Identifying Fallopian Tube Precursor Lesions in Women with Ovarian Tumors.
Studies of prophylactic salpingo-oophorectomies in high-risk population led to incidental finding of precursor lesions in the fimbrial end of fallopian tube rather than the ovary. Early detection of these precursor lesions can be helpful in the prevention of ovarian tumors, and the presence of these lesions can be more efficiently studied by applying Sectioning and Extensively Examining the FIMbriated End (SEE-FIM) protocol. To study precursor lesions of fallopian tubes associated with ovarian tumors by applying SEE-FIM protocol. Sixty specimens of hysterectomy with bilateral salpingo-oophorectomy, clinically diagnosed as ovarian tumor (study group), were examined by SEE-FIM protocol. Specimens without ovarian tumor were taken as the control group, and same protocol was applied on them. Histological changes in fallopian tube were grouped either as tubal intraepithelial carcinoma (TIC), tubal intraepithelial lesion (TIL), only stratification and negative for any changes. Out of 60 cases in the study group, 10.00% (6/60) cases showed TIC, 38.34% (23/60) cases revealed TIL, 23.33% (14/60) cases showed changes of stratification and the rest were negative for any changes. Among these 60 cases, there were 7 cases of high-grade serous carcinoma, 5 (71.43%) of them showed changes of TIC. In the control group, out of 60 cases, none showed TIC changes, TIL was noted in 6.66% (4/60) cases, changes of stratification were seen in 26.67% (16/60) cases and the rest were negative for any changes. SEE-FIM protocol maximizes the examination of fimbrial end and is helpful in identifying precursor lesions of ovarian epithelial tumors.


Profound effect of study design factors on ventilator-associated pneumonia incidence of prevention studies: benchmarking the literature experience.
The ventilator-associated pneumonia incident proportion (VAP-IP) is highly variable among control groups of studies of methods for its prevention. The objective here is to develop and validate a literature-derived benchmark against which these groups can be profiled. A literature search yielded 95 cohort groups and control and intervention groups of 150 studies of either non-antimicrobial or antimicrobial methods of VAP prevention. The 95 cohort groups comprise a benchmark set (30 groups), from which the reference funnel plot (RFP) was derived, and a search set (65 groups), against which the benchmark was validated. The VAP-IP data of the benchmark set were found in five published systematic reviews, whereas the VAP-IP data of the search set were abstracted directly from the literature. Among the 95 cohort groups, the VAP-IP of groups with size >399 was significantly lower than the VAP-IP of smaller groups. Compared with the RFP, 15 of 51 (29%) control groups from studies of antimicrobial methods of VAP prevention with concurrent design were high outlier versus 2 of 110 (2%) control groups from other types of study design (P < 0.001). There were only 22 (14%) outlier groups, all low outlier, among the 162 intervention groups. Study design factors such as concurrency and study size have potentially greater influence on the VAP-IP than do the VAP prevention methods under study. The outlier status of control groups were inapparent in the individual studies and the meta-analyses and yet would have confounded the estimates of treatment effect.


Behavioural, electroencephalographic and neuropathological effects of the intrahippocampal injection of the venom of the South American rattlesnake (Crotalus durissus terrificus).
Venom was microinjected into the dorsal hippocampus of rats and electroencephalographic recordings were obtained from the hippocampus and occipital cortex. Behavioural alterations consisted of circling, wet shaking and scratching that evolved to head and body jerks and isolated clonic episodes and then to wild running followed by tonic-clonic generalized seizures and status epilepticus. Electroencephalographic alterations consisted of high frequency and high voltage spikes together with epileptiform seizures beginning in the hippocampus and evolving to the cortex. However there was only a poor electrographic-behavioural correlation between the generalized tonic-clonic seizures preceded by wild running and the electrical recordings from hippocampus and occipital cortex. Histology revealed lesions at the site of injection as well as at distant sites. Severity of neuronal damage was associated with seizure intensity. Damaged areas were almost the same as found within other models of epilepsy. Nevertheless a remarkable difference was the highly lesioned hypothalamus seen in this experiment. We discuss our results in relation to results obtained with other methods of inducing epilepsy. This venom may be a useful tool for studying the nervous system.


Effects of tapering on performance in endurance athletes: A systematic review and meta-analysis.
To assess the responses to taper in endurance athletes using meta-analysis. Systematic searches were conducted in China National Knowledge Infrastructure, PubMed, Web of Science, SPORTDiscus, and EMBASE databases. Standardized mean difference (SMD) and 95% confidence interval (CI) of outcome measures were calculated as effect sizes. 14 studies were included in this meta-analysis. Significant improvements were found between pre- and post-tapering in time-trial (TT) performance (SMD = -0.45; P < 0.05) and time to exhaustion (TTE) performance (SMD = 1.28; P < 0.05). However, There were no improvements in maximal oxygen consumption ([Formula: see text]) and economy of movement (EM) (P > 0.05) between pre- and post-tapering. Further subgroup analysis showed that tapering combined with pre-taper overload training had a more significant effect on TT performance than conventional tapering (P < 0.05). A tapering strategy that reduced training volume by 41-60%, maintained training intensity and frequency, lasted ≤7 days, 8-14 days, or 15-21 days, used a progressive or step taper could significantly improve TT performance (P < 0.05). The tapering applied in conjunction with pre-taper overload training seems to be more conducive to maximize performance gains. Current evidence suggests that a ≤21-day taper, in which training volume is progressively reduced by 41-60% without changing training intensity or frequency, is an effective tapering strategy.


COVID-19 and the future of work in the hospitality industry.
The COVID-19 pandemic has significantly disrupted the hospitality industry. This research combines different data to examine the US labor market trends during COVID-19. It is found that low-preparation jobs in leisure and hospitality are the hardest hit and slow to recover. The pandemic has highlighted growing issues in workplace safety, skill gaps, technology adoption, and work reorganization in the hospitality industry. This paper develops two propositions about preparing hospitality workers for the future of work and providing flexible work arrangements.


RNA-seq analysis identifies potential modulators of gravity response in spores of Ceratopteris (Parkeriaceae): evidence for modulation by calcium pumps and apyrase activity.
Gravity regulates the magnitude and direction of a trans-cell calcium current in germinating spores of Ceratopteris richardii. Blocking this current with nifedipine blocks the spore's downward polarity alignment, a polarization that is fixed by gravity ∼10 h after light induces the spores to germinate. RNA-seq analysis at 10 h was used to identify genes potentially important for the gravity response. The data set will be valuable for other developmental and phylogenetic studies. De novo Newbler assembly of 958 527 reads from Roche 454 sequencing was executed. The sequences were identified and analyzed using in silico methods. The roles of endomembrane Ca(2+)-ATPase pumps and apyrases in the gravity response were further tested using pharmacological agents. Transcripts related to calcium signaling and ethylene biosynthesis were identified as notable constituents of the transcriptome. Inhibiting the activity of endomembrane Ca(2+)-ATPase pumps with 2,5-di-(t-butyl)-1,4-hydroquinone diminished the trans-cell current, but increased the orientation of the polar axis to gravity. The effects of applied nucleotides and purinoceptor antagonists gave novel evidence implicating extracellular nucleotides as regulators of the gravity response in these fern spores. In addition to revealing general features of the transcriptome of germinating spores, the results highlight a number of calcium-responsive and light-receptive transcripts. Pharmacologic assays indicate endomembrane Ca(2+)-ATPases and extracellular nucleotides may play regulatory roles in the gravity response of Ceratopteris spores.


Amino acid metabolism in tumor: New shine in the fog?
Alterations in amino acid metabolism is closely related to the occurrence of clinical diseases. The mechanism of tumorigenesis is complex, involving the complicated relationship between tumor cells and immune cells in local tumor microenvironment. A series of recent studies have shown that metabolic remodeling is intimately related to tumorigenesis. And amino acid metabolic reprogramming is one of the important characteristics of tumor metabolic remodeling, which participates in tumor cells growth, survival as well as the immune cell activation and function in the local tumor microenvironment, thereby affecting tumor immune escape. Recent studies have further shown that controlling the intake of specific amino acids can significantly improve the effect of clinical intervention in tumors, suggesting that amino acid metabolism is gradually becoming one of the new promising targets of clinical intervention in tumors. Therefore, developing new intervention strategies based on amino acid metabolism has broad prospects. In this article, we review the abnormal changes in the metabolism of some typical amino acids, including glutamine, serine, glycine, asparagine and so on in tumor cells and summarize the relationship among amino acid metabolism, tumor microenvironment and the function of T cells. In particular, we discuss the current issues that need to be addressed in the related fields of tumor amino acid metabolism, aiming to provide a theoretical basis for the development of new strategies for clinical interventions in tumors based on amino acid metabolism reprogramming.


Drug safety: Pregnancy rating classifications and controversies.
This contribution consolidates data on international pregnancy rating classifications, including the former US Food and Drug Administration (FDA), Swedish, and Australian classification systems, as well as the evidence-based medicine system, and discusses discrepancies among them. It reviews the new Pregnancy and Lactation Labeling Rule (PLLR) that replaced the former FDA labeling system with narrative-based labeling requirements. PLLR emphasizes on human data and highlights pregnancy exposure registry information. In this context, the review discusses important data on the safety of most medications used in the management of skin disease in pregnancy. There are also discussions of controversies relevant to the safety of certain dermatologic medications during gestation.


IgM response is a prognostic biomarker of primary biliary cholangitis treated with ursodeoxycholic acid and bezafibrate.
Primary biliary cholangitis (PBC) patients who are refractory to ursodeoxycholic acid (UDCA) are at risk for progression to cirrhosis and liver failure. Bezafibrate could be an alternative second-line therapeutic option in these patients. This study aimed to evaluate the long-term outcome(s) of combined UDCA and bezafibrate therapy in UDCA-refractory PBC patients and identify prognostic factors. Among 445 patients treated with UDCA, 150 patients inadequately responded to UDCA monotherapy and received long-term UDCA plus bezafibrate (median, 15 years). Data from these patients were used for this retrospective analysis. Combination therapy resulted in significant improvements in serum biochemistry and liver transplantation risk estimated using the UK-PBC-risk and the GLOBE scores. The cumulative normalization rates of alkaline phosphatase, gamma-glutamyltransferase, and immunoglobulin M (IgM) were significantly higher in patients without cirrhosis-related symptoms or liver-related events than in those with them. Overall, IgM constantly emerged as a significant factor associated with cirrhosis-related symptoms and liver-related events at all time points. Cumulative survival rates were significantly lower in patients with IgM ≥ 240 mg/dL than in patients with IgM < 240 mg/dL. Thus, normalization of IgM levels was a good surrogate predictor of long-term prognosis. None of the patients discontinued combination therapy due to any adverse events during the follow-up period. Our findings point to the beneficial effects of long-term UDCA plus bezafibrate combination therapy for UDCA-refractory PBC patients, and IgM response can be a useful predictive biomarker of long-term clinical outcomes.


Intravascular coagulation resulting from intravenous injection of C. parvum in mice.
In mice, i.v. C. parvum induces intravascular coagulation. This is a prolonged reaction lasting up to 7 days. It results in thrombosis in hepatic vessels with consequent hepatic necrosis, and thrombosis in pulmonary and splenic vessels. This may be important in the assessment of the tumour-inhibitory activity of C. parvum.


Evaluation of brain iron content based on magnetic resonance imaging (MRI): comparison among phase value, R2* and magnitude signal intensity.
Several magnetic resonance imaging (MRI) techniques are being exploited to measure brain iron levels increasingly as iron deposition has been implicated in some neurodegenerative diseases. However, there remains no unified evaluation of these methods as postmortem measurement isn't commonly available as the reference standard. The purpose of this study was to make a comparison among these methods and try to find a new index of brain iron. We measured both phase values and R2* in twenty-four adults, and performed correlation analysis among the two methods and the previously published iron concentrations. We also proposed a new method using magnitude signal intensity and compared it with R2* and brain iron. We found phase value correlated with R2* in substantia nigra (r = -0.723, p<0.001) and putamen (r = -0.514, p = 0.010), while no correlations in red nucleus (r = -0.236, p = 0.268) and globus pallidus (r = -0.111, p = 0.605). And the new magnitude method had significant correlations in red nucleus (r = -0.593, p = 0.002), substantia nigra (r = -0.521, p = 0.009), globus pallidus (r = -0.750, p<0.001) and putamen (r = -0.547, p = 0.006) with R2*. A strong inverse correlation was also found between the new magnitude method and previously published iron concentrations in seven brain regions (r = -0.982, P<0.001). Our study indicates that phase value may not be used for assessing the iron content in some brain regions especially globus pallidus. The new magnitude method is highly consistent with R2* especially in globus pallidus, and we assume that this approach may be acceptable as an index of iron content in iron-rich brain regions.


Novel hybrid neuro-fuzzy model to anticipate the heat transfer in a heat exchanger equipped with a new type of self-rotating tube insert.
In this investigation, a combination of the wingsuit flying search (WFS) and teaching-learning-based optimization (TLBO) algorithms is developed as a new combinatorial optimization algorithm. The proposed combinatorial algorithm is tested over some well-known benchmark functions and then integrated with the artificial neural network (ANN) to construct a novel hybrid model. After that, the obtained hybrid model is employed to anticipate the experimentally obtained values of the average Nusselt number (Nu), average friction coefficient (f) as well as thermal-hydraulic performance ratio (η), in a heat exchanger equipped with a new type of self-rotating tube insert, against governing parameters. The insert is placed in the tube side of the water heater to heat natural gas. The proposed insert consists of various numbers of self-rotating modules. Indeed, the rotating insert is introduced to create effective secondary sweeping flow on the inner side of the tube. Since this type of tube insert simultaneously provides heat transfer enhancement and undesired pressure drop, a thermal-hydraulic performance ratio is defined to consider both of them. The governing parameters are the number of inserts (0 ≤ N ≤ 30), reservoir's temperature (40 °C ≤ TR ≤ 50 °C) as well as Reynolds number (6 × 103 ≤ Re ≤ 18 × 103). It was found that the WFS-TLBO enhances the effectiveness of the main ANN in anticipating the Nusselt number (Nu), average friction coefficient (f) as well as performance ratio (η). Moreover, introducing the WFS-TLBO algorithm into the neural network provides an enhancement in the effectiveness of the hybrid models based on the single WFS and TLBO algorithms in anticipating the same parameters.


Colour vision in normal subjects tested by the colour arrangement test 'Roth 28-hue desaturated'.
The aim of the study was to obtain normal values for the colour-arrangement test, Roth 28-hue desaturated. In 146 healthy non-smokers colour vision was tested monocularly. The subjects were divided into four age groups: 0-19, 20-39, 40-59, and 60-79 years. The overall error score for all groups was 54 +/- 24 (median +/- mean absolute deviation). The values for the 20-39 year group were significantly lower than those for the other groups (Kruskal-Wallis: P < 0.0001 with subsequent multiple Mann-Whitney test). An increasing predominance of errors along the blue-yellow-axis was observed with increasing age. The error scores of normal subjects tested by the Roth 28-hue desaturated were comparable with those on the well-known Farnsworth-Munsell 100-hue (FM-100). Because the Roth 28-hue desaturated is shorter and simpler to administer, it is an alternative to the FM-100 in situations that need to assess colour discrimination and error axis quantitatively and quickly.


Location of the inhibitory region of smooth muscle myosin light chain kinase.
Proteolysis by trypsin of gizzard myosin light chain kinase (MLC kinase) in the absence of Ca2+-calmodulin produced a 64,000-dalton inactive fragment which was converted to a 61,000-dalton Ca2+-calmodulin-independent active fragment. This confirmed previous results (Ikebe, M., Stepinska, M., Kemp, B. E., Means, A. R., and Hartshorne, D. J. (1987) J. Biol. Chem. 262, 13828-13834). On the other hand, proteolysis of MLC kinase in the presence of Ca2+-calmodulin initially produced a 66,000-dalton Ca2+-calmodulin-dependent active fragment which was converted to a 61,000-dalton Ca2+-calmodulin-independent active fragment with further proteolysis. The amino acid sequences from the N terminus of the 66,000-dalton, 64,000-dalton, and 61,000-dalton fragments were determined. The sequence was not found in the reported partial amino acid sequence of MLC kinase (C-terminal 60% of whole sequence) (Guerriero, V., Jr., Russo, M. A., Olson, N. J., Putkey, J. A., and Means, A. R. (1986) Biochemistry 25, 8372-8381), and, therefore, the cleavage sites are in the remaining 40% N-terminal portion of the sequence of MLC kinase. The C terminus of these MLC kinase fragments was determined by employing the carboxypeptidases A, B, and Y digestion followed by the amino acid analysis of the released amino acids. As a result, it was concluded that the C terminus of the 66,000-dalton, 64,000-dalton, and 61,000-dalton MLC kinase fragments are arginine 522, lysine 490 and arginine 494, and lysine 473, respectively. These results show that the inhibitory domain is in the amino acid sequence of 474-490, and that the amino acid sequence 494-522 confers the calmodulin-dependent kinase activity.


Role of different mechanisms in pro-inflammatory responses triggered by traffic-derived particulate matter in human bronchiolar epithelial cells.
Traffic-derived particles are important contributors to the adverse health effects of ambient particulate matter (PM). In Nordic countries, mineral particles from road pavement and diesel exhaust particles (DEP) are important constituents of traffic-derived PM. In the present study we compared the pro-inflammatory responses of mineral particles and DEP to PM from two road tunnels, and examined the mechanisms involved. The pro-inflammatory potential of 100 µg/mL coarse (PM10-2.5), fine (PM2.5-0.18) and ultrafine PM (PM0.18) sampled in two road tunnels paved with different stone materials was assessed in human bronchial epithelial cells (HBEC3-KT), and compared to DEP and particles derived from the respective stone materials. Release of pro-inflammatory cytokines (CXCL8, IL-1α, IL-1β) was measured by ELISA, while the expression of genes related to inflammation (COX2, CXCL8, IL-1α, IL-1β, TNF-α), redox responses (HO-1) and metabolism (CYP1A1, CYP1B1, PAI-2) was determined by qPCR. The roles of the aryl hydrocarbon receptor (AhR) and reactive oxygen species (ROS) were examined by treatment with the AhR-inhibitor CH223191 and the anti-oxidant N-acetyl cysteine (NAC). Road tunnel PM caused time-dependent increases in expression of CXCL8, COX2, IL-1α, IL-1β, TNF-α, COX2, PAI-2, CYP1A1, CYP1B1 and HO-1, with fine PM as more potent than coarse PM at early time-points. The stone particle samples and DEP induced lower cytokine release than all size-fractionated PM samples for one tunnel, and versus fine PM for the other tunnel. CH223191 partially reduced release and expression of IL-1α and CXCL8, and expression of COX2, for fine and coarse PM, depending on tunnel, response and time-point. Whereas expression of CYP1A1 was markedly reduced by CH223191, HO-1 expression was not affected. NAC reduced the release and expression of IL-1α and CXCL8, and COX2 expression, but augmented expression of CYP1A1 and HO-1. The results indicate that the pro-inflammatory responses of road tunnel PM in HBEC3-KT cells are not attributed to the mineral particles or DEP alone. The pro-inflammatory responses seem to involve AhR-dependent mechanisms, suggesting a role for organic constituents. ROS-mediated mechanisms were also involved, probably through AhR-independent pathways. DEP may be a contributor to the AhR-dependent responses, although other sources may be of importance.


A comparison between an interview and a self-report method of insight assessment in chronic schizophrenia.
We examined the relationship between a researcher-rated and a self-report method of insight assessment in patients with schizophrenia. Previous research has established that a moderate correlation exists between several researcher-rated and self-report insight scales. Hence, we wanted to investigate this association using another combination of assessment techniques. Accordingly, 34 patients with chronic schizophrenia were administered the Scale to Assess Unawareness of Mental Disorder (SUMD) and the Birchwood self-report Insight Scale (IS). We found a significantly lower report of insight on the Birchwood IS, regardless of administration order. These findings suggest that inherent bias within the patient-examiner interaction may be responsible for this discrepancy. Overall, a significant positive correlation was observed between total scores on the SUMD and the Birchwood self-report IS. Unexpectedly, there was a remarkable difference in correlation with respect to the order of test administration. The "self-report first" group's scores were strongly correlated, whereas the "researcher-rated first" group's scores showed little relation. These results demonstrate the importance of investigating the effects of administration order, and also question the reliability of other correlational studies between researcher-rated and self-report insight scales that have failed to employ a counterbalanced research design.


Thyroid autoimmunity in children with features of both type 1 and type 2 diabetes.
To assess the prevalence of autoimmune thyroid disease (ATD) in insulin-treated youth with clinical features of type 2 diabetes mellitus (T2DM). We evaluated prevalence of thyroid peroxidase (TPO) and thyroglobulin (TGA) antibodies at onset of insulin-treated diabetes and follow-up in 183 White and Black children. Of these, 136 had a body mass index (BMI) <85th percentile with 122 (89%) positive for beta-cell autoimmunity [type 1 diabetes mellitus (T1DM)/group I], 25 were overweight (BMI >or=85 th percentile) with or without acanthosis nigricans with beta-cell autoimmunity ['double' diabetes (DD)/group II], and 22 were overweight with no conventional beta-cell autoantibodies (group III). The prevalence of TPO and/or TGA was 39 and 29% (p = 0.19) in White and Black children and 39, 32, and 0% (p = 0.007) in groups I, II, and III, respectively. After a median follow-up of 60 months, 3.7, 4.3, and 0% developed hypothyroidism (increased thyroid-stimulating hormone with or without decreased free T4) in groups I, II, and III, respectively (p = 0.6). In subjects with TPO and/or TGA, hypothyroidism developed in 10 and 14% of groups I and II, respectively (p = 0.7). No child without thyroid antibodies developed hypothyroidism. In patients with clinical features of T2DM who have evidence of beta-cell autoimmunity (DD), the frequency of thyroid antibodies and ATD is similar to that in classical T1DM. This suggests that TIDM comorbidities may be common in clinical T2DM patients who have beta-cell autoimmunity. Despite their obesity, youth with insulin-requiring diabetes should be screened for thyroid and possibly other T1DM-associated autoimmune diseases.


Lithium transport across red cell membrane: a cell membrane abnormality in manic-depressive illness.
In the families of manic-depressive patients, relatives with a history of affective disorders had a significantly higher ratio of mean red cell lithium to plasma lithium in vitro than relatives with no such history. A genetically controlled abnormality in lithium-sodium transport, the mechanism that determines the lithium ratio, may play a role in the etiology of some forms of affective disorders.


Understanding impacts of cropland pattern dynamics on grain production in China: A integrated analysis by fusing statistical data and satellite-observed data.
Detailed information on spatial distribution of croplands and grain yields is crucial for agricultural management and food security, but is often limited by a lack of geospatial data. By integrating satellite observation and statistical data, this study produced new geospatial data of cropland areas and grain yields in China during 2000-2020. We found that the decrease of relatively high-yielding croplands in southern China mainly caused by the expansion of constructed land. Yet, the increase of croplands largely occurred in temperature/water-limited regions of Northern Arid and Semiarid Region (NASR) and Northeast China Plain (NCP). Croplands' decrease in southern China and expansion in NCP and NASR jointly led to the continuous northward shift of the centre of gravity of croplands and grain yields. This spatial transfer of croplands resulted in relatively lower-than- average grain yield per unit area (AGYA) croplands decreasing from 38.96% (2000) to 35.75% (2020), but also relatively higher-than-AGYA croplands decreasing from 38.41% (2000) to 35.01% (2020), implying spatial challenges of grain production. Generally, every 1 km2 of cropland loss in traditional high-yield zones required nearly 1-3 times expansion in area in NASR and NCP to balance grain yield losses. The new geospatial data and these findings from this study could provide valuable information for regional agriculture development and policy marking.


Characterization of coloured compounds obtained by enzymatic extraction of bakery products.
Melanoidins, the brown-colored polymers formed through Maillard type reaction in several heat-treated foods, represent a significant part of our diet, with an average intake of grams per day. Most of the studies on the physiological effects of these compounds have been performed using the water soluble melanoidin fractions. But dietary melanoidins formed on the surface of bakery products are poorly soluble in water as well as in organic solvents. In this work, an enzymatic solubilization procedure was developed on a gluten-glucose model system and it was applied to bread and biscuits. The soluble material obtained was tested for its antioxidant activity, for its effect on phase-I and phase-II xenobiotic enzymes and for potential cytotoxic effects. Soluble melanoidins from model system and biscuits exhibit a strong antioxidant activity and do not show any cytotoxicity on Caco-2 cells. Melanoidins extracted from biscuits was able to inhibit the activity of Phase I (NADPH-cytochrome-c reductase) and Phase II (Glutathione-S-transferase) enzymes, whereas the low molecular weight melanoidins isolated from gluten-glucose model system inhibit the activity of NADPH-cytochrome-c reductase.


Biochemical and evolutionary aspects of arthropod predation on ferns.
The widely held assumption that very few arthropods feed on ferns was questioned following field observations of arthropod damage on ferns in the state of Veracruz, Mexico. The extent and type of damage was recorded and it was found that in a measured locality, ferns were no less attacked than the angiospermous flora. As chemistry and arthropod host relationships have been shown to be so closely intertwined, plants collected in the field were analysed for both condensed tannins and cyanogenic glycosides, compounds known to be effective deterrents in temperate climates. Although all ferns tested contained tannins these did not appear to inhibit predation. Cyanogenic glycosides were present in only 3% of the fern species analysed, and it is, therefore, unlikely that they play a significant role as defensive compounds in the ferns examined.A literature search revealed a large number of ferns cited as being arthropod hosts. Approximately 420 named species of arthropods have been recorded, the majority of which are from the orders Coleoptera, Hymenoptera, Lepidoptera, and Hemiptera. Both evolutionary primitive (sawflies) and advanced (moths) arthropods are reported to be present on ferns suggesting possible coevolution of arthropods and ferns both before and after the radiation of angiosperms.


Immunocytochemical and ultrastructural studies of upper motor neurons in amyotrophic lateral sclerosis.
The pathological alterations in upper motor neurons were investigated in 27 cases of adult-onset sporadic amyotrophic lateral sclerosis (ALS). No significant cytoskeletal alterations were found in the Betz cells of any of the cases except one, although cytoskeletal pathology was consistently present in lower motor neurons. The one case had severe circumscribed atrophy of the precentral gyrus and, microscopically, had argentophilic intracytoplasmic inclusions in Betz cells and other pyramidal neurons in the primary motor area as eell as in the lower motor neurons. Immunocytochemically these inclusions contained the epitope of phosphorylated neurofilament and ubiquitin and ultrastructurally consisted of granule-associated filaments with neurofilaments. This is the first demonstration of alterations of cytoskeleton and ubiquitination in the giant cells of Betz, an established subset of upper motor neurons in ALS. Thus, although uncommon, cytoskeletal changes can be found in upper motor neurons in some ALS cases.


Cloning and functional characterisation of the mouse P2X7 receptor.
We have isolated a 1785-bp complementary DNA (cDNA) encoding the murine P2X7 receptor subunit from NTW8 mouse microglial cells. The encoded protein has 80%, and 85% homology to the human and rat P2X7 subunits, respectively. Functional properties of the heterologously expressed murine P2X7 homomeric receptor broadly resembled those of the P2X7 receptor in the native cell line. However, marked phenotypic differences were observed between the mouse receptor, and the other P2X7 receptor orthologues isolated with respect to agonist and antagonist potencies, and the kinetics of formation of the large aqueous pore.


Publication Expansion of United States Pharmacopeial Conventions's Veterinary Standards and Clinical Information.
The United States Pharmacopeial Convention is actively involved in providing comprehensive information for compounded veterinary formulations and their clinical use. Several United States Pharmacopeia Expert Committees are working to develop information establishing the safety and efficacy of necessary formulations, drug substance monographs for each active pharmaceutical ingredient, and compounding formulation monographs for each dosage form required.