Non-Gaussian state generation from linear elements via feedback.
We present a feedback scheme to produce quantum non-Gaussian states from linear optical elements. Instead of traditional additive control methods, we introduce a mutiplicative feedback control and apply it to the deterministic generation of quantum superposition states. The protocol of feedback control is based on quantum nondemolition measurement of a quadrature, multifeedback structure, and Lyapunov stability for feedback design.


IRF3 and IRF8 Regulate NF-κB Signaling by Targeting MyD88 in Teleost Fish.
MyD88 is a conserved intracellular adaptor, which plays an important role in the innate immune system. MyD88 transmits signals for downstream of toll-like and IL-1 receptors to activate NF-κB signaling pathway, which is tightly controlled in the immune response to maintain immune intensity and immune homeostasis at different stages. NF-κB signaling pathway has been extensively studied in mammals, but regulatory molecular mechanism is still unclear in teleost fish. We determined that IRF3 and IRF8 can regulate MyD88-mediated NF-κB signaling pathway in fish. Interestingly, MyD88 is precisely regulated by IRF3 and IRF8 through the same mechanism but in completely opposite ways. IRF3 promotes MyD88-mediated NF-κB signaling pathway, whereas IRF8 inhibits the signaling pathway. MyD88 is regulated via ubiquitin-proteasome degradation, whereas IRF3 or IRF8 inhibited or promoted MyD88 degradation in this pathway. Specifically, in the early stage of lipopolysaccharide (LPS) stimulation or Vibrio infection, up-regulation of IRF3 and down-regulation of IRF8 eventually increased MyD88 expression to activate the NF-κB signaling pathway to trigger immune response. In the late stage of stimulation, down-regulated IRF3 and up-regulated IRF8 synergistically regulate the expression of MyD88 to a normal level, thus maintaining the immune balance of homeostasis and preventing serious damage from persistent over-immunization. This study presents information on Myd88-NF-κB signaling pathway in teleost fish and provides new insights into its regulatory mechanism in fish immune system.


Self-induced photosensitive absence seizures with ictal pleasure.
A 32-year-old woman was treated for self-induced photosensitive seizures that included strong subjective feelings of pleasure and masturbatory behavior. Electroencephalograms demonstrated generalized polyphasic spike-wave discharges in response to stroboscopic stimulation. The behavioral sequences leading to seizures and the effects of treatment can be explained in terms of operant conditioning theory. Data from human and animal studies indicate a correlation between ictal pleasure or reinforcement and the subject's ability to induce seizures. Ictal pleasure is rare in spontaneous seizures that are not under the control of the patient.


Vomiting Larry: a simulated vomiting system for assessing environmental contamination from projectile vomiting related to norovirus infection.
Infectious diseases such as norovirus can induce emesis (vomiting), which can be of a projectile nature. Although studies have been carried out on transmission, prevalence and decontamination of such micro-organisms within various environments, little is known about the extent to which the surrounding environment is contaminated when an individual vomits. This is an important consideration for infection control purposes. The aim of this study was to develop a simulated vomiting system (Vomiting Larry) to be used for assessing the extent to which projected fluid can contaminate the environment. Vomiting Larry was set up within a Controlled Atmosphere Chamber (CAC) facility at the Health and Safety Laboratory (HSL). Simulated vomiting was undertaken using water as a vomitus substitute containing a fluorescent marker enabling small splashes, ordinarily missed, to be visualised using UV lighting. Experiments revealed that splashes and droplets produced during an episode of projectile vomiting can travel great distances (>3 m forward spread and 2.6 m lateral spread). The research highlighted that small droplets can be hard to see and therefore cleaning all contaminated surfaces is difficult to achieve. Evidence from this study suggests that areas of at least 7.8 m2 should be decontaminated following an episode of projectile vomiting.


Evaluation of the Patient-Reported Outcomes Measurement Information System Upper Extremity Computer Adaptive Test.
The Patient-Reported Outcomes Measurement Information System Upper Extremity Computer Adaptive Test (UE CAT) has recently been made available by the National Institutes of Health to measure physical function outcomes in the upper extremity. We hypothesized that the UE CAT would psychometrically outperform the Disabilities of the Arm, Shoulder, and Hand (DASH) and the Patient-Reported Outcomes Measurement Information System Physical Function Computer Adaptive Test (PF CAT) in a hand patient population. The UE CAT, PF CAT, and DASH were each electronically administered to all adult patients who presented to a tertiary hand and upper extremity (nonshoulder) orthopedic clinic. Patient responses were retrospectively studied to determine the validity, reliability, and floor/ceiling effects of all 3 instruments using the Rasch Partial Credit Model. Responder burden and Pearson correlations were calculated for each instrument. A total of 379 patients completed the UE CAT, PF CAT, and the DASH. On average, 6 UE CAT, 9 PF CAT, and 30 DASH questions were administered to each patient. All 3 instruments were each highly correlated with each other. Floor effects were low and similar between all instruments; however, ceiling effects were higher in the UE CAT (10.82%) than in the PF CAT (1.32%) or DASH (5.28%). High person reliability (PR) and item reliability (IR) were found for all 3 metrics: UE CAT (α = 0.99; PR = 0.91; IR = 0.94); PF CAT (α = 0.95; PR = 0.89; IR = 0.96); and DASH (α = 0.97; PR = 0.95; IR = 0.99). The UE CAT questions had the best item-fit: only 1 of 15 UE CAT items had poor fit in contrast to 4 of 30 DASH items and 7 of 33 PF CAT items. The psychometric properties of the UE CAT compare favorably with the PF CAT and the DASH in nonshoulder upper extremity patients. The relatively large ceiling effect found in the UE CAT could be improved with item bank expansion to include items at the upper end of function. The UE CAT is a useful patient-reported outcome measure that merits further investigation.


Home versus In-Center Dialysis and Day of the Week Hospitalization: A Cohort Study.
The dialysis treatment day after the 2-day interdialytic interval (Monday/Tuesday) is associated with a heightened risk of hospitalization for patients on in-center hemodialysis (ICHD). In this national cohort study, we sought to characterize hospitalizations by day of the week for patients receiving ICHD, home HD (HHD), and peritoneal dialysis (PD) and to identify whether there were differences in the probability of a Monday/Tuesday admission for each modality type. Patients on maintenance dialysis in Canada were analyzed from 2005 to 2014 using the Canadian Organ Replacement Register. Patients on hemodialysis were categorized as those receiving ICHD, HHD, frequent ICHD, or frequent HHD (the latter two included short daily and nocturnal HD). Hospitalizations were attributed to the previous treatment if they occurred within 30 days of a treatment change. Differences in the proportion of patients experiencing a Monday/Tuesday admission with all other days of the week were compared using a generalized linear model with binomial distribution and reported using adjusted odds ratios (OR) with 95% CIs. Overall, 27,430 individuals experienced 111,748 hospitalization episodes. Rates per 1000 patient days were 3.76, 2.98, 2.71, 2.16, and 2.13 for each of frequent ICHD, ICHD, PD, HHD, and frequent HHD, respectively. Compared with those on ICHD, only patients receiving frequent HHD (OR, 0.89; 95% CI, 0.81 to 0.97) and PD (OR, 0.95; 95% CI, 0.93 to 0.97) had a lower odds of experiencing a Monday/Tuesday admission. The OR was lower when restricted to hospitalization episodes for cardiovascular reasons comparing frequent HHD with ICHD (OR, 0.68; 95% CI, 0.48 to 0.96). In this nationally representative cohort, we identified that the probability of a Monday/Tuesday admission was lower for frequent HHD and PD compared with ICHD, most notably for hospitalizations due to cardiovascular causes. Gaining a better understanding of the reasons behind this observation may help to develop future strategies to reduce overall and cause-specific hospitalization for patients receiving dialysis.


Cytochrome c oxidase inhibition in the rice weevil Sitophilus oryzae (L.) by formate, the toxic metabolite of volatile alkyl formates.
Volatile alkyl formates are potential replacements for the ozone-depleting fumigant, methyl bromide, as postharvest insecticides and here we have investigated their mode of insecticidal action. Firstly, a range of alkyl esters, ethanol and formic acid were tested in mortality bioassays with adults of the rice weevil, Sitophilus oryzae (L.) and the grain borer, Rhyzopertha dominica (F.) to determine whether the intact ester or one of its components was the toxic moiety. Volatile alkyl formates and formic acid caused similar levels of mortality (LC(50) 131-165 micromol l(-1)) to S. oryzae and were more potent than non-formate containing alkyl esters and ethanol (LC(50)>275 micromol l(-1)). The order of potency was the same in R. dominica. Ethyl formate was rapidly metabolised in vitro to formic acid when incubated with insect homogenates, presumably through the action of esterases. S. oryzae and R. dominica fumigated with a lethal dose of ethyl formate had eight and 17-fold higher concentrations of formic acid, respectively, in their bodies than untreated controls. When tested against isolated mitochondria from S. oryzae, alkyl esters, alcohols, acetate and propionate salts were not inhibitory towards cytochrome c oxidase (EC 184.108.40.206), but sodium cyanide and sodium formate were inhibitory with IC(50) values of 0.0015 mM and 59 mM, respectively. Volatile formate esters were more toxic than other alkyl esters, and this was found to be due, at least in part, to their hydrolysis to formic acid and its inhibition of cytochrome c oxidase.


Adequate trust avails, mistaken trust matters: on the moral responsibility of doctors as proxies for patients' trust in biobank research.
In Sweden, most patients are recruited into biobank research by non-researcher doctors. Patients' trust in doctors may therefore be important to their willingness to participate. We suggest a model of trust that makes sense of such transitions of trust between domains and distinguishes adequate trust from mistaken trust. The unique position of doctors implies, we argue, a Kantian imperfect duty to compensate for patients' mistaken trust. There are at least three kinds of mistaken trust, each of which requires a different set of countermeasures. First, trust is mistaken when necessary competence is lacking; the competence must be developed or the illusion dispelled. Second, trust is irrational whenever the patient is mistaken about his actual reasons for trusting. Care must therefore be taken to support the patient's reasoning and moral agency. Third, some patients inappropriately trust doctors to recommend only research that will benefit them directly. Such trust should be counteracted by nurturing a culture where patients expect to be asked occasionally to contribute to the common good.


Shared decision-making in older children and parents considering elective adenotonsillectomy.
Shared decision-making describes a collaborative process in which healthcare providers and patients/families make treatment decisions using the best available evidence, while taking into account the patient's values and preferences. The objectives of this study were to assess the level of decisional conflict and shared decision-making experienced by older children and their parents when considering elective adentonsillectomies. A prospective cohort study. Paediatric otolaryngology clinic in a teaching hospital. Participants included 53 children older than 9 years and their parents who underwent consultation for tonsillectomy with or without adenoidectomy. Children and parents completed the Decisional Conflict Scale (DCS) and Shared Decision-Making Questionnaire-Patient Version (SDM-Q-9). Surgeons completed the Shared Decision-Making Questionnaire-Physician Version (SDM-Q-Doc). Overall, 10 (19%) parents and 18 (34%) children reported clinically significant decisional conflict. Parents who opted not to proceed with surgery had significantly higher DCS scores than those who decided to proceed with surgery. Both parents and children SDM-Q-9 and total DCS scores were significantly negatively correlated. Physician SDM-Q-Doc and parent total DCS scores were negatively correlated, while parent and physician SDM scores were positively correlated. Many older children and parents reported significant decisional conflict when considering elective paediatric otolaryngology surgery. Decisional conflict levels for both children and parents decreased with greater perceived levels of shared decision-making. Older children did not appear to discern the same levels of shared decision-making as parents and surgeons. Future research should assess methods to implement shared decision-making into clinical practice for clinicians, parents and children when appropriate.


Molecular epidemiology and phylodynamics of goose haemorrhagic polyomavirus.
Goose haemorrhagic polyomavirus (GHPV, or Anser anser polyomavirus 1) is a small dsDNA virus of the Polyomaviridae family. The virus infects the internal organs causing haemorrhagic nephritis and enteritis of geese that may be fatal for goslings. In this study, GHPV positivity was examined in goose and duck samples collected in Hungary between 2005 and 2019. In this period, 384 of the investigated 1,111 specimens were diagnosed as GHPV-positive by PCR assay. Twenty-two GHPV genomes were sequenced and subjected to phylogenetic and evolutionary analysis. Based on the sequence data, the mean evolutionary rates were estimated 6.57 × 10-6 -5.82 × 10-5 s/s/y for both GHPV complete genomes and individual genes, with negative selection acting on each gene. When GHPV VP1 sequences originating from wild birds were also included in the analyses, the nt and aa mutations inflated the substitution rate to 1.54 × 10-4 s/s/y that may imply adaptation of the virus to novel host species. Our data suggested the co-circulation of various GHPV strains in Hungarian goose farms; the source of these may be persistently infected domesticated or migratory wild birds. Detection and characterization of GHPV in wild birds and domestic waterfowls may help to elaborate new strategies for more effective disease control and prevention.


Catalytic hydrodechlorination of benzyl chloride promoted by Rh-N-heterocyclic carbene catalysts.
The rhodium(I) complexes [Rh(Cl)(COD)(R-NHC-(CH2 )3 Si(OiPr)3 )] [COD=cyclooctadiene; R=2,6-diisopropylphenyl (1 a); n-butyl (1 b)] are effective catalyst precursors for the homogeneous hydrodechlorination of benzyl chloride using HSiEt3 as hydrogen source. This reaction is selective to the formation of toluene. However, in presence of a stoichiometric amount of potassium tert-butoxide (KtBuO) the formation of mixtures containing toluene together with 17-19 mol % of the C--C homocoupling product, namely PhCH2 CH2 Ph, is observed. A mechanism proposal based on experimental insights and theoretical calculations at the DFT level that allows explanation of the experimental findings is included. Moreover, the heterogeneous catalytic system based on catalyst 1 a supported on MCM-41 has been demonstrated to be effective for the solvent-free hydrodechlorination of benzyl chloride using HSiEt3 and HSiMe(OSiMe3 )2 .


Relationships Between eHealth Literacy and Health Behaviors in Korean Adults.
The Internet is a useful and accessible source for health-related information for modern healthcare consumers. Individuals with adequate eHealth literacy have an incentive to use the Internet to access health-related information, and they consider themselves capable of using Web-based knowledge for health. This cross-sectional study aimed to describe the relationship between eHealth literacy and health behaviors. A total of 230 adults aged 18 to 39 years and residing in South Korea participated in the study. The mean (SD) score for eHealth literacy was 25.52 (4.35) of a total possible score of 40. The main source of health information was the Internet. Using hierarchical linear regression, the results showed that eHealth literacy was the strongest predictor of health behaviors after adjusting for general characteristics. These findings indicate that eHealth literacy can be an important factor in promoting individual health behaviors. Further research on eHealth literacy and actual health behaviors including intention and self-reported health behaviors are required to explain the impact of eHealth literacy on overall health status.


Systematic review of traditional Chinese medicine for geriatrics.
The Japan Geriatrics Society revised its criteria for the medical treatment and safety of the elderly in 2015. The Japan Geriatrics Society guidelines contain a chapter for traditional Chinese medicine (TCM; traditional medicines in East Asian countries, such as China, Japan, Korea, Taiwan, Vietnam and Singapore), because it is widely used for elderly patients and is sometimes covered by national medical insurance in Japan. The updated guidelines should be improved based on a comprehensive, systematic review and evidence grading. TCM is rapidly expanding in the literature, and is under intensive investigation in clinical trials. The objective of the present trial was to review TCM systematically and reflect the results to update the TCM chapter of the Japan Geriatrics Society guidelines. Here, we introduce the results of the systemic review of TCM for geriatrics. Geriatr Gerontol Int 2017; 17: 679-688.


Vaginal cones or balls to improve pelvic floor muscle performance and urinary continence in women post partum: A quantitative systematic review.
the vaginal use of cones or balls aims to increase muscle performance and thereby prevent or treat urinary incontinence. To date, no systematic review has focused on the effectiveness of these devices specifically during the postpartum period. The objectives of this review were: to compare the effectiveness of vaginal cones or balls for improvement of pelvic floor muscle performance and urinary continence in the postpartum period to no treatment, placebo, sham treatment or active controls; to gather information on effect on perineal descent or pelvic organ prolapse, adverse effects and economical aspects. quantitative systematic review. 14 scientific databases (including PubMed and CINAHL) and the world-wide web; experts were contacted for published and unpublished data. studies had to be randomised/quasi-randomised trials and have female participants up to one year after childbirth. The intervention is compared to no treatment, placebo, sham treatment or active controls. Outcome measures relate to pelvic floor muscle performance or urinary incontinence. Studies were selected, 'risk of bias' assessed, and data extracted by two reviewers independently with inter-reviewer agreement. one study met the inclusion criteria; its original data were re-analysed. In an intention-to-treat analysis, compared with the control group, the cone group showed a statistically significant lower rate of urinary incontinence; compared with the exercise group, the prevalence was similar. However, the validity of the analysis is limited. the evidence gained from this systematic review is very limited. The use of cones may be helpful for urinary incontinence after childbirth, but further research is needed.


Progress in Synthesis of Highly Active and Stable Nickel-Based Catalysts for Carbon Dioxide Reforming of Methane.
In recent decades, rising anthropogenic greenhouse gas emissions (mainly CO2 and CH4 ) have increased alarm due to escalating effects of global warming. The dry carbon dioxide reforming of methane (DRM) reaction is a sustainable way to utilize these notorious greenhouse gases. This paper presents a review of recent progress in the development of nickel-based catalysts for the DRM reaction. The enviable low cost and wide availability of nickel compared with noble metals is the main reason for persistent research efforts in optimizing the synthesis of nickel-based catalysts. Important catalyst features for the rational design of a coke-resistant nickel-based nanocatalyst for the DRM reaction are also discussed. In addition, several innovative developments based on salient features for the stabilization of nickel nanocatalysts through various means (which include functionalization with precursors, synthesis by plasma treatment, stabilization/confinement on mesoporous/microporous/carbon supports, and the formation of metal oxides) are highlighted. The final part of this review covers major issues and proposed improvement strategies pertaining to the rational design of nickel-based catalysts with high activity and stability for the DRM reaction.


Getting to the heart of regeneration in zebrafish.
A scientific and clinical prerogative of the 21st century is to stimulate the regenerative ability of the human heart. While the mammalian heart shows little or no natural regeneration in response to injury, certain non-mammalian vertebrates possess an elevated capacity for cardiac regeneration. Adult zebrafish restore ventricular muscle removed by surgical resection, events that involve little or no scarring. Recent studies have begun to reveal cellular and molecular mechanisms of this regenerative process that have exciting implications for human cardiac biology and disease.


Placental growth factor in cancer.
Placental growth factor (PLGF) belongs to the VEGF family, which among the three VEGF receptors binds exclusively to VEGFR1, present on various cell types. Isoform PLGF-2 also binds the neuropilin co-receptors. PLGF is dispensable for development and health but has a prominent role in pathology including cancer. This has triggered the question whether PLGF targeting might offer an alternative to current antiangiogenesis therapy, which encounters problems of refractoriness and acquired resistance. This article reviews the available literature on the characteristics of PLGF, its role(s) in cancer and the findings on PLGF inhibition in preclinical models with attention to as yet unresolved questions and summarizes data from initial clinical trials. Preclinical studies show that inhibition of PLGF, either by genetic inhibition or by pharmacological blockade using distinct independently generated anti-PLGF antibodies, slows down tumor growth and metastasis and even induces regression of pre-existing medulloblastoma, the most frequent brain cancer in children. These promising preclinical findings, together with the acceptable safety profile of anti-PLGF administration in Phase I clinical trials, have attracted attention to PLGF as a potential target for therapy.


Guillain-Barré syndrome among recipients of Menactra meningococcal conjugate vaccine--United States, June-July 2005.
On January 14, 2005, a quadrivalent (A, C, Y, and W135) meningococcal conjugate vaccine (Meningococcal Polysaccharide Diphtheria Toxoid Conjugate Vaccine, Menactra, Sanofi-Pasteur, Swiftwater, Pennsylvania) (MCV4) was licensed in the United States. MCV4 is a tetravalent vaccine; each 0.5-mL dose contains 4 microg each of capsular polysaccharide from Neisseria meningitidis serogroups A, C, Y, and W-135 conjugated to 48 microg of diphtheria toxoid. In February 2005, the Advisory Committee on Immunization Practices (ACIP) recommended routine vaccination of adolescents at the preadolescent health-care visit (at ages 11-12 years). For persons who have not been vaccinated previously, ACIP recommended vaccination before high-school entry (at approximately age 15 years). Routine vaccination also is indicated for first-year college students living in dormitories and for other persons at increased risk.


Necroptosis and parthanatos are involved in remote lung injury after receiving ischemic renal allografts in rats.
Early renal graft injury could result in remote pulmonary injury due to kidney-lung cross talk. Here we studied the possible role of regulated necrosis in remote lung injury in a rat allogeneic transplantation model. In vitro, human lung epithelial cell A549 was challenged with TNF-α and conditioned medium from human kidney proximal tubular cells (HK-2) after hypothermia-hypoxia insults. In vivo, the Brown-Norway rat renal grafts were extracted and stored in 4 °C Soltran preserving solution for up to 24 h and transplanted into Lewis rat recipients, and the lungs were harvested on day 1 and day 4 after grafting for further analysis. Ischemia-reperfusion injury in the renal allograft caused pulmonary injury following engraftment. PARP-1 (marker for parthanatos) and receptor interacting protein kinase 1 (Rip1) and Rip3 (markers for necroptosis) expression was significantly enhanced in the lung. TUNEL assays showed increased cell death of lung cells. This was significantly reduced after treatment with necrostatin-1 (nec-1) or/and 3-aminobenzamide (3-AB). Acute immune rejection exacerbated the remote lung injury and 3-AB or/and Nec-1 combined with cyclosporine A conferred optimal lung protection. Thus, renal graft injury triggered remote lung injury, likely through regulated necrosis. This study could provide the molecular basis for combination therapy targeting both pathways of regulated necrosis to treat such complications after renal transplantation.


Pressure-enhanced superconductivity in cage-type quasiskutterudite Sc5Rh6Sn18single crystal.
Sc5Rh6Sn18with a cage-type quasiskutterudite crystal lattice and type II superconductivity, with superconducting transition temperatureTc= 4.99 K, was investigated under hydrostatic high-pressure (HP) using electrical transport, synchrotron x-ray diffraction (XRD) and Raman spectroscopy. Our data show that HP enhance the metallic nature andTcof the system.Tcis found to show a continuous increase reaching to 5.24 K at 2.5 GPa. Although the system is metallic in nature, Raman spectroscopy investigations at ambient pressure revealed the presence of three weak modes at 165.97, 219.86 and 230.35 cm-1, mostly related to the rattling atom Sc. The HP-XRD data revealed that the cage structure was stable without any structural phase transition up to ∼7 GPa. The lattice parameters and volume exhibited a smooth decrease without any anomalies as a function of pressure in this pressure range. In particular, a second order Birch-Murnaghan equation of state can describe the pressure dependence of the unit cell volume well, yielding a bulk modulus of ∼97 GPa. HP Raman investigations revealed a linear shift of all the three Raman modes to higher wavenumbers with increasing pressure up to ∼8 GPa. As the pressure enhances the bond overlap, thus inducing more electronic charges into the system, HP-XRD and Raman results may indicate the possibility of obtaining higherTcwith increasing pressures in this pressure range.


[TIA - immediate acute care and treatment decrease the risk of stroke substantially].
TIA is defined as an episode of neurological deficit with sudden onset, caused by focal cerebral or retinal ischemia lasting less than 24 hours. A tissue-based definition has been proposed but its application has been challenging, in part as its use requires magnetic resonance imaging. In most cases the diagnosis is solely based on history as provided by the patient. The diagnosis can therefore be challenging, and interobserver agreement between physicians is only fair. The importance of a TIA is its subsequent substantial risk of stroke, especially within the first weeks. Immediate acute care and treatment has been shown to decrease the risk of stroke substantially and is therefore crucial. Diagnostic procedures include imaging of the brain and neck vessels, ECG and cardiac rhythm monitoring, and blood pressure measuring. Treatment decisions are based on the diagnostic findings and include antithrombotic therapy, statins, blood pressure lowering medications, and carotid surgery if indicated.


Comparative transmission of SARS-CoV-2 Omicron (B.1.1.529) and Delta (B.1.617.2) variants and the impact of vaccination: national cohort study, England.
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant (B.1.1.529) rapidly replaced Delta (B.1.617.2) to become dominant in England. Our study assessed differences in transmission between Omicron and Delta using two independent data sources and methods. Omicron and Delta cases were identified through genomic sequencing, genotyping and S-gene target failure in England from 5-11 December 2021. Secondary attack rates for named contacts were calculated in household and non-household settings using contact tracing data, while household clustering was identified using national surveillance data. Logistic regression models were applied to control for factors associated with transmission for both methods. For contact tracing data, higher secondary attack rates for Omicron vs. Delta were identified in households (15.0% vs. 10.8%) and non-households (8.2% vs. 3.7%). For both variants, in household settings, onward transmission was reduced from cases and named contacts who had three doses of vaccine compared to two, but this effect was less pronounced for Omicron (adjusted risk ratio, aRR 0.78 and 0.88) than Delta (aRR 0.62 and 0.68). In non-household settings, a similar reduction was observed only in contacts who had three doses vs. two doses for both Delta (aRR 0.51) and Omicron (aRR 0.76). For national surveillance data, the risk of household clustering, was increased 3.5-fold for Omicron compared to Delta (aRR 3.54 (3.29-3.81)). Our study identified increased risk of onward transmission of Omicron, consistent with its successful global displacement of Delta. We identified a reduced effectiveness of vaccination in lowering risk of transmission, a likely contributor for the rapid propagation of Omicron.


Pharmacokinetics of cefaclor in normal subjects and patients with chronic renal failure.
We studied the pharmacokinetics of cefaclor, a new cephalosporin antibiotic, in normal subjects and subjects with chronic renal failure. Cefaclor was largely, but not entirely, eliminated by the kidneys. The cefaclor half-life in normal subjects was 40 to 60 min; in subjects with essentially no renal function, it increased to 3 h. In normal subjects, 50 to 70% of a 250-mg dose was excreted in the urine within 8 h. The linear relationship between the elimination constant and creatinine clearance allowed the construction of a useful dosage modification nomogram.


Intravitreal bevacizumab for subfoveal choroidal neovascularization associated with pattern dystrophy.
To assess the effects of intravitreal bevacizumab injections in the treatment of subfoveal choroidal neovascularization (CNV) associated with pattern dystrophy (PD) of the retinal pigment epithelium. The study was a prospective, nonrandomized, open-label, interventional clinical trial in which 12 patients were prospectively enrolled. Patients with a diagnosis of PD complicated by subfoveal CNV were considered for the study. All patients underwent a complete ophthalmic examination, including ETDRS visual acuity measurement, electroretinogram, electrooculogram, optical coherence tomography, and fluorescein angiography. The treatment protocol began with a loading dose of three consecutive injections at 1-month intervals, followed by injections administered as needed, according to OCT parameters and angiographic features observed during a 24-month follow-up period. The number of eyes with a visual acuity loss of fewer than 15 letters (<3 ETDRS lines), compared with baseline measures, was recorded at the 6-, 12-, and 24-month examinations. Twelve patients completed the planned visits and were included in the study. A visual acuity loss of fewer than 15 letters was not registered in any case at the 6- and 12-month examinations and was found in only one (8%) patient at the 24-month examination. The mean best corrected visual acuity (BCVA) and the mean central macular thickness (CMT) at baseline were 0.73+/-0.34 (logMAR+/-SD) and 276+/-95 microm (SD), respectively. At the 3-month examination, the mean BCVA significantly improved to 0.48+/-0.27, whereas the mean CMT decreased to 220+/-71 microm. At the 12-month examination, the mean BCVA was 0.45+/-0.24, and the mean CMT was 209+/-53 microm. At the 24-month (last) follow-up, the BCVA showed substantial stabilization and the CMT decreased to 199+/-34 microm. No side effects or complications were registered. Intravitreal bevacizumab injection is a beneficial treatment for subfoveal CNV associated with PD. Further studies are warranted to confirm these initial results and to analyze the morphofunctional changes during the follow-up. (ClinicalTrials.gov number, NCT00391144.).


Syntheses of (+)-alismoxide and (+)-4-epi-alismoxide.
The first total syntheses of (+)-alismoxide and (+)-4-epi-alismoxide are reported. Formal chemo-, regio-, and stereoselective addition of water to 10alpha-acetoxy-1alphaH,5betaH-guaia-3,6-diene afforded the target compounds after reduction. The absolute stereochemistry of (+)-alismoxide has been established. The low [alpha](D) +8.6 value indicates that significant amounts of alismoxide result from biosynthetic processes. Furthermore, the structure of the natural guaienediol isolated from Silphium perfoliatum has been corrected to (-)-alismoxide.


Long-term effects of felodipine on blood pressure and renal hemodynamics in severe hypertension.
Felodipine, a dihydropyridine calcium antagonist, was used to treat eight patients with severe uncontrolled hypertension: five had essential hypertension, two had renovascular disease, and one chronic pyelonephritis. Mean blood pressure (BP) was 221 +/- 14/120 +/- 4 mm Hg despite treatment with three or more antihypertensive drugs. All patients experienced an immediate and pronounced lowering of BP after adding felodipine, which persisted during long-term treatment in combination with previous medication except for vasodilating drugs. In all cases, an increase in glomerular filtration rate (51Cr-EDTA clearance) after 6 and 12 months of felodipine treatment was seen (59 +/- 10 to 63 +/- 7 and 70 +/- 6 ml/min, respectively, p less than 0.05). Renal plasma flow (PAH clearance) exhibited only a slight increase (315 +/- 68 to 340 +/- 63 and 314 +/- 69 ml/min), giving a nonsignificant rise in filtration fraction (18 +/- 1 to 21 +/- 1 and 20 +/- 1%, respectively). It is concluded that felodipine decreases BP dramatically in patients with previously refractory hypertension and that the drug causes an improved renal function in these patients.


Associations among job satisfaction, optimism, pessimism, and psychosomatic symptoms for employees in the government sector in Kuwait.
The present study examined associations among job satisfaction and optimism, pessimism, and psychosomatic symptoms in a sample of 718 Kuwaiti employees (350 men and 368 women). Men scored significantly higher than women on both the scales of Job Satisfaction and Optimism, while women scored significantly higher than men on both scales for Pessimism and Psychosomatic Symptoms. Job satisfaction scores correlated significantly and positively with Optimism scores and negatively with Pessimism scores. There was also a significant negative correlation between scores on Optimism and Pessimism, and a significant negative correlation between scores on Optimism and Psychosomatic symptoms. Results were discussed within the Kuwaiti context.


Dipoles Inside of Dipoles: Insertion Complexes of Polar versus Nonpolar Molecules in Ion Pairs.
Highly polar molecular systems are in demand as a means of enabling many important practical applications based on light-matter interactions. In the present work, the insertion complexes of recently synthesized polar molecules trapped between alkali halide counterions are studied. For specific selected compositions, the M-molecule-X systems are predicted to be stable to dissociation into molecule + alkali halide. It is found that unlike their nonpolar molecule-based counterparts, the polar molecule complexes can be even more stable than their common dipole-dipole MX-molecule isomers. This makes them thermodynamically stable, highly polar species, with very large dipoles of about 20 D, and they could be used, for example, to develop efficient light sensors. Furthermore, due to the neutralization of the M-X charge transfer in the excited triplet state, such complexes represent unique spin-controlled dipole-switch molecular systems with the large dipole turned off and even inverted by the spin state for the nonpolar and polar molecule complexes, respectively. This potentially could allow various spintronic and optoelectronic applications. In addition, the IR intensity spectra are predicted to sensitively indicate the formation of both the M-molecule-X and MX-molecule isomers, thus facilitating their reliable detection and differentiation in experiments.


Persistent cardiac troponin I elevation in stabilized patients after an episode of acute coronary syndrome predicts long-term mortality.
In patients with non-ST-elevation acute coronary syndrome, any troponin elevation is associated with an increased risk for cardiovascular events. However, the prevalence and prognostic importance of persistent troponin elevation in stabilized patients after an episode of non-ST-elevation acute coronary syndrome are unknown and were therefore assessed in this study. Cardiac troponin I (cTnI) was measured in 1092 stabilized patients at 6 weeks and 3 and 6 months after enrollment in the FRagmin and Fast Revascularization during InStability in Coronary artery disease (FRISC-II) trial. cTnI was analyzed with the Access AccuTnI assay with the application of different prognostic cutoffs. Outcomes were assessed through 5 years. Elevated cTnI levels >0.01 microg/L were found in 48% of the study patients at 6 weeks, in 36% at 6 months, and in 26% at all 3 measurements. cTnI elevation was associated with increased age and other cardiovascular high-risk features. The lowest tested cTnI cutoff (0.01 microg/L) was prognostically most useful and was independently predictive of mortality (hazard ratio, 2.1 [95% confidence interval, 1.3 to 3.3]; P=0.001) on multivariable analysis adjusted for cardiovascular risk factors and randomization to an invasive versus noninvasive treatment strategy, whereas it was related to myocardial infarction only on univariate analysis. Persistent minor cTnI elevation can be detected frequently in patients stabilized after an episode of non-ST-elevation acute coronary syndrome with the use of a sensitive assay. Elevated cTnI levels >0.01 microg/L predict mortality during long-term follow-up. Our results emphasize the importance of further troponin testing in non-ST-elevation acute coronary syndrome patients after hospital discharge.


Direct and indirect effects of a combination of adipose-derived stem cells and platelet-rich plasma on bone regeneration.
A key goal for successful bone regeneration is to bridge a bone defect using healing procedures that are stable and durable. Adipose-derived stem cells (ASCs) have the potential to differentiate into bone. Meanwhile, platelet-rich plasma (PRP) is an interesting biological means to repair tissue by inducing chemotactic, proliferative, and anabolic cellular responses. This study evaluated bone regeneration using a combination of ASCs and PRP in a rat calvarial defect model. ASCs were isolated from inguinal fat pads of F344 inbred rats, while PRP was prepared from these rats. ASCs were cultured in control medium supplemented with 10% fetal bovine serum or 5% PRP in vitro. After 1 week, levels of growth factors including insulin-like growth factor-1, transforming growth factor-β1, hepatocyte growth factor, and vascular endothelial growth factor in the culture supernatant were measured by enzyme-linked immunosorbent assays. Moreover, the ASC/PRP admixture was transplanted into the rat calvarial defect. Microcomputed tomography, histological, and immunohistochemical (osteopontin and osteocalcin) analyses were performed at 4 and 8 weeks after transplantation. The in vitro study showed that the levels of growth factors secreted by ASCs were significantly increased by the addition of PRP. Transplantation of the ASC/PRP admixture had dramatic effects on bone regeneration overtime in comparison with rats that received other transplants. Furthermore, some ASCs directly differentiated into osteogenic cells in vivo. These findings suggest that the combination of ASCs and PRP has augmentative effects on bone regeneration. The ASC/PRP admixture may be a promising source for the clinical treatment of cranial defects.


West Nile virus encephalitis with thalamic involvement in an immunocompromised child.
West Nile virus has been an increasingly important pathogen in the United States since it was first reported in 1999. Neuroinvasive West Nile virus has been infrequently reported in the pediatric population. We report a case of severe West Nile virus encephalitis with cranial magnetic resonance imaging findings not yet described in children.


Biosensor immunoassay of ivermectin in bovine milk.
A rapid and sensitive biosensor immunoassay was developed for determination of ivermectin residues in bovine milk. A detection limit of 16.2 ng/mL was achieved. A Biacore optical biosensor based on surface plasmon resonance was used, and a range of extraction techniques was investigated. In the final assay procedure, ivermectin was extracted with acetonitrile followed by C8 solid-phase extraction cleanup. It was proven experimentally that 2 methods of milk storage, freezing or addition of mercury-containing compounds as preservatives, could be used without considerable change in detected concentrations (samples were fortified with ivermectin after storage). The average values for milk samples spiked at 100 and 50 ng/mL concentrations were 102.6 and 51.5 ng/mL, respectively. Extraction and analysis of 20 milk samples were performed within a single working day.


Networking Nanoswitches for ON/OFF Control of Catalysis.
The nanoswitches 1 and 2 are interdependently linked in so-called network states (NetStates). In NetState I, defined by presence of [Cu(1)]+ and 2, the organocatalyst N-methylpyrrolidine catalyzes a conjugate addition. Addition of iron(II) ions as an external chemical trigger to NetState I discharges Cu+ from [Cu(1)]+. The liberated copper(I) ion acts as a second messenger and changes the toggling state at nanoswitch 2. The resulting nanoswitch [Cu(2)]+ captures the catalytically active species from solution and the conjugate addition is turned OFF. Removal of the original trigger reverses the sequence and turns catalysis ON. The ON/OFF catalytic cycle was run three times in situ.


Traumatic bilateral ureteric rupture in two dogs.
Two cases of bilateral ureteric rupture in dogs are reported. Both dogs were presented following road traffic accidents with signs of depression and abdominal distension. Both animals were azotaemic and abdominal fluid analysis was consistent with uroabdomen. In case 1, the injuries affected the proximal portion of both ureters and the dog was euthanased. In case 2, the ruptures were located more distally and a ureteroneocystostomy was performed, with contralateral ureteronephrectomy. This dog is clinically normal 16 months postoperatively.


Dissociation of vasoconstrictor-stimulated basic fibroblast growth factor expression from hypertrophic growth in cultured vascular smooth muscle cells. Relevant roles of protein kinase C.
Thromboxane A2 (TXA2) and angiotensin II (Ang II) stimulate vascular smooth muscle hypertrophy by upregulating endogenous synthesis of basic fibroblast growth factor (bFGF). Because mitogenic phorbol esters can also stimulate bFGF formation, we investigated the role of protein kinase C (PKC) in vascular smooth muscle cell (VSMC) bFGF formation and hypertrophy. Preliminary characterization of PKC isoform expression in VSMC by use of polymerase chain reaction identified PKC alpha, delta, epsilon, and zeta. Western analysis confirmed the presence of these isoforms in cultured VSMC lines and demonstrated downregulation of PKC alpha, delta, and epsilon by phorbol 12-myristate 13-acetate (PMA) but not TXA2 or Ang II. PKC activation with 100 nmol/L PMA stimulated VSMC mitogenesis measured as incorporation of [3H]leucine and [3H]thymidine and increased cell number. Like TXA2 and Ang II, PMA increased endogenous VSMC bFGF in a time-dependent manner, whereas an inactive phorbol ester had no such effect. Addition of an antisense oligodeoxynucleotide against bFGF prevented PMA-stimulated bFGF expression and inhibited PMA-stimulated growth, suggesting that bFGF synthesis is necessary for VSMC growth stimulated by PMA. To clarify the role of PKC in vasoconstrictor-stimulated VSMC production of bFGF and hypertrophy, PKC was down-regulated by prolonged exposure to PMA or was inhibited with calphostin C or staurosporine before the addition of TXA2 or Ang II. PKC inhibition prevented TXA2-stimulated and Ang II--stimulated VSMC hypertrophy without attenuating the observed increase in bFGF expression. Furthermore, PKC inhibition with calphostin C inhibited VSMC mitogenesis stimulated by exogenous bFGF.(ABSTRACT TRUNCATED AT 250 WORDS)


Low-dose oral anticoagulation in patients with mechanical heart valve prostheses: final report from the early self-management anticoagulation trial II.
In mechanical heart valve recipients, low-dose international normalized ratio (INR) self-management of oral anticoagulants can reduce the risk of developing thrombo-embolic events and improve long-term survival compared with INR control by a general practitioner. Here, we present data on the safety of low-dose INR self-management. In a prospective, randomized multi-centre trial, 1346 patients with a target INR range of 2.5-4.5 and 1327 patients with a target INR range of 1.8-2.8 for aortic valve recipients and an INR range of 2.5-3.5 for mitral or double valve recipients were followed up for 24 months. The incidence of thrombo-embolic events that required hospital admission was 0.37 and 0.19% per patient year in the conventional and low-dose groups, respectively (P = 0.79). No thrombo-embolic events occurred in the subgroups of patients with mitral or double valve replacement. The incidence of bleeding events that required hospital admission was 1.52 and 1.42%, respectively (P = 0.69). In the majority of patients with bleeding events, INR values were < 3.0. Mortality rate did not differ between the study groups. Data demonstrate that low-dose INR self-management does not increase the risk of thrombo-embolic events compared with conventional dose INR self-management. Even in patients with low INR target range, the risk of bleeding events is still higher than the risk of thrombo-embolism.


Keratomycosis in and around Chandigarh: a five-year study from a north Indian tertiary care hospital.
To find out the prevalence and epidemiological features of keratomycosis in Chandigarh, the present study was carried out jointly by the Departments of Microbiology and Ophthalmology, Government Medical College Hospital, Chandigarh, over a period of 5 years from January 1999 to December 2003. Corneal scrapings were collected from a total of 154 suspected patients of keratomycosis and were processed and identified by standard laboratory techniques. The study revealed that a total of 64 cases (41.55%) were positive for fungal agents. Direct microscopy was positive in 52 cases (76.47%) and culture in 34 cases (53.12%). Most common fungal isolates were Aspergillus species 14 (41.18%), Fusarium species 8 (23.53%), Candida species 3 (8.82%), Curvularia species 2 (5.88%) and Bipolaris species 2 (5.88%). Thus, hyaline filamentous fungi were the most common etiological agents and mechanical trauma with vegetative matter was the most common predisposing factor. Males in age group of 21-50 years were more commonly affected.


CXC ligand 9 response to malaria during pregnancy is associated with low-birth-weight deliveries.
Placental infection with Plasmodium falciparum is associated with increased levels of proinflammatory cytokines, including tumor necrosis factor alpha (TNF-α) and gamma interferon (IFN-γ), and previous studies have associated increased levels of these cytokines with low birth weight (LBW), especially for malaria-infected primigravidae. To define the contribution of TNF-α and IFN-γ networks to placental-malaria-associated LBW, we measured chemokines induced by TNF-α and IFN-γ and related them to birth weight in a birth cohort of 782 mother-infant pairs residing in an area of P. falciparum holoendemicity in Tanzania. Among primigravidae, levels of CCL2, CXC ligand 9 (CXCL9), and CXCL13 were significantly higher during malaria infection in both the placenta and peripheral blood. Placental CXCL9 and CXCL13 levels were also higher in placental blood from secundigravidae and multigravidae. In multivariate analyses adjusted for known predictors of birth weight, malaria-infected primigravidae with placental CXCL9 levels in the lowest tertile gave birth to babies who weighed 610 g more than babies born to mothers with high CXCL9 levels. CXCL9 expression is induced by IFN-γ, and the strong association between birth weight and placental CXCL9 is consistent with previous observations relating IFN-γ to poor pregnancy outcomes.


Psoriasis Incidence and Lifetime Prevalence: Suggestion for a Higher Mortality Rate in Older Age-classes among Psoriatic Patients Compared to the General Population in Italy.
Data on the psoriasis incidence and prevalence in the Italian population are limited, and a timely and accurate understanding of the disease epidemiology is needed. This ad hoc study investigated psoriasis incidence and lifetime prevalence in a representative sample (n = 14,705) of the Italian population. Information on lifetime history of skin disorders with details about their onset, duration, and treatment was collected. Psoriasis incidence showed a bimodal distribution pattern, with peaks in age classes characteristic of early-onset (35-44 years) and late-onset (65-74 years) psoriasis. Late-onset psoriasis showed some variations according to the sex, with females being diagnosed earlier than males. Lifetime prevalence of psoriasis was 2.7% (95% confidence interval: 2.5-3.0): it increased to 3.5% at age 60-64 years, then decreased steadily after age 64, to 1.7% at age > 74 years. This decrease, despite a peak in incidence rates, after age 64, may suggest a higher mortality rate among psoriasis patients in older age classes, compared to the general population.


Oral absorption, distribution, metabolism, and excretion of icaritin in rats by Q-TOF and UHPLC-MS/MS.
Icaritin (ICT) displays numerous pharmacological activities for the treatment of various cancers, osteoporosis, inflammation, and angiocardiopathy. The absorption, distribution, metabolism, and excretion of ICT still remain unknown. ICT was administered to rats at 2 mg/kg for intravenous injection or 40 mg/kg for oral route. Major metabolite of ICT was identified using quadrupole time-of-flight (Q-TOF), and ICT and its major metabolite were quantified in plasma, tissues, urine, faeces, and bile by ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS). A total of 24 metabolites of ICT in plasma were identified and mono C-7 glucuronide glucuronidated icaritin (GICT) was the major metabolite of ICT after oral administration. The absolute bioavailability of ICT was 4.33% although ICT was rapidly absorbed into the blood. For oral administration, concentrations of GICT at various time points was 6.38-8.81-fold higher than those of ICT, and the area under the curve (AUC) of GICT was about 8-fold higher than that of ICT, while AUC values of ICT and GICT were almost equal for intravenous injection. Approximately 65.7% ICT and 42.7% GICT were distributed in liver and kidney, respectively. Unabsorbed ICT was mainly excreted as the parent form in faeces with at least 60% of administered dose during 24 h, whereas absorbed ICT was predominantly excreted as GICT from urine with 2.74% of administered dose accounting for 63.28% of absorbed drug. ICT was rapidly absorbed into the blood although a large amount of ICT remained unabsorbed, and then rapidly and mainly metabolized to GICT. ICT mainly distributed in liver, while GICT predominantly distributed in kidney. Absorbed ICT and GICT were predominantly excreted via urine, and unabsorbed ICT was mainly excreted as the parent form in faeces. Copyright © 2017 John Wiley & Sons, Ltd.


Ginsenoside Rb1 Promotes Hepatic Glycogen Synthesis to Ameliorate T2DM Through 15-PGDH/PGE2/EP4 Signaling Pathway.
Ginsenoside Rb1 (Rb1), one of the crucial bioactive constituents in Panax ginseng C. A. Mey., possesses anti-type 2 diabetes mellitus (T2DM) property. Nevertheless, the precise mechanism, particularly the impact of Rb1 on hepatic glycogen production, a crucial process in the advancement of T2DM, remains poorly understood. 15-hydroxyprostaglandin dehydrogenase (15-PGDH) is responsible for prostaglandin E2 (PGE2) inactivation. A recent study has reported that inhibition of 15-PGDH promoted hepatic glycogen synthesis and improved T2DM. Therefore, herein, we aimed to investigate whether Rb1 ameliorated T2DM through 15-PGDH/PGE2-regulated hepatic glycogen synthesis. By combining streptozotocin with a high-fat diet, we successfully established a mouse model for T2DM. Afterward, these mice were administered Rb1 or metformin for 8 weeks. An insulin-resistant cell model was established by incubating LO2 cells with palmitic acid. Liver glycogen and PGE2 levels, the expression levels of 15-PGDH, serine/threonine kinase AKT (AKT), and glycogen synthase kinase 3 beta (GSK3β) were measured. Molecular docking was used to predict the binding affinity between 15-PGDH and Rb1. Rb1 administration increased the phosphorylation levels of AKT and GSK3β to enhance glycogen synthesis in the liver of T2DM mice. Molecular docking indicated that Rb1 had a high affinity for 15-PGDH. Moreover, Rb1 treatment resulted in the suppression of elevated 15-PGDH levels and the elevation of decreased PGE2 levels in the liver of T2DM mice. Furthermore, in vitro experiments showed that Rb1 administration might enhance glycogen production by modulating the 15-PGDH/PGE2/PGE2 receptor EP4 pathway. Our findings indicate that Rb1 may enhance liver glycogen production through a 15-PGDH-dependent pathway to ameliorate T2DM, thereby offering a new explanation for the positive impact of Rb1 on T2DM and supporting its potential as an effective therapeutic approach for T2DM.


A gene for isolated congenital ptosis maps to a 3-cM region within 1p32-p34.1.
Hereditary isolated congenital ptosis is an autosomal dominant disorder with incomplete penetrance characterized by a variable degree of unilateral or bilateral drooping of the upper eyelids. We report linkage of this disorder in a large family to markers on chromosome 1p. In our sample of 37 meioses, nine informative markers did not recombine with the disease. D1S2677 gave a maximum two-point LOD score of 8.8 on the assumption of 90% penetrance (theta = 0). D1S447/2733 and D1S1616 flank the disease locus, with two-point LOD scores of 5.6/6.6 (theta = .04) and 4.9 (theta = .05), respectively, defining a region of 2.8 cM. FISH of YACs containing flanking recombinant markers localizes the gene to chromosome 1p32-p34.1. These data establish a map location for an isolated congenital ptosis gene and demonstrate that this disorder is genetically distinct from other extraocular muscle-specific disorders such as congenital fibrosis of the extraocular muscles and blepharophimosis.


Ring systems in mutagenicity databases.
The distribution of ring systems in public mutagenicity databases is analyzed. An automated enumeration of substructures permits determination of the occurrence of different scaffolds in data sets. The counts are used to perform population analysis via proportions and odds ratios of mutagenic compounds. Pairwise calculations of odds ratios between scaffolds allow comparison of ring systems for isostere replacement studies. These findings are presented in tables that readily show which scaffold is likely to occur in mutagenic compounds. Also, rings identified in public domain mutagenicity data sets are compared to rings in drugs data sets; unfortunately, public mutagenicity data sets do not reflect the types of scaffolds in drugs and those typically used in medicinal chemistry. The findings bring into question the utility of predictive models that were derived from public domain data sets. The automated ring identification and statistical approaches used here can be applied to other pharmacological properties to yield information about chemical scaffolds.


[Isoproterenol, denopamine, and atenolol-induced alterations in beta-adrenergic receptor-adenylate cyclase system of rat myocardium].
Catecholamines (CAs) had been used for the treatment of congestive heart failure (CHF). However, since continuous administration of CAs develops tolerance in hemodynamics presumably due to desensitization of beta-adrenergic receptor (beta AR)-adenylate cyclase (AC) system, beta antagonist, instead of beta agonist, has recently been employed to treat CHF, in that it may recover beta AR-AC system. In this study, the precise mechanisms of alterations in cardiac beta AM-AC system after chronic administration of beta agonist or antagonist, were investigated. The rats were treated continuously for 14 days with saline, isoproterenol (ISO), atenolol (ATENO), or denopamine (DENO), a new positive inotropic agent with beta 1 selective AR agonistic properties, which is reported to hardly cause the tolerance in clinical studies. beta AR density (Bmax) was markedly reduced by ISO and slightly increased by ATENO. Forskolin stimulated cyclase activity was reduced markedly by ISO. Total amount of the pertussis toxin substrates (inhibitory G-protein; Gi) and cholera toxin substrates (stimulatory G-protein; Gs) were not different among 4 groups. However, Gs activity measured by human platelet reconstitutive assay was reduced by ISO and DENO. These results indicate that ISO-induced desensitization in caused by the reduction in Gs and AC-catalytic activity as well as by the down-regulation of beta AR. Furthermore, it is suggested that DENO may cause slight desensitization of beta AR-AC system due to reduced Gs activity.


Bleeding detection in wireless capsule endoscopy videos - Color versus texture features.
Wireless capsule endoscopy (WCE) is an effective technology that can be used to make a gastrointestinal (GI) tract diagnosis of various lesions and abnormalities. Due to a long time required to pass through the GI tract, the resulting WCE data stream contains a large number of frames which leads to a tedious job for clinical experts to perform a visual check of each and every frame of a complete patient's video footage. In this paper, an automated technique for bleeding detection based on color and texture features is proposed. The approach combines the color information which is an essential feature for initial detection of frame with bleeding. Additionally, it uses the texture which plays an important role to extract more information from the lesion captured in the frames and allows the system to distinguish finely between borderline cases. The detection algorithm utilizes machine-learning-based classification methods, and it can efficiently distinguish between bleeding and nonbleeding frames and perform pixel-level segmentation of bleeding areas in WCE frames. The performed experimental studies demonstrate the performance of the proposed bleeding detection method in terms of detection accuracy, where we are at least as good as the state-of-the-art approaches. In this research, we have conducted a broad comparison of a number of different state-of-the-art features and classification methods that allows building an efficient and flexible WCE video processing system.


Glutamine Transporter SLC1A5 Regulates Ionizing Radiation-Derived Oxidative Damage and Ferroptosis.
Ionizing radiation-derived oxidative stress and ferroptosis are one of the most important biological effects on destroying the liver tumor, whereas radioresistance of liver tumor remains a leading cause of radiotherapy (RT) failure mainly because of the protective antiferroptosis, in which oxidative stress and subsequent lipid peroxidation are the key initiators. Thus, it is of great importance to overcome ferroptosis resistance to improve the therapeutic efficacy of RT in liver tumor patients. Irradiation-resistant HepG2 cells (HepG2-IRR) were established by long-term exposure to X-ray (2 to 8 Gy), and targeted metabolomics analysis revealed an obvious increase in intracellular amino acids in HepG2-IRR cells upon ferroptosis stress. Among these amino acids with obvious changes, N-acetylglutamine, a derivative of glutamine, is essential for the redox homeostasis and progression of tumor cells. Interestingly, the treatment of glutamine starvation could promote the ferroptosis effect significantly, whereas glutamine supplementation reversed the ferroptosis effect completely. Consistent with the changes in amino acids pattern, the glutamine transporter SLC1A5 was verified in liver tumor samples from TCGA training and validation cohorts as an independent prognostic amino acid-ferroptosis gene (AFG). A risk score for screening prognosis based on the SLC1A5, SLC7A11, ASNS, and TXNRD1 demonstrated that a high-risk score was correlated with poor survival. In vitro studies had shown that the knockdown of SLC1A5 resulted in a significant decrease in cell viability and promoted lipid peroxidation and oxidative damage introduced by irradiation (10 Gy). Collectively, our findings indicated that SLC1A5 may act as a suppressor gene against ferroptosis and can be a potential target for ionizing radiation mediated effects.


Single-Cell Genomics Reveals the Divergent Mitochondrial Genomes of Retaria (Foraminifera and Radiolaria).
Mitochondria originated from an ancient bacterial endosymbiont that underwent reductive evolution by gene loss and endosymbiont gene transfer to the nuclear genome. The diversity of mitochondrial genomes published to date has revealed that gene loss and transfer processes are ongoing in many lineages. Most well-studied eukaryotic lineages are represented in mitochondrial genome databases, except for the superphylum Retaria-the lineage comprising Foraminifera and Radiolaria. Using single-cell approaches, we determined two complete mitochondrial genomes of Foraminifera and two nearly complete mitochondrial genomes of radiolarians. We report the complete coding content of an additional 14 foram species. We show that foraminiferan and radiolarian mitochondrial genomes contain a nearly fully overlapping but reduced mitochondrial gene complement compared to other sequenced rhizarians. In contrast to animals and fungi, many protists encode a diverse set of proteins on their mitochondrial genomes, including several ribosomal genes; however, some aerobic eukaryotic lineages (euglenids, myzozoans, and chlamydomonas-like algae) have reduced mitochondrial gene content and lack all ribosomal genes. Similar to these reduced outliers, we show that retarian mitochondrial genomes lack ribosomal protein and tRNA genes, contain truncated and divergent small and large rRNA genes, and contain only 14 or 15 protein-coding genes, including nad1, -3, -4, -4L, -5, and -7, cob, cox1, -2, and -3, and atp1, -6, and -9, with forams and radiolarians additionally carrying nad2 and nad6, respectively. In radiolarian mitogenomes, a noncanonical genetic code was identified in which all three stop codons encode amino acids. Collectively, these results add to our understanding of mitochondrial genome evolution and fill in one of the last major gaps in mitochondrial sequence databases. IMPORTANCE We present the reduced mitochondrial genomes of Retaria, the rhizarian lineage comprising the phyla Foraminifera and Radiolaria. By applying single-cell genomic approaches, we found that foraminiferan and radiolarian mitochondrial genomes contain an overlapping but reduced mitochondrial gene complement compared to other sequenced rhizarians. An alternative genetic code was identified in radiolarian mitogenomes in which all three stop codons encode amino acids. Collectively, these results shed light on the divergent nature of the mitochondrial genomes from an ecologically important group, warranting further questions into the biological underpinnings of gene content variability and genetic code variation between mitochondrial genomes.


Cerebrospinal Fluid Biomarkers for Diagnosis and the Prognostication of Acute Ischemic Stroke: A Systematic Review.
Despite the high incidence and burden of stroke, biological biomarkers are not used routinely in clinical practice to diagnose, determine progression, or prognosticate outcomes of acute ischemic stroke (AIS). Because of its direct interface with neural tissue, cerebrospinal fluid (CSF) is a potentially valuable source for biomarker development. This systematic review was conducted using three databases. All trials investigating clinical and preclinical models for CSF biomarkers for AIS diagnosis, prognostication, and severity grading were included, yielding 22 human trials and five animal studies for analysis. In total, 21 biomarkers and other multiomic proteomic markers were identified. S100B, inflammatory markers (including tumor necrosis factor-alpha and interleukin 6), and free fatty acids were the most frequently studied biomarkers. The review showed that CSF is an effective medium for biomarker acquisition for AIS. Although CSF is not routinely clinically obtained, a potential benefit of CSF studies is identifying valuable biomarkers from the pathophysiologic microenvironment that ultimately inform optimization of targeted low-abundance assays from peripheral biofluid samples (e.g., plasma). Several important catabolic and anabolic markers can serve as effective measures of diagnosis, etiology identification, prognostication, and severity grading. Trials with large cohorts studying the efficacy of biomarkers in altering clinical management are still needed.


Assisted breech delivery with transverse vaginal septum.
The incidence of vaginal septum is rare. The infrequency of this anomaly makes accurate estimates of the true incidence very difficult to obtain. Diagnosis is based on careful historyand examination. This is the case of a patient who presented with transverse vaginal septum in labour and breech presentation. The septum was resected and the foetus delivered normally. Careful vaginal examination should be performed in pregnant women at term before labour to detect such manageable abnormalities.


Development of devices for self-injection: using tribological analysis to optimize injection force.
This article describes the use of analytical models and physical measurements to characterize and optimize the tribological behavior of pen injectors for self-administration of biopharmaceuticals. One of the main performance attributes of this kind of device is its efficiency in transmitting the external force applied by the user on to the cartridge inside the pen in order to effectuate an injection. This injection force characteristic is heavily influenced by the frictional properties of the polymeric materials employed in the mechanism. Standard friction tests are available for characterizing candidate materials, but they use geometries and conditions far removed from the actual situation inside a pen injector and thus do not always generate relevant data. A new test procedure, allowing the direct measurement of the coefficient of friction between two key parts of a pen injector mechanism using real parts under simulated use conditions, is presented. In addition to the absolute level of friction, the test method provides information on expected evolution of friction over lifetime as well as on expected consistency between individual devices. Paired with an analytical model of the pen mechanism, the frictional data allow the expected overall injection system force efficiency to be estimated. The test method and analytical model are applied to a range of polymer combinations with different kinds of lubrication. It is found that material combinations used without lubrication generally have unsatisfactory performance, that the use of silicone-based internal lubricating additives improves performance, and that the best results can be achieved with external silicone-based lubricants. Polytetrafluoroethylene-based internal lubrication and external lubrication are also evaluated but found to provide only limited benefits unless used in combination with silicone.


Epidemiology and changes in patient-related factors from 1997 to 2009 in clinical yeast isolates related to dermatology, gynaecology, and paediatrics.
From 1997 to 2009, 1,862 dermatology, gynaecology, and paediatrics (DGP) associated clinical yeast isolates were analysed for species occurrence, specimen origin and type, (multi-) resistance pattern, and testing period. The top seven of the isolated DGP-associated species remained the same as compared to total medical wards, with Candida albicans (45%) as most frequent pathogen. However, the DGP wards and DGP ICUs showed species-specific profiles; that is, the species distribution is clinic-specific similar and however differs in their percentage from ward to ward. By applying the "one fungus one name" principle, respectively, the appropriate current taxonomic species denominations, it has been shown that no trend to emerging species from 1998 to 2008 could be detected. In particular the frequently isolated non-Candida albicans species isolated in the DGP departments have already been detected in or before 1997. As yeasts are part of the cutaneous microbiota and play an important role as opportunistic pathogens for superficial infections, proper identification of the isolates according to the new nomenclature deems to be essential for specific and calculated antifungal therapy for yeast-like DGP-related infectious agents.


Phosphorylated resveratrol as a protein aggregation suppressor in vitro and in vivo.
The stability of proteins in solution poses a great challenge for both technical applications and molecular biology, including neurodegenerative diseases. In this work, a phosphorylated resveratrol material was examined for its anti-aggregation properties in vitro and in vivo. Here, an anti-fibrillation effect could be measured for amyloid beta and human insulin in vitro and general anti-aggregation properties for crude chicken egg white in solution. Using a drosophila fly model for the overexpression of amyloid beta protein, changes in physiological protein aggregation and improved locomotor abilities could be observed in the presence of dietary phosphorylated resveratrol.


First report of grapevine virus H (GVH) in grapevine in Greece.
Grapevine virus H (GVH) is a member of the genus Vitivirus in the family Betaflexiviridae (subfamily Trivirinae, order Tymovirales) that infects grapevine (Candresse et al., 2018). GVH was first identified in a symptomless grapevine of an unknown cultivar from Portugal in 2018 (Candresse et al. 2018), and since then the virus has been reported only from California (Diaz‑Lara et al. 2019). Several vitiviruses have been detected in Greek vineyards (Avgelis and Roubos 2000; Dovas and Katis 2003a; 2003b; Panailidou et al. 2019; Lotos et al. 2020), but no information was available on the presence of GVH. In the fall of 2020, in order to investigate the virome of a commercial vineyard of the cultivar Assyrtiko in northern Greece, a composite sample was made of leaves and petioles from nine vines exhibiting leafroll disease symptoms. Total RNA was extracted from the composite sample according to the protocol of White et al. (2008) and subjected to rRNA depletion, library construction (TruSeq Stranded Total RNA kit), and high-throughput sequencing (HTS) in a NovaSeq6000 platform (Illumina Inc.) at Macrogen (Korea). The resulting ~42 million 101-nt paired-end reads were analyzed in Geneious Prime 2020, and the assembled de novo contigs were subjected to a local BLASTn search, which revealed the presence of 18 grapevine infecting viruses and viroids, among which also a GVH-like contig (GeA-9). GeA-9 was 7,404 nucleotides (nt) long, covering 99.4% of the full virus genome and shared 98.2 % nt identity with a GVH isolate from the USA (MN716768). To confirm the presence of GVH, the nine samples of the cultivar Assyrtiko, used initially to produce the composite sample for HTS analysis, were tested individually by RT-PCR, using the primers GVH_F_2504 (5'-CTGCTTCGCTGAACATATGC-3') and GVH_R_2835 (5'-ATCATTRTGATCGAGAGAGTAGTG-3') that amplify a 331-nt segment of ORF1. GVH was detected in five out of the nine tested samples and one of these was reamplified and subjected to Sanger sequencing. The fragment of ORF1 obtained by Sanger sequencing (MW460005) was 97.5% identical to the nucleotide sequence of the corresponding GVH-like de novo contig (GeA-9) from HTS analysis and it shared 97.2% nt identity with GVH sequences reported from Portugal and USA, respectively (NC_040545 and MN716768), confirming the presence of GVH in the tested samples. This is the first report of GVH in grapevine in Greece, thus further increasing the number of vitiviruses known to infect Greek vineyards and also expanding the number of geographic locations in which GVH is recorded so far.


Prenatal diagnosis of type 1 fibular hemimelia.
Fibular hemimelia (FH) is a congenital longitudinal limb deficiency characterized by complete or partial absence of the fibula. Typically, it has been diagnosed at birth, when the neonate is seen to have lower limb shortening and a foot with missing toes. Although it is the most frequent lower limb deficiency anomaly, there are few published reports of prenatally diagnosed cases. Most of these published cases have involved the complete absence of the fibula, which is relatively easy to diagnose with antenatal ultrasound. In our opinion, our case is the first case of unilateral partial absence of the fibula detected using prenatal ultrasound imaging. Herein, we report a FH case associated with foot equinovalgus, and absence of the fourth and fifth foot rays diagnosed at 24 weeks' gestation. The anomaly was confirmed after birth by X-ray, and conservative orthopedic management was chosen. Our case shows that partial limb defects can also be detected by prenatal ultrasound imaging.


Torque expression by active and passive self-ligating brackets in patients with four premolar extractions: A retrospective study.
Appropriate torque expression contributes to ideal treatment outcomes both clinically and aesthetically. Whether active and passive self-ligating brackets (SLBs) have different torque-control capability in vivo has never been reported. The purpose of present study was to explore whether there was difference in torque expression in active and passive SLBs. In this retrospective study, 225 patients with four first premolar extractions were enrolled. For each patient, the digital lateral cephalometric radiographs were taken before and after treatment. The study consisted of 2 groups: 111 subjects were treated with passive SLBs (Damon Q, Ormco) and 114 subjects with active SLBs (Empower 2, American Orthodontics). Measurements to determine skeletal changes and incisor inclination were obtained from cephalometric tracings using Dolphin software (version 11.8, USA). Comparisons in both groups and intergroups were compared using t tests and chi-square test. Significant differences in the variation of U1-SN(°), U1-NA(°), L1-NB(°) and L1-FH(°) were found between two groups. More labially inclined maxillary incisors were found in active SLB group, while more labially inclined mandibular incisors were observed in passive SLB group. With the present prescription set in the two brackets, active SLBs achieved more proclined maxillary incisors and retroclined mandibular incisors. Clinicians should take torque expression of brackets into consideration during orthodontic treatment.


High-frequency measurements of blast wave propagation.
Blast wave propagation measurements were conducted to investigate nonlinear propagation effects on blast waveform evolution with distance. Measurements were made with a wide-bandwidth capacitor microphone for comparison with conventional 3.175-mm (1/8-in.) microphones with and without baffles. It was found that the 3.175-mm microphone did not have sufficient high-frequency response to capture the actual rise times in some regions. For a source of 0.57 kg (1.25 lb) of C-4 plastic explosive, the trend observed is that nonlinear effects steepened the waveform, thereby decreasing the shock rise time, up to a range of 50 m. At 100 m, the rise times had increased slightly.


[Magnetic resonance imaging of the mediastinal vessels in pediatric patients].
The appearance of new and better magnetic resonance imaging (MRI) techniques have made the MRI a very important imaging method for the evaluation of thoracic vessels in pediatrics. The 3D angio-MRI using GD is capable of clearly demonstrating the morphology of the aorta and pulmonary vessels. The MRI may significantly reduce the number of angiographies needed and, in some patients, may even provide additional information to the angiography.


Sodium polyanethol sulfonate inactivation of aminoglycosides.
Sodium polyanethol sulfonate and another polyanion (dextran sulfate) both inhibited aminoglycoside activity in vitro. This effect was not produced by an otherwise similar neutral carbohydrate (dextran) or by neutral detergents (Brij-35, Triton X-100) but was antagonized by an anion-exchange resin (Dowex 1X8-50). We conclude that the inactivation of aminoglycosides by sodium polyanethol sulfonate results from its polyanionic nature and is unrelated to its detergent properties.


The goat alphas1-casein gene: gene structure and promoter analysis.
The level of alphas1-casein in goat milk shows strong variations determined by at least 15 alleles associated with four different efficiencies of protein synthesis. The nucleotide sequence of the whole goat alphas1-casein-encoding gene (CSN1S1) plus 1973 nucleotides at the 5' flanking region and 610 nucleotides at the 3' flanking region was determined and aligned with its bovine counterpart. The gene is spread over 16.7 kb and consists of 19 exons varying in length from 24 bp (exons 5, 6, 7, 8, 10, 13 and 16) to 385 bp (exon 19) and 18 introns from 90 bp of intron 10 to 1685 bp of intron 2. Furthermore, highly conserved sequences, mainly located in the 5' flanking region, were found between this gene and other casein-encoding genes. Finally, seven interspersed repeated elements (10 in the bovine CSN1S1 gene) were also identified at four different locations of the sequenced region: 5' untranscribed region and introns 2, 8 and 11.


Hydroxyapatite-Derived Heterogeneous Ru-Ru2 P Electrocatalyst and Environmentally-Friendly Membrane Electrode toward Efficient Alkaline Electrolyzer.
Alkaline membrane water electrolysis is a promising production technology, and advanced electrocatalyst and membrane electrode design have always been the core technology. Herein, an ion-exchange method and an environmentally friendly in situ green phosphating strategy are successively employed to fabricate Ru-Ru2 P heterogeneous nanoparticles by using hydroxyapatite (HAP) as a phosphorus source, which is an exceptionally active electrocatalyst for hydrogen evolution reaction (HER). Density functional theory calculation results reveal that strong electronic redistribution occurs at the heterointerface of Ru-Ru2 P, which modulates the electronic structure to achieve an optimized hydrogen adsorption strength. The obtained Ru-Ru2 P possesses excellent HER performance (24 mV at 10 mA cm-2 ) and robust stability (1000 mA cm-2 for 120 h) in alkaline media. Furthermore, an environmentally friendly membrane electrode with a sandwich structure is assembled by HAP nanowires as an alkaline membrane, Ru-Ru2 P as a cathodic catalyst, and NiFe-LDH as an anodic catalyst, respectively. The voltage of (-) Ru-Ru2 P || NiFe-LDH/CNTs (+) (1.53 V at 10 mA cm-2 ) is lower than that of (-) 20 wt% Pt/C || RuO2 (+) (1.60 V at 10 mA cm-2 ) for overall water splitting. Overall, the studies not only design an efficient catalyst but also provide a new route to achieve a high-stability electrolyzer for industrial H2 production.


Effective diameters of ion channels formed by homologs of the antibiotic chrysospermin.
Radii of ion channels formed in the lipid bilayer by 4 homologs of the alamethicin-like antibiotic, chrysospermin, were determined using hydrophilic nonelectrolytes. It is shown that the replacement of isovaline amino acid at position 15 of the polypeptide chain by alpha-aminoisobutyric acid results in the decrease in the channel effective radius from 1.2 +/- 0.15 to 0.94 +/- 0.1 nm and a respective 2.5-fold decrease in channel conductance.


Sterol-dependent regulation of sphingolipid metabolism in Saccharomyces cerevisiae.
We had previously isolated the temperature-sensitive erg26-1 mutant and characterized the sterol defects in erg26-1 cells (Baudry, K., Swain, E., Rahier, A., Germann, M., Batta, A., Rondet, S., Mandala, S., Henry, K., Tint, G. S., Edlind, T., Kurtz, M., and Nickels, J. T., Jr. (2001) J. Biol. Chem. 276, 12702-12711). We have now determined the defects in sphingolipid metabolism in erg26-1 cells, examined their effects on cell growth, and initiated studies designed to elucidate how might changes in sterol levels coordinately regulate sphingolipid metabolism in Saccharomyces cerevisiae. Using [(3)H]inositol radiolabeling studies, we found that the biosynthetic rate and steady-state levels of specific hydroxylated forms of inositolphosphorylceramides were decreased in erg26-1 cells when compared with wild type cells. [(3)H]Dihydrosphingosine radiolabeling studies demonstrated that erg26-1 cells had decreased levels of the phytosphingosine-derived ceramides that are the direct precursors of the specific hydroxylated inositol phosphorylceramides found to be lower in these cells. Gene dosage experiments using the sphingolipid long chain sphingoid base (LCB) hydroxylase gene, SUR2, suggest that erg26-1 cells may accumulate LCB, thus placing one point of sterol regulation of sphingolipid synthesis possibly at the level of ceramide metabolism. The results from additional genetic studies using the sphingolipid hydroxylase and copper transporter genes, SCS7 and CCC2, respectively, suggest a second possible point of sterol regulation at the level of complex sphingolipid hydroxylation. In addition, [(3)H]inositol radiolabeling of sterol biosynthesis inhibitor-treated wild type cells and late sterol pathway mutants showed that additional blocks in sterol biosynthesis have profound effects on sphingolipid metabolism, particularly sphingolipid hydroxylation state. Finally, our genetic studies in erg26-1 cells using the LCB phosphate phosphatase gene, LBP1, suggest that increasing the levels of the LCB sphingoid base phosphate can remediate the temperature-sensitive phenotype of erg26-1 cells.


Transcriptomic analysis of the late stages of grapevine (Vitis vinifera cv. Cabernet Sauvignon) berry ripening reveals significant induction of ethylene signaling and flavor pathways in the skin.
Grapevine berry, a nonclimacteric fruit, has three developmental stages; the last one is when berry color and sugar increase. Flavors derived from terpenoid and fatty acid metabolism develop at the very end of this ripening stage. The transcriptomic response of pulp and skin of Cabernet Sauvignon berries in the late stages of ripening between 22 and 37 °Brix was assessed using whole-genome micorarrays. The transcript abundance of approximately 18,000 genes changed with °Brix and tissue type. There were a large number of changes in many gene ontology (GO) categories involving metabolism, signaling and abiotic stress. GO categories reflecting tissue differences were overrepresented in photosynthesis, isoprenoid metabolism and pigment biosynthesis. Detailed analysis of the interaction of the skin and pulp with °Brix revealed that there were statistically significantly higher abundances of transcripts changing with °Brix in the skin that were involved in ethylene signaling, isoprenoid and fatty acid metabolism. Many transcripts were peaking around known optimal fruit stages for flavor production. The transcript abundance of approximately two-thirds of the AP2/ERF superfamily of transcription factors changed during these developmental stages. The transcript abundance of a unique clade of ERF6-type transcription factors had the largest changes in the skin and clustered with genes involved in ethylene, senescence, and fruit flavor production including ACC oxidase, terpene synthases, and lipoxygenases. The transcript abundance of important transcription factors involved in fruit ripening was also higher in the skin. A detailed analysis of the transcriptome dynamics during late stages of ripening of grapevine berries revealed that these berries went through massive transcriptional changes in gene ontology categories involving chemical signaling and metabolism in both the pulp and skin, particularly in the skin. Changes in the transcript abundance of genes involved in the ethylene signaling pathway of this nonclimacteric fruit were statistically significant in the late stages of ripening when the production of transcripts for important flavor and aroma compounds were at their highest. Ethylene transcription factors known to play a role in leaf senescence also appear to play a role in fruit senescence. Ethylene may play a bigger role than previously thought in this non-climacteric fruit.


Upper gastrointestinal bleeding from duodenal vascular ectasia in a patient with cirrhosis.
We report a cirrhotic patient with duodenal vascular ectasia and spontaneous bleeding. The bleeding was successfully controlled with argon plasma coagulation. Duodenal vascular ectasia may be a cause of upper gastrointestinal bleeding in patients with cirrhosis, and argon plasma coagulation may be effective and safe to achieve hemostasis of this lesion.


Serum lipids in patients with psoriasis.
In 13 patients with psoriasis a lower total cholesterol (TC) concentration was found compared to healthy controls of the same population. No differences in the concentration of serum triglyceride (TG) or phospholipids (PL) were detected between these two groups. In the same patients, serum triglyceride fatty acid analyses showed a reduced concentration of linoleic acid and a raised level of palmitoleic and myristic acids. No differences were detected in the major phospholipid fractions. The increase in plasma free fatty acids (FFA) following intravenous heparin was comparable in the psoriatic patient and in the controls. It is concluded that no basic abnormality of serum lipids exists and that the changes described were due to a selective loss via the scales or due to malabsorption.


Targeted Evolution of Embedded Librarian Services: Providing Mobile Reference and Instruction Services Using iPads.
The University at Buffalo Health Sciences Library provides reference and instructional services to support research, curricular, and clinical programs of the University at Buffalo. With funding from an NN/LM MAR Technology Improvement Award, the University at Buffalo Health Sciences Library (UBHSL) purchased iPads to develop embedded reference and educational services. Usage statistics were collected over a ten-month period to measure the frequency of iPad use for mobile services. While this experiment demonstrates that the iPad can be used to meet the library user's needs outside of the physical library space, this article will also offer advice for others who are considering implementing their own program.


Pneumonitis, pleural effusion and pericarditis following treatment with dantrolene.
A patient developed pulmonary infiltration, pleural effusions and pericarditis three months after starting dantrolene sodium. Peripheral blood eosinophilia and a raised ESR were present. Symptoms and signs resolved after the drug was discontinued. Dantrolene toxicity should be considered in the differential diagnosis of pneumonitis and pleuro-pericarditis.


Angiotensin II type 1 receptor blockers prevent aortic arterial stiffness in elderly patients with hypertension.
Backgrounds and aims: Increased arterial stiffness may increase cardiovascular morbidity and mortality. Angiotensin II type 1 receptor blockers (ARBs) are potentially useful in controlling the central blood pressure and arterial stiffness in mild to moderate essential hypertension, while the effects of ARBs in aged patients with essential hypertension are not entirely investigated. Methods: The carotid-femoral arterial pulse wave velocity (PWV) was measured in aged patients with essential hypertension. Results: In a cross-sectional study, PWV value was significantly higher in these old patients with essential hypertension, compared to patients without essential hypertension. In correlation analysis, PWV was associated positively with age, hypertension duration, and carotid atherosclerosis. However, there was no relationship between PWV and gender in aged patients with essential hypertension. In a perspective study, 6-12 months administration of ARBs (losartan, 50 mg/day; telmisartan, 40 mg/day; valsartan 80 mg/day; irbesartan, 150 mg/day) remarkably reduced PWV in aged patients with essential hypertension. Regression analyses of multiple factors indicated that the effects of ARBs on arterial stiffness were not associated with the reduction of blood pressure. Conclusion: ARB treatment is a negative risk factor of arterial stiffness in aged patients with essential hypertension.


A survey of magnetic fields in the dental operatory.
Recently, there has been growing concern regarding the biological effects of occupational exposure to weak time-varying magnetic fields, especially those in the extremely low-frequency range (0.1-100.0 Hz). This study examined some potential sources and intensities of 60 Hz magnetic fields produced in the dental environment. A random sample of general dental offices and selected specialty offices was visited, and the magnetic fields associated with ultrasonic scalers, amalgamators, composite light curing units, X-ray view boxes and chair lights were measured. The median 60 Hz field strengths measured at various running speeds (off, standby, low and high) and the distances from the equipment (0, 15 and 30 cm) ranged from 1.2 to 2,225 milligauss (mG). Field strengths fell off quickly with distance, but were less affected by the running speed of the equipment. They also varied among the five types of equipment tested. This was likely due to variations in the make, model and age of the equipment. The 60 Hz magnetic field strengths recorded in the dental operatory were comparable to those reported from measurements of common household appliances. However, in view of recent concerns with respect to the possible effects of magnetic fields, it is suggested that exposures be minimized and the concept of prudent avoidance be employed.


Melatonin, immune modulation and aging.
Melatonin is a hormone secreted by the pineal gland in response to photoperiods and influences many important biological processes. For one, Melatonin has been shown to produce resistance to cancer and infectious diseases in aged animals. Studies in animals have demonstrated melatonin-related mechanisms of action on immunoregulation. Additionally, melatonin has been successfully used in humans, along with interleukin-2, as a treatment of solid tumors. In vivo and in vitro studies show melatonin enhances both natural and acquired immunity in animals. Despite all of this intriguing evidence, melatonin's mechanism of action on the immune system is only partially defined. It does, however, appear to act through lymphocyte receptors, and perhaps, receptors on other immune tissues, to modulate immune cells. In order to understand immunomodulation and anti-cancer effects, information on melatonin and it's interactions with other endocrine hormones are summarized.


Seasonal variations of severe hypoglycemia in patients with type 1 diabetes mellitus, type 2 diabetes mellitus, and non-diabetes mellitus: clinical analysis of 578 hypoglycemia cases.
Blood glucose control in patients with diabetes mellitus (DM) is reportedly influenced by the seasons, with hemoglobin A1c (HbA1c) levels decreasing in the summer or warm season and increasing in the winter or cold season. In addition, several studies have shown that sepsis is also associated with the seasons. Although both blood glucose control and sepsis can strongly affect the occurrence of severe hypoglycemia, few studies have examined the seasonal variation of severe hypoglycemia. The aim of the present study is to examine the association between severe hypoglycemia and the seasons in patients with type 1 diabetes mellitus (T1DM), type 2 diabetes mellitus (T2DM), and non-diabetes mellitus (non-DM). We retrospectively reviewed all the patients with severe hypoglycemia at a national center in Japan between April 1, 2006 and March 31, 2012. A total of 57,132 consecutive cases that had visited the emergency room by ambulance were screened, and 578 eligible cases of severe hypoglycemia were enrolled in this study. The primary outcome was to assess the seasonality of severe hypoglycemia. In the T1DM group (n = 88), severe hypoglycemia occurred significantly more often in the summer than in the winter (35.2% in summer vs 18.2% in winter, P = 0.01), and the HbA1c levels were highest in the winter and lowest in the summer (9.1% [7.6%-10.1%] in winter vs 7.7% [7.1%-8.3%] in summer, P = 0.13). In the non-DM group (n = 173), severe hypoglycemia occurred significantly more often in the winter than in the summer (30.6% in winter vs 19.6% in summer, P = 0.01), and sepsis as a complication occurred significantly more often in winter than in summer (24.5% in winter vs 5.9% in summer, P = 0.02). In the T2DM group (n = 317), the occurrence of severe hypoglycemia and the HbA1c levels did not differ significantly among the seasons. The occurrence of severe hypoglycemia might be seasonal and might fluctuate with temperature changes. Patients should be treated more carefully during the season in which severe hypoglycemia is more common.


Lung proliferation is dependent on the duration not the timepoint of tracheal occlusion in nitrofen rats with diaphragmatic hernia.
Prenatal tracheal occlusion (TO) promotes lung growth and is applied clinically in fetuses with congenital diaphragmatic hernia (CDH). Limited data are available regarding the effect of duration versus timepoint of TO. Our objective was to document the impact of TO on lung development in the near-term period in rats with nitrofen-induced CDH. Nitrofen was administered on embryonic day (ED)9 and fetal TO was performed on ED18.5, 19, or 20 (term = ED22). Sham-operated and untouched littermates served as controls. Lungs were harvested in 0.5-day steps and only fetuses with a left-sided CDH were included in further analyses. Healthy fetuses provided a reference for normal near-term lung development. Duration of TO in the nitrofen rat model for CDH predicts lung growth in terms of lung-body-weight ratio as well as an increased mRNA level of the proliferation marker Ki67. Longer TO also induced a more complex airway architecture. The timepoint of TO was not predictive of lung growth. In the nitrofen rat model of CDH, a longer period of TO leads to enhanced lung growth and more refined airway architecture.


Overexpression of MYC binding protein promotes invasion and migration in gastric cancer.
Gastric cancer (GC) is the second leading cause of cancer-associated mortality worldwide. Although the mortality rate of patients with GC has improved, it remains a significant health issue. The MYC proto-oncogene protein serves key roles in cellular proliferation, differentiation, transformation and apoptosis. Previous studies have identified the abnormal expression of MYC-binding protein (MYCBP) during tumorigenesis in multiple types of cancer. Furthermore, evidence demonstrates that the abnormal expression of MYCBP contributes to the invasion and migration of human cancer types, including colon cancer and glioma; however, its influence on GC remains unclear. In the present study, the expression of MYCBP in GC cells and tissues was analyzed by reverse transcription-quantitative polymerase chain reaction. Additionally, GC cell lines were transfected with small interfering RNAs against MYCBP or lymphoid enhancer-binding factor 1 (LEF-1) and assessed by in vitro transwell migration and invasion assays. The results indicated that the expression of MYCBP in GC cells and tissues was markedly increased compared with a normal gastric epithelial cell line and adjacent normal gastric mucosal tissues, respectively. Furthermore, MYCBP downregulation notably inhibited the metastatic capacity of GC cells, and LEF-1 knockdown was found to downregulate the expression of MYCBP. On the basis of the findings of the present study, MYCBP may be a direct target of the β-catenin/LEF-1 pathway via binding LEF-1, and could potentially be used as a biomarker for the diagnosis and prognosis of GC.