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The Mg(2+)-dependent ATPase activity of human erythrocyte ghosts undergoes biphasic activation in the presence of ATP (K0.5 approximately 20 microM and 400 microM). Inhibition by vanadate is also biphasic with the most sensitive component (IC50 approximately 100 microM) responsible for the remaining activity. La3+ inhibits approximately 70% of activity (IC50 approximately 25 microM) while Cd2+ can fully inhibit activity (IC50 approximately 60 microM). Partially purified activity was obtained by extracting ghosts with Triton X-100, followed by chromatography over Sepharose CL-2B. Triton distorts the curves for inhibition by vanadate and the activation by ATP. The partially purified activity is inhibited by Ca2+ (IC50 approximately 0.4 mM). These results, together with data from other studies, suggest that the total Mg(2+)-ATPase activity in the membrane represents at least two separate enzymes. Only the activity which is highly sensitive to vanadate appears to be involved in erythrocyte shape change.

Sixteen isozyme markers have been assigned to the chromosome complement of the neotropical primate species Ateles paniscus chamek using three somatic cell hybrid panels. Several genetic associations were found to be common between humans and this species, despite the fact that Ateles is a karyologically rearranged taxon. Conversely, several human gene clusters were disrupted, resulting in gene associations not previously found in other primates. A comparison with other primates and mammalian orders, for which gene maps are available, was carried out for a comprehensive evaluation of genome evolution in these disparate taxa.

This study investigated the development of children's ability to find the optimal balance between flexibility and stability as a function of the frequency of required task switches. This question was addressed in two situations contrasting the dynamics of engagement of reconfiguration processes (reactive vs. proactive). A cued task-switching paradigm was presented to kindergartners and fourth graders, who are known to differ in their preferential mode of control engagement. Flexibility adaptation was examined through the modulation of switching costs by switch proportion, the so-called list-wide switch proportion (LWSP) effect. When the situation forced the use of reactive control (Experiment 1: simultaneous presentation of the cue and the stimulus), we found the LWSP effect with a greater magnitude in kindergartners than in fourth graders. In the situation inducing proactive control (Experiment 2: task cue presented before and until the stimulus), flexibility adaptation was obtained when error rates were considered but not response times. By demonstrating that even young children are capable of flexibility adaptation to contextual demands, these findings support the hypothesis that implicitly triggered adaptation of control may develop as early as the end of the preschool years despite the immaturity of cognitive control during this period.

In recent years, a variety of in vitro models for the cultivation of hair follicles and their constituents have been developed. Outer root sheath (ORS) keratinocytes (KC) have been mainly studied in explant cultures, planted on bovine eye lens capsules, collagen substrata, 3T3 cell feeder layers, or dermal equivalents, yielding outgrowth of a multilayered stratified epithelium with some biochemical and ultrastructural characteristics of keratinocytic differentiation. More recently, ORS KC cultures have also been initiated from single cell suspensions, and organotypic cultures have been obtained by recombination with dermal cells, inducing a higher degree of epidermal differentiation. Presumptive human hair matrix cells have been isolated from plucked anagen hair follicles and have been successfully propagated on 3T3 cell or normal human fibroblast feeder layers, giving rise to multilayered stratified KC cultures. In contrast, only preliminary data exist concerning the cultivation of bulge cells that have been suggested to represent follicular stem cells. In conclusion we dispose of several in vitro models today to cultivate ORS KC and hair matrix cells that have increased our knowledge on the regulation of the human hair cycle by soluble factors and dermal-epidermal interactions. Further comparative studies on ORS KC, bulge cells and matrix cells have to be carried out to confirm the distinct character of these hair KC subsets.

This study was done to provide an analytical overview on the latest malaria infection clusters by evaluating temporal trends during 2010-2019 in Korea. Incheon was the most likely cluster (MLC) for all cases of malaria during the total period. MLCs for P. falciparum, vivax, malariae, ovale, and clinically diagnosed malaria without parasitological confirmation were Jeollanam-do, Incheon, Gangwon-do, Gyeongsangnam-do, and Jeollabuk-do, respectively. Malaria was decreasing in most significant clusters, but Gwangju showed an increase for all cases of malaria, P. vivax and clinically diagnosed cases. Malaria overall, P. falciparum and P. vivax seem to be under control thanks to aggressive health measures. This study might provide a sound scientific basis for future control measures against malaria in Korea.

HIV-1 isolates Ug06 and Ug23 were established in culture from peripheral blood mononuclear cells (PBMCs) of Ugandan subjects. The isolates were studied for phylogenetic and serological relationships with each other and with the laboratory strains, HTLV-IIIB and HIV-1MN. The results suggest that the Ugandan isolates are related to different subgroups of African viruses with 17.3% of genetic distance between UG06 and the U455 provirus (Uganda); and 12.6% of genetic distance between UG23 and the JY1 provirus (Zaire). Analysis of the predicted amino acid sequences for Ug06 and Ug23 showed marked sequence heterogeneity in the V3 region and CD4-binding site. A conserved amino acid sequence was identified in the C-terminal immunodominant region of the envelope glycoprotein gp120. The isolates were compared in virus-neutralization experiments with HTLV-IIIB and HIV-1MN stocks, using panels of Western blot-positive North American and Ugandan sera. The North American serum samples showed broad neutralizing activity against both of the Ugandan isolates. However, the Ugandan serum panel demonstrated strain-specific activity against either Ug06 or Ug23. Furthermore, the African serum specimens showed higher prevalence and titers of neutralizing activity against the HIV-1MN stock as compared with HTLV-IIIB.

Cerebral hyperperfusion syndrome has been proposed to be caused by rapidly increased blood flow into chronically hypoperfused parenchyma with resultant impaired autoregulation, and has been noted after clipping of intracranial aneurysms and carotid stenting. The occurrence of the syndrome after endovascular flow diversion, however, has not been previously described. A 52-year-old woman was admitted electively for flow diverter treatment of a recurrent ventral paraclinoid aneurysm arising within a dysplastic segment of the left internal carotid artery. During the immediate postprocedural period the patient was found to have confusion, right hemiparesis, facial droop and dysarthria, which resolved with blood pressure control. Subsequent CT perfusion on day 11 demonstrated mildly elevated cerebral blood flow, cerebral blood volume and permeability values in the left hemisphere.

The morbidity and mortality in thalassemia patients are predominantly caused by iron overload cardiomyopathy (IOC). Iron-induced cardiac intracellular Ca²⁺ ([Ca²⁺]_i) dysregulation is among the core pathophysiological processes in IOC-related heart failure. Although cardioprotective roles of deferiprone (DFP) and N-acetylcysteine (NAC) have been reported, their effect on cardiac [Ca²⁺]_i transients and Ca²⁺-regulatory protein expression in thalassemic mice is unknown. In the present study, iron overload condition was induced in wild-type (WT) and heterozygous β-thalassemic (HT) mice by a high-iron diet. The iron-overloaded mice subsequently received a vehicle, DFP, NAC, or DFP plus NAC co-therapy. In both WT and HT iron-overloaded mice, DFP and NAC had similar efficacy in decreasing plasma non-transferrin-bound iron, decreasing cardiac iron concentration (CIC) and relieving systolic dysfunction. DFP plus NAC co-therapy, however, was better than the monotherapy in reducing CIC and restoring cardiac [Ca²⁺]_i transient amplitude and rising rate. All regimens produced no change in cardiac Ca²⁺-regulatory protein expression. We provided the first evidence regarding the synergistic effect of combined iron chelator-antioxidant therapy on cardiac [Ca²⁺]_i homeostasis in iron-overloaded thalassemic mice, with consistent improvement of cardiac contractility.

Tumor-suppressive miR-34a, a direct target of p53, has been shown to target several molecules of cell survival pathways. Here, we show that capsaicin-induced oxidative DNA damage culminates in p53 activation to up-regulate expression of miR-34a in non-small cell lung carcinoma (NSCLC) cells. Functional analyses further indicate that restoration of miR-34a inhibits B cell lymphoma-2 (Bcl-2) protein expression to withdraw the survival advantage of these resistant NSCLC cells. In such a proapoptotic cellular milieu, where drug resistance proteins are also down-regulated, p53-transactivated Bcl-2 associated X protein (Bax) induces apoptosis via the mitochondrial death cascade. Our results suggest that p53/miR-34a regulatory axis might be critical in sensitizing drug-resistant NSCLC cells.

Thirty hypertriglyceridemic patients were treated under metabolic ward conditions for 10 days with either placebo, clofibrate (500 mg t.i.d.) or bezafibrate (200 mg t.i.d.) in a randomized, double-blind study. In addition, patients received an isocaloric prudent diet. On day 10 a diurnal lipid and lipoprotein profile was carried out. Compliance to medication was good. Each treatment led to significant reductions of fasting triglycerides and cholesterol. Lowering of fasting and integrated diurnal triglycerides was greatest with bezafibrate. HDL-cholesterol profiles were highest with this drug. A strong correlation between fasting and diurnal triglycerides was observed. Triglyceride-lowering therapy must therefore aim at fasting triglyceride values as low as possible.

A multidisciplinary approach was used to identify and optimize a quinazolinedione-based ligand that would decrease the flexibility of the substrate-covering loop (catalytic loop) of the type II dehydroquinase from Helicobacter pylori. This enzyme, which is essential for the survival of this bacterium, is involved in the biosynthesis of aromatic amino acids. A computer-aided fragment-based protocol (ALTA) was first used to identify the aromatic fragments able to block the interface pocket that separates two neighboring enzyme subunits and is located at the active site entrance. Chemical modification of its non-aromatic moiety through an olefin cross-metathesis and Seebach's self-reproduction of chirality synthetic principle allowed the development of a quinazolinedione derivative that disables the catalytic loop plasticity, which is essential for the enzyme's catalytic cycle. Molecular dynamics simulations revealed that the ligand would force the catalytic loop into an inappropriate arrangement for catalysis by strong interactions with the catalytic tyrosine and by expelling the essential arginine out of the active site.

Among 21 intravenous heroin abusers with cutaneous and ocular manifestations of disseminated Candida infection, a single C. albicans strain type (serotype A, biotype 153/7) was isolated from skin lesions in 14 cases. This suggests that central contamination of the heroin with C. albicans is less likely to be the source of infection than an endogenous source, and that one particular strain type is either better adapted than others to grow in the lemon juice used as a heroin solvent, or more likely than others to cause the specific pathology seen in these patients.

The evolution of various spin structures in Yb doped GdMnO₃ distorted orthorhombic perovskite system was investigated from their magnetic, dielectric and magnetodielectric characteristics. The Gd_1-x Yb _x MnO₃ (0  ⩽  x  ⩽  0.15) revealed an enhanced magnetodielectric coupling when their magnetic structure is guided from ab to the bc-cycloidal spin structure upon Yb doping. The compounds exhibit magnetic field and temperature controlled spin-flop from c to a-axis. Additionally, magnetodielectric reversal is observed for the x  =  0.1 sample which depends on both magnetic field and temperature. The resultant correlation between magnetic and electric orderings is discussed in the frame of symmetric and antisymmetric exchange interaction models. These findings provide further insight in understanding the magnetoelectric materials and importantly show a way to tune the magnetic and magnetodielectric properties towards better application potential.

Three different types of nanoparticles, 1D Cloisite 30B clay nanoplatelets, 2D halloysite nanotubes (HNTs), and 3D nanobamboo charcoals (NBCs) were employed to investigate the impact of nanoparticle shapes and structures on the material performance of polyvinyl alcohol (PVA) bionanocomposite films in terms of their mechanical and thermal properties, morphological structures, and nanomechanical behaviour. The overall results revealed the superior reinforcement efficiency of NBCs to Cloisite 30B clays and HNTs, owing to their typical porous structures to actively interact with PVA matrices in the combined formation of strong mechanical and hydrogen bondings. Three-dimensional NBCs also achieved better nanoparticle dispersibility when compared with 1D Cloisite 30B clays and 2D HNTs along with higher thermal stability, which was attributed to their larger interfacial regions when characterised for the nanomechanical behaviour of corresponding bionanocomposite films. Our study offers an insightful guidance to the appropriate selection of nanoparticles as effective reinforcements and the further sophisticated design of bionanocomposite materials.

It is very important to extract all four coupling-of-modes (COM) parameters of the electrode cells for the simulation and optimal design of a low loss surface acoustic wave (SAW) filter. A new approach for fast and full extraction of the COM parameters for multielectrode-type grating is proposed. The field distribution of the wave under the periodic shorted grating is calculated by periodic Green's function method. The phase of the reflection is determined from the positions of the standing wave node. The transduction coefficient and its phase are determined by the charge distribution at low frequency. The COM parameters of the commonly used electrode width controlled (EWC) single phase unidirectional transducer (SPUDT) is computed. It shows that this is a simple and direct way to extract all the COM parameters for SPUDT and, accordingly, is a powerful tool for the optimization of the filter structure.

Male Sprague-Dawley rats were exposed in inhalation chambers to halothane and enflurane in concentrations from 50 to 1000 p.p.m. (0.0025 MAC-0.05 MAC) 6 h a day for 3-11 days. No signs of general toxicity were found. There was a normal increase in weight, and normal food consumption, organ to body weight ratios and normal histological findings in liver, kidney and lung. Exposure to 500 p.p.m. (0.05 MAC) of halothane induced the activity of NADPH-cytochrome-c-reductase in the liver, decreased the concentration of cytochrome P-450 in the kidney and decreased all the enzyme concentrations measured in lung microsomes. Exposure to halothane 50 p.p.m. (0.005 MAC) and enflurane produced only minor changes. It is concluded that the inhalation of halothane, in contrast to enflurane, may affect drug metabolism and thereby drug kinetics and toxicity. Halothane may increase its own toxicity by increasing the activity of NADPH-cytochrome-c-reductase in liver. An organ differentiation in enzymatic response was observed.

The reactivity of IgG and IgE antibodies from egg allergy patients to ovomucoid and its domain fragments was examined quantitatively, and compared with that of rabbit and mouse IgG anti-ovomucoid antibodies. The human antibodies reacted with the carbohydrate-containing domain fragments more strongly than the animal antibodies. In contrast, the human antibodies did not react with the carbohydrate-free third domain, whereas the animal antibodies definitely reacted. These results suggested that the sites and structures recognized by allergic individuals as ovomucoid antigenic determinants are not necessarily the same as those recognized by laboratory animals.

GOLPH2 gene SNP variants Rs10868366 and Rs7019241 were reported to decrease the risk of Alzheimer's disease in a recent Whole Genome Association Study. We have investigated these genetic variants in 2470 individuals from Spain to conduct an independent replication study of the proposed SNP markers. We found no evidence of association between GOLPH2 markers and susceptibility to Alzheimer's disease in our series. We concluded that GOLPH2 gene does not contribute to risk of disease in this study sample.

Mycobacterial growth inhibitory factor (MycoIF), found in supernatant fluids of mouse spleen cell cultures that have been stimulated in vitro with homologous antigen, inhibited the intracellular multiplication of virulent tubercle bacilli within normal mouse peritoneal macrophages in vitro. Antigenically stimulated H37Ra-immunized mouse spleen cells required 72 h of incubation to produce supernatant fluids that would cause intracellular inhibition. Supernatant fluids from 48-h mouse spleen cell cultures were not able to produce intracellular inhibition. Investigation of the culture conditions showed that at lease 1.0% human serum was required in the tissue culture medium for the production of MycoIF by spleen cells from immunized mice. MycoIF activity was noted only in supernatant fluids from spleen cell cultures incubated with antigen for 72 h. MycoIF was nondialyzable and unaffected by freezing, lyophilization, or incubation at 60 C for 30 min. However, MycoIF was inactivated after incubation at 80 C for 30 min. MycoIF was unaffected by low hydrogen ion concentrations (pH 7 to 12), but exposure to higher hydrogen ion concentrations (pH 6, pH 5) significantly decrease MycoIF activity, and exposure to pH 4 to 2 abolished all activity. Supernatant fluids diluted 1:32 were still able to produce significant intracellular inhibition of growth of virulent tubercle bacilli.

Integrative research on water resources requires a wide range of socio-environmental datasets to better understand human-water interactions and inform decision-making. However, in transboundary watersheds, integrating cross-disciplinary and multinational datasets is a daunting task due to the disparity of data sources and the inconsistencies in data format, content, resolution, and language. This paper introduces a socio-environmental geodatabase that transcends political and disciplinary boundaries in the Rio Grande/Río Bravo basin (RGB). The geodatabase aggregates 145 GIS data layers on five main themes: (i) Water & Land Governance, (ii) Hydrology, (iii) Water Use & Hydraulic Infrastructures, (iv) Socio-Economics, and (v) Biophysical Environment. Datasets were primarily collected from public open-access data sources, processed with ArcGIS, and documented through the FGCD metadata standard. By synthesizing a broad array of datasets and mapping public and private water governance, we expect to advance interdisciplinary research in the RGB, provide a replicable approach to dataset compilation for transboundary watersheds, and ultimately foster transboundary collaboration for sustainable resource management.

A microalgae (<i>Pseudokirchneriella subcapitata</i>) biosensor chip for pesticide sensing has been developed by attaching the immobilized microalgae biofilm pon the microarray dye spots (size 100 &#956;m and pitch 200 &#956;m). The dye spots (ruthenium complex) were printed upon SO₃-modified glass slides using a polydimethylsiloxane (PDMS) stamp and a microcontact printer (&#956;CP). Emitted fluorescence intensity (FI) variance due to photosynthetic activity (O₂ production) of microalgae was monitored by an inverted fluorescent microscope and inhibition of the oxygen generation rate was calculated based on the FI responses both before and after injection of pesticide sample. The calibration curves, as the inhibition of oxygen generation rate (%) due to photosynthetic activity inhibition by the pesticides, depicted that among the 6 tested pesticides, the biosensor showed good sensitivity for 4 pesticides (diuron, simetryn, simazine, and atrazine) but was insensitive for mefenacet and pendimethalin. The detection limits were 1 ppb for diuron and 10 ppb for simetryn, simazine, and atrazine. The simple and low-cost nature of sensing of the developed biosensor sensor chip has apparently created opportunities for regular water quality monitoring, where pesticides are an important concern.

The mortality rate of post-hepatectomy liver failure (PHLF) remains very high, and liver transplantation is the only effective treatment regimen for PHLF. Cell transplantation is a potential treatment for liver diseases. Previous studies have proved that mesenchymal stem cells (MSCs) have immunomodulatory functions. In the present study, we found that MSCs promoted glycogen synthesis and liver regeneration in the treatment of PHLF. MSC transplantation also improved the survival rate of rats after 90% partial hepatectomy (PH). In our current study, we aimed to determine the efficacy and mechanism of MSC transplantation in the treatment of PHLF.

Many drugs and chemical agents can cause enteritis and colitis, producing clinical gastrointestinal side effects, the most common of which are diarrhoea, constipation, nausea and vomiting. Significant histological overlap exists between some patterns of medication or chemical injury and various disease entities. A particular medication may cause multiple patterns of injury and may mimic common entities such as coeliac disease, Crohn's disease, infectious enteritis and colitis. Thus, given the common absence of specific histopathological features, the diagnosis often relies upon thorough clinicopathological correlation. This review concentrates on selected examples of medication-induced injury of the intestinal tract in which the pathology can be recognized, particularly on biopsies, with a focus on newly described medication-induced gastrointestinal effects.

Bromelain and N-acetylcysteine are two natural, sulfhydryl-containing compounds with good safety profiles which have been investigated for their benefits and application in health and disease for more than fifty years. As such, the potential values of these agents in cancer therapy have been variably reported in the literature. In the present study, the efficacy of bromelain and N-acetylcysteine in single agent and combination treatment of human gastrointestinal carcinoma cells was evaluated in vitro and the underlying mechanisms of effect were explored.

On-chip microsyringes are developed by integrating parallel micro actuators and a microfluidic chip. Sliders of an Electrostatically Controlled Linear Inchworm Actuator (ECLIA) are applied to manipulate microsyringes in the nanometer range, which allows liquid control on the picoliter scale. ECLIA drives sliders in parallel with high accuracy and a large stroke. The requirements for syringe performance, such as parallel and precise liquid control, can be satisfied by the above features of ECLIA. A total volume of a few microL is manipulated at a flow rate of 19-27 pL s(-1) by the stepwise motion of ECLIA sliders in a fluidic channel. Microsyringes integrated into the driving mechanism are a key component of Micro Total Analysis Systems (microTAS) due to the possibility of on-chip integration. In addition, the proposed approach has a significant implication in MEMS in that the electrostatic micro actuator performs a physical task that affects the outside structure.

Prader-Willi syndrome (PWS) and Angelman syndrome (AS) are two clinically distinct neurogenetic disorders arising from a loss of expression of imprinted genes within the human chromosome region 15q11-q13. Recent evidence suggests that the SNRPN gene, which is defective in PWS, plays a central role in the imprinting-center regulation of the PWS/AS region. To increase our understanding of the regulation of expression of this imprinted gene, we have developed single-cell-sensitive procedures for the analysis of expression of the SNRPN gene during early human development. Transcripts of SNRPN were detected in human oocytes and at all stages of preimplantation development analyzed. Using embryos heterozygous for a polymorphism within the SNRPN gene, we showed that monoallelic expression from the paternal allele occurs by the 4-cell stage. Thus, the imprinting epigenetic information inherited in the gametes is recognized already in the preimplantation embryo. The demonstration of monoallelic expression in embryos means that efficient preimplantation diagnosis of PWS may be made by analysis for the presence or absence of SNRPN mRNA.

The host/guest interactions in water of a star polymer consisting of a β-cyclodextrin (β-CD) core bearing six poly(ethylene oxide) arms linked to the C6 positions of β-CD (β-CD-PEO7, Mn 5000 g mol(-1)) and α,ω-di-(adamantylethyl)poly(N-isopropylacrylamide) (Ad-PNIPAM-12K, Mn 12,000 g mol(-1)) were studied by 1D and 2D (1)H and (13)C NMR spectroscopy, isothermal calorimetry (ITC), and light scattering (LS). In cold water (T < 26 °C) supramolecular "dumbbell" assemblies, consisting of PNIPAM chains with β-CD/Ad inclusion complexes at each end, formed viaβ-CD-insertion of the terminal Ads through the β-CD secondary face. Light scattering, microcalorimetry (DSC), and DOSY NMR studies indicated that mixed aqueous solutions of β-CD-PEO7 and Ad-PNIPAM-12K undergo a reversible heat-induced phase transition at ∼32 °C, accompanied by a release of a fraction of the Ad-bound β-CD-PEO7 into bulk solution and the formation of aggregated Ad-PNIPAM-12K stabilized by a β-CD-PEO7 shell.

The authors combined a monopolar electrode and a suction/irrigation channel with a 0 degrees, 4-mm Hopkins rigid telescope into a single multifunctional unit. This three-in-one instrument is inserted through a lightweight 7.5-mm outer sheath, which is fixed separately. A fourth instrument (for example, a balloon catheter or a biopsy forceps) can be introduced and manipulated independently with the other hand. All endoscopic procedures were performed with a trephine to create a 15-mm craniotomy. After opening the dura mater, ventricles were tapped with a brain needle, which was followed by the insertion of the rigid scope for visualization. The telescope was then withdrawn momentarily; the outer sheath was introduced into the ventricle and fixed over the area of interest. The definitive procedure was then performed with ease by using the multifunctional three-in-one instrument in one hand and a fourth instrument in the other hand. This novel neuroendoscopic system has been used in clinical testing at the Vidyasagar Institute of Mental Health and Neurosciences since May 1998. Thus far, 83 neuroendoscopic procedures have been successfully performed with the aid of this instrumentation system, which has proven to be safe, versatile, and cost-effective, allowing a greater degree of freedom for the neurosurgeon.

Seventeen cases of soft tissue sarcoma (STS) developing in the pleural cavity were collected from Japanese hospitals, and their clinical and pathologic findings summarized. Eight of the 17 patients had a 15-year to 50-year (mean, 28.8) history of chronic pleural inflammatory disease (pleuritis, pyothorax, and pulmonary tuberculosis) before the onset of the pleural sarcoma. Histologically, malignant fibrous histiocytoma was the most common tumor type (11 cases), followed by angiosarcoma (four). The age at diagnosis of the sarcoma ranged from 15 to 74 years (mean, 58); the male-to-female ratio was 3.3:1. In the eight cases of sarcoma associated with chronic pleural inflammatory disease, male preponderance was more marked (7:1). The commonest presenting symptom was chest pain. A mass could be detected by chest roentgenograms in 13 patients and computed tomographic scans in 15 patients. No patient had distant metastases at first admission. Thirteen patients were treated by surgery, chemotherapy, and/or radiation therapy. Thirteen of the 17 patients died 1 to 87 months (mean, 14.2) after therapy for STS. The actuarial 1-year survival rate was 38.5%. These findings suggest that long-standing pleural inflammation might be an etiologic factor for development of pleural STS.

The efficacy of baclofen in the treatment of chronic hiccup is demonstrated in two cases. These cases highlight the present state of knowledge related to hiccup. This discussion focuses on the definition and classification of hiccup, etiologies, postulated theories to explain its function, the few studies performed to date, and non-pharmacologic and pharmacologic treatment. Baclofen appears to be the agent most efficacious in the treatment of chronic hiccup. Its commonest side effect is sedation; insomnia, dizziness, weakness, ataxia, and confusion also can occur. Following regular use, abrupt discontinuation can lead to withdrawal symptoms, such as seizure, and gradual discontinuation is recommended.

Morpholine, a six-membered heterocycle containing one nitrogen and one oxygen atom, is a moiety of great significance. It forms an important intermediate in many industrial and organic syntheses. Morpholine containing drugs are of high therapeutic value. Its wide array of pharmacological activity includes anti-diabetic, anti-emetic, growth stimulant, anti-depressant, bronchodilator and anticancer. Multi-drug resistance in cancer cases have emerged in the last few years and have led to the failure of many chemotherapeutic drugs. Newer treatment methods and drugs are being developed to overcome this problem. Target based drug discovery is an effective method to develop novel anticancer drugs. To develop newer drugs, previously reported work needs to be studied. Keeping this in mind, last five year's literature on morpholine used as anticancer agents has been reviewed and summarized in the paper herein.

The number of V1b vasopressin receptors (V1bR) in the anterior pituitary plays an important role during adaptation of the hypothalamic-pituitary-adrenal axis to stress in rats. Regulation of V1bR expression involves transcriptional and translational mechanisms. One of the elements mediating transcriptional activation of the rat V1bR gene is a long stretch of GAGA repeats (GAGA box) in the promoter located near the transcription start point capable of binding a protein complex of 127 kDa present in pituitary nuclear extracts. There is a lack of correlation between changes in V1bR mRNA and the number of VP binding sites, suggesting that V1bR expression depends on the efficiency of V1b R mRNA translation into protein. Two mechanisms by which the 5' untranslated region (5'-UTR) of the rat V1bR mRNA can mediate either inhibition or activation of V1bR mRNA translation have been identified. First, upstream open reading frames (ORF) present in the 5'-UTR repress translation of the major ORF encoding the V1b receptor, and secondly, an internal ribosome entry site (IRES) activates V1bR translation. Stimulation of IRES activity through protein kinase C-mediated pathways results in V1bR mRNA translation increasing V1bR protein levels. The existence of multiple loci of regulation for the V1bR at transcriptional and translational levels provides a mechanism to facilitate plasticity of regulation of the number of pituitary vasopressin receptors according to physiological demand.

Plasma cell-free DNA is the soluble DNA and tumor-derived DNA in plasma which has the same mutation as the tumor cellular DNA. This study aimed at comparing the properties of plasma cell-free DNA with the biopsy's DNA in order to evaluate the clinical significance of IgH and TCRγ gene rearrangement in plasma cell-free DNA from patients with non-Hodgkin's Lymphoma. A total of 360 samples were studied. IgH (FR3A/VLJH) and TCRγ (TVG/TJX) were amplified by PCR. Results of plasma cell-free DNA were compared with biopsy's DNA and mononuclear cellular DNA respectively. Plasma cell-free DNA were successfully extracted from 288 cases of newly diagnosed, refractory and relapsed NHL in total 360 patients (80%).But nothing was found in the other 72 remittent patients. The positive percentage of IgH rearrangement in patients with B-NHL was 81% in plasma cell-free DNA and 77% in biopsy's DNA (P>0.05). As to the ratio of TCRγ rearrangement in patients with T-NHL, the former was 44%, and the latter was 39% (P>0.05). These results show tumor-derived DNA could be detected in tumor loaded plasma, even of underlying cancer patients. For NHL patients, detecting IgH and TCRγ gene rearrangement of plasma cell-free DNA has the same clinical significance as biopsy's DNA. Moreover, it's more simple, convenient and non-invasive.

To investigate analgesic neural circuits activated by electroacupuncture (EA) at different sets of acupoints in the brain, goats were stimulated by EA at set of Baihui-Santai acupoints or set of Housanli acupoints for 30 min. The pain threshold was measured using the potassium iontophoresis method. The levels of c-Fos were determined with Streptavidin-Biotin Complex immunohistochemistry. The results showed pain threshold induced by EA at set of Baihui-Santai acupoints was 44.74% ± 4.56% higher than that by EA at set of Housanli acupoints (32.64% ± 5.04%). Compared with blank control, EA at two sets of acupoints increased c-Fos expression in the medial septal nucleus (MSN), the arcuate nucleus (ARC), the nucleus amygdala basalis (AB), the lateral habenula nucleus (HL), the ventrolateral periaqueductal grey (vlPAG), the locus coeruleus (LC), the nucleus raphe magnus (NRM), the pituitary gland, and spinal cord dorsal horn (SDH). Compared with EA at set of Housanli points, EA at set of Baihui-Santai points induced increased c-Fos expression in AB but decrease in MSN, the paraventricular nucleus of the hypothalamus, HL, and SDH. It suggests that ARC-PAG-NRM/LC-SDH and the hypothalamus-pituitary may be the common activated neural pathways taking part in EA-induced analgesia at the two sets of acupoints.

Polygonum multiflorum Thunb. has been used widely in East Asia in treatment of diseases associated with aging. However, there are many reports referred to the toxicity of P. multiflorum, especially for liver adverse reactions. The toxicity of it is caused by over dosage or by the herb itself remains unclear. The aim of this study was to study the toxicity of different extractions, components and constituents of P. multiflorum, which were assessed in zebrafish embryos. Firstly, the difference of extracting solvent to the toxicity of P. multiflorum was researched to probe the influence of usages to the safety of P. multiflorum. The toxicity of 70% EtOH extract is considerably higher than that of other extracts. Secondly, 70% EtOH extract was subjected to macroporous resin (DM-8) eluting with a gradient of water and EtOH (H₂O, 25% EtOH, 40% EtOH and 95% EtOH) to give four components (A-D). The toxicity of the component (D) showed higher than the other components (A-C). Thus, the component (D) was taken more attentions to research. Lastly, study on the chemical constituents of the component (D), 27 compounds, including 7 anthraquinones (1-7), 8 stilbenes (8-15), 7 anthrones (16-22), 3 cinnamic acid amides (23-25), 2 naphthols (26-27) were isolated and assessed in zebrafish embryos. Compounds 1-3, 16-22 and 26-27 showed severe toxicity against the zebrafish embryos while other compounds, such as stilbenes, showed no obvious toxicity.

New low-energy electron injection systems based on indirectly heated dispenser cathodes facilitate electron capture dissociation (ECD) in Fourier transform ion cyclotron resonance (FTICR) mass spectrometry. In this joint report, details are presented of the design and performance of these systems on two commercial FTICR instruments, 9.4 T Bruker BioAPEX in Uppsala and 4.7 T IonSpec Ultima in Odense. New results include obtaining meaningful one-scan MS/MS data for isolated precursor ions with millisecond irradiation times. The ECD rate improvement is not only due to the larger total electron current, but the larger emitting area as well.

A 66 year-old man with a previous history of Sjögren's syndrome was admitted with anastomotic pseudoaneurysm and aortic dissection in the ascending aorta, which developed after Bentall's surgery, a procedure that has severe complications and high mortality. Using the reverse extra-anatomical aortic arch debranching technique, zone 0 thoracic endovascular aortic repair was performed emergently. The postoperative course was uneventful. Twenty months later, computed tomography showed remodeling of the dissection, resolution of the pseudoaneurysm, and patency of the reverse extra-anatomical aortic arch debranching graft.

Lysosomes play a critical role in the autophagy process. The impairment of lysosomes can affect the degradation of autophagic cargo, leading to the blockage of autophagy at the lysosomal stage and subsequent cell death. Herein, two phosphorescent Re(i) tricarbonyl complexes (Re1 and Re2) bearing β-carboline derivatives have been synthesized and characterized. Both complexes show pH-dependent phosphorescence, which can be used to specifically image the lysosomes. Cytotoxicity assay shows that they exhibit high anticancer activity and are able to overcome cross-resistance to cisplatin. Re2 can induce autophagy, which is blocked at the lysosomal stage due to lysosomal dysfunction, such as the decrease of cathepsin B activity, subsequently leading to both autophagy and apoptosis dependent cell death. In vivo studies revealed that it could significantly inhibit tumor growth.

An important aspect in the problem of interactions between microorganisms in the conditions of oil pollution is how to preserve the viability of phototrophic organisms if active oil-oxidizing microflora is present in the environment. As was illustrated using a closed model ecosystem, the association 'cyanobacteria--oil-oxidizing bacteria' is capable of withstanding the negative effect of oil pollution, but within the range of hydrocarbon concentrations which can be oxidized by oil-oxidizing bacteria during a very short time. The biological equilibrium in the ecosystem was maintained and the number of viable cells of the phototrophic component in the ecosystem increased if the oil-oxidizing bacteria started to function at the same time as toxic compounds commenced to produce their effect on the microorganisms.

We treated eight patients with Kienböck's disease (two patients each with stage 1, 2, 3a and 3b disease by Lichtman's classification) by removing a pedicled, vascularised bone segment from the dorsal aspect of the distal radius and engrafting it into the lunate. Additional shortening of the radius was performed in patients with the ulna-minus or null variant. Shortening of the capitate and capito-hamate fusion were also performed in patients with stage 3 disease. All patients were relieved of their wrist pain at rest and during movement, and the mean grip strength increased from 37% of that in the contralateral hand before surgery to 80% after surgery. The mean post-operative range of motion in the affected wrist was 92% of that in the opposite wrist in patients with stage 1 and 2 disease, and 53% in patients with stage 3 disease. Post-operative assessment revealed that four patients had excellent results, three had good results, and one had a fair result.

Erectile dysfunction (impotence) is a well-known complication of blunt pelvic and perineal trauma. The mechanism of injury is usually related to the trauma itself, via shearing of the penile blood vessels in the pelvis, or via direct trauma to the blood vessels in the perineum. The diagnostic evaluation of these patients should include evaluation of the nervous supply of the penis, the penile arterial tree and the veno-occlusive mechanism. Penile revascularization is a reasonable treatment option for this group in that many injured patients are young and show arterial injury, with minimal or no veno-occlusive dysfunction. Proper patient selection and precise operative technique should allow for restoration of erectile dysfunction in these patients.

Pimecrolimus is a topical calcineurin inhibitor currently approved for second-line use in the management of mild-to-moderate atopic dermatitis in patients age 2 years and older. Given the safety profile and nonsteroidal mechanism of pimecrolimus, there has been significant interest in its use in the treatment of a variety of dermatological conditions. This article reviews research that has been published on the off-label uses of topical pimecrolimus, with a focus on published RCTs. Convincing evidence exists supporting pimecrolimus' efficacy in oral lichen planus and seborrheic dermatitis. For other conditions studied to date, pimecrolimus may prove to be a useful treatment alternative when conventional agents fail. Adverse events seen with its off-label use were typically application site reactions, the most common being a transient burning sensation. In summary, pimecrolimus appears to be an effective agent in the treatment of multiple dermatological conditions and may be worth considering as a pharmacologic alternative in several conditions when first-line treatment fails, or for areas that are more susceptible to the adverse effects of topical corticosteroids.

Methanol is known as a strong inhibitor of hydrate formation, but clathrate hydrates of ethanol and 1-propanol can be formed in the presence of help gases. To elucidate the hydrophilic and hydrophobic effects of alcohols, their interactions with simple solute species are investigated in glassy, liquid, and crystalline water using temperature-programmed desorption and time-of-flight secondary ion mass spectrometry. Nonpolar solute species embedded underneath amorphous solid water films are released during crystallization, but they tend to withstand water crystallization under the coexistence of methanol additives. The CO₂ additives are released after crystallization along with methanol desorption. These results suggest strongly that nonpolar species that are hydrated (i.e., caged) associatively with methanol can withstand water crystallization. In contrast, ethanol and 1-propanol additives weakly affect the dehydration of nonpolar species during water crystallization, suggesting that the former tend to be caged separately from the latter. The hydrophilic vs. hydrophobic behavior of alcohols, which differs according to the aliphatic group length, also manifests itself in the different abilities of surface segregation of alcohols and their effects on the water crystallization kinetics.

Plasmodium vivax reemerged in the Republic of Korea (ROK) in 1993, and is likely to continue to affect public health. The purpose of this study was to measure levels of anti-P. vivax antibodies using indirect fluorescent antibody test (IFAT) in border areas of ROK, to determine the seroprevalence of malaria (2003-2005) and to plan effective control strategies. Blood samples of the inhabitants in Gimpo-si, Paju-si, and Yeoncheon-gun (Gyeonggi-do), and Cheorwon-gun (Gangwon-do) were collected and kept in Korea Centers for Disease Control and Prevention (KCDC). Out of a total of 1,774 serum samples tested, the overall seropositivity was 0.94% (n=17). The seropositivity was the highest in Paju-si (1.9%, 7/372), followed by Gimpo-si (1.4%, 6/425), Yeoncheon-gun (0.67%, 3/451), and Cheorwon-gun (0.19%, 1/526). The annual parasite incidence (API) in these areas gradually decreased from 2003 to 2005 (1.69, 1.09, and 0.80 in 2003, 2004, and 2005, respectively). The highest API was found in Yeoncheon-gun, followed by Cheorwon-gun, Paju-si, and Gimpo-si. The API ranking in these areas did not change over the 3 years. The seropositivity of Gimpo-si showed a strong linear relationship with the API of 2005 (r=0.9983, P=0.036). Seropositivity data obtained using IFAT may be useful for understanding malaria prevalence of relevant years, predicting future transmission of malaria, and for establishing and evaluating malaria control programs in affected areas.

There is association between migraine, particularly migraine with aura, and large persistent foramen ovale (PFO) and other right-to-left shunts. Migraine is often improved by closure of a PFO in patients who have a large shunt. Inheritance of migraine is linked to the inheritance of large atrial shunts in some families. The data indicate that in some patients PFOs play a causal role in migraine with aura. These observations may also improve understanding of the etiology of migraine in patients who do not have a shunt.

A computationally tractable form of the rate-level model proposed by Sachs and Abbas (1974) is presented. The first stage of the model is a compressive nonlinearity whose input-output function is chosen to reflect current data on basilar-membrane displacement. The output of this nonlinearity is converted to driven discharge rate by the saturating nonlinearity originally used by Sachs and Abbas (1974). In fitting the model to data four model parameters are chosen to minimize the mean squared error between rate functions generated by the model and the data. With parameters chosen in this way, the model provides good fits to the range of rate-level shapes from flat saturations to sloping saturations. One important parameter in the model is the 'threshold for compression'. For low- and medium-spontaneous rate fibers with similar best frequencies (BFs), the minimum mean squared error compression threshold is roughly constant at about 30 dB above the thresholds of the most sensitive (high-spontaneous rate) fibers at that BF.

Chronic lymphocytic leukemia (CLL) is one of the most common types of leukemia in the western world which affects mainly the elderly population. Progress of the disease is very heterogeneous both in terms of necessity of treatment and life expectancy. The current scoring system for prognostic evaluation of patients with CLL is called CLL-IPI and predicts the general progress of the disease but is not a measure or a decision aid for the necessity of treatment. Due to the heterogeneous behavior of CLL it is important to develop tools that will identify if and when patients will necessitate treatment for CLL. Recently, Machine Learning (ML) has spread to many public health fields including diagnosis and prognosis of diseases.

Provider burnout is a significant health care concern. It is unclear whether high reliability organization (HRO) practices can prevent it. The Truman Veterans Affairs Medical Center (VAMC) undertook an initiative implementing HRO principles and assessed for impact on burnout metrics. This became known as the Transformative HRO Initiative Via Employee Engagement (THRIVE2) model. THRIVE2 consisted of Just Culture training, Clinical Team Training, and continuous process improvement through Lean. Truman VAMC was compared with other Veterans Health Affairs (VHA) facilities regarding burnout and employee satisfaction metrics. Truman VAMC saw significant changes in multiple HRO metrics (P < 0.001) as well as improvements in work group psychological safety and employee exhaustion (P < 0.001). High burnout rates decreased by 52% (6.2%-2.95%; P < 0.001). Truman VAMC went from 75th to the No. 1 ranked VHA facility regarding Best Places to Work. These findings have significant national policy implications given the effects of burnout.

A highly performing proton conducting composite was prepared through the impregnation of EMIMCl ionic liquid in the mesoporous MIL-101(Cr)-SO₃H MOF. The resulting EMIMCl@MIL-101(Cr)-SO₃H composite displays high thermal and chemical stability, alongside retention of a high amount of EMIMCl even at temperatures as high as 500 K, as well as under moisture conditions. Remarkably, this composite exhibits outstanding proton conductivity not only at the anhydrous state (<i>&#963;</i>_{473 K} = 1.5 &#215; 10^-3 S cm^-S) but also under humidity (<i>&#963;</i>_{(343 K/60%-80%RH)} &#8805; 0.10 S cm^-1) conditions. This makes EMIMCl@MIL-101(Cr)-SO₃H a unique candidate to act as a solid state proton conductor for PEMFC applications under versatile conditions.

Daytime sleepiness is a risk factor in community life and road traffic. The German legislator has reacted to the alarmingly high number of traffic accidents caused by exhaustion and tiredness, and added directives in matters of insomnia and sleep disturbance into the regulations concerning driving licences (FeV). Paragraph 11 implies that the holder of a driving licence has met the necessary physical and mental requirements. The requirements are not fulfilled when a disease or defect according to annex 4 or 5 of the regulation concerning driving licence exists. Number 11.2 of annex 4 contains regulations about the aptitude to conduct automobiles with regard to people suffering from chronic insomnia. Following the text of the directive, unaccompanied people with insomnia no longer have the authorisation to conduct automobiles when they suffer of a measurably pronounced somnolence during the daytime. Only people with treated insomnia remain suitable to conduct automobiles under the restriction that no measurably pronounced somnolence exists. As a condition for the aptitude to obtain and keep a driving licence the person has to undergo continuous checks of his/her disease. People with special driving licence classes according to annex 5, i. e. for heavy goods vehicles, buses and taxis, are regularly screened and have to by examined by a doctor if they have typical symptoms of insomnia.

A new way to approaching highly emissive BODIPY dyes in both solution and solid state is achieved by introducing intramolecular charge transfer (ICT). A hybrid excited state that shows behaviors of both the ICT excited state and local excited state is discovered to be beneficial in avoiding the disturbance from the rotation vibration of the flexible phenyl substituents. Thus, the nonradiative transition process is suppressed, and the fluorescence efficiency goes up. By modification of the excited state, we realize emission enhancement of crystalline BODIPY derivatives with a PLQY from 0.08 to 0.27, and the compound expresses a good potential application prospect in organic semiconductors.

The question of how science, medicine and medical practice are related also compromises the crucial issue of the character of medicine. At the beginning of the 19th century, medicine tried to overcome the ancient contradiction within the unity of scientific thought and the deduction of guidelines and techniques for medical practice. This aim was partly achieved in medico-theoretical reasoning and practical procedures as well as for nosology, casuistic thinking and diagnostics. But medicine is a discipline directed towards healing. So the intentions of medicine and the reality of clinical healing possibilities, however, showed an increasing divergence since the middle of the 19th century. This divergence triggered considerable reactions not only from "Schulmedizin" and from other disciplines but also from practicing doctors and mainly from (disappointed) patients. Together with the continuous changes in empirical clinical research these internal and especially external reactions to medicine showed fundamental differences between medicine and the sciences. During the decades of this development it has become obvious that medicine will never become a pure science, not even an applied science. As medicine is concerned with patients who need to be considered as individual subjects, medical knowledge and medical practice consequently form a dialectic unity which is directed by the patient as a subject.

Lenalidomide is an immunomodulatory drug (IMiD), which is well established and approved in the treatment of multiple myeloma (MM) and 5q-myelodysplastic syndrome (MDS). The mode of action includes immune modulation, anti-angiogenetic, anti-inflammatory, and anti-proliferative effects. Development of lenalidomide initiated a profound shift in therapeutic approaches especially toward MM. This chapter will discuss the mode of action of lenalidomide as well as its clinical applications. Important clinical phase II and III data of lenalidomide are presented. Currently, lenalidomide is not only investigated in MM and MDS, but also in malignant lymphomas and other entities.

The purpose of this study was to determine the minimum thickness of cortical bone required for the accurate measurement of cortical material density by computed tomography (CT) and to establish normal reference values. A phantom with several wall thicknesses of bone-like material was constructed to simulate various cortical widths. The CT density at each level of thickness was measured on a GE 9800 CT scanner and on the OsteoQuant, a special CT scanner optimized for the measurement of bone in the extremities. The minimum width required to attain the correct material density was determined for each scanner. Additionally, the material density and width of the cortex in the radius and/or femur were measured by CT in 761 healthy subjects, ages 4-84 years. The minimum thickness necessary for an accurate density evaluation of the walls of the phantom by CT was 2-2.5 mm; below these thresholds the values fell in a linear way relative to width. In humans, the material density of cortical bone in the appendicular skeleton was not influenced by height or weight, and the values were similar for all subjects, as long as the cortical width was above 2-2.5 mm. The cortical width increased with age up to 30 years and decreased from 50 years on. We conclude that the material density of cortical bone in the appendicular skeleton can be measured accurately by CT if the thickness of the cortex exceeds 2-2.5 mm.

Over the years, the definition of implant failure has varied, with some investigators accounting for all implants placed, while others discard failures that occurred before clinical loading. The influence of stresses transmitted to various bone densities, by different prosthetic appliances as well as the method used to determine failures, needs to be clearly understood. This paper reports on the influence of two different methods of determining 36-month survival of implants used to support different dental prostheses.

The physiological benefits of dietary flavonoids have been attributed to their antioxidant and signaling properties. Our previous study revealed that hesperetin exhibits neuroprotection in PC12 cells by diverse mechanisms. Biological activities of flavonoids might be determined by their chemical structures. Here, we further studied the effects of hesperetin and its structural counterparts, isorhamnetin and isosakuranetin, on kinases related to survival signaling as well as other cytoprotective actions. Pretreatment with flavonoids (0.8 or 50 microM) increased cell viability and catalase activity (CA) and decreased membrane damage, reactive oxygen species (ROS) generation, intracellular calcium level ([Ca2+]i), and caspase-3 activity in H2O2-treated PC12 cells. Increased CA, [Ca2+]i, and ROS levels, but lower caspase-3 activities, were obtained upon treatment with 50 microM isorhamnetin or isosakuranetin. Based on their structural differences and the concentrations used, these flavonoids differentially activated pro-survival signaling molecules, including Akt/protein kinase B, p38 mitogen-activated protein kinase, and inhibited the activation of c-jun N-terminal kinase, which triggers apoptosis. Our results demonstrate that signaling actions of thses flavonoids are involved in their neuroprotection against oxidative stress and that they act more as signaling molecules than antioxidants.

Nonalcoholic fatty liver disease is the most common noninfectious liver disease in clinical practice, and there is an increasing need for new therapeutic approaches for the treatment of this liver disease. Here, we examined the effect of the thyroid hormone triiodothyronine (T3) and the agonist of the thyroid hormone receptor beta isoform (TRbeta), GC-1, on fatty liver and steatohepatitis induced in rodents by a choline-methionine deficient (CMD) diet. Male Fischer 344 rats fed a CMD diet for 1 wk developed a marked fatty liver and mild hepatitis. Concurrent administration of T3 resulted in a complete prevention of the fatty change associated with increased fatty acid mitochondrial and peroxisomal beta-oxidation. To investigate whether T3 could also reverse fully established fatty liver, rats were fed a CMD diet for 10 wk and then cofed T3 for 1 wk. Coadministration of T3 resulted in a complete regression of liver steatosis associated with a decrease of lipid peroxidation, cyclooxygenase-2 expression, and activation of phospho-STAT3 and phospho-SAPK/JNK. Finally, additional experiments showed that GC-1, which has no significant side effects on heart rate, prevented and reverted CMD-induced fat accumulation, and ameliorated steatohepatitis. These results indicate that TR agonists have the potential to inhibit or reverse hepatic steatosis induced by a nutritional model.

Digital health management is increasingly pivotal in the care of patients with diabetes. The aim of this review was to evaluate the clinical benefits of using smart insulin pens with connectivity for diabetes management. The search was performed using PubMed and PubMed Central on May 15, 2019, to identify publications investigating the use of insulin pens. Studies evaluating insulin pens with connectivity via Bluetooth/Near Field Communication, with an associated electronic device enabling connectivity, or with a memory function were included in the review. Nine studies were identified in the search. Overall, these studies lacked data on smart insulin pens with a connectivity function, with eight of the available studies investigating only pens with a memory function. The studies focused primarily on assessing patient preference, usability, and technical accuracy. The number of studies assessing clinical outcomes was small (<i>n</i>&#8201;=&#8201;3). However, the majority of studies (<i>n</i>&#8201;=&#8201;8) reported that patients preferred smart insulin pens because they increased confidence with regard to diabetes self-management. These results suggest a lack of published data regarding smart insulin pens with connectivity for the management of diabetes. However, the available published data on usability and patient preference suggest that the use of smart insulin pens holds promise for improving and simplifying diabetes self-management.

The delta-globin genes of a normal Japanese and a Japanese patient with homozygous delta-thalassemia were cloned, and the nucleotide sequence of a region including the gene was determined. Comparison of the nucleotide sequences of these two individuals with that of pH delta 1, delta-globin clone from the gene library constructed by Maniatis et al., showed differences in the large intervening sequence (IVS 2), at positions 137, 151, 186, 188, 291, 292 and 540 as one base substitutions, at 339 and 823 as one base additions, at 548 as a one base deletion, and a 9 bp duplication between positions 651 and 659, and differences in the 3'-flanking sequence at 51 and 98 nucleotides 3' to the AATAAA sequence. However, in the region studied, no differences was observed in the nucleotide sequences of the normal subject and the patient with delta-thalassemia. Therefore, these differences may represent polymorphisms of the delta-globin gene present in Japanese individuals. These data suggest that IVS 2 is more divergent than other regions, and that a DNA region(s) other than the globin gene may affect expression of the gene.

Following ovariectomy, the vaginal epithelium of the mouse is reduced to two layers of cells, the basal layer that constitutes the germinative compartment and surface layer. Under estrogenic influence, this tissue undergoes keratinization at the expense of asal cell only. The initially superficial cells are progressively sloughed, without taking part in the cornification process. We have shown previously that within the first 12 hours after estrogen administration (that is, before any change in mitotic activity is detected) an intermediate layer of cells is formed. Thurs, a migratory process is induced, which leads to a very rapid redistribution to basal cells into two layers...

This study evaluated pulsed TDI variables including the isovolumic time interval and duration of the major wave in a population of large healthy dogs. Longitudinal myocardial motion at the septal mitral annulus was evaluated with pulsed TDI in 45 healthy adult dogs. Maximal myocardial velocities, isovolumic time intervals, and duration of the myocardial waves were measured. The correlation between time intervals and velocity variables was also investigated. The mean maximal systolic velocity was 6.92 ± 1.78 cm/sec, the mean early diastolic velocity (Em) was 6.58 ± 1.81 cm/sec, the mean late diastolic velocity (Am) was 5.10 ± 2.00 cm/sec, the mean isovolumic contraction time (IVCT) was 53.61 ± 95.13 msec, and the mean isovolumic relaxation time (IVRT) was 26.74 ± 57.24 msec. The early diastolic mitral inflow velocity (E)/Em ratio was 10.94 ± 3.27 while the Em/Am ratio was 1.40 ± 0.40. There was a negative correlation between Am duration and Am amplitude, and a positive correlation between the IVRT and Em/Am ratio (p < 0.05). The normal LV parameter using pulsed TDI method could be used as the reference range for identifying myocardial dysfunction in dogs.

The natural ends of linear chromosomes require unique genetic and structural adaptations to facilitate the protection of genetic material. This is achieved by the sequestration of the telomeric sequence into a protective nucleoprotein cap that masks the ends from constitutive exposure to the DNA damage response machinery. When telomeres are unmasked, genome instability arises. Balancing capping requirements with telomere replication and the enzymatic processing steps that are obligatory for telomere function is a complex problem. Telomeric proteins and their interacting factors create an environment at chromosome ends that inhibits DNA repair; however, the repair machinery is essential for proper telomere function.

Research suggests that family efficacy-defined as a family's beliefs in its capability to manage different situations in order to achieve a desired outcome-is linked to a decreased likelihood of adolescents to engage in risky health behaviors. It is not clear, however, if this is true for immigrant families when they are encountering with increased challenges in their host countries. To provide holistic nursing care to immigrant families, it is important to know the sources of family efficacy particularly for immigrant adolescents when they are developing health behavior. This integrative review examined existing literature to learn about the sources of family efficacy among immigrant adolescents and how different domain of family efficacy is related to risky behaviors. We examined 22 studies on the topics of immigration, adaptation, risky adolescent behavior, and family function. Findings showed that multidimensional sources of family efficacies (specifically those in the relational, pragmatic, and value-laden domains) exert significant positive effects on immigrant adolescents' health behaviors.

Increasing the environmental benignity of lithium-ion batteries is one of the greatest challenges for their large-scale deployment. Toward this end, we present herein a strategy to enable the aqueous processing of high-voltage LiNi_0.5 Mn_1.5 O₄ (LNMO) cathodes, which are considered highly, if not the most, promising for the realization of cobalt-free next-generation lithium-ion cathodes. Combining the addition of phosphoric acid with the cross-linking of sodium carboxymethyl cellulose by means of citric acid, aqueously processed electrodes with excellent performance are produced. The combined approach offers synergistic benefits, resulting in stable cycling performance and excellent coulombic efficiency (98.96&#8201;%) in lithium-metal cells. Remarkably, this approach can be easily incorporated into standard electrode preparation processes with no additional processing step.

Giant axonal neuropathy (GAN) is a very rare autosomal recessive disorder characterized by abnormally large and dysfunctional neuronal axons. Mutations in the <i>GAN</i> gene have been identified as the cause of this disorder. In this report, we performed a detailed phenotypic assessment of a Chinese patient with GAN. An array-based exon capture test and targeted next-generation sequencing were used to detect the suspected mutation sites. Compound heterozygous mutations of p.S79L (c.236C &gt; T) in the BTB domain and p.T489S (c.1466C &gt; G) in the kelch domain were identified in the proband's genome. S79L was a known mutation, and T489S was reported for the first time. The p.S79L and p.T489S were confirmed in the proband's mother and father, respectively. Both mutations were located in highly conserved regions and affected the predicted protein crystal structures. The proband's sural biopsy revealed the classical GAN phenotype of swollen axons filled with closely packed neurofilaments. The combined application of the next-generation sequencing platform and bioinformatics analyses was an effective method for diagnosing GAN. The novel compound mutations of S79L and T489S in the <i>GAN</i> gene were likely the cause of the patient's GAN symptoms. Our findings enrich the spectrum of mutations associated with this rare type of axonopathy.

The data suggest that estradiol enhances the formation of histamine in rat uterus by induction of histidine decarboxylase; histamine activates adenylate cyclase providing accumulation of cyclic 3',5'-AMP, which, probably, induces glycolytic enzymes via phosphorylation of chromatin proteins, and mediates other estradiol effects. The chain of successively acting enzymes and mediators constitutes, obviously, a cascade amplifying the estradiol action. Since histamine is known to act as an intercellular mediator, attempts were made to find out the distribution of estradiol, histamine, and cyclic 3',5'-AMP among uterine cells. Autoradiography has shown that 3H-estradiol is bound by the nuclei of myometrium cells, 3H-histamine was found in the cytoplasm of these cells, 3H-cyclic 3',5'-AMP is selectively bound by the cells of capillary endothelium of the uterus. The estradiol mediators seem to spread their effect on different types of cells which form together a kind of a multicellular functional system.

A series of seven dyad molecules have been prepared utilizing a [Ru(tpy)(NN)I](+) type oxidation catalyst (NN = 2,5-di(pyrid-2'-yl) pyrazine (1), 2,5-di-(1',8'-dinaphthyrid-2'-yl) pyrazine (2), or 4,6-di-(1',8'-dinaphthyrid-2'-yl) pyrimidine (3). The other bidentate site of the bridging ligand was coordinated with 2,2'-bipyridine (bpy), 1,10-phenanthroline (phen), or a substituted derivative. These dinuclear complexes were characterized by their (1)H NMR spectra paying special attention to protons held in the vicinity of the electronegative iodide. In one case, 10a, the complex was also analyzed by single crystal X-ray analysis. The electronic absorption spectra of all the complexes were measured and reported as well as emission properties for the sensitizers. Oxidation and reduction potentials were measured and excited state redox properties were calculated from this data. Turnover numbers, initial rates, and induction periods for oxygen production in the presence of a blue LED light and sodium persulfate as a sacrificial oxidant were measured. Similar experiments were run without irradiation. Dyad performance correlated well with the difference between the excited state reduction potential of the photosensitizer and the ground state oxidation potential of the water oxidation dyad. The most active system was one having 5,6-dibromophen as the auxiliary ligand, and the least active system was the one having 4,4'-dimethylbpy as the auxiliary ligand.

Experiments have been performed to examine the effects of activating the carotid body chemoreceptors and the arterial baroreceptors on the discharge of neurones within the hypothalamic supraoptic nucleus of the rat. Chemoreceptors were activated by intracarotid injection of 0.9% NaCl solution equilibrated with 100% CO2. The baroreceptors of the carotid sinus and aortic arch were activated by raising the blood pressure with an intravenous injection of phenylephrine. Chemoreceptor stimulation activated and baroreceptor stimulation inhibited the discharge of all the phasically discharging neurones tested. Neither stimulus had any consistent effect on non-phasically discharging neurones, although slight inhibition occasionally occurred. Anaesthesia of the carotid bifurcation abolished the effects of cardiovascular stimulation on the supraoptic neurones. Responses resumed when the anaesthesia wore off. However, the anaesthesia also seemed to alter the phasic pattern of discharge. The results are discussed with reference to the influence of the cardiovascular receptors upon the neurones in the supraoptic nucleus, and with reference to possible roles for the cardiovascular reflexes in control of vasopressin secretion.

Hemangiopericytoma (HPC) is a soft-tissue neoplasm composed of proliferating capillary pericytes. It has variable and unpredictable malignancy and most commonly occurs in the fifth or sixth decade of life. Diagnosis is based on the histological aspect. HPC is exceedingly rare in childhood. In both adults and children, curative surgery is the most important predictor of survival. The place of chemotherapy in the treatment of HPC is not well established. We describe a case of adult-type metastatic HPC of the thigh in a 13-year-old boy. The response to neoadjuvant chemotherapy was excellent, and local control of this initially unresectable tumor was achieved without radiation therapy or mutilating surgery. The child is alive and well and has had 8 years of follow-up after treatment.

Idiopathic plasmacytic lymphadenopathy (IPL) with polyclonal hyperimmunoglobulinemia is considered identical to multicentric Castleman's disease (MCD) reported in western countries. Clinically, both IPL and MCD are characterized by multicentric lymphadenopathy, prominent polyclonal hypergammaglobulinemia, elevated erythrocyte sedimentation rate, elevated serum interleukin-6 concentration, bone marrow plasmacytosis, and various abnormal laboratory data such as anemia and positive autoantibodies. However, IPL has a significantly better 5-year survival rate than that of MCD. Moreover, none of the present 16 cases developed Kaposi's sarcoma or B-cell lymphoma. Histologically, the interfollicular area contains a sheet of polytypic mature plasma cells in both IPL and MCD. In MCD, the majority of lymphoid follicles had hyaline-vascular germinal centers. However, lymphoid follicles of IPL usually exhibit a hyperplastic germinal center. Immunostaining also demonstrated a normal/reactive follicular dendritic cell network pattern in the germinal center of IPL. Moreover, there were no human herpes virus-8-positive cells detected by immunohistochemistry. The overall clinicopathologic and immunohistochemical findings of our 16 cases suggest that IPL is distinct from MCD reported in Western countries.

The saphenous vein is among the most commonly used conduits for renal artery revascularization in adults. Vein grafts are more durable in the renal artery bed than in coronary and peripheral beds, and mechanisms of potential graft failure vary. Coronary vein grafts often fail because of atherosclerotic degeneration, whereas lower extremity grafts fail because of intimal hyperplasia or progression of underlying disease. In contrast, renal vein grafts may dilate over time but seldom fail. This may relate to the distinct hemodynamic environment of the renal bed with low-resistance, high-velocity blood flow. However, frank aneurysmal degeneration of renal vein grafts is rare with only a single report of rupture in the literature. We report an additional case of rupture of a late graft aneurysm and review the literature and our own experience with renal revascularization to underscore the rarity of this serious complication. The saphenous vein for aortorenal bypass grafting continues to be a favorable conduit for renal revascularization. Long-term duplex ultrasound scanning follow-up is recommended to survey the reconstructed artery and perhaps more important, to evaluate progression of subclinical disease in the contralateral renal artery.

Prostaglandin synthesis in endothelial cells may be initiated by the addition of exogenous substrate (arachidonic acid) or by addition of thrombin or the CA2+-ionophore A23187, which leads to prostacyclin formation from endogenous substrates. We noticed that endothelial cells produce more than twice the amount of prostacyclin when incubated with thrombin and arachidonic acid together than with arachidonic acid alone. In addition, it was found that the thrombin-induced conversion of endogenous substrates was inhibited by exogenous arachidonic acid. This means that the conversion of exogenous added arachidonic acid to prostacyclin was stimulated by thrombin. This activation of the enzymes involved in prostacyclin synthesis lasted about 5 min and could be inhibited by phospholipase inhibitors such as mepacrine and p-bromophenyl-acylbromide but not by the cAMP analogue dibutyryl cAMP, an inhibitor of arachidonic acid release from cellular phospholipids. These data demonstrate that, in addition to causing release of endogenous substrate, thrombin and the Ca2+-ionophore also activate the enzyme system involved in the further transformation of arachidonic acid.

Providing efficient and effective aged care services is one of the greatest public policy concerns currently facing governments. Increasing the integration of care services has the potential to provide many benefits including increased access, promoting greater efficiency, and improving care outcomes. There is little research, however, investigating how integrated aged care can be successfully achieved. The PRISMA (Program of Research to Integrate Services for the Maintenance of Autonomy) project, from Quebec, Canada, is one of the most systematic and sustained bodies of research investigating the translation and outcomes of an integrated care policy into practice. The PRISMA research program has run since 1988, yet there has been no independent systematic review of this work to draw out the lessons learnt.

Various commercially available one-step immunoassays for detection of human (primate) blood have been developed. This study evaluated two hemoglobin tests, ABAcard(®) HemaTrace(®) and HemDirect Hemoglobin against glycophorin A test-RSID™-Blood for following parameters: sensitivity, specificity, effectiveness using various substrates, stain remover and aged blood stains. The highest blood detection limit was observed if HemaTrace(®) was used. When compared with HemaTrace(®), ten times lower sensitivity was observed for HemDirect Hemoglobin test. No false positives were obtained for HemDirect Hemoglobin while ABAcard(®) HemaTrace(®), probably due to its extreme sensitivity, showed high percent of false positives with saliva. The lowest sensitivity and 40% of false positives with saliva was exhibited by RSID™-Blood. In addition, this test encountered the lowest efficacy if aged blood-stains or blood treated with stain remover were used. As expected, none of the tested substrates (wood, metal, brick, and soil), influenced on blood testing, although soil substrate affected STR amplification. Conducted studies established HemDirect Hemoglobin test as more reliable for evaluated parameters than ABAcard(®) HemaTrace(®) and RSID™-Blood.

The influence of general anaesthesia for operations devoid of substantial tissue traumas on the postoperative pattern of hepatic enzymes was studied in 40 patients undergoing ophthalmologic surgery. 20 had neurolept analgesia, 20 had halothane anaesthesia. The duration of anaesthesia, age of the patients and their previous history corresponded fairly closely to those of a group of patients who had gynaecological operations and were the subject of a previous study. In contrast to the latter group total protein, cholinesterase, GOT, GPT, LDH, GLDH, AP, LAP and gamma-GT remained normal up to 12 days after the operation. The exception were changes in the total bilirubin levels which were similar to those observed in the gynaecological cases. Possible causes are discussed.

Powder bed fusion with laser beam of metals (PBF-LB/M) is a widely used technology to produce parts with a high freedom in design paired with excellent mechanical properties. The casting alloy AlSi10Mg features a wide process window and a microstructure with excellent mechanical properties which are not obtainable through conventional manufacturing. One possibility for achieving this is by influencing the solidification which then directly affects the local part properties. In this study, the effect of different laser beam profiles with gaussian and top-hat intensity distributions, as well as the influence of varying parameter sets on the microstructure and microhardness within the same specimen, was examined. A test specimen consisting of many small cubes was built with different parameters. It was found that the local properties can be varied in a wide range. Build-height-dependent in-situ aging effects can thereby be exploited for tailoring the local material properties. Thus, an extra degree of freedom is added to the design of additively manufactured parts.

Standard algorithms for pairwise protein sequence alignment make the simplifying assumption that amino acid substitutions at neighboring sites are uncorrelated. This assumption allows implementation of fast algorithms for pairwise sequence alignment, but it ignores information that could conceivably increase the power of remote homolog detection. We examine the validity of this assumption by constructing extended substitution matrices that encapsulate the observed correlations between neighboring sites, by developing an efficient and rigorous algorithm for pairwise protein sequence alignment that incorporates these local substitution correlations and by assessing the ability of this algorithm to detect remote homologies.

In recent years, the interaction between the gut microflora and liver diseases has attracted much attention. The intestinal microflora is composed of bacteria, archaea, fungi and viruses. There are few studies on the intestinal virome, and whether it has a causal relationship with bacterial changes in the gut is still unclear. However, it is undeniable that the intestinal virome is also a very important portion of the blueprint for the development of liver diseases and the diagnosis and therapeutic modalities in the future.

It has been reported that, in early pregnancy in mice, there is an increase in the number of immunoglobulin-secreting cells in the lymph nodes which drain the uterus. This paper describes the results of further investigations provoked by interest in these early changes. Increases in the numbers of immunoglobulin-secreting cells were observed in syngeneically, but scarcely or not at all in allogeneically, mated mice. Increases were not observed in surgically sterilized female mice inseminated by normal males. However, subcutaneous injection of sperm provoked massive increases in the numbers of immunoglobulin-secreting cells in the lymph nodes draining the injection site. The changes were compared with those provoked by the injection of spleen cells and LPS. The results are discussed in relation to the nature of the interactions provoking the increases in the number of immunoglobulin-secreting cells and their possible relationship to immunosuppression, and the relative immunological unresponsiveness which the female shows to the challenge of inseminated sperm.

This paper presents a two-component framework to detect model-plant mismatch (MPM) in cross-directional (CD) processes on paper machines under model-predictive control. First, routine operating data is used for system identification in closed loop; second, a one-class support vector machine (SVM) is trained to predict MPM. The iterative identification method alternates between identifying the finite impulse response coefficients of the spatial and temporal models. It converges, and the parameter estimates are asymptotically consistent. Coefficient estimates drawn from normal operation are used to train a one-class SVM, which then detects model-plant mismatch in subsequent routine operation. This approach applies to routine operating data without requiring external excitations. It can also distinguish mismatches in the process model from changes in the noise model. Examples of CD processes on paper machines are provided to verify the effectiveness of both components.

This chapter describes the visual problems likely to be encountered in Parkinson's disease (PD) and whether such signs are useful in differentiating the parkinsonian syndromes. Visual dysfunction in PD may involve visual acuity, contrast sensitivity, color discrimination, pupil reactivity, saccadic and pursuit eye movements, motion perception, visual fields, and visual processing speeds. In addition, disturbance of visuospatial orientation, facial recognition problems, rapid eye movement (REM) sleep behavior disorder, and chronic visual hallucinations may be present. Problems affecting pupil reactivity, stereopsis, pursuit eye movement, and visuomotor adaptation, when accompanied by REM sleep behavior disorder, could be early features of PD. Dementia associated with PD is associated with enhanced eye movement problems, visuospatial deficits, and visual hallucinations. Visual dysfunction may be a useful diagnostic feature in differentiating PD from other parkinsonian symptoms, visual hallucinations, visuospatial dysfunction, and variation in saccadic eye movement problems being particularly useful discriminating features.

Least mean square (LMS) adaptive filter has been used to extract life signals from serious ambient noises and interferences in biomedical applications. However, a LMS adaptive filter with a fixed step size always suffers from slow convergence rate or large signal distortion due to the diversity of the application environments. An ideal adaptive filtering system should be able to adapt different environments and obtain the useful signals with low distortion. Adaptive filter with gradient adaptive step size is therefore more desirable in order to meet the demands of adaptation and convergence rate, which adjusts the step-size parameter automatically by using gradient descent technique. In this paper, a novel gradient adaptive step size LMS adaptive filter is presented. The proposed algorithm utilizes two adaptive filters to estimate gradients accurately, thus achieves good adaptation and performance. Though it uses two LMS adaptive filters, it has a low computational complexity. An active noise cancellation (ANC) system with two applications for extracting heartbeat and lung sound signals from noises is used to simulate the performance of the proposed algorithm.

Opening-wedge high tibial osteotomy is an increasingly performed procedure for treatment of varus gonarthrosis and correction of malalignment during meniscal transplantation or cartilage restoration. Precise preoperative planning and meticulous surgical technique are required to achieve an appropriate mechanical axis correction. We describe our technique of arthroscopic and computer-assisted high tibial osteotomy using commonly available total knee arthroplasty navigation software as an intraoperative goniometer. We believe that our technique, by providing intraoperative real-time guidance of the degree of correction that is accurate and reliable, represents a useful tool for the surgeon who uncommonly performs high tibial osteotomy.

An insulin-secreting islet cell tumour of the Syrian hamster has been transplanted serially in the congenitally immune-deficient nude mouse, in order to test the potential usefulness of this mouse mutant as a graft carrier of heterologous tumours with stable differentiated phenotypes. The incidence of tumour growth was very high, and the hamster tumour retained its functional and histologic characteristics during consecutive passages in nude mice. These results show that nude mice may be useful carriers of differentiated tumours from non-inbred species including man, and for the isolation of cell lines from such tumours.

We evaluated the effect of monocyte chemotactic protein-1 (MCP-1) on the induction of nitric oxide synthase activity in J774 cells. MCP-1 was able to inhibit the production of nitric oxide induced by LPS and IFN-gamma in a dose-dependent manner. Moreover, the inhibition was only achieved when the cells were pretreated with MCP-1. No inhibition was observed when MCP-1 was added after stimulation with LPS and IFN-gamma. These results demonstrate that MCP-1 is able to inhibit the induction of nitric oxide synthesis.

Behavioural addictions are characterized by an inability to resist an urge or drive resulting in actions that are harmful to oneself or others. Behavioural addictions share characteristics with substance and alcohol abuse, and in areas such as natural history, phenomenology, and adverse consequences. Behavioural addictions include pathological gambling, kleptomania, pyromania, compulsive buying, compulsive sexual behaviour, Internet addiction, and binge eating disorder. Few studies have examined the efficacy of pharmacological and psychological treatment for the various behavioural addictions, and therefore, currently, no treatment recommendations can be made.

This paper is focused on the human factors analysis comparing a standard neuronavigation system with an augmented reality system. We use a passive articulated arm (Microscribe, Immersion technology) to track a calibrated end-effector mounted video camera. In real time, we superimpose the live video view with the synchronized graphical view of CT-derived segmented object(s) of interest within a phantom skull. Using the same robotic arm, we have developed a neuronavigation system able to show the end-effector of the arm on orthogonal CT scans. Both the AR and the neuronavigation systems have been shown to be within 3mm of accuracy. A human factors study was conducted in which subjects were asked to draw craniotomies and answer questions to gage their understanding of the phantom objects. The human factors study included 21 subjects and indicated that the subjects performed faster, with more accuracy and less errors using the Augmented Reality interface.

Eighty consecutive patients undergoing pulmonary resection at the University College Hospital, Ibadan were studied to determine the factors predictive of postoperative morbidity and mortality. The operative mortality was 10% while complications occurred in 66% of the patients. Complications were significantly more frequent (p less than 0.01) in those with benign disease (73%) than with malignant conditions (31%). Benign disease and pneumonectomy were predictors of wound infection (p less than 0.05 & p less than 0.02 respectively); haemoptysis and pneumonectomy, predictors of bronchopleural fistula (p less than 0.02 and p less than 0.05 respectively); benign disease predictor of empyema (p less than 0.02); and age over 50 years predictor of mortality (p less than 0.01). It is concluded that improved care of patients with these predictive factors would result in reduction of morbidity and mortality.

There has been in increase in the use of systems for organizing lay responders for suspected out-of-hospital cardiac arrests (OHCAs) dispatch using smartphone-based technology. The purpose is to increase survival rates; however, such systems are dependent on people's commitment to becoming a lay responder. Knowledge about the characteristics of such volunteers and their motivational factors is lacking. Therefore, we explored characteristics and quantified the underlying motivational factors for joining a smartphone-based cardiopulmonary resuscitation (CPR) lay responder system.

The hepatotoxic effect of venom sac extract (VSE) of the Oriental hornet has already been demonstrated using the well-known models of experimental toxicology: in vivo, isolated in situ and in vitro. The present work deals with a series of 48 rats treated daily with 5 mg VSE/kg body weight for 1-14 days. Serum activities of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), and gamma-glutamyl transferase (GGT) were measured. Liver tissue fractionation was performed. Detailed information on the topographical and functional aspects of some enzyme changes was obtained in respect to the number of envenomations. The biochemical alterations are partially reversible. The biochemically proven liver damage induced by VSE correlated well with previous electron microscopic observations of damage to mitochondria and cell membranes.

The TM1 domain of the large conductance mechanosensitive (MS) channel of Escherichia coli was used as a genetic probe to search the genomic database of the archaeon Methanoccoccus jannashii for MscL homologs. We report that the hypothetical protein MJ0170 of M. jannashii exhibited 38.5% sequence identity with the TM1 domain of Eco-MscL. Moreover, MJ0170 was found to be a conserved homolog of MscS, the second type of E. coli MS channel encoded by the yggB gene. Furthermore, we identified a cluster of charged residues KIKEE in the C-terminus of MJ0170 that strikingly resembled the charged C-terminal amino acid cluster present in Eco-MscL (RKKEE). We cloned and expressed MJ0170 in E. coli, which when reconstituted into liposomes or expressed in the cell membrane of giant E. coli spheroplasts, exhibited similar activity to the bacterial MS channels. Our study suggests that the M. jannashii MS channel and its homologs evolved as a result of gene duplication of the ancestral MscL-like molecule with the TM1 domain remaining the most conserved structural motif among prokaryotic MS channels.

Chiasmata established by recombination are normally sufficient to ensure accurate chromosome segregation during meiosis by physically interlocking homologs until anaphase I. Drosophila melanogaster female meiosis is unusual in that it is both exceptionally tolerant of nonexchange chromosomes and competent in ensuring their proper segregation. As first noted by Puro and Nokkala [Puro, J., Nokkala, S., 1977. Meiotic segregation of chromosomes in Drosophila melanogaster oocytes. A cytological approach. Chromosoma 63, 273-286], nonexchange chromosomes move precociously towards the poles following formation of a bipolar spindle. Indeed, metaphase arrest has been previously defined as the stage at which nonexchange homologs are symmetrically positioned between the main chromosome mass and the poles of the spindle. Here we use studies of both fixed images and living oocytes to show that the stage in which achiasmate chromosomes are separated from the main mass does not in fact define metaphase arrest, but rather is a component of an extended prometaphase. At the end of prometaphase, the nonexchange chromosomes retract into the main chromosome mass, which is tightly repackaged with properly co-oriented centromeres. This repackaged state is the true metaphase arrest configuration in Drosophila female meiosis.

Preeclampsia/eclampsia, also known as toxemia of pregnancy, remains one of the great triad of obstetric complications. The outlook for the preeclamptic woman and the fetus has improved as a result of increased knowledge of uteroplacental-fetal physiology and of the physiologic deviations involved in preeclampsia, although the basic cause of preeclampsia remains unknown. Careful screening of women at risk for preeclampsia along with early detection and treatment can help reduce the toll taken in stillbirths, prematurity, and maternal death. Current concepts of pathophysiology are reviewed as is nursing care during the antepartum and intrapartum periods.

During my career in Plant Pathology/Nematology, many major advancements have occurred in the study of nematodes-even with their being largely soilborne and thus often overlooked. These biotrophic organisms include the most widespread and important group of plant pathogens-the root-knot nematodes Meloidogyne species-which attack most major crops, as well as thousands of non-crop plant species. Landmark achievements that catalyzed research on these organisms included the discovery of effective nematicides, ectoparasitic forms, elucidation of disease complexes, nematodes as virus vectors, development of host resistance, and new technologies for research. Evolving research thrusts involve interfacing traditional and molecular systematics/diagnostics, adoption of the Caenorhabditis elegans-molecular genetics resource for general nematological research, focus on genetics of parasitism, use of molecular tools in developing host resistance, ecological and quantitative facets, and soil-biology-ecology based integrated management. Educational and international programs are encountering many changes and challenges, as is support for nematology in general.

Symptomatic splenomegaly, a frequent manifestation of myelofibrosis (MF), represents a therapeutic challenge. It is frequently accompanied by constitutional symptoms and by anemia or other cytopenias, which make treatment difficult, as the latter are often worsened by most current therapies. Cytoreductive treatment, usually hydroxyurea, is the first-line therapy, being effective in around 40% of the patients, although the effect is often short lived. The immunomodulatory drugs, such as thalidomide or lenalidomide, rarely show a substantial activity in reducing the splenomegaly. Splenectomy can be considered in patients refractory to drug treatment, but the procedure involves substantial morbidity as well as a certain mortality risk and, therefore, patient selection is important. For patients not eligible for splenectomy, transient relief of the symptoms can be obtained with local radiotherapy that, in turn, can induce severe and long-lasting cytopenias. Allogeneic hemopoietic stem cell transplantation is the only treatment with the potential for curing MF but, due to its associated morbidity and mortality, is usually restricted to a minority of patients with poor risk features. A new class of drugs, the JAK2 inhibitors, although also palliative, are promising in the splenomegaly of MF and will probably change the therapeutic algorithm of this disease.

Retinitis pigmentosa (RP) is a group of retinal degeneration characterized by progressive visual field loss, night blindness and pigmentary retinopathy. Its prevalence is in the region of 1-2 in 5,000 of the general population, making it one of the commoner causes of blindness in early and middle life. Although 36-48% of RP patients are isolated cases, the remainder show autosomal dominant, autosomal recessive or X-linked modes of inheritance. The X-linked variety ( XLRP ) is found in 14-22% of RP families in the UK. In the present study, X chromosome-specific recombinant DNA probes which can detect restriction fragment length polymorphisms have been used to localize the XLRP gene(s) to a subregion of the X chromosome using linkage analysis. One of the probes, L1.28, has been shown to be closely linked to XLRP in five kindreds, with 95% confidence limits of 0-15 centimorgans (maximum LOD score of 7.89 at a distance of 3 centimorgans). This suggests that the XLRP locus lies on the proximal part of the short arm of the X chromosome. This probe is potentially useful for carrier detection and early diagnosis in about 40% of cases, provided that genetic heterogeneity can be excluded by analysis of further families.

Recent development of powerful image processing systems provides computation of angiocardiographic image series. Thus, acquisition and display of specific cardiac and circulatory parameters has become feasible. The simplest processing mode utilizes repetitive image subtraction, for example for the documentation of left ventricular wall motion abnormalities. A qualitative aspect of organ perfusion (myocardium, lungs) is obtained by color coding of serial DSA-images. Quantitative studies of vascular perfusion, however, require complex parameter extraction techniques according to the theory of indicator dilution. Great advancements have been achieved for arterial flow distribution measurements to study peripheral vascular disease. The actual interest in cardiology concerns measurements of coronary flow reserve that are based either on perfusion time or contrast mass measurements. However, limitations in quantitative flow studies must be considered in relation to the physico-chemical effects of contrast media.

Different concentrations of a hot water extract of Desmodium adscendens, a plant used in Ghana to control asthmatic attacks, were used in drinking water to evaluate the plant's anti-anaphylactic properties in guinea pigs. The results show that the extract's inhibition of histamine-induced ileal contraction is largely competitive and that its effect of reducing lung histamine content is dose-dependent. The results also show that the extract causes a dose-dependent reduction in the amount of spasmogens released anaphylactically and in anaphylactic-induced contraction of ileal muscle.

Alcohol consumption is one of the strongest predictors of suboptimal adherence to antiretroviral therapy (ART), however, there is little research that has investigated both within- and between-person associations of alcohol consumption and ART adherence at the event-level. In this secondary data-analysis, (N = 22) HIV-positive MSM prospectively reported daily alcohol consumption and ART adherence for 42-days. Multilevel models demonstrated (1) days in which participants reported consuming any alcohol was associated with 2.48 increased odds of ART non-adherence, compared to days in which participants reported no alcohol consumption, and (2) there was a non-significant trend indicating days in which participants reported consuming greater than their own average levels of alcohol was associated with increased odds of ART non-adherence. Findings highlight the importance of combining intervention efforts that address alcohol consumption and suboptimal ART adherence, and indicate a need for future research to investigate the mechanisms by which alcohol influences ART adherence.

Risk ratios (RRs) for hospital admissions due to alcohol poisoning, alcoholism, and alcohol psychosis were calculated by direct age standardization and, if not applicable, from regression models for various marital status and social class combinations among 25-64 year-old females. Data, derived from the Finnish National Hospital Discharge Register for the years 1970-1975, pertained to 4212 females. RRs increased clearly for all three principal diagnoses of hospital admission by marital status but only for alcoholism by social class. In each diagnostic group, married farmers had the lowest and divorced unskilled workers the highest admission rates. The RRs for the latter compared to the former were 8 for alcohol poisoning, 20 for alcohol psychosis and 75 for alcoholism. These results are discussed in relation to findings pertaining to female alcoholism.