Surveillance of Charadriiformes in northern Australia shows species variations in exposure to avian influenza virus and suggests negligible virus prevalence.
The virologic surveillance of 4248 Charadriiformes since 1992 primarily from coastal northwest Australia did not detect any evidence of avian influenza virus (AIV) excretion (test prevalence = 0%; 95% confidence interval [CI]: 0%-0.09%). Past exposure to AIV was evident from serologic testing using nucleoprotein (NP) competitive-ELISA (c-ELISA) with an overall seroprevalence of 8.8% (95% CI: 8%-9.7%). The c-ELISA seroprevalence of family Scolopacidae and genus Numenius was significantly higher when compared with other families and genera, respectively. Exposure risk profiles, based on c-ELISA seroprevalence, were compiled for 40 species with the following species having significantly higher values when compared with the combined value of all other species: eastern curlew (Numenius madagascariensis), whimbrel (Numenius phaeopus), ruddy turnstone (Arenaria interpres), grey plover (Pluvialis squatarola), little curlew (Numenius minutus), red knot (Calidris canutus), sharp-tailed sandpiper (Calidris acuminata), and red-necked stint (Calidris ruficollis). From hemagglutination inhibition (HI) testing, the more prevalent HI reactions were against H2, H5, H6, and H9 subtypes, with no reactions against subtypes H11, H14, H15, and H16. Serologic testing using c-ELISA provided species risk profiles for optimizing a surveillance strategy for AIV in diverse populations of wild birds. The paucity of knowledge about the role of waders in the ecology of AIV and the overall very low to negligible virus prevalence reported globally, and in this study, suggests that waders are spillover hosts in shared ecosystems with a lesser role than previously considered.


[HL-A antigens in bronchogenic carcinoma].
A decrease in the frequency of HLA-A2 was noticed in 37 bronchogenic carcinoma patients studied. HLA-B8 was found to be increased in the prolonged survivors of bronchogenic carcinoma.


Validity and usefulness of the short form of the Drinking Motives Questionnaire Revised (DMQ-R SF) among patients with schizophrenia.
Drinking motives are considered to be major predictors of alcohol consumption and alcohol-related problems. However, these motives have been poorly investigated in patients with schizophrenia. The aim of the present study among patients with schizophrenia was twofold: 1) assess the validity of the short form of the Drinking Motives Questionnaire-Revised (DMQ-R SF); and 2) investigate the relationship between drinking motives and comorbid alcohol use disorder (AUD). A total of 179 patients with schizophrenia were approached to participate in the study. DSM-5 criteria were used to identify patients with comorbid AUD (AUD+; n = 42) and non-abstainers patients without comorbid AUD (AUD-; n = 71). A confirmatory factor analysis conducted on items of the DMQ-R SF for the whole sample revealed adequate goodness-of-fit values, while internal consistency indices were globally satisfactory. Group comparisons revealed higher use of alcohol and other substances, as well as stronger drinking motives among AUD + patients, while groups were comparable concerning clinical features of schizophrenia, including psychotic symptom dimensions and severity. Regression analysis showed that the Alcohol Use Disorder Identification Test score was significantly associated with two internal drinking motives: enhancement and coping. Findings suggest that the DMQ-R SF is a reliable tool for assessing drinking motives among patients with schizophrenia. Enhancement and coping motives seem to play a major role in comorbid AUD among these patients. Community-based and clinical treatment programs should take the drinking motives of dual-diagnosis patients into consideration, in order to improve their outcomes.


Benign afebrile convulsions in the course of mild acute gastroenteritis: a study of 28 patients and a literature review.
Since the description of afebrile convulsions in the course of mild acute gastroenteritis (AGE) in 1982 by Morooka in Japan, there have been few reports of further cases outside Asia. The aim of this study was to share our casuistry--from a non-Asian country. This is a retrospective study of identified cases in our center from January 2002 to December 2007. A total of 28 patients were studied. All were previously healthy patients who experienced convulsions with mild AGE without dehydration and with normal blood analysis. The mean age was 17.25 months (range, 6-48 months), with 93% younger than 24 months. Seizures were generalized tonic-clonic (61%), followed by generalized tonic (31%), and hypotonic (5.2%), with 2 (2.6%) partial. Only 8 patients (28.6%) presented one convulsion, and in 13 patients (46%), the seizures were in clusters from 3 to 6. Eleven patients (39%) presented 2 different types of convulsion. The duration of the crises ranged from 30 seconds to 10 minutes, and all of them occurred within 24 hours of the first. Electroencephalograms, obtained for all patients, were normal. Rotavirus was the main infectious agent in the AGEs, found in 11 patients with 22 determinations. In one patient, Salmonella serotype Enteritidis was isolated. All of the patients developed favorably, with no sequelae or epilepsy during the follow-up period. Afebrile convulsion in the course of mild gastroenteritis exists in our environment. It is a banal symptom in the course of the disease with good prognosis. Recognition of this fact may help avoid needless explorations and treatment in patients of this kind.


An animal model for studying the pathogenesis of chikungunya virus infection.
Newborn and 14-day-old mice inoculated subcutaneously with chikungunya virus (CHIKV) developed lethargy, difficulty walking, dragging of hind limbs, and reduced weight gain within 7-10 days after infection (PI). During the initial 6-7 days PI, the animals had viremia; high levels (10(6)-10(8) PFU) of CHIKV were also present in leg muscle. The virus persisted in muscle for several days after viremia disappeared. The major histopathologic changes were in skeletal muscle, which were focal necrosis and inflammation, followed by fibrosis and dystrophic calcification. Some mice also showed dystrophic calcification in the joint cartilage, but there were few deaths, and most of the animals eventually recovered. CHIKV antigen was shown by immunohistochemistry in the muscle for several weeks after infection. Based on the clinical and pathologic similarities with CHIKV infection in humans, young ICR and CD-1 mice offer a useful and realistic model for further study of the pathogenesis and treatment of CHIKV infection.


Metabolism of aceclofenac in humans.
Metabolism of the new nonsteroidal antiinflammatory drug aceclofenac ([2-(2',6'-dichlorophenylamino)phenyl]acetoxyacetic acid) was investigated both in the in vitro hepatic human models and in vivo. Aceclofenac is metabolized in human hepatocytes and human microsomes to form [2-(2',6'-dichloro-4'-hydroxy- phenylamino)phenyl]acetoxyacetic acid as the major metabolite, which is then further conjugated. Minor metabolites were [2-(2',6'-dichlorophenylamino)-5-hydroxyphenyl]acetoxyacetic acid and [2-(2',6'-dichlorophenylamino)phenyl]acetic acid, as well as the hydroxylated derivatives [2-(2',6'-dichloro-4'- hydroxyphenylamino)phenyl]acetic acid and [2-(2',6'-dichlorophenylamino)- 5-hydroxyphenyl]acetic acid. After oral administration to human volunteers (100 mg, single dose), aceclofenac reached a Cmax value of 7.6 +/- 1.3 micrograms/ml and a tmax of 2.6 +/- 1.8. The same metabolites as those detected in cell culture or microsome incubations were found in 12-hr urine after an oral administration of 100 mg aceclofenac to human volunteers. Cytochrome 2C9 is the enzyme responsible for the hydroxylation at position 4'. This could be demonstrated by: 1) selective inhibition by sulfaphenazole; 2) correlation between the formation of the hydroxylated metabolite and tolbutamide hydroxylase activity; and 3) formation of this metabolite only when incubated with microsomes obtained from cells expressing human cytochrome 2C9. However, no conclusive information could be obtained concerning the cytochrome catalyzing the hydroxylation at position 5. The comparison between human microsomes and human hepatocytes metabolism on one hand, and human in vivo metabolism on the other, supports human hepatocytes in primary culture as the model that best anticipated the metabolism of the drug in vivo.


NaCl deposition in the vestibule: a simple, safe, and effective method of cochleovestibular deafferentation.
Chemical cochleovestibular deafferentation was performed on 21 individuals suffering from disabling vertigo caused by unilateral Menière's disease. Patients ranged in age from 31 to 60 years, with a mean age of 47.4. The duration of the disease spanned 3 to 14 years, mean duration being 5.8 years. Subjects displayed pure-tone thresholds higher than 50 dB HL in the affected ear and better than 25 dB HL in the contralateral ear. The frequency of vertigo, evaluated during the 6 months before surgery, ranged from 1 crisis a month to 2 a week; mean duration of crises was 1 to 6 hours. Medical treatment had failed in all cases. The surgical procedure consisted of stapedectomy, deposition of several crystals of NaCl in the vestibule, and sealing of the oval window with a vein graft. Postoperative recovery was rapid, allowing patients to be discharged 4 to 6 days after surgery. All subjects reported complete relief of vertigo. Tinnitus disappeared in 47.6% of the subjects, was reduced in 33.3% and unchanged in 19.1%. Most patients complaining of aural fullness preoperatively reported relief of this symptom after surgery. The outcomes of the present study indicate that NaCl deposition into the vestibule is a simple, safe, and effective technique of cochleovestibular deafferentation.


Molecular signatures to improve diagnosis in peripheral T-cell lymphoma and prognostication in angioimmunoblastic T-cell lymphoma.
Peripheral T-cell lymphoma (PTCL) is often challenging to diagnose and classify. Gene expression profiling was performed on 144 cases of PTCL and natural killer cell lymphoma and robust molecular classifiers were constructed for angioimmunoblastic T-cell lymphoma (AITL), anaplastic lymphoma kinase-positive (ALK(+)) anaplastic large-cell lymphoma (ALCL), and adult T-cell leukemia/lymphoma. PTCL-unclassifiable was molecularly heterogeneous, but we were able to identify a molecular subgroup with features of cytotoxic T lymphocytes and a poor survival compared with the remaining PTCL-not otherwise specified cases. Many of the pathologic features and substantial components of the molecular signature of AITL are contributed by the follicular dendritic cells, B-cell, and other stromal components. The expression of Th17-associated molecules in ALK(+) ALCL was noted and may represent aberrant activation of Th17-cell differentiation by abnormal cytokine secretion. Adult T-cell leukemia/lymphoma has a homogeneous molecular signature demonstrating high expression of human T-lymphotropic virus type 1-induced genes. These classifiers reflect the biology of the tumor cells as well as their microenvironment. We also constructed a molecular prognosticator for AITL that appears to be largely related to the microenvironmental signature, and the high expression of 2 immunosuppressive signatures are associated with poor outcome. Oncogenic pathways and tumor-host interactions also were identified, and these findings may lead to better therapies and outcome in the future.


Coronary flow in neonates with impaired intrauterine growth.
Subclinical myocardial injury has been reported in newborns with fetal weights < 2 SDs for gestational age. Intrauterine growth restriction might affect cardiac function and coronary flow (CF). Seventeen newborns with intrauterine growth restriction and 15 age-matched healthy controls were enrolled in the study. Blood flow in the umbilical artery and maternal uterine artery was assessed using Doppler velocimetry. Cardiac function and left anterior descending coronary artery CF were measured using transthoracic Doppler echocardiography at 1 week of age. The mean growth deviation of the newborns from normal was -2.5 ± 0.2 SDs. Percentage left ventricular shortening fraction was 39 ± 4.3% in patients and 42 ± 4.1% in controls (P = .40), and the mean left ventricular mass index was 86.6 g/m(2) in patients and 73.7 g/m(2) in controls (P < .01). The mean left anterior descending coronary artery diameter was 0.99 ± 0.1 mm in patients and 0.8 ± 0.1 mm in controls (P = .002). The left anterior descending coronary artery flow velocity-time integral was correlated with left ventricular mass index (r = 0.31, P = .007) and with mitral peak E/A ratio (r = 0.74, P = .01). Intrauterine growth restriction was associated with increased peak flow velocity in diastole (34.5 ± 4 vs 19 ± 6 cm/sec in controls, P = .0001), as well as increased CF (37 ± 7.3 vs 8.2 ± 3.0 mL/min in controls, P = .001). CF is significantly increased in neonates with impaired intrauterine growth. Left ventricular mass index is increased, but systolic and diastolic function remains normal. The clinical significance of increased CF is unclear, but it might lead to decreased CF reserve.


Intra-individual plasticity of the TAZ gene leading to different heritable mutations in siblings with Barth syndrome.
Infantile-onset skeletal myopathy Barth syndrome (OMIM #302060) is caused by mutations in the X-linked TAZ gene and hence usually manifests itself only in hemizygous males. Confirmatory testing is provided by mutational analysis of the TAZ gene and/or by biochemical dosage of the monolysocardiolipin/tetralinoleoyl cardiolipin ratio. Heterozygous females do not usually display a clinical phenotype but may undergo molecular genetic prenatal diagnosis during pregnancy. We characterized two novel and non-identical TAZ gene rearrangements in the offspring of a single female carrier of Barth syndrome. The hg19chrX:g.153634427_153644361delinsKP_123427.1 TAZ gene rearrangement was identified in her affected son, whereas the NM_000116.3(TAZ)c.-72_109+51del TAZ gene deletion was identified in a male foetus during a subsequent pregnancy. The unaffected mother was surprisingly found to harbour both variants in addition to a wild-type TAZ allele. A combination of breakpoint junction sequencing, linkage analysis and assessment of allelic dosage revealed that the two variants had originated independently from an apparently unstable/mutable TAZ maternal allele albeit via different mutational mechanisms. We conclude that molecular prenatal diagnosis in Barth syndrome families with probands carrying TAZ gene rearrangements should include investigation of the entire coding region of the TAZ gene. The identification of the breakpoint junctions of such gross gene rearrangements is important to ensure accurate ascertainment of carriership with a view to providing appropriate genetic counselling.


SMART tracking: Simultaneous anatomical imaging and real-time passive device tracking for MR-guided interventions.
This study demonstrates a proof of concept of a method for simultaneous anatomical imaging and real-time (SMART) passive device tracking for MR-guided interventions. Phase Correlation template matching was combined with a fast undersampled radial multi-echo acquisition using the white marker phenomenon after the first echo. In this way, the first echo provides anatomical contrast, whereas the other echoes provide white marker contrast to allow accurate device localization using fast simulations and template matching. This approach was tested on tracking of five 0.5 mm steel markers in an agarose phantom and on insertion of an MRI-compatible 20 Gauge titanium needle in ex vivo porcine tissue. The locations of the steel markers were quantitatively compared to the marker locations as found on a CT scan of the same phantom. The average pairwise error between the MRI and CT locations was 0.30 mm for tracking of stationary steel spheres and 0.29 mm during motion. Qualitative evaluation of the tracking of needle insertions showed that tracked positions were stable throughout needle insertion and retraction. The proposed SMART tracking method provided accurate passive tracking of devices at high framerates, inclusion of real-time anatomical scanning, and the capability of automatic slice positioning. Furthermore, the method does not require specialized hardware and could therefore be applied to track any rigid metal device that causes appreciable magnetic field distortions.


Endo- and exovesiculation and the structure of the human red cell membrane.
Experiments were designed to study functional associations of proteins in human red cell membranes as the membranes are induced to undergo the critical membrane events of invagination or evagination followed by constriction and fusion. Three examples were chosen for study: the inside-out vesicle (IOV) produced in white ghosts by hypotonic removal of cytoskeletal proteins; the endocytic vacuole produced in white ghosts by incubation with Mg-adenosine triphosphate; and the exocytic vesicle produced by metabolic depletion of intact red blood cells. The resulting particles were harvested, and analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis for membrane protein content and by enzymic analysis to detect the presence or absence of the exofacial enzyme acetylcholinesterase (ACE), the cytosol facing enzyme glyceraldehyde phosphate dehydrogenase (GAPD), and the integral protein adenosine triphosphatases (ATPases). Each of the vesicles is variably depleted of spectrin and actin, and each retains the exofacial enzyme ACE as well as Mg-ATPase. These findings suggest that there must be local partial depletion of cytoskeletal proteins before invagination or evagination occurs and that in each case part of the exoface of the membrane containing ACE is carried along into the resulting vesicle. The two forms of endocytosis differ with regard to their ATPase content with the energized endocytic vacuole retaining Ca-Mg-ATPase and actin-activated ATPase. The large amount of hemoglobin present in the exocytic vesicle is best explained by trapping of free cytosol and probably reflects a direct interaction of cytosolic components containing hemoglobin with the phospholipid bilayer.


Binding measurements as surrogate biological assays: surface plasmon resonance biosensors for characterizing vaccine components.
There is considerable interest in the possibility of using surrogate physico-chemical assays for the quality control of vaccine components. Since biological activity always depends on a first binding step, the primary criterion for assessing biological activity is the ability of a vaccine component to bind specifically in a binding assay. Biosensor instruments that measure binding kinetics with considerable ease and precision are used increasingly to assess the quality of antigens intended for vaccination as well as the binding affinity of antibodies elicited by vaccination. The most widely used biosensor instrument is the BIACORE and its mode of operation is briefly described. The use of biosensors for measuring the active concentration of biomolecules and for assessing the probable effectiveness of vaccine-induced antibodies is described.


Efficient generation and characterization of spectrally factorable biphotons.
Spectrally unentangled biphotons with high single-spatiotemporal-mode purity are highly desirable for many quantum information processing tasks. We generate biphotons with an inferred heralded-state spectral purity of 99%, the highest to date without any spectral filtering, by pulsed spontaneous parametric downconversion in a custom-fabricated periodically-poled KTiOPO4 crystal under extended Gaussian phase-matching conditions. To efficiently characterize the joint spectral intensity of the generated biphotons at high spectral resolution, we employ a commercially available dispersion compensation module (DCM) with a dispersion equivalent to 100 km of standard optical fiber and with an insertion loss of only 2.8 dB. Compared with the typical method of using two temperature-stabilized equal-length fibers that incurs an insertion loss of 20 dB per fiber, the DCM approach achieves high spectral resolution in a much shorter measurement time. Because the dispersion amount and center wavelengths of DCMs can be easily customized, spectral characterization in a wide range of quantum photonic applications should benefit significantly from this technique.


Personal recovery and socio-structural disadvantage: A critical conceptual review.
Despite its seeming breadth and diversity, the bulk of the personal (mental health) recovery literature has remained strangely 'silent' about the impact of various socio-structural inequalities on the recovery process. Such an inadequacy of the empirical literature is not without consequences since the systematic omission or downplaying, at best, of the socio-structural conditions of living for persons with lived experience of mental health difficulties may inadvertently reinforce a reductionist view of recovery as an atomised, individualised phenomenon. Motivated by those limitations in extant scholarship, a critical literature review was conducted to identify and critique relevant research to problematise the notion of personal recovery in the context of socio-structural disadvantage such as poverty, homelessness, discrimination and inequalities. The review illuminates the scarcity of empirical research and the paucity of sociologically-informed theorisation regarding how recovery is shaped by the socio-structural conditions of living. Those inadequacies are especially pertinent to homelessness research, whereby empirical investigations of personal recovery have remained few and undertheorised. The gaps in the research and theorising about the relational, contextual and socio-structural embeddedness of recovery are distilled. The critical review concludes that personal recovery has remained underresearched, underproblematised and undertheorised, especially in the context of homelessness and other forms of socio-structural disadvantage. Understanding how exclusionary social arrangements affect individuals' recovery, and the coping strategies that they deploy to negotiate those, is likely to inform anti-oppressive interventions that could eventually remove the structural constraints to human emancipation and flourishing.


The association of tissue anti-TNF drug levels with serological and endoscopic disease activity in inflammatory bowel disease: the ATLAS study.
The aim of this study was to assess the correlation between serum and intestinal anti-tumour necrosis factor (TNF) levels, and their relationship to endoscopic disease activity and levels of TNF. Cross-sectional study of 30 patients receiving treatment with infliximab or adalimumab for Crohn's disease or UC. For each patient, a sample of serum was matched to tissue biopsies. Endoscopic and histological disease activity was recorded for each tissue sample. There was a significant positive correlation between anti-TNF in serum and tissue (r=0.3920, p=0.002), especially in uninflamed tissue (r=0.50, p<0.001), but not with those samples that had inflammation (r=0.19, p=0.54). Anti-TNF concentration in tissue correlated with degree of endoscopic inflammation, except for tissue with severe inflammation in which anti-TNF levels were again lower (mean normalised anti-TNF in tissue: uninflamed=0.93, mild=2.17, moderate=13.71, severe=2.2 inflammation (p=0.0042)). The ratio of anti-TNF-to-TNF in tissue was highest in uninflamed areas and lowest in severely inflamed areas. Patients with active mucosal disease had a higher rate of serum to tissue drug level mismatch when compared to those in remission (73.3% vs 33.3%, respectively; p=0.03). Our data suggest that local tissue inflammation characterised by high levels of TNF serves as a sink for anti-TNF. We further postulate that some patients with high serum anti-TNF levels have active disease because tissue levels of anti-TNF are insufficient to neutralise local TNF production.


Poststroke restless legs syndrome and lesion location: anatomical considerations.
Several case studies have reported on restless legs syndrome (RLS) associated with stroke. In this study, we investigated the prevalence and the lesion topography of poststroke RLS. There were 137 patients with ischemic stroke included in this study. The diagnosis of RLS was made 1 month after the index stroke using the criteria established by the International RLS Study Group. All patients enrolled underwent magnetic resonance imaging within 7 days of the onset of the stroke. The prevalence of stroke-related RLS was calculated, and the topography of the associated ischemic lesions was analyzed. Among 137 patients, 17 patients (12.4%) were diagnosed with RLS after a stroke. Stroke-related RLS was found in 10 out of 33 patients with a basal ganglia/corona radiata infarct (30.3%), 1 out of 8 patients with an internal capsular infarct (12.5%), and 1 out of 7 patients with a thalamic infarct (14.3%). In addition, one out of 54 with a cortical lesion with/without subcortical involvement (1.9%), and 4 out of 18 patients with a pontine lesion (22.2%) had RLS. The analysis of the lesions in the cortical and subcortical group showed only 1 patient in the cortical group had stroke-related RLS, whereas 16 in the subcortical group had stroke-related RLS. The results of this study suggest that lesions of the subcortical brain areas such as the pyramidal tract and the basal ganglia-brainstem axis, which are involved in motor functions and sleep-wake cycles, may lead to RLS symptoms in patients after an ischemic stroke.


Properties of erythromycin-inducible transposon Tn917 in Streptococcus faecalis.
Streptococcus faecalis strain DS16 harbors two plasmids, a conjugative plasmid, pAD1, which encodes hemolysin and bacteriocin activities, and a nonconjugative plasmid, pAD2, encoding resistance to streptomycin, kanamycin, and erythromycin, the latter of which is inducible. The erythromycin resistance determinant is located on a 3.3-megadalton transposable element designated Tn917, which could be transposed to pAD1 as well as to two other plasmids, pAm gamma 1 and pAM alpha 1. When strain DS16 was exposed to low (inducing) concentrations of erythromycin for a few hours, the frequency of Tn917 transposition from pAD2 to pAD1 increased by an order of magnitude. This induction paralleled induction of erythromycin resistance and was prevented by exposing the cells to inhibitors of deoxyribonucleic acid, ribonucleic acid or protein synthesis. The exposure of strain DS16 to inducing concentrations of erythromycin also enhanced the frequency of erythromycin-resistant transconjugants appearing during mating. Initially, cointegrate molecules, whose molecular weights were approximately the sum of pAD1 and pAD2, accounted for these transconjugants; however, as the induction time increased, pAD1::Tn917 became increasingly prominent.


Restoration of absolute diffraction efficiency and blaze angle of carbon contaminated gratings by ultraviolet cleaning.
An UV cleaning technique has been used for the removal of carbon contamination from grating surface, using oxygen free-radicals generated by the absorption of UV radiation (172 nm) in atmospheric oxygen. The extent of restoration of absolute diffraction efficiency (ADE) and grating blaze angle of a carbon-contaminated variable line-spaced concave grating (average line spacing of 1200 lines/mm, blaze angle 3.2 deg, and blaze wavelength 10 nm) has been studied over a 5-70 nm wavelength range. The contamination (due to prolonged use in extreme-ultraviolet spectrograph) resulted in a drastic reduction in the diffraction efficiency of grating, along with a change in the blaze angle. The UV cleaning led to the restoration of blaze angle as well as to an increase in the ADE by more than an order of magnitude for the first two diffraction orders (i.e., from ~0.2 to ~7.2%) for the first diffraction order and 0.1 to ~5% for the second diffraction order at the blaze wavelength. The study is useful for the restoration of carbon-contaminated costly optics.


High frequency ultrasound imaging using an active optical detector.
Optical detection of ultrasound has numerous advantages over traditional piezoelectric methods. These systems offer noncontact inspection, rapid scanning capabilities, fine spatial sampling, and large bandwidths. In addition, difficulties associated with conventional ultrasound imaging systems such as cross-talk between elements, electrical connections, and electromechanical resonances are greatly reduced or even eliminated. Because of this, high frequency phased arrays for ultrasound detection can be emulated by accurately positioning and focusing optical beams on a suitable surface, which defines array elements. However, optical systems have lower sensitivity than their piezoelectric counterparts, limiting their widespread use in ultrasound imaging. Active optical detection offers a solution. An active ultrasound detector consisting of a neodymium-doped glass waveguide laser with an optical demodulation system, was built demonstrating enhanced sensitivity while preserving the benefits of traditional passive optical detection.


Recent discovery and development on SARS-CoV-2: A review of current literature.
The origin and spread of current novel coronavirus had raised serious concerns among stakeholders around the globe. Different speculations that may unfold the mystery in the future are taking roots, but now there is no globally acceptable opinion about the origin and spread of this novel coronavirus. It is reported that Wuhan city of Hubei Province of central China was the epicenter of this outbreak of novel coronavirus. However, initial inadequate preventive measures allowed the infection to cross the borders of China and that pulls the world into drastic public health and economic crisis. This coronavirus disease now named as COVID-19 by World Health Organization (WHO) and the responsible coronavirus is named as "severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)." The spread of SARS-CoV-2 is alarming even after 5 months of inception and WHO further warns the world to be prepared for more intense spread of COVID-19. Different diagnostic tools to detect SARS-CoV-2 are being used around the globe, but the identification of asymptomatic carriers of the disease is a serious challenge in countering the COVID-19 pandemic. There is no specific treatment available, only preventive, symptomatic, and supportive treatments are being used for clinical management of COVID-19. The available knowledge is limited, therefore, any escalation of information on the disease will help to combat this global challenge of COVID-19. In this review, we have discussed and summarized the available multi-factorial information and recent updates on the SARS-CoV-2 which can help support future research and may help in the strategic management of the current COVID-19 pandemic. The articles available online before June 30, 2020, on bioRxiv, medRxiv, ChemRxiv, Google Scholar, and PubMed have been assessed for the compilation of this review. Information on the official portal of WHO, CDC, ICMR, etc., were also assessed and used with due credit.


Impact of wheat-Leymus racemosus added chromosomes on wheat adaptation and tolerance to heat stress.
Adaptation of wheat (Triticum aestivum L.) to high temperatures could be improved by introducing alien genes from wild relatives. We evaluated the responses of wheat-Leymus racemosus chromosome introgression lines to high temperature to determine their potentiality for developing improved wheat cultivars. Introgression lines and their parent Chinese Spring were evaluated in a growth chamber at the seedling stage and in the field at the reproductive stage in two heat-stressed environments in Sudan. Optimum and late planting were used to ensure exposure of the plants to heat stress at the reproductive stage. The results revealed the impact of several Leymus chromosomes in improving wheat adaptation and tolerance to heat. Three lines possessed enhanced adaptation, whereas two showed high heat tolerance. Two addition lines showed a large number of kernels per spike, while one possessed high yield potential. Grain yield was correlated negatively with the heat susceptibility index, days to heading and maturity and positively with kernel number per spike and triphenyl tetrazolium chloride assay under late planting. The findings suggest that these genetic stocks could be used as a bridge to introduce the valuable Leymus traits into a superior wheat genetic background, thus helping maximize wheat yield in heat-stressed environments.


Single-nucleus transcriptome sequencing reveals hepatic cell atlas in pigs.
As the largest substantive organ of animals, the liver plays an essential role in the physiological processes of digestive metabolism and immune defense. However, the cellular composition of the pig liver remains poorly understood. This investigation used single-nucleus RNA sequencing technology to identify cell types from liver tissues of pigs, providing a theoretical basis for further investigating liver cell types in pigs. The analysis revealed 13 cells clusters which were further identified 7 cell types including endothelial cells, T cells, hepatocytes, Kupffer cells, stellate cells, B cells, and cholangiocytes. The dominant cell types were endothelial cells, T cells and hepatocytes in the liver tissue of Dahe pigs and Dahe black pigs, which accounts for about 85.76% and 82.74%, respectively. The number of endothelial cells was higher in the liver tissue of Dahe pigs compared to Dahe black pigs, while the opposite tendency was observed for T cells. Moreover, functional enrichment analysis demonstrated that the differentially expressed genes in pig hepatic endothelial cells were significantly enriched in the protein processing in endoplasmic reticulum, MAPK signaling pathway, and FoxO signaling pathway. Functional enrichment analysis demonstrated that the differentially expressed genes in pig hepatic T cells were significantly enriched in the thyroid hormone signaling pathway, B cell receptor signaling pathway, and focal adhesion. Functional enrichment analysis demonstrated that the differentially expressed genes in pig hepatic hepatocytes were significantly enriched in the metabolic pathways. In summary, this study provides a comprehensive cell atlas of porcine hepatic tissue. The number, gene expression level and functional characteristics of each cell type in pig liver tissue varied between breeds.


Plant Actin-Depolymerizing Factors Possess Opposing Biochemical Properties Arising from Key Amino Acid Changes throughout Evolution.
Functional divergence in paralogs is an important genetic source of evolutionary innovation. Actin-depolymerizing factors (ADFs) are among the most important actin binding proteins and are involved in generating and remodeling actin cytoskeletal architecture via their conserved F-actin severing or depolymerizing activity. In plants, ADFs coevolved with actin, but their biochemical properties are diverse. Unfortunately, the biochemical function of most plant ADFs and the potential mechanisms of their functional divergence remain unclear. Here, in vitro biochemical analyses demonstrated that all 11 ADF genes in Arabidopsis thaliana exhibit opposing biochemical properties. Subclass III ADFs evolved F-actin bundling (B-type) function from conserved F-actin depolymerizing (D-type) function, and subclass I ADFs have enhanced D-type function. By tracking historical mutation sites on ancestral proteins, several fundamental amino acid residues affecting the biochemical functions of these proteins were identified in Arabidopsis and various plants, suggesting that the biochemical divergence of ADFs has been conserved during the evolution of angiosperm plants. Importantly, N-terminal extensions on subclass III ADFs that arose from intron-sliding events are indispensable for the alteration of D-type to B-type function. We conclude that the evolution of these N-terminal extensions and several conserved mutations produced the diverse biochemical functions of plant ADFs from a putative ancestor.


Uneven frequency of Vibrio alginolyticus-group isolates among different populations of Galápagos marine iguana (Amblyrhynchus cristatus).
The presence of Vibrio isolates was investigated in cloacal swabs from the Galápagos marine iguana (Amblyrhyncus cristatus). Such unique iguana is endemic to the Galápagos Archipelago, it is listed as vulnerable in the IUCN Red List (2009), and is strictly protected by CITES and Ecuador laws. Our results revealed an uneven isolation frequency of vibrios from animals living in different settings: maximal among the Santa Fe population, scarce at Bahía Tortuga but practically absent in the samples from Puerto Ayora and Plaza Sur. A 16S sequencing confirmed that the isolates belonged to the genus Vibrio, placing them within the V. alginolyticus group; the biochemical identification was, indeed, consistent with V. alginolyticus features. The reason of the observed discrepancy is not clear, but could be either linked to a higher pollution in the inhabited or more touristic places or to differential influence of chemical and physical parameters at a local scale. As V. alginolyticus is an opportunistic pathogen for man and it is known to cause disease in sea-living animals, the ability of these vibrios to enter and persist to a certain extent in the marine iguana gut should be regarded as a risk for health of both the animals and the human personnel involved in monitoring activities.


Situational anxiety in head and neck cancer: Rates, patterns and clinical management interventions in a regional cancer setting.
Research indicates that the immobilisation mask required for radiation therapy (RT) for head and neck cancers can provoke intense anxiety. However, little is known about the rates of this anxiety, whether it changes over a course of treatment and how it is managed in clinical practice. This study aimed to describe the rates and patterns of situational anxiety in patients undergoing RT for head and neck cancer and the use of anxiety management interventions in current clinical practice in a major regional cancer setting in New South Wales, Australia. Situational anxiety rates and patterns were assessed at five time points using the State-Trait Anxiety Inventory prior to treatment planning (SIM), the first three treatment sessions (Tx 1, Tx 2 and Tx 3) and treatment 20 (Tx 20). Sessions were observed to record the use of general supportive interventions (music and support person) and anxiety-specific interventions (break from the mask, relaxation techniques and anxiolytic medication). Sociodemographic and clinical information was extracted from the medical record. One hundred and one patients were recruited. One-third had clinically significant anxiety at any of the first three time points (33.3-40%), and a quarter at Tx 3 (26.4%) and Tx 20 (23.4%). Of the sample, 55.4% had available data for categorisation into one of four pattern groups: 'No Anxiety' (46.4%); 'Decreasing Anxiety' (35.7%); 'Increasing Anxiety' (7.1%); and 'Stable High Anxiety' (10.7%). Most participants had social support present at SIM (53.5%) and listened to music during treatment (86.7-92.9%). Few participants received relaxation techniques alone (1.2-2.3%). Anxiolytic medication was provided for 10% of patients at some stage during the treatment journey and 5% required a break from the mask at SIM, with frequency decreasing throughout the treatment course. In this regional cancer setting, situational anxiety was common, but generally decreased throughout treatment. Some patients experience persistent or increasing anxiety, with up to 10% of patients receiving specific anxiety management interventions.


Dynamics of renal histamine in normal rat kidney and in nephrosis induced by aminonucleoside of puromycin.
Histamine is known to have a profound effect on capillary permeability in nonrenal tissues and this effect is presumably mediated by cyclic (c)AMP. Because in our previous experiments we found that histamine stimulates cAMP accumulation in glomeruli (Torres, V. E., T. E. Northryn, R. M. Edwards, S. V. Shah, and T. P. Dousa. 1978. Modulation of cyclic nucleotides in isolated rat glomeruli. J. Clin. Invest.62: 1334.), we now explored whether this amine is formed in renal tissue, namely in glomeruli, and whether its renal metabolism is altered in experimental nephrosis induced by puromycin aminonucleoside (PA) in rats. In normal rats, histamine content was higher (Delta + 240%) in cortex than in medulla. In glomeruli isolated from renal cortex, histamine content was significantly higher (Delta + 260%) than in tubules. Incubation of isolated glomeruli with l-histidine resulted in a time-dependent increase of histamine content in glomeruli, but no change was found in tubules. The increase in glomerular histamine was blocked by the histidine decarboxylase inhibitor bromocresine. In rats with PA nephrosis induced by a single intraperitoneal injection of PA (15 mg/100 g body wt) urinary excretion of histamine was markedly increased (>Delta + 200%), but control rats did not differ from rats with PA nephrosis in urinary excretions of l-histidine and of creatinine. At the peak of proteinuria (day 9 after injection of PA) the plasma level of histamine was slightly elevated, and plasma histidine slightly decreased in animals that developed PA nephrosis. The content of histamine was markedly higher and the level of histidine was significantly lower in the renal cortex of PA-nephrotic rats as compared with controls; PA-nephrotic and control rats did not differ in the content of histidine and histamine in the liver. In addition, the content of histamine was higher in glomeruli isolated from PA-nephrotic rats; lesser difference was found in cortical tubules. The results further indicate that PA-nephrotic rats have higher content of histamine in the renal cortex, predominently in glomeruli with increased urinary histamine excretion. The elevated renal cortical histamine is not due to higher availability of histamine precursor l-histidine. Results thus show that glomeruli are a major site of intrarenal histamine synthesis and accumulation, and also suggest that abnormal renal metabolism of this amine in PA nephrosis may be related, as a cause or as a consequence, to the pathogenesis of this disease.


Continuing Versus New Prescriptions for Sedative-Hypnotic Medications: United States, 2005-2012.
To assess trends in continuing and new prescriptions for sedative-hypnotic medications, including benzodiazepines (BZDs) and non-BZD receptor agonists (nBZRAs). Data came from the National Ambulatory Medical Care Survey and comprised 287 288 randomly sampled patient visits. Physicians reported medications prescribed and whether they were "continuing" or "new" prescriptions. We assessed trends in continuing BZD, new BZD, continuing nBZRA, and new nBZRA prescriptions from 2005 to 2012. Proportions of visits with continuing prescriptions increased from 3.4% in 2005 to 4.7% in 2012 (P < .01) for BZDs, and from 1.0% to 1.7% (P < .01) for nBZRAs. We noted no changes in new prescriptions. We observed the same patterns across patient age and physician specialties, except psychiatry. Despite no growth over time, the prevalence of visits involving continuing and new BZD and nBZRA prescriptions was much higher in psychiatry than in primary care and other specialties. Increased sedative-hypnotic prescribing in recent years may be attributable to long-term growth in continuing prescriptions, rather than new prescriptions. Public Health Implications. Findings call for renewed efforts to limit continuing prescribing of sedative-hypnotics to reduce their use in the population.


Kidney transplant program waitlisting rate as a metric to assess transplant access.
Kidney transplant program performance in the United States is commonly measured by posttransplant outcomes. Inclusion of pretransplant measures could provide a more comprehensive assessment of transplant program performance and necessary information for patient decision-making. In this study, we propose a new metric, the waitlisting rate, defined as the ratio of patients who are waitlisted in a center relative to the person-years referred for evaluation to a program. Furthermore, we standardize the waitlisting rate relative to the state average in Georgia, North Carolina, and South Carolina. The new metric was used as a proof-of-concept to assess transplant-program access compared to the existing transplant rate metric. The study cohorts were defined by linking 2017 United States Renal Data System (USRDS) data with transplant-program referral data from the Southeastern United States between January 1, 2012 and December 31, 2016. Waitlisting rate varied across the 9 Southeastern transplant programs, ranging from 10 to 22 events per 100 patient-years, whereas the program-specific waitlisting rate ratio ranged between 0.76 and 1.33. Program-specific waitlisting rate ratio was uncorrelated with the transplant rate ratio (r = -.15, 95% CI, -0.83 to 0.57). Findings warrant collection of national data on early transplant steps, such as referral, for a more comprehensive assessment of transplant program performance and pretransplant access.


Comparison of Cognitive Performance on the Cogstate Brief Battery When Taken In-Clinic, In-Group, and Unsupervised.
Repeat cognitive assessment comparing post-injury performance to a pre-injury baseline is common in concussion management. Although post-injury tests are typically administered in clinical settings, baseline tests may be conducted individually with one-on-one supervision, in a group with supervision, or without supervision. The extent to which these different test settings affect cognitive performance is not well understood. To assess if performance on the Cogstate Brief Battery (CBB) differs across these settings, tests completed individually with one-on-one supervision were compared to those taken either in a group with supervision or individually but without supervision. A crossover study design was utilized to account for any effect of individual variability or test order to provide an unbiased examination of the effect of test setting on cognitive performance. Young adult participants completed an individually supervised test either before or after also completing a group or unsupervised test. CBB scores from the same individuals were not significantly different across test settings. Effect sizes ranged in magnitude from .09 to .12 for supervised versus unsupervised tests and from .01 to .37 for individual versus group tests across CBB tasks. These results suggest that cognitive testing with the CBB in alternate settings can provide valid cognitive data comparable to data obtained during individually supervised testing.


Lung function in patients with ankylosing spondylitis. A study of the influence of disease activity and treatment with nonsteroidal antiinflammatory drugs.
Progressive ankylosis of the thoracic skeleton in ankylosing spondylitis (AS) causes restrictive pulmonary function impairment characterized by a reduction in vital capacity (VC). After a wash-out period of 2 weeks, 33 men with active AS were treated with either diflunisal or phenylbutazone according to a double blind randomized design for 12 weeks, followed by an open extension period of 36 weeks. A spirometric study was performed at baseline, Week 12, and Week 48. In the active phase of the disease a correlation was found between VC and chest expansion, whereas neither of these variables was related to the thoracic pain and over-all disease activity. We also found that the VC correlated with the lumbar flexion index, but not with the erythrocyte sedimentation rate or IgA. Although all clinical efficacy variables showed an improvement during treatment with both drugs, no change in VC was found, even in patients with the most restricted ventilatory impairment. We conclude that the VC is not an appropriate variable for the evaluation of short term therapy in AS.


Systemic serotonin inhibits brown adipose tissue sympathetic nerve activity via a GABA input to the dorsomedial hypothalamus, not via 5HT1A receptor activation in raphe pallidus.
Serotonin (5-hydroxytryptamine, 5-HT), an important neurotransmitter and hormone, modulates many physiological functions including body temperature. We investigated neural mechanisms involved in the inhibition of brown adipose tissue (BAT) sympathetic nerve activity (SNA) and BAT thermogenesis evoked by 5-HT. Electrophysiological recordings, intravenous (iv) injections and nanoinjections in the brains of anaesthetized rats. Cooling-evoked increases in BAT SNA were inhibited by the intra-rostral raphé pallidus (rRPa) and the iv administration of the 5-HT1A receptor agonist, 8-OH-DPAT or 5-HT. The intra-rRPa 5-HT, the intra-rRPa and the iv 8-OH-DPAT, but not the iv 5-HT-induced inhibition of BAT SNA were prevented by nanoinjection of a 5-HT1A receptor antagonist in the rRPa. The increase in BAT SNA evoked by nanoinjection of NMDA in the rRPa was not inhibited by iv 5-HT, indicating that iv 5-HT does not inhibit BAT SNA by acting in the rRPa or in the sympathetic pathway distal to the rRPa. In contrast, under a warm condition, blockade of 5HT1A receptors in the rRPa increased BAT SNA and BAT thermogenesis, suggesting that endogenous 5-HT in the rRPa contributes to the suppression of BAT SNA and BAT thermogenesis. The increases in BAT SNA and BAT thermogenesis evoked by nanoinjection of NMDA in the dorsomedial hypothalamus (DMH) were inhibited by iv 5-HT, but those following bicuculline nanoinjection in the DMH were not inhibited. The systemic 5-HT-induced inhibition of BAT SNA requires a GABAergic inhibition of BAT sympathoexcitatory neurones in the DMH. In addition, during warming, 5-HT released endogenously in rRPa inhibits BAT SNA.


Metabolomic study of the soybean pastes fermented by the single species Penicillium glabrum GQ1-3 and Aspergillus oryzae HGPA20.
Penicillium glabrum GQ1-3 and Aspergillus oryzae HGPA20 isolated from home-made soybean pastes were separately inoculated into soybean paste subjected to brine fermentation for 90 days. The amino acid nitrogen contents of the two fermentation systems were detected every 10 days, and both reached the maximum level at 40 days. The samples fermented for 40 days were analyzed via gas chromatography-time of flight mass spectrometry. Using univariate, multivariate and KEGG analyses, 72 differential metabolites were obtained, and 7 metabolic pathways closely related to fermentation were screened. The relative contents of 2-oxoglutarate, ornithine, glutamine, and citrulline were higher in GQ1-3, whereas those of l-homoserine, aspartic acid, and asparagine were higher in HGPA20. These findings indicate that α-ketoglutaric acid-derived amino acid synthesis is preponderant in GQ1-3, whereas oxaloacetate-derived type is predominant in HGPA20. The different pathways of amino acid synthesis lead to the distinct nutrients and umami substances in the fermented soybean pastes.


ARID1A loss activates MAPK signaling via DUSP4 downregulation.
ARID1A, a tumor suppressor gene encoding BAF250, a protein participating in chromatin remodeling, is frequently mutated in endometrium-related malignancies, including ovarian or uterine clear cell carcinoma (CCC) and endometrioid carcinoma (EMCA). However, how ARID1A mutations alter downstream signaling to promote tumor development is yet to be established. We used RNA-sequencing (RNA-seq) to explore transcriptomic changes in isogenic human endometrial epithelial cells after deleting ARID1A. Chromatin immunoprecipitation sequencing (ChIP-seq) was employed to assess the active or repressive histone marks on DUSP4 promoter and regulatory regions. We validated our findings using genetically engineered murine endometroid carcinoma models, human endometroid carcinoma tissues, and in silico approaches. RNA-seq revealed the downregulation of the MAPK phosphatase dual-specificity phosphatase 4 (DUSP4) in ARID1A-deficient cells. ChIP-seq demonstrated decreased histone acetylation marks (H3K27Ac, H3K9Ac) on DUSP4 regulatory regions as one of the causes for DUSP4 downregulation in ARID1A-deficient cells. Ectopic DUSP4 expression decreased cell proliferation, and pharmacologically inhibiting the MAPK pathway significantly mitigated tumor formation in vivo. Our findings suggest that ARID1A protein transcriptionally modulates DUSP4 expression by remodeling chromatin, subsequently inactivating the MAPK pathway, leading to tumor suppression. The ARID1A-DUSP4-MAPK axis may be further considered for developing targeted therapies against ARID1A-mutated cancers.


Sequential changes in hematologic and biochemical parameters in African tick bite fever.
To evaluate the sequential changes and to estimate the frequencies of abnormalities in some commonly measured biological variables in patients with African tick bite fever (ATBF), an emerging spotted fever group (SFG) rickettsiosis in international travelers to rural sub-Saharan Africa. A study was done of hemoglobin, total leukocyte count, absolute lymphocyte count, blood platelet count and serum levels of C-reactive protein (S-CRP), alanine aminotransferase (S-ALAT), aspartate aminotransferase, lactic dehydrogenase, gamma-glutamyl transferase, alkaline phosphatase, bilirubin, sodium and creatinine during the first two weeks of illness and prior to the institution of antirickettsial therapy in 108 patients with travel-associated ATBF. There were significant falls in mean total leukocyte count, mean absolute lymphocyte count, and mean platelet count, and significant increases in mean S-CRP and S-ALAT. During the first ten days of illness, elevated S-CRP, lymphopenia and elevated S-ALAT were detected in 91.7%, 73.3% and 40.7% of patients, respectively. Most abnormalities were mild. For 55 patients who underwent both S-CRP and absolute lymphocyte count determination, at least one parameter was abnormal in 52 (94.5%) patients. The sequential changes in many biological parameters during the acute phase of ATBF mimic those reported in other SFG rickettsioses. Mild abnormalities are frequent, with increased S-CRP and lymphopenia being the two most consistent findings.


Enhanced proliferation of murine T cell lines following interaction of poly(Glu60,Phe40) (GPhe) and antigen-presenting accessory cells. I. GPhe-stimulated enhancement of antigen-dependent proliferative responses.
Following interaction of the random polymer (Glu60,Phe40)n (GPhe) with antigen-presenting accessory cells (APC), unusual costimulatory activities were noted in several murine T cell systems. When GPhe, in contrast with other random copolymers (GT,GL), was added during "inhibition" and T cell "repertoire" studies as a (negative) control to GLA-reactive nonclonal T cell lines of haplotypes H-2d (DCL-2) or H-2bm12, augmentation of T cell proliferation ([3H]thymidine incorporation ([3HT]) to homologous antigen was observed. Augmentation by GPhe was also observed in the response of a GLPhe-reactive (H-2s X H-2d)F1 T cell line and the allogeneic response of the clonal T cell line D10.G4.1. This augmentation was critically dependent on the concentration of adherent accessory cells. Although the mechanism of action of GPhe remains, as yet, undefined, the GPhe-mediated enhancement of DCL-2 (a TH2, H-2d anti-GLA, T cell line) proliferation was not dependent upon the production of either IL-1 or IL-6 by accessory cells. In addition, enhanced DCL-2 proliferation was not accompanied by a significant increase in detectable IL-4 release.


RNA Binding Proteins in the miRNA Pathway.
microRNAs (miRNAs) are short ~22 nucleotides (nt) ribonucleic acids which post-transcriptionally regulate gene expression. miRNAs are key regulators of all cellular processes, and the correct expression of miRNAs in an organism is crucial for proper development and cellular function. As a result, the miRNA biogenesis pathway is highly regulated. In this review, we outline the basic steps of miRNA biogenesis and miRNA mediated gene regulation focusing on the role of RNA binding proteins (RBPs). We also describe multiple mechanisms that regulate the canonical miRNA pathway, which depends on a wide range of RBPs. Moreover, we hypothesise that the interaction between miRNA regulation and RBPs is potentially more widespread based on the analysis of available high-throughput datasets.


Antiprogesterone activity of RU 486 and its contragestive and other applications.
RU 486 is the first antiprogesterone to be used clinically. It inhibits the action of the hormone at the receptor level in target tissues. Its action is particularly significant in the endometrium where it prevents the initiation and progression of pregnancy in the first weeks (contragestive effect). The data indicate that the compound can be used for: voluntary interruption of pregnancy between 6 and 10 weeks; induction of menstruation during the fifth week of amenorrhoea, and post-coital contraception. Current trials include its use as a once-a-month menses inducer. It can also be utilized for therapeutic interruption at a late stage of pregnancy, and tried as adjuvant treatment in some cases of breast cancer. The data on RU 486 have been obtained through studies in physio-pharmacological endocrinology and biochemistry. The development of this antihormone represents a concerted research link between biology and medicine.


Reversible positioning head tilt observed in 14 cats with hypokalaemic myopathy.
Positioning head tilt (PHT) is a dynamic neurological sign in which the head tilts to the opposite side to which it is moving. This sign is triggered in response to head movement and is thought to be due to the lack of inhibition of vestibular nuclei by the cerebellar nodulus and uvula (NU). The occurrence of PHT in animals has been suggested to be an indicator of NU dysfunction. Here, we describe the acute onset of PHT in 14 cats. All the cats were diagnosed with hypokalaemic myopathy caused by a range of pathologies. The PHT resolved along with other signs related to myopathy, such as cervical flexion and generalised weakness, after electrolyte correction in all cats. Hypokalaemic myopathy was the likely cause of PHT in the present feline cases.


Prophylaxis against venous thromboembolism in orthopedic surgery.
Venous thromboembolism (VTE), which is manifested as deep vein thrombosis (DVT) and pulmonary embolism (PE), represents a significant cause of death, disability, and discomfort. They are frequent complications of various surgical procedures. The aging population and the survival of more severely injured patients may suggest an increasing risk of thromboembolism in the trauma patients. Expanded understanding of the population at risk challenges physicians to carefully examine risk factors for VTE to identify high-risk patients who can benefit from prophylaxis. An accurate knowledge of evidence-based risk factors is important in predicting and preventing postoperative DVT, and can be incorporated into a decision support system for appropriate thromboprophylaxis use. Standard use of DVT prophylaxis in a high-risk trauma population leads to a low incidence of DVT. The incidence of VTE is common in Asia. The evaluation includes laboratory tests, Doppler test and phlebography. Screening Doppler sonography should be performed for surveillance on all critically injured patients to identify DVT. D-Dimer is a useful marker to monitor prophylaxis in trauma surgery patients. The optimal time to start prophylaxis is between 2 hours before and 10 hours after surgery, but the risk of PE continues for several weeks. Thromboprophylaxis includes graduated compression stockings and anticoagulants for prophylaxis. Anticoagulants include Warfarin, which belongs to Vitamin K antagonists, unfractionated heparin, low molecular weight heparins, factor Xa indirect inhibitor Fondaparinux, and the oral IIa inhibitor Melagatran and ximelagatran. Recombinant human soluble thrombomodulin is a new and highly effective antithrombotic agent. Prophylactic placement of vena caval filters in selected trauma patients may decrease the incidence of PE. The indications for prophylactic inferior vena cava filter insertion include prolonged immobilization with multiple injuries, closed head injury, pelvic fracture, spine fracture, multiple long bone fracture, and attending discretion. Multiple-trauma patients are at increased risk for DVT but are also at increased risk of bleeding, and the use of heparin may be contraindicated. Serial compression devices (SCDs) are an alternative for DVT prophylaxis. Compression devices provide adequate DVT prophylaxis with a low failure rate and no device-related complications. Immobilization is one of important reasons of VTE. The ambulant patient is far less likely to develop complications of inactivity, not only venous thrombosis, but also contractures, decubitus ulcers, or osteoporosis (with its associated fatigue fractures), as well as bowel or bladder complications.


Lifestyle change and the prevention of cognitive decline and dementia: what is the evidence?
Effective pharmaceutical treatment of dementia is currently unavailable. Epidemiological work has, however, identified modifiable lifestyle factors, such as poor diet and physical and cognitive inactivity, that are associated with the risk of dementia. These factors may be useful targets for the prevention of cognitive impairment and dementia. Much recent research has, therefore, adopted an interventional focus. We review this work, highlight some methodological limitations, and provide recommendations for future research. Change from a sedentary lifestyle to moderate physical activity has beneficial effects on cognitive functioning, and preliminary evidence suggests that such change may reduce the incidence of dementia. The evidence on cognitive benefits of lifestyle changes towards more intellectual engagement is insufficient. Nutritional supplements to treat deficiency may improve cognitive performance, but supplements on top of a healthy diet cannot be recommended. Introduction of physical activity can reduce the risk of cognitive impairment in old age. Future research on nutritional supplements must consider the principle of an inverted U-shaped association between nutritional level and cognitive function. Work on the effects of cognitive training must use transfer tasks as primary outcome measures, and investigate whether effects of cognitive training generalize beyond the trained cognitive tasks.


Cardiac contractility modulation device-new hope for refractory heart failure patients.
A large number of patients with advanced heart failure (HF) are refractory to optimal standard medical therapy. This has given rise to development and testing of a host of new device based therapies. One recent and potentially broadly applicable treatment under investigation is cardiac contractility modulation (CCM) electrical signals. The CCM signals are relatively high-voltage electrical impulses applied to the myocardium during the absolute refractory period. These signals do not initiate a new contraction or modify activation sequence as is the case with other therapies such as cardiac resynchronization therapy. Rather, CCM signals are intended to enhance systolic function of the failing myocardium. A device similar to a pacemaker is typically implanted in the right pectoral region. Three standard pacemaker leads are placed intravenously. One right arterial lead is used to sense atrial activity, and two right ventricular leads are used to sense ventricular activity and deliver the CCM pulse trains. The electrodes of the ventricular leads are placed on the right ventricular septum at least 2cm apart. In contrast to a Pacemaker and defibrillator the system is designed to modulate the strength of contraction of the heart muscle rather than the rhythm. Application of CCM signals to the failing heart is associated with improved gene expression which ultimately causes LV global, cellular and biochemical remodeling as a result improved LV systolic function.


Particle platforms for cancer immunotherapy.
Elevated understanding and respect for the relevance of the immune system in cancer development and therapy has led to increased development of immunotherapeutic regimens that target existing cancer cells and provide long-term immune surveillance and protection from cancer recurrence. This review discusses using particles as immune adjuvants to create vaccines and to augment the anticancer effects of conventional chemotherapeutics. Several particle prototypes are presented, including liposomes, polymer nanoparticles, and porous silicon microparticles, the latter existing as either single- or multiparticle platforms. The benefits of using particles include immune-cell targeting, codelivery of antigens and immunomodulatory agents, and sustained release of the therapeutic payload. Nanotherapeutic-based activation of the immune system is dependent on both intrinsic particle characteristics and on the immunomodulatory cargo, which may include danger signals known as pathogen-associated molecular patterns and cytokines for effector-cell activation.


Determinants of the microbial community structure of eutrophic, hyporheic river sediments polluted with chlorinated aliphatic hydrocarbons.
Chlorinated aliphatic hydrocarbons (CAHs) often discharge into rivers as contaminated groundwater baseflow. As biotransformation of CAHs in the impacted river sediments might be an effective remediation strategy, we investigated the determinants of the microbial community structure of eutrophic, CAH-polluted sediments of the Zenne River. Based on PCR-DGGE analysis, a high diversity of Bacteria, sulfate-reducing bacteria, Geobacteraceae, methanogenic archaea, and CAH-respiring Dehalococcoides was found. Depth in the riverbed, organic carbon content, CAH content and texture of the sediment, pore water temperature and conductivity, and concentrations of toluene and methane significantly contributed to the variance in the microbial community structure. On a meter scale, CAH concentrations alone explained only 6% of the variance in the Dehalococcoides and sulfate-reducing communities. On a cm-scale, however, CAHs explained 14.5-35% of the variation in DGGE profiles of Geobacteraceae, methanogens, sulfate-reducing bacteria, and Bacteria, while organic carbon content explained 2-14%. Neither the presence of the CAH reductive dehalogenase genes tceA, bvcA, and vcrA, nor the community structure of the targeted groups significantly differed between riverbed locations showing either no attenuation or reductive dechlorination, indicating that the microbial community composition was not a limiting factor for biotransformation in the Zenne sediments.


Electrochemical detection coupled with high-performance liquid chromatography in pharmaceutical and biomedical analysis: a mini review.
Recent advances in electrochemical detection techniques coupled with high-performance liquid chromatography (HPLC-ECD) in pharmaceutical and biomedical analysis are reviewed. ECD classification and modes including common amperometric, coulometric, conductimetric, and potentiometric detector, are outlined and the some typical examples of determinations in pharmaceutical and biomedical analysis are described. The electrochemical detection system can offer superior merits over other detectors commonly used with HPLC. These techniques have great potential owing to their prominent characteristics in high-throughput screening procedures of drugs in various matrices. Fundamental 67 references from last 5 years related with a field are cited in this review.


Antioxidant and antiproliferative activities of strawberries.
Strawberries contain high levels of antioxidants, which have been correlated with a decreased risk of chronic disease. To more fully characterize the antioxidant profiles and possible associated health benefits of this fruit, the total free and bound phenolic, total flavonoid, and total anthocyanin contents of eight strawberry cultivars (Earliglow, Annapolis, Evangeline, Allstar, Sable, Sparkle, Jewel, and Mesabi) were measured. Cultivar effects on phenolic contents were compared with antioxidant capacities, as measured by the total oxyradical scavenging capacity (TOSC) assay, and to antiproliferative activities, as measured by inhibition of HepG(2) human liver cancer cell proliferation in vitro. Free phenolic contents differed by 65% between the highest (Earliglow) and the lowest (Allstar) ranked cultivars. The water soluble bound and ethyl acetate soluble bound phenolic contents averaged 5% of the total phenolic content of the cultivars. The total flavonoid content of Annapolis was 2-fold higher than that of Allstar, which had the lowest content. The anthocyanin content of the highest ranked cultivar, Evangeline, was more than double that of the lowest ranked cultivar, Allstar. Overall, free phenolic content was weakly correlated with total antioxidant activity, and flavonoid and anthocyanin content did not correlate with total antioxidant activity. The proliferation of HepG(2) human liver cancer cells was significantly inhibited in a dose-dependent manner after exposure to all strawberry cultivar extracts, with Earliglow exhibiting the highest antiproliferative activity and Annapolis exhibiting the lowest. No relationship was found between antiproliferative activity and antioxidant content.


From soil to cacao bean: Unravelling the pathways of cadmium translocation in a high Cd accumulating cultivar of Theobroma cacao L.
The research on strategies to reduce cadmium (Cd) accumulation in cacao beans is currently limited by a lack of understanding of the Cd transfer pathways within the cacao tree. Here, we elucidated the transfer of Cd from soil to the nib (seed) in a high Cd accumulating cacao cultivar. Here, we elucidated the transfer of Cd from soil to the nib (seed) in a high Cd accumulating cacao cultivar through Cd stable isotope fractionation, speciation (X-Ray Absorption Spectroscopy), and localization (Laser Ablation Inductively Coupled Plasma Mass Spectrometry). The plant Cd concentrations were 10-28 higher than the topsoil Cd concentrations and increased as placenta< nib< testa< pod husk< root< leaf< branch. The retention of Cd in the roots was low. Light Cd isotopes were retained in the roots whilst heavier Cd isotopes were transported to the shoots (Δ 114/110 Cd shoot-root = 0.27 ± 0.02 ‰ (weighted average ± standard deviation)). Leaf Cd isotopes were heavier than Cd in the branches (Δ 114/110 Cd IF3 leaves-branch = 0.18 ± 0.01 ‰), confirming typical trends observed in annual crops. Nibs and branches were statistically not distinguishable (Δ 114/110 Cd nib-branch = -0.08‰ ± 0.06 ‰), contrary to the leaves and nibs (Δ 114/110 Cd nib-IF3 leaves = -0.25‰ ± 0.05 ‰). These isotope fractionation patterns alluded to a more direct transfer from branches to nibs rather than from leaves to nibs. The largest fraction (57%) of total plant Cd was present in the branches where it was primarily bound to carboxyl-ligands (60-100%) and mainly localized in the phloem rays and phelloderm of the bark. Cadmium in the nibs was mainly bound to oxygen ligands (60-90%), with phytate as the most plausible ligand. The weight of evidence suggested that Cd was transferred like other nutrients from root to shoot and accumulated in the phloem rays and phelloderm of the branches to reduce the transfer to foliage. Finally, the data indicated that the main contribution of nib Cd was from the phloem tissues of the branch rather than from leaf remobilization. This study extended the limited knowledge on Cd accumulation in perennial, woody crops and revealed that the Cd pathways in cacao are markedly different than in annual crops.


Kraft Black Liquor as a Carbonaceous Source for the Generation of Porous Monolithic Materials and Applications toward Hydrogen Adsorption and Ultrastable Supercapacitors.
High internal phase emulsions (HIPEs) have templated self-standing porous carbonaceous materials (carboHIPEs) while employing Kraft Black Liquor, a paper milling industry byproduct, as a carbon precursor source. As such, the starting emulsion has been prepared through a laboratory-made homogenizer, while native materials have been characterized at various length scales either with Raman spectrometry, X-ray diffraction (XRD), mercury intrusion porosimetry, and nitrogen absorption. After thermal carbonization, specific surface areas ranging from ∼600 m2 g-1 to 1500 m2 g-1 have been reached while maintaining a monolithic character. Despite a poor graphitization yield, the carbonaceous materials offer good electronic transport properties, reaching 31 S m-1. When tested toward energy storage applications, the native unwashed materials revealed a hydrogen storage of 0.07 wt % at 40 bar and room temperature (RT), while hydrogen retention is reaching 0.37 wt % at 40 bar and RT for the washed sample. When employed as supercapacitor electrodes, these carbonaceous foams are able to deliver high capacities of ∼140 F/g at 1 A/g, thereby matching the ones obtained from a commercial carbon reference, while additionally providing a restored remnant capacity of 120 F/g at 2 A/g over 5000 cycle numbers.


Pseudotyped zoonotic thogotoviruses exhibit broad entry range in mammalian cells.
Viruses in the thogotovirus genus of the family Orthomyxoviridae are much less well-understood than influenza viruses despite documented zoonotic transmission and association with human disease. This study therefore developed a cell-cell fusion assay and three pseudotyping tools and used them to assess envelope function and cell tropism. Envelope glycoproteins of Dhori (DHOV), Thogoto (THOV), Bourbon, and Sinu viruses were all revealed to exhibit pH-dependent triggering of membrane fusion. Lentivirus vectors were robustly pseudotyped with these glycoproteins while influenza virus vectors showed pseudotyping compatibility, albeit at lower efficiencies. Replication-competent vesicular stomatitis virus expressing DHOV or THOV glycoproteins were also successfully generated. These pseudotyped viruses mediated entry into a wide range of mammalian cell lines, including human primary cells. The promiscuousness of these viruses suggests the use of a relatively ubiquitous receptor and their entry into numerous mammalian cells emphasize their high potential as veterinary and zoonotic diseases.


MT1-MMP and MMP-2 mRNA expression in human ovarian tumors: possible implications for the role of desmoplastic fibroblasts.
Expression of activated MMP-2 (72 kDa type IV collagenase) is highly associated with the malignant phenotype in adenocarcinomas, but predominant expression of the mRNA appears to be in stromal cells. MT1-MMP (membrane type 1-matrix metalloproteinase) is implicated in tumor-epithelial cell surface activation of latent pro-MMP-2, indicating a mechanism for tumor-stromal interaction in invasion. We determined the relative mRNA distribution of these MMPs in human ovarian tumors with a view to analyzing potential variations in the epithelial-mesenchymal interactions dictating ovarian tumor cell spread. In situ hybridization using 35S-labeled riboprobes was used to analyze 33 human ovarian tumors and mouse xenografts of human ovarian (DOV 13, SKOV3) and breast (MCF 7) tumor cell lines known to express MT1-MMP and MMP-2. MMP-2 mRNA was expressed in 31 of 33 and MT1-MMP mRNA was expressed in 29 of 33 tumor cases. MMP-2 mRNA was predominantly expressed in desmoplastic fibroblasts and in the subepithelial stroma. MT1-MMP mRNA showed some colocalization with MMP-2 in stromal cells. Neoplastic epithelial cell labeling for MT1-MMP mRNA was present in borderline and malignant tumors but not in benign tumors, and was invariably less than stromal labeling. Xenografts of DOV 13, SKOV 3, and MCF 7 cells showed some stromal localization of MMP-2 mRNA and weak labeling of DOV 13 cells. There was variable labeling for MT1-MMP mRNA in the neoplastic cells only. The colocalization of MT1-MMP and MMP-2 mRNAs in ovarian carcinoma stroma supports the view that MT1-MMP is closely associated with MMP-2 expression and function. It suggests that either additional mechanisms are involved in regulating MMP-2 activation at the tumor cell surface, or more intriguingly, that desmoplastic fibroblasts may be the primary mediators of extracellular matrix remodeling with respect to this system.


Mutation caused by human phagocytes.
Histidine-requiring mutants of Salmonella typhimurium TA100 were incubated with human peripheral blood leukocytes. More of these bacteria reverted to histidine independence than controls not incubated with cells. Phagocyte-rich suspensions were mutagenic, while heat-killed cells, lymphocytes, or mixed blood leukocytes of a patient with chronic granulomatous disease were not. Production of reactive oxygen metabolites could explain the capacity of phagocytes to induce mutation.


Disaster and associated changes in physical and mental health in older residents.
Long-term health consequences of disasters have not been studied extensively, one reason amongst others is that no pre-disaster observation is available. This study focuses on an aeroplane crash on an Amsterdam suburb. The ongoing Longitudinal Aging Study Amsterdam has one pre-disaster and several post-disaster observations, making it possible to study changes in health, taking pre-disaster health characteristics into account. Three exposure groups are distinguished: those living within a radius of 1 km from the disaster (initial n=39), those living between a radius of 1 and 2 km from the disaster (initial n=56), and those living in the rest of the city of Amsterdam (initial n=508). Health measures include general health, health in comparison with age peers, functional limitations, disability and cognitive functioning. These measures are based on self-ratings, interviewer observations, or both. Older persons living closest to the disaster area are likely to experience health decline in the wake of a disaster, over and above the health decline that would occur normally with aging. The disaster-associated health decline is small, and most obvious in the ability to perform actions (such as mobility), but is not observed in either disability in daily functioning, nor in self-perceptions of health. Cognitive functioning even shows a short-term improvement. These findings suggest substantial resilience in older adults, despite their common health problems.


Trapeziometacarpal osteoarthritis. Staging as a rationale for treatment.
Painful arthrosis of the basal joints of the thumb covers a spectrum of arthritic disease. The painful hypermobile thumb with articular cartilage preserved requires an entirely different type of treatment than does the similarly painful basal joint, which has stiffness and degeneration of more than one facet of the trapezium. By careful radiographic evaluation of the trapezial articulations, particularly in the lateral projection, a reasonable set of radiographic guidelines for staging of the degenerative process can be provided. One must be prepared to adjust this preoperative staging should direct inspection of the articular surfaces at surgery indicate more damage than perceived on the radiograph. Once the ultimate staging of the disease has been established, the means of treatment is considerably simplified and the multiple procedures that have been proposed for "basal joint arthritis" can be applied more accurately.


Evolutionary changes in the cochlea and labyrinth: Solving the problem of sound transmission to the balance organs of the inner ear.
This review article examines the evolutionary adaptations in the vertebrate inner ear that allow selective activation of auditory or vestibular hair cells, although both are housed in the same bony capsule. The problem of separating acoustic stimuli from the vestibular end organs in the inner ear has recently reemerged with the recognition of clinical conditions such as superior canal dehiscence syndrome and enlarged vestibular aqueduct syndrome. In these syndromes, anatomical defects in the otic capsule alter the functional separation of auditory and vestibular stimuli and lead to pathological activation of vestibular reflexes in response to sound. This review demonstrates that while the pars superior of the labyrinth (utricle and semicircular canals) has remained fairly constant throughout evolution, the pars inferior (saccule and other otolith, macular, and auditory end organs) has seen considerable change as many adaptations were made for the development of auditory function. Among these were a relatively rigid membranous labyrinth wall, a variably rigid otic capsule, immersion of the membranous labyrinth in perilymph, a perilymphatic duct to channel acoustic pressure changes away from the vestibular organs, and different operating frequencies for vestibular versus auditory epithelia. Even in normal human ears, acoustic sensitivity of the labyrinth to loud clicks or tones is retained enough to be measured in a standard clinical test, the vestibular-evoked myogenic potential test.


From complete genomes to measures of substitution rate variability within and between proteins.
Accumulation of complete genome sequences of diverse organisms creates new possibilities for evolutionary inferences from whole-genome comparisons. In the present study, we analyze the distributions of substitution rates among proteins encoded in 19 complete genomes (the interprotein rate distribution). To estimate these rates, it is necessary to employ another fundamental distribution, that of the substitution rates among sites in proteins (the intraprotein distribution). Using two independent approaches, we show that intraprotein substitution rate variability appears to be significantly greater than generally accepted. This yields more realistic estimates of evolutionary distances from amino-acid sequences, which is critical for evolutionary-tree construction. We demonstrate that the interprotein rate distributions inferred from the genome-to-genome comparisons are similar to each other and can be approximated by a single distribution with a long exponential shoulder. This suggests that a generalized version of the molecular clock hypothesis may be valid on genome scale. We also use the scaling parameter of the obtained interprotein rate distribution to construct a rooted whole-genome phylogeny. The topology of the resulting tree is largely compatible with those of global rRNA-based trees and trees produced by other approaches to genome-wide comparison.


Dietary Diversity and Meal Frequency Practices among Infant and Young Children Aged 6-23 Months in Ethiopia: A Secondary Analysis of Ethiopian Demographic and Health Survey 2011.
Background. Appropriate complementary feeding practice is essential for growth and development of children. This study aimed to assess dietary diversity and meal frequency practice of infants and young children in Ethiopia. Methods. Data collected in the Ethiopian Demographic and Health Survey (EDHS) from December 2010 to June 2011 were used for this study. Data collected were extracted, arranged, recoded, and analyzed by using SPSS version 17. A total of 2836 children aged 6-23 months were used for final analysis. Both bivariate and multivariate analysis were done to identify predictors of feeding practices. Result. Children with adequate dietary diversity score and meal frequency were 10.8% and 44.7%, respectively. Children born from the richest households showed better dietary diversity score (OR = 0.256). Number of children whose age less than five years was important predictor of dietary diversity (OR = 0.690). Mothers who had exposure to media were more likely to give adequate meal frequency to their children (OR = 0.707). Conclusion. Dietary diversity and meal frequency practices were inadequate in Ethiopia. Wealth quintile, exposure to media, and number of children were affecting feeding practices. Improving economic status, a habit of eating together, and exposure to media are important to improve infant feeding practices in Ethiopia.


Synaptic maturation at cortical projections to the lateral amygdala in a mouse model of Rett syndrome.
Rett syndrome (RTT) is a neuro-developmental disorder caused by loss of function of Mecp2--methyl-CpG-binding protein 2--an epigenetic factor controlling DNA transcription. In mice, removal of Mecp2 in the forebrain recapitulates most of behavioral deficits found in global Mecp2 deficient mice, including amygdala-related hyper-anxiety and lack of social interaction, pointing a role of Mecp2 in emotional learning. Yet very little is known about the establishment and maintenance of synaptic function in the adult amygdala and the role of Mecp2 in these processes. Here, we performed a longitudinal examination of synaptic properties at excitatory projections to principal cells of the lateral nucleus of the amygdala (LA) in Mecp2 mutant mice and their wild-type littermates. We first show that during animal life, Cortico-LA projections switch from a tonic to a phasic mode, whereas Thalamo-LA synapses are phasic at all ages. In parallel, we observed a specific elimination of Cortico-LA synapses and a decrease in their ability of generating presynaptic long term potentiation. In absence of Mecp2, both synaptic maturation and synaptic elimination were exaggerated albeit still specific to cortical projections. Surprisingly, associative LTP was unaffected at Mecp2 deficient synapses suggesting that synaptic maintenance rather than activity-dependent synaptic learning may be causal in RTT physiopathology. Finally, because the timing of synaptic evolution was preserved, we propose that some of the developmental effects of Mecp2 may be exerted within an endogenous program and restricted to synapses which maturate during animal life.


Nonclassical IL-1 beta secretion stimulated by P2X7 receptors is dependent on inflammasome activation and correlated with exosome release in murine macrophages.
Several mechanistically distinct models of nonclassical secretion, including exocytosis of secretory lysosomes, shedding of plasma membrane microvesicles, and direct efflux through plasma membrane transporters, have been proposed to explain the rapid export of caspase-1-processed IL-1 beta from monocytes/macrophages in response to activation of P2X7 receptors (P2X7R) by extracellular ATP. We compared the contribution of these mechanisms to P2X7R-stimulated IL-1 beta secretion in primary bone marrow-derived macrophages isolated from wild-type, P2X7R knockout, or apoptosis-associated speck-like protein containing a C-terminal CARD knockout mice. Our experiments revealed the following: 1) a novel correlation between IL-1 beta secretion and the release of the MHC-II membrane protein, which is a marker of plasma membranes, recycling endosomes, multivesicular bodies, and released exosomes; 2) a common and absolute requirement for inflammasome assembly and active caspase-1 in triggering the cotemporal export of IL-1 beta and MHC-II; and 3) mechanistic dissociation of IL-1 beta export from either secretory lysosome exocytosis or plasma membrane microvesicle shedding on the basis of different requirements for extracellular Ca(2+) and differential sensitivity to pharmacological agents that block activation of caspase-1 inflammasomes. Thus, neither secretory lysosome exocytosis nor microvesicle shedding models constitute the major pathways for nonclassical IL-1 beta secretion from ATP-stimulated murine macrophages. Our findings suggest an alternative model of IL-1 beta release that may involve the P2X7R-induced formation of multivesicular bodies that contain exosomes with entrapped IL-1 beta, caspase-1, and other inflammasome components.


Transport of lactate and pyruvate in the intraerythrocytic malaria parasite, Plasmodium falciparum.
The mature, intraerythrocytic form of the human malaria parasite, Plasmodium falciparum, is reliant on glycolysis for its energetic requirements. It produces large quantities of lactic acid, which have to be removed from the parasite's cytosol to maintain the cell's integrity and metabolic viability. Here we show that the monocarboxylates lactate and pyruvate are both transported across the parasite's plasma membrane via a H(+)/monocarboxylate symport process that is saturable and inhibited by the bioflavonoid phloretin. The results provide direct evidence for the presence at the parasite surface of a H(+)-coupled monocarboxylate transporter with features in common with members of the MCT (monocarboxylate transporter) family of higher eukaryotes.


Age related changes in cellularity, mitotic activity and pyknotic cell number in the mouse subependymal layer.
The mouse subependymal layer shows a decrease in cellularity between 22 and 31 months of age after having remained fairly constant between 6 and 22 months. The mitotic index falls from 2.32% at 6 months to 1.19% at 18 months before rising to 2.37% at 28 months. The variation in the mitotic index prevents the number of mitotic cells decreasing between 22 and 28 months along with decreasing cellularity. There is no statistical correlation between the number of mitotic cells and the number of pyknotic cells in the subependymal layer although, at all ages, mitotic cells out-number pyknotic cells.


Occurrence and correlations between coliphages and anthropogenic viruses in the Massachusetts Bay using enrichment and ICC-nPCR.
We evaluated a two-step enrichment procedure to detect coliphages and an integrated cell culture-nested polymerase chain reaction (ICC-nPCR) to detect human astrovirus, enteroviruses, rotavirus and adenovirus type 40 and 41 in marine water samples collected by the Massachusetts Water Resource Authority (MWRA). MWRA has been monitoring its receiving waters for coliphages, anthropogenic viruses and indicator bacteria in order to evaluate the impact of Boston's Deer Island Sewage Treatment Plant discharge. Coliphages and enteric viruses were originally assayed using single agar overlay and most probable number cell culture (MPN) methods, respectively. Reanalysis of these samples for enteric viruses by ICC-nPCR demonstrated that 46% were positive for at least one virus compared with 23% with the MPN method. Use of the enrichment method showed a 47% increase in the detection of male specific and somatic coliphages compared with the single agar overlay method. Correlations between the presence of coliphages, enteric viruses and indicator bacteria were based on proximity to the treatment plant discharge, seasonal variations and site levels. The presence of enteric viruses was significantly correlated to coliphages but not to indicator bacteria. Preliminary comparative results demonstrate that effective and efficient monitoring of anthropogenic contamination can be achieved using these more sensitive and specific techniques.


Alcohol-dependent liver cell necrosis in vitro: a new model.
In alcoholic liver injury, necrosis is involved in the progression from benign fatty liver to alcoholic hepatitis and cirrhosis. However, there is no practical model of alcohol-dependent liver cell necrosis. The calcium-dependent killing of cultured rat hepatocytes by two different membrane-active hepatotoxins, galactosamine and phalloidin, is potentiated by ethyl alcohol. This indicates that some general physical effect of alcohol on cellular membranes renders cells susceptible to otherwise nonlethal injuries. The in vitro model described in this report may thus be used to search for a general mechanism underlying alcohol-related tissue injury.


Kinetic studies of 6-phosphogluconate dehydrogenase from sheep liver.
The steady-state kinetics of the oxidative decarboxylation of 6-phosphogluconate catalysed by 6-phosphogluconate dehydrogenase from sheep liver in triethanolamine and phosphate buffers (pH 7.0) have been reinvestigated. In triethanolamine buffer the enzyme is inhibited by high NADP+ concentrations in the presence of low fixed concentrations of 6-phosphogluconate. Data are consistent with an asymmetric sequential mechanism in which NADP+ and 6-phosphogluconate bind randomly and product release is ordered. The pathway through the enzyme--6-phosphogluconate complex appears to be preferred in triethanolamine buffer. Pre-steady-state studies of the oxidative decarboxylation reaction at pH 6.0-8.0 show that hydride transfer is greater than 900 s-1. After the fast formation of NADPH in amounts equivalent to about half of the enzyme-active-centre concentration, the rate of NADPH formation is equal to the steady-state rate. Two possible interpretations are considered. Rapid fluorescence measurements of the displacement of NADPH from its complex with the enzyme at pH 6.0 and 7.0 indicate that the dissociation of NADPH is fast (greater than 800 s-1) and cannot be the rate-limiting step in oxidative decarboxylation. Coenzyme binding studies at equilibrium have been extended to include the determination of the dissociation constants for the binary complexes of enzyme with NADPH and NADP+ at pH 6.0-8.0 and the dissociation constant for NADPH in the ternary enzyme--6-phosphogluconate--NADPH complex in triethanolamine buffer, pH 7.0.


Computerized prediction of risk for developing breast cancer based on bilateral mammographic breast tissue asymmetry.
This study developed and assessed a computerized scheme to detect breast abnormalities and predict the risk of developing cancer based on bilateral mammographic tissue asymmetry. A digital mammography database of 100 randomly selected negative cases and 100 positive cases for having high-risk of developing breast cancer was established. Each case includes four images of cranio-caudal (CC) and medio-lateral oblique (MLO) views of the left and right breast. To detect bilateral mammographic tissue asymmetry, a pool of 20 computed features was assembled. A genetic algorithm was applied to select optimal features and build an artificial neural network based classifier to predict the likelihood of a test case being positive. The leave-one-case-out validation method was used to evaluate the classifier performance. Several approaches were investigated to improve the classification performance including extracting asymmetrical tissue features from either selected regions of interests or the entire segmented breast area depicted on bilateral images in one view, and the fusion of classification results from two views. The results showed that (1) using the features computed from the entire breast area, the classifier yielded the higher performance than using ROIs, and (2) using a weighted average fusion method, the classifier achieved the highest performance with the area under ROC curve of 0.781±0.023. At 90% specificity, the scheme detected 58.3% of high-risk cases in which cancers developed and verified 6-18 months later. The study demonstrated the feasibility of applying a computerized scheme to detect cases with high risk of developing breast cancer based on computer-detected bilateral mammographic tissue asymmetry.


Multiple Splenic Infarcts Complicating Plasmodium vivax Malaria.
Splenic infarct is a rare complication in Plasmodium vivax malaria. We report a case of splenic infarction with acute kidney injury in a case of P. vivax malaria in a 13-year-old male child who presented to the emergency department with severe pain in the left hypochondrium. The patient was managed with intravenous artesunate and oral primaquine. Pain in left hypochondrium in children with P. vivax malaria due to splenic infarction needs to be evaluated for any surgical emergency like rupture or abscess. A review of literature of the unusual but serious complication is presented along with the case report.


[Study of a respiratory syncytial virus diagnostic test kit based on immunochromatography].
We carried out clinical and basic studies of the Directigen Lateral Flow RSV (Becton, Dickinson and Company, USA), a rapid test kit that detects respiratory syncytial virus (hereinafter referred to as "RSV") antigens based on immunochromatography. For the clinical study, 103 nasopharyngeal aspirates from patients with acute respiratory infections were used to evaluate the kit. Compared to the cell culture method, the Directigen Lateral Flow RSV showed a sensitivity of 100% (16/16) and a specificity of 94.3% (82/87), and an agreement rate of 95.1% (98/103). When compared to conventional testing kits, we found that the total agreement rate with the Directigen RS (Nippon Becton Dickinson and Company) was 88.3% (91/103) and with RSV TestPack (Dainabot Co., Ltd.) was 91.3% (94/103). The detection limit of the Directigen Lateral Flow RSV was 2 x 10(3) PFU/ml for both RSV subgroups A and B. In the crossreactivity test, only RSV was found positive. No other microorganisms were crossreactive. We also studied storage stability of nasopharyngeal aspirates and found that stability was not affected by storage at room and refrigerator temperatures for 14 days. Taken all together, the Directigen Lateral Flow RSV is useful for the diagnosis of RSV infection in a clinical setting because its performance is equivalent to conventional testing kits and is easy to use.


Urinary metabolites in patients undergoing coronary catheterization via the radial versus femoral artery approach.
The transradial approach (TRA) for coronary angiography and percutaneous coronary intervention is associated with lower rates of vascular complications and acute kidney injury when compared to the transfemoral approach (TFA). Urine metabolites and proteins may be useful in identifying the dynamic changes at the vascular endothelial cell level. We attempted to explore the changes in the measurable signals of endothelial and nephron injury within 60 to 90 minutes after catheterization among those with the TRA and TFA approaches. Consecutive patients of a single interventionist who underwent coronary angiography between June 2015 and May 2016 were included. Of the 60 patients included in the analysis, the baseline characteristics were similar between those with a TRA (n = 30) and TFA (n = 30) approach. The values of the biomarkers were natural log transformed for the analysis. We found that the mean values of heat shock protein 27, taurine, and sulfuric acid did not significantly change after the procedure. However, the median value of thioredoxin decreased (P = 0.002) and that of talose increased (P = 0.01) after the procedure. None of the patients in our cohort experienced vascular complications or acute kidney injury. No differences in the values of urinary metabolites (pre, post, and delta) were found between TRA and TFA except for postprocedural thioredoxin. In conclusion, this exploratory study showed no difference in the patterns of acute vascular/renal injury metabolic markers before and after catheterization irrespective of the arterial access site.