New developments in flavivirus vaccines with special attention to yellow fever.
Here we review recent epidemiological trends in flavivirus diseases, findings related to existing vaccines, and new directions in flavivirus vaccine research. We emphasize the need for stepped-up efforts to stop further spread and intensification of these infections worldwide. Although the incidence and geographic distribution of flavivirus diseases have increased in recent years, human vaccines are available only for yellow fever, Japanese encephalitis, tick-borne encephalitis and Kyasanur forest disease. Factors contributing to resurgence include insufficient supplies of available vaccines, incomplete vaccination coverage and relaxation in vector control. Research has been underway for 60 years to develop effective vaccines against dengue, and recent progress is encouraging. The development of vaccines against West Nile, virus recently introduced to North America, has been initiated. In addition, there is considerable interest in improving existing vaccines with respect to increasing safety (e.g. eliminating the newly recognized syndrome of yellow fever vaccine-associated viscerotropic adverse disease), and to reducing the cost and number of doses required for effective immunization. Traditional approaches to flavivirus vaccines are still employed, while recent advancements in biotechnology produced new approaches to vaccine design, such as recombinant live virus, subunit and DNA vaccines. Live chimeric vaccines against dengue, Japanese encephalitis and West Nile based on yellow fever 17D virus (ChimeriVax) are in phase I/II trials, with encouraging results. Other chimeric dengue, tick-borne encephalitis and West Nile virus candidates were developed based on attenuated dengue backbones. To further reduce the impact of flavivirus diseases, vaccination policies and vector control programs in affected countries require revision.


Fast interactive segmentation of the pulmonary lobes from thoracic computed tomography data.
Automated lung lobe segmentation methods often fail for challenging and clinically relevant cases with incomplete fissures or substantial amounts of pathology. We present a fast and intuitive method to interactively correct a given lung lobe segmentation or to quickly create a lobe segmentation from scratch based on a lung mask. A given lobar boundary is converted into a mesh by principal component analysis of 3D lobar boundary markers to obtain a plane where nodes correspond to the position of the markers. An observer can modify the mesh by drawing on 2D slices in arbitrary orientations. After each drawing, the mesh is immediately adapted in a 3D region around the user interaction. For evaluation we participated in the international lung lobe segmentation challenge LObe and lung analysis 2011 (LOLA11). Two observers applied the method to correct a given lung lobe segmentation obtained by a fully automatic method for all 55 CT scans of LOLA11. On average observer 1/2 required 8 ± 4/25 ± 12 interactions per case and took 1:30 ± 0:34/3:19 ± 1:29 min. The average distances to the reference segmentation were improved from an initial 2.68 ± 14.71 mm to 0.89 ± 1.63/0.74 ± 1.51 mm. In addition, one observer applied the proposed method to create a segmentation from scratch. This took 3:44 ± 0:58 minutes on average per case, applying an average of 20 ± 3 interactions to reach an average distance to the reference of 0.77 ± 1.14 mm. Thus, both the interactive corrections and the creation of a segmentation from scratch were feasible in a short time with excellent results and only little interaction. Since the mesh adaptation is independent of image features, the method can successfully handle patients with severe pathologies, provided that the human operator is capable of correctly indicating the lobar boundaries.


Curcumin-Encapsulated Nanomicelles Improve Cellular Uptake and Cytotoxicity in Cisplatin-Resistant Human Oral Cancer Cells.
Oral cancer has a high mortality rate, which is mostly determined by the stage of the disease at the time of admission. Around half of all patients with oral cancer report with advanced illness. Hitherto, chemotherapy is preferred to treat oral cancer, but the emergence of resistance to anti-cancer drugs is likely to occur after a sequence of treatments. Curcumin is renowned for its anticancer potential but its marred water solubility and poor bioavailability limit its use in treating multidrug-resistant cancers. As part of this investigation, we prepared and characterized Curcumin nanomicelles (CUR-NMs) using DSPE-PEG-2000 and evaluated the anticancer properties of cisplatin-resistant cancer cell lines. The prepared CUR-NMs were sphere-shaped and unilamellar in structure, with a size of 32.60 ± 4.2 nm. CUR-NMs exhibited high entrapment efficiency (82.2%), entrapment content (147.96 µg/mL), and a mean zeta potential of -17.5ζ which is considered moderately stable. The cellular uptake and cytotoxicity studies revealed that CUR-NMs had significantly higher cytotoxicity and cellular uptake in cisplatin drug-resistant oral cancer cell lines and parental oral cancer cells compared to plain curcumin (CUR). The DAPI and FACS analysis corroborated a high percentage of apoptotic cells with CUR-NMs (31.14%) compared to neat CUR (19.72%) treatment. Conclusively, CUR-NMs can potentially be used as an alternative carrier system to improve the therapeutic effects of curcumin in the treatment of cisplatin-resistant human oral cancer.


Partner Type, Sexual Double Standard Endorsement, and Ambivalence Predict Abdication and Unprotected Sex Intentions in a Community Sample of Young Women.
In-the-moment ambivalence about having sex may influence sexual decisions but has rarely been examined. We investigated how ambivalence about sex might be related to intentions to abdicate sexual decisions to a male partner and to engage in unprotected sex in a community sample of young women. Predictors of abdication and unprotected sex intentions included partner type (new casual versus previous relationship), sexual double standard (SDS) endorsement, and two types of ambivalence. After completing a SDS endorsement measure, women (N = 360) projected themselves into a hypothetical sexual situation and completed dependent measures. In the new casual partner condition, SDS endorsement indirectly negatively predicted unprotected sex intentions through its associations with ambivalence and abdication. In both partner conditions SDS endorsement positively predicted abdication, which then positively predicted unprotected sex intentions. Ambivalence indirectly predicted unprotected sex intentions through its negative association with abdication intentions. Results suggest the importance of ambivalence for sexual decisions and the complexity of understanding the sexual decision making processes for women who endorse the SDS.


Comparative efficacy of Bentonite clay, activated charcoal and Trichosporon mycotoxinivorans in regulating the feed-to-tissue transfer of mycotoxins.
Mycotoxins contamination in animal products and by-products is a persistent threat to the food and feed industry. The present study was designed to evaluate the comparative inhibitory effects of Bentonite (BN), activated charcoal (AC) and a newly discovered yeast, Trichosporon mycotoxinivorans (TM), against feed-to-tissue transfer of mycotoxins. A dose dependent increase as determined by HPLC, in the residues of aflatoxin B1 (AFB1) and ochratoxin A (OTA) was exhibited in the groups of birds fed AFB1 and OTA alone. The dietary addition of BN and AC to AFB1-contaminated diets resulted in a 41-87% and 16-72% decrease in AFB1 residues in liver of the birds, respectively. However, this decrease was non-significant with addition of TM as AFB1 binder. A partial to non-significant protection was observed by dietary BN and AC, against OTA residues, while a significant decrease in OTA residues (38-84%) was noted in TM-OTA co-fed groups. The order of efficacy in terms of lowering AFB1 residues in the liver was BN > AC > TM, while against OTA it was TM > BN > AC. The findings of present study suggest that, based upon the nature of target mycotoxins, a mixture of multi-mycotoxins binders/detoxifiers should be incorporated in the animal feeds. © 2017 Society of Chemical Industry.


The Effectors and Sensory Sites of Formaldehyde-responsive Regulator FrmR and Metal-sensing Variant.
The DUF156 family of DNA-binding transcriptional regulators includes metal sensors that respond to cobalt and/or nickel (RcnR, InrS) or copper (CsoR) plus CstR, which responds to persulfide, and formaldehyde-responsive FrmR. Unexpectedly, the allosteric mechanism of FrmR from Salmonella enterica serovar Typhimurium is triggered by metals in vitro, and variant FrmR(E64H) gains responsiveness to Zn(II) and cobalt in vivo Here we establish that the allosteric mechanism of FrmR is triggered directly by formaldehyde in vitro Sensitivity to formaldehyde requires a cysteine (Cys(35) in FrmR) conserved in all DUF156 proteins. A crystal structure of metal- and formaldehyde-sensing FrmR(E64H) reveals that an FrmR-specific amino-terminal Pro(2) is proximal to Cys(35), and these residues form the deduced formaldehyde-sensing site. Evidence is presented that implies that residues spatially close to the conserved cysteine tune the sensitivities of DUF156 proteins above or below critical thresholds for different effectors, generating the semblance of specificity within cells. Relative to FrmR, RcnR is less responsive to formaldehyde in vitro, and RcnR does not sense formaldehyde in vivo, but reciprocal mutations FrmR(P2S) and RcnR(S2P), respectively, impair and enhance formaldehyde reactivity in vitro Formaldehyde detoxification by FrmA requires S-(hydroxymethyl)glutathione, yet glutathione inhibits formaldehyde detection by FrmR in vivo and in vitro Quantifying the number of FrmR molecules per cell and modeling formaldehyde modification as a function of [formaldehyde] demonstrates that FrmR reactivity is optimized such that FrmR is modified and frmRA is derepressed at lower [formaldehyde] than required to generate S-(hydroxymethyl)glutathione. Expression of FrmA is thereby coordinated with the accumulation of its substrate.


Pilot Study on Oral Health Status as Assessed by an Active Matrix Metalloproteinase-8 Chairside Mouthrinse Test in Adolescents.
Matrix metalloproteinase (MMP)-8 is a major destructive collagenase involved in periodontitis and can be regarded as a periodontitis biomarker. A neutrophil collagenase 2 (active MMP-8 [aMMP-8]) oral fluid immunoassay has recently been demonstrated to be a periodontitis risk indicator among adults. The aim of this study is to investigate whether a point-of-care mouthrinse test based on an aMMP-8 immunoassay could identify patients with oral inflammatory burden (periodontitis and caries) among adolescents with early pathologic findings. This cross-sectional study was carried out at the Kotka Health Center, Finland. First, the aMMP-8 chairside mouthrinse test was performed on enrolled individuals (adolescents aged 15 to 17 years, n = 47), and the results were read based on a color change within 5 minutes. Then, full-mouth clinical parameters of oral health were assessed, including periodontal, oral mucosal, and caries status. The sensitivity and specificity of the test for bleeding on probing were 71.8% and 77.5%, respectively (P = 0.05); for ≥1 site with probing depth (PD) ≥4 mm, 48.3% and 100% (P <0.001); for ≥2 sites with PD ≥4 mm, 63.6% and 100% (P <0.001); and for >2 sites with PD ≥4 mm, 76.5% and 96.7% (P <0.01). Regarding periodontitis (≥1 site with PD ≥4 mm), hardly any false-positive results were identified. The sensitivity of the immunoassay for ≥1 caries lesions was 76.5%, and the specificity was 96.7% (P <0.01). In 5 minutes, the aMMP-8 chairside test showed promising results, recognizing oral inflammatory burden in adolescents with early initial signs of periodontitis. Caries lesions could also be detected, but less efficiently.


Doxycycline protects human intestinal cells from hypoxia/reoxygenation injury: Implications from an in-vitro hypoxia model.
Intestinal ischemia/reperfusion (I/R) injury is a grave clinical emergency and associated with high morbidity and mortality rates. Based on the complex underlying mechanisms, a multimodal pharmacological approach seems necessary to prevent intestinal I/R injury. The antibiotic drug doxycycline, which exhibits a wide range of pleiotropic therapeutic properties, might be a promising candidate for also reducing I/R injury in the intestine. To investigate possible protective effects of doxycycline on intestinal I/R injury, human intestinal CaCo-2 cells were exposed to doxycycline at clinically relevant concentrations. In order to mimic I/R injury, CaCo-2 were thereafter subjected to hypoxia/reoxygenation by using our recently described two-enzyme in-vitro hypoxia model. Investigations of cell morphology, cell damage, apoptosis and hydrogen peroxide formation were performed 24h after the hypoxic insult. Hypoxia/reoxygenation injury resulted in morphological signs of cell damage, elevated LDH concentrations in the respective culture media (P<0.001) and increased protein expression of proapoptotic caspase-3 (P<0.05) in the intestinal cultures. These events were associated with increased levels hydrogen peroxide (P<0.001). Preincubation of CaCo-2 cells with different concentrations of doxycycline (5µM, 10µM, 50µM) reduced the hypoxia induced signs of cell damage and LDH release (P<0.001 for all concentrations). The reduction of cellular damage was associated with a reduced expression of caspase-3 (5µM, P<0.01; 10µM, P<0.01; 50µM, P<0.05), while hydrogen peroxide levels remained unchanged. In summary, doxycycline protects human intestinal cells from hypoxia/reoxygenation injury in-vitro. Further animal and clinical studies are required to prove the protective potential of doxycycline on intestinal I/R injury under in-vivo conditions.


Residual B-cell function in insulin dependent (Type 1) and non insulin-dependent (Type 2) diabetics (relationship between 24-hour C-peptide excretion and the clinical features of diabetes).
Residual B-cell function was studied by measuring 24-hour C-peptide excretion in the urine of 73 Type 1 and 63 Type 2 (28 orally-controlled and 35 insulin-treated) diabetics. Urine C-peptide excretion correlated highly significantly with serum C-peptide concentrations in both the control (r = 0.74, P less than 0.01) and the three diabetic groups (r = 0.89, r = 0.74 and r = 0.89 respectively, P less than 0.001 for all). C-peptide in urine was measurable in 31 of 73 Type 1 diabetics (42%). The earlier the onset and the longer the duration of diabetes, the lower was the proportion of patients with detectable B-cell rest secretion. Preserved residual B-cell function was inversely correlated with the degree of metabolic lability. A significant inverse correlation was also found in this group between 24-hour C-peptide excretion and daily insulin demand (r = 0.78, P less than 0.001). Twenty-nine of the 35 insulin-treated Type 2 diabetics had secondary failure to sulfonylureas and were treated with insulin at the time of the study. Although their daily C-peptide excretion (6.11 +/- 3.71 nmol/24 h) was significantly lower than either the control value (11.30 +/- 0.94 nmol/1, P less than 0.001) or that of orally controlled patients (9.28 +/- 6.16 nmol/l, P less than 0.05) all patients had urine C-peptide concentration in the measurable range. The development of secondary failure to sulfonylureas does not therefore imply complete exhaustion of pancreatic B-cells.(ABSTRACT TRUNCATED AT 250 WORDS)


Environmental dependency phenomena in schizophrenia: a pilot study.
Environmental dependency phenomena refer to the enslavement of patients' performances under the characteristics of the tasks and were first described in case of prefrontal lobe damage. Two forms of environmental dependency, executive and social, may be dissociated, which involve respectively dorsolateral and orbital prefrontal cortex (PFC) dysfunction. Schizophrenia is widely considered to be caused by PFC dysfunction, but no study to date has addressed environmental dependency in this pathology. We compared patients (N = 17) and healthy controls (N = 28) on a task dedicated to the study of environmental dependency. Our results demonstrate the presence of environmental dependency in schizophrenia. Each form of environmental dependency can be highlighted independently, as previously demonstrated by studies with prefrontal patients. These findings suggest specific prefrontal dysfunction for each subgroup of patients and demonstrate a dissociation between socio-cognitive and neurocognitive performance in schizophrenia. Additionally, we found relationships between symptomatology and environmental dependency. This pilot study supports the relevance of studying environmental dependency to highlight specific patterns of prefrontal disorders in schizophrenia, which may contribute to a better understanding of PFC dysfunction in schizophrenia.


Neurophysiological measures for users' training objective assessment during simulated robot-assisted laparoscopic surgery.
Minimally invasive surgery can be performed with robotic assistance, as evolution of laparoscopic surgery. Robots for assisted surgery are far from being user friendly and require extensive training. To this end, ad-hoc devices and experimental set-ups are needed. The da Vinci system is one of the most diffused surgical robotics technology. The aim of the study was two-fold: i) to propose a neurophysiological measure by which objectively assess the learning progress of the users by means of a simulator of the da Vinci system, and ii) to demonstrate the advantages of cognitive assessment with respect to the standard methodologies for the evaluation of training efficiency.


Families with children conceived by donor insemination: a follow-up at age twelve.
Growing public awareness of the use of donor insemination (DI) to enable infertile couples to become parents has been accompanied by increasing concern regarding the potentially negative consequences for family relationships and child development. Findings are presented from a prospective study of the quality of parenting and psychological adjustment of DI children at age 12. Thirty-seven DI families, 49 adoptive families, and 91 families with a naturally conceived child were compared on standardized interview and questionnaire measures administered to mothers, fathers, children, and teachers. The differences between DI families and the other family types reflected greater expressive warmth of DI mothers toward their children and less involvement in the discipline of their children by DI fathers. The DI children were well adjusted in terms of their social and emotional development. The findings are discussed with respect to the secrecy surrounding DI and the imbalance in genetic relatedness between the parents and the child.


A new diagnosis of Williams-Beuren syndrome in a 49-year-old man with severe bullous emphysema.
Williams-Beuren syndrome (WBS) is a chromosomal microdeletion syndrome typically presenting with intellectual disability, a unique personality, a characteristic facial appearance, and cardiovascular disease. Several clinical features of WBS are thought to be due to haploinsufficiency of elastin (ELN), as the ELN locus is included within the WBS critical region at 7q11.23. Emphysema, a disease attributed to destruction of pulmonary elastic fibers, has been reported in patients without WBS who have pathogenic variants in ELN but only once (in one patient) in WBS. Here we report a second adult WBS patient with emphysema where the diagnosis of WBS was established subsequent to the discovery of severe bullous emphysema. Haploinsufficiency of ELN likely contributed to this pulmonary manifestation of WBS. This case emphasizes the contribution of rare genetic variation in cases of severe emphysema and provides further evidence that emphysema should be considered in patients with WBS who have respiratory symptoms, as it may be under-recognized in this patient population.


Pictorial essay: Orbital tuberculosis.
Tuberculosis of the orbit is rare, even in places where tuberculosis is endemic. The disease may involve soft tissue, the lacrimal gland, or the periosteum or bones of the orbital wall. Intracranial extension, in the form of extradural abscess, and infratemporal fossa extension has been described. This pictorial essay illustrates the imaging findings of nine histopathologically confirmed cases of orbital tuberculosis. All these patients responded to antituberculous treatment.


Adaptive trends in respiratory control: a comparative perspective.
In 1941, August Krogh published a monograph entitled The Comparative Physiology of Respiratory Mechanisms (Philadelphia, PA: University of Pennsylvania Press, 1941). Since that time comparative studies have continued to contribute significantly to our understanding of the fundamentals of respiratory physiology and the adaptive trends in these processes that support a broad range of metabolic performance under demanding environmental conditions. This review specifically focuses on recent advances in our understanding of adaptive trends in respiratory control. Respiratory rhythm generators most likely arose from, and must remain integrated with, rhythm generators for chewing, suckling, and swallowing. Within the central nervous system there are multiple "segmental" rhythm generators, and through evolution there is a caudal shift in the predominant respiratory rhythm-generating site. All sites, however, may still be capable of producing or modulating respiratory rhythm under appropriate conditions. Expression of the respiratory rhythm is conditional on (tonic) input. Once the rhythm is expressed, it is often episodic as the basic medullary rhythm is turned on/off subject to a hierarchy of controls. Breathing patterns reflect differences in pulmonary mechanics resulting from differences in body wall and lung architecture and are modulated in different species by various combinations of upper and lower airway mechanoreceptors and arterial chemoreceptors to protect airways, reduce dead space ventilation, enhance gas exchange efficiency, and reduce the cost of breathing.


Effect of baseline glycosylated hemoglobin A1c on glycemic control and diabetes management following initiation of once-daily insulin detemir in real-life clinical practice.
The SOLVE study investigated the initiation of basal insulin in patients with type 2 diabetes on oral antidiabetic (OAD) treatment and outcomes in patients with varying levels of glycemic control at baseline. This was an observational cohort study conducted in 10 countries using insulin detemir. Data were collected at 3 clinic visits (baseline, 12-week interim, and 24-week final visit). A total of 13,526 (77.9%) patients were included in the glycosylated hemoglobin A1c (HbA1c) subset analysis. Patients were grouped according to pre-insulin HbA1c values as follows: HbA1c <7.6% (n = 2,797); HbA1c 7.6-9% (n = 5,366), and HbA1c >9% (n = 5,363). A total of 27 patients experienced serious adverse drug reactions (SADRs) and/or severe hypoglycemia (3, 10, and 11 patients with pre-insulin HbA1c <7.6%, 7.6-9.0%, and >9.0%, respectively). All patient subgroups realized improvements in HbA1c, with the pre-insulin HbA1c >9% subgroup having the largest HbA1c reduction (-2.4% versus -0.9% and -0.2% for HbA1c subgroups 7.6-9% and <7.6%, respectively). In the total cohort (n = 17,374), the incidence of severe hypoglycemia decreased from 4 events per 100 person years to <1 event per 100 person years by final visit; the incidence of minor hypoglycemia increased from 1.6 to 1.8 events per person year. In this study, insulin initiation was delayed until late in disease course, and overall concordance with internationally recognized guidelines was low. The initiation of once-daily insulin detemir was associated with substantial improvements in glycemic control and was not associated with an increase in severe hypoglycemia or weight gain.


Alcohol use and alcohol use disorder differ in their genetic relationships with PTSD: A genomic structural equation modelling approach.
Posttraumatic Stress Disorder (PTSD) is associated with increased alcohol use and alcohol use disorder (AUD), which are all moderately heritable. Studies suggest the genetic association between PTSD and alcohol use differs from that of PTSD and AUD, but further analysis is needed. We used genomic Structural Equation Modeling (genomicSEM) to analyze summary statistics from large-scale genome-wide association studies (GWAS) of European Ancestry participants to investigate the genetic relationships between PTSD (both diagnosis and re-experiencing symptom severity) and a range of alcohol use and AUD phenotypes. When we differentiated genetic factors for alcohol use and AUD we observed improved model fit relative to models with all alcohol-related indicators loading onto a single factor. The genetic correlations (rG) of PTSD were quite discrepant for the alcohol use and AUD factors. This was true when modeled as a three-correlated-factor model (PTSD-AUD rG:.36, p < .001; PTSD-alcohol use rG: -0.17, p < .001) and as a Bifactor model, in which the common and unique portions of alcohol phenotypes were pulled out into an AUD-specific factor (rG with PTSD:.40, p < .001), AU-specific factor (rG with PTSD: -0.57, p < .001), and a common alcohol factor (rG with PTSD:.16, NS). These results indicate the genetic architecture of alcohol use and AUD are differentially associated with PTSD. When the portions of variance unique to alcohol use and AUD are extracted, their genetic associations with PTSD vary substantially, suggesting different genetic architectures of alcohol phenotypes in people with PTSD.


A medicinal extract of Scutellaria baicalensis and Acacia catechu acts as a dual inhibitor of cyclooxygenase and 5-lipoxygenase to reduce inflammation.
A mixed extract containing two naturally occurring flavonoids, baicalin from Scutellaria baicalensis and catechin from Acacia catechu, was tested for cyclooxygenase (COX) and 5-lipoxygenase (5-LOX) inhibition via enzyme, cellular, and in vivo models. The 50% inhibitory concentration for inhibition of both ovine COX-1 and COX-2 peroxidase enzyme activities was 15 microg/mL, while the mixed extract showed a value for potato 5-LOX enzyme activity of 25 microg/mL. Prostaglandin E2 generation was inhibited by the mixed extract in human osteosarcoma cells expressing COX-2, while leukotriene production was inhibited in both human cell lines, immortalized THP-1 monocyte and HT-29 colorectal adenocarcinoma. In an arachidonic acid-induced mouse ear swelling model, the extract decreased edema in a dose-dependent manner. When arachidonic acid was injected directly into the intra-articular space of mouse ankle joints, the mixed extract abated the swelling and restored function in a rotary drum walking model. These results suggest that this natural, flavonoid mixture acts via "dual inhibition" of COX and LOX enzymes to reduce production of pro-inflammatory eicosanoids and attenuate edema in an in vivo model of inflammation.


[The use of drugs to improve athletic performance].
In sports, medical drugs are applied for supposedly ergogenic effects. Forbidden drug use (doping) implies that the drug enhances performance, which is not always the case. Amphetamines are ergogenic particularly during short-term, explosive exercise. Amphetamines exert an ergolytic effect on high-intensity endurance exercise. Caffeine has an ergogenic effect on endurance performance in dosages of 3 to 6 mg/kg. Doping regulations allow a small amount of caffeine intake. Androgenic and anabolic steroids elicit an increase in muscle growth and strength. In females low doses appear to be ergogenic in all sport types. beta 2-adrenergic agonists appear to have a positive effect on strength and muscle growth. The effects on endurance performance are still unknown. Although growth hormone is used in sports, scientific studies show that compared with placebo no difference in strength and muscle volume is observed. Blood doping and administration of erythropoietin are effective in enhancing endurance performance.


The endoplasmic reticulum-based acetyltransferases, ATase1 and ATase2, associate with the oligosaccharyltransferase to acetylate correctly folded polypeptides.
The endoplasmic reticulum (ER) has two membrane-bound acetyltransferases responsible for the endoluminal N(ϵ)-lysine acetylation of ER-transiting and -resident proteins. Mutations that impair the ER-based acetylation machinery are associated with developmental defects and a familial form of spastic paraplegia. Deficient ER acetylation in the mouse leads to defects of the immune and nervous system. Here, we report that both ATase1 and ATase2 form homo- and heterodimers and associate with members of the oligosaccharyltransferase (OST) complex. In contrast to the OST, the ATases only modify correctly folded polypetides. Collectively, our studies suggest that one of the functions of the ATases is to work in concert with the OST and "select" correctly folded from unfolded/misfolded transiting polypeptides.


Determination of CH4, CO2 and N2O in air samples and soil atmosphere by gas chromatography mass spectrometry, GC-MS.
A method for determination of the climate gases CH4, CO2 and N2O in air samples and soil atmosphere was developed using GC-MS. The method uses straightforward gas chromatography (separation of the gases) with a mass spectrometric detector in single ion mode (specific determination). The gases were determined with high sensitivity and high sample throughput (18 samples h(-1)). The LOD (3sigma) for the gases were 0.10 micro L L(-1) for CH4, 20 microL L(-1) for CO2 and 0.02 microL L(-1) for N2O. The linear range (R2 = 0.999) was up to 500 microL L(-1) for CH4, 4000 microL L(-1) for CO2 and 80 microL L(-1) for N2O. The samples were collected in 10 mL vials and a 5 microL aliquot was injected on column. The method was tested against certified gas references, the analytical data gave an accuracy within +/-5% and a precision of +/-3%. The presence of < or = 10% by volume of C2H2 (often used experimentally to prevent N2 formation from N2O) did not interfere with detection for the targeted trace gases.


Multi-gene panel testing for hereditary cancer predisposition in unsolved high-risk breast and ovarian cancer patients.
Many women with an elevated risk of hereditary breast and ovarian cancer have previously tested negative for pathogenic mutations in BRCA1 and BRCA2. Among them, a subset has hereditary susceptibility to cancer and requires further testing. We sought to identify specific groups who remain at high risk and evaluate whether they should be offered multi-gene panel testing. We tested 300 women on a multi-gene panel who were previously enrolled in a long-term study at UCSF. As part of their long-term care, all previously tested negative for mutations in BRCA1 and BRCA2 either by limited or comprehensive sequencing. Additionally, they met one of the following criteria: (i) personal history of bilateral breast cancer, (ii) personal history of breast cancer and a first or second degree relative with ovarian cancer, and (iii) personal history of ovarian, fallopian tube, or peritoneal carcinoma. Across the three groups, 26 women (9%) had a total of 28 pathogenic mutations associated with hereditary cancer susceptibility, and 23 women (8%) had mutations in genes other than BRCA1 and BRCA2. Ashkenazi Jewish and Hispanic women had elevated pathogenic mutation rates. In addition, two women harbored pathogenic mutations in more than one hereditary predisposition gene. Among women at high risk of breast and ovarian cancer who have previously tested negative for pathogenic BRCA1 and BRCA2 mutations, we identified three groups of women who should be considered for subsequent multi-gene panel testing. The identification of women with multiple pathogenic mutations has important implications for family testing.


Computational distributed fiber-optic sensing.
Ghost imaging allows image reconstruction by correlation measurements between a light beam that interacts with the object without spatially resolved detection and a spatially resolved light beam that never interacts with the object. The two light beams are copies of each other. Its computational version removes the requirement of a spatially resolved detector when the light intensity pattern is pre-known. Here, we exploit the temporal analogue of computational ghost imaging, and demonstrate a computational distributed fiber-optic sensing technique. Temporal images containing spatially distributed scattering information used for sensing purposes are retrieved through correlating the "integrated" backscattered light and the pre-known binary patterns. The sampling rate required for our technique is inversely proportional to the total time duration of a binary sequence, so that it can be significantly reduced compared to that of the traditional methods. Our experiments demonstrate a 3 orders of magnitude reduction in the sampling rate, offering great simplification and cost reduction in the distributed fiber-optic sensors.


A care substitution service in the Netherlands: impact on referral, cost, and patient satisfaction.
In care substitution services, medical specialists offer brief consultations to provide general practitioners (GPs) with advice on diagnosis, treatment, or hospital referral. When GPs serve as gatekeepers to secondary care, these regional services could reduce pressures on healthcare systems. The aim is to determine the impact of implementing a care substitution service for dermatology, orthopaedics, and cardiology on the hospital referral rate, health care costs, and patient satisfaction. A before-after study was used to evaluate hospital referral rates and health care costs during a follow-up period of 1 year. The study population comprised patients with eligible International Classification of Primary Care codes for referral to the care substitution service (only dermatology, orthopaedic, cardiology indications), as pre-defined by GPs and medical specialists. We compared referral rates before and after implementation by χ2 tests and evaluated patient preference by qualitative analysis. In total, 4,930 patients were included, 2,408 before and 2,522 after implementation. The care substitution service decreased hospital referrals during the follow-up period from 15 to 11%. The referral rate decreased most for dermatology (from 15 to 9%), resulting in a cost reduction of €10.59 per patient, while the other two specialisms experienced smaller reductions in referral rates. Patients reported being satisfied, mainly because of the null cost, improved organisation, improved care, and positive experience of the consultation. The care substitution service showed promise for specialisms that require fewer hospital facilities, as exemplified by dermatology.


The genetic architecture of inflammatory bowel disease: past, present and future.
Genome-wide association studies (GWAS) have helped to understand the genetic basis and pathogenesis of inflammatory bowel disease (IBD). However, understanding the functional and clinical consequences of the associated alleles has not followed the same pace. In this review, we discuss how studying the genetic predisposition to IBD has increased our understanding about IBD pathogenesis and how epigenetics is becoming more and more important. We describe the potential clinical applications of genetics, and provide important challenges in the field and the future steps to be taken. GWAS and meta-analyses have identified 163 loci associated with IBD, and have implicated key pathways in IBD pathogenesis. Only few of the association signals correspond to nonsynonymous coding variation with a clear effect on protein function. The majority of signals involve noncoding genetic variation, of which a large part is related to gene expression changes. More recently, expression and epigenetic studies in IBD are increasingly being reported, and have shown that many effects seem to be highly cell-type specific.Predictive genetic testing will not be for the immediate future for the majority of IBD patients. However, for the subset of patients with very-early onset IBD, several causal mutations have been found. Predictive genetic panels for these adolescents presenting with a very severe disease course, and/or families with high penetrance of disease will be of benefit. Genetic, transcriptomic and epigenetic studies have offered exciting clues about IBD pathogenesis but are unlikely to provide all answers. To fully grasp the function of disease-associated genetic variants, identifying causal genes and translating this knowledge into predictive biomarkers and new treatments, we should now integrate all these disciplines.


In-vitro and in-vivo characteristics of a modified-release double-pulse formulation for a water soluble drug.
The aim of the present study was to evaluate the in-vitro dissolution and in-vivo pharmacokinetic profile of a novel two-phase modified-release formulation for diltiazem hydrochloride, as a water-soluble drug. The delivery system consisted of two tablets inserted into a capsule. Both tablets comprised a coated drug core-matrix. The coating of the first tablet was intended to produce a first phase with a relatively fast release profile, while that of the second tablet included a unique controlling membrane designed to achieve a delayed controlled-release profile. Three different formulations were tested for their dissolution profiles both in water media and in buffer with a pH of 6.8. These formulations were also evaluated for their pharmacokinetic profile in healthy volunteers after single administration of a 240 mg dose. Serial venous blood samples were collected over 36 h post administration to measure diltiazem levels by HPLC. In addition the in-vivo /in-vitro correlation (IVIVC) was calculated for these formulations. The in-vitro characteristics of these formulations demonstrated a controlled release profile in both media but with different characteristics, as in Formulation 3 where faster dissolution profile obtained in water but slower one in pH 6.8 buffer. In-vivo the pharmacokinetic profile of these formulations showed that arabinogalactan containing formulations achieved plasma levels which allow a once daily administration. IVIVC calculation demonstrated that dissolution tested in buffer 6.8 media better correlates with the percent absorbed in-vivo and the best results were achieved with the formulation containing the highest amount of polysaccharide in the coating. It is concluded that the developed formulations achieved a controlled release profile both in-vitro and in-vivo which are suitable for once-daily administration.


Virus Sensitivity Index of UV disinfection.
A new concept of Virus Sensitivity Index (VSI) is defined as the ratio between the first-order inactivation rate constant of a virus, ki, and that of MS2-phage during UV disinfection, kr. MS2-phage is chosen as the reference virus because it is recommended as a virus indicator during UV reactor design and validation by the US Environmental Protection Agency. VSI has wide applications in research, design, and validation of UV disinfection systems. For example, it can be used to rank the UV disinfection sensitivity of viruses in reference to MS2-phage. There are four major steps in deriving the equation between Hi/Hr and 1/VSI. First, the first-order inactivation rate constants are determined by regression analysis between Log I and fluence required. Second, the inactivation rate constants of MS2-phage are statistically analysed at 3, 4, 5, and 6 Log I levels. Third, different VSI values are obtained from the ki of different viruses dividing by the kr of MS2-phage. Fourth, correlation between Hi/Hr and 1/VSI is analysed by using linear, quadratic, and cubic models. As expected from the theoretical analysis, a linear relationship adequately correlates Hi/Hr and 1/VSI without an intercept. VSI is used to quantitatively predict the UV fluence required for any virus at any log inactivation (Log I). Four equations were developed at 3, 4, 5, and 6 Log I. These equations have been validated using external data which are not used for the virus development. At Log I less than 3, the equation tends to under-predict the required fluence at both low Log I such as 1 and 2 Log I. At Log I greater than 3 Log I, the equation tends to over-predict the fluence required. The reasons for these may very likely be due to the shoulder at the beginning and the tailing at the end of the collimated beam test experiments. At 3 Log I, the error percentage is less than 6%. The VSI is also used to predict inactivation rate constants under two different UV disinfection scenarios such as under sunlight and different virus aggregates. The correlation analysis shows that viruses will be about 40% more sensitive to sunlight than to UV254. On the other hand, virus size of 500 nm will reduce their VSI by 10%. This is the first attempt to use VSI to predict the required fluence at any given Log I. The equation can be used to quantitatively evaluate other parameters influencing UV disinfection. These factors include environmental species, antibiotic-resistant bacteria or genes, photo and dark repair, water quality such as suspended solids, and UV transmittance.


Efficacy and safety of ezetimibe coadministered with atorvastatin or simvastatin in patients with homozygous familial hypercholesterolemia.
Patients with homozygous familial hypercholesterolemia (HoFH) have a high incidence of cardiovascular morbidity and mortality from premature atherosclerosis, and the efficacy of pharmacological therapy has been limited. We evaluated the efficacy, safety, and tolerability of ezetimibe, a novel cholesterol absorption inhibitor, in a multicenter, double-blind, randomized trial of HoFH patients receiving atorvastatin or simvastatin. Methods and Results- Fifty patients with a diagnosis of HoFH on the National Cholesterol Education Program Step 1 or stricter diet and taking open-label atorvastatin 40 mg/d or simvastatin 40 mg/d (statin-40) with (n=25) or without (n=25) concomitant LDL apheresis were randomized to 1 of 3 double-blind treatments: atorvastatin or simvastatin 80 mg/d (statin-80, n=17); ezetimibe 10 mg/d plus atorvastatin or simvastatin 40 mg/d (n=16); or ezetimibe 10 mg/d plus atorvastatin or simvastatin 80 mg/d (n=17) for 12 weeks. The primary end point was mean percentage change in LDL cholesterol (LDL-C) from statin-40 baseline to the end point for patients receiving statins alone (statin-80) versus patients receiving ezetimibe plus atorvastatin or simvastatin at either dose (ezetimibe plus statin-40/80). Ezetimibe plus statin-40/80 significantly reduced LDL-C levels compared with statin-80 (-20.7% versus -6.7%, P=0.007). In the high-dose statin cohorts, ezetimibe plus statin-80 reduced LDL-C by an additional 20.5% (P=0.0001) versus statin-80. Similar significant reductions in LDL-C concentrations were observed for patients with genotype-confirmed HoFH (n=35). Ezetimibe was safe and well tolerated. Ezetimibe coadministered with atorvastatin or simvastatin in patients with HoFH produced clinically important LDL-C reductions compared with best current therapy. Ezetimibe provides a new, complementary pharmacological approach for this high-risk population.


Psychosocial short stature with psychosis: a case report.
Our objective was to report and describe a case of psychosocial short stature in an adolescent girl with psychotic features. Psychosocial short stature is a rare condition in which emotional stress or deprivation in childhood profoundly reduces growth, leading to persistent short stature. This disorder is variably known as psychosocial dwarfism, hyperphagic short stature or maternal deprivation dwarfism. In the literature, psychosocial short stature has not been associated previously with psychosis. We formulate that our patient's short stature, developmental regression and psychotic features were culminations of insecure mother-child attachment, personal traumatic experiences, immigrant status, high family expressed emotions and social isolation. Neuropsychiatric influences were critically regarded due to our patient's fluctuations in behaviour and affect, in the setting of cortical volume loss on brain MRI. Diagnostic hypotheses included childhood disintegrative disorder or childhood-onset schizophrenia. The management plan involved inpatient family psychoeducation, a pharmacological trial with an atypical antipsychotic and community mental health service follow-up for family therapy and psychotherapy.


An update on the use of helminths to treat Crohn's and other autoimmunune diseases.
This review updates our previous one (Reddy and Fried, Parasitol Research 100: 921-927, 2007) on Crohn's disease and helminths. The review considers the most recent literature on Trichuris suis therapy and Crohn's and the significant literature on the use of Necator americanus larvae to treat Crohn's and other autoimmune disorders. The pros and cons of helminth therapy as related to autoimmune disorders are discussed in the review. We also discuss the relationship of the bacterium Campylobacter jejuni and T. suis in Crohn's disease. The significant literature on helminths other than N. americanus and T. suis as related to autoimmune diseases is also reviewed.


Solid waste containing persistent organic pollutants in Serbia: From precautionary measures to the final treatment (case study).
Sustainable solid waste management needs more dedicated attention in respect of environmental and human health protection. Solid waste containing persistent organic pollutants is of special concern, since persistent organic pollutants are persistent, toxic and of high risk to human health and the environment. The objective of this investigation was to identify critical points in the Serbian system of solid waste and persistent organic pollutants management, to assure the life cycle management of persistent organic pollutants and products containing these chemicals, including prevention and final destruction. Data were collected from the Serbian competent authorities, and led us to identify preventive actions for solid waste management that should reduce or minimise release of persistent organic pollutants into the environment, and to propose actions necessary for persistent organic pollutants solid waste. The adverse impact of persistent organic pollutants is multidimensional. Owing to the lack of treatment or disposal plants for hazardous waste in Serbia, the only option at the moment to manage persistent organic pollutants waste is to keep it in temporary storage and when conditions are created (primarily financial), such waste should be exported for destruction in hazardous waste incinerators. Meanwhile, it needs to be assured that any persistent organic pollutants management activity does not negatively impact recycling flows or disturb progress towards a more circular economy in Serbia.


CD4+PD-1+ T cells acting as regulatory cells during the induction of anterior chamber-associated immune deviation.
To study the expression and functional characteristics of programmed death-1 (PD-1) and its ligands in the spleens of mice undergoing anterior chamber-associated immune deviation (ACAID). ACAID was induced in BALB/c mice by intracameral injection of ovalbumin (OVA). The expression of PD-1 and its ligands in the spleens of ACAID mice was determined by quantitative real-time PCR, Western blotting, and flow cytometry. In vitro proliferation assays, enzyme-linked immunosorbent assays, and adoptive transfer assays were used to investigate the functional characteristics of splenic CD4+PD-1+ T cells of ACAID mice. Both mRNA and protein of PD-1, PD-L1, and PD-L2 were markedly upregulated in the spleens of ACAID mice compared with controls. CD4+PD-1+ T cells from ACAID mice produced large amounts of IL-10 and exhibited in vitro antigen-specific suppressive activity. CD4+PD-1+ T cells from ACAID mice were able to significantly inhibit the antigen-specific, delayed-type hypersensitivity response when adoptively transferred to naive mice. CD4+PD-1+ T cells from ACAID mice, as regulatory cells, are involved in the induction of antigen-specific suppression in association with enhanced expression of IL-10. CD4+PD-1+ T cells in the murine spleen may represent a substantial population of regulatory T cells possibly responsible for the induction of ACAID after intracameral injection of antigen.


Electrotransformation of Yersinia ruckeri by plasmid DNA.
Yersinia ruckeri, a fish pathogenic bacterium in aquaculture, was used to evaluate the electroporation as a new transformation method for this species. DNA used for the electrotransformation were plasmids of molecular mass ranging from 2.3 kb to 33 kb, and diverse replicons. To optimize this method we used Y. ruckeri 11.29 strain (from serotype 02) and pSU2718 DNA. The best transformation efficiency (6.0 x 10(5) transformants/micrograms DNA) was obtained with 12.5 kV/cm, 25 microF, 400 omega and 2 hours of incubation after pulse. When these conditions were applied to other strains belonging to different serotypes and other plasmids, we obtained transformants in all strains assayed, but only when using low molecular weight plasmids. Plasmid vectors and resident plasmid were not modified in host strains after electrotransformation. In studies of conformation we confirmed that only circular DNA was able for transformation. The utilization of this technique for direct cloning in Y. ruckeri makes possible further studies on recombinant DNA.


Novel pyridinium based cobalt carbonyl ionic liquids: synthesis, full characterization, crystal structure and application in catalysis.
Through an optimized synthetic strategy, a series of novel alkylpyridinium cobalt tetracarbonyl salts, [C(1)Py][Co(CO)(4)] (), [C(4)Py][Co(CO)(4)] () and [C(16)Py][Co(CO)(4)] () (C(n)Py = N-C(n)H(2n+1)-pyridinium), were successfully prepared in good yields, using a water-organic biphasic system. All the three compounds melt well below 100 degrees C and could be classified as ionic liquids. The compounds were fully characterized using IR, UV-Vis, (1)H NMR, (13)C NMR, ESI-MS and elemental analysis, and was structurally characterized by X-ray single crystal analysis. Compound has been found to be an efficient and reusable catalyst for the alkoxycarbonylation of propylene oxide without the aid of a base additive.


Plasma and amniotic fluid PPARγ is involved in the lipid metabolism of maternal-fetal interface cells.
The aim of this study was at detecting the expression of peroxisome proliferator-activated receptor γ (PPARγ) in patients with gestational diabetes mellitus (GDM) and to investigate whether PPARγ regulates the lipid metabolism of maternal-fetal interface cells. We detected the expression of PPARγ in the maternal plasma, fetal plasma and amniotic fluid of two groups of women with GDM or normal pregnancy using ELISA and western blot. Establish the cell models of the indirect coculture model and the separate culture model using BeWo cells and endometrial stromal cells (ESCs). Oil red O staining was used to detect the lipid uptake, and the mRNA levels of the rate-limiting enzyme stearoyl CoA desaturase (SCD) and glucose transporter 1 (GLUT1) were detected by RT-PCR. PPARγ is detectable in maternal plasma, fetal plasma and amniotic fluid. Levels of PPARγ in GDM maternal plasma were significant higher than other groups in vitro, with increasing PPARγ, the cytoplasmic lipid uptake levels of BeWo cells and ESCs were both increased in coculture conditions. GLUT1 and SCD mRNA rose significantly with increasing PPARγ in indirect coculture conditions, but both did not respond to PPARγ in ESC-absent culture conditions. The extracellular concentration of PPARγ may be involved in the lipid transport of maternal-fetal interface cells and may play a role in the abnormal lipid metabolism of GDM patients.


Recurrent pyoderma gangrenosum and agnogenic myeloid metaplasia.
Pyoderma gangrenosum has been associated with myelogenous leukemia and plasma cell dyscrasia. When associated with leukemia, pyoderma gangrenosum often has a distinctive clinical presentation with an advancing bullous margin. The pathogenesis of this disorder is unknown, although defective immune mechanisms may be operative. The occurrence of pyoderma gangrenosum and agnogenic myeloid metaplasia in the same patient has now been reported sufficiently to make it a recognized association.


Exploring the Mechanism of the miRNA-145/Paxillin Axis in Cell Metabolism During VEGF-A-Induced Corneal Angiogenesis.
Paxillin (PXN) is a key component of focal adhesions and plays an important role in angiogenesis. The aim of the present study was to investigate the effect of PXN in vascular endothelial growth factor A (VEGF-A)-induced angiogenesis in human umbilical vein endothelial cells (HUVECs). HUVECs were transfected with PXN overexpression and PXN interference vectors. Biochemical detection was used to detect adenosine triphosphate and lactic acid production. The morphology of mitochondria was observed under an electron microscope, and flow cytometry was conducted to measure mitochondrial membrane potential. Transwell experiments were used to detect the migration and tube formation ability of each group of cells. The expression of hexokinase (HK)1, HK2, glucose transporter 1 (GLUT1), phosphorylated phosphatidylinositol 3-kinase (PI3K), phosphorylated AKT, and phosphorylated mechanistic target of rapamycin (mTOR) was evaluated by western blot. PXN silencing reduced the levels of lactic acid and adenosine triphosphate, downregulated HK1, HK2, and GLUT1, suppressed PI3K/AKT/mTOR signaling activation, and inhibited VEGF-A-induced mitochondria injury in VEGF-A-induced HUVECs. We also determined that miR-145-5p decreased the VEGF-A-induced expression of PXN and inhibited the invasion and angiogenesis of HUVECs. Also, miR-145-5p inhibition blocked the protective effect of PXN interference on VEGF-A-induced HUVEC injury. Furthermore, PXN interference significantly decreased lactic acid and adenosine triphosphate levels, inhibited PI3K/AKT/mTOR activation, and decreased the levels of HK1, HK2, and GLUT1 in VEGF-A-treated mouse corneal. The results indicate that PXN silencing inhibited the VEGF-A-induced invasion and angiogenesis of HUVECs via regulation of cell metabolism and mitochondrial damage, suggesting that PXN may be a potential target for antiangiogenic therapies.


Outcomes of Total Endovascular Aortic Arch Repair with Surgeon-Modified Fenestrated Stent-Grafts on Zone 0 Landing for Aortic Arch Pathologies.
This study evaluated the feasibility and safety of total endovascular aortic arch repair with surgeon-modified fenestrated stent-graft on zone 0 landing for aortic arch pathologies. Between June 2016 and October 2019, 37 consecutive patients underwent total endovascular arch repair with surgeon-modified fenestrated stent-grafts on zone 0 landing. Outcomes included technical success, perioperative and follow-up morbidity and mortality, and branch artery patency. During the study period, 37 patients were treated with total endovascular aortic arch repair with surgeon-modified fenestrated stent-graft. Twenty-one (56.8%) patients were diagnosed with aortic dissections, 15 (40.5%) patients with aneurysms, and 1 (2.7%) patient required reintervention due to endoleak and sac expansion from previous thoracic endovascular aortic repair for thoracoabdominal aneurysm. The proximal landing zone for all patients were in zone 0, and all branch arteries of aortic arch were reconstructed. Technical success was achieved in 34 cases (91.9%). Three (8.1%) patients had fenestrations misaligned with target arteries, and the chimney technique was applied as a complementary measure. Thirty-day mortality rate was 5.4% (n=2). Thirty-day stroke rate was 5.4% (n=2). Thirty-day reintervention rate was 2.7% (n=1). At a median follow-up of 20 months (range, 3-49 months), 5 (13.5%) patients died, including 2 aortic-related deaths, 1 nonaortic-related death, and 2 deaths of unknown reason. One (2.7%) patient had stroke. Four patients (10.8%) had reintervention during the follow-up, including 2 cases of left subclavian artery occlusion and 2 cases of type II endoleak. The estimated survival (±SE) at 2 years was 72.4%±9.7% (95% CI 53.4%-91.4%). The estimated freedom from reintervention (±SE) at 2 years was 87.4%±5.9% (95% CI 75.84%-98.96%). Total endovascular aortic arch repair with surgeon-modified fenestrated stent-grafts on zone 0 landing is an alternate option for the treatment of aortic arch pathologies in experienced centers.


Serotonin syndrome caused by minimum doses of SSRIS in a patient with spinal cord injury.
There have been only a few reports of serotonin syndrome developing after mono-therapy with a selective serotonin reuptake inhibitor (SSRI). We report a case of serotonin syndrome caused by long-term therapy with fluvoxamine prior to treatment with paroxetine. An 18-year-old man with spinal cord injury (SCI) at thoracic level 2-3 presented with onset of serotonin syndrome after taking fluvoxamine (50 mg per day) for 8 weeks prior to treatment with paroxetine (10 mg per day) for 6 days. He had confusion, agitation, severe headache, tachycardia (124 beats/minute), hypertension (165/118 mmHg), high fever (39.1 degrees C), and myoclonus. All of the symptoms disappeared within 24 hours after discontinuation of administration of paroxetine. This is an interesting case of serotonin syndrome that developed after minimum doses of single therapy with an SSRI in a patient with SCI.


What can hand grip strength tell us about type 2 diabetes?: mortality, morbidities and risk of diabetes.
Hand grip strength (HGS) has been determined as a simple and cost effective method for evaluating overall skeletal muscle strength and quality. It has been used in numerous clinical studies to examine the association between skeletal muscle and type 2 diabetes (T2D). Previous studies have shown that HGS is significantly associated with mortality and cardiovascular disease (CVD) in patients with T2D. As the prevalence of T2D has seen a steady increase globally, HGS measurement can be useful and essential in managing T2D. This narrative review summarizes the current evidence regarding the association between HGS and T2D. HGS has been considered a useful tool for identifying risks for T2D, CVD, and mortality and evaluating skeletal muscle strength and quality. HGS should be measured in all patients with T2D together with height, weight, and waist circumference. However, there is yet no standard method used in measuring for HGS. T2D patients with a low HGS can engage in resistance training more effectively with appropriate advice based on HGS. Future studies clarifying the genetic association between skeletal muscle and T2D are needed to provide individualized exercise therapy.


Versatile Multi-Wavelength Light-Responsive Metal-Organic Frameworks Micromotor through Porphyrin Metalation for Water Sterilization.
Traditional metal-organic frameworks (MOFs) based micro/nanomotors (MOFtors) can achieve three-dimensional (3D) motion mainly depending on noble metal (e.g., Pt), toxic fuels (e.g., hydrogen peroxide), and surfactants, or under external magnetic fields. In this study, light-driven MOFtors are constructed based on PCN-224(H) and regulated their photothermal and photochemical properties responding to the light of different wavelengths through porphyrin metalation. The resulting PCN-224(Fe) MOFtors presented a strong 3D motion at a maximum speed of 1234.9 ± 367.5 µm s-1 under visible light due to the various gradient fields by the photothermal and photochemical effects. Such MOFtors exhibit excellent water sterilization performance. Under optimal conditions, the PCN-224(Cu) MOFtors presented the best antibacterial performance of 99.4%, which improved by 23.4% compared to its static counterpart and 43.7% compared to static PCN-224(H). The underlying mechanism demonstrates that metal doping could increase the production of reactive oxygen species (ROS) and result in a more positive surface charge under light, which are short-distance effective sterilizing ingredients. Furthermore, the motion of MOFtors appears very important to extend the short-distance effective sterilization and thus synergistically improve the antibacterial performance. This work provides a new idea for preparing and developing light-driven MOFtors with multi-responsive properties.


Exercise training enhances baroreflex control of heart rate by a vagal mechanism in rabbits with heart failure.
Moderate exercise training (Ex) enhances work capacity and quality of life in patients with chronic heart failure (CHF). We investigated the autonomic components of resting heart rate (HR) and the baroreflex control of HR in conscious, instrumented rabbits with pacing-induced CHF after Ex. Sham and CHF rabbits were exercise trained for 4 wk at 15-18 m/min, 6 days/wk. Arterial pressure and HR were recorded before and after metoprolol (1 mg/kg iv) or after atropine (0.2 mg/kg iv). Mean arterial pressure was altered by infusions of sodium nitroprusside and phenylephrine. The data were fit to a sigmoid (logistic) function. Baseline HRs were 266.5 +/- 8.4 and 232.1 +/- 1.6 beats/min in CHF and CHF Ex rabbits, respectively (P < 0.05). In the unblocked state, CHF rabbits had a significantly depressed peak baroreflex slope (1.7 +/- 0.3 vs. 5.6 +/- 0.7 beats. min(-1). mmHg(-1); P < 0.001) and HR range (128.6 +/- 34.5 vs. 253.2 +/- 20.3 beats/min; P < 0.05) compared with normal subjects. Ex increased baroreflex slope to 4.9 +/- 0.3 from 1.7 +/- 0.3 beats. min(-1). mmHg(-1) in unblocked rabbits (P < 0.001 compared with CHF non-Ex). Ex did not alter baroreflex function in sham animals. After metoprolol, baroreflex slope was significantly increased in CHF Ex rabbits (1.5 +/- 0.2 vs. 3.0 +/- 0.2 beats. min(-1). mmHg(-1); P < 0.05). After atropine, there was no significant change in baroreflex slope or HR range between CHF Ex and CHF rabbits. These data support the view that enhancement of baroreflex control of HR after Ex is due to an augmentation of vagal tone.


Gold-catalyzed tandem cycloisomerization-hydroalkoxylation of homopropargylic alcohols.
The tandem cycloisomerization-hydroalkoxylation of various homopropargylic alcohols in the presence of an alcohol and a dual catalyst system, consisting of a gold precatalyst and a Brønsted acid, provides an efficient route to tetrahydrofuranyl ethers under mild reaction conditions. The reaction can be carried out in various solvents, including alcohol, with both terminal and internal alkynes as the substrate.


Effectiveness of a community-based health programme on the blood pressure control, adherence and knowledge of adults with hypertension: A PRECEDE-PROCEED model approach.
To determine the effectiveness of a community-based health programme grounded on the PRECEDE-PROCEED model, on the knowledge, adherence and blood pressure control of community-dwelling adults with hypertension. Hypertension has consistently been a leading cause of morbidity and mortality in different countries and has continuously increased in prevalence. Albeit manageable with lifestyle modification and anti-hypertensive medications, adequate knowledge and poor adherence to these treatment regimens are issues that have led to poor blood pressure control. Quasi-experimental, one-group pretest-post-test design. The PRECEDE-PROCEED model was used to develop and evaluate the effectiveness of the community-based health programme. From August to October 2017, a total of 50 community-dwelling adults with hypertension participated in the programme which included blood pressure monitoring, targeted health educations, motivational interviews, individualised lifestyle modification plans and house-to-house visits. Knowledge, adherence and blood pressure were assessed at the start and at the end of the 2-month programme. Gathered data were analysed using descriptive statistics and RM-MANOVA. The TREND checklist was followed in reporting this study (See Appendix S1). After 2 months, the mean adherence, systolic blood pressure and diastolic blood pressure significantly improved, attributing more than 25% of the change. Although knowledge scores were significantly higher after the programme, it only accounted 9% of the improvement. This study provides evidence on the effectiveness of a community-based health programme grounded on the PRECEDE-PROCEED model on the knowledge, adherence and blood pressure control of community-dwelling adults with hypertension. The community-based health programme is beneficial to community-dwelling adults with hypertension in promoting knowledge and adherence to treatment regimen and improving BP control. This study also provides a framework for developing new or enhancing existing programmes on hypertension in the Philippines.


Dual-linker gold nanoparticles as adjuvanting carriers for multivalent display of recombinant influenza hemagglutinin trimers and flagellin improve the immunological responses in vivo and in vitro.
Vaccination is the most cost-effective means of infectious disease control. Although current influenza vaccines are effective in battling closely matched strains, such vaccines have major limitations such as the requirement to produce new vaccines every season, an egg-dependent production system, long production periods, uncertainty in matching the vaccine to circulating strains, and the inability to react to new influenza pandemics resulting from genetic drift or shift. To overcome the intrinsic limitations of the conventional influenza vaccine, we have designed dual-linker gold nanoparticles (AuNPs) conjugated with both recombinant trimetric A/Aichi/2/68 (H3N2), hemagglutinin (HA) and TLR5 agonist flagellin (FliC) as a novel vaccine approach. Click chemistry and metal-chelating reactions were used to couple the two proteins. The conjugated proteins were found to possess high coupling specificity, high stability in harsh environments, high conjugation efficiency, and the ability to keep the appropriate protein conformations for immunogenicity and immunostimulation. Both AuNPs-HA/FliC and AuNPs-HA formulations induced higher levels of antibody responses than a mixture of soluble HA and FliC proteins when administered via a single intranasal immunization in mice. To further investigate the adjuvancy of these nanoparticles, in vitro experiments were conducted in both the JAWS II dendritic cell (DC) line and bone marrow-derived DC (BMDC) models. The results showed that dual-conjugated AuNPs were rapidly targeted and taken up by DCs. Consequently, DCs were induced toward maturation, as demonstrated by high levels of cytokine secretions and membrane costimulatory molecule expression. T cell proliferation was observed when splenic T cells were cocultured with AuNPs-HA/FliC-primed BMDCs. These results suggest that dual-conjugated AuNPs are effective at simultaneously displaying antigens and adjuvants in an oriented, multivalent format and can promote a strong immune response by activating DCs and T cells.


Dopaminergic influence on the excitability of antidromically activated Renshaw cells in the lumbar spinal cord of the rat.
The interaction between dopaminergic and cholinergic systems in the mammalian central nervous system, which is thought to have important implications in the pathophysiology of major extrapyramidal disorders, has never been adequately demonstrated in vivo. Renshaw cell burst responses to single electrical shocks to lumbar ventral roots in spinalized and decerebrated rats were studied. In this monosynaptic cholinergic pathway, apomorphine, a dopaminergic receptor agonist, inhibited whereas the D2-antagonist sulpiride facilitated the burst responses. The mutual antagonism of the two drugs and the depression coupled with the faster decay of post-tetanic potentiation of Renshaw cells by apomorphine demonstrate the involvement of presynaptic D2-receptors through which dopamine can modulate acetylcholine-mediated central synaptic transmission in vivo. The study also provides further evidence for the involvement of the spinal cord in extrapyramidal disorders.


Comparison of assay methods used to measure antiepileptic drugs in plasma.
The various techniques used to measure the concentration of antiepileptic drugs in plasma have been compared using data from the HEATH-CONTROL external quality control scheme. Assay methods were categorized as gas-liquid chromatography with and without derivatization (GLC + D, GLC-ND), radio- and enzyme multiplied immunoassay (RIA, EMIT), thin-layer and high-pressure liquid chromatography (TLC, HPLC), and spectrophotometry and colourimetry. The accuracy of the methods was determined from differences of measurements from the levels of drugs spiked into the samples. Most methods significantly underestimated the spiked drug concentrations. Comparisons of assay precision were made with the standard deviation of measurements or from the performance of individual laboratories in a ranking procedure. Comparable significant differences were found in both analyses. RIA followed by GLC-ND were the least variable methods for phenytoin; EMIT and then GLC-ND were the best for both phenobarbitone and primidone. Spectrophotometric measurements of phenobarbitone were unacceptably variable. TLC and colourimetry performed well for carbamazepine, whereas the GLC methods were the most variable. HPLC topped the list for ethosuximide, whereas EMIT had difficulty with this drug. Methods used for valproic acid were similar in precision. GLC + D was consistently less effective for all drugs when compared with GLC-ND.


Channel catfish virus: a new herpesvirus of ictalurid fish.
Channel catfish virus was studied in ictalurid fish cell culture, the only system of fish, amphibian, avian, and mammalian cells found to be susceptible. Channel catfish virus infection resulted in intranuclear inclusions and extensive syncytium formation. Replication occurred from 10 to 33 C, but not higher. Best growth was from 25 to 33 C, and the amount of virus released nearly equalled the amount which remained cell-associated. The virus was labile to lipid solvents, and indirect determinations with labeled precursors and a metabolic inhibitor showed evidence of deoxyribonucleic acid. Electron microscopy showed progeny virus, about 100 nm in diameter, in various stages of development in cell nuclei by 4 hr. Present also were nuclear masses of exceptionally electron-dense lamellar material, with a unit dimension of 10 to 15 nm. Virus was enveloped at the nuclear membrane and in cytoplasmic vacuoles, resulting in virions having a diameter of 175 to 200 nm. Negative staining demonstrated icosehedral symmetry and 162 capsomeres. Our data indicate that channel catfish virus is a herpesvirus.


Extensive sampling of Saccharomyces cerevisiae in Taiwan reveals ecology and evolution of predomesticated lineages.
The ecology and genetic diversity of the model yeast Saccharomyces cerevisiae before human domestication remain poorly understood. Taiwan is regarded as part of this yeast's geographic birthplace, where the most divergent natural lineage was discovered. Here, we extensively sampled the broadleaf forests across this continental island to probe the ancestral species' diversity. We found that S. cerevisiae is distributed ubiquitously at low abundance in the forests. Whole-genome sequencing of 121 isolates revealed nine distinct lineages that diverged from Asian lineages during the Pleistocene, when a transient continental shelf land bridge connected Taiwan to other major landmasses. Three lineages are endemic to Taiwan and six are widespread in Asia, making this region a focal biodiversity hotspot. Both ancient and recent admixture events were detected between the natural lineages, and a genetic ancestry component associated with isolates from fruits was detected in most admixed isolates. Collectively, Taiwanese isolates harbor genetic diversity comparable to that of the whole Asia continent, and different lineages have coexisted at a fine spatial scale even on the same tree. Patterns of variations within each lineage revealed that S. cerevisiae is highly clonal and predominantly reproduces asexually in nature. We identified different selection patterns shaping the coding sequences of natural lineages and found fewer gene family expansion and contractions that contrast with domesticated lineages. This study establishes that S. cerevisiae has rich natural diversity sheltered from human influences, making it a powerful model system in microbial ecology.


Haloperidol differentially potentiates tonic immobility, the dorsal immobility response, and catalepsy in the developing rat.
The effects of a single subcutaneous injection of haloperidol (1 or 10 mg/kg) or the vehicle solution on three kinds of behavioral inhibition were investigated in rats of 10, 15, and 20 days of age. The behaviors measured were tonic immobility, a response induced by placing an animal on its back supported by a V-shaped trough; the dorsal immobility response, which can be elicited in young rodents by grasping the skin of the dorsal surface of the neck and lifting the animal into the air; and catalepsy, a form of immobility in which animals remain in unusual postures but are capable of righting themselves, and which can be elicited by drugs which block dopamine receptors. Haloperidol (10 mg/kg) significantly potentiated the duration of tonic immobility only at 10 days of age; potentiated catalepsy at all age levels, but significantly less in the 15-day-old rats than in the 10- or 20-day-old rats; and potentiated the duration of the dorsal immobility response in the 10- and 20-day-old animals but not in the 15-day-olds. These results are discussed with respect to the development of neurotransmitter systems in the brain.


Fluoroscopy-guided laparoscopy in the management of intraabdominal foreign body.
Appendicitis or perforation as a result of intraluminal foreign body is uncommon. The method of diagnosis and proper approach for an elective appendectomy in an otherwise silent intraluminal foreign body is under dispute. A laparoscopic exploration under intraoperative fluoroscopy guidance was performed in a mentally retarded 9-year-old boy with asymptomatic foreign bodies in the right lower abdominal quadrant. The authors recommend laparoscopic appendectomy, assisted by intraoperative fluoroscopy for patients with pointed foreign bodies in the appendix.


Nitrogen requirement and utilization in dairy cattle.
Formulation of dairy cow rations should consider the following points regarding nitrogen utilization by lactating cows. (a) Maintenance of ruminal ammonia nitrogen in excess of 5 mg/100 ml rumen fluid has no effect on microbial protein production. (b)Supplemental nonprotein nitrogen is not utilized in typical dairy and feedlot beef rations containing more than 12 to 13% crude protein(dry matter basis). (c)Nonprotein nitrogen is approximately equal to true protein as a source of nitrogen in typical dairy and feedlot rations containing not more than 12 to 13% crude protein. (d)A scheme based upon metabolizable protein (absorbable protein) for calculating requirements and comparing protein sources is superior to crude or digestible protein designations. Ultimate expression of the requirement may be in terms of crude protein for the sake of simplicity. (e)One kilogram of crude protein, regardless of nitrogen source, equals about .75kg metabolizable protein in typical dairy and feedlot beef rations containing not more than 12 to 13% crude protein. One kilogram of plant protein (true protein) fed in excess of an amount equivalent to 12 to 13% dietary protein equals about .3 kg metabolizable protein. (f)Protein supplementation of lactating cows might be related more to stage of lactation than to milk production. (g)Lactating cows having above average lactational ability may benefit from dietary protein as high as 16 to 17% (dry matter basis) during the first third of lactation. (h)Cows in the latter two-thirds of lactation appear to require 12.5% dietary protein or less. (i)Plant protein (true protein) should be the supplemental sources of nitrogen during the first third of lactation, with NPN providing most, if not all, the supplemental nitrogen during the last two-thirds of lactation.


A complicated case of orbital cellulitis: When the fog doesn't clear.
Orbital cellulitis is a potential sight-threatening infection of the ocular adnexal structures posterior to the orbital septum. Acute bacterial sinusitis remains the most common cause of orbital cellulitis in the paediatric age group. Simultaneous intracranial and orbital complications from orbital cellulitis are rare. We describe a case of orbital cellulitis, which proceeded to sub-periosteal abscess formation and intracranial abscess within days of the initial presentation. The specific features of this case including the rapid progression of the orbital inflammation, failure of improvement over 48 h despite maximal medical treatment and incorrect initial reporting of computed tomography imaging all contributed to the complications seen in this case.


Brain natriuretic peptide inhibits hypoxic pulmonary hypertension in rats.
Brain natriuretic peptide (BNP) is a pulmonary vasodilator that is elevated in the right heart and plasma of hypoxia-adapted rats. To test the hypothesis that BNP protects against hypoxic pulmonary hypertension, we measured right ventricular systolic pressure (RVSP), right ventricle (RV) weight-to-body weight (BW) ratio (RV/BW), and percent muscularization of peripheral pulmonary vessels (%MPPV) in rats given an intravenous infusion of BNP, atrial natriuretic peptide (ANP), or saline alone after 2 wk of normoxia or hypobaric hypoxia (0.5 atm). Hypoxia-adapted rats had higher hematocrits, RVSP, RV/BW, and %MPPV than did normoxic controls. Under normoxic conditions, BNP infusion (0.2 and 1.4 micro g/h) increased plasma BNP but had no effect on RVSP, RV/BW, or %MPPV. Under hypoxic conditions, low-rate BNP infusion (0.2 micro g/h) had no effect on plasma BNP or on severity of pulmonary hypertension. However, high-rate BNP infusion (1.4 micro g/h) increased plasma BNP (69 +/- 8 vs. 35 +/- 4 pg/ml, P < 0.05), lowered RV/BW (0.87 +/- 0.05 vs. 1.02 +/- 0.04, P < 0.05), and decreased %MPPV (60 vs. 74%, P < 0.05). There was also a trend toward lower RVSP (55 +/- 3 vs. 64 +/- 2, P = not significant). Infusion of ANP at 1.4 micro g/h increased plasma ANP in hypoxic rats (759 +/- 153 vs. 393 +/- 54 pg/ml, P < 0.05) but had no effect on RVSP, RV/BW, or %MPPV. We conclude that BNP may regulate pulmonary vascular responses to hypoxia and, at the doses used in this study, is more effective than ANP at blunting pulmonary hypertension during the first 2 wk of hypoxia.


Hydrothermal synthesis and photoluminescent properties of YBO3:Eu3+ nanophosphor under ultraviolet and vacuum ultraviolet excitation.
YBO3:Eu3+ Nanophosphors were prepared by hydrothermal reaction (HR) with different reaction times. When the reaction times increased, the grain sizes of phosphor did not change obviously, but the particle size, morphology, and aggregation state were different. This transformation has influenced luminescent properties. The change trends of luminescent intensity under ultraviolet (UV) and vacuum ultraviolet (VUV) excitation are almost contrary: the nanophosphor that has better intensity in UV region is lower in the VUV region and vice versa. The emission under UV excitation decreases first and increases later as time increases. However, the emission under VUV excitation increases first and decreases later. In the UV region, orange emissions (at 592 nm) are higher than red emissions (at 611 nm), but in VUV regions, red emissions are higher. All results indicated that luminescence properties of nanophosphors in VUV regions differ greatly from those of nanophosphors in UV regions. In a certain nanoscale, the decreased particle size will lead to enhanced luminescence under VUV excitation but weaker luminescence under UV excitation. The related phenomena and possible explanations are also discussed.


Providing care and facing death: nursing during Ebola outbreaks in central Africa.
Few studies have focused on describing the experiences of health care workers during rapid killing epidemics. In this article, the views and experiences of nurses during three outbreaks of Ebola hemorrhagic fever (EHF) in Central Africa are examined. These three outbreaks occurred in Kikwit, Democratic Republic of Congo (DRC, 1995); Gulu, Uganda (2000-2001); and Republic of Congo (ROC, 2003). Open-ended and semistructured interviews with individuals and small groups were conducted during the outbreaks in Uganda and ROC; data from DRC are extracted from published sources. Three key themes emerged from the interviews: (a) lack of protective gear, basic equipment, and other resources necessary to provide care, especially during the early phases of the outbreaks; (b) stigmatization by family, coworkers, and community; and (c) exceptional commitment to the nursing profession in a context where the lives of the health care workers were in jeopardy.


Metal ion modulated electron transfer in photosynthetic proteins.
Photosynthetic purple bacterial reaction center (RC) proteins are ideal native systems for addressing basic questions regarding the nature of biological electron transfer because both the protein structure and the electron-transfer reactions are well-characterized. Metal ion binding to the RC can affect primary photochemistry and provides a probe for understanding the involvement of local protein environments in electron transfer. The RC has two distinct transition metal ion binding sites, the well-known non-heme Fe(2+) site buried in the protein interior and a recently discovered Zn(2+) site located on the surface of the protein. Fe(2+) removal and Zn(2+) binding systematically affect different electron-transfer steps in the RC. Factors involved in the metal ion alteration of RC electron transfer may provide a paradigm for other biological systems involved in electron transfer.


Vestibular migraine: who is the patient?
Vestibular migraine has been classified as a specific entity in which vestibular symptomatology is defined as part of the migrainous disorder. New and appropriate diagnostic criteria have been proposed by the Barany and International Headache Societies. The diagnosis of vestibular migraine mainly depends on the patient history. The NIVE project is a prospectic multicentric study on vestibular migraine. The aim of this project is to evaluate demographics, epidemiology, clinical manifestations of migraine and vertigo in a large cohort of Caucasian patients affected by vestibular migraine.


Precise sequence control in linear and cyclic copolymers of 2,5-bis(2-thienyl)pyrrole and aniline by DNA-programmed assembly.
A series of linear and cyclic, sequence controlled, DNA-conjoined copolymers of aniline (ANi) and 2,5-bis(2-thienyl)pyrrole (SNS) were synthesized. In one approach, linear copolymers were prepared from complementary DNA oligomers containing covalently attached SNS and ANi monomers. Hybridization of the oligomers aligns the monomers in the major groove of the DNA. Treatment of the SNS- and ANi-containing duplexes with horseradish peroxidase (HRP) and H2O2 causes rapid and efficient polymerization. In this way, linear copolymers (SNS)4(ANi)6 and (ANi)2(SNS)2(ANi)2(SNS)2(ANi)2 were prepared and analyzed. A second approach to the preparation of linear and cyclic copolymers of ANi and SNS employed a DNA encoded module strategy. In this approach, single-stranded DNA oligomers composed of a central region containing (SNS)6 or (ANi)5 covalently attached monomer blocks and flanking 5'- and 3'-single-strand DNA recognition sequences were combined in buffer solution. Self-assembly of these oligomers by Watson-Crick base pairing of the recognition sequences creates linear or cyclic arrays of SNS and ANi monomer blocks. Treatment of these arrays with HRP/H2O2 causes rapid and efficient polymerization to form copolymers having patterns such as cyclic BBA and linear ABA, where B stands for an (SNS)6 block and A stands for an (ANi)5 block. These DNA-conjoined copolymers were characterized by melting temperature analysis, circular dichroism spectroscopy, native and denaturing polyacrylamide gel electrophoresis, and UV-visible-near-IR optical spectroscopy. The optical spectra of these copolymers are typical of those of conducting polymers and are uniquely dependent on the specific order of monomers in the copolymer.


The topography of the anterior surface of the cat's cornea.
The topography of the cornea in nine unanaesthetised domestic cats was studied by the computer analysis of photokeratographs obtained using a Wessley Jessen P.E.K. 2000 photokeratoscope . Mean figures were obtained for: Central corneal radius in the steeper (9.06 mm) and flatter (9.20 mm) corneal meridians. Corneal astigmatism (0. 61D ). Corneal shape factor in the steeper (0.33) and flatter (0.31) corneal meridians and the diameter of the corneal cap in the vertical (6.23 mm) and horizontal (7.08 mm) meridians. The results are discussed and compared with previous such estimates for corneal topography. Dimensions for an hydrophilic contact lens suitable for general therapeutic or research use in the cat are suggested.


In Situ Constructing Coordination Compounds Interphase to Stabilize Zn Metal Anode for High-Performance Aqueous Zn-SeS2 Batteries.
Aqueous zinc (Zn) metal batteries have been regarded as the most promising aqueous batteries due to their low redox potential, high theoretical capacity, and abundant Zn resources. Unfortunately, Zn dendrite growth and serious side reactions drastically curtail the cycle life, severely affecting their large-scale application. Herein, a multifunctional ordered Zn-aminotrimethylene phosphonic acid (Zn-ATMP) film is in situ modified on the surface of metal Zn via a facile etching process. The modified layer can not only retard the side reactions and suppress the corrosion rate, but also lower the Zn nucleation overpotential and accelerate diffusion and homogenize deposition of Zn2+ due to the strong Zn affinity. Consequently, the as-prepared Zn-ATMP@Zn anode in the symmetric cell enables long-term lifespan (over 1000 h) at 10.0 mA cm-2 with a high areal capacity of 5 mAh cm-2 . Furthermore, when assembled with a SeS2 -based cathode, a long lifespan for over 280 cycles at 2 C can be achieved for the aqueous Zn-SeS2 battery. This work provides a reliable strategy for constructing stabilized Zn anode and accelerating the development of an aqueous energy storage system.


Effects of candesartan and perindopril on renal function, TGF-beta1 plasma levels and excretion of prostaglandins in stable renal allograft recipients.
Although on account of their nephroprotective effects, ACE inhibitors and angiotensin receptor antagonists appear to be advantageous for patients after renal transplantation, their use in these patients has been limited up to now. This is in part due to the risk of inducing a decrease in the glomerular filtration pressure gradient with subsequent impairment of allograft function. The aim of the present study was to investigate the effects of ACE inhibitors and angiotensin receptor antagonists on renal function, excretion of prostaglandins as a parameter of glomerular hemodynamics and TGF-beta1 plasma levels during an 8-week withdrawal phase in pretreated patients. Sixteen patients with stable long-term allograft function undergoing therapy with candesartan (group 1) and 16 patients with stable long-term allograft function undergoing therapy with perindopril (group 2) were included in the study. Any signs of chronic allograft dysfunction were defined as exclusion criteria. Renal function, albuminuria, TGF-beta1 plasma levels as well as the excretion of thromboxane B2 and 6-keto-prostaglandin-F-1alpha were monitored during an 8-week withdrawal phase of the angiotensin receptor antagonist or ACE inhibitor, respectively. Normotension was maintained throughout the study period through adjustment of other anti-hypertensive drugs. Creatinine clearance as well as TGF-beta1 plasma levels and the excretion of prostaglandins remained unchanged after discontinuation of candesartan or perindopril. However, after withdrawal of the substances a significant increase in albuminuria was noted in both patient groups throughout the observation period. After 8 weeks, median albuminuria had increased by 63% in group 1 and by 163% in group 2. We were able to demonstrate that the use of ACE inhibitors and angiotensin receptor antagonists in patients after renal transplantation is safe. Favorable effects of both substances on albuminuria were detectable in patients who showed no signs of chronic allograft dysfunction according to the usual criteria. Therefore, a nephroprotective effect of candesartan as well as of perindopril, is highly probable in patients after renal transplantation. Further investigations regarding routine use in these patients are therefore mandatory.


Formation, Structure, and Frequency-Doubling Effect of a Modification of Strontium Cyanurate (α-SCY).
The low-temperature modification of Sr3(O3C3N3)2 was prepared and assigned as α-SCY after the high-temperature phase (now called β-SCY) and its frequency-doubling properties were reported recently. The crystal structure of α-SCY was solved and refined by single-crystal X-ray diffraction. Both modifications of SCY crystallize in noncentrosymmetric space groups, with the low-temperature phase (α-SCY) adopting the lower symmetry structure (Cc). Atomic positions in α-SCY (Cc) reveal only small deviations in comparison to those in the structure of β-SCY (R3c). The reversible phase transition between both modifications of SCY was studied by means of temperature-dependent powder X-ray diffraction. NLO measurements of both SCY modifications are reported in comparison to the commercial frequency-doubling material KTiOPO4 (KTP).


Circadian rhythm and quality of life in older adults.
Sleep is critical to physical and mental health for people of all ages, but older adults are particularly vulnerable to the consequences of poor sleep health. The purpose of this pilot study was to explore patterns of sleep and the relationships between circadian rhythm disorders and quantity of life in 34 community-dwelling older adults. Participants were primarily female, and single. Of participants, 44% reported poor sleep quality, and 29% had a circadian rhythm disorder. Those with circadian rhythm disorders had lower physical health quality of life score than other participants although this was not significant. No differences were seen in mental health quality of life scores. Further research is needed to explore sleep and circadian rhythm disorders in this population to target interventions to improve sleep quality.


Interactive agent based modeling of public health decision-making.
Agent-based models have yielded important insights regarding the transmission dynamics of communicable diseases. To better understand how these models can be used to study decision making of public health officials, we developed a computer program that linked an agent-based model of pertussis with an agent-based model of public health management. The program, which we call the Public Health Interactive Model & simulation (PHIMs) encompassed the reporting of cases to public health, case investigation, and public health response. The user directly interacted with the model in the role of the public health decision-maker. In this paper we describe the design of our model, and present the results of a pilot study to assess its usability and potential for future development. Affinity for specific tools was demonstrated. Participants ranked the program high in usability and considered it useful for training. Our ultimate goal is to achieve better public health decisions and outcomes through use of public health decision support tools.


Socioeconomic Disparities in Alcohol-Related Mortality in Sweden, 1991-2006: A Register-Based Follow-Up Study.
To examine whether apparent stability of overall alcohol-related mortality in Sweden during a period when traditionally strict alcohol policies went through a series of liberalizations and overall alcohol mortality remained stable, concealed a heterogeneity across socioeconomic groups (defined by educational level); and whether an increase occurred in the contribution of alcohol-related mortality to overall mortality differentials. Drawing on cause of death data linked to census records for the period 1991-2006, we computed annual age-standardized and sex-specific rates of alcohol-related mortality for groups with low, intermediate and high education. Alcohol-related mortality was considerably higher in lower educational groups for both men and women. For men, the trends in alcohol-related mortality were roughly stable for all education groups, and there were no signs of increasing inequalities by education. For women, alcohol-related mortality increased significantly for the low-education group whereas the two higher education groups showed no significant time trends, thus resulting in a widened educational gap in alcohol mortality for women. Alcohol's contribution to the overall mortality differentials declined for men and was basically unchanged for women. The findings provide only partial support to the hypothesis that the liberalizations of Swedish alcohol policy have been followed by a general increase in socioeconomic disparities in alcohol-related mortality.


Reduction of Arachidonate Is Associated With Increase in B-Cell Activation Marker in Infants: A Randomized Trial.
Infants who are not breast-fed benefit from formula with both docosahexaenoic acid (C22:6n3) and arachidonic acid (ARA; C20:4n6). The amount of ARA needed to support immune function is unknown. Infants who carry specific fatty acid desaturase (FADS) polymorphisms may require more dietary ARA to maintain adequate ARA status. The aim of the study was to determine whether ARA intake or FADS polymorphisms alter ARA levels of lymphocytes, plasma, and red blood cells in term infants fed infant formula. Infants (N = 89) were enrolled in this prospective, double-blind controlled study. Infants were randomized to consume formula containing 17 mg docosahexaenoic acid and 0, 25, or 34 mg ARA/100 kcal for 10 weeks. Fatty acid composition of plasma phosphatidylcholine and phosphatidylethanolamine, total fatty acids of lymphocytes and red blood cells, activation markers of lymphocytes, and polymorphisms in FADS1 and FADS2 were determined. Lymphocyte ARA was higher in the 25-ARA formula group than in the 0- or 34-ARA groups. In plasma, 16:0/20:4 and 18:0/20:4 species of phosphatidylcholine and phosphatidylethanolamine were highest and 16:0/18:2 and 18:0/18:2 were lowest in the 34-ARA formula group. In minor allele carriers of FADS1 and FADS2, plasma ARA content was elevated only at the highest level of ARA consumed. B-cell activation marker CD54 was elevated in infants who consumed formula containing no ARA. ARA level in plasma is reduced by low ARA consumption and by minor alleles in FADS. Dietary ARA may exert an immunoregulatory role on B-cell activation by decreasing 16:0/18:2 and 18:0/18:2 species of phospholipids. ARA intake from 25 to 34 mg/100 kcal is sufficient to maintain cell ARA level in infants across genotypes.


Optical and structural properties of an Eu implanted gallium nitride quantum dots/aluminium nitride superlattice.
GaN/AIN structures made of GaN quantum dots (QDs) separated by AIN spacer layers, were doped with Europium by ion implantation. Rutherford Backscattering/Channelling measurements showed that Eu is incorporated mainly on near-substitutional cation sites within the superlattice region. Only slight deterioration of the crystal quality and no intermixing of the different layers are observed after implantation and annealing. After thermal annealing, photoluminescence associated with Eu3+ ions was observed. From its behaviour under different photon energy excitation and sample temperature we concluded that the Eu-related emitting centres are located inside the GaN QDs or dispersed in the GaN and AIN buffer or spacer layers. The 624 nm PL line, associated with Eu-doped GaN QDs, shows very low thermal quenching, suggesting recombination of confined carriers through rare-earth ion excitation.


Three-Dimensional Cardiac Imaging: A Necessity to the Diagnosis and Treatment of Swiss-Cheese Atrial Septal Defect.
Swiss-cheese atrial septal defect (ASD) is a malformation characterized by multi-fenestrated interatrial defects. Here, we describe a vignette of a 23-year-old man with Swiss-Cheese ASD characterized by two defects with areas of 0.74 cm2 and 0.44 cm2, complicated with an atrial septal aneurysm successfully repaired with a cribriform amplatzer septal occluder (ASO) via the percutaneous transcatheter approach. This case emphasizes the importance of attaining a clear view of three-dimensional structures for proper device selection and deployment in repair as additional structural defects such as concomitant aneurysms impose significant challenges.