Microfluidic platform for three-dimensional cell culture under spatiotemporal heterogeneity of oxygen tension.
Cells in a tumor microenvironment are exposed to spatial and temporal variations in oxygen tension due to hyperproliferation and immature vascularization. Such spatiotemporal oxygen heterogeneity affects the behavior of cancer cells, leading to cancer growth and metastasis, and thus, it is essential to clarify the cellular responses of cancer cells to oxygen tension. Herein, we describe a new double-layer microfluidic device allowing the control of oxygen tension and the behavior of cancer cells under spatiotemporal oxygen heterogeneity. Two parallel gas channels were located above the media and gel channels to enhance gas exchange, and a gas-impermeable polycarbonate film was embedded in the device to prevent the diffusion of atmospheric oxygen. Variations in oxygen tension in the device with the experimental parameters and design variables were investigated computationally and validated by using oxygen-sensitive nanoparticles. The present device can generate a uniform hypoxic condition at oxygen levels down to 0.3% O2, as well as a linear oxygen gradient from 3% O2 to 17% O2 across the gel channel within 15 min. Moreover, human breast cancer cells suspended in type I collagen gel were introduced in the gel channel to observe their response under controlled oxygen tension. Hypoxic exposure activated the proliferation and motility of the cells, which showed a local maximum increase at 5% O2. Under the oxygen gradient condition, the increase in the cell number was relatively high in the central mild hypoxia region. These findings demonstrate the utility of the present device to study cellular responses in an oxygen-controlled microenvironment.


[Self-rated oral health among Brazilian adults and older adults in Southeast Brazil: results from the SB-Brasil Project, 2003].
The aim of this study was to determine which characteristics (predisposing and enabling, oral health, perceived need for dental treatment, and behavior) are independently associated with self-rated oral health among adults and older adults in Southeast Brazil. The study was based on 3,240 participants in the SB-Brasil Project/ Southeast. The characteristics of those who rated their oral health as good/very good were compared to those who rated it as fair, poor, or very poor. The following characteristics were significantly and independently associated with better self-rated oral health among adults: monthly household income > US 60.00 dollars, no current perceived need for dental treatment, place of residence in cities with > 50,000 inhabitants, and visit to the dentist > 3 years previously. Among older adults the factors were: monthly household income > US 60.00 dollars, no current perceived need for dental treatment, and 1-19 permanent teeth. Our results confirm those observed in other countries, showing associations between self-rated oral health and predisposing and enabling factors, oral health, perceived need for dental treatment, and behavior.


Sodium periodate-induced human suppressor cells for polyclonal B cell activation.
Sodium periodate (SP) induces proliferation of mature T cells. In this study, human peripheral blood mononuclear cells (MNC) pretreated for 10 minutes at room temperature with increasing concentrations (0.1 to 5 mM) of SP before culture for 7 days in the presence of pokeweed mitogen (PWM) exhibited a dose-dependent inhibition of IgG production, contrasting with an increase in 3H-thymidine uptake. When MNC from 70 normal individuals were pretreated with 1 and 2 mM SP, IgG production in culture was suppressed by 46.8 +/- 4.5% and 60.4 +/- 4.4% (mean +/- S.E.M.), respectively, as compared to IgG synthesis in the presence of PWM alone. Longitudinal studies of MNC obtained from the same normal individuals over 6-10 months showed similar degrees of suppression, indicating that the level of SP-inducible suppressor cell activity remains relatively constant, although the degree of suppression varies among normal persons. Both T cells and monocytes were required for PWM-driven IgG production and for SP-induced suppression. A soluble factor elaborated by SP-treated monocytes was also able to suppress IgG production. This model should provide useful information about abnormal regulation of IgG synthesis in various pathological conditions.


Perinatal mortality in rural China: retrospective cohort study.
To explore the use of local civil registration data to assess the perinatal mortality in a typical rural county in a less developed province in China, 1999-2000. Retrospective cohort study. Pregnancies in a cohort of women followed from registration of pregnancy to outcome of infant seven days after birth. Routine family planning records in 20 rural townships in eastern China. 3697 pregnancies registered by the local family planning system during 1999. Abortions, stillbirths, early neonatal mortality, perinatal mortality. Only three cases were lost to follow up. The average age of the women at pregnancy was 25.9 years. Three hundred and twelve pregnancies were aborted and 240 ended in miscarriage (total 552, 15%). The perinatal mortality rate was 69 per 1000 births, the rate of stillbirth was 24 per 1000 births, and the early neonatal mortality was 46 per 1000 live births. The early neonatal mortality was 29 in boys and 69 in girls per 1000 live births. The perinatal mortality rate increased notably with parity and was higher in townships having lower income per capita. The family planning system at the most local level is a useful data source for studying perinatal mortality in rural China. The perinatal mortality rate in the study county was higher than previously reported for both rural and urban areas in China. The results by parity and sex of the infant raise concern over the impact of the one child policy.


Cognitive Dysfunction in Huntington's Disease: Humans, Mouse Models and Molecular Mechanisms.
Huntington's disease (HD) is an autosomal dominant progressive neurodegenerative disorder due to an expanded CAG/polyglutamine repeat in the coding region of the huntingtin (htt) gene that causes the preferential degeneration of striatal neurons. Although HD is classically considered a motor disorder, cognitive decline manifests even before the appearance of motor symptoms, and reflects the impairment of additional neuronal populations, such as cortical and hippocampal neurons, in the presence of mutant htt (mhtt). Studies on cognitive dysfunction in HD patients have focused on the cortico-striatal pathway. Here we will describe that HD patients and mouse models share many cognitive defects. Alterations in hippocampal synaptic plasticity and function found in HD mouse models highlight that changes in the functioning of the hippocampal formation contribute to cognitive dysfunction in humans. The similarity between the cognitive dysfunction in HD patients and mouse models has helped to understand better how cognitive dysfunction takes place. Moreover, it validates the use of HD mice to study the molecular mechanisms involved in HD cognitive decline. Several studies in HD mouse models indicate that altered synaptic composition/function, deficient neurotrophic support, kinase/phosphatase imbalance, and transcription dysregulation play an important role in cognitive impairment. This knowledge opens the possibility of identifying relevant therapeutic targets to fight cognitive decline in HD. The finding that in HD many mechanisms are similarly altered in hippocampal and striatal neurons suggests the possibility of a common therapeutic strategy to ameliorate both cognitive and motor dysfunction.


3D-Printed glycerol microfluidic fuel cell.
A 3D-printed microfluidic fuel cell is presented. Fused deposition modeling is used to build a microchannel with a 0.015 cm2 cross-sectional area for stable colaminar flow conditions. A new 3D-Printed cell fed by glycerol displays a power density of 175 mW cm-2 at 0.9 V and 1.8 V of open-circuit voltage.


Gene flow between the Korean peninsula and its neighboring countries.
SNP markers provide the primary data for population structure analysis. In this study, we employed whole-genome autosomal SNPs as a marker set (54,836 SNP markers) and tested their possible effects on genetic ancestry using 320 subjects covering 24 regional groups including Northern (=16) and Southern (=3) Asians, Amerindians (=1), and four HapMap populations (YRI, CEU, JPT, and CHB). Additionally, we evaluated the effectiveness and robustness of 50K autosomal SNPs with various clustering methods, along with their dependencies on recombination hotspots (RH), linkage disequilibrium (LD), missing calls and regional specific markers. The RH- and LD-free multi-dimensional scaling (MDS) method showed a broad picture of human migration from Africa to North-East Asia on our genome map, supporting results from previous haploid DNA studies. Of the Asian groups, the East Asian group showed greater differentiation than the Northern and Southern Asian groups with respect to Fst statistics. By extension, the analysis of monomorphic markers implied that nine out of ten historical regions in South Korea, and Tokyo in Japan, showed signs of genetic drift caused by the later settlement of East Asia (South Korea, Japan and China), while Gyeongju in South East Korea showed signs of the earliest settlement in East Asia. In the genome map, the gene flow to the Korean Peninsula from its neighboring countries indicated that some genetic signals from Northern populations such as the Siberians and Mongolians still remain in the South East and West regions, while few signals remain from the early Southern lineages.


Enhancement of the differentiation-inducing properties of 6-thioguanine by hypoxanthine and its nucleosides in HL-60 promyelocytic leukemia cells.
Previous work has shown that 6-thioguanine (TGua) is an effective inducer of differentiation of Friend and HL-60 leukemia cells which lack hypoxanthine-guanine phosphoribosyltransferase but is at best only weakly active in inducing maturation in parental wild-type cells. Studies in wild-type and mutant HL-60 cells have provided evidence that the free-base TGua is the form of this drug that induces differentiation, while the formation of TGua nucleotides leads to cytotoxicity and inhibits differentiation. To attempt to increase the potential of TGua to serve as an inducer of parental HL-60 leukemia cells, physiological purine and pyrimidine nucleosides were tested for their ability to protect HL-60 cells against TGua-induced cytotoxicity. Adenosine, deoxyadenosine, inosine, and deoxyinosine completely prevented the toxic action of the purinethiol, while guanosine and deoxyguanosine were only partially effective. The capacity of adenosine and deoxyadenosine to prevent the cytotoxicity of TGua was abolished by the inhibitor of adenosine deaminase, deoxycoformycin, implying that inosine and deoxyinosine were the active forms of the protecting agents. The protective activities of inosine and deoxyinosine appeared to depend on phosphorolysis catalyzed by purine nucleoside phosphorylase, since exogenously added hypoxanthine was as effective as inosine in reducing the cytotoxicity of the purine antimetabolite. Accumulation of TGua nucleotides in the acid-soluble fraction of HL-60 cells treated with TGua was significantly decreased by the presence of inosine. Inosine also served under these circumstances as a D-ribose 1-phosphate donor to TGua, as evidenced by its increased conversion to 6-thioguanosine. The prevention of the cytotoxicity of TGua by the simultaneous administration of hypoxanthine or its nucleosides resulted in an expression of the differentiation-inducing properties of TGua in HL-60 cells, as measured by the accumulation of nitroblue tetrazolium-positive cells. These findings support the concept that the processes of cytotoxicity and differentiation are separable events produced by different metabolic forms of the purine antimetabolite.


Biological iron-sulfur storage in a thioferrate-protein nanoparticle.
Iron-sulfur clusters are ubiquitous in biology and function in electron transfer and catalysis. They are assembled from iron and cysteine sulfur on protein scaffolds. Iron is typically stored as iron oxyhydroxide, ferrihydrite, encapsulated in 12 nm shells of ferritin, which buffers cellular iron availability. Here we have characterized IssA, a protein that stores iron and sulfur as thioferrate, an inorganic anionic polymer previously unknown in biology. IssA forms nanoparticles reaching 300 nm in diameter and is the largest natural metalloprotein complex known. It is a member of a widely distributed protein family that includes nitrogenase maturation factors, NifB and NifX. IssA nanoparticles are visible by electron microscopy as electron-dense bodies in the cytoplasm. Purified nanoparticles appear to be generated from 20 nm units containing ∼6,400 Fe atoms and ∼170 IssA monomers. In support of roles in both iron-sulfur storage and cluster biosynthesis, IssA reconstitutes the [4Fe-4S] cluster in ferredoxin in vitro.


Elucidation of the Origin of Thixotropic-Inducing Properties of Additive Amphiphiles and the Creation of a High-Performance Triamide Amphiphile.
The spontaneous growth of helical fibers of amphiphilic diamide derivatives containing hydrocarbons with asymmetric carbon centers in their constituent hydrocarbons was investigated. 12-Hydroxystearic acid and a gemini-type surfactant obtained by the bimolecular condensation of this compound with hexamethylenediamine both impart thixotropic ability to a solvent. Although this thixotropic behavior is based on the growth of hierarchical crystalline nanofibers in the solvents, the degree of fiber growth itself was not the origin of the thixotropy. In this study, it has adopted the methods of the Langmuir monolayer and Langmuir-Blodgett films as technique to selectively and individually evaluate the behavior of 12-hydroxyl stearyl and/or stearyl chains themselves. The ability to impart thixotropy to the solvent via fiber organization was related to the intermolecular hydrogen bonding between the added amphiphiles. Additionally, homogeneous right-handed helical fibers were formed in the spin-cast films of the diamide derivatives, and a positive Cotton effect was observed in their circular dichroism spectra. It is suggested that fibers that do not form helical arrangements cannot impart sufficient thixotropy to the solvent even when extensive fiber growth is achieved, and the structure-dependent development of chirality is the driving force. In addition, to further the development of highly functional thixotropic agents, a trefoil-like triamide derivative containing three chains was synthesized. By using this molecule, solvent gelation occurred at 78% as an addition to the diamide case, and a supramolecular assembly was formed in the corresponding two-dimensional film.


Multi-Regional Adaptation in Human Auditory Association Cortex.
In auditory cortex, neural responses decrease with stimulus repetition, known as adaptation. Adaptation is thought to facilitate detection of novel sounds and improve perception in noisy environments. Although it is well established that adaptation occurs in primary auditory cortex, it is not known whether adaptation also occurs in higher auditory areas involved in processing complex sounds, such as speech. Resolving this issue is important for understanding the neural bases of adaptation and to avoid potential post-operative deficits after temporal lobe surgery for treatment of focal epilepsy. Intracranial electrocorticographic recordings were acquired simultaneously from electrodes implanted in primary and association auditory areas of the right (non-dominant) temporal lobe in a patient with complex partial seizures originating from the inferior parietal lobe. Simple and complex sounds were presented in a passive oddball paradigm. We measured changes in single-trial high-gamma power (70-150 Hz) and in regional and inter-regional network-level activity indexed by cross-frequency coupling. Repetitive tones elicited the greatest adaptation and corresponding increases in cross-frequency coupling in primary auditory cortex. Conversely, auditory association cortex showed stronger adaptation for complex sounds, including speech. This first report of multi-regional adaptation in human auditory cortex highlights the role of the non-dominant temporal lobe in suppressing neural responses to repetitive background sounds (noise). These results underscore the clinical utility of functional mapping to avoid potential post-operative deficits including increased listening difficulties in noisy, real-world environments.


[Current state of problem of improving tools for plague vaccine prophylaxis].
Literature data on main immunobiological characteristics of 1st generation plague vaccines as well as ways of development of new tools for specific prophylaxis of plague: recombinant live, chemical, antiidiotypic, and DNA vaccines are presented in the review. Their expected advantages and disadvantages, perspectives of development and practical use in system of antiepidemic measures are assessed.


High NPM1 mutant allele burden at diagnosis correlates with minimal residual disease at first remission in de novo acute myeloid leukemia.
Acute myeloid leukemia (AML) with mutated NPM1 is a newly recognized separate entity in the revised 2016 WHO classification, and is associated with a favorable prognosis. While previous studies have evaluated NPM1 in a binary fashion, we recently demonstrated a significant independent negative prognostic effect of high NPM1 mutant allele burden (VAF) at diagnosis in a cohort of de novo AML patients. Although the importance of minimal residual disease (MRD) monitoring in NPM1-mutated AML has been well characterized, the potential relationship between diagnostic allele burden and MRD is unknown. We retrospectively evaluated for MRD at first remission (CR1). We used either next-generation sequencing (NGS) [n = 71], and/or immunohistochemistry (IHC) for mutant NPM1 (NPM1c) [n = 60], in a subset of patients from our recently examined cohort. We identified a statistically significant positive correlation between the VAF at diagnosis, and at CR1 (Spearman r = 0.4, P = .006), and enrichment for MRD in high diagnostic VAF patients (P = .05), as previously defined. IHC-positivity also correlated significantly with a higher median diagnostic NPM1 VAF (0.42 vs 0.39, P = .02), and with the VAF at CR1 (Spearman r = 0.7, P = .003). In multivariable analyses, both high diagnostic VAF (P = .003) and MRD (P = .02) were independent predictors of shorter event-free survival (EFS). Our findings suggest a relationship between the NPM1 mutant allele burden at diagnosis, and the presence of MRD at first remission. Our findings support IHC as a potentially useful adjunctive tool for disease monitoring.


Teenagers' struggles with contraceptive use - what improvements can be made?
To study the experiences of teenagers using contraceptives at an out-patient abortion clinic and to explore the reasons behind their choices. Twelve teenagers who had applied for induced abortion were interviewed three to four weeks after abortion. The interviews comprised open questions about contraceptive experiences focusing on hindrance for contraceptive use. Qualitative content analysis was used. One theme was identified: Struggling with feelings of uncertainty and patterns of behaviour. Three categories emerged from the analysis. Uncertainty dealt with decisions and behaviours that varied with time and between the different individuals. Factors that influence contraceptive use dealt with the persons that the participants had discussed contraceptives with, how they acquired knowledge about contraceptive use and the nature of their behaviour. Anxiety dealt with the side effects of contraception and feelings of fear related to contraceptive use. The participants had feelings of uncertainty, anxiety and fear towards contraceptive use which led to non use and inconsistent use. Guidance from health care providers and access to youth clinics varied and was unsatisfactory. Parents were supportive of contraceptive use but not active in the process of getting their child to initiate it. Friends and the Internet were the main sources for acquiring information.


Mitochondrial dysfunction underlying sporadic inclusion body myositis is ameliorated by the mitochondrial homing drug MA-5.
Sporadic inclusion body myositis (sIBM) is the most common idiopathic inflammatory myopathy, and several reports have suggested that mitochondrial abnormalities are involved in its etiology. We recruited 9 sIBM patients and found significant histological changes and an elevation of growth differential factor 15 (GDF15), a marker of mitochondrial disease, strongly suggesting the involvement of mitochondrial dysfunction. Bioenergetic analysis of sIBM patient myoblasts revealed impaired mitochondrial function. Decreased ATP production, reduced mitochondrial size and reduced mitochondrial dynamics were also observed in sIBM myoblasts. Cell vulnerability to oxidative stress also suggested the existence of mitochondrial dysfunction. Mitochonic acid-5 (MA-5) increased the cellular ATP level, reduced mitochondrial ROS, and provided protection against sIBM myoblast death. MA-5 also improved the survival of sIBM skin fibroblasts as well as mitochondrial morphology and dynamics in these cells. The reduction in the gene expression levels of Opa1 and Drp1 was also reversed by MA-5, suggesting the modification of the fusion/fission process. These data suggest that MA-5 may provide an alternative therapeutic strategy for treating not only mitochondrial diseases but also sIBM.


Stress neuroendocrine profiles in five pig breeding lines and the relationship with carcass composition.
Stress neuroendocrine systems (hypothalamic-pituitary-adrenal axis and sympathetic nervous system) were studied in 100 female pigs from each of the five main genetic lines used in Europe for pork production: Piétrain, Large White, Landrace, Duroc and Meishan. Levels of cortisol and catecholamines were measured in urine collected at the farm, after transportation to the slaughterhouse and the next morning before slaughter. With the exception of the Piétrain line that showed intermediate levels of cortisol despite its extreme leanness, a significant positive relationship was found between basal cortisol levels and fatness, both across and within (except in Piétrain and Duroc) lines. Basal cortisol levels were 2.46-fold higher in Meishan (20.46 ng/mg creatinine) than in Large White pigs (8.30 ng/mg creatinine), the two extreme breeds. Post-transportation levels were highest but proportional to basal levels, suggesting that the adrenal reactivity to adrenocorticotropic hormone is a major source of variability between lines. Levels of catecholamines were less variable between lines but correlated also with fatness, partlyviapartial correlations with cortisol levels. In serum collected at exsanguination, creatine kinase activity was correlated with muscularity across the five breeds. However, this was due to a much larger activity than expected in Piétrain pigs, although all animals were negative for the allele of the ryanodine receptor gene responsible for stress sensitivity. Serum glucose levels were inversely related to fatness. These data show that the differences between breeds or lines can be utilised by cross-breeding and that this can lead to changes in stress hormones and in turn to some degree of changes in carcass traits.


The effects of prior exposure to sulphur dioxide and nitrogen dioxide on the water relations of timothy grass (Phleum pratense) under drought conditions.
Studies of the growth and water relations of the grass Phleum pratense L. (Timothy) were made after simultaneous exposure to SO(2) and NO(2) at concentrations ranging from 80 + 57.4 microg m(-3) to 240 + 172.2 microg m(-3) (SO(2) + NO(2)). Decreased partitioning to the roots was evident during exposure to the pollutants, but when the plants were returned to clean air restrictions in root growth did not persist. Shoot to root partitioning was, however, complicated by the additional factor of changes in the nutritional status of the soil after additional columns of fresh soil were attached to the original tubes. The rate of use of soil water was nevertheless substantially increased by the pollution treatment and after a period of 23 days in which water was withheld, a clear pollution x water stress interaction was seen. The ability of polluted leaves to conserve water under severe water stress was tested by excising the leaves and measuring their water loss over time. The results from this second experiment showed that conservation of water by the leaves was appreciably affected after exposure to 80 + 57.4 microg m(-3) or 133.3 + 95.6 microg m(-3) SO(2) + NO(2). It seems likely that damage to the cells in the epidermal layer, leading to malfunctioning of stomata, is mainly responsible for the reduced ability to conserve water under conditions of extreme stress.


A multiplex reverse transcriptase-PCR assay for the genotyping of avian infectious bronchitis viruses.
Infectious bronchitis viruses (IBVs) in Taiwan have been divided into two genogroups, Taiwan group I (TW-I) and Taiwan group II (TW-II). Heterologous Mass-type strains are widely used as vaccines in the field. This work reports on a rapid and reliable multiplex reverse transcriptase-polymerase chain reaction (mRT-PCR) assay for the genotyping of IBVs. Multiplex primer sets were designed to amplify the region covering hypervariable regions 1 and 2 of the S1 glycoprotein gene. Several local strains and commercially available vaccines were used for evaluating the viral genotyping assay, and a number of field isolates were examined for clinical application. The results showed that all of the examined IBVs were accurately genotyped by identifying the corresponding bands on agarose gels (TW-I: 322 bp, TW-II: 161 bp, Mass type: 256 bp) after the mRT-PCR, in agreement with the viral genome sequence data. The mRT-PCR assay was able to detect viral RNA copies as low as 10(3), 10(50, and 10(3) for the TW-I, TW-II, and Mass-type strains, respectively. The mRT-PCR assay accurately detected and discriminated vaccine viruses from wildtype strains in the field. This assay may be beneficial for virus identification and differentiation in routine disease surveillance.


Neurodegeneration and cell replacement.
The past decade has witnessed ground-breaking advances in human stem cell biology with scientists validating adult neurogenesis and establishing methods to isolate and propagate stem cell populations suitable for transplantation. These advances have forged promising strategies against human neurodegenerative diseases. For example, growth factor administration could stimulate intrinsic repair from endogenous neural stem cells, and cultured stem cells engineered into biopumps could be transplanted to deliver neuroprotective or restorative agents. Stem cells could also be transplanted to generate new neural elements that augment and potentially replace degenerating central nervous system (CNS) circuitry. Early efforts in neural tissue transplantation have shown that these strategies can improve functional outcome, but the ultimate success of clinical stem cell-based strategies will depend on detailed understanding of stem cell biology in the degenerating brain and detailed evaluation of their functional efficacy and safety in preclinical animal models.


Does psychedelic drug use reduce risk of suicidality? Evidence from a longitudinal community-based cohort of marginalised women in a Canadian setting.
This study aimed to longitudinally investigate whether ever having used a psychedelic drug can have a protective effect on incidence of suicidality among marginalised women. Longitudinal community-based cohort study. Data were drawn from a prospective, community-based cohort of marginalised women in Metro Vancouver, Canada. 766 women completed the baseline questionnaire between January 2010 and August 2014. Participants who did not report suicidality at baseline and who completed at least one follow-up visit were included. Extended Cox regression was used to model predictors of new suicidality (suicide ideation or attempts) over 54-month follow-up. Nearly half (46%; n=355) of participants reported prior suicidality and were thus excluded from the present analyses. Of 290 women eligible at baseline, 11% (n=31) reported recent suicidality during follow-up, with an incidence density of 4.42 per 100 person-years (95% CI 3.10 to 6.30). In multivariable analysis, reported lifetime psychedelic drug use was associated with a 60% reduced hazard for suicidality (adjusted HR (AHR) 0.40; 95% CI 0.17 to 0.94). Crystal methamphetamine use (AHR 3.25; 95% CI 1.47 to 7.21) and childhood abuse (AHR 3.54; 95% CI 1.49 to 8.40) remained independent predictors of suicidality. The high rate of suicidality identified in this study is of major concern. Alongside emerging evidence on the potential of psychedelic-assisted therapy to treat some mental illness and addiction issues, our findings demonstrate that naturalistic psychedelic drug use is independently associated with reduced suicidality, while other illicit drug use and childhood trauma predispose women to suicidality. While observational, this study supports calls for further investigation of the therapeutic utility of psychedelic drugs in treating poor mental health and promoting mental wellness.


Bridging the discharge process.
Current mental health initiatives are decreasing the number of psychiatric beds and thus increasing the number of clients with serious mental illness who are being served in the community. Such changes have implications for clients' quality of life and health care economics. To implement the changes while addressing the unique needs of psychiatric clients, appropriate models of discharge planning and community integration are critical.


Unambiguous identification of α-Gal epitopes in intact monoclonal antibodies by NMR spectroscopy.
The α-Gal epitope consisting of the terminal trisaccharide Galα1,3Galβ1,4GlcNAc exposed on cell or protein surfaces can cause severe immune reactions, such as hypersensitivity reactions, in humans. This epitope is also called the xenotransplantation epitope because it is one of the main reasons for the rejection of non-human organ transplants by the human innate immune response. Recombinant therapeutic proteins expressed in murine cell lines may contain α-Gal epitopes, and therefore their absence or presence needs to be tightly monitored to minimize any undesired adverse effects. The analytical identification of α-Gal epitopes in glycoproteins using the common standard techniques based on liquid chromatography and mass spectrometry is challenging, mainly due to the isobaricity of hexose stereoisomers. Here, we present a straightforward NMR approach to detect the presence of α-Gal in biotherapeutics based on a quick screen with sensitive 1H-1H TOCSY spectra followed by a confirmation using 1H-13C HSQC spectra.Abbreviations: α-Gal: α1,3-linked galactose; AGC: automatic gain control; CHO: Chinese hamster ovary; CE: capillary electrophoreses coupled to mass spectrometry; COSY: correlation spectroscopy; DSS: 2,2-dimethyl-2-silapentane-5-sulfonate; DTT: dithiothreitol; GlcNAc: N-acetyl glusomamine; HCD: higher-energy collisional dissociation; HMBC: heteronuclear multiple-bond correlation; HPLC: high-performance liquid chromatography; HSQC: heteronuclear single-quantum corre; LacNAc: N-acetyl lactosamine; mAb: monoclonal antibody; MS: mass spectrometry; NMR: nuclear magnetic resonance; NOESY: 2D) nuclear Overhauser spectroscopy; PEG: polyethylenglycol; pH*: observed pH meter reading without correction for isotope effects; PTM: post-translational modification; TCEP: tris(2-carboxyethyl) phosphine hydrochloride; TOCSY: total correlation spectroscopy; xCGE-LIF: multiplex capillary gel electrophoresis with laser-induced fluorescence detection.


Complement Receptor C3aR1 Contributes to Paclitaxel-Induced Peripheral Neuropathic Pain in Mice and Rats.
Cancer chemotherapy-induced neuropathic pain is a devastating pain syndrome without effective therapies. We previously reported that rats deficient in complement C3, the central component of complement activation cascade, showed a reduced degree of paclitaxel-induced mechanical allodynia (PIMA), suggesting that complement is integrally involved in the pathogenesis of this model. However, the underlying mechanism was unclear. Complement activation leads to the production of C3a, which mediates inflammation through its receptor C3aR1. In this article, we report that the administration of paclitaxel induced a significantly higher expression level of C3aR1 on dorsal root ganglion (DRG) macrophages and expansion of these macrophages in DRGs in wild-type (WT) compared with in C3aR1 knockout (KO) mice. We also found that paclitaxel induced less severe PIMA, along with a reduced DRG expression of transient receptor potential channels of the vanilloid subtype 4 (TRPV4), an essential mediator for PIMA, in C3aR1 KO than in WT mice. Treating WT mice or rats with a C3aR1 antagonist markedly attenuated PIMA in association with downregulated DRG TRPV4 expression, reduced DRG macrophages expansion, suppressed DRG neuron hyperexcitability, and alleviated peripheral intraepidermal nerve fiber loss. Administration of C3aR1 antagonist to TRPV4 KO mice further protected them from PIMA. These results suggest that complement regulates PIMA development through C3aR1 to upregulate TRPV4 on DRG neurons and promote DRG macrophage expansion. Targeting C3aR1 could be a novel therapeutic approach to alleviate this debilitating pain syndrome.


Soil organic carbon dust emission: an omitted global source of atmospheric CO2.
Soil erosion redistributes soil organic carbon (SOC) within terrestrial ecosystems, to the atmosphere and oceans. Dust export is an essential component of the carbon (C) and carbon dioxide (CO(2)) budget because wind erosion contributes to the C cycle by removing selectively SOC from vast areas and transporting C dust quickly offshore; augmenting the net loss of C from terrestrial systems. However, the contribution of wind erosion to rates of C release and sequestration is poorly understood. Here, we describe how SOC dust emission is omitted from national C accounting, is an underestimated source of CO(2) and may accelerate SOC decomposition. Similarly, long dust residence times in the unshielded atmospheric environment may considerably increase CO(2) emission. We developed a first approximation to SOC enrichment for a well-established dust emission model and quantified SOC dust emission for Australia (5.83 Tg CO(2)-e yr(-1)) and Australian agricultural soils (0.4 Tg CO(2)-e yr(-1)). These amount to underestimates for CO(2) emissions of ≈10% from combined C pools in Australia (year = 2000), ≈5% from Australian Rangelands and ≈3% of Australian Agricultural Soils by Kyoto Accounting. Northern hemisphere countries with greater dust emission than Australia are also likely to have much larger SOC dust emission. Therefore, omission of SOC dust emission likely represents a considerable underestimate from those nations' C accounts. We suggest that the omission of SOC dust emission from C cycling and C accounting is a significant global source of uncertainty. Tracing the fate of wind-eroded SOC in the dust cycle is therefore essential to quantify the release of CO(2) from SOC dust to the atmosphere and the contribution of SOC deposition to downwind C sinks.


Cellular K+ permeation across the cortical collecting tubule: effects of Na+-K+ pump inhibition and membrane depolarization.
These experiments examined the possibility that alterations in cell cation content and/or membrane voltage could influence cell K+ permeability of the cortical collecting tubule. Using the amiloride-treated isolated perfused rabbit cortical collecting tubule, ouabain or a K+-free bath reduced the magnitude of the K+ diffusion voltage. In addition, both methods of Na+-K+-ATPase inhibition reduced the K+ efflux (lumen-to-bath) rate coefficient (KK) without affecting the Na+ efflux rate coefficient. The magnitude of the reduction of KK could not be explained by a model of simple diffusion across two membranes in series even if the intracellular voltage were abolished. Thus, pump inhibition reduced cell K+ permeability. To determine whether membrane depolarization could induce a change in membrane permeability, [K+] was increased to 20 mM in both perfusate and bath. The reduction in KK was within the range predicted by the three-compartment model (36%). Differential membrane depolarization by raising lumen [K+] or bath [K+] produced disparate results. Apical depolarization reduced KK but basolateral depolarization did not. Taken together these results indicate that intracellular ion content may play a major role in regulating cell K+ permeability independent of voltage-dependent effects. In addition, under these experimental conditions, the apical membrane may be the rate-limiting barrier to cellular transfer.


Impact of a standard medication chart on prescribing errors: a before-and-after audit.
(1) To develop and implement a standard medication chart, for recording prescribing (medication orders) and administration of medication in public hospitals in Queensland. (2) To assess the chart's impact on the frequency and type of prescribing errors, adverse drug reaction (ADR) documentation and safety of warfarin prescribing. (3) To use the chart to facilitate safe medication management training. The medication chart was developed through a process of incident analysis and work practice mapping by a multidisciplinary collaborative. Observational audits by nurse and pharmacist pairs, of all available prescriptions before and after introduction of the standard medication chart, were undertaken in five sites. Similar numbers of both patients (730 pre-implementation and 751 post-implementation; orders, 9772 before and 10 352 after) were observed. The prescribing error rate decreased from 20.0% of orders per patient before to 15.8% after (Mann-Whitney U test, p = 0.03). Previous ADRs were not documented for 19.5% of 185 patients before and 11.2% of 197 patients after (chi(2), p = 0.032). Prescribing errors involving selection of a drug to which a patient had had a previous ADR decreased from 11.3% of patients before to 4.6% after (chi(2), p = 0.021). International normalised ratios (INRs) >5 decreased from 1.9% of 14 405 INRs in the 12 months before to 1.45% of 15 090 INRs after (chi(2), p = 0.004). After minor modifications, the chart was introduced into all hospitals statewide, which enabled standardised medication training and safer rotation of staff. The chart also formed the basis for the National Inpatient Medication Chart. Introduction of a standard revised medication chart significantly reduced the frequency of prescribing errors, improved ADR documentation and decreased the potential risks associated with warfarin management. The standard chart has enabled uniform training in medicine management.


Evaluation of in vivo genotoxicity induced by N-ethyl-N-nitrosourea, benzo[a]pyrene, and 4-nitroquinoline-1-oxide in the Pig-a and gpt assays.
The recently developed Pig-a mutation assay is based on flow cytometric enumeration of glycosylphosphatidylinositol (GPI) anchor-deficient red blood cells caused by a forward mutation in the Pig-a gene. Because the assay can be conducted in nontransgenic animals and the mutations accumulate with repeat dosing, we believe that the Pig-a assay could be integrated into repeat-dose toxicology studies and provides an alternative to transgenic rodent (TGR) mutation assays. The capacity and characteristics of the Pig-a assay relative to TGR mutation assays, however, are unclear. Here, using transgenic gpt delta mice, we compared the in vivo genotoxicity of single oral doses of N-ethyl-N-nitrosourea (ENU, 40 mg/kg), benzo[a]pyrene (BP, 100 and 200 mg/kg), and 4-nitroquinoline-1-oxide (4NQO, 50 mg/kg) in the Pig-a (peripheral blood) and gpt (bone marrow and liver) gene mutation assays. Pig-a assays were conducted at 2, 4, and 7 weeks after the treatment, while gpt assays were conducted on tissues collected at the 7-week terminal sacrifice. ENU increased both Pig-a and gpt mutant frequencies (MFs) at all sampling times, and BP increased MFs in both assays but the Pig-a MFs peaked at 2 weeks and then decreased. Although 4NQO increased gpt MFs in the liver, only weak, nonsignificant increases (two- or threefold above control) were detected in the bone marrow in both the Pig-a and the gpt assay. These findings suggest that further studies are needed to elucidate the kinetics of the Pig-a mutation assay in order to use it as an alternative to the TGR mutation assay.


CitAB Two-Component System-Regulated Citrate Utilization Contributes to Vibrio cholerae Competitiveness with the Gut Microbiota.
Citrate is a ubiquitous compound and can be utilized by many bacterial species, including enteric pathogens, as a carbon and energy source. Genes involved in citrate utilization have been extensively studied in some enteric bacteria, such as Klebsiella pneumoniae; however, their role in pathogenesis is still not clear. In this study, we investigated citrate utilization and regulation in Vibrio cholerae, the causative agent of cholera. The putative anaerobic citrate fermentation genes in V. cholerae, consisting of citCDEFXG, citS-oadGAB, and the two-component system (TCS) genes citAB, are highly homologous to those in K. pneumoniae Deletion analysis shows that these cit genes are essential for V. cholerae growth when citrate is the sole carbon source. The expression of citC and citS operons was dependent on citrate and CitAB, whose transcription was autorepressed and regulated by another TCS regulator, ArcA. In addition, citrate fermentation was under the control of catabolite repression. Mouse colonization experiments showed that V. cholerae can utilize citrate in vivo using the citrate fermentation pathway and that V. cholerae likely needs to compete with other members of the gut microbiota to access citrate in the gut.


Knowledge on hypertension in Myanmar: levels and groups at risk.
Background: Non-communicable diseases, specifically the burden of hypertension, have become a major public health threat to low- and middle-income countries, such as Myanmar. Inadequate knowledge of hypertension and its management among people may hinder its effective prevention and treatment with some groups at particular increased risks, but evidence on this is lacking for Myanmar. The aims of this study were therefore to assess the level of knowledge of risk factors, symptoms and complications of hypertension, by hypertension treatment status, community group-membership, and sociodemographic and socioeconomic factors in Myanmar. Methods: Data was collected through structured questionnaires in 2020 on a random sample of 660 participants, stratified by region and existence of community groups. Knowledge of hypertension was measured with the 'Knowledge' part of a validated 'Knowledge, Attitude and Practice' survey questionnaire and categorised into ill-informed and reasonably to well-informed about hypertension. Results: The majority of respondents seem reasonably to well-informed about risk factors, symptoms and complications of hypertension. This did not vary by hypertension treatment status and community group membership. People with jobs (B=0.96; 95%-confidence interval 0.343 to 1.572) and higher education (B=1.96; 0.060 to 3.868) had more hypertension knowledge than people without jobs or low education. Adherence to treatment among hypertensive people was low. Conclusion: This study shows a majority of participants in this study in Myanmar seem reasonably to well-informed, with no differences by hypertension status, treatment status, and community group-membership. People without jobs and low education have less hypertension knowledge, making them priority groups for tailored education on health care level as well as community level, lowering the burden of hypertension. Almost half of the hypertensive patients did not take their medicines and therefore, adherence to treatment of hypertension should be an important element for future health education.


Testing the tilt-constancy theory of visual illusions.
Prinzmetal and Beck (2001) Journal of Experimental Psychology: Human Perception and Performance 27 206 - 217) argued that a subset of visual illusions is caused by the same mechanisms that are responsible for the perception of vertical and horizontal a theory they referred to as the tilt-constancy theory of visual illusions. They argued that these illusions should increase if the observer's head or head and body are tilted because extra reliance would then be placed on the illusion-inducing local visual context. Exactly that result had previously been reported in the case of the tilted-room and the rod-and-frame illusions. Prinzmetal and Beck reported similar increases in the tilt illusion (TI), as well as the Zöllner, Poggendorff, and Ponzo illusions. In two experiments, we re-examined the effect of head tilt on the TI. In experiment 1, we used more conventional TI stimuli, more standard experimental methods, and a more complete experimental design than Prinzmetal and Beck, and additionally extended the investigation to attraction as well as repulsion effects. Experiment 2 more closely replicated the Prinzmetal and Beck stimuli. Although we found that head tilt did increase TIs in both experiments, the increases were of the order of 1 degrees -2 degrees, more modest than the 7 degrees reported by Prinzmetal and Beck. Significantly, the TI increase was larger when inducing tilts and head tilts were in the same direction than when they were in opposite directions, suggesting that the tilt-constancy theory may be oversimplified. In addition, because previous evidence renders unlikely the claim that the Poggendorff illusion can be explained simply in terms of misperceived orientation of the transversals, the question arises whether there might be some other explanation for the increase in the Zöllner, Poggendorff, and Ponzo illusions with body tilt that Prinzmetal and Beck reported.


Effects of calcium salts of fatty acids and protein source on ruminal fermentation and nutrient flow to duodenum of cows.
Four Holstein cows fitted with ruminal and duodenal cannulas were used in a 4 x 4 Latin square to investigate the effects of calcium salts of long-chain fatty acids (fat) and source of protein (fish meal or soybean meal) on ruminal fermentation, flow of nutrients to the small intestine, and animal performance. Cows were fed for ad libitum intake a diet of 30% alfalfa haylage, 20% corn silage, and 50% concentrate on a DM basis. Treatments, arranged in a 2 x 2 (fat x protein) factorial, were 1) soybean meal, no fat; 2) soybean meal, fat; 3) fish meal, no fat; and 4) fish meal, fat. Intake of DM was not affected by fat or protein source, but feeding fat decreased the amount of OM truly digested in the rumen. Starch intake was decreased, but flow of starch to the duodenum was not altered by feeding fat. Nonammonia N and microbial N flows to the duodenum were not affected by treatment comparisons. However, efficiency of microbial growth was increased by feeding fat, but not by source of protein. Passage of amino acids to the duodenum was not affected by source of protein, probably because fish meal contributed only 17% of the total dietary CP, and microbial N constituted about 50% of the NAN passing to the duodenum; this had an equalizing effect on the pattern and quantity of amino acids that passed to the duodenum. Feeding fat or different sources of protein did not alter milk production. Milk fat percentage was increased, and protein percentage was decreased when fat was fed, but yields of milk fat and protein were not different.


Interleukin-6 (IL-6) and soluble receptors for interleukin-2 (sIL-2R) in the diagnosis of early severe infection in the critically ill newborns.
The aim of our study was to evaluate the diagnostic accuracy of serial determination of interleukin-6 (IL-6) and soluble receptors of interleukin-2 (sIL-2R) in the diagnosis of early infection in the critically ill newborns and compare it with the routinely used C-reactive protein (CRP). Fourty-six critically ill newborns (median age 8 h, range 1-96 h), treated at the multidisciplinary intensive care unit, Division for Paediatric Surgery and Intensive Care, University Medical Centre Ljubljana, were included in the study. Newborns were divided into three groups: group I microbiologically confirmed severe infection (n = 14), group II suspected but not confirmed infection (n = 12) and group III respiratory distress syndrome without laboratory signs of infection. Serum concentrations of IL-6, sIL-2R and CRP were determined on admission and at 12 and 24 h after admission. On admission the concentrations of IL-6 and sIL-2R were significantly higher in group I than in group III, but there was no difference between groups I and II. On admission area under receiver operating characteristic (ROC) curve for IL-6 was 0.756, for IL-2R 0.821 and for CRP 0.799. Repeated determination at 12 h improved diagnostic accuracy for sIL-R and CRP but not for IL-6.


Autism in Saudi Arabia: presentation, clinical correlates and comorbidity.
Although autism is a global disorder, relatively little is known about its presentation and occurrence in many developing countries, such as Saudi Arabia. This article describes the reasons for referral and clinical characteristics of a sample of 49 children (37 males and 12 females) diagnosed with an autistic spectrum disorder at a tertiary referral center in Saudi Arabia. The diagnosis of autism was based on DSM-IV criteria supplemented by information obtained from parent and child interviews, rating scales, and examination of school and hospital records. Females were older than males at the time of referral. Eleven patients had a history of seizure disorder and one patient had a chromosome abnormality. Twenty-five patients were taking psychotropic medications and 14 patients were the product of consanguineous marriages. Clinical and research implications of these findings are discussed.


A 12-chemokine gene signature is associated with the enhanced immunogram scores and is relevant for precision immunotherapy.
Advances in the understanding of checkpoint blockade immunotherapy have suggested that boosting the cancer-immunity cycle (CIC) can help induce regression of tumors. However, good efficacy only occurs in a subset of patients. Predictive biomarkers that can reflect the tumor microenvironment (TME) and CIC may have great potential. More recently, the presence of intratumoral tertiary lymphoid structures (TLSs) has also been correlated with clinical benefit in patients. In this study, we comprehensively measured the immunogram scores (IGSs) for the CIC and explored the associations between immunological and mutational features and a 12-chemokine metagene TLS signature in data from The Cancer Genome Atlas (TCGA). Three immunotherapy datasets were further applied for validation. In the TCGA dataset, we observed that the 12-chemokine TLS signature score was positively associated with the enhanced IGSs as represented by increased tumor mutational burden (TMB) and neoantigen burden (TNB), enriched immune cell (IC) infiltration, and elevated cytolytic activity and checkpoint expression. Specifically, in bladder cancer and melanoma, the high 12-chemokine TLS signature score was found to potentially reflect an expanded cancer-immunity status characterized by high TNB and an immune-inflamed feature. The predictive and prognostic value of the 12-chemokine TLS signature was further validated in several immunotherapy datasets. The score of the 12-chemokine TLS signature may serve as a pancancer marker of the immune-active phenotype. The 12-chemokine TLS signature showed promise as a predictive and prognostic biomarker for ICB efficacy, especially in melanoma and bladder cancer.


Nuclear epidermal growth factor receptor (EGFR) interacts with signal transducer and activator of transcription 5 (STAT5) in activating Aurora-A gene expression.
Loss of the maintenance of genetic material is a critical step leading to tumorigenesis. It was reported that overexpression of Aurora-A and the constitutive activation of the epidermal growth factor (EGF) receptor (EGFR) are implicated in chromosome instability. In this study, we examined that when cells treated with EGF result in centrosome amplification and microtubule disorder, which are critical for genetic instability. Interestingly, the expression of Aurora-A was also increased by EGF stimulus. An immunofluorescence assay indicated that EGF can induce the nuclear translocation of EGFR. Chromatin immunoprecipitation (ChIP) and re-ChIP assays showed significant EGF-induced recruitment of nuclear EGFR and signal transducer and activator of transcription 5 (STAT5) to the Aurora-A promoter. A co-immunoprecipitation assay further demonstrated that EGF induces nuclear interaction between EGFR and STAT5. A small interfering (si)RNA knockdown assay also showed that EGFR and STAT5 are indeed involved in EGF-increased Aurora-A gene expression. Altogether, this study proposes that the nuclear EGFR associates with STAT5 to bind and increase Aurora-A gene expression, which ultimately may lead to chromosome instability and tumorigenesis. The results also provide a novel linkage between the EGFR signaling pathway and overexpression of Aurora-A in tumorigenesis and chromosome instability.


Evidence for force-feedback inhibition in chronic stroke.
The presence of force-feedback inhibition was explored during reflex responses in five subjects with known incidence of stroke. Using constant velocity stretches, it was previously found that after movement onset, active reflex force progressively increases with increasing joint angle, at a rate proportional to a fractional exponent of the speed of stretch. However, after the reflex force magnitude exceeds a particular level, it begins rolling off until maintaining a steady-state value. The magnitudes of these force plateaus are correlated with the speed of stretch, such that higher movement speeds result in higher steady-state forces. Based upon these previous studies, we hypothesized that force plateau behavior could be explained by a force-feedback inhibitory pathway. To help facilitate an understanding of this stretch reflex force roll off, a simple model representing the elbow reflex pathways was developed. This model contained two separate feedback pathways, one representing the monosynaptic stretch reflex originating from muscle spindle excitation, and another representing force-feedback inhibition arising from force sensitive receptors. It was found that force-feedback inhibition altered the stretch reflex response, resulting in a force response that followed a sigmoidal shape similar to that observed experimentally. Furthermore, simulated reflex responses were highly dependent on force-feedback gain, where predicted reflex force began plateauing at decreasing levels with increases in this force-feedback gain. The parameters from the model fits indicate that the force threshold for force-sensitive receptors is relatively high, suggesting that the inhibition may arise from muscle free nerve endings rather than Golgi tendon organs. The experimental results coupled with the simulations of elbow reflex responses suggest the possibility that after stroke, the effectiveness of force-feedback inhibition may increase to a level that has functional significance. Practical implications of these findings are discussed in relation to muscle weakness commonly associated with stroke.


Ancient and modern mitochondrial DNA sequences and the colonization of the Pacific.
Mitochondrial DNA (mtDNA) is a valuable tool for the study of recent human evolution because it is easy to analyse, is inherited uniparentally and has a relatively rapid rate of evolution. mtDNA analysis has been used extensively for the elucidation of the pattern of migrations of human populations. Several studies have focused on the Pacific because Polynesia was settled by humans for the first time relatively recently and there is a wealth of archaeological and linguistic data to complement genetic data on the region. Results of mtDNA analyses on modern-day Pacific populations indicate reduced genetic variability, and suggest that the Polynesians descend from people who migrated relatively recently from island Southeast Asia and that a population bottleneck occurred during the settlement of the central Pacific. Several informative polymorphisms have been identified in the hypervariable control region of mtDNA in modern-day Pacific populations that are helpful in tracing the ancestral affinities of these people. Studies of these mtDNA polymorphisms in ancient bones of prehistoric Pacific islanders indicate that the proto-Polynesian colonizers may have descended from the early settlers of island Melanesia. Although fraught with technical difficulties, studies of ancient DNA can provide valuable evidence on the genetic affinities of past peoples.


[Anticoagulant treatment in pulmonary embolism : how to initiate and how to pursue ?]
Pulmonary embolism (PE) is associated with significant morbidity and mortality in the absence of properly prescribed anticoagulant treatment. Direct oral anticoagulants (DOACs) are currently the anticoagulant treatment of first choice. The quality of anticoagulation in the acute phase of PE is a major determinant of patients' prognosis. The dose regimens for the initiation phase must therefore be rigorously respected to ensure the efficacy of the treatment. For the maintenance phase, the reduced doses used in atrial fibrillation are not applicable in venous thromboembolism (VTE) except for edoxaban. Finally, for long-term secondary prevention in patients at risk of VTE recurrence, reduced dose DOACs are currently a very interesting option in terms of benefit-risk balance for the majority of patients.


Regulation of OsSPL14 by OsmiR156 defines ideal plant architecture in rice.
Increasing crop yield is a major challenge for modern agriculture. The development of new plant types, which is known as ideal plant architecture (IPA), has been proposed as a means to enhance rice yield potential over that of existing high-yield varieties. Here, we report the cloning and characterization of a semidominant quantitative trait locus, IPA1 (Ideal Plant Architecture 1), which profoundly changes rice plant architecture and substantially enhances rice grain yield. The IPA1 quantitative trait locus encodes OsSPL14 (SOUAMOSA PROMOTER BINDING PROTEIN-LIKE 14) and is regulated by microRNA (miRNA) OsmiR156 in vivo. We demonstrate that a point mutation in OsSPL14 perturbs OsmiR156-directed regulation of OsSPL14, generating an 'ideal' rice plant with a reduced tiller number, increased lodging resistance and enhanced grain yield. Our study suggests that OsSPL14 may help improve rice grain yield by facilitating the breeding of new elite rice varieties.


Initial injury care in Nairobi, Kenya: a call for trauma care regionalisation.
To describe the emergency care of injuries at a main city hospital. A prospective study. Data were collected between February 1st, 1999 and 30th April, 1999 from the records of the 2000 bed Kenyatta National Hospital (KNH) in Nairobi, Kenya. Two hundred and forty injury patients admitted at KNH were analysed. All patients were analysed for demographics, environment of injury hospital arrival and Emergency Department times. The effects of injury severity, place of injury and time of day on these time intervals were analysed statistically. Road injury admissions formed 31% of all injury admissions. The mean age was 30 years. Males comprised 84.6% of all patients. The proportions of patients under 20 years of age was 20% with a peak age of 20-29 years. Majority (43.3%) of the injured resided in deprived neighbourhood of East Nairobi. The mean pre-hospital time was 2.56 hours. The Emergency Department disposition time was 3.36 hours. Injuries of all severities, as determined by the Injury Severity Score (ISS), were treated. The pace of care did not match severity of the injuries. Only 17.5% reached their areas of definitive care within sixty minutes. Injuries following road traffic accidents (RTAs) are common in Nairobi. The response to injury is slow and haphazard. The insitution of a care incorporating the city's health centers and pre-hospital triage may optimise care.


Forward planned intensity modulated radiotherapy (IMRT) for whole breast postoperative radiotherapy. Is it useful? When?
The purpose was to compare the dosimetric results observed in 201 breast cancer patients submitted to tangential forward intensity-modulated radiation therapy (IMRT) with those observed in 131 patients treated with a standard wedged 3D technique for postoperative treatment of whole breast, according to breast size and supraclavicular node irradiation. Following dosimetric parameters were used for the comparison: D(max), D(min), D(mean), V(95%) and V(107%) for the irradiated volume; D(max), D(mean), V(80%) and V(95%) for the ipsilateral lung; D(max), D(mean), V(80%) and V(95%) for the heart. Stratification was made according to breast size and supraclavicular (SCV) nodal irradiation. As respect to irradiated volume, a significant reduction of V(107%) (mean values: 7.0 ± 6.6 versus 2.4 ± 3.7, p < 0.001) and D(max) (mean % values: 111.2 ± 2.7 versus 107.7 ± 6.3, p < 0.001), and an increase of D(min) (mean % values: 65.0 ± 17.4 versus 74.9 ± 12.9, p < 0.001) were observed with forward IMRT. The homogeneity of dose distribution to target volume significantly improved with forward IMRT in all patient groups, irrespective of breast size or supraclavicular nodal irradiation. When patients treated with supraclavicular nodal irradiation were excluded from the analysis, forward IMRT slightly reduced V(80%) (mean values: 3.7 ± 2.6 versus 3.0 ± 2.4, p = 0.03) and V(95%) (mean values 1.9 ± 1.8 versus 1.2%± 1.5; p = 0.001) of the ipsilateral lung. The dose to the heart tended to be lower with IMRT but this difference was not statistically significant. Tangential forward IMRT in postoperative treatment of whole breast improved dosimetric parameters in terms of homogeneity of dose distribution to the target in a large sample of patients, independent of breast size or supraclavicular nodal irradiation. Lung irradiation was slightly reduced in patients not undergoing to supraclavicular irradiation.


Castroviejo Lecture 2009: 40 years in search of the perfect contact lens.
To identify the pathophysiological changes produced by contact lens wear that predispose the cornea to infection and search for prospective modifiable risk factors that could reduce the incidence of this critical complication in millions of patients worldwide. Significant experimental and clinical publications are reviewed, and the results of ongoing studies are presented. Pseudomonas aeruginosa (PA) is the most common pathogen causing lens-related infectious keratitis over 3 decades. Contact lens wear can increase the risk of infection by increasing surface cell PA binding, thereby promoting invasion between broken tight junctions and initiating direct intracellular invasion mediated by lens-induced membrane lipid rafts. Prevention of upregulation of specific surface-binding receptors for PA with concomitant increase in infection risk is a zero damage game where independent interactions among lens type, mode of wear, oxygen transmissibility, polymer, and toxic effects of associated care solutions ideally should collectively produce no increased ability for PA to attach and/or to invade, thus minimizing the risk for lens-associated infections. The specific hypothesis tested is, "no increased epithelial surface damage... no increased PA binding or invasion... no increased risk for infection." Testing of this new paradigm has been performed in vitro and in animal and human clinical trials and correlated clinically with relative risk results from robust current epidemiological studies. Results to date clearly support the use of lens-related increases in PA binding (bench) as a noninvasive clinical predictor of risk for lens-related infection in subsequent large-scale population studies (bedside). Currently, results suggest that use of common commercial multipurpose lens care solutions with soft lenses may alone significantly increase infection risk by enhancing lens-related PA binding as compared with use of nonpreserved solutions (hydrogen peroxide). Clinical testing also shows that only peroxide solutions show significant disinfection capability against amoebic cysts. Further case-control studies to examine relative risk for infection by lens type and lens care solution are urgently needed. Millions of patients are dependent on contact lenses for vision worldwide; over 3 decades, lens use has increased, although risk for lens-related infection has remained stubbornly unchanged. Unfortunately, recent introduction of a new generation of hyper-oxygen transmissible lenses used with traditional multipurpose lens care solutions has not lowered overall risks for lens-related infections; however, similar lenses used with nonpreserved care solutions (peroxide) recently demonstrated no significant increases in PA binding in a 1-year clinical trial. Collectively, these findings along with the urgent need for amoebic cysticidal disinfection have led to a current recommendation to patients to use nonpreserved (hydrogen peroxide) care solutions in soft lens wear.


What Role Does Substance Use Play in Intimate Partner Violence? A Narrative Analysis of In-Depth Interviews With Men in Substance Use Treatment and Their Current or Former Female Partner.
Few studies have examined intimate partner violence (IPV) in relationships where one or both partners are in treatment for substance use, from the perspectives of both members of a couple. This study used thematic and narrative analysis of the accounts of 14 men recruited from substance use services and 14 women who were their current or former intimate partners. Separate researchers interviewed men and women from the same dyad pair. The psychopharmacological effects of substance use (including intoxication, craving, and withdrawal) were rarely the only explanation offered for IPV. Violence was reported to be primed and entangled with sexual jealousy, with perceptions of female impropriety and with women's opposition to male authority. Both partners reported adversities and psychological vulnerabilities that they considered relevant to conflict and abuse. Male participants were more likely to describe IPV as uncharacteristic isolated events that arose from specific disputes-either aggravated by intoxication or withdrawal or about substance use and its resourcing-whereas women described enduring patterns of abusive behavior often linked to intoxication, craving, withdrawal, and to disputes linked to raising funds for substances. In relationships where both partners used substances, men described the need to protect their partners from addiction and from unscrupulous others while women described highly controlling behavior. In relationships where women were not dependent substance users, they reported the combined effects of psychological and financial abuse often linked to recurring patterns of substance use and relapse. These findings highlight the challenges faced by practitioners working with male perpetrators who use substances as well as the need of those working with women who have been abused to engage with the ways in which hesitance to leave male abusers can be complicated by shared drug dependency.


The effect of the subspinal Le Fort I-type osteotomy on interalar rim width.
The postoperative increase in interalar rim width was measured in two groups undergoing Le Fort I impaction or advancement. In the control group, 19 patients with a conventional osteotomy, an absorbable alar cinch suture, and V-Y closure were followed for 20 months on average. In the experimental group, 12 patients with a "subspinal" Le Fort I osteotomy (without alar cinch or V-Y closure) were followed for 15 months on average. Interalar rim width was measured with a slide gauge preoperatively, at several times during surgery, and at the 6-month and late follow-up appointments. At surgery, the alar cinch suture decreased the interalar rim width by 50% in the control group. Still, after extubation, there was no statistical difference between groups. At the 6-month follow-up measurement, the interalar rim width was significantly (1.92 mm) smaller in the subspinal group. At the late follow-up, this difference had decreased by a mean of 0.61 mm.


[Observations on the corneal endothelium in glaucoma].
The corneal endothelia in 87 cases of unilateral glaucoma were studied with the TOCEB-160 IV specular photomicroscope, and the healthy fellow eyes served as controls. The endothelial cell density was found decreased in majority of the morbid eyes by an average 12.7% in acute angle-closure glaucoma (34 cases), by 5.34% in chronic angle-closure glaucoma (23 cases), and by 12.4% in glaucoma cyclitis syndrome (30 cases). The average diminution of endothelial cell densities after filtering operations in 16 eyes was 10.2%, and after Nd:YAG laser iridotomy it was 5.11%. The authors are of the opinion that estimation of endothelial cells before operations and precautions against endothelial damage during operations invading the anterior chamber are necessary, especially for cases with risk factors such as trauma, uveitis, persistent high IOP, old age, or history of intra-ocular surgery.


Modulation of left ventricular dilation remodeling with epicardial restraint devices in postmyocardial infarction heart failure.
Myocardial infarction initiates progressive changes in the biology of the myocyte and nonmyocyte components of the myocardium, as well as the geometry of the left ventricle. Despite the use of evidence-based strategies to postmyocardial infarction, heart failure supervenes and is attended by an unacceptably high mortality rate. Given that left ventricular (LV) remodeling may contribute independently to disease progression, several innovative approaches have been designed to attenuate and reverse LV remodeling. This review discusses the emerging role of epicardial restraint devices in the treatment of postmyocardial cardiac remodeling.


Matrix metalloproteinases regulate ECM accumulation but not larval heart growth in Drosophila melanogaster.
The Drosophila heart provides a simple model to examine the remodelling of muscle insertions with growth, extracellular matrix (ECM) turnover, and fibrosis. Between hatching and pupation, the Drosophila heart increases in length five-fold. If major cardiac ECM components are secreted remotely, how is ECM "self assembly" regulated? We explored whether ECM proteases were required to maintain the morphology of a growing heart while the cardiac ECM expanded. An increase in expression of Drosophila's single tissue inhibitor of metalloproteinase (TIMP), or reduced function of metalloproteinase MMP2, resulted in fibrosis and ectopic deposition of two ECM Collagens; type-IV and fibrillar Pericardin. Significant accumulations of Collagen-IV (Viking) developed on the pericardium and in the lumen of the heart. Congenital defects in Pericardin deposition misdirected further assembly in the larva. Reduced metalloproteinase activity during growth also increased Pericardin fibre accumulation in ECM suspending the heart. Although MMP2 expression was required to remodel and position cardiomyocyte cell junctions, reduced MMP function did not impair expansion of the heart. A previous study revealed that MMP2 negatively regulates the size of the luminal cell surface in the embryonic heart. Cardiomyocytes align at the midline, but do not adhere to enclose a heart lumen in MMP2 mutant embryos. Nevertheless, these embryos hatch and produce viable larvae with bifurcated hearts, indicating a secondary pathway to lumen formation between ipsilateral cardiomyocytes. MMP-mediated remodelling of the ECM is required for organogenesis, and to prevent assembly of excess or ectopic ECM protein during growth. MMPs are not essential for normal growth of the Drosophila heart.


A lump on the tongue: a diagnostic dilemma?
This paper is a case report of an oral lesion detected in a female patient in her twenties. The aetiology and pathology was not immediately clear-cut but the patient's history provided a clue to its origins and histopathological examination confirmed the diagnosis. It was a "Pregnancy Tumour" which had failed to regress after parturition. This case report will make medical and dental practitioners more aware of lumps and lesions in the mouth. It will also provide a more rational and scientific approach to the management of "Pregnancy Tumours".


Impact of Cosmetics on the Physical Dimension and Optical Performance of Silicone Hydrogel Contact Lenses.
To evaluate the impact of cosmetics on silicone hydrogel (SiHy) contact lens shape, lens power, and optical performance. In this in vitro experiment, 7 SiHy materials were coated with 9 marketed brands of cosmetics, including hand creams (HCs) (3), eye makeup removers (MRs) (3), and mascaras (3). Diameter, sagittal depth, and base curve were determined using the Chiltern (Optimec Limited), whereas lens power and optical performance were assessed using the Contest Plus (Rotlex). Six replicates were used for each lens and cosmetic combination. Measurements were repeated after a cleaning cycle using a one-step hydrogen peroxide solution. Makeup removers had the greatest impact on diameter, sagittal depth, and base curve, resulting in changes of up to 0.5, 0.15, and 0.77 mm, respectively. The HCs and mascaras had little impact on these parameters; however, differences were observed between lens types. Optical performance was reduced with all mascaras, and a decrease of greater than 2 units on a 0 to 10 scale (10=uniform power distribution) was seen for 5 lens types exposed to waterproof mascara (P<0.01). Most HCs and MRs had minimal impact on image quality. Lens power did not change with any of the cosmetics (± 0.25 diopter; P>0.05). Lens cleaning resulted in some recovery of the lens parameters, and efficiency varied between cosmetics. Some eye MRs and waterproof mascaras changed the shape and optical performance of some SiHy lenses. Further research is needed to understand the clinical implications for SiHy lens wearers using cosmetics.


Human alpha and gamma interferon analogs in rabbits with herpetic keratitis.
Complete gene synthesis methods have been used to construct analogs of human interferons (IFNs): these include a consensus of the known human IFN-alpha S, designated IFN-alpha Con1 and a variant of human IFN-gamma, designated IFN-gamma 4A. These interferons, in purified form, were used topically against herpes simplex virus type 1 (HSV-1) induced ocular keratitis in rabbits. Eyes pretreated with IFN-alpha Con1 had decreased signs of infection and a lower incidence of HSV-1 positive trigeminal ganglia (3 of 14 positive) compared to the placebo treated (10 of 14 positive). IFN-alpha Con1 was as effective as natural IFN-alpha subtypes on a units basis, despite the very high specific activity of this analog. IFN-gamma 4A used under similar conditions do not result in beneficial effects with treatments beginning 24 or 48 hr before or 4 hr after virus inoculation. Rabbits with confirmed latent HSV infection were treated topically with IFN-alpha Con1 (10(6) units per eye each day) either before or before and after attempts to intentionally reactivate the infection by bilateral iontophoresis of 6-hydroxydopamine plus topical epinephrine treatment of the corneas. These IFN-alpha Con1 treatment regimens along with intentional reactivation during latency did not: (1) lessen the frequency of inducible ocular shedding episodes; (2) alter the mean time of 3-5 days between attempts to reactive latent infection and the appearance of HSV in tears; or (3) significantly change the incidence of HSV-positive trigeminal ganglia (83-100% HSV positive).


Calcium and Vitamin D Deficiency in Vietnamese: Recommendations for an Intervention Strategy.
In recent years, reports have described various roles of vitamin D in human health. Vitamin D deficiency has emerged as a significant public health problem throughout the world. Even in the Vietnamese context, it has been reported to be present in a majority of the population in spite of the wide availability of sunlight. Vitamin D and calcium are essential nutrients for bone health. The proposed health benefits of vitamin D and calcium have attracted increased interest from health care professionals, the media, and the public. The aim of this paper is to summarize the published data on vitamin D and calcium intake as well as on the prevalence of vitamin D deficiency in the Vietnamese population, and to provide recommendations for a proper strategy to control calcium and vitamin D deficiency in this population. The national authorities should adopt policies aimed at improving vitamin D and calcium status by using measures such as dietary recommendations, food fortification, vitamin D supplementation, and judicious sun exposure.


Shoaling in zebrafish: what we don't know.
Zebrafish have been gaining increasing popularity in behavioral neuroscience. However, the number of behavioral test paradigms specifically designed for zebrafish, and in general the amount of information available on the behavior of this species, is relatively small when compared with classical laboratory model organisms such as the mouse, the rat, and the fruit fly. A particularly typical behavioral feature of zebrafish is shoaling, i.e., group formation. Given the importance of social behavior in our own species and the fact that zebrafish possess several characteristics similar to those of other vertebrates, including humans, at many levels of biological organization (e.g., neuroanatomy, neurochemistry, biochemical processes, and amino acid sequence of proteins or nucleotide sequence of genes), the zebrafish is expected to be an excellent tool not only for basic research but perhaps also for translational research. Briefly, we propose that once social behavior of the zebrafish is better characterized and once appropriate behavioral methods have been developed, this species can be utilized for the analysis of the mechanisms of social behavior of other vertebrates including our own. In this review, we discuss general principles of shoaling and highlight what we know and what we do not know about this behavior as it pertains to zebrafish.


An experimental study on the stiffness of size-isolated microbubbles using atomic force microscopy.
To fully assess contrast-enhanced acoustic bioeffects in diagnostic and therapeutic procedures, the mechanical properties of microbubbles need to be considered. In the present study, direct measurements of the microbubble stiffness were performed using atomic force microscopy by applying nanoscale compressions (up to 25 nN/s) on size-isolated, lipidcoated microbubbles (diameter ranges of 4 to 6 μm and 6 to 8 μm). The stiffness was found to lie between 4 and 22 mN/m and to decrease exponentially with the microbubble size within the diameter range investigated. No cantilever spring constant effect was found on the measured stiffness. The Young's modulus of the size-isolated microbubbles used in our study ranged between 0.4 and 2 MPa. Microstructures on the surface of the microbubbles were found to influence the overall microbubble elasticity. Our results indicated that more detailed theoretical models are needed to account for the size-dependent microbubble mechanical properties to accurately predict their acoustic behavior. The findings provided useful insights into guidance of cavitation-induced drug and gene delivery and could be used as part of the framework in studies on the shear stresses induced on the blood vessel walls by oscillating microbubbles.


Strain in a single wrinkle on an MoS2 flake for in-plane realignment of band structure for enhanced photo-response.
Since 2D transition metal dichalcogenides (TMDs) exhibit strain-tunable bandgaps, locally confining strain can allow lateral manipulation of their band structure, in-plane carrier transport and optical transitions. Herein, we show that a single wrinkle (width = 10 nm-10 μm) on an MoS2 flake can induce confined uniaxial strain to reduce the local bandgap (40-60 meV per % deformation), producing a microscopic exciton funnel with an enhancement in photocurrent over flat MoS2 devices. This study also shows that wrinkles can spatially reconfigure the distribution of dopants and enhance the light absorption in the MoS2 layer via Fabry-Perot interference in its nanocavity. In the field-effect transistor studies on the MoS2 flat-wrinkle-flat device-structure, a higher carrier mobility and an improvement in the on/off ratio were exhibited in the devices with a single wrinkle. This phenomenon is attributed to the built-in potential induced by the bandgap reduction at the wrinkle site and the change in doping of the suspended wrinkle. The wrinkle-induced tunability of the local bandgap and manipulation of the spatial transport barriers, and the enhanced light absorption can enable development of next-generation electronic and optoelectronic devices guided by in-plane deformation of 2D nanomaterials.


Alcohol consumption and later risk of hospitalization with psychiatric disorders: prospective cohort study.
The potential effects of alcohol intake upon the risk of psychiatric disorders have not often been investigated. The purpose of this study was to investigate, in a population sample, the association between self-reported amount of alcohol intake and the later risk of being registered in a Danish hospital with a psychiatric disorder. The prospective cohort study, the Copenhagen City Heart Study (n=18,146), was used, containing three updated sets of alcohol intake and lifestyle covariates and up to 26 years follow-up. Alcohol intake was measured by self-report while psychiatric disorders were measured through registers. For women, the overall pattern showed that drinking above the sensible limits increased the risk of psychiatric disorders in general, especially for anxiety disorders where women drinking above the sensible drinking limits had a risk of 2.00 (confidence interval: 1.31-3.04) compared to women drinking below the sensible drinking limits. For men, the risk functions were slightly U-shaped; thus, a weekly low or moderate alcohol intake seemed to have a protective effect towards developing psychiatric disorders. The findings suggest sex differences in the association between alcohol consumption and risk of psychiatric disorders.


[Anatomical and physiological bases of labor onset].
The induction of labor involves a series of complex mechanisms, the control of which is only partially explained in humans. It is accepted today that the maturing of the uterine cervix is independent of the onset of uterine contractions. These two phenomena are regulated by a complex system where prostaglandins play a key role.


[Various aspects of amino acid metabolism in humans exposed to 120-day anti-orthostatic hypokinesia].
The free amino acid pool of blood of man exposed to 120-day head-down tilt (at -4 degrees) was examined. Beginning with bed rest day 28 and till the end of the study, the amino acid pool increased. The increase involved most free amino acids which was produced by a decline of anabolic and stimulation of catabolic processes during hypokinesia.


Debulking the tricuspid valve with FlowTriever aspiration: A case series.
Intracardiac masses adhering to the tricuspid valve can occur as a result of right-sided infective endocarditis, malignancy, clot formation in the right atrium, or clots-in-transit passing through the right atrium. Early surgical intervention is recommended for tricuspid valve vegetation in some patients, although open heart surgery is not always an option. Treatment options for right heart thrombi include anticoagulation, thrombolysis, surgical embolectomy, or mechanical aspiration. We present a case series of tricuspid valve debulking using aspiration with the FlowTriever System.


Partial or entire: Distinct responses of two types of chloroplast autophagy.
Autophagy carries out intracellular degradation of cytoplasmic components, which is important for the removal of dysfunctional organelles and for efficient nutrient recycling in eukaryotic cells. Most proteins in plant green tissues are found in chloroplasts, mainly as photosynthetic proteins that constantly accumulate damage caused by sunlight. Our recent study investigated the involvement of autophagy in the turnover of damaged chloroplasts and found that entire photodamaged chloroplasts are transported into the vacuole for degradation via an autophagy process termed chlorophagy. Our previous studies also established that autophagy can also degrade chloroplast components piecemeal: chloroplast stroma is transported for degradation via autophagy vesicles termed Rubisco-containing bodies (RCB). During sugar starvation-induced senescence in darkened leaves, the RCB pathway is preferentially active. By contrast, we observed active chlorophagy without prior induction of RCB production in photodamaged leaves. These distinct responses between the RCB pathway and chlorophagy support the notion that the induction of the partial-type and entire-organelle-type chloroplast autophagy are differentially regulated by individual upstream molecules. This finding further suggests that the two types of autophagy are coordinated to achieve the controlled chloroplast turnover in response to specific conditions.


Characterization of Chinese hamster ovary cells stably transformed by a plasmid with an inducible APRT gene.
A plasmid was constructed by fusion of a selectable mammalian gene, hamster adenine phosphoribosyltransferase (APRT), to the Zn(2+)-inducible sheep metallothionein I (MT I) promoter. This plasmid was used to produce stable Chinese hamster ovary (CHO) cell transformants by electroporation to study the effects of induced gene expression on DNA-mediated transformation. The sheep MT Ia promoter was chosen for these experiments because it regulates gene expression differently than murine MT promoters, exhibiting low basal levels of gene expression in uninduced conditions. We have shown that in the absence of Zn2+, there is very low expression of a sheep MT I-APRT fusion gene in stable CHO cells transformants; induction of APRT mRNA and enzyme activity by Zn2+ produced a "threshold" response, from low basal levels to high induced levels, in Zn2+ responsive stable transformant clones. In electroporation experiments, transformation frequencies were unaffected by Zn2+ treatments during a preselection period, but the presence of Zn2+ during selection increased the recovery of stable transformant clones 8- to 10-fold. All stable transformants analyzed displayed Zn(2+)-inducible APRT enzyme activity. Our results indicate that stable mammalian cell transformants with inducible genes under regulation of the sheep MT I promoter should be useful, because of low basal and high induced expression, for studies in which modulation of transcriptional activity is required.


Recent Advances in Mycotoxin Determination for Food Monitoring via Microchip.
Mycotoxins are one of the main factors impacting food safety. Mycotoxin contamination has threatened the health of humans and animals. Conventional methods for the detection of mycotoxins are gas chromatography (GC) or liquid chromatography (LC) coupled with mass spectrometry (MS), or enzyme-linked immunosorbent assay (ELISA). However, all these methods are time-consuming, require large-scale instruments and skilled technicians, and consume large amounts of hazardous regents and solvents. Interestingly, a microchip requires less sample consumption and short analysis time, and can realize the integration, miniaturization, and high-throughput detection of the samples. Hence, the application of a microchip for the detection of mycotoxins can make up for the deficiency of the conventional detection methods. This review focuses on the application of a microchip to detect mycotoxins in foods. The toxicities of mycotoxins and the materials of the microchip are firstly summarized in turn. Then the application of a microchip that integrates various kinds of detection methods (optical, electrochemical, photo-electrochemical, and label-free detection) to detect mycotoxins is reviewed in detail. Finally, challenges and future research directions in the development of a microchip to detect mycotoxins are previewed.


Interactions of gephyrotoxin with the acetylcholine receptor-ionic channel complex. I. Blockade of the ionic channel.
The novel tricyclic alkaloid, gephyrotoxin ( GyTX ), found in the skin secretions of the frog Dendrobates histrionicus , potentiates and blocks the indirectly elicited muscle twitch in a concentration-dependent manner. GyTX prolongs the falling phase of the muscle action potential and decreases delayed rectification, supporting the idea that the alkaloid blocks the voltage-sensitive potassium conductance of the electrically excitable membrane. The peak amplitude of the end-plate currents (EPC) and miniature end-plate currents ( MEPC ) were depressed, but no significant deviation from linearity relative to control was seen in the current-voltage relationship. The decay time constant of the EPC (tau EPC) was markedly shortened by GyTX , the effect being greater at 10 degrees than at 22 degrees. The relationship between the log of tau EPC and membrane potential disclosed a linear relationship at all concentrations tested, but a progressive loss of voltage sensitivity of tau EPC was seen when GyTX concentrations were increased. Also, the plot of 1/tau EPC against GyTX concentration revealed a linear relationship. The lack of voltage and time dependence suggests that GyTX has little effect on the ACh receptor-ionic channel complex in the closed conformation. Single-channel conductance studied by means of fluctuation analysis did not change after GyTX application, but the channel lifetime decreased by about 40% at clamp potentials of -105 mV and at a toxin concentration of 7.5 microM. Repetitive nerve stimulation led to a pronounced " rundown " in the EPCs which was frequency-dependent. These findings were taken as evidence that GyTX interacts with the acetylcholine receptor complex, causing a blockade of its channel mainly in the open conformation.


Cardiac troponins in patients with chronic kidney disease and kidney transplant recipients without acute cardiac symptoms.
Cardiovascular diseases are the most common causes of death in chronic kidney disease (CKD) and kidney transplant patients. This study aimed to evaluate cardiac troponins in transplant recipients and CKD patients without cardiac symptoms. Two groups of patients (CKD and kidney transplant recipients) were evaluated for troponins T and I levels. These values were associated with renal replacement therapy and demographic and clinical characteristics of the patients. Eighty CKD patients and 80 kidney transplant recipients were studied. There was a significant difference in Troponins T and I levels were significantly higher in the CKD group than in the transplant recipients. In the CKD group, 14 patients (17.5%) had an elevated troponin T level and 8 (10.0%) had an elevated troponin I, all of whom were in stage 4 of CKD. None of the kidney transplant patients had a positive troponin. Among CKD patients, decreased glomerular filtration rate was associated with elevated troponin I level. Elevated troponin T level was significantly associated with age and decreased glomerular filtration rate. In multivariable analysis, significant associations were found between troponin T level and age, serum creatinine, and glomerular filtration rate. A significant relationship was also found between troponin I and cholesterol and glomerular filtration rate. The assessment of troponin T and I in CKD and kidney transplant patients shows that in patients with CKD and without any symptoms of acute coronary syndrome, serum level of cardiac troponins increase and it is linked to serum creatinine and GFR.


Comparative transcriptomics in Syllidae (Annelida) indicates that posterior regeneration and regular growth are comparable, while anterior regeneration is a distinct process.
Annelids exhibit remarkable postembryonic developmental abilities. Most annelids grow during their whole life by adding segments through the action of a segment addition zone (SAZ) located in front of the pygidium. In addition, they show an outstanding ability to regenerate their bodies. Experimental evidence and field observations show that many annelids are able to regenerate their posterior bodies, while anterior regeneration is often limited or absent. Syllidae, for instance, usually show high abilities of posterior regeneration, although anterior regeneration varies across species. Some syllids are able to partially restore the anterior end, while others regenerate all lost anterior body after bisection. Here, we used comparative transcriptomics to detect changes in the gene expression profiles during anterior regeneration, posterior regeneration and regular growth of two syllid species: Sphaerosyllis hystrix and Syllis gracilis; which exhibit limited and complete anterior regeneration, respectively. We detected a high number of genes with differential expression: 4771 genes in S. hystrix (limited anterior regeneration) and 1997 genes in S. gracilis (complete anterior regeneration). For both species, the comparative transcriptomic analysis showed that gene expression during posterior regeneration and regular growth was very similar, whereas anterior regeneration was characterized by up-regulation of several genes. Among the up-regulated genes, we identified putative homologs of regeneration-related genes associated to cellular proliferation, nervous system development, establishment of body axis, and stem-cellness; such as rup and JNK (in S. hystrix); and glutamine synthetase, elav, slit, Hox genes, β-catenin and PL10 (in S. gracilis). Posterior regeneration and regular growth show no significant differences in gene expression in the herein investigated syllids. However, anterior regeneration is associated with a clear change in terms of gene expression in both species. Our comparative transcriptomic analysis was able to detect differential expression of some regeneration-related genes, suggesting that syllids share some features of the regenerative mechanisms already known for other annelids and invertebrates.


A retrospective cohort study on the risk of stroke in relation to a priori health knowledge level among people with type 2 diabetes mellitus in Taiwan.
Intervention of diabetes care education with regular laboratory check-up in outpatient visits showed long-term benefits to reduce the risk of macrovascular complications among people with type 2 diabetes. However, research on the level of a priori health knowledge to the prevention of diabetic complications in community settings has been scarce. We therefore aimed to investigate the association of health knowledge and stroke incidence in patients with type 2 diabetes in Taiwan. A nationally representative sample of general Taiwanese population was selected using a multistage systematic sampling process from Taiwan National Health Interview Survey (NHIS) in 2005. Subjects were interviewed by a standardized face-to-face questionnaire in the survey, obtaining information of demographics, socioeconomic status, family medical history, obesity, health behaviors, and 15-item health knowledge assessment. The NHIS dataset was linked to Taiwan National Health Insurance claims data to retrieve the diagnosis of type 2 diabetes in NHIS participants at baseline and identify follow-up incidence of stroke from 2005 to 2013. Univariate and multivariate Cox regressions were used to estimate the effect of baseline health knowledge level to the risk of stroke incidence among this group of people with type 2 diabetes. A total of 597 diabetic patients with a mean age of 51.28 years old and nearly half of males were analyzed. During the 9-year follow-up period, 65 new stroke cases were identified among them. Kaplan-Meier curves comparing the three groups of low/moderate/high knowledge levels revealed a statistical significance (p-value of log-rank test <0.01). After controlling for potential confounders, comparing to the group of low health knowledge level, the relative risk of stroke was significantly lower for those with moderate (adjusted hazard ratio [AHR] = 0.63; 95% CI, 0.33-1.19; p-value = 0.15) and high level of health knowledge (AHR = 0.43; 95% CI, 0.22-0.86; p-value = 0.02), with a significant linear trend (p-value = 0.02). An exposure-response gradient of moderate to high health knowledge levels to the prevention of stroke incidence among people with type 2 diabetes in community was found with 9 years of follow-up in Taiwan. Development and delivery of health education on stroke prevention to people with type 2 diabetes are warranted.


High performance of membrane capacitive deionization with ZnS/g-C3N4 composite electrodes.
Capacitive deionization (CDI) is considered a promising technology for desalination of sea or brackish water. In this study, a ZnS/g-C3N4 composite was synthesized through a one-step high-temperature method and used as the main material to fabricate CDI electrodes. The results of SEM and TEM showed that spherical-like nanoparticles of ZnS were uniformly distributed on the g-C3N4 sheet. The g-C3N4 phase facilitates the ZnS particles precipitate and restrain their agglomeration, which contributes to a high specific surface area of ZnS. Furthermore, the electrochemical test results indicated that ZnS/g-C3N4 composite had a good capacitance characteristic, low resistance, and high electrochemical stability. Finally, the desalinization performance of the ZnS/g-C3N4 composite electrodes was tested in traditional mode and membrane capacitive deionization (MCDI) mode. The results showed that ZnS/g-C3N4//ZnS/g-C3N4 (MCDI) exhibited an optimal desalination capacity. The adsorption amount was 27.65, 50.26, and 65.34 mg/g for NaCl initial concentration of 200, 400, and 600 mg/L, respectively, with the voltage of 1.2 V and flow rate of 5 mL/min. Increasing initial concentration enhanced the conductivity and ion migration rate so as to increase the NaCl adsorption amount. ZnS/g-C3N4 composite can be used as potential electrode material for high performance of MCDI.