Two discrete cis elements control the Abaxial side-specific expression of the FILAMENTOUS FLOWER gene in Arabidopsis.
Our previous studies showed that a member of the YABBY gene family, FILAMENTOUS FLOWER (FIL), plays a role in specifying the abaxial side tissues in the development of lateral organs such as cotyledons, leaves, young flower buds, and flower organs. We examined the expression pattern of FIL and found a temporal change of expression domains in the developmental process of the floral meristem. We also examined the cis control regions by constructing a series of transgenic plants that carry green fluorescent protein under the control of the FIL promoter with several types of deletions, base changes, and tandem repeats and showed that the unique expression pattern is dependent on at least two cis-acting elements in the 5' regulatory region. One element proximal to the FIL gene would be responsible for the expression of both the abaxial and adaxial sides, and the other element of the 12-bp sequence would work to repress expression on the adaxial side.


Metabolic trade-offs between biomass synthesis and photosynthate export at different light intensities in a genome-scale metabolic model of rice.
Previously we have used a genome scale model of rice metabolism to describe how metabolism reconfigures at different light intensities in an expanding leaf of rice. Although this established that the metabolism of the leaf was adequately represented, in the model, the scenario was not that of the typical function of the leaf-to provide material for the rest of the plant. Here we extend our analysis to explore the transition to a source leaf as export of photosynthate increases at the expense of making leaf biomass precursors, again as a function of light intensity. In particular we investigate whether, when the leaf is making a smaller range of compounds for export to the phloem, the same changes occur in the interactions between mitochondrial and chloroplast metabolism as seen in biomass synthesis for growth when light intensity increases. Our results show that the same changes occur qualitatively, though there are slight quantitative differences reflecting differences in the energy and redox requirements for the different metabolic outputs.


Turnaround Times in Melanoma BRAF Testing and the Impact on the Initiation of Systemic Therapy at a Single Tertiary Care Cancer Center.
The identification of BRAF mutations in melanoma enables targeted therapy and improves patient outcomes. Barriers to BRAF molecular testing affect the quality of care and therapeutic options. This retrospective study mapped BRAF testing timelines in adult patients with melanoma at the Princess Margaret Cancer Centre to identify obstacles to timely BRAF reporting and its impact on the initiation of therapy. Sixty-six cases were included. The median time between BRAF request and result was 12 days (95% CI, 8 to 15) when the BRAF test was ordered by pathology, compared with 20 days (95% CI, 16 to 23) if the test was requested by another specialist (P < .001). When the BRAF test and biopsy were performed within the same institution, the BRAF median turnaround time (TAT) was 13 days (95% CI, 6 to 19) compared with 19 days (95% CI, 16 to 21) if the sample was transferred from another institution (P = .02). Forty-seven patients received systemic therapy, and 20 had metastatic disease. In the metastatic subgroup, if the BRAF result was available at the first medical oncology visit, the initiation of treatment was 20 days (95% CI, 9.6 to 30.3), but was delayed to 31 days (95% CI, 10.8 to 51.1) if the BRAF result was not available (P = .03). This study showed variations in BRAF test results in TAT. One factor affecting this timeline is the transfer time, which can be streamlined by pathology reflex testing. Delays in TAT affect the timing and type of therapeutic intervention, especially in patients with stage IV disease.


Effects of Plant-Derived Polyphenols on the Antioxidant Activity and Aroma of Sulfur-Dioxide-Free Red Wine.
Significant efforts have been made in recent years to produce healthier wines, with the primary goal of reducing the use of sulfur dioxide (SO2), which poses health risks. This study aimed to assess the effectiveness of three plant-derived polyphenols (dihydromyricetin, resveratrol, and catechins) as alternatives to SO2 in wine. After a three-month aging process, the wines were evaluated using analytical techniques such as high-performance liquid chromatography, colorimetry, gas chromatography-olfactometry-mass spectrometry, as well as electronic nose and electronic tongue analyses, with the purpose to assess parameters including antioxidant activity, color, contents of volatile aroma compounds, and sensory characteristics. The results demonstrated various degrees of improvement in the antioxidant activity, aromatic intensity, and sensory characteristics of wines using polyphenols. Notably, dihydromyricetin (200 mg/L) exhibited the strongest antioxidant activity, with increases of 18.84%, 23.28%, and 20.87% in 2,2-diphenyl-1-picrylhydrazyl, 2,2'azino-bis(3-ethylbenzothiazoline-6-sulfonic acid), and ferric-ion-reducing antioxidant power assays, respectively. Resveratrol (200 mg/L) made the most significant contribution to volatile aroma compounds, with an 8.89% increase in the total content of alcohol esters. In E-nose analysis, catechins (200 mg/L) showed the highest response to aromatic compounds and the lowest response to volatile sulfur compounds, while also exhibiting the best sensory characteristics. Therefore, the three plant-derived polyphenols investigated here exhibited the potential to enhance wine quality as alternatives to SO2. However, it is important to consider the specific impact of different polyphenols on wine; hence, suitable antioxidants should be selected in wine production according to specific requirements.


Effect of slicing and storage temperatures on biochemical aspects of membrane integrity in two different genotypes of tomato.
Fresh-cut vegetables are subjected to multiple stressing agents including: (i) slicing, which induces cellular decompartmentalization; (ii) low refrigeration temperatures, responsible for chilling injury in the most sensitive products (e.g. tomatoes), and (iii) storage time because tissue senescence and aging can occur and reduce the shelf-life. In tomato slices, one of the most important issues is the membrane, which is responsible for several disorders related to the alteration of physiological processes, including ethylene biosynthesis. Electrolyte leakage and the content of thiobarbituric acid reactive substances in sliced tomatoes increased over time at two storage temperatures (4 °C and 15 °C) compared with intact fruit for the commercial variety (cultivar) Jama used as reference. However, in the tomato Italian landrace Canestrino, electrolyte leakage in sliced fruits increased after 120 h of storage compared to intact tomatoes, while the thiobarbituric acid reactive substance content increased rapidly over time at both storage temperatures. In the packages, higher ethylene content and carbon dioxide concentrations were detected in sliced tomatoes compared with intact fruits for both genotypes. In the most sensitive genotype for slicing (Jama), phospholipase C activity increased in tomato slices after 24 h of storage, but phospholipase D reached a higher value only at 168 h after processing at 4 °C of storage. The results evidence that the main damage in slices of full ripe tomatoes is more related to cutting, rather than chilling injury due to storage temperatures, with differences related to the genotype. Slicing enhanced membrane catabolism, ethylene production, and enzyme activity of phospholipases with a significant genotype effect. © 2021 Society of Chemical Industry.


Efficient orbital structures segmentation with prior anatomical knowledge.
We present a fully automatic method for segmenting orbital structures (globes, optic nerves, and extraocular muscles) in CT images. Prior anatomical knowledge, such as shape, intensity, and spatial relationships of organs and landmarks, were utilized to define a volume of interest (VOI) that contains the desired structures. Then, VOI was used for fast localization and successful segmentation of each structure using predefined rules. Testing our method with 30 publicly available datasets, the average Dice similarity coefficient for right and left sides of [0.81, 0.79] eye globes, [0.72, 0.79] optic nerves, and [0.73, 0.76] extraocular muscles were achieved. The proposed method is accurate, efficient, does not require training data, and its intuitive pipeline allows the user to modify or extend to other structures.


cDNA cloning and functional analysis of minipig uridine diphosphate-glucuronosyltransferase 1A1.
Uridine diphosphate (UDP)-glucuronosyltransferase 1A1 (UGT1A1) plays important roles in the glucuronidation of various drugs and endogenous substances. Minipigs have been used as experimental animals in pharmacological and toxicological studies, because many of their physiological characteristics are similar to those of humans. In this study, the similarities and differences in enzymatic properties of UGT1A1 between humans and minipigs were precisely identified. Minipig UGT1A1 (mpUGT1A1) cDNA was firstly cloned by the rapid amplification of cDNA ends (RACE) method, and the corresponding protein as well as human UGT1A1 (hUGT1A1) enzyme was expressed in insect cells. Then the kinetics of estradiol at 3-hydroxy position (E-3OH) and 7-ethyl-10-hydroxycamptothecin (SN-38) glucuronidation by recombinant UGT1A1s as well as human and minipig liver microsomes were analyzed. The homology between mpUGT1A1 and hUGT1A1 at the amino acid level was 80.9%. E-3OH and SN-38 glucuronidation by recombinant hUGT1A1 and mpUGT1A1 showed allosteric sigmoidal kinetics. The CL value (29.1 µL/min/mg protein) for E-3OH glucuronidation of mpUGT1A1 was significantly higher (1.4-fold) than that of hUGT1A1, whereas the CL value (0.83 µL/min/mg protein) for SN-38 glucuronidation was significantly lower (27%) than that of hUGT1A1; however, the kinetic models and parameter levels for E-3OH and SN-38 glucuronidation by human and minipig liver microsomes did not parallel those in the respective species. These findings suggest that the enzymatic properties of UGT1A1 are considerably different between humans and minipigs. The information on species differences in UGT1A1 function gained in this study should help with in vivo extrapolation of xenobiotic metabolism and toxicity.


Oxygen-dependent fragmentation of cellular DNA by nitric oxide.
Although active oxygen species and related metabolites, such as nitric oxide (NO), have been postulated to play important roles in the apoptosis of various cells, a precise mechanism leading to cell death remains to be elucidated. Recently we found that the lifetime of NO depends greatly on the concentration of environmental oxygen and that NO reversibly inhibits mitochondrial respiration and ATP synthesis; the inhibitory effect is stronger at physiologically low oxygen tension than under atmospheric conditions (Arch. Biochem. Biophys. 323, 27-32, 1995). The present work describes the effects of the NO-generating agent, 1-hydroxy-2-oxo-3,3-bis(2-aminoethyl)-1-triazene (NOC 18) and oxygen tension on the respiration, ATP synthesis and apoptosis of HL-60 cells. When respiration was inhibited by NOC 18, cellular ATP levels decreased significantly and DNA fragmentation was elicited. Both events were enhanced by decreasing oxygen tension and suppressed by adding NO-trapping agents, such as 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (carboxy-PTIO) and oxyhemoglobin. The fragmentation of cellular DNA was inhibited in a dose dependent manner by herbimycin A, a tyrosine kinase inhibitor. Fragmentation of the DNA of HL-60 cells was also induced either by peroxynitrite, superoxide or hydroxyl radical by some mechanism which was diminished by lowering the oxygen tension. These results indicated that the decrease in cellular ATP and activation of tyrosine kinase might play important roles in NO-induced apoptosis particularly under physiologically low oxygen tensions.


Physiologic anisocoria under various lighting conditions.
To evaluate the measurement of anisocoria in a group of ocular healthy subjects using a standardized protocol in scotopic, mesopic, and photopic lighting conditions, and determine the optimal threshold of difference in pupil diameter in determining physiologic anisocoria. Right and left pupil diameters of 126 ocular healthy subjects with a mean age 30.5±7.8 years (40 males and 86 females) were measured sequentially under photopic conditions using a monocular infrared pupillometer. A sub-group of 51 individuals had right and left pupil measurements performed under three additional lighting conditions, allowing for a 2-minute recovery between measurements. A white light emitting diode (LED) in the eyecup of the pupillometer produced three controlled light settings: scotopic (0 lux), low mesopic (0.3 lux), and high mesopic (3 lux). The criterion for anisocoria was defined as ≥0.4 mm difference in pupil diameter between the eyes. In the 126 subjects tested, 23.8% (n=30) exhibited anisocoria in photopic conditions. In the sub-group measured under three additional light settings, 43.1% (n=22) exhibited anisocoria in scotopic conditions, 43.1% (n=22) in low mesopic conditions, and 47.1% (n=24) in high mesopic conditions. Approximately 73% of subjects exhibited anisocoria in at least one light setting, while only approximately 8% had anisocoria in every light setting. When the criterion for anisocoria was shifted to ≥0.2 mm or ≥0.6 mm, the prevalence of anisocoria shifted significantly. Using a higher cutoff of ≥0.6 mm effectively reduced the number of healthy individuals who exhibit anisocoria in every light setting to almost zero. Based on our data, anisocoria is more prevalent under varied lighting conditions. To ensure the anisocoria is due to physiologic reasons, one should ensure that it is present under all lighting conditions to avoid excessive false positives.


Biological properties of hyaluronan in aqueous solution are controlled and sequestered by reversible tertiary structures, defined by NMR spectroscopy.
Hyaluronan (HA) is a ubiquitous polysaccharide of (predominantly) animal origin that has important medical applications in joint, skin, and eye conditions. Biological activities shown by HA fragments in angiogenesis, inflammation, etc. are absent from highly polymerized HA. We propose that HA physiological properties are controlled by molecular mass dependent transitions between tertiary structures (e.g., beta sheets) and 2-fold helices, - reversible "denaturation", which is central to HA solution behavior. We demonstrate this phenomenon by 13C NMR. Four different acetamido C=O resonances, assigned to secondary, tertiary, and disordered HA structures, monitored "denaturation" by (a) warming, (b) alkalinizing to pH >12.0, (c) hyaluronidase digestion, and (d) methylation of carboxylates. (a) and (b) acted reversibly but (c) and (d) are irreversible. 1H NMR implicated H-bonded acetamido NH in (b). Temperature dependencies of other 13C chemical shifts were small and unspecific. Arrhenius plots indicate that hyaluronan tertiary structures are on the edge of instability under physiological conditions. The results help to explain the appearance of biological activities on "denaturation" or degradation of HA.


Development of tissue paper-based chemosensor and demonstration for the selective detection of Cu2+ and Hg2+ ions.
Heavy metals emanate from natural and man-made sources, such as agricultural chemicals including fertilisers and pesticides, medical waste, and chemicals released from industries. Detection and monitoring toxic metal ions is one of the challenges confronting scientists in biological, environmental, and chemical systems. This study describes the design and synthesis of a new imidazole-based fluorescent and colourimetric chemosensor (DPICDT) for highly selective sensing of Hg2+ and Cu2+ ions in aqueous acetonitrile medium. The probe was synthesised by coupling benzil and substituted aldehyde using ethanolic ammonium acetate. The structure of DPICDT was confirmed via IR spectra, NMR, and HR-MS spectra. The DPICDT probe displayed a rapid naked-eye response towards Cu2+ ions from colourless to red-purple and significant fluorescence quenching response towards Hg2+ over other competitive metal ions in both solution and solid support. The binding modes of DPICDT with Cu2+ and Hg2+ ions were found to be at a 1 : 1 ratio as determined using Job plot, ESI HR-MS, and the sensing mechanism was evolved by 1H NMR titrations, HR-MS spectra, and DFT calculations. The lower detection limit was 15.1 nM for Cu2+, eventually far less than the World Health Organization guideline for drinking water (Cu2+ - 31.5 μM) and 1.17 μM for Hg2+ (permissible concentration 2 ppb). Promisingly, the tissue paper-based DPICDT test strips and silica-supported DPICDT were developed and demonstrated for on-site application without resorting to expensive instruments.


Implant-prosthetic treatment in HIV-infected patients receiving highly active antiretroviral therapy: report of cases.
Since 1997, the use of highly active antiretroviral therapy (HAART) has significantly improved systemic health and life expectancy of patients who test positive for the human immunodeficiency virus (HIV) in industrialized countries. Therefore, although implant-supported prosthetic rehabilitation has been restricted to immunocompetent individuals, it may be considered for these patients. The treatment course of implant-prosthetic rehabilitation in 3 patients is reported. Patient 1 (male, age 64 years) was under 4-drug therapy; patient 2 (male, age 38 years) and patient 3 (female, age 49 years) were under 3-drug therapy. Two patients had suffered from AIDS-defining diseases prior to HAART. Oral manifestations of HIV infection were not diagnosed throughout the observation period. Patients had CD4+ cell counts between 250 and 800/mL, and viral load was below 50/mL. Perioperative antibiotic treatment was not applied. Two patients presented with edentulous mandibles. In the third patient, single-tooth replacement of both mandibular first molars was performed. A total of 10 Frialit-2 implants were placed without augmentation procedures. One implant failed after 3 months and was successfully replaced. Two patients received magnet-retained overdentures in the mandible, and 1 patient was treated with single crowns. All implants and restorations are successfully in function. Neither radiographic nor clinical signs of inflammation were detected during the observation period (range, 7 to 32 months). The outcomes of the 3 patients suggest that immunologically stable HIV-positive patients on HAART may be considered for implant-prosthetic rehabilitation.


Multiple epidermal cysts in lowe syndrome.
Lowe syndrome is a rare genetic disease that appears to cause various clinical symptoms involving the eye, nervous system, and kidney. While a mutation of the OCRL1 gene is known to be responsible for this syndrome, the exact pathophysiology remains unclear. Various multi-organ symptoms are characteristic of Lowe syndrome, but skin lesions have rarely been described. Recently, mechanisms for the association of Lowe syndrome and skin lesions have been proposed. We report this case of Lowe syndrome involving multiple epidermal cysts on the scalp in a 6-year-old male child.


Thoraco-abdominal ectopia cordis in southwest Cameroon.
Ectopia cordis is a rare congenital defect where the heart is completely displaced outside the chest wall. Cantrell's pentalogy is an embryologic anomaly with five classic midline deficiencies often associated with ectopia cordis. Here we present a case of thoraco-abdominal ectopia cordis, brief literature review, and possible implications for changes in antenatal care.


Androgen treatment of depressive symptoms in older men: a systematic review of feasibility and effectiveness.
To determine the feasibility and effectiveness of androgen treatment of depressive symptoms in older men. We searched MEDLINE, PsycINFO, Eric, HealthStar, and the Cochrane Database of Systematic Reviews for potentially relevant articles. The bibliographies of relevant articles were searched for additional references and experts were consulted. Seventeen reports (8 open and 12 randomized trials; 3 articles reported studies of 2 designs) met the following inclusion criteria: original investigation; published in English or French, use of acknowledged criteria or scale for depression, and open or randomized trial of androgen treatment. Four criteria assessed study validity: randomization, double blinding, comparability of treatment and control groups at baseline, and description of dropouts. We abstracted, tabulated, and compared information from each article. Most studies had methodological limitations. With regard to feasibility, there were few reported withdrawals due to adverse events. With regard to effectiveness, 6 of 8 open trials had positive results, and 5 of 12 randomized trials had positive results, although 1 was equivocal. However, testosterone was combined with antidepressant medication in 3 of these positive randomized trials. Only 2 open trials enrolled subjects whose mean age was 60 years or over. One had positive results, and the other had negative results. Androgen therapy may be feasible in the short term, but there is little evidence that it is an effective treatment for depressive symptoms in older men.


Remarkable fluorescence enhancement of benzo[g]chromen-2-ones induced by hydrogen-bonding interactions with protic solvents.
A coumarin analogue, 8-methoxy-4-methyl-2H-benzo[g]chromen-2-one (MMBC), is almost non-fluorescent in non-polar media, whereas it exhibits dramatically enhanced fluorescence in polar protic solvents. This study investigates the mechanistic features of the significant solvent effects on the fluorescence properties of MMBC and a related compound, 4-methyl-2H-benzo[g]chromen-2-one (MBC), by time-resolved fluorescence and photoacoustic measurements and by theoretical calculations. Time-resolved photoacoustic measurements reveal that the extremely fast non-radiative processes of MBC and MMBC in non-polar solvents can be attributed predominantly to internal conversion. The internal conversion rates of MBC and MMBC are remarkably reduced in a rigid matrix of 3-methylpentane at 77 K, suggesting that internal conversion is a thermally activated process. The photophysical properties of MBC and MMBC examined in selected solvents with different polarities and hydrogen-bond donating abilities show that the internal conversion rate is greatly reduced by hydrogen-bonding interactions with protic solvents. Furthermore, remarkable fluorescence enhancement is observed by adding a small amount of trifluoroethanol to n-hexane solutions of MBC and MMBC, indicating that internal conversion is suppressed by formation of hydrogen-bonded complexes with protic solvents. In light of theoretical considerations based on time-dependent density functional theory (TD-DFT) and INDO/S-CI calculations, the occurrence of fast internal conversion in MBC and MMBC can be explained in terms of the proximity effect, i.e., pseudo Jahn-Teller coupling between energetically close S(1) and S(2) states.


Hierarchical Manipulation of Block Copolymer Patterns on 3D Topographic Substrates: Beyond Graphoepitaxy.
Templates of complex nanopatterns in a form of hierarchically sequenced dots and stripes can be generated in block copolymer films on lithography-free 3D topographic substrates. The approach exploits thickness- and swelling-responsive morphological behavior of block copolymers, and demonstrates novel possibilities of topography-guided registration of nanopatterns due to periodic confinement and spontaneous orthogonal flow-fields.


Diffraction gratings: a sign convention on order numbers for use in a computer program.
In ray tracing an optical system containing diffraction gratings on a computer, a sign convention on order numbers is necessary. The purpose of this paper is to present a method for easily determining the sign of an order number and to compare the results of this method with those of several commercially available computer programs.


Co-trimoxazole prophylaxis in adults, including pregnant women, with HIV: a systematic review and meta-analysis.
Co-trimoxazole prophylaxis is used to reduce morbidity and mortality in people with HIV. We systematically reviewed three topics related to co-trimoxazole prophylaxis to update WHO guidelines: initiation, discontinuation, and dose. We searched PubMed, Embase, WHO Global Index Medicus, and clinical trial registries in November, 2013, for randomised controlled trials and observational studies including co-trimoxazole prophylaxis and a comparator group. Studies were eligible if they reported death, WHO clinical stage 3 or 4 events, admittance to hospital, severe bacterial infections, tuberculosis, pneumonia, diarrhoea, malaria, or treatment-limiting adverse events. Infant mortality, low birthweight, and placental malaria were additional outcomes for the comparison of co-trimoxazole prophylaxis and intermittent preventive treatment for malaria in pregnant women (IPTp). We compared a dose of 480 mg co-trimoxazole once a day with one of 960 mg co-trimoxazole once a day. We used a 10% margin for non-inferiority and equivalence analyses. We used random-effects models for all meta-analyses. This study is registered with PROSPERO, number CRD42014007163. 19 articles, published from 1995 to 2014 and including 35 328 participants, met the inclusion criteria. Co-trimoxazole prophylaxis reduced rates of death (hazard ratio [HR] 0·40, 95% CI 0·26-0·64) when started at CD4 counts of 350 cells per μL or lower with antiretroviral therapy (ART) worldwide. Co-trimoxazole prophylaxis started at higher than 350 cells per μL without ART reduced rates of death (0·50, 0·30-0·83) and malaria (0·25, 0·10-0·57) in Africa. Co-trimoxazole prophylaxis was non-inferior to IPTp with respect to infant mortality (risk difference [RD] -0·05, 95% CI -0·12 to 0·02), low birthweight (0·00, -0·07 to 0·07), and placental malaria (0·00, -0·10 to 0·10). Co-trimoxazole prophylaxis continuation after ART-induced recovery with CD4 counts higher than 350 cells per μL reduced admittances to hospital (HR 0·42, 95% CI 0·22-0·80), pneumonia (0·73, 0·61-0·88), malaria (0·03, 0·01-0·10), and diarrhoea (0·61, 0·48-0·78) in Africa. A dose of 480 mg co-trimoxazole prophylaxis once a day did not reduce treatment-limiting adverse events compared with 960 mg once a day (RD -0·07, 95% CI -0·52 to 0·39). Co-trimoxazole prophylaxis should be given with ART in people with CD4 counts of 350 cells per μL or lower in low-income and middle-income countries. Co-trimoxazole prophylaxis should be provided irrespective of CD4 count in settings with a high burden of infectious diseases. Pregnant women with HIV in Africa should use co-trimoxazole rather than IPTp to prevent malaria complications in infants. Further research is needed to inform dose optimisation and co-trimoxazole use in the context of expanded ART in different epidemiological settings. None.


Interplay between metabolic reprogramming and post-translational modifications: from glycolysis to lactylation.
Cellular metabolism plays a critical role in determining the fate and function of cells. Metabolic reprogramming and its byproducts have a complex impact on cellular activities. In quiescent T cells, oxidative phosphorylation (OXPHOS) is the primary pathway for survival. However, upon antigen activation, T cells undergo rapid metabolic reprogramming, characterized by an elevation in both glycolysis and OXPHOS. While both pathways are induced, the balance predominantly shifts towards glycolysis, enabling T cells to rapidly proliferate and enhance their functionality, representing the most distinctive signature during activation. Metabolic processes generate various small molecules resulting from enzyme-catalyzed reactions, which also modulate protein function and exert regulatory control. Notably, recent studies have revealed the direct modification of histones, known as lactylation, by lactate derived from glycolysis. This lactylation process influences gene transcription and adds a novel variable to the regulation of gene expression. Protein lactylation has been identified as an essential mechanism by which lactate exerts its diverse functions, contributing to crucial biological processes such as uterine remodeling, tumor proliferation, neural system regulation, and metabolic regulation. This review focuses on the metabolic reprogramming of T cells, explores the interplay between lactate and the immune system, highlights the impact of lactylation on cellular function, and elucidates the intersection of metabolic reprogramming and epigenetics.


Unusual spiral wave tip trajectories in a parametrically forced nonequilibrium system.
The effect of parametric modulations on spiral waves that form in a thin layer of liquid crystal under rotating magnetic field is studied in laboratory experiments and numerical simulations. Parametric forcings that are sinusoidal in time make a simply rotating spiral tip to meander, rendering a compound tip trajectory that is composed of a main circular orbit and a satellite orbit with an unusual crescent shape. No evidence of frequency locking is found. The underlying mechanism for the unusual shape of the satellite orbit is elucidated, and the dependence of the rotation frequency of the main circular orbit f(o) on the perturbation parameters are discussed.


The enrichment of HBV immune-escape mutations during nucleoside/nucleotide analogue therapy.
Drug-resistant HBV mutants frequently arise during nucleoside/nucleotide analogue (NA) therapy, while the resistance mutations on polymerase also have consequent changes in the S protein. The enrichment of immune-escape mutations was negatively correlated with hepatitis B surface antigen (HBsAg) clearance under NA therapy. This study aims to characterize the variability of HBV polymerase and surface antigen in patients with virological breakthrough under NA therapy. From 2012 to 2014, serum samples were collected from 156 patients with chronic hepatitis B infection, who had experienced NA therapy for at least 24 weeks and displayed virological breakthrough, while 165 HBV carriers without NA treatment were also enrolled. HBV DNA was quantified and polymerase reverse transcriptase domain was amplified and sequenced. A total of 97 patients in the NA treatment group had resistance mutations, with rtM204I/V/S being the most common substitution (78 of 97), while no resistance mutations were detected in the treatment-naive group. Various escape mutations were detected, and the detection rate was significantly higher in the NA treatment group (38, 24.4%) than that of treatment-naive group (18, 10.9%; P<0.05). Except for the combination of sP120T+sA128V, other double combinations (n=11) were only detected in the NA treatment group, and nine of these combinations in the treatment group were detected in HBV variants without antiviral resistance mutations. Antiviral resistance mutations were selected by a long duration of NA therapy. Virological breakthrough was not only attributed to the emergence of resistance mutations, but may also be associated with the enrichment of immune-escape mutations.


Anti-inflammatory activity of inhaled IL-4 receptor-alpha antisense oligonucleotide in mice.
The Th2 cytokines IL-4 and IL-13 mediate allergic pulmonary inflammation and airways hyperreactivity (AHR) in asthma models through signaling dependent upon the IL-4 receptor-alpha chain (IL-4Ralpha). IL-13 has been further implicated in the overproduction of mucus by the airway epithelium and in lung remodeling that commonly accompanies chronic inflammation. IL-4Ralpha-deficient mice are resistant to allergen-induced asthma, highlighting the therapeutic promise of selective molecular inhibitors of IL-4Ralpha. We designed a chemically modified IL-4Ralpha antisense oligonucleotide (IL-4Ralpha ASO) that specifically inhibits IL-4Ralpha protein expression in lung eosinophils, macrophages, dendritic cells, and airway epithelium after inhalation in allergen-challenged mice. Inhalation of IL-4Ralpha ASO attenuated allergen-induced AHR, suppressed airway eosinophilia and neutrophilia, and inhibited production of airway Th2 cytokines and chemokines in previously allergen-primed and -challenged mice. Histologic analysis of lungs from these animals demonstrated reduced goblet cell metaplasia and mucus staining that correlated with inhibition of Muc5AC gene expression in lung tissue. Therapeutic administration of inhaled IL-4Ralpha ASO in chronically allergen-challenged mice produced a spectrum of anti-inflammatory activity similar to that of systemically administered Dexamethasone with the added benefit of reduced airway neutrophilia. These data support the potential utility of a dual IL-4 and IL-13 oligonucleotide inhibitor in allergy/asthma, and suggest that local inhibition of IL-4Ralpha in the lung is sufficient to suppress allergen-induced pulmonary inflammation and AHR.


Catalytic scaffolding ligands: an efficient strategy for directing reactions.
The design and application of a scaffolding ligand that promotes branch and diastereoselective hydroformylation of terminal olefins as well as the regio- and diastereoselective hydroformylation of disubstituted olefins is reported. It is shown that the ligand covalently and reversibly bonds to the substrate, allowing for directed hydroformylation. As the substrate ligand interaction is dynamic, hydroformylations are catalytic in ligand and do not require any additional synthetic steps to add or remove the directing group. Using a catalytic quantity of a scaffolding ligand (20-25 mol %), excellent regioselectivity for disubstituted olefins (up to 98:2) and high branch selectivity (up to 88:12) for terminal olefins were obtained.


Minimal systemic and high faecal exposure to cadazolid in patients with severe Clostridium difficile infection.
Cadazolid is under development as an oral treatment for Clostridium difficile infection (CDI), which is the most common infectious cause of antibiotic-associated diarrhoea. Low systemic cadazolid exposures were previously reported in healthy subjects following both single and multiple oral dosing. The main objective of this study was to investigate systemic cadazolid exposure in patients with severe CDI with potential disrupted lining of the gastrointestinal tract. A single 3000 mg oral dose of cadazolid was administered to six patients with microbiologically-confirmed severe CDI. Plasma and faeces were collected up to 144 h post-dose for determination of cadazolid concentrations. Safety assessments were conducted over the 144-h investigational period. Cadazolid was well tolerated in patients with severe CDI, with no reported drug-related adverse events. Cadazolid systemic exposure following a single 3000 mg oral dose was very low, with a peak plasma concentration (C(max)) of 2.64 ng/mL and an area under the concentration-time curve (AUC(0-144)) of 125 ng×h/mL. The median peak daily faecal cadazolid concentration was 5675 times the C. difficile MIC(90) of 0.25 mg/L. In subjects with severe CDI, cadazolid systemic exposure was very low following a single high oral dose. Cadazolid plasma concentrations were similar in magnitude to those previously reported for healthy subjects, whereas total systemic exposure was ca. 5-6 times higher, but was still low. Peak daily faecal cadazolid concentrations were 5675 times the 0.25 mg/L C. difficile MIC(90), and on Day 4 five of the six patients presented a daily faecal cadazolid concentration ≥1651 times the MIC(90) [ClinicalTrial.gov ID: NCT02053181].


[Recent trend of nonaqueous enzymology and biocatalysis in nonaqueous media].
With the rapid development of industrial biotechnology, breakthrough in enzymology and biocatalysis has been made in recent years, especially in areas of stability and activity of enzyme in nonaqueous media, screening, construction and modification of solvent-tolerant biocatalysts, as well as the development of green solvent with excellent biological and environmental compatibility. Recent trend and future focus include: in silico virtual screening and construction of solvent-tolerant biocatalysts based on bioinformatic technology, modification and construction of native solvent-tolerant biocatalysts, the development of environmental friendly green solvent such as ionic liquids.


Re-engineering and evaluation of anti-DNA autoantibody 3E10 for therapeutic applications.
A key challenge in the development of novel chemotherapeutics is the design of molecules capable of selective toxicity to cancer cells. Antibodies have greater target specificity compared to small molecule drugs, but most are unable to penetrate cells, and predominantly target extracellular antigens. A nuclear-penetrating anti-DNA autoantibody isolated from the MRL/lpr lupus mouse model, 3E10, preferentially localizes to tumors, inhibits DNA repair, and selectively kills cancer cells with defects in DNA repair. A murine divalent single chain variable fragment of 3E10 with mutations for improved DNA binding affinity, 3E10 (D31N) di-scFv, has previously been produced in P. pastoris and yielded promising pre-clinical findings, but is unsuitable for clinical testing. The present study reports the design, expression and testing of a panel of humanized 3E10 (D31N) di-scFvs, some of which contain CDR substitution. These variants were expressed in a modified CHO system and evaluated for their physicochemical attributes and ability to penetrate nuclei to selectively cause DNA damage accumulation in and kill cancer cells with DNA repair defects. Secondary structure was conserved and most variants retained the key characteristics of the murine 3E10 (D31N) di-scFv produced in P. pastoris. Moreover, several variants with CDR substitutions outperformed the murine prototype. In conclusion, we have designed several humanized variants of 3E10 (D31N) di-scFv that have potential for application as monotherapy or conjugates for targeted nuclear drug delivery.


[Intraoperative use of an open mid-field MR scanner in the surgical treatment of cerebral gliomas].
The aim of the present study was to evaluate the effectiveness of intraoperative MRI guidance in achieving more gross-total resection in case of primary brain tumors. We studied 12 patients with low-grade glioma and 19 patients with high-grade glioma who underwent surgery within a vertically open 0.5 T MR system. After initial imaging, the resection was stopped at the point in which the neurosurgeon considered the resection complete by viewing the operation field. At this time, intraoperative MRI was repeated ("first control") to identify any residual tumor. Areas of tumor-suspected tissue were localized and resected, with the exception of tissue adjacent to eloquent areas. Final imaging was carried out before closing the craniotomy. Comparison of "first control" and final imaging revealed a decrease of residual tumor volume from 32% to 4.3% in low-grade gliomas, and from 29% to 10% in high-grade gliomas. Intraoperative MRI allows a clear optimization of microsurgical resection of both low-grade and high-grade gliomas.


Chemotherapy-induced palmar-plantar erythrodysesthesia syndrome--recall following different chemotherapy agents.
Radiation recall is a phenomenon commonly seen in patients receiving chemotherapy treatment who have previously been exposed to radiation. A phenomenon not clearly described is that of a side effect induced by one chemotherapy agent and later recalled when the patient is given a different chemotherapy regimen. Troxacitabine is an anti-leukemic agent which can be associated with palmar-plantar erythrodysesthesia syndrome (PPES). Here, we report six cases of troxacitabine-induced PPES that was later recalled by various chemotherapy regimens. The recall PPES was mild to moderate and self-limiting in all cases. All of these patients recovered from the recall side effects with minimal medical intervention. We conclude that a recall phenomenon similar to that described after radiotherapy might occur after certain chemotherapy agents. This phenomenon should be considered when evaluating toxicity from chemotherapy, particularly when using new and investigational agents.


[Expression of high mobility group protein-B1 in mice with hyperoxia-induced bronchopulmonary dysplasia].
To study the effect of hyperoxia exposure on high mobility group protein-B1 (HMGB1) expression in neonatal mice and the role of HMGB1 in the pathogenesis of bronchopulmonary dysplasia (BPD). C57BL/6 mice were randomly exposed to 60% O2 or air 1 day after birth. BPD was induced by 60% O2 exposure. The pulmonary tissue samples were harvested 3, 7 and 14 days after exposure. The pathologic changes of pulmonary tissues were observed by hematoxylin and eosin staining, Masson staining and radical alveolar count. The expression of HMGB1 protein in lungs was detected by immunofluorescence. The expression of HMGB1 mRNA was detected by real-time fluorescent quantitative PCR. In the BPD group, the lungs developed decreased alceolar septation, swollen alveolar epithelium, stroma edema, interstitial fibrosis and developmental lag when compared with the control group. These changes became more obvious with more prolonged hyperoxia exposure. The expression of HMGB1 protein and mRNA 7 and 14 days after exposure increased significantly in the BPD group compared with that in the control group. Hyperoxia exposure results in an increase in lung HMGB1 expression. The increased HMGB1 expression may be associated with the development of BPD.


Characterization of a conserved interaction between DNA glycosylase and ParA in Mycobacterium smegmatis and M. tuberculosis.
The chromosome partitioning proteins, ParAB, ensure accurate segregation of genetic materials into daughter cells and most bacterial species contain their homologs. However, little is known about the regulation of ParAB proteins. In this study, we found that 3-methyladenine DNA glycosylase I MsTAG(Ms5082) regulates bacterial growth and cell morphology by directly interacting with MsParA (Ms6939) and inhibiting its ATPase activity in Mycobacterium smegmatis. Using bacterial two-hybrid and pull-down techniques in combination with co-immunoprecipitation assays, we show that MsTAG physically interacts with MsParA both in vitro and in vivo. Expression of MsTAG under conditions of DNA damage induction exhibited similar inhibition of growth as the deletion of the parA gene in M. smegmatis. Further, the effect of MsTAG on mycobacterial growth was found to be independent of its DNA glycosylase activity, and to result instead from direct inhibition of the ATPase activity of MsParA. Co-expression of these two proteins could counteract the growth defect phenotypes observed in strains overexpressing MsTAG alone in response to DNA damage induction. Based on protein co-expression and fluorescent co-localization assays, MsParA and MsTAG were further found to co-localize in mycobacterial cells. In addition, the interaction between the DNA glycosylase and ParA, and the regulation of ParA by the glycosylase were conserved in M. tuberculosis and M. smegmatis. Our findings provide important new insights into the regulatory mechanism of cell growth and division in mycobacteria.


Utility of transcranial sonography in the diagnosis of drug-induced parkinsonism: a prospective study.
Drug-induced parkinsonism usually resolves after discontinuation of the causative agent. However, it persists in some patients, who actually have subclinical neurodegenerative parkinsonism. Identification of this condition is important because these patients could benefit from therapeutic measures. The objective of this study was to prove whether transcranial sonography, a technique used in the diagnosis of neurodegenerative parkinsonism, can be used for the said identification. In this prospective study, patients with drug-induced parkinsonism were followed for at least 6 months after discontinuation of the causative drug and performance of blinded transcranial sonography. Patients were categorized as having iatrogenic parkinsonism if the clinical presentation had resolved or subclinical drug-exacerbated parkinsonism if it persisted. Once the patient was classified into one of the two groups, an expert assessed the transcranial sonography findings and their agreement with the clinical diagnosis. Twenty patients composed the group for analysis of results. Assessing hyperechogenicity in the substantia nigra >20 mm2 and/or hyperechogenic lentiform nucleus, differences were detected between the iatrogenic parkinsonism and the subclinical drug-exacerbated parkinsonism groups, although they did not reach statistical significance (Fisher's exact test 0.09). Joint assessment of sonographic alterations in both structures had a negative predictive value of 85.7% for diagnosis of drug-induced parkinsonism, with a negative likelihood ratio of 0.3. Although in our study statistically significant differences were not found between the transcranial sonography characteristics of subclinical drug-exacerbated parkinsonism and iatrogenic parkinsonism patients, we believe that transcranial sonography is a valid technique for diagnosis of drug-induced parkinsonism.


Influence of oxygen, albumin and pH on copper dissolution in a simulated uterine fluid.
The aim of this paper is to study the influence of albumin content, from 5 to 45 g/L, on copper dissolution and compounds composition in a simulated uterine solution. Experiments were performed in atmospheric pressure conditions and with an additional oxygen pressure of 0.2 atmospheres, at 6.3 and 8.0 pH values, and at a temperature of 37 +/- 0.1 degrees C for 1, 3, 7, and 30 days experimentation time. The copper dissolution rate has been determined using absorbance measurements, finding the highest value for pH 8.0, 35 g/L albumin, and with an additional oxygen pressure of 0.2 atmospheres: 674 microg/day for 1 day, and 301 microg/day for 30 days. X-ray photoelectron spectroscopy (XPS) results show copper(II) as the main copper oxidation state at pH 8.0; and copper(I) and metallic copper at pH 6.3. The presence of albumin up to 35 g/L, accelerates copper dissolution. For high albumin content a stabilisation on the copper dissolution takes place. Corrosion product layer morphology is poorly protective, showing paths through which copper ions can release.


Protective effects of BMSCs in combination with erythropoietin in bronchopulmonary dysplasia-induced lung injury.
Bronchopulmonary dysplasia (BPD) is the most common type of chronic lung disease in infancy, for which no effective therapy is currently available. The aim of the present study was to investigate the effect of treatment with bone marrow mesenchymal stem cells (BMSCs) in combination with recombinant human erythropoietin (rHuEPO) on BPD‑induced mouse lung injury, and discuss the underlying mechanism. The BPD model was established by the exposure of neonatal mice to continuous high oxygen exposure for 14 days, following which 1x106 BMSCs and 5,000 U/kg rHuEPO were injected into the mice 1 h prior to and 7 days following exposure to hyperoxia. The animals received four treatments in total (n=10 in each group). After 14 days, the body weights, airway structure, and levels of matrix metalloproteinase‑9 (MMP‑9) and vascular endothelial growth factor (VEGF) were detected using histological and immunohistochemical analyses. The effect on cell differentiation was observed by examining the presence of platelet endothelial cell adhesion molecule (PECAM) and VEGF using immunofluorescence. Compared with the administration of BMSCs alone, the body weight, airway structure, and the levels of MMP‑9 and VEGF were significantly improved in the BMSCs/rHuEPO group. The results of the present study demonstrated that the intravenous injection of BMSCs significantly improved lung damage in the hyperoxia‑exposed neonatal mouse model. Furthermore, the injection of BMSCs in combination with intraperitoneal injection of rHuEPO had a more marked effect, compared with BMSCs alone, and the mechanism may be mediated by the promoting effects of BMSCs and EPO. The results of the present study provided information, which may assist in future clinical trials.


[Cellular defense system of some synanthropic dipterans inhabitant of bacterially aggressive environment].
The hemocytic count and defense reaction within 4 families of higher Diptera: Tabanidae, Syrphidae, Muscidae and Sarcophagidae, whose larvae inhabit bacterially aggressive environment, were investigated. The least hemocytes types (3) were revealed in Tabanidae and Syrphidae larvae--prohemocytes, plasmatocytes and prophenoloxydase-containing unstable hyaline cells (oenocytoids). In Sarcophaga crassipalpis and Musca domestica stable hyaline cells and thrombocytoids or podocytoid-like cells can be added to this set. At the time of pupariation in Sarcophaga, new generation of prohemocytes is segregated into the hemolymph, which form small round or spindle-shaped hyaline cells. So, the number of plasmatocyte types in Sarcophaga increase to six. Typical to Calliphoridae juvenile plasmatocytes in the members of investigated families are absent. Among the one hemocyte type morphology also can vary, especially in unstable prophenoloxydase hyaline cells. In Drosophila there are crystal cells containing in the cytoplasm paracrystalloidal inclusions. In Calliphoridae there are big hyaline cells with homogenous cytoplasm producing circumferential bubbles. Both in Sarcophaga and Tabanidae they contain in their cytoplasm big globules. However in Sarcophaga they rapidly disintegrate, while in Tabanidae are maintained unchanged during hours. In Muscidae and Syrphidae prophenoloxydase extrusion occurs very early and these cells obtain pycnotic nuclei and very liquid cytoplasm with strings of granules. Thrombocytoids in Musca larvae are represented by big flattened anucleated irregular cytoplasm and "naked" nuclei and cytoplasmic fragments often with fan-like projections. Plasmatocytes in all species studied are the cells with pronounced phylopodies. In larvae they contain cytoplasmic catabolic inclusions and in pupa--ragments of apoptotic tissues. Clearance of hemolymph from alien particles in Sarcophagidae and Muscidae occur by thrombocytoides, while in Tabanidae by plasmatocyte nodulation. A differing case is Syrphidae whe-e charcoal injection produce depletion of hemolymph both from particles and all types of hemocytes. So the specimen of different higher Diptera families can use different schemes of cellular defense reaction.


Combined genetic and chemical screens indicate protective potential for EGFR inhibition to cardiomyocytes under hypoxia.
The return of blood flow to ischemic heart after myocardial infarction causes ischemia-reperfusion injury. There is a clinical need for novel therapeutic targets to treat myocardial ischemia-reperfusion injury. Here we screened for targets for the treatment of ischemia-reperfusion injury using a combination of shRNA and drug library analyses in HL-1 mouse cardiomyocytes subjected to hypoxia and reoxygenation. The shRNA library included lentiviral constructs targeting 4625 genes and the drug library 689 chemical compounds approved by the Food and Drug Administration (FDA). Data were analyzed using protein-protein interaction and pathway analyses. EGFR inhibition was identified as a cardioprotective mechanism in both approaches. Inhibition of EGFR kinase activity with gefitinib improved cardiomyocyte viability in vitro. In addition, gefitinib preserved cardiac contractility in zebrafish embryos exposed to hypoxia-reoxygenation in vivo. These findings indicate that the EGFR inhibitor gefitinib is a potential candidate for further studies of repurposing the drug for the treatment of myocardial infarction.


Robust spectral clustering using statistical sub-graph affinity model.
Spectral clustering methods have been shown to be effective for image segmentation. Unfortunately, the presence of image noise as well as textural characteristics can have a significant negative effect on the segmentation performance. To accommodate for image noise and textural characteristics, this study introduces the concept of sub-graph affinity, where each node in the primary graph is modeled as a sub-graph characterizing the neighborhood surrounding the node. The statistical sub-graph affinity matrix is then constructed based on the statistical relationships between sub-graphs of connected nodes in the primary graph, thus counteracting the uncertainty associated with the image noise and textural characteristics by utilizing more information than traditional spectral clustering methods. Experiments using both synthetic and natural images under various levels of noise contamination demonstrate that the proposed approach can achieve improved segmentation performance when compared to existing spectral clustering methods.


Viscoelasticity Investigation of Semiconductor NP (CdS and PbS) Controlled Biomimetic Nanoparticle Hydrogels.
The viscoelastic properties of colloidal nanoparticles (NPs) make opportunities to construct novel compounds in many different fields. The interparticle forces of inorganic particles on colloidal NPs are important for forming a mechanically stable particulate network especially the NP-based soft matter in the self-assembly process. Here, by capping with the same surface ligand L-glutathione (GSH), two semiconductor NP (CdS and PbS) controlled biomimetic nanoparticle hydrogels were obtained, namely, CdS@GSH and PbS@GSH. The dependence of viscoelasticity of colloidal suspensions on NP sizes, concentrations, and pH value has been investigated. The results show that viscoelastic properties of CdS@GSH are stronger than those of PbS@GSH because of stronger surface bonding ability of inorganic particles and GSH. The hydrogels formed by the smaller NPs demonstrate the higher stiffness due to the drastic change of GSH configurations. Unlike the CdS@GSH hydrogel system, the changes of NP concentrations and pH value had great influence on the PbS@GSH hydrogel system. The higher the proportion of water in the small particle size PbS@GSH hydrogel system, the greater the mechanical properties. The stronger the alkalinity in the large particle size PbS@GSH hydrogel system, the greater the hardness and storage modulus. Solution-state nuclear magnetic resonance (NMR) indicated that the ligand GSH forms surface layers with different thickness varying from different coordination modes which are induced by different semiconductor NPs. Moreover, increasing the pH value of the PbS@GSH hydrogel system will dissociate the surface GSH molecules to form Pb2+ and GSH complexes which could enhance the viscoelastic properties.


Some nematodes of fishes from central China, with the redescription of Procamallanus (Spirocamallanus)fulvidraconis (Camallanidae).
The present paper comprises a systematic survey of nematodes based on helminthological examinations of 176 specimens of freshwater fishes, belonging to 22 species, from central China (mostly lakes in Hubei Province) collected during the autumn of 2001. The following six species were recorded: Procamallanus (Spirocamallanus)fulvidraconis Li, 1935, Camallanus cotti Fujita, 1927, Dentiphilometra monopteri Moravec et Wang, 2002, Pingus sinensis Hsü, 1933, Proleptinae gen. sp. larv., and Eustrongylides sp. larv. Data on their morphology, morphological variability, host range, prevalence, intensity and distribution are provided. SEM studies of P. fulvidraconis and larval Physalopterinae, used for the first time in these species, revealed some additional morphological details and made it possible to redescribe the former. In contrast to the existing description of P. fulvidraconis, this species was found to possess two spicules and a V-shaped gubernaculum with unequal arms (originally mistaken for the left spicule), as well as deirids, whose location can be considered an important taxonomic feature. Larvae of the Physalopterinae have not previously been reported from fishes in China. The finding of larval Eustrongylides in Paramisgurnus dabryanus represents a new host record. All but one nematode species from this zoogeographically interesting region are briefly described and illustrated.


Metachronous Bilateral Acinic Cell Carcinoma of the Parotid Gland in a Young Woman.
Bilateral involvement of major salivary glands by carcinoma of an identical histologic subtype is uncommon. In this study, a 26-year old female patient was diagnosed to have a low-grade acinic cell carcinoma (ACC) in the left parotid gland. After superficial parotidectomy, she was referred to the oncological dispensary care without further oncological therapeutic intervention. During 11 years of follow-up, she had no evidence of locoregional recurrence or metastasis. However, at the age of 37, she was recognized to have another tumor mass in the contralateral parotid gland. Right superficial parotidectomy was done, and histology confirmed an ACC showing the same picture as it was found previously. A year after the operation, no sign of tumor relapse was seen. Although metachronous bilateral ACC of the parotid gland is very rare, it is occasionally encountered in medical practice. Such an event may occur many years after a diagnosis of the initial tumor. Every patient once treated for parotid ACC warrants periodical clinical examinations and long-term follow-up (more than 10 years), even with attention to the contralateral non-affected parotid gland.


Tailoring Solution-Processable Li Argyrodites Li6+xP1-xMxS5I (M = Ge, Sn) and Their Microstructural Evolution Revealed by Cryo-TEM for All-Solid-State Batteries.
Owing to their high Li+ conductivities, mechanical sinterability, and solution processability, sulfide Li argyrodites have attracted much attention as enablers in the development of high-performance all-solid-state batteries with practicability. However, solution-processable Li argyrodites have been developed only for a composition of Li6PS5X (X = Cl, Br, I) with insufficiently high Li+ conductivities (∼10-4 S cm-1). Herein, we report the highest Li+ conductivity of 0.54 mS cm-1 at 30 °C (Li6.5P0.5Ge0.5S5I) for solution-processable iodine-based Li argyrodites. A comparative investigation of three iodine-based argyrodites of unsubstituted and Ge- and Sn-substituted solution-processed Li6PS5I with varied heat-treatment temperature elucidates the effect of microstructural evolution on Li+ conductivity. Notably, local nanostructures consisting of argyrodite nanocrystallites in solution-processed Li6.5P0.5Ge0.5S5I have been directly captured by cryogenic transmission electron microscopy, which is a first for sulfide solid electrolyte materials. Specifically, the promising electrochemical performances of all-solid-state batteries at 30 °C employing LiCoO2 electrodes tailored by the infiltration of Li6.5P0.5Ge0.5S5I-ethanol solutions are successfully demonstrated.


A study on the physical fitness of children with juvenile rheumatoid arthritis.
[Purpose] This study was conducted to assess the physical fitness of children with juvenile rheumatoid arthritis (JRA). [Subjects and Methods] In total, 26 children with juvenile rheumatoid arthritis (JRA) and 25 healthy controls participated in this study. Using the physical fitness measurement instruments, the Inbody 720 and Quark b2, the elements of physical fitness that were assessed included muscular strength, muscular endurance, flexibility, lung capacity, and body composition. [Results] The results revealed significant differences in muscular strength, muscular endurance, lung capacity, body composition, functional ability, and health-related quality of life between the children with juvenile rheumatoid arthritis (JRA) and the control group. [Conclusion] These results suggested that children with juvenile rheumatoid arthritis (JRA) have inferior physical fitness when compared to healthy children. The present study was conducted to develop an accurate evaluation standard to assess the physical fitness of children with juvenile rheumatoid arthritis (JRA).


Spillover Effects in Health Service Use: Evidence From Mental Health Care Using First-Year College Housing Assignments.
Spillover effects in health service use may represent an important externality of individual treatment decisions and are important for understanding the consequences of interventions to improve access to health care. This study is the first to our knowledge to examine causal spillover effects for mental health service use. We exploit the natural experiment of first-year student housing assignments at two universities using survey data that we collected. When the peer group is defined at the roommate level, we do not find any spillover effects on service use. When the peer group is defined at the hall level, we find positive spillover effects--peers' service use increases one's own service use--and this effect is driven by individuals with prior experience with mental health services. We also find some evidence that the mechanism behind this effect is improved beliefs about treatment effectiveness.


Uremic Toxins - Novel Arrhythmogenic Factor in Chronic Kidney Disease - Related Atrial Fibrillation.
Atrial fibrillation (AF) is the most common cardiac arrhythmia. Chronic kidney disease (CKD) is associated with a high prevalence of AF, and uremic toxins are an important risk factor for cardiovascular diseases associated with CKD. Uremic toxins can produce pro-fibrotic, pro-hypertrophic, and pro-inflammatory effects on cardiac tissues and enhance oxidative stress or neurohormonal phenomena of cardiovascular injury, which are recognized as arrhythmogenic factors of AF. This article reviews the clinical, molecular, and electrophysiological data of uremic toxins in CKD considered to induce AF through multiple mechanisms on structural and electrical remodeling of the cardiovascular system.


Male infertility and donor insemination: couples' decisions, reactions and counselling needs.
This paper reports findings of a postal survey of 205 couples belonging to the National Association for the Childless, whose infertility had been attributed to the male partner. Spontaneous resolution was seldom reported, but 36 couples had become parents by donor insemination (DI) and 28 through adoption. Almost a third of respondents had managed to resolve their childlessness. Although reasons for rejecting DI or preferring other options were offered by 60 couples, 125 had taken active steps towards it. Most of the 80 couples who had been counselled had found this helpful. Regardless of counselling, of the 76 couples who had considered whether or not to tell their children of their mode of conception, 56 (74%) stated that they had no intention of doing so. Quantitative indices from two self-report scales confirm that male infertility is commonly a source of distress, especially for the female partner. However, the data also suggest that this is not necessarily associated with chronic marital discord. Couples who had already decided for or against DI reported less distress than others. The need for mutual support may well be enhanced until the couple's quest for a child has been either achieved or abandoned.


Significant Association of Interleukin-16 Genetic Variations to Taiwanese Lung Cancer.
Interleukin-16 has been reported to exhibit tumoricidal effects, however, the contribution of IL-16 genotypes to lung cancer is still largely unrevealed. This study aimed at investigating whether IL-16 genotypes contribute to lung cancer susceptibility. IL-16 rs4778889, rs11556218, and rs4072111 genotypic characteristics were determined among 358 lung cancer patients and 716 controls via the polymerase chain reaction-based restriction fragment length polymorphism (PCR-RFLP) methodology. The highlight finding is that the distributions of genotypic (p=8.6E-10) and allelic (p=0.0001) frequencies of IL-16 rs11556218 was significantly different between cases and controls. In detail, the frequencies of IL-16 rs11556218 heterozygous variant TG and homozygous variant GG were 36.6 and 7.3% among the lung cancer patients, significantly higher than those among the controls (22.5% and 2.6%). On the other way, no difference was observed regarding IL-16 rs4778889 or IL-16 rs4072111. The present study indicates IL-16 rs11556218 G allele is significantly associated with increased Taiwan lung cancer risk.


Effect of viloxazine on serum carbamazepine levels in epileptic patients.
The present study describes the interaction between carbamazepine (CBZ) and viloxazine, a recently synthesized antidepressant agent. Seven epileptic patients on chronic anticonvulsant therapy showed a significant (p less than 0.005) increase in steady-state serum CBZ levels (from 8.1 +/- 2.5 SD to 12.1 +/- 2.5 SD micrograms/ml) when viloxazine (300 mg/day) was added to the therapy. The effect was associated with the appearance of mild CBZ intoxication. The symptoms of this intoxication (i.e., dizziness, ataxia, fatigue, drowsiness) disappeared rapidly, and serum CBZ levels decreased to the basal values, when viloxazine administration was stopped.


Guava (Psidium guajava) leaf extract enhances immunity, growth, and resistance against Vibrio parahaemolyticus in white shrimp Penaeus vannamei.
This study investigated the effects of guava leaf extract (GLE) on immune responses, growth performance, and resistance to Vibrio parahaemolyticus in white shrimp (Penaeus vannamei). To examine the effect of GLE on the immune response of white shrimps, they were treated with various concentrations of GLE on hemocyte (in vitro) and were orally administered (in vivo) feed containing various concentrations of 0, 1, 5, and 10 g kg-1 GLE (control, GLE1, GLE5, and GLE10, respectively) for 28 days. Furthermore, their growth performance was evaluated for 56 days. In a separate experiment, the shrimps were challenged with V. parahaemolyticus injection after 7 days of culture. In vitro experiments indicated that GLE is nontoxic and can activate immune response. In vivo experiments revealed that the GLE5 led to the highest total hemocyte count, phenoloxidase activity, phagocytic activity, and superoxide anion production and the highest upregulation of lipopolysaccharide, β-1,3-glucan-binding protein, peroxinectin, lysozyme, crustin, penaeidin 2, penaeidin 3, clotting protein, superoxide dismutase, and glutathione peroxidase. Moreover, better growth performance was observed in the GLE groups, with GLE5 exhibiting the highest specific growth rate, weight gain, and feed conversion rate. In addition, GLE5 enhanced resistance to V. parahaemolyticus, with a survival rate of 72.27%. In conclusion, GLE was found to be effective in enhancing nonspecific immune response and growth performance and in reducing V. parahaemolyticus infection in white shrimp.


Oxidation of alpha 1-protease inhibitor: role of lipid peroxidation products.
Previously we demonstrated that in vivo exposure of humans to NO2 resulted in significant inactivation of alpha 1-protease inhibitor (alpha 1-PI) in the bronchoalveolar lavage fluid. However, alpha 1-PI retains its elastase inhibitory activity in vitro when exposed to 10 times the concentration of NO2 used in vivo. We suggested exogenous oxidants such as O2 and NO2 exert their effect in vivo in part through lipid peroxidation. We investigated the mechanism of inactivation of alpha 1-PI in the presence or absence of lipids under oxidant atmosphere. alpha 1-PI in solutions containing phosphate buffer (control), 0.1 mM stearic acid (saturated fatty acid, 18:0), or 0.1 mM linoleic acid (polyunsaturated fatty acid, 18:2) was exposed to either N2 or NO2 (50 ppm for 4 h). Elastase inhibitory capacity of alpha 1-PI was significantly diminished in the presence of 0.1 mM linoleic acid and under NO2 atmosphere (75 +/- 8% of control, P less than 0.01), whereas there was no change in elastase inhibitory capacity of alpha 1-PI in the presence or absence (buffer only) of 0.1 mM stearic acid under a similar condition (109 +/- 11 and 94 +/- 6%, respectively). The inactivated alpha 1-PI as the result of peroxidized lipid could be reactivated by dithiothreitol and methionine sulfoxide peptide reductase, suggesting oxidation of methionine residue at the elastase inhibitory site. Furthermore the inhibitory effect of peroxidized lipid on alpha 1-PI could be prevented by glutathione and glutathione peroxidase and to some extent by alpha-tocopherol.


(+/-)-3-Allyl-6-bromo-7,8-dihydroxy-1-phenyl-2,3,4,5-tetrahydro-1H-3- benzazepin, a new high-affinity D1 dopamine receptor ligand: synthesis and structure-activity relationship.
The 7,8-dihydroxy-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepines form a series of compounds having a high affinity at the D1 dopamine receptor. The 6-chloro derivative has been previously shown to have enhanced affinity, selectivity, and agonist activity. In an attempt to study the effect of substitution of a 6-bromo group in place of the 6-chloro, we have synthesized a series of compounds and evaluated them for their affinity for the D1 receptor. The results show that the 6-bromo derivatives have virtually identical affinities to their 6-chloro counterparts, a finding similar to that found in the D1 antagonist 7-halo-8-hydroxy-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine series. From the present work, 3-allyl-6-bromo-7,8-dihydroxy-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepi ne (6-Br-APB) has been identified as a suitable candidate for further in vivo studies and resolution into its active and inactive enantiomers.


An update on gastrointestinal endoscopy-associated infections and their contributing factors.
During clinical use, gastrointestinal endoscopes are grossly contaminated with patient's native flora. These endoscopes undergo reprocessing to prevent infectious transmission upon future use. Endoscopy-associated infections and outbreaks have been reported, with a recent focus on the transmission of multi-drug resistant organisms. This review aims to provide an update on endoscopy-associated infections, and the factors contributing to their occurrence. PubMed, ScienceDirect, and CINAHL were searched for articles describing gastrointestinal endoscopy-associated infections and outbreaks published from 2008 to 2018. Factors contributing to their occurrence, and the outcomes of each outbreak were also examined. This review found 18 articles, 16 of which described duodenoscope-associated infections, and the remaining two described colonoscope- and gastroscope-associated infection respectively. Outbreaks were reported from the United States, France, China, Germany, the Netherlands and the United Kingdom. The causative organisms reported were Klebsiella pneumoniae, Pseudomonas aeruginosa, Escherichia coli and Salmonella enteritidis. A number of factors, including lapses in reprocessing, biofilm formation, endoscope design issues and endoscope damage, contribute to gastrointestinal endoscopy associated infection. Methods of improving endoscope reprocessing, screening for contamination and evaluating endoscope damage may be vital to preventing future infections and outbreaks.


Apoptosis of peritoneal leucocytes during early stages of Fasciola hepatica infections in sheep.
Several immunomodulatory properties have been described in Fasciola hepatica infections. Apoptosis has been shown to be an effective mechanism to avoid the immune response in helminth infections. The aim of the present work was to study apoptosis in peritoneal leucocytes of sheep experimentally infected with F. hepatica during the early stages of infection. Five groups (n=5) of sheep were used. Groups 2-5 were orally infected with 200 metacercariae (mc) and sacrificed at 1, 3, 9 and 18days post-infection (dpi), respectively. Group 1 was used as the uninfected control (UC). Apoptosis was detected using three different methods 1) immunocytochemistry (ICC) with a polyclonal antibody anti-active caspase-3; 2) an annexin V flow cytometry assay using the Annexin V-FITC/propidium iodide (PI); and 3) transmission electron microscopy (TEM). The differential leucocyte count revealed that the majority of peritoneal granulocytes were eosinophils, which increased significantly at 9 and 18 dpi with respect to the uninfected controls. The ICC study revealed that the percentage of caspase-3+ apoptotic peritoneal leucocytes increased significantly from 3 dpi onwards with respect to the uninfected controls. The flow cytometry annexin V assay detected a very significant (P<0.001) increase of apoptotic peritoneal macrophages, lymphocytes and granulocytes, which remained higher than in the UC until 18 dpi. Transmission electron microscopy studies also confirmed the presence of apoptosis in peritoneal eosinophils at 18 dpi. This is the first report of apoptosis induced by F. hepatica in the peritoneal leucocytes of sheep in vivo. The results of this work suggest the importance of apoptosis induction for the survival of the juvenile parasites in the peritoneal migratory stages of infection.


[Conformation limited nucleoside-5'-phosphates as termination substrates for DNA-polymerases].
We have investigated the ability of some nucleoside 5'-triphosphate analogues to terminate the DNA synthesis catalyzed by calf thymus DNA polymerase alpha and terminal deoxynucleotidyl transferase, rat liver DNA polymerase beta, E. coli DNA polymerase I (Klenow's fragment) and AMV reverse transcriptase. It has been shown that lyxoanhydronucleoside 5'-triphosphates terminate DNA synthesis catalyzed by reverse transcriptase and terminal deoxynucleotydil transferase. 2',3'-O-Isopropylidenecytidine 5'-triphosphate inhibits the DNA synthesis catalyzed by reverse transcriptase and DNA polymerase beta and its moiety was incorporated in the place of dTMP residue. Riboanhydroadenosine 5'-triphosphate reveals the properties of an effective termination substrate for all the DNA polymerases studied. This is the first attempt to investigate nucleotide analogues with the restricted conformation of the carbohydrate moiety as termination substrates for several prokaryotic and eukaryotic DNA polymerases.


Enabling ITK-based processing and 3D Slicer MRML scene management in ParaView.
This paper documents on-going work to facilitate ITK-based processing and 3D Slicer scene management in ParaView. We believe this will broaden the use of ParaView for high performance computing and visualization in the medical imaging research community. The effort is focused on developing ParaView plug-ins for managing VTK structures from 3D Slicer MRML scenes and encapsulating ITK filters for deployment in ParaView. In this paper, we present KWScene, an open source cross-platform library that is being developed to support implementation of these types of plugins. We describe the overall design of the library and provide implementation details and conclude by presenting a concrete example that demonstrates the use of the KWScene library in computational anatomy research at Johns Hopkins Center for Imaging Science.


Delayed hemopericardium after penetrating chest trauma: thoracoscopic pericardial window as a therapeutic option.
A 41-year-old male developed a hemothorax after sustaining a stab wound in the right chest. The patient was managed conservatively with thoracostomy tube drainage for 3 days and was subsequently discharged home. Two weeks later the patient returned to the hospital with pleuritic chest pain and shortness of breath. Imaging studies revealed a right-sided pleural effusion and an enlarged cardiac silhouette, which was consistent with pericardial effusion as per ultrasonography. Thoracoscopic exploration revealed an enlarged heart, that following pericardiotomy drained 400 mL of frank blood. Subsequently, cardiac contractility improved, and no further bleeding was evident.


Plasma-mirror frequency-resolved optical gating using a liquid-sheet jet in ultraviolet region.
We demonstrate plasma-mirror frequency-resolved optical gating (PM-FROG) using a liquid-sheet jet of water and characterize a waveform of a high-repetition laser pulse (1 kHz) in the ultraviolet (UV) region. The measured PM-FROG trace is reconstructed by the least-squares generalized projections algorithm. The retrieved UV spectral phase is consistent with that by self-diffraction FROG. The complex reflection coefficient of a plasma mirror is discussed in terms of the free electron density dependence. The PM-FROG technique is applicable to not only the pulse characterization, but also the investigation of ionization dynamics of a liquid.


Nomenclatural changes in Ochlerini (Hemiptera: Heteroptera: Pentatomidae: Discocephalinae).
Several nomenclatural problems were found while studying the types of Ochlerini in the Natural History Museum, London. These problems are addressed and corrected: Hemingius Distant, 1899 syn. nov. is removed from the synonymy with Moncus Stål, 1867, and considered a new junior synonym of Ochlerus Spinola, 1837; Ochlerus scaber Walker, 1867 is removed from the synonymy with Ochlerus obscurus Dallas, 1851, and it is proposed as a senior synonym of Ochlerus cotylophorus Breddin, 1910 syn. nov. Herrichella Distant, 1911 is a senior synonym of Alitocoris Sailer, 1950 syn. nov., with the resulting new combinations: Herrichella grandis (Garbelotto Campos, 2013) comb. nov., Herrichella lateralis (Garbelotto Campos, 2013) comb. nov., Herrichella ornata (Garbelotto Campos, 2013) comb. nov., and Herrichella schraderi (Sailer, 1950) comb. nov. A key for the species of Herrichella is also given. Eritrachys antennata (Distant, 1911) comb. nov. is a senior synonym of Eritrachys bituberculata Ruckes, 1959 syn. nov. Phereclus punctatus (Dallas, 1851) is transferred to the genus Lincus Stål, 1867 as Lincus punctatus (Dallas, 1851) comb. nov.


Mobile computed tomography : three year clinical experience in Korea.
Obtaining real-time image is essential for neurosurgeons to minimize invasion of normal brain tissue and to prompt diagnosis of intracranial event. The aim of this study was to report our three-year experience with a mobile computed tomography (mCT) for intraoperative and bedside scanning. A total of 357 mCT (297 patients) scans from January 2009 to December 2011 in single institution were reviewed. After excluding post-operative routine follow-up, 202 mCT were included for analysis. Their medical records such as diagnosis, clinical application, impact on decision making, times, image quality and radiologic findings were assessed. Two-hundred-two mCT scans were performed in the operation room (n=192, 95%) or intensive care unit (ICU) (n=10, 5%). Regarding intraoperative images, extent of resection of tumor (n=55, 27.2%), degree of hematoma removal (n=42, 20.8%), confirmation of catheter placement (n=91, 45.0%) and monitoring unexpected complications (n=4, 2.0%) were evaluated. A total of 14 additional procedures were introduced after confirmation of residual tumor (n=7, 50%), hematoma (n=2, 14.3%), malpositioned catheter (n=3, 21.4%) and newly developed intracranial events (n=2, 14.3%). Every image was obtained within 15 minutes and image quality was sufficient for interpretation. mCT is feasible for prompt intraoperative and ICU monitoring with enhanced diagnostic certainty, safety and efficiency.


Hematological and clinical features of sickle cell diseases: a review.
The differentiation, hematologic features and clinical manifestations of patients with the various sickling disorders are reviewed. The deficiencies in our current knowledge about the spectrum of the clinical course of patients with these conditions is discussed. The interaction of alpha thalassemia with sickle cell anemia and its possible effect upon the severity of the disease is summarized. The apparent milder disease in certain groups of patients with sickle cell anemia in whom there is an associated elevation of hemoglobin F is contrasted with the controversy surrounding the effects of hemoglobin F levels in the patients of African origin.


Loss of the co-repressor GPS2 sensitizes macrophage activation upon metabolic stress induced by obesity and type 2 diabetes.
Humans with obesity differ in their susceptibility to developing insulin resistance and type 2 diabetes (T2D). This variation may relate to the extent of adipose tissue (AT) inflammation that develops as their obesity progresses. The state of macrophage activation has a central role in determining the degree of AT inflammation and thus its dysfunction, and these states are driven by epigenomic alterations linked to gene expression. The underlying mechanisms that regulate these alterations, however, are poorly defined. Here we demonstrate that a co-repressor complex containing G protein pathway suppressor 2 (GPS2) crucially controls the macrophage epigenome during activation by metabolic stress. The study of AT from humans with and without obesity revealed correlations between reduced GPS2 expression in macrophages, elevated systemic and AT inflammation, and diabetic status. The causality of this relationship was confirmed by using macrophage-specific Gps2-knockout (KO) mice, in which inappropriate co-repressor complex function caused enhancer activation, pro-inflammatory gene expression and hypersensitivity toward metabolic-stress signals. By contrast, transplantation of GPS2-overexpressing bone marrow into two mouse models of obesity (ob/ob and diet-induced obesity) reduced inflammation and improved insulin sensitivity. Thus, our data reveal a potentially reversible disease mechanism that links co-repressor-dependent epigenomic alterations in macrophages to AT inflammation and the development of T2D.


Hypertension due to a renin-secreting tumour localised by segmental renal vein sampling.
An 18-year-old female was found to be hypertensive on routine medical examination. Further investigation disclosed persistent hypokalaemia and elevated plasma renin activity in peripheral venous blood. Segmental renal vein sampling with assay of blood samples located the source of excess renin secretion in the lower mid-zone of the left kidney. This localization was not confirmed by either angiography or by palpation of the exposed kidney before nephrectomy but macroscopic examination of the freshly sectioned kidney revealed a small tumour in the region suggested by renal vein sampling. The tumour had the morphologic pattern fo an haemangiopericytoma with abundant ultrastructural specific granules and very high renin activity by tissue assay. Plasma renin activity fell precipitously after nephrectomy and remained very low for the first week. Although the immediate post-operative blood pressure fell to normal, hypertension recurred temporarily and was associated with elevated plasma aldosteron, producing a syndrome similar to primary aldosteronism. All variables returned to normal without specific therapy and hypertension has not subsequently recurred.


pH sensing characteristics and biosensing application of solution-gated reduced graphene oxide field-effect transistors.
Solution-gated reduced graphene oxide field-effect transistors (R-GO FETs) were investigated for pH sensing and biochemical sensing applications. A channel of a networked R-GO film formed by self-assembly was incorporated as a sensing layer into a solution-gated FET structure for pH sensing and the detection of acetylcholine (Ach), which is a neurotransmitter in the nerve system, through enzymatic reactions. The fabricated R-GO FET was sensitive to protons (H(+)) with a pH sensitivity of 29 mV/pH in terms of the shift of the charge neutrality point (CNP), which is attributed to changes in the surface potential caused by the interaction of protons with OH surface functional groups present on the R-GO surface. The R-GO FET immobilized with acetylcholinesterase (AchE) was used to detect Ach in the concentration range of 0.1-10mM by sensing protons generated during the enzymatic reactions. The results indicate that R-GO FETs provide the capability to detect protons, demonstrating their applicability as a biosensing device for enzymatic reactions.


Anticipating and managing opioid side effects in the elderly.
Pain is a common complaint in the elderly, and opioids are useful agents for management of both acute and chronic pain. Opioids are known to cause a variety of adverse effects, and these adverse effects can be particularly problematic for the frail elderly patient and may limit their use. As a result, this can lead to undertreatment of pain and poor patient outcome. Understanding, anticipating, and managing opioid side effects is an important component of care for the elderly patient.


Adapting Evaluations of Alternative Payment Models to a Changing Environment.
To identify the most robust methods for evaluating alternative payment models (APMs) in the emerging health care delivery system environment. We assess the impact of widespread testing of alternative payment models on the ability to find credible comparison groups. We consider the applicability of factorial research designs for assessing the effects of these models. The widespread adoption of alternative payment models could effectively eliminate the possibility of comparing APM results with a "pure" control or comparison group unaffected by other interventions. In this new environment, factorial experiments have distinct advantages over the single-model experimental or quasi-experimental designs that have been the mainstay of recent tests of Medicare payment and delivery models. The best prospects for producing definitive evidence of the effects of payment incentives for APMs include fractional factorial experiments that systematically vary requirements and payment provisions within a payment model.


Ethnic Diversity, Inter-group Attitudes and Countervailing Pathways of Positive and Negative Inter-group Contact: An Analysis Across Workplaces and Neighbourhoods.
This study advances the current literature investigating the relationship between contextual out-group exposure, inter-group attitudes and the role of inter-group contact. Firstly, it introduces the concept of contact-valence into this relationship; that is, whether contact is experienced positively or negatively. Secondly, it presents a comparative analysis of how processes of out-group exposure and frequency of (valenced) contact affect prejudice across both neighbourhoods and workplaces. Applying path analysis modelling to a nationally-representative sample of white British individuals in England, we demonstrate, across both contexts, that increasing out-group exposure is associated with higher rates of both positively- and negatively-valenced contact. This results in exposure exhibiting both positive and negative indirect associations with prejudice via more frequent inter-group mixing. These countervailing contact-pathways help explain how out-group exposure is associated with inter-group attitudes. In neighbourhoods, increasing numbers of individuals experiencing positive-contact suppress an otherwise negative effect of neighbourhood diversity (driven partly by increasing numbers of individuals reporting negative contact). Across workplaces the effect differs such that increasing numbers of individuals experiencing negative-contact suppress an otherwise positive effect of workplace diversity (driven largely by increasing numbers of individuals experiencing positive contact).


Provision of Prosthetic Services Following Lower Limb Amputation in Malaysia.
The incidence of lower limb amputation is high across the globe and continues to be a major threat to morbidity and mortality. Consequently, the provision of high quality and effective prosthetics services have been known as an essential component for a successful rehabilitation outcome. In Malaysia, amputation prevalence has been increasing in which several main components of service delivering aspects (such as service intervention, prosthetic personnel) should be anticipated to accommodate for the increasing demand. This article highlights the hurdles experienced in providing prosthetic services in Malaysia from multiple aspects such as financial burden to acquire the prosthesis and lack of expertise to produce quality prosthesis. This paramount issues consequently justify for the urgency to carry out national level survey on the current statistics of lower limb amputation and to ascertain the available workforce to provide a quality prosthetics services. Only with accurate and current information from the national survey, strategies and policies aimed at enhancing the outcome from prosthetics services can be achieved.


Overexpression of miR-202 resensitizes imatinib resistant chronic myeloid leukemia cells through targetting Hexokinase 2.
Chronic myeloid leukemia (CML) is a myeloproliferative disease which uniquely expresses a constitutively active tyrosine kinase, BCR/ABL. As a specific inhibitor of the BCR-ABL tyrosine kinase, imatinib becomes the first choice for the treatment of CML due to its high efficacy and low toxicity. However, the development of imatinib resistance limits the long-term treatment benefits of it in CML patients. In the present study, we aimed to investigate the roles of miR-202 in the regulation of imatinib sensitivity in CML cell lines and the possible mechanisms involved in this process. We found miR-202 was down-regulated in seven CML cell lines by quantitative reverse-transcription PCR (qRT-PCR) analysis. Overexpression of miR-202 significantly suppressed proliferation rates of CML cells. By establishing imatinib resistant cell lines originating from K562 and KU812 cells, we observed expressions of miR-202 were down-regulated by imatinib treatments and imatinib resistant CML cell lines exhibited lower level of miR-202 On the contrary, imatinib resistant CML cell lines displayed up-regulated glycolysis rate than sensitive cells with the evidence that glucose uptake, lactate production, and key glycolysis enzymes were elevated in imatinib resistant cells. Importantly, the imatinib resistant CML cell lines were more sensitive to glucose starvation and glycolysis inhibitors. In addition, we identified Hexokinase 2 (HK2) as a direct target of miR-202 in CML cell lines. Overexpression of miR-202 sensitized imatinib resistant CML through the miR-202-mediated glycolysis inhibition by targetting HK2. Finally, we provided the clinical relevance that miR-202 was down-regulated in CML patients and patients with lower miR-202 expression displayed higher HK2 expression. The present study will provide new aspects on the miRNA-modulated tyrosine kinase inhibitor (TKI) sensitivity in CML, contributing to the development of new therapeutic anticancer drugs.


Sequence studies of the Fd section of the heavy chain of rabbit immunoglobulin G.
A partial amino acid sequence was given by Cebra, Steiner & Porter (1968b) of the N-terminal half of the heavy chain of rabbit immunoglobulin G. This was extended and in part corrected to give a continuous sequence of 136 residues, which together with other work accounts for three-quarters of the total sequence. Evidence is given suggesting that there is a limited region of 10-15 residues that are exceptionally variable in the heavy chains from pooled rabbit immunoglobulin G.


Measurement of Sex and Gender Identity in the Behavioral Risk Factor Surveillance System Survey, 2014 to 2020.
Effective measurement of sex and gender identity is challenging. Questions measuring gender identity were added as an optional module of the Behavioral Risk Factor Surveillance System (BRFSS) in 2014 and were modified repeatedly in following years. This study examines BRFSS participant responses to gender identity and sex questions, 2014-2020. About 70% of participants who identified as transgender male-to-female reported male sex while 30% reported female sex. Participants who identified as transgender female-to-male reported female sex about 65% of the time and reported male sex 35% of the time. Despite changes in sex question wording, these percentages were consistent over time. Reported sex is used in computing health-related variables and in routing participants to questions about birth control, pregnancy, HPV vaccines, and cancer screenings. Without better measurement, it is challenging to assess health and health risks and inform guidelines, programs, and policies protecting the health of transgender people.


Development of an environmental high-voltage electron microscope for reaction science.
Environmental transmission electron microscopy and ultra-high resolution electron microscopic observation using aberration correctors have recently emerged as topics of great interest. The former method is an extension of the so-called in situ electron microscopy that has been performed since the 1970s. Current research in this area has been focusing on dynamic observation with atomic resolution under gaseous atmospheres and in liquids. Since 2007, Nagoya University has been developing a new 1-MV high voltage (scanning) transmission electron microscope that can be used to observe nanomaterials under conditions that include the presence of gases, liquids and illuminating lights, and it can be also used to perform mechanical operations to nanometre-sized areas as well as electron tomography and elemental analysis by electron energy loss spectroscopy. The new instrument has been used to image and analyse various types of samples including biological ones.


Atypical Presentation: Metastatic Uveal Melanoma in a Young Patient without Visual Complaints.
Uveal melanoma is a rare and aggressive subtype of melanoma, with singular characteristics that separate it from the most famous cutaneous melanoma. This uncommon condition becomes even rarer if we look at young population. Common chemotherapy regimens does not work with this aggressive disease in its metastatic scenario, and the new armament like targeted and immunotherapies are still looking for more robust evidence. We report a rare case of uveal melanoma in a patient younger than 20 years, with abdominal pain as his initial complaint. He did not present the typical visual symptoms of the primary site because of an auto accident suffered 4 months before the presentation, letting him blind of the eye affected by the tumor development. There is always a possibility of the diagnosis of uveal melanoma in cases with associated isolated hepatic metastases, even in a young population, where this hypothesis is often rejected by the epidemiological frequency of other tumors. This rare case is a useful example.


The development of the anaesthetic vaporizer. The contribution of A.G. Levy.
The innovatory features incorporated into A.G. Levy's regulating chloroform inhaler, and their contribution to modern vaporizer design, are examined. Levy may be credited with the important realisation that the gas mixture which leaves the vaporizing chamber is fully saturated at all flow rates; with the concept of the splitting ratio; with appreciation of the importance of the application of Reynolds' researches on laminar and turbulent flow to the design of anaesthetic apparatus; and with the provision of a facility to compensate for changes of temperature in the vaporizing chamber.


"Psychotherapy" versus "treatment".
Presents a comment on "Psychological treatments" by D. H. Barlow. Barlow proposed that we distinguish between the terms "treatment" and "psychotherapy." The author believes that not only is the distinction unnecessary, but that its implications could have negative consequences for the field of clinical psychology. It is the proposed distinguishing feature that treatments are "specifically tailored to the pathological process that is causing the impairment and distress" that is most problematic. Clinical psychology does not need a distinction that further exacerbates the split between researchers and practitioners.


Cr0.5Nb24.5O62 Nanowires with High Electronic Conductivity for High-Rate and Long-Life Lithium-Ion Storage.
Intercalation-type TiNbxO2+2.5x (x = 2, 5, and 24) anode materials have recently become more interesting for lithium-ion batteries (LIBs) due to their large theoretical capacities of 388-402 mAh g-1. However, the Ti4+/Nb5+ ions in TiNbxO2+2.5x with empty 3d/4d orbitals usually lead to extremely low electronic conductivity of <10-9 S cm-1, greatly restricting their practical capacity and rate capability. Herein, we report a class of highly conductive Cr0.5Nb24.5O62 nanowires as an intercalation-type anode material for high-performance LIBs. The as-made Cr0.5Nb24.5O62 nanowires show an open shear ReO3 crystal structure (C2 space group) with 4% tetrahedra and a conducting characteristic with ultrahigh electronic conductivity of 3.6 × 10-2 S cm-1 and a large Li+-ion diffusion coefficient of 2.19 × 10-13 cm2 s-1. These important characteristics make them deliver outstanding electrochemical properties in term of the largest reversible capacity (344 mAh g-1 at 0.1 C) in all the known niobium- and titanium-based anode materials, safe working potential (∼1.65 V vs Li/Li+), high first-cycle Coulombic efficiency (90.8%), superior rate capability (209 mAh g-1 at 30 C), and excellent cycling stability, making them among the best for LIBs in niobium- and titanium-based anode materials.