Comparison of the Neuroprotective and Anti-Inflammatory Effects of the Anthocyanin Metabolites, Protocatechuic Acid and 4-Hydroxybenzoic Acid.
Anthocyanins are being increasingly investigated for their neuroprotective and antineuroinflammatory effects; however, the overall bioavailability of many anthocyanins is relatively low. In contrast, phenolic acids, metabolites of many polyphenols, including anthocyanins, have been shown to accumulate in tissue at higher concentrations than those of parent compounds, suggesting that these metabolites may be the bioactive components of anthocyanin-rich diets. We examined the neuroprotective capacity of two common phenolic acids, 4-hydroxybenzoic acid (HBA) and protocatechuic acid (PCA), in primary cultures of cerebellar granule neurons. Both HBA and PCA are capable of mitigating oxidative stress induced by hydrogen peroxide, which is thought to contribute to neuronal cell death in neurodegeneration. Under conditions of nitrosative stress, which occur during inflammation in the central nervous system, only PCA was neuroprotective, despite similar structural characteristics between HBA and PCA. Intriguingly, this trend was reversed under conditions of excitotoxicity, in which only HBA was neuroprotective. Lastly, we explored the anti-inflammatory activity of these compounds in microglial cells stimulated with lipopolysaccharide. PCA was an effective anti-inflammatory agent, reducing nitric oxide production, while HBA had no effect. These data indicate that phenolic acids possess distinct neuroprotective and anti-inflammatory characteristics that could make them suitable for the treatment of neurodegeneration.


Astragaloside IV protects LO2 cells from oxidative damage caused by radiation-induced bystander effect through Akt/Nrf2 pathway.
The protective effects of astragaloside IV (ASIV) on various diseases are well known, but its potential impact on radiation-induced bystander effect (RIBE) has remained unclear. This study aimed to explore the protective mechanism of ASIV against oxidative damage caused by RIBE in LO2 cells. To construct the RIBE model, the conditioned medium from HepG2 cells irradiated with radiation was transferred to nonirradiated LO2 cells. LY294002, a commonly used phosphatidylinositol 3-kinase/Akt pathway inhibitor, was added to LO2 cells 1 h before exposing HepG2 cells to radiation. LO2 cells were then collected for analyses after RIBE exposure. The study found that ASIV significantly improved cell proliferation and promoted the recovery of mitochondrial membrane potential while reducing the rate of apoptosis. Western blot analyses demonstrated that ASIV upregulated B-cell lymphoma 2 and downregulated B-cell lymphoma 2-related X protein and cleaved-caspase 3. Measurement of reactive oxygen species, superoxide dismutase, glutathione peroxidase, and malondialdehyde levels showed that ASIV effectively restored the oxidative stress state induced by RIBE. Additionally, immunofluorescence and western blots analyses confirmed that ASIV enhanced the translocation of Nrf2 to the nucleus and activated downstream nicotinamide adenine dinucleotide phosphate: quinine oxidoreductase 1 and heme oxygenase 1. Importantly, Akt pathway inhibitor repressed ASIV-induced activation of Nrf2 and its protective effect against RIBE. This study demonstrates that ASIV protects LO2 cells against oxidative damage caused by RIBE through activation of the Akt/Nrf2 pathway.


Decarboxylative Alkylcarboxylation of α,β-Unsaturated Acids Enabled by Copper-Catalyzed Oxidative Coupling.
A facile and general method for copper-catalyzed decarboxylative alkylcarboxylation of cinnamic acids with dimethyl 2,2'-azobis(2-methylpropionate) has been developed. The scope and versatility of the reaction was demonstrated, and a broad range of substrates bearing electron-donating and -withdrawing groups on the aromatic rings were all compatible with this reaction to provide desired β,γ-unsaturated esters in moderate to good yields. Moreover, α,β-unsaturated acids with a carbonyl group on the γ-position of acrylic acids also smoothly proceeded to furnish the desired products in good yields.


Iridoids from Pentas lanceolata.
From the aerial parts of Pentas lanceolata, belonging to the family Rubiaceae, a series of iridoid glucosides was isolated by preparative HPLC. Seven iridoid glucosides were identified. Besides asperuloside and asperulosidic acid, characteristic iridoids for Rubiaceae, five new iridoids were isolated, namely, tudoside (1), 13R-epi-gaertneroside (2), 13R-epi-epoxygaertneroside (3), and a mixture of E-uenfoside (4) and Z-uenfoside (5). Further, it was shown that the compound reported as citrifolinin B (6) is in fact the same as tudoside and should be revised. Also, the configuration of the previously reported iridoids gaertneroside and epoxygaertneroside has been elucidated.


[Hemoperfusion with coated activated charcoal for treating acute poisoning by remedies, plant protectants, and fungi. I. Remedies (author's transl)].
Hemoperfusion with coated activated charcoal is a novel procedure for treating acute poisoning. It enables the elimination of both, water-soluble and liposoluble toxins. Hemoperfusion with coated activated charcoal has proved to be superior to hemodialysis in the treatment of barbiturate or bromocarbamide poisoning both under experimental conditions as well as in the ward. Analogous statements may be made for the therapy of glutethimide poisoning. Methaqualone, on the other hand, could not be eliminated sufficiently well in animal trials. Intoxications by "mild" analgetics, such as paracetamol and acetylsalicylic acid, may be treated successfully with hemoperfusion. Treatment of acetylsalicylic acid poisoning is equally effective with hemoperfusion as with hemodialysis. Prospects for the success of hemoperfusion in treating intoxication from tricyclic antidepressants and neuroliptics are slight. It is simply the danger of antidepressant poisoning that justifies using this method of treatment in the first few hours after ingestion in order to reduced the flow of the psychopharmaceutical substance into the tissue.


Protein transduction domain can enhance the humoral immunity and cross-protection of HPV16L2 peptide vaccines.
Due to type-specificity, commercially available human papillomavirus (HPV) vaccines are only effective against homologous HPV serotypes, providing limited protection. Recent studies have highlighted the role of HPV minor capsid protein (known as L2) in inducing cross-protection. The N-terminal peptides of L2 contain conserved cross-response epitopes that can induce neutralizing antibodies against heterogeneous HPVs. However, when compared with L1, these peptides have lower immunogenicity, which limits the application of these vaccines. The protein transduction domain (PTD), located in the Tat protein of human immunodeficiency virus, facilitates delivery of DNA, peptides, proteins and virus particles into cells by unknown mechanisms, and has been reported to enhance immunogenicity of several antigens. In the present study, two peptides derived from the N-terminal of HPV16L2 were chosen as model antigens and constructed a series of L2 peptide vaccines by either fusing or mixing with PTD. Subsequently their immunogenicity was evaluated. The results indicated that the L2 peptides fused with PTD show considerably enhanced humoral immunity. In particular, they increased the titer of cross-neutralizing antibodies, while L2 peptides that had only been mixed with PTD induced only small cross-protection responses. Overall, the data suggest that fusion of L2 peptides with PTD significantly enhances their cross-protection and may be a promising strategy for the development of broad-spectrum HPV prophylactic vaccines.


Current management of traumatic chylothorax.
The development of a traumatic chylothorax is an uncommon but serious clinical entity. Two cases of traumatic chylothorax are reported. The anatomy and physiology of the thoracic duct and the etiology, diagnosis and management of traumatic chylothorax are discussed.


Medical futility.
"Medical futility" may be provisionally defined as a medical conclusion that a therapy is of no value to a patient and should not be prescribed. The current debate about medical futility is one of the most important and contentious in medical ethics. Proponents believe that allowing physicians to determine and withhold futile therapies can be done without disturbing the current paradigm of medical ethics which respects patient autonomy with regard to informed consent and the right to refuse treatment. Others conclude that medical futility is simply an unacceptable form of medical paternalism. Some adopt a middle position that doctors can predict medical futility; they believe that attempting this does not necessarily justify imposing decisions to forgo life-sustaining therapy on patients. Regardless of its policy outcome, this important debate is leading to a reexamination of the nature of a patient's entitlement to health care and of the ends of medicine. It has two aspects. A definitional debate examines the concept of medical futility and its derived clinical criteria. A second debate considers the nature of the authority and procedures to act on the conclusion that a therapy is futile by withholding or withdrawing treatment.


Decrease in infant mortality and sudden infant death syndrome among Northwest American Indians and Alaskan Natives--Pacific Northwest, 1985-1996.
Although the infant mortality rate (IMR) has steadily declined in the United States since the early 1900s, the rate varies among racial/ethnic populations. A goal of the national health objectives for 2010 is to eliminate racial/ethnic health disparities (U.S. Department of Health and Human Services, unpublished data, 1999). Historically, IMRs among American Indians and Alaskan Natives (AI/AN) have been high. In addition, IMRs have varied among AI/AN populations. To determine recent trends in infant mortality among Northwest AI/AN, the Northwest Portland Area Indian Health Board (NPAIHB) analyzed annual IMRs among AI/AN in Idaho, Oregon, and Washington. In addition, because sudden infant death syndrome (SIDS) is the major contributor to excess infant mortality in Northwest AI/AN, NPAIHB analyzed SIDS rates to determine whether the decline in SIDS rates in the United States also was occurring among Northwest AI/AN. This report summarizes the results of this analysis and documents dramatic decreases in both SIDS and non-SIDS infant mortality.


Supervised drug administration in patients with refractory hypertension unmasking noncompliance.
Noncompliance with medication is common, particularly in asymptomatic conditions such as hypertension that require long-term treatment, and is often unsuspected. We describe two patients with refractory hypertension in whom noncompliance was confirmed by a precipitous fall in blood pressure when antihypertensive medications were given under direct supervision.


Clinical follow-up practices after cervical cancer screening by co-testing: A population-based study of adherence to U.S. guideline recommendations.
Failure to follow-up women after abnormal cervical screening could lead to cervical cancers, yet little is known about adherence to recommended follow-up after abnormal co-testing [cytology and high-risk human papillomavirus (hrHPV) testing]. We documented clinical management following cervical screening by co-testing in a diverse population-based setting. A statewide surveillance program for cervical screening, diagnosis, and treatment was used to investigate all cytology, hrHPV and biopsy reports in the state of New Mexico from January 2015 through August 2019. Guideline-adherent follow-up after co-testing required 1) biopsy within 6 months for low-grade cytology if positive for hrHPV, for high-grade cytology irrespective of hrHPV, and for HPV 16/18 positive results irrespective of cytology and; 2) repeat co-testing within 18 months if cytology was negative and hrHPV test was positive (excluding types 16/18). Screening co-tests (2015-2017) for 164,522 women were analyzed using descriptive statistics, Kaplan Meier curves, and pairwise comparisons between groups. Guideline adherence was highest when both cytology and hrHPV tests were abnormal, ranging from 61.7% to 80.3%. Guideline-adherent follow-up was lower for discordant results. Women with high-grade cytology were less likely to receive a timely biopsy when hrHPV-testing was negative (48.1%) versus positive (83.3%) (p < 0.001). Only 47.9% of women received biopsies following detection of HPV16/18 with normal cytology, and 30.8% received no follow-up within 18-months. Among women with hrHPV-positive normal cytology without evidence of HPV 16/18 infection, 51% received no follow-up within 18 months. Provider education and creation of robust recall systems may help ensure appropriate follow-up of abnormal screening results.


Fetal bradycardia associated with maternal hypothermia.
A case of fetal bradycardia associated with severe maternal hypothermia (92.9F) is reported. Until maternal temperature was corrected, the baseline fetal heart rate (FHR) remained between 90-110 beats per minute without other evidence of fetal distress and despite normal maternal blood pressure and pulse. With rewarming, the FHR gradually returned to normal. Upon return of maternal hypothermia, fetal bradycardia recurred, again responding only to rewarming. This evidence suggests that low maternal temperature alone may lead to alterations of FHR.


Characterization of Ambroxol and Its Hydrochloride Salt Crystals by Bromine K-Edge X-Ray Absorption Near-Edge Structure Spectroscopy and X-Ray Crystal Structure Analysis.
Polymorphic crystals of ambroxol, forms I and II, and form A ambroxol hydrochloride crystals were characterized with bromine K-edge X-ray absorption near-edge structure (XANES) spectroscopy and single-crystal X-ray structure analysis. The XANES spectra had unique shapes depending on the crystal forms. Refined single-crystal structures revealed different interatomic interactions around bromine atoms, such as C-H…Br and N-H…Br hydrogen bonds, Br…O halogen bonds, and N-H…π interactions. Differences in these weak interactions could affect the electronic states of the bromines, resulting in differences in the XANES spectra. The results demonstrated that weak non-conventional interatomic interactions could alter the shape of XANES spectra. Hence, the spectra could be used for evaluating polymorphs of active pharmaceutical ingredients.


[Clinical significance of HLA-DRB1 and HLA-DPB1 gene polymorphisms in cirrhosis patients].
To investigate the genetic association between cirrhosis and polymorphisms in the genes encoding major histocompatibility complex, class II (HLA)-DR beta 1 (DRB1) and HLA-DP beta 1 (DPB1). A population of 168 parent/offspring trios, in which the proband had a diagnosis of hepatitis B virus infection with clinical signs of cirrhosis.The HLA-DRB1 and DPB 1 gene polymorphisms of rs24755213 and rs202176660 were detected by PCR and single nucleotide polymorphism (SNP) genotyping.Correlation analysis and haplotype relative risk analysis were carried out. A/G genotypes were detected in rs24755213 of HLA-DRB1 and C/T genotypes were detected in rs202176660 of DPB1.The rs24755213 allele was associated with cirrhosis (P=0.014), with the G allele identified as a protective factor (Z=-2.33) and the A allele identified as a hazard factor (Z=2.33).The rs202176660 allele was also associated with cirrhosis (P =0.026), with the T allele identified as a protective factor (Z=-2.06) and the C allele identified as a hazard factor (Z=2.06).The haplotypes of G/T and A/C in rs24755213 and rs202176660 respectively were associated with cirrhosis (P =0.037 and 0.002, Z=-2.12 and 2.09 respectively). In this group of Chinese patients with hepatitis B virus-related cirrhosis, polymorphisms in the HLA-DRB 1 and DPB1 genes were associated with cimhosis.


Recording blood pressure and eGFR in primary care after the Belgrade screening study.
In 2009, Belgrade nephrologists and general practitioners from thirteen health centers carried out screening for chronic kidney disease (CKD). Three years later, medical records of patients from four health centers participating in the screening study were retrospectively analyzed in order to check whether general practitioners had continued to control patients at risk for CKD in accordance with the recommendations provided. The study included 460 patients who visited their doctor at least once in the three-year period. Data on blood pressure, ACEI use, estimated glomerular filtration rate (eGFR) and comorbidities were taken from patients' medical records. Blood pressure was not recorded in any of the three years in 42.8% and eGFR in 36.7% of the patients, but blood pressure was registered every year in 7.8% and eGFR in 4.3% of them. Over the three years, the relative number of patients with recorded blood pressure decreased from 41.7% to 17.8%, and with recorded eGFR from 41.7% to 21.5%. Multivariate linear regression found that Health Center, systolic and diastolic blood pressure and presence of hypertension were negatively associated with number of years with recorded blood pressure. Health Center, systolic blood pressure and sum of years with recorded eGFR below 60 ml/min/1.73m2 were associated with number of years with recorded eGFR. Under-recording of blood pressure and eGFR in primary care health centers suggests lack of adherence to current guidelines and insufficient care of CKD patients. This implies the necessity for continuous education of physicians.


Aeromonas species: an opportunistic enteropathogen in patients with inflammatory bowel diseases? A single center cohort study.
The role of Aeromonas species as an enteropathogen in patients with and without inflammatory bowel disease (IBD) is still debated. The aim was to explore the significance of positive Aeromonas stool cultures in IBD and patients without IBD. Observational retrospective study including all patients with a stool culture positive for Aeromonas between January 2011 and October 2013 at the Leuven University Hospitals. Demographics, clinical, and endoscopic outcomes and laboratory results were analyzed. A total of 77 patients (11 IBD) were identified. In 37 cases, Aeromonas caused a mild self-limited gastrointestinal infection. Among the 40 patients needing antibiotics, 22 presented a mild-to-moderate gastrointestinal infection; 4 suffered from extraintestinal complications; and 4 were coinfected by Campylobacter spp. A. veronii caused more frequently severe infection than the other species (25% versus 5%; P = 0.046). In 2 patients with ulcerative colitis, Aeromonas triggered a moderate-to-severe flare and 2 cases appeared in the context of de novo Crohn's disease. In contrast, in 1 patient with ulcerative colitis and 2 patients with Crohn's disease, Aeromonas caused a mild gastrointestinal infection not worsening the disease activity and in 4 patients with Crohn's disease, it presented in the context of active disease with no clear pathogenic role. Patients with IBD were treated more often with antibiotics (82 versus 41%, P = 0.012) and had more complications (46 versus 14%, P = 0.024). Aeromonas caused mostly mild infections but also moderate and severe infections. A. veronii was more prevalent in patients with IBD and was associated with worse clinical outcomes. Aeromonas caused milder infections in patients without IBD. Other risk factors for severe infection were not found.


Pressure garments in the control of hypertrophic scarring and rehabilitation of the burn patient: an occupational therapy approach.
During the first 2 years of its existence, the Jobst Service of the Soroka Medical Center treated 150 patients, including 29 casualties of the Lebanon War, 1982, for postburn hypertrophic scarring. The Jobst pressure-gradient burn garments were successful in the control of hypertrophic scars, and in shortening the patient's rehabilitation time. The discussion stems from the perspective of the occupational therapist for treatment planning, paying special attention to the physical and psychosocial problems that confront the thermally injured patient, and to the need for total patient care.


Anterior fusion and posterior correction of severe cervical kyphosis using pedicle screw fixation in a patient with neurofibromatosis: a case report.
We present a 15-year-old boy with severe cervical kyphosis due to neurofibromatosis (NF), who underwent one-stage anterior fusion and posterior correction using pedicle screw fixation. The kyphosis was corrected from 72 degrees to 35 degrees. At the follow-up 16 months postoperatively, anterior fusion and posterior stabilization had been obtained without correction loss. Cervical pedicle screw fixation is a useful method for the correction of severe cervical kyphosis in patients with NF.


[Pharmacological study of mequitazine (LM-209) (II). Anti-allergic action (author's transl)].
The anti-allergic effect of Mequitazine (LM-209) which was found to have an anti-histaminic activity was investigated in guinea-pigs. The inhibitory activities of LM-209 on the Schultz-Dale reaction and ileum contraction by some mediators released from the sensitized guinea-pig lung were the same as those of clemastine fumarate (CL) but with 5 times the potency. LM-209 and CL, but these activities were less potent than in the case of disodium cromoglycate. The various anaphylactic reactions mediated by IgG in guinea-pigs were inhibited by LM-209, CL and chlorpheniramine maleate (CPM). The homologous PCA mediated IgE in rats was also inhibited by LM-209, CL and CPM, but the duration of the action with LM-209 was markedly longer. In experimentally-induced asthma, the decrease of respiratory rate and volume was significantly inhibited by LM-209, but was not affected by CL. Thus, LM-209 seems to inhibit the allergic reaction mainly by an antagonistic action on allergic mediators.


Molecule action mechanisms of NM-3 on human gastric cancer SGC-7901 cells in vivo or in vitro.
To study the molecule action mechanisms of NM-3 on the growth of human gastric cancer SGC-7901 cells in vivo or in vitro. SGC-7901 from human non-differentiated gastric cancer cell line was cultured with NM-3 at 100 mg/ml for 24 h. We observed its inhibitory rate and the density of micro-vascular growth in grafted mice with human gastric cancer SGC-7901. The apoptosis of human gastric cancer SGC-7901 was revealed in NM-3 treatment group by using terminal deoxynucleotidyl transferase-mediated deoxy-uridine triphosphate-fluorescene nick end labeling (TUNEL) method and flow cytometry analysis. The growth of SGC-7901 cells was markedly inhibited compared with control growp, which was smaller than that in normal saline control group (4.17 g+/-0.22 g vs 9.45 g+/-1.38 g, P<0.01). The level of apoptosis of human gastric cell line SGC-7901 was obviously increased in NM-3 treatment group at 1 mg.L(-1) for 24 h. NM-3 inducing apoptotic index in NM-3 plus carboplatin group was 3.5 times that of carboplatin control group (TUNEL: 27.98+/-6.12% vs 12.94+/-2.12%, FACScan: 26.86+/-5.69% vs 11.86+/-1.09%, P<0.01). Western blot analysis showed that the apoptotic index of human gastric cancer was elevated for 12, 24 and 36 h with an evident time-effect relationship in groups at 100 mg.L(-1). NM-3 enhanced the inhibitive effects and sensitivity of chemotherapy for human gastric cancer in nude mice. These results suggested that NM-3 played a key inhibitive role in the growth of grafted human gastric cancer in nude mice. NM-3 can inhibit the growth of human gastric cancer cell line SGC-7901, and enhance the sensitivity of carboplatin on SGC-7901 and induced its apoptosis.


A model on the origin of RNA.
The theory of the liquid-glass transition is extended to describe the polymerization of RNA in a nucleotide-condensed state. In the glassy state the ribose subunits are joined by a 2'-5' or 3'-5' phosphodiester linkage to form the ribose-phosphate backbone similar to oligosaccharides and polysaccharides. The occurrence of the glass transition requires two conditions: (1) a supercooled state in a nucleotide-condensed state should exist below the temperature at which the whole RNA hydrolyzes; (2) the Gibbs free energy due to the Kauzmann entropy, which obeys a Curie law with a negative sign, must be larger than the height of the potential barrier for nucleotides to overcome to form the binding.


The controlled single subject trial.
Randomized controlled trials in single subjects ('N of 1 RCT') are double-blind, multi crossover trials in which the effects of two or more treatments are compared within one individual. The aim is to provide a controlled assessment of the efficacy of a new drug in a specific patient. Suitable diseases for single subject trials are particularly those which significantly impair the quality of life and in which there are uncertain treatment effects. Appropriate drugs should have a prompt action, a minimum of carry-over effect, and no side-effects. The trial design is determined by the length, number, and order of successive treatment periods, the outcome measures, and the statistical requirements. Each of these elements may be altered and tailored to the clinical entity and drug(s) applied, thus, providing a large potential for design options.


Simplified toxicologic monitoring of adriamycin, its major metabolites and nogalamycin by reverse-phase high pressure liquid chromatography, Part I: Analytical techniques for isolated human plasma.
A simplified method is presented for routine toxicologic analysis of the antineoplastic drug, adriamycin, and its major metabolites in human plasma. This method employs a single solvent extraction of plasma using an acetonitrile-aqueous NaOH mixture, followed by reverse-phase isocratic high pressure liquid chromatographic (HPLC) analysis. Recoveries of greater than 95% are obtained for adriamycin and its two major derivatives over the range of concentration: 0.2 to 8.0 nmol/mL of plasma. This method of drug and metabolite isolation and HPLC analysis from human plasma provides an efficient and accurate approach to the individualized toxicologic monitoring of adriamycin pharmacokinetics and metabolism.


Osterix-driven LINC complex disruption in vivo diminishes bone microarchitecture in 8-week male mice but not after 6-week voluntary wheel running.
The Linker of Nucleoskeleton and Cytoskeleton (LINC) complex is a crucial connective component between the nuclear envelope and the cytoskeleton involving various cellular processes including nuclear positioning, nuclear architecture, and mechanotransduction. How LINC complexes regulate bone formation in vivo, however, is not well understood. To start bridging this gap, here we created a LINC disruption murine model using transgenic mice expressing Cre recombinase enzyme under the control of the Osterix (Osx-Cre) which is primarily active in pre-osteoblasts and floxed Tg(CAG-LacZ/EGFP-KASH2) mice. Tg(CAG-LacZ/EGFP-KASH2) mice contain a lox-STOP-lox flanked LacZ gene which is deleted upon cre recombination allowing for the overexpression of an EGFP-KASH2 fusion protein. This overexpressed protein disrupts endogenous Nesprin-Sun binding leading to disruption of LINC complexes. Thus, crossing these two lines results in a Osx-driven LINC disruption (ODLD) specific to pre-osteoblasts. In this study, we investigated how this LINC disruption affects exercise induced bone accrual. ODLD cells had decreased osteogenic and adipogenic potential in vitro compared to non-disrupted controls and sedentary ODLD mice showed decreased bone quality at 8-weeks. Upon access to a voluntary running wheel ODLD animals showed increased running time and distance; however, our 6-week exercise intervention did not significantly affect bone microarchitecture and bone mechanical properties.


Seawater Activation of Escherichia coli Gene Promoter Elements: Dominance of rpoS Control.
The release of non-disinfected wastewater into the marine environment is a common practice in many countries; nevertheless, the molecular mechanisms involved in determining the survival of enteric bacteria in seawater are poorly understood, in spite of the obvious public health implications. In a methodological attempt to address this issue, a plasmid-based collection of 687 Escherichia coli distinct promoter::luxCDABE fusions was screened to identify promoters that are induced upon exposure to seawater. The luminescence driven by 22 out of these promoters reproducibly increased at least two-fold in an artificial seawater medium; only 9 of the corresponding genes have previously been assigned a function. The most prominent characteristic of the induced genes was that most (18 out of 22) were under rpoS control. The induction of these seawater-responsive promoters was evaluated in different media to identify the cause of the increased transcription. Salinity or osmolarity was instrumental in only four cases, and in three promoters, increased pH also seemed to play a role; however, the most significant environmental effector in inducing the majority of the seawater-induced promoters appeared to be nutrient limitation.


The glucagon-insulin antagonism and glucagon-dexamethasone synergism in the induction of phosphoenolpyruvate carboxykinase in cultured rat hepatocytes.
In hepatocytes precultured for 24 h with dexamethasone glucagon increased phosphoenolpyruvate carboxykinase activity 3-4-fold with a half maximal activity increase at 30 pM. The half maximal effective glucagon concentration was enhanced 10-fold to 300 pM when insulin was added simultaneously. The glucagon-insulin antagonism was maximally expressed when glucagon was present at low physiological concentrations. At equimolar doses it was only in the concentration range around 0.1 nM that glucagon and insulin became powerful antagonists; at higher levels glucagon was the dominant hormone. In hepatocytes not pretreated with dexamethasone glucagon still enhanced phosphoenolpyruvate carboxykinase activity, but the half maximal effective dose raised more than 30-fold to 1 nM. The degree of stimulation, however, remained essentially unchanged. Thus dexamethasone shifted the glucagon sensitivity of the cells into the physiological concentration range; it exerted a half maximal effect at 10 nM. Dexamethasone was not required for the enzyme induction proper if the cells had been pretreated with the glucocorticoid. The amount of the glucagon-stimulated enzyme induction was dependent on the time period of cell pretreatment with dexamethasone. Glucagon enhanced enzyme activity to the same constant suboptimal level irrespective of whether cells had been pretreated with glucocorticoid for 1 or for 14 h. If cells were pretreated for more than 15 h, glucagon linearly increased enzyme activity further until the maximal value was reached after 24 h pretreatment. The glucagon-insulin antagonism and the glucagon-glucocorticoid synergism were observed at physiological hormone concentrations indicating that the interaction should be effective also in vivo. Dexamethasone does not seem to be generally permissive for the inducing action of glucagon, but rather sensitizes the cell towards lower physiological hormone concentrations.


[Treatment of external fixator in young patients with valgus deformity of the knee companied with leg shortening].
To explore the efficacy and experience of callus distraction technique with the external fixator for valgus deformity of the knee companied with leg shortening in young patients and to provide evidence for selecting reasonable therapy. From January 2002 to January 2009, the clinical data of 28 young patients (17 males and 11 females, aged 8 to 14, mean age 11.9 years) treated with callus distraction, who had valgus deformity of the knee, companied with leg shortening, were analyzed retrospectively. Three had bilateral total valgus deformity of the knee, with a total of 31 knees. Before the operation, the abnormal limbs shortened from 3 to 7 cm (average 4.1 cm) companied with the normal one. The tibiofemoral angle ranged from 138° to 160° (mean angle 148°) and the Condyle interval from 5 to 33 cm (mean interval 15.2 cm). The 28 patients were followed up for 35 to 84 ( mean 62 ) months. The extent length ranged from 4.5 to 10.1 cm (average 6.8 cm). The tibiofemoral angle ranged from 169° to 175° (mean 173°) after the union. The patients resumed the normal length of limbs, and the severe valgus deformity of the knee was corrected. Callus distraction with external fixator is effective for serious valgus deformity of the knee companied with leg shortening.


Sequestration of Sulphide from Biogas by thermal-treated iron nanoparticles synthesized using tea polyphenols.
Dark tea-iron nanoparticles (DT-Fe NPs) were prepared using extracts of dark tea leaves as a reducing agent, and further underwent thermal treatment in air. The H2S removal performances of thermal-treated DT-Fe NPs for biogas were further evaluated using a custom-designed fixed-bed reactor (reaction temperature of 250°C, H2S content of 1%). Significant morphology and chemical composition differences were observed when DT-Fe NPs were treated at different temperatures (300-800oC). X-ray diffractometer analysis revealed that a phase transition from γ-Fe2O3 to α-Fe2O3 occurred under heat treatment. When the thermal treatment temperature was 300°C, only α-Fe2O3 was detected. Both α-Fe2O3 and γ-Fe2O3 were present in the sample treated at 400°C. When the thermal treatment temperature was 500-800°C, γ-Fe2O3 in the sample was completely converted to α-Fe2O3. The H2S removal capacity is 14.72 mg H2S/g for DT-Fe NPs without treatment. However, the value increased significantly to 408.30 mg H2S/g after 400°C thermal treatment, which can be explained by the formation of highly active γ-Fe2O3. The reaction product of thermal-treated DT-Fe NPs at 400°C and H2S were further characterized by X-ray diffractometer and X-ray photoelectron spectroscopy. The results showed that it is composed of FeS2 and FeS, in which 72.6% of the sulphur existed as disulphide and 27.4% as monosulphide.


Effect of size and N-terminal residue characteristics on bacterial cell penetration and antibacterial activity of the proline-rich peptide Bac7.
Bac7 is a proline-rich antimicrobial peptide, selective for Gram-negative bacteria, which acts intracellularly after membrane translocation. Progressively shortened fragments of Bac7 allowed determining the minimal sequence required for entry and antimicrobial activity as a 16-residue, N-terminal fragment, while further shortening led to a marked decrease in both functions. Furthermore, two N-terminal arginine residues were required for efficient translocation and activity. Analogues in which these residues were omitted, or where the side chain steric or physicochemical characteristics were systematically altered, were tested on different Escherichia coli strains, including a mutant with a destabilized outer membrane and one lacking the relevant SbmA membrane transport protein. H-bonding capacity, stereochemistry, and charge, in that order, played a determining role for efficient transit through both the outer and cytoplasmic membranes. Our studies allowed building a more detailed model for the mode-of-action of Bac7, and confirming its potential as an anti-infective agent, also suggesting it may be a vehicle for internalization of other antibiotic cargo.


Nurses' Positive Experiences in Caring for Older Adults With Dementia: A Qualitative Analysis.
A qualitative study was conducted to explore nurses' positive experiences in caring for older adults with dementia in South Korea. Researchers collected data through in-depth, face-to-face interviews, and the recorded interviews were analyzed using grounded theory. A total of 33 codes, 12 categories, and 21 sub-categories were derived, and the categories were further analyzed using the paradigm model. A conceptual framework, the Gratified in Caring Model, was developed by integrating and abstracting the core category from nurses' positive experiences, and can be used by nurses to provide effective care and educators to train nurses to care for older adults. Findings also emphasize the need for nurses to collaborate with family members, as collaboration has been found to influence nurses' positive experiences. [Journal of Gerontological Nursing, 45(1), 31-37.].


Effects of a calcium supplement on bone mineral density in male cyclists.
The purpose of this study was to maintain or improve bone density in male road cyclists through provision of calcium and vitamin D3 supplementation ingested before cycling. Participants were male cyclists (N=17), with a mean (±SD) age of 42.7 (9.4) years. Measurements of lumbar spine and hip areal bone mineral density (aBMD) were performed at the start and end of a cycling season. Cyclists were randomized into the calcium supplement (CAL) or the control group (CON) group based on lumbar spine T-scores. The CAL group was instructed to consume 1600 mg calcium and 1000 IU vitamin D3 prior to cycling for the 5-month period. Femoral trochanter aBMD significantly decreased during the 5 month cycling season. There was no difference in aBMD between CAL and CON groups. Negative effects of competitive cycling on aBMD in hip structures can be observed within 5 months. Calcium and vitamin D3 ingested prior to cycling does not ameliorate this effect. This proof of concept paper provides evidence that more work is needed to find mechanisms to protect cyclists from destructive bone loss in hip structures.


L-arginine-NO pathway and CNS oxygen toxicity.
The involvement of the L-arginine-nitric oxide (NO) pathway in the pathogenesis of hyperoxia-induced seizures was studied by using agents controlling NO levels. We selected two inhibitors of nitric oxide synthase, the systemic inhibitor Nomega-nitro-L-arginine methyl ester (L-NAME) and the novel cerebral-specific inhibitor 7-nitroindazole, and two generators of NO, the NO donor S-nitroso-N-acetylpenicillamine and the physiological precursor L-arginine. Rats with chronic cortical electrodes were injected intraperitoneally with different doses of one of the agents or their vehicles before exposure to 0.5 MPa O2 and O2 with 5% CO2 at an absolute pressure of 0.5 MPa. The duration of the latent period until the onset of electrical discharges in the electroencephalogram was used as an index of central nervous system O2 toxicity. The two nitric oxide synthase inhibitors L-NAME and 7-nitroindazole significantly prolonged the latent period to the onset of seizures on exposure to both hyperbaric O2 and to the hypercapnic-hyperoxic mixture. Pretreatment with the NO donor S-nitroso-N-acetylpenicillamine significantly shortened the latent period, whereas L-arginine, the physiological precursor of NO, significantly prolonged the latent period to onset of seizures. Our results suggest that the L-arginine-NO pathway is involved in the pathophysiology of hyperoxia-induced seizures via various regulating mechanisms.


On the self-aggregation and fluorescence quenching aptitude of surfactant ionic liquids.
The aggregation behavior in aqueous solution of a number of ionic liquids was investigated at ambient conditions by using three techniques: fluorescence, interfacial tension, and (1)H NMR spectroscopy. For the first time, the fluorescence quenching effect has been used for the determination of critical micelle concentrations. This study focuses on the following ionic liquids: [Cnmpy]Cl (1-alkyl-3-methylpyridinium chlorides) with different linear alkyl chain lengths (n=4, 10, 12, 14, 16, or 18), [C12mpip]Br (1-dodecyl-1-methylpiperidinium bromide), [C12mpy]Br (1-dodecyl-3-methylpyridinium bromide), and [C12mpyrr]Br (1-dodecyl-1-methylpyrrolidinium bromide). Both the influence of the alkyl side-chain length and the type of ring in the cation (head) on the CMC were investigated. A comparison of the self-aggregation behavior of ionic liquids based on 1-alkyl-3-methylpyridinium and 1-alkyl-3-methylpyridinium cations is provided. It was observed that 1-alkyl-3-methylpyridinium ionic liquids could be used as quenchers for some fluorescence probes (fluorophores). As a consequence, a simple and convenient method to probe early evidence of aggregate formation was established.


Physiologically-Based Pharmacokinetic (PBPK) Modeling of Buprenorphine in Adults, Children and Preterm Neonates.
Buprenorphine plays a crucial role in the therapeutic management of pain in adults, adolescents and pediatric subpopulations. However, only few pharmacokinetic studies of buprenorphine in children, particularly neonates, are available as conducting clinical trials in this population is especially challenging. Physiologically-based pharmacokinetic (PBPK) modeling allows the prediction of drug exposure in pediatrics based on age-related physiological differences. The aim of this study was to predict the pharmacokinetics of buprenorphine in pediatrics with PBPK modeling. Moreover, the drug-drug interaction (DDI) potential of buprenorphine with CYP3A4 and P-glycoprotein perpetrator drugs should be elucidated. A PBPK model of buprenorphine and norbuprenorphine in adults has been developed and scaled to children and preterm neonates, accounting for age-related changes. One-hundred-percent of the predicted AUClast values in adults (geometric mean fold error (GMFE): 1.22), 90% of individual AUClast predictions in children (GMFE: 1.54) and 75% in preterm neonates (GMFE: 1.57) met the 2-fold acceptance criterion. Moreover, the adult model was used to simulate DDI scenarios with clarithromycin, itraconazole and rifampicin. We demonstrate the applicability of scaling adult PBPK models to pediatrics for the prediction of individual plasma profiles. The novel PBPK models could be helpful to further investigate buprenorphine pharmacokinetics in various populations, particularly pediatric subgroups.


[Efficacy of ACEI in the treatment of hypertension and the effect of secondary prevention in patients complicated with coronary heart disease and stroke].
To investigate the efficacy of ACEI drugs in the treatment of hypertension patients and the effect of two levels of prevention of hypertension complicated with coronary heart disease and stroke. 210 cases of hypertension patients in our hospital from January 2012 to December 2015 were randomly divided into experimental group and control group, 105 cases in each group. According to the conventional symptomatic treatment, the experimental group was given lisinopril treatment, while control group was given the captopril treatment. Changes of blood pressure parameters and the level of baPWV in two groups were observed before and after treatment coronary heart disease and stroke, recurrence rate and death rate were compared in these two groups. No significant difference of SBP, DBP, PP and baPWV between two groups before treatment (P>0.05). The indexes of the two groups were significantly decreased after 1 months and 3 months, and the level of patients in the experimental group was lower than that of the control group (P<0.05). The recurrence rate in the experimental group was lower than those in the control group (P<0.05). ACEI drugs in the treatment of hypertension can effectively reduce the level of blood pressure, improve arterial elasticity function, reduce the recurrence rate and mortality rate of coronary heart disease and stroke. The effect of antihypertensive and two levels of prevention of hypertension complicated with coronary heart disease and stroke of lisinopril is positive.


Role of ITGAE in the development of autoimmune diabetes in non-obese diabetic mice.
There is compelling evidence that autoreactive CD8(+)T cells play a central role in precipitating the development of autoimmune diabetes in non-obese diabetic (NOD) mice, but the underlying mechanisms remain unclear. Given that ITGAE (CD103) recognizes an islet-restricted ligand (E-cadherin), we postulated that its expression is required for initiation of disease. We herein use a mouse model of autoimmune diabetes (NOD/ShiLt mice) to test this hypothesis. We demonstrate that ITGAE is expressed by a discrete subset of CD8(+)T cells that infiltrate pancreatic islets before the development of diabetes. Moreover, we demonstrate that development of diabetes in Itgae-deficient NOD mice is significantly delayed at early but not late time points, indicating that ITGAE is preferentially involved in early diabetes development. To rule out a potential contribution by closely linked loci to this delay, we treated WT NOD mice beginning at 2 weeks of age through 5 weeks of age with a depleting anti-ITGAE mAb and found a decreased incidence of diabetes following anti-ITGAE mAb treatment compared with mice that received isotype control mAbs or non-depleting mAbs to ITGAE. Moreover, a histological examination of the pancreas of treated mice revealed that NOD mice treated with a depleting mAb were resistant to immune destruction. These results indicate that ITGAE(+) cells play a key role in the development of autoimmune diabetes and are consistent with the hypothesis that ITGAE(+)CD8(+)T effectors initiate the disease process.


Same-Day Medical Visit Increases Viral Suppression, Peter Ho Memorial Clinic, 2014-2015 and 2016-2017.
Viral suppression (VS) in patients newly diagnosed with HIV is critical to reducing morbidity, mortality, and new transmissions. Rapid initiation of antiretroviral therapy (ART) is a promising model to improve VS, but patients must be seen expeditiously by a prescribing provider. Our retrospective study compared patients achieving VS after introduction of medical visits on the same day as HIV diagnoses from 2014 to 2017. The time to VS was evaluated using survival analysis. Wilcoxon two-sample tests evaluated median times to VS (after diagnosis and ART receipt). When 2016-2017 was compared with 2014-2015, a higher proportion of patients achieved VS (96% and 90%, respectively; p = .0292); the median time to VS decreased to 88 from 101 days after diagnosis and to 44 from 70 days after receipt of ART. As clinicians consider rapid ART initiation, a medical visit on the same day as HIV diagnosis is an intermediate intervention that may improve VS.


Endometrial Factor in Unexplained Infertility and Recurrent Implantation Failure.
Unexplained infertility (UI) and recurrent implantation failure (RIF) are diagnoses based on failed pregnancy attempts within current infertility treatment models. Both diagnoses are made when fertility is unexplained based on current diagnostic methods and has no clear cause; UI is diagnosed when testing is inconclusive, and RIF is diagnosed after three failed in vitro fertilization cycles. In both cases, interventions are often introduced without an understanding of the cause of the infertility, frequently leading to frustration for patients and caregivers. Here, we review evidence to support an influence of endometrial factor in patients given these poorly defined diagnoses and possible treatments targeting the endometrium to improve outcomes in these patients.


[Cytodiagnosis of Ewing sarcoma].
Pelvic Ewing's sarcomas were studied by fine needle aspiration biopsy in two young male patients. Local pain, subfebrility, high ESR had occurred in both cases. X ray examination showed osteolytic lesions in both patients. The differential diagnostic question was, are the lesions osteomyelitis or malignant tumors? Fine needle aspiration biopsies and cytological examinations were performed in order to determine the nature of the lesions. The aspirates consisted of monotonous population of small undifferentiated tumor cells. The nuclei were monomorph with small nucleoli and finely granular chromatin. The tumor cells contained large amounts of PAS positive diastase-digestible granular cytoplasmic glycogen. The aspirated material was examined by immunocytochemistry and electronmicroscopy in one of the cases. Both of these methods had diagnostic value in our patients in the detection of Ewing's sarcoma.


Simplistic approach in extracellular synthesis of silver nanoparticles via bioreducing potential of Planococcus plakortidis strain BGCC-51 isolated from dye industry effluent soil.
Here, extracellular synthesis of silver nanoparticles (AgNPs) was carried out by Planococcus plakortidis strain BGCC-51 isolated from dye industry effluent soil. The microbes were isolated, screened, and characterised by molecular analysis (accession number KX776160). The optimisation of synthesis of AgNPs to determine the optimum substrate level (1-5 mM), pH (5-9), and temperature (25-55°C) were further carried out. P. plakortidis strain BGCC-51 gave best yield of AgNPs at substrate concentration 5 mM, pH 8, and at 35°C. Synthesised AgNPs were characterised by scanning electron microscope and high-resolution transmission electron microscope. The size of synthesised AgNPs was in the range of 20-40 nm having spherical morphology. The AgNPs were found to show antimicrobial activity against bacteria such as Escherichia coli (ATCC 25922), Pseudomonas aeruginosa (ATCC 27853), and Staphylococcus aureus (ATCC 29213).


In vitro effects of dexamethasone on mouse ovarian function and pre-implantation embryo development.
The effect of dexamethasone (5-80 microg/ml) on ovarian function and embryo development was studied in mice. The follicle bio-assay revealed no effects of DEX up to 40 microg/ml on folliculogenesis and oogenesis, whereas 80 microg/ml hampered follicle differentiation and oocyte maturation. Androgen, estrogen and progestin secretion patterns were strongly impaired at all doses levels. However, the ovulation-induced progesterone increase indicating that the steroid pathway was activated in presence of DEX. Applying the oil-free mouse embryo assay no alteration of DEX on the first cleavage stages were observed whereas blastocyst rate decreased from 20 microg/ml DEX onwards, and hatching capacity was already impaired in presence of 10 microg/ml DEX. In conclusion, steroidogenesis was affected from 5 microg/ml onwards and the minimum effective inhibitory dose was set at 10 microg/ml for early embryo development. Based on these in vitro findings, physiological or therapeutic levels of glucocorticosteroids are unlikely to affect female fertility.


Vitamins A, C, E and β-carotene as protective factors for some cancers.
The importance of the antioxidant micronutrients vitamins A, C, E and β-carotene in cancer prevention is currently a widely debated human health issue. Generally supported by laboratory findings, and persuasively linked to the lower cancer risk associated with high intakes of fruit and vegetables, the hypothesis is now being tested in many prospective studies around the world. Increasingly, oxidative damage has been implicated in the etiology of several degenerative diseases including cancer, thus highlighting the need to ensure replete antioxidant nutriture as a central measure in preventive medicine.


Parity, contraception, infertility, and the risk of epithelial ovarian cancer.
A case-control study of reproductive factors and cancer of the ovary was conducted during 1989-1992 in metropolitan Toronto and nearby areas of Southern Ontario, Canada. In total, 450 women aged 35-79 years with histologically verified new primary epithelial ovarian cancers were interviewed concerning their reproductive histories. Over the same time period, 564 randomly selected population controls, frequency-matched to the cases according to three 15-year age groups, were also interviewed. Continuous unconditional logistic regression methods were used for analysis. It was found that childbearing and use of oral contraceptives were associated with significant decreasing trends in risk of ovarian cancer; the respective odds ratios were 0.78 for each full-term pregnancy (p < 10(-8)) and 0.92 for each year of use (p < 10(-6)). Hysterectomy was also associated with reduced risk, even after more than 20 years. Among parous women, infertility did not appear to affect risk; for nulliparous women, some evidence of increased risk was present, although fertility problems were reported by only a small fraction of nulliparae. It is suggested that the relatively lower parity of cases as compared with controls may be due to voluntary choices for having fewer children.


Is It Time to Stop Using Single-dose Oral Metronidazole for the Treatment of Trichomoniasis in Women?
The 2015 Centers for Disease Control Sexually Transmitted Disease treatment guidelines currently recommend a single 2-g dose of oral metronidazole as the preferred regimen for treatment of trichomoniasis in human immunodeficiency virus (HIV)-negative women. Mounting recent evidence has shown that the 7-day oral metronidazole dosing regimen is more efficacious than the single 2-g dose. This commentary reviews the implications associated with these new data and discusses issues surrounding it that should be considered moving forward.


Single-ventricle infant home monitoring programs: outcomes and impact.
Patients with single-ventricle, shunt-dependent physiology are at increased risk for interstage death due to the inherent instability of parallel circulation. Enhanced surveillance and early identification of deteriorating physiology via interstage home monitoring result in significant reduction in mortality. These programs are an important focus of improving outcomes for patients with single-ventricle heart disease. In the multi-institutional Pediatric Heart Network Single-Ventricle Reconstruction Trial, interstage mortality was 12%, highlighting the continued opportunity to improve on this metric. A number of single-center series have demonstrated significant benefit of interstage monitoring on survival and growth. The focus on interstage monitoring by the National Pediatric Cardiology Quality Improvement Collaborative of the Joint Council on Congenital Heart Disease should improve our understanding of patients at greatest risk and help establish best practices for interstage care. In addition, a number of pilot projects utilizing newer communication technologies seek to improve the connection between program and patient. Interstage home monitoring programs are a model of collaborative care that improves outcomes. Continued research in this area will refine the elements of home monitoring programs and continue to guide improved results. In addition, this model may serve as a template for the care of other populations of medically complex infants.


In vivo nutritive value of rice feed for sheep and its application for cattle feed.
The objective of this study was to evaluate the nutritive value of polished rice (PR) vs unpolished rice (UPR) as a potential feedstuff for sheep in order to use as a replacer to corn in sheep diet, and as well as to present the application in the formulation of cattle diet. Six corriedale ewe were randomly assigned to each treatment. UPR and PR were provided as a dietary treatment together with timothy grass as a basal diet in a crossover design for two period with 15-d duration for each period. The ratio of experimental and basal feeds were 33.3% and 66.7%, respectively. The differences in the total digestible nutrient (TDN) contents between sheep and cattle was determined according to the references. The number of data collected sheep and cattle was 9 and 17, respectively. The PR showed higher nutrients digestibility than UPR. Similarly, higher TDN content was observed PR than UPR (p < 0.05). As a result, the replacement of corn in the formulate feed with UPR and PR feed rice could be possible with the ratio of 91.2% and 100.0%, respectively. The result of comparation the TDN contents of UPR and PR in sheep and cattle, the PR has no difference in the nutritive value which suggests the applicability of the results of sheep to cattle. On the other hand, UPR has known to have different nutritive value between sheep and cattle, so caution should be taken when preparing formula feeds for cattle.


Macrophage therapy of cancer metastasis.
The biological heterogeneity of metastatic neoplasms and the production of metastases that are resistant to therapy is the major cause of death from cancer. The successful therapy of disseminated metastases must therefore circumvent the problems of neoplastic heterogeneity and the development of resistance to therapy by tumour cells. Macrophages can be activated in situ by interaction with liposomes containing various immunomodulators. Repeated administration of such liposomes has eradicated cancer metastases in several tumour systems. Macrophage destruction of cancer metastases is limited by the ratio of effector to target cells. Thus, destruction of small metastases is effective but once metastases exceed a certain number of cells the therapeutic efficacy is diminished. For this reason we have been investigating various methods of reducing the tumour burden in metastases by modalities such as chemotherapy or radiotherapy and of using tumoricidal macrophages to treat the few tumour cells that escape destruction by conventional therapeutics.


A Combined Methodology to Eliminate Artifacts in Multichannel Electrogastrogram Based on Independent Component Analysis and Ensemble Empirical Mode Decomposition.
Cutaneous measurements of electrogastrogram (EGG) signals are heavily contaminated by artifacts due to cardiac activity, breathing, motion artifacts, and electrode drifts whose effective elimination remains an open problem. A common methodology is proposed by combining independent component analysis (ICA) and ensemble empirical mode decomposition (EEMD) to denoise gastric slow-wave signals in multichannel EGG data. Sixteen electrodes are fixed over the upper abdomen to measure the EGG signals under three gastric conditions, namely, preprandial, postprandial immediately, and postprandial 2 h after food for three healthy subjects and a subject with a gastric disorder. Instantaneous frequencies of intrinsic mode functions that are obtained by applying the EEMD technique are analyzed to individually identify and remove each of the artifacts. A critical investigation on the proposed ICA-EEMD method reveals its ability to provide a higher attenuation of artifacts and lower distortion than those obtained by the ICA-EMD method and conventional techniques, like bandpass and adaptive filtering. Characteristic changes in the slow-wave frequencies across the three gastric conditions could be determined from the denoised signals for all the cases. The results therefore encourage the use of the EEMD-based technique for denoising gastric signals to be used in clinical practice.


Acquired rectovaginal fistula.
Nine girls presented with an acquired rectovaginal fistula shortly after birth. All mothers tested were seropositive for HIV. It is suggested that an acquired rectovaginal fistula is an early manifestation of HIV infection in girls.


Effect and mechanism of acupuncture on Alzheimer's disease: A review.
With the development trend of an aging society, Alzheimer's disease (AD) has become an urgent problem in the field of medicine worldwide. Cognitive impairment in AD patients leads to a decline in the ability to perform daily living and abnormalities in behavior and personality, causing abnormal psychiatric symptoms, which seriously affect the daily life of patients. Currently, mainly drug therapy is used for AD patients in the clinic, but a large proportion of patients will experience drug efficacy not working, and even some drugs bring severe sleep disorders. Acupuncture, with its unique concept and treatment method, has been validated through a large number of experiments and proved its reliability of acupuncture in the treatment of AD. Many advances have been made in the study of the neurobiological mechanisms of acupuncture in the treatment of AD, further demonstrating the good efficacy and unique advantages of acupuncture in the treatment of AD. This review first summarizes the pathogenesis of AD and then illustrates the research progress of acupuncture in the treatment of AD, which includes the effect of acupuncture on the changes of biochemical indicators in AD in vivo and the specific mechanism of action to exert the therapeutic effect. Changes in relevant indicators of AD similarly further validate the effectiveness of acupuncture treatment. The clinical and mechanistic studies of acupuncture in the treatment of AD are intensified to fit the need for social development. It is believed that acupuncture will achieve new achievements in the treatment of AD as research progresses.


Medial temporal lobe amnesia impairs performance on a free association task.
A growing body of evidence suggests that the hippocampus contributes to performance (or is implicated) in non-memory domains from perception to problem solving. In a previous study we found that hippocampal contribution to exemplar generation in a fluency task was determined jointly by the open-endedness of the task and its ability to elicit episodic memories (Sheldon and Moscovitch (2012) Hippocampus 22:1451-1466). In the current study, we extend these observations by exploring the role of the hippocampus in generative, goal-directed open-ended thought in patients with medial temporal lobe (MTL) amnesia on a free association task (think of words as they come to mind). Patients and control participants were asked to associate freely for one minute to cue words that varied in the open-endedness of the responses they elicited (greater for low- than high-frequency words), and in the ease with which episodic memories were evoked (greater for high imageable than low imageable words). As predicted, MTL amnesia patients generated fewer words than control participants when cues were highly imageable and low in frequency, but performed equivalently to them in the other conditions. These results support our prediction that the hippocampus contributes to free association, and possibly more generally to other generative tasks that are open-ended, creative, or that elicit the use of contextual and likely episodic memories in order to derive relevant information.


Genetic markers that influence feed efficiency phenotypes also affect cattle temperament as measured by flight speed.
Flight speed is a predictive indicator of cattle temperament and is associated with feed efficiency phenotypes. Genetic markers associated with both traits may assist with selection of calmer animals with improved economic value. A preliminary genome-wide association study determined chromosomal regions on BTA9, and 17 were associated with flight speed. The genes quaking (QKI), glutamate receptor, ionotropic, AMPA 2 (GRIA2) and glycine receptor β (GLRB) were identified in these regions as potential functional candidates. Beef steers (n = 1057) were genotyped with SNPs located within and flanking these genes. One SNP located near QKI and one near GRIA2 were nominally associated with flight speed (P ≤ 0.05) although neither was significant after Bonferroni correction. Several studies have shown a correlation between flight speed and feed intake or gain; therefore, we also analyzed SNPs on BTA6:38-39 Mb known to be associated with average daily gain (ADG) and average daily feed intake (ADFI) for association with flight speed. Several SNPs on BTA6 were associated with flight speed (P ≤ 0.005), and three were significant after Bonferroni correction. These results suggest that the genes tested are unlikely to contribute to flight speed variation for our cattle population, but SNPs on BTA6 associated with ADG and ADFI may influence temperament. Use of these markers to select for economically important feed efficiency phenotypes may produce cattle with more desirable temperaments.


PCTAIRE1/CDK16/PCTK1 is overexpressed in cutaneous squamous cell carcinoma and regulates p27 stability and cell cycle.
PCTAIRE1 (also known as cyclin-dependent kinase 16 (Cdk16) and PCTK1) is a Cdk family protein that has been implicated in spermatogenesis. We recently revealed the function of PCTAIRE1 in the tumorigenesis of malignancies, including breast and prostate cancers; however, the tumorigenic function of PCTAIRE1 in cutaneous squamous cell carcinoma (SCC) remains unclear. In this study, we investigated the role of PCTAIRE1 in the tumorigenesis of cutaneous SCCs. In cutaneous/oral SCC A431, DJM-1, HSC-3 cells, PCTAIRE1 gene-knockdown was found to diminish cell proliferation as assessed by cell counting and clonogenic assays. FACS analyses of annexin V-PI staining and DNA content showed PCTAIRE1 knockdown to cause G2/M arrest followed by apoptosis. The depletion of PCTAIRE1 was found to lead to the accumulation of tumor suppressor p27 and down-regulation of c-Myc. In tumor xenografts of A431 cells, the conditional knockdown of PCTAIRE1 restores p27 protein expression and suppresses tumor growth. Clinically, in primary tumors from patients with SCC, PCTAIRE1 is more highly expressed in malignant lesions than in adjacent normal epidermis. Conversely, expression levels of p27 are significantly lower in SCC than in normal epidermis. Our findings reveal a crucial function for PCTAIRE1 in regulating p27, c-Myc levels and tumor growth in cutaneous SCC cells, suggesting that PCTAIRE1 could be a novel target for skin tumor treatment.


Multi-exposure Laser Speckle Contrast Imaging (MECI)-Based Prediction of Blood Flow Using Random Forest (RF) With K-Means (KM).
Blood flow prediction is very important for medical diagnosis, drug development, tissue engineering, and continuous monitoring. One commonly used method for studying blood flow is called multi-exposure laser speckle contrast imaging (MECI). It provides valuable insights into how blood flows through tissues and helps in diagnosing circulatory diseases. In our study, we used MECI to measure blood flow in real-time by taking multiple measurements with different exposure times and contrasts. To predict different blood flow rates ranging from 0.1 to 1 mm/s, we employed machine learning (ML) techniques like clustering and random forest (RF) or support vector machine (SVM) algorithms. The study showed that RF with K-means performance is found to be the most accurate technique for flow classification, with an accuracy of 98.5%, a precision of 92%, a specificity of 98.9%, and a classification error of 1.5%. Our study demonstrates that employing clustering and RF algorithms in MECI provides a robust and effective approach to predicting blood flow. This technique holds great potential for a wide range of applications in the medical and healthcare fields.


Prolactin: its role in advanced tongue cancer.
Serum prolactin was measured pretherapeutically and sequentially thereafter using immunoradiometric assay method in 37 male patients with advanced tongue cancer and compared with 23 healthy, age-matched controls. Prolactin levels were correlated with age, various clinicopathologic parameters, overall survival, and patients with response and those with progressive disease. Patients with advanced tongue cancer had higher prolactin levels than controls (P < 0.02), but intergroup variation in prolactin was not observed when considering the age, site of the lesion, disease stage, histologic grade, and keratin. Of the patients, 30% had hyperprolactinemia (prolactin > 15.0 ng/ml). To assess the prognostic significance of pretherapeutic prolactin level, the patients were divided according to the cutoff level of prolactin (15.0 ng/ml). Hyperprolactinemic patients had more unfavourable prognosis than patients with prolactin < 15.0 ng/ml (X2 = 2.91, df = 1, P < 0.0037). In monitoring disease course, patients who responded to treatments had decreased prolactin levels at the end of 18 months as compared to their pretherapeutic levels (P < 0.01). In patients who subsequently developed progressive disease within 18 months, prolactin levels reduced initially at response, whereas with disease progression, prolactin levels increased significantly (P < 0.05). The positive and negative predictive value of prolactin was 100%. Immunohistochemical localization confirmed the ectopic production of prolactin by tongue tumors. In conclusion, our data indicate that hyperprolactinemia may be an independent predictor of short-term prognosis; circulating prolactin may be used as a marker for monitoring disease course in patients with advanced tongue cancer, and prolactin is produced ectopically by tongue tumors.


EHR in the UK: shedding some light from a manager's perspective.
Much has been written recently about the National Health Service electronic health record initiative which, from outside the United Kingdom, may sound to some like the envy of the world. The National Health Service Connecting for Health is the body which now oversees the National Programme for Information Technology, which is responsible for delivering England's electronic health record or National Care Record Service. Questions have been raised as to whether the reported progress toward this admirable goal is an example of spin or reality. A health information management professional from the United States, who has been working inside the UK eye of the storm, sheds some light from a health information management perspective.


Age-related motor dysfunction: Manual slowing in Gorilla gorilla gorilla.
Aging in humans and rhesus monkeys is commonly associated with motor function decrements including dexterity, speed, and strength. Despite their longevity and phylogenetic relatedness to humans, the effects of aging on motor function in non-human apes have been minimally studied. We conducted two experiments with western lowland gorillas (11-54 years of age) to determine whether aged gorillas exhibit motor deficits similar to those seen in other species. In experiment one, gorillas extracted up to 12 food rewards lodged in holes of a Lexan board. Extraction rates were calculated for eight test sessions. A repeated measures ANOVA revealed no main effects of session or sex on extraction rate, but a significant main effect of age. Comparisons between the first and last sessions showed that experience significantly improved extraction rates in young but not aged gorillas. In experiment two, gorillas retrieved a hex nut from three differently shaped rods with each hand for a reward. Latencies of retrieval were calculated for 16 test sessions. A repeated measures ANOVA revealed significant main effects of age class, sex, and session. There were significant interactions between session and sex, session and age, and session, sex, and age. These findings held when analyzing each rod shape separately. Post hoc comparisons revealed that young gorillas were significantly faster at the task than aged gorillas, and females were faster than males. This finding held only for the question mark shaped rod when analyzing each rod shape separately. Comparisons between the first and last sessions showed that experience did not significantly improve latencies in either age or sex class. The direction of these results are congruent with previous findings in humans and monkeys and suggest that aged gorillas experience deficits in bimanual coordination compared to younger gorillas and that age and sex influence fine motor ability in gorillas.


Regulation of vascular endothelial growth factor receptor 2-mediated phosphorylation of focal adhesion kinase by heat shock protein 90 and Src kinase activities.
Exposure of endothelial cells to vascular endothelial growth factor (VEGF) induced tyrosine phosphorylation of focal adhesion kinase (FAK) on site Tyr(407), an effect that required the association of VEGF receptor 2 (VEGFR2) with HSP90. The association of VEGFR2 with HSP90 involved the last 130 amino acids of VEGFR2 and was blocked by geldanamycin, a specific inhibitor of HSP90. Moreover, geldanamycin inhibited the VEGF-induced activation of the small GTPase RhoA, which resulted in an inhibition of phosphorylation of FAK on site Tyr(407). In this context, the inhibition of RhoA kinase (ROCK) with Y27632 or by expression of dominant negative forms of RhoA or ROCK impaired the VEGF-induced phosphorylation of Tyr(407) within FAK. In contrast to phosphorylation of Tyr(861), the phosphorylation of site Tyr(407) was insensitive to Src kinase inhibition by 4-amino-5-(4-chlorophenyl)-7-(t-butyl) pyrazolo[3,4-d] pyrimidine (PP2). We also found that the recruitment of paxillin to FAK was inhibited by geldanamycin but not by PP2, whereas both geldanamycin and PP2 inhibited the recruitment of vinculin to FAK. In accordance, the recruitment of paxillin and vinculin to FAK was inhibited in cells that express the mutant FAK-Y407F, whereas the expression of the mutant Y861F inhibited the recruitment of paxillin but not of vinculin. Importantly, cell migration was abolished in cells in which the signal from the VEGFR2-HSP90 pathway was blocked by the expression of Delta130VEGFR2, a deletant of VEGFR2 that does not associate with HSP90. Our findings underscore for the first time the key role played by the VEGFR2-HSP90-RhoA-ROCK-FAK/Tyr(407) pathway in transducing the VEGF signal that leads to the assembly of focal adhesions and endothelial cell migration.


[Effectiveness and biomechanical analysis of three fixation methods in treatment of posterior Pilon fractures].
To investigate the effectiveness and biomechanical analysis of 3 fixation methods of screw anterior-posterior fixation (SAPF), screw posterior-anterior fixation (SPAF), and buttress plate fixation (BPF) in treatment of posterior Pilon fractures. Fifteen fresh-frozen skeleto-ligamentous lower leg specimens were harvested to establish the models of posterior Pilon fracture, and then fracture was fixed with BPF (n = 5), SAPF (n = 5), and SPAF (n = 5). Vertical force was loaded to internal fixation failure in a speed of 1 cm/minute with servohydraulic testing machine. The instantaneous loads of 1 mm and 2 mm steps and the failure modes were recorded. Between May 2008 and December 2011, 56 patients with posterior Pilon fracture were treated with SAPF (SAPF group) in 11 cases, or SPAF (SPAF group) in 26 cases, or BPF (BPF group) in 19 cases. There was no significant difference in age, gender, injury cause, side, disease duration, and complications among groups (P > 0.05). Clinical and radiographic examinations were used to assess the reduction and healing of fracture; the American Orthopaedic Foot and Ankle Society (AOFAS) ankle-hindfoot score and the visual analogue scale (VAS) were used to evaluate the functional outcomes. No breaking or bending was observed in all specimens, fixation failure was caused by cancellous bone compression. The instantaneous loads of 1 mm and 2 mm steps were the largest in BPF group, larger in SPAF group, and smallest in SAPF group, showing significant differences among 3 groups (P < 0.05). A total of 47 cases were followed up 16-54 months (9 in SAPF group, 22 in SPAF group, and 16 in BPF group), with a mean time of 35.2 months. Fixation failure was found in 2 cases of SAPF group; the other cases obtain bony union within 3 to 4 months (mean, 3.2 months) with no fixation failure. The AOFAS score was significantly lower in SAPF group than in SPAF and BPF groups (P < 0.05), but no significant difference was found between SPAF and BPF groups (P > 0.05). The VAS score was significantly higher in SAPF group than in SPAF and BPF groups (P < 0.05), but no significant difference was found between SPAF and BPF groups (P > 0.05). SAPF could not reach enough fixation strength for the posterior Pilon fracture; both SPAF and BPF could reach rigid fixation, and have good effectiveness. And from the biomechanical points, BPF could reach better fixation strength than screw fixations.


Relationship between growth, maturation and musculoskeletal conditions in adolescents: a systematic review.
To determine whether there is a relationship between physical growth and development, as determined by markers of biological maturation, and musculoskeletal conditions in adolescents. Systematic review. Electronic databases (PubMed, EMBASE and the Cumulative Index to Nursing and Allied Health Literature) were searched up to 6 September 2017. Studies that evaluated the association between biological maturation or growth and musculoskeletal conditions in adolescents (chronological age 10-19 years). From 20 361 titles identified by the searches, 511 full-text articles were retrieved and assessed for eligibility; 56 studies, all at high risk of bias, evaluating the relationship between maturation and/or growth and musculoskeletal conditions were included. A total of 208 estimates of association were identified across the included studies, which generally indicated no association or an unclear association between maturation, growth and musculoskeletal conditions. While the relationship between maturation, growth and musculoskeletal conditions remains plausible, the available evidence is not supportive. The current body of knowledge is at high risk of bias, which impedes our ability to establish whether biological maturity and growth are independent risk factors for musculoskeletal conditions.


Frontal Control Process in Intentional Forgetting: Electrophysiological Evidence.
In this study, we aimed to seek for the neural evidence of the inhibition control process in directed forgetting (DF). We adopted a modified item-method DF paradigm, in which four kinds of cues were involved. In some trials, the words were followed by only a forgetting (F) cue. In the other trials, after a word was presented, a maintenance (M) cue was presented, followed by an explicit remembering (M-R) cue or an forgetting (M-F) cue. Data from 19 healthy adult participants showed that, (1) compared with the remembering cue (i.e., M-R cue), forgetting cues (i.e., M-F cue and F cue) evoked enhanced frontal N2 and reduced parietal P3 and late positive complex (LPC) components, indicating that the forgetting cues might trigger a more intensive cognitive control process and that fewer amounts of cognitive resources were recruited for the further rehearsal process. (2) Both the M cue and the F cue evoked enhanced N2 and decreased P3 and LPC components than the M-R or M-F cue. These results might indicate that compared with the M-R and M-F cues, both the M and F cues evoked a more intensive cognitive control process and decreased attentional resource allocation process. (3) The F cue evoked a decreased P2 component and an enhanced N2 component relative to the other cues (i.e., M-R, M-F, M), indicating that the F cue received fewer amounts of attentional resources and evoked a more intensive cognitive control process. Taken together, forgetting cues were associated with enhanced N2 activity relative to the maintenance rehearsal process or the remembering process, suggesting an enhanced cognitive control process under DF. This cognitive control process might reflect the role of inhibition in DF as attempting to suppress the ongoing encoding.


Chryseobacterium haifense sp. nov., a psychrotolerant bacterium isolated from raw milk.
Strain H38(T) was isolated during a study on the diversity of culturable psychrotolerant bacteria in raw milk. Comparative 16S rRNA gene sequence analysis showed that strain H38(T) belongs to the genus Chryseobacterium (family Flavobacteriaceae, phylum Bacteroidetes), with the highest similarity (96.7 %) to Chryseobacterium hispanicum VP48(T). Strain H38(T) grows aerobically, at 4-41 degrees C, with 0-2.5 % NaCl and at pH 6.5-10.5. Light induces the formation of yellow carotenoid pigments. The dominant cellular fatty acids are 15 : 0 iso (41.6 %), 15 : 0 anteiso (16.6 %) and 17 : 0 iso 3-OH (10.3 %). The G+C content of the DNA is 37.8 mol%. On the basis of its phenotypic properties and phylogenetic distinctiveness, strain H38(T) (=LMG 24029(T) =DSM 19056(T)) is classified in the genus Chryseobacterium as the type strain of a novel species, for which the name Chryseobacterium haifense sp. nov. is proposed.


Tenascin-C stimulates glioma cell invasion through matrix metalloproteinase-12.
The capacity of glioma cells to invade extensively within the central nervous system is a major cause of the high morbidity rate of primary malignant brain tumors. Glioma cell invasion involves the attachment of tumor cells to extracellular matrix (ECM), degradation of ECM components, and subsequent penetration into adjacent brain structures. These processes are accomplished in part by matrix metalloproteinases (MMP) within a three-dimensional milieu of the brain parenchyma. As the majority of studies have used a two-dimensional monolayer culture system, we have used a three-dimensional matrix of collagen type I gel to address glioma-secreted proteases, ECM, and invasiveness of glioma cells. We show that in a three-dimensional collagen type I matrix, the presence of tenascin-C, commonly elevated in high-grade gliomas, increased the invasiveness of glioma cells. The tenascin-C-mediated invasiveness was blocked by metalloproteinase inhibitors, but this did not involve the gelatinases (MMP-2 and MMP-9) commonly implicated in two-dimensional glioma growth. A thorough analysis of 21 MMPs and six members of a disintegrin and metalloproteinase domain showed that MMP-12 was increased in gliomas by tenascin-C in three-dimensional matrix. Furthermore, examinations of resected specimens revealed high MMP-12 levels in the high-grade glioblastoma multiforme tumors. Finally, a function-blocking antibody as well as small interfering RNA to MMP-12 attenuated the tenascin-C-stimulated glioma invasion. These results identify a new factor, MMP-12, in regulating glioma invasiveness through interaction with tenascin-C.


Mortality-related risk factors of COVID-19: a systematic review and meta-analysis of 42 studies and 423,117 patients.
Mortality rates of coronavirus disease-2019 (COVID-19) continue to rise across the world. The impact of several risk factors on coronavirus mortality has been previously reported in several meta-analyses limited by small sample sizes. In this systematic review, we aimed to summarize available findings on the association between comorbidities, complications, smoking status, obesity, gender, age and D-dimer, and risk of mortality from COVID-19 using a large dataset from a number of studies. Electronic databases including Google Scholar, Cochrane Library, Web of Sciences (WOS), EMBASE, Medline/PubMed, COVID-19 Research Database, and Scopus, were systematically searched till 31 August 2020. We included all human studies regardless of language, publication date or region. Forty-two studies with a total of 423,117 patients met the inclusion criteria. To pool the estimate, a mixed-effect model was used. Moreover, publication bias and sensitivity analysis were evaluated. The findings of the included studies were consistent in stating the contribution of comorbidities, gender, age, smoking status, obesity, acute kidney injury, and D-dimer as a risk factor to increase the requirement for advanced medical care. The analysis results showed that the pooled prevalence of mortality among hospitalized patients with COVID-19 was 17.62% (95% CI 14.26-21.57%, 42 studies and 423,117 patients). Older age has shown increased risk of mortality due to coronavirus and the pooled odds ratio (pOR) and hazard ratio (pHR) were 2.61 (95% CI 1.75-3.47) and 1.31 (95% CI 1.11-1.51), respectively. A significant association were found between COVID-19 mortality and male (pOR = 1.45; 95% CI 1.41-1.51; pHR = 1.24; 95% CI 1.07-1.41), and current smoker (pOR = 1.42; 95% CI 1.01-1.83). Furthermore, risk of mortality among hospitalized COVID-19 patients is highly influenced by patients with Chronic Obstructive Pulmonary Disease (COPD), Cardiovascular Disease (CVD), diabetes, hypertension, obese, cancer, acute kidney injury and increase D-dimer. Chronic comorbidities, complications, and demographic variables including acute kidney injury, COPD, diabetes, hypertension, CVD, cancer, increased D-dimer, male gender, older age, current smoker, and obesity are clinical risk factors for a fatal outcome associated with coronavirus. The findings could be used for disease's future research, control and prevention.


Minimization vs tailoring: Where do we stand with personalized immunosuppression during renal transplantation in 2015?
The introduction of novel immunosuppressive agents over the last two decades and the improvement of our diagnostic tools for early detection of antibody-mediated injury offer us an opportunity, if not a mandate, to better match the immunosuppression needs of the individual patients with side effects of the therapy. However, immunosuppressive regimens in the majority of programs remain mostly protocol-driven, with relatively little inter-program heterogeneity in certain areas of the world. Emerging data showing different outcomes with a particular immunosuppressive strategy in populations with varying immunological risks underscore a real potential for "personalized medicine" in renal transplantation. Studies demonstrating marked differences in the adverse-effect profiles of individual drugs including the risk for viral infections, malignancy and renal toxicity call for a paradigm shift away from a "one size fits all" approach to an individually tailored immunosuppressive therapy for renal transplant recipients, assisted by both screening for predictors of graft loss and paying close attention to dose or class-related adverse effects. Our paper explores some of the opportunities during the care of these patients. Potential areas of improvements may include: (1) a thorough assessment of immunological and metabolic risk profile of each renal transplant recipient; (2) screening for predictors of graft loss and early signs of antibody-mediated rejection with donor-specific antibodies, protocol biopsies and proteinuria (including close follow up of adverse effects with dose adjustments or conversions as necessary); and (3) increased awareness of the possible link between poor tolerance of a given drug at a given dose and non-adherence with the prescribed regimen. Altogether, these considerations may enable the most effective use of the drugs we already have.


Septic shock: new pharmacotherapy options or better trial design?
Over the last two decades, many of the mechanisms underlying the pathophysiology of sepsis have been uncovered, but this has not led to the development of effective therapies for sepsis. Despite improvements in the general care of critically ill patients in recent years, mortality rates for patients with severe sepsis and septic shock remain high at 30 to 50% and there is an urgent need to develop new, effective therapeutic strategies. Attempts to develop a therapy for sepsis have focused on modulating this immune response. Past and present clinical research in this field are reviewed and promising candidates and approaches for the future are discussed. Many reasons have been put forward over the years to explain the many negative results from trials of immunomodulatory therapies. Future studies need to be designed to specifically target patients who can benefit from the intervention being studied rather than at the sepsis population in general. The timing of administration of potential therapies also needs to be taken more into consideration.


Sympathetic reflex responses presumably specific for nociceptive stimulation.
1. In superficially anaesthetized and in unanaesthetized decerebrate cats, tetanic stimulation of A or A + C afferent fibres of the tibial nerve evoked in renal and inferior cardiac nerves a three-phasic change of activity, which consisted of a short powerful burst of discharges, followed by an inhibitory pause and then, by a moderate excitation. When such a command appeared in sympathetic nerves, reflex rising of systemic arterial pressure was extremely fast. 2. The latencies of the three-phasic command and of the so-called very late A response are almost the same. The very late A response is evident if the central nervous system is in the same state as when repetitive stimulation of A afferents evokes the three phasic command in sympathetic nerves and a steep rise of systemic arterial pressure. This permits the assumption that the very late A response reflects the excitation of just those central structures that on repetitive stimulation organize the three-phasic command. 3. A command of this kind is shown to ensure the optimal-time-control of the heart and blood vessels. Such a control (three-phasic command) is supposed to be evoked by nociceptive stimulation, i.e., to be specific for the defence reaction.


Wogonin induced differentiation and G1 phase arrest of human U-937 leukemia cells via PKCdelta phosphorylation.
Wogonin, a natural monoflavonoid, has been shown to have tumor therapeutic potential in vitro and in vivo. Recently many studies have focused on the induction of apoptosis of tumor cells by wogonin. In this study, we found that wogonin could induce differentiation and G1 phase arrest of human U-937 leukemia cells. The growth of U-937 cells incubated with wogonin was inhibited in a time- and concentration-dependent manner. After treatment with wogonin, U-937 cells exhibited the characteristics of mature granulocytes, such as increased cytoplasmic-to-nuclear ratio, enhanced prominence of cytoplasmic granules, membrane ruffling, a higher NBT-reducing ability, and an increased expression of CD11b. Moreover, wogonin could induce G1 phase arrest and influenced the expression of associated proteins. For example, the expression of phorsphorylated protein kinase C (PKC) delta, p21 increased, while that of cyclin D1/cyclin-dependent kinase (CDK) 4, p-Rb decreased. The upregulation of p21 could be reversed by rottlerin, an inhibitor of PKCdelta. Taken together, wogonin induced U-937 cells to undergo granulocytic differentiation and G1 phase arrest via PKCdelta phosphorylation-induced upregulation of p21 proteins.


Nontuberculous mycobacterial infection after lung transplantation: a report of four cases.
Nontuberculous mycobacterium (NTM) infection in a patient in an immunosuppressed state caused by increased use of immunosuppressive or biological agents is a serious clinical problem. Mycobacterium avium complex is the most common involved pathogen, followed by Mycobacterium abscessus (MABSC), while Mycobacterium kansasii is not a major concern. The rate of infection rate in lung transplant recipients is reported to range from 1.5-22.4%. We report here four cases of NTM pulmonary infection and disease among 63 patients who underwent lung or heart-lung transplantation at our hospital. Those four occurred following living-donor transplantation in two patients, one with pulmonary arterial hypertension and one with bronchiectasia, and deceased donor lung transplantation in two patients, lymphangioleiomyomatosis and interstitial pneumonia, respectively. NTM was not detected in any of the patients prior to transplantation. The involved pathogens were Mycobacterium gordonae in one, MAC in one, and MABSC in two of these patients, which were isolated from broncho-alveolar lavage (BAL) in two and sputum in two. The one case of MAC and two of MABSC were symptomatic with consolidation shown in chest CT images indicating possible pneumonia, while the one with M. gordonae had no symptoms and was detected by surveillance BAL. Onset time from detection of NTM was greater than 3 years in the three with MABSC and M. gordonae and less than 3 years in the one with MAC. Each patient required a decrease in immunosuppressive agents according to their condition, while antibiotics therapy was performed in the three who were symptomatic. Sputum culture findings became negative after several months and were maintained thereafter in all. An NTM infection leading to pulmonary disease can occur at any time following lung transplantation. Treatment should be considered depending on the involved pathogens, individual status, and disease severity.


Synthesis, Characterization, and Device Application of Antimony-Substituted Violet Phosphorus: A Layered Material.
Two-dimensional (2D) nanoflakes have emerged as a class of materials that may impact electronic technologies in the near future. A challenging but rewarding work is to experimentally identify 2D materials and explore their properties. Here, we report the synthesis of a layered material, P20.56(1)Sb0.44(1), with a systematic study on characterizations and device applications. This material demonstrates a direct band gap of around 1.67 eV. Using a laser-cutting method, the thin flakes of this material can be separated into multiple segments. We have also fabricated field effect transistors based on few-layer P20.56(1)Sb0.44(1) flakes with a thickness down to a few nanometers. Interestingly, these field effect transistors show strong photoresponse within the wavelength range of visible light. At room temperature, we have achieved good mobility values (up to 58.96 cm2/V·s), a reasonably high on/off current ratio (∼103), and intrinsic responsivity up to 10 μA/W. Our results demonstrate the potential of P20.56(1)Sb0.44(1) thin flakes as a two-dimensional material for applications in visible light detectors.


Role of selective alpha and beta adrenergic receptor mechanisms in rat jejunal longitudinal muscle contractility.
Gut motility is modulated by adrenergic mechanisms. The aim of our study was to examine mechanisms of selective adrenergic receptors in rat jejunum. Spontaneous contractile activity of longitudinal muscle strips from rat jejunum was measured in 5-ml tissue chambers. Dose-responses (six doses, 10(-7) -3 x 10(-5)M) to norepinephrine (NE, nonspecific), phenylephrine (PH, alpha1), clonidine (C, alpha2), prenalterol (PR, beta1), ritodrine (RI, beta2), and ZD7714 (ZD, beta3) were evaluated with and without tetrodotoxin (TTX, nerve blocker). NE(3 x 10(-5)M) inhibited 74 +/- 5% (mean +/- SEM) of spontaneous activity. This was the maximum effect. The same dose of RI(beta2), PH(alpha1), or ZD(beta(3)) resulted in an inhibition of only 56 +/- 5, 43 +/- 4, 33 +/- 6, respectively. The calculated concentration to induce 50% inhibition (EC50) of ZD(beta3) was similar to NE, whereas higher concentrations of PH(alpha1) or RI(beta2) were required. C(alpha2) and PR(beta1) had no effect. TTX changed exclusively the EC50 of RI from 4.4 +/- 0.2 to 2.7 +/- 0.8% (p < 0.04). Contractility was inhibited by NE (nonspecific). PH(alpha1), RI(beta2), and ZD(beta3) mimic the effect of NE. TTX reduced the inhibition by RI. Our results suggest that muscular alpha1, beta2, and beta3 receptor mechanisms mediate adrenergic inhibition of contractility in rat jejunum. beta2 mechanisms seem to involve also neural pathways.


Electrical and Raman scattering studies of ZnO:P and ZnO:Sb thin films.
A study on the structure, electrical and optical properties of ZnO thin films produced by r.f. magnetron sputtering and implanted either with phosphorous (P) or antimony (Sb) is reported in this work. Raman spectroscopy, X-ray diffraction, optical transmittance and Hall effect measurements have been employed to characterize the samples. X-ray diffraction and Raman scattering patterns confirm that, after a 500 degrees C annealing, the doped films keep a polycrystalline nature with (002) preferred orientation. These films are very transparent and Hall effect results show that all have p-type conduction, despite doping ion and dose. The electric resistivity reaches values of 0.012 (omega cm) and 0.042 (omega cm) for the P and Sb-doped samples, respectively.


Efficient Photoswitch System Combining a Dimethyldihydropyrene Pyridinium Core and Ruthenium(II) Bis-Terpyridine Entities.
Terpyridine ruthenium complexes linked to the dimethyldihydropyrene (DHP) photochromic unit have been synthesized and fully characterized by cyclic voltammetry and absorption and emission spectroscopy. The study of the photoisomerization reaction undergone by the DHP motif under visible light irradiation is reported. In comparison to previous work, the introduction of an electron-withdrawing pyridinium spacer between the chelating terpyridine unit and the DHP skeleton has considerably tuned the photochromic properties of the free ligands and their corresponding complexes in term of time response and photoreversibility. A rapid, reversible, and complete conversion between the closed and the open forms has been clearly evidenced under visible light irradiation. Only slight perturbations have been induced by the presence of ruthenium centers. Experimental findings and their interpretation have been supported by theoretical calculations.


Immunocytochemical localization of the GABAA receptor in the cerebral cortex of the lizard Psammodromus algirus.
This study examined the distribution and localization of the gamma-aminobutyric acid (GABA)A receptor in the brain cortex of a reptile by light and electron microscopy, to test whether cortical GABA inhibition is mainly mediated through the GABAA receptor complex. We used preembedding immunocytochemistry and a monoclonal antibody, raised against the receptor complex, that recognizes the beta 2 and beta 3 subunits of the receptor. GABAA receptors were distributed throughout the entire cerebral cortex except the dorsomedial cortex. The immunostaining consisted of fine granules restricted to the plexiform layers of the cortex as seen by light microscopy. This granular aspect of the immunoreactivity most likely corresponds to the immunopositive dendritic and axonal profiles observed under the electron microscope. Some neurons in the medial and lateral cortices displayed patches of immunoreactivity along the cell body and processes, and as a result their morphology was outlined. We discuss the possibility that these neurons were GABAergic as well. The immunocytochemical data demonstrate that the distribution and localization of GABAA receptors in discrete regions of the reptilian cerebral cortex resemble that of parts of the hippocampal formation of humans and rats, suggesting that the basic configuration of the GABA system in these regions is conserved.


A viscous pump bioreactor.
The fluid dynamic design and characterization of a low mechanical stress agitator and bioreactor vessel for large-scale bioprocessing using anchorage dependent mammalian cells is considered. The complex and fragile nature of mammalian cells puts stringent constraints on the design of agitators for stirred tank bioreactors. Traditional agitators have difficulty meeting the competing requirements of fluidization and mixing while maintaining low enough mechanical stress levels to avoid cell damage. A rotating disc agitator design is proposed. Flow visualization and laser Doppler velocimeter measurements reveal fluidization of microcarriers with a gentle (low turbulence level), highly three-dimensional flow characterized by good mixing at low hydrodynamic shear stress levels.