High-k Fluoropolymer Gate Dielectric in Electrically Stable Organic Field-Effect Transistors.
A detailed study of a high-k fluoropolymer gate dielectric material, poly(vinylidene fluoride- co-hexafluoropropylene) [P(VDF-HFP)], is presented as a guide to achieve low operational voltage and electrically stable device performance. The large dipole moment of C-F dipoles in P(VDF-HFP) is responsible for its high dielectric constant as well as its potentially ferroelectric behavior that must be minimized to avoid hysteretic current-voltage characteristics. A range of material grades and processing conditions are explored and are shown to have a significant effect on the degree of hysteresis observed in device-transfer characteristics. The percentage of HFP monomer in the P(VDF-HFP) dielectric has an effect on gate-dependent mobility induced by disorder at the semiconductor-dielectric interface. Most importantly, we present the considerations that must be made to achieve optimal performance in multiple device architectures of organic field-effect transistors when using P(VDF-HFP) as a dielectric layer.


Physicochemical and textural characteristics and volatile compounds of semihard goat cheese as affected by starter cultures.
Today, cheese is valued because of its high nutritional value and unique characteristics. Improving the texture and flavor of cheese by selecting suitable starter cultures is an important way to promote the development of cheese industry. The effect of starter cultures on the physicochemical and textural properties and volatile compounds during the ripening of semihard goat cheese were investigated in this work. Different starter cultures-mesophilic (M) and thermophilic starters (T), Lactobacillus plantarum ssp. plantarum ATCC 14917 (Lp), a mix of the M and T starters (M1), and mix of the M, T, and Lp starters (M2)-were used in the production of the goat cheeses. Volatile compounds were determined by a solid-phase microextraction/gas chromatography-mass spectrometric (SPME/GC-MS) method. The results showed that the moisture content of cheeses produced with the 5 kinds of starter cultures decreased after maturation, whereas ash content increased. The pH values of goat cheeses decreased first and then increased during maturity, and the pH value of M2 cheese was the lowest among the cheeses. The hardness and chewiness of the cheeses increased with increasing maturity, whereas cohesiveness, springiness, and resilience showed the opposite tendency. The 60-d-old cheese made with Lp had the highest chewiness, cohesiveness, springiness, and resilience, whereas the 60-d-old cheese made with M2 had the highest hardness. A total of 53 volatile components were identified by SPME/GC-MS, and carboxylic acids, alcohols, ketones, and esters were the 4 major contributors to the characteristic flavors of the cheeses. Volatile components and their contents differed greatly among the produced cheeses. The M2 cheese contained the highest relative content of the main volatile compounds (90.10%), especially butanoic acid and acetoin. Through a comprehensive comparison of the results, we concluded that M2 cheese had a dense texture and milky flavor, and M2 is a potential starter culture candidate for the production of goat cheese.


Microfiber-based few-layer MoS2 saturable absorber for 2.5 GHz passively harmonic mode-locked fiber laser.
We reported on the generation of high-order harmonic mode-locking in a fiber laser using a microfiber-based molybdenum disulfide (MoS(2)) saturable absorber (SA). Taking advantage of both the saturable absorption and large third-order nonlinear susceptibilities of the few-layer MoS(2), up to 2.5 GHz repetition rate HML pulse could be obtained at a pump power of 181 mW, corresponding to 369th harmonic of fundamental repetition frequency. The results provide the first demonstration of the simultaneous applications of both highly nonlinear and saturable absorption effects of the MoS(2), indicating that the microfiber-based MoS(2) photonic device could serve as high-performance SA and highly nonlinear optical component for application fields such as ultrafast nonlinear optics.


Electrical devices designed based on inorganic clusters.
The idea of exploring the bottom brink of material science has been carried out for more than two decades. Clusters science is the frontmost study of all nanoscale structures. Being an example of 0-dimensional quantum dot, nanocluster serves as the bridge between atomic and conventionally understood solid-state physics. The forming mechanism of clusters is found to be the mutual effects of electronic and geometric configuration. It is found that electronic shell structure influences the properties and geometric structure of the cluster until its size becomes larger, where electronic effects submerge in geometric structure. The discrete electronic structures depend on the size and conformation of clusters, which can be controlled artificially for potential device applications. Especially, small clusters with a size of 1-2 nm, whose electronic states are possibly discrete enough to overcome thermal fluctuations, are expected to build a single-electron transistor with room temperature operation. However, exciting as the progress may be seen, cluster science still falls within the territory of merely the extension of atomic and molecular science. Its production rate limits the scientific and potential application research of nanoclusters. It is suggested in this review that the mass-produce ability without losing the atomic precision selectivity would be the milestone for nanoclusters to advance to material science.


Severe hemolytic disease of the newborn in a group B African-American infant delivered by a group O mother.
Maternal-fetal ABO incompatibility is a common hematological problem affecting the newborn. In general, hemolysis is minimal and the clinical course is relatively benign, rarely causing the escalating levels of hyperbilirubinemia and significant anemia commonly associated with Rh hemolytic disease of the newborn (HDN). The incidence of HDN ranges from one in 150 births to 1:3000 births, depending on the degree of anemia and level of serum bilirubin. The etiology of ABO hemolytic disease of the newborn (ABO-HDN) is complex because anti-A and anti-B antibodies are composed mainly of IgM. Since only IgG antibodies cross the placenta, those pregnant women with high levels of IgG anti-A,B, anti-A, or anti-B with an ABO incompatible fetus will be the ones to give birth to an infant with ABO-HDN. We describe a case of a B/Rh positive term newborn born to an O/Rh negative African-American mother demonstrating aggressive hemolysis and a robust response of the bone marrow. This case was successfully managed with phototherapy and simple RBC transfusion without the need for exchange transfusion.


The effects of epidermal fatty acid profiles, 1-oleoglycerol, and triacylglycerols on the susceptibility of hibernating bats to Pseudogymnoascus destructans.
White Nose Syndrome (WNS) greatly increases the over-winter mortality of little brown (Myotis lucifugus), Indiana (M. sodalis), northern (M. septentrionalis), and tricolored (Perimyotis subflavus) bats, and is caused by cutaneous infections with Pseudogymnoascus destructans (Pd). Big brown bats (Eptesicus fuscus) are highly resistant to Pd infections. Seven different fatty acids (myristic, pentadecanoic, palmitic, palmitoleic, oleic, and, linoleic acids) occur in the wing epidermis of both M. lucifugus and E. fuscus, 4 of which (myristic, palmitoleic, oleic, and, linoleic acids) inhibit Pd growth. The amounts of myristic and linoleic acids in the epidermis of M. lucifugus decrease during hibernation, thus we predicted that the epidermal fatty acid profile of M. lucifugus during hibernation has a reduced ability to inhibit Pd growth. Laboratory Pd growth experiments were conducted to test this hypothesis. The results demonstrated that the fatty acid profile of M. lucifugus wing epidermis during hibernation has a reduced ability to inhibit the growth of Pd. Additional Pd growth experiments revealed that: a) triacylglycerols composed of known anti-Pd fatty acids do not significantly affect growth, b) pentadecanoic acid inhibits Pd growth, and c) 1-oleoglycerol, which is found in the wing epidermis of E. fuscus, also inhibits the growth of this fungus. Analyses of white adipose from M. lucifugus also revealed the selective retention of oleic and linoleic acids in this tissue during hibernation.


Effect of Process-Based Multi-Task Cognitive Training Program on Executive Function in Older Adults With Mild Cognitive Impairment: Study Rationale and Protocol Design for a Randomized Controlled Trial.
Recent research from both human and animal studies confirms that cognitive training gains a considerable effect on multiple cognitive domains in older adults with mild cognitive impairment. Previous studies have yet paid scant attention to executive function training. Little is known about whether this specific benefit translates to maintaining long-term effectiveness and transfer effects are. This study is designed as an effort to address this issue. The program aimed to evaluate the effect of process-based multi-task cognitive training on executive function and further explore its long-term effects and transfer effects in older adults with MCI. Furthermore, we will explore the neural correlates latent the changed performances underlying the cognitive intervention. This program is a single-blinded, randomized, prospective clinical trial to test the effect of process-based multi-task cognitive training in older adults with MCI. Ninety participants with MCI will be recruited and randomly assigned to the cognitive training group (n=45) and the wait-list control group (n=45). The cognitive training group will receive 10 weeks of process-based multi-task cognitive training and health education twice a week, at 40~60 min per session. While the wait-list control group will only receive 10 weeks of health education during the research period. The effect is measured using the executive function, neuropsychological assessment performance and related brain activity assessed with electroencephalogram parameters (slowness and complexity of the EEG) at baseline, after 10 weeks of training, and a 3-month follow-up. The study is currently ongoing. Recruitment began in March 2019 and will conclude at the end of 2020. Effects of the process-based multi-task cognitive training on executive function in older adults with MCI will be described in intention-to-treat analysis and protocol set principle. We will also explore the potential long-term effects and transfer effects. If a process-based multi-task cognitive training program results in positive changes to executive function in older adults with MCI, this might provide a viable and potential approach to delay the cognitive decline. Clinical Trial Registration: ChiCTR1900020585. Registered on January 09, 2019. http://www.chictr.org.cn/showproj.aspx?proj=34664.


Kinetics of transformation of 1,1,1-trichloroethane by Fe(II) in cement slurries.
This study examines the applicability of the iron-based degradative solidification/stabilization (DS/S-Fe(II)) process to 1,1,1-trichloroethane (1,1,1-TCA), which is one of common chlorinated aliphatic hydrocarbons (CAHs) of concern at contaminated sites. DS/S-Fe(II) combines contaminant degradation by Fe(II) and immobilization by the hydration reactions of Portland cement. The transformation of 1,1,1-TCA by Fe(II) in 10% Portland cement slurries was studied using a batch slurry reactor system. The effects of Fe(II) dose, pH, and initial concentration of 1,1,1-TCA on the kinetics of 1,1,1-TCA degradation were evaluated. Degradation of 1,1,1-TCA in cement slurries including Fe(II) was very rapid and could be described by a pseudo-first-order rate law. The half-lives for 1,1,1-TCA were measured between 0.4 and 5h when Fe(II) dose ranged from 4.9 to 39.2mM. The pseudo-first-order rate constant increased with pH to a maximum near pH 12.5. A saturation rate equation was able to predict degradation kinetics over a wide range of target organic concentrations and at higher Fe(II) doses. The major transformation product of 1,1,1-TCA in mixtures of Fe(II) and cement was 1,1-dichloroethane (1,1-DCA), which indicates that degradation occurred by a hydrogenolysis pathway. A small amount of ethane was observed. The conversion of 1,1,1-TCA to ethane was better described by a parallel reaction model than by a consecutive reaction model.


Individual- and population-level responses of a keystone predator to geographic variation in prey.
Investigating how food supply regulates the behavior and population structure of predators remains a central focus of population and community ecology. These responses will determine the strength of bottom-up processes through the food web, which can potentially lead to coupled top-down regulation of local communities. However, characterizing the bottom-up effects of prey is difficult in the case of generalist predators and particularly with predators that have large dispersal scales, attributes that characterize most marine top predators. Here we use long-term data on mussel, barnacle, limpet, and other adult prey abundance and recruitment at sites spread over 970 km to investigate individual- and population-level responses of the keystone intertidal sunstar Heliaster helianthus on the coast of Chile. Our results show that this generalist predator responds to changes in the supply of an apparently preferred prey, the competitively dominant mussel Perumytilus purpuratus. Individual-level parameters (diet composition, per capita prey consumption, predator size) positively responded to increased mussel abundance and recruitment, whereas population-level parameters (density, biomass, size structure) did not respond to bottom-up prey variation among sites separated by a few kilometers. No other intertidal prey elicited positive individual predator responses in this species, even though a large number of other prey species was always included in the diet. Moreover, examining predator-prey correlations at approximately 80, 160, and 200 km did not change this pattern, suggesting that positive prey feedback could occur over even larger spatial scales or as a geographically unstructured process. Thus individual-level responses were not transferred to population changes over the range of spatial scales examined here, highlighting the need to examine community regulation processes over multiple spatial scales.


LINC00883 Promotes Drug Resistance of Glioma Through a microRNA-136/NEK1-Dependent Mechanism.
Accumulating evidence has highlighted the roles of long noncoding RNAs (lncRNAs) as competing endogenous RNAs (ceRNAs) of microRNAs (miRNAs) through their binding sites in the progression of glioma. Hereby, we aim to explore the role of LINC00883 as a regulator of miR-136 and its target, NIMA-related kinase 1 (NEK1), thus, its involvement in the drug resistance of glioma cells. Mechanistic investigations by dual-luciferase reporter, RNA pull-down, and RNA-binding protein immunoprecipitation (RIP) assays indicated that LINC00883 bound to miR-136, thereby blocking miR-136-induced downregulation of NEK1. Through gain-of-function experiments in U251 cells that presented a high drug resistance, we found that ectopic expression of LINC00883 resulted in increased MRP (encoding multidrug resistance-associated protein), limited cell apoptosis, and increased proliferation. Expectedly, depleting LINC00883 yielded tumor-suppressive and anti-chemoresistance effects on U251 cells by increasing miR-136 and inhibiting NEK1. Next, drug-resistant glioma cell line SOWZ1, drug-sensitive glioma cell line SOWZ2, and drug-resistant glioma cell line SOWZ2-BCNU (SOWZ2 cultured in BCNU) were applied to validate the roles of LINC00883 in the regulation of multidrug resistance. LINC00883 knockdown suppressed the viability of SWOZ1, SWOZ2, and SWOZ2-BCNU cells. In conclusion, LINC00883 knockdown reduces drug resistance in glioma. Hence, our study provides a future strategy to prevent drug resistance-induced therapeutic failure in glioma.


Determination of sophoraflavanone G and kurarinone in rat plasma by UHPLC-MS/MS and its application to a pharmacokinetic study.
This study aimed to develop and validate a simple and sensitive ultra high performance liquid chromatography tandem mass spectrometry method for the simultaneous determination of sophoraflavanone G and kurarinone in rat plasma by using rutin as the internal standard. Then, the developed method was applied to investigate the pharmacokinetics of sophoraflavanone G and kurarinone in rats after dosing the flavonoid extract from Sophora flavescens. Plasma samples were processed using a liquid-liquid extraction procedure with ethyl acetate. The analysis was performed on a triple quadrupole tandem mass spectrometer by multiple reaction monitoring with an electrospray ionization source in negative ionization mode. Quantitative ion transitions of m/z 423.2→161.2, 437.2→161.1, and 609.3→300.3 were monitored for sophoraflavanone G, kurarinone, and rutin, respectively. The calibration curves of the two analytes exhibited good linearity (r2 >0.9923) over the range of 0.1-200 ng/mL for sophoraflavanone G and 0.1-1000 ng/mL for kurarinone. Relative standard deviations were less than 13.2% for the intra- and inter-day precisions and no more than 12.6% for the recovery, showing good precision and satisfactory accuracy of the developed method. The validated method was successfully applied to the pharmacokinetic study of sophoraflavanone G and kurarinone after a single intravenous (25 mg/kg) and oral (500 mg/kg) administration of the flavonoid extract from S. flavescens, and the absolute bioavailability for sophoraflavanone G and kurarinone was about 36 and 17%, respectively.


Nitrogen loads through baseflow, stormflow, and underflow to Rehoboth Bay, Delaware.
A detailed study of water and nitrogen (N) discharge from a small, representative subwatershed of Rehoboth Bay, Delaware, was conducted to determine total N loads to the bay. The concentrations of ammonium (NH4(+)), nitrate + nitrite (NO3(-) + NO2(-)), and dissolved and particulate organic N were determined in baseflow and storm waters discharging from Bundicks Branch from October 1998 to April 2002. A novel hydrographic separation model that accounts for significant decreases in baseflow during storm events was developed to estimate N loads during unsampled storms. Nitrogen loads based on gauged flows alone (7100-19,100 kg/yr) significantly underestimated those based on land use-land cover (LULC) and estimated N export factors from different classes of LULC (32,000-40,600 kg/yr). However, when ungauged underflow and associated N loads were included in the total loads (25,500-33,800 kg/yr), there was much better agreement with LULC export models. This suggests that in permeable coastal plain sediments, underflow contributes significantly to N fluxes to estuarine receiving waters, particularly in drier years. Based on the similarity in LULC, N loads from the Bundicks Branch subwatershed were used to estimate upland loads to the entire Rehoboth Bay Watershed (259,000-316,000 kg/yr). These N loads from the watershed were much greater than those from direct atmospheric deposition (49,000-64,500 kg/yr) and from a local wastewater treatment plant (9700-13,700 kg/yr). While the watershed was the principal source of N at all times during the year, the relative contributions from the watershed, wastewater, and direct atmospheric deposition varied predictably with season.


The Prognostic Value of Circumferential Resection Margin Involvement in Patients with Extraperitoneal Rectal Cancer.
The prognostic influence of circumferential resection margin (CRM) status in extraperitoneal rectal cancer probably differs from that of intraperitoneal rectal cancer because of its different anatomical and biological behaviors. However, previous reports have not provided the data focused on extraperitoneal rectal cancer. Therefore, the aim of this study was to examine the prognostic significance of the CRM status in patients with extraperitoneal rectal cancer. From January 2005 to December 2008, 248 patients were treated for extraperitoneal rectal cancer and enrolled in a prospectively collected database. Extraperitoneal rectal cancer was defined based on tumors located below the anterior peritoneal reflection, as determined intraoperatively by a surgeon. Cox model was used for multivariate analysis to examine risk factors of recurrence and mortality in the 248 patients, and multivariate logistic regression analysis was performed to identify predictors of recurrence and mortality in 135 patients with T3 rectal cancer. CRM involvement for extraperitoneal rectal cancer was present in 29 (11.7%) of the 248 patients, and was the identified predictor of local recurrence, overall recurrence, and death by multivariate Cox analysis. In the 135 patients with T3 cancer, CRM involvement was found to be associated with higher probability of local recurrence and mortality. In extraperitoneal rectal cancer, CRM involvement is an independent risk factor of recurrence and survival. Based on the results of the present study, it seems that CRM involvement in extraperitoneal rectal cancer is considered an indicator for (neo)adjuvant therapy rather than conventional TN status.


Increase in linolenic Acid is not a prerequisite for development of freezing tolerance in wheat.
Seedlings of winter wheat (Triticum aestivum L. cv. Kharkov) were acclimated at 2 C in the dark in the presence of two inhibitors of linolenic acid synthesis, 4-chloro-5(dimethylamino)-2-phenyl-3(2H)pyridazinone-(BASF 13-338) and 4-chloro-5(dimethylamino)-2-(alpha,alpha,alpha-trifluoro-m-tolyl)- 3(2H)pyridazinone (Sandoz 6706). Although the increase in the proportion of linolenic acid generally observed at low temperature was completely inhibited, the development of freezing tolerance was unaffected. These results demonstrated that an enrichment in linolenic acid is not a prerequisite for low temperature acclimation.


Reagent preparation and storage for amplification of microarray hybridization targets with a fully automated system.
The advent of automated systems for gene expression profiling has accentuated the need for the development of convenient and cost-effective methods for reagent preparation. We have developed a method for the preparation and storage of pre-aliquoted cocktail plates that contain all reagents required for amplification of nucleic acid by reverse transcription and in vitro transcription reactions. Plates can be stored at -80 degrees C for at least 1 month and kept in a hotel at 4 degrees C for at least 24 h prior to use. Microarray data quality generated from these pre-aliquoted reagent plates is not statistically different between cRNA amplified with stored cocktails and cRNA amplified with freshly prepared cocktails. Deployment of pre-aliquoted, stored cocktail plates in a fully automated system not only increases the throughput of amplifying cRNA targets from thousands of RNA samples, but could also considerably reduce reagent costs and potentially improve process robustness.


Enteral Immunomodulatory Diet (Omega-3 Fatty Acid, γ-Linolenic Acid and Antioxidant Supplementation) for Acute Lung Injury and Acute Respiratory Distress Syndrome: An Updated Systematic Review and Meta-Analysis.
Enteral immunomodulatory nutrition is considered as a promising therapy for the treatment of acute lung injury and acute respiratory distress syndrome (ALI/ARDS). However, there are still some divergences, and it is unclear whether this treatment should be recommended for patients with ALI/ARDS. Therefore, we conducted this systematic review and meta-analysis to assess the efficacy and safety of an enteral immunomodulatory diet on the clinical outcomes of ALI/ARDS patients. We retrieved potentially relevant clinical trials though electronic databases. All trials of enteral immunomodulatory diet for ALI/ARDS were included. Analyses of the overall all-cause mortality, 28-day ventilator-free days and 28-day intensive care unit (ICU) free days were conducted. In total six controlled trials were evaluated. The pooled results did not show a significant reduction in the risk of all-cause mortality (M-H RR (the overall Mantel-Haenszel relative risk), 0.81 (95% CI, 0.50-1.31); p = 0.38; 6 trials, n = 717) in ALI/ARDS patients treated with the immunomodulatory diet. This treatment also did not extend the ventilator-free days and ICU-free days. However, patients with high mortality might benefit from this treatment. The enteral immunomodulatory diet could not reduce the severity of the patients with ALI/ARDS. Whereas, for ALI/ARDS patients with high mortality, this treatment might reduce the all-cause mortality, but its use should be treated with discretion.


Task demands determine hand posture bias on conflict processing in a Simon task.
A huge body of research in humans and monkeys has provided evidence for altered processing of items that are presented close to the hands. At the same time, the underlying mechanisms that explain why objects close to the hands are processed differently from objects far from the hands are still debated. Empirical demonstrations have provided evidence for the involvement of bottom-up influences, but also for top-down influences of task relevance. Objects close to the hands change spatial attentional processing or are subject to increased cognitive control. The present study demonstrated that variations in the task-processing demands predicted the hand posture influence on conflict resolution in a Simon task. Participants responded with their hands either at the monitor (close to the stimuli) or on their knees (far from the stimuli). The Simon effect was significantly reduced for the hands-close as compared to the hands-far condition when participants performed a numerical size judgment (Exps. 1 and 2). In contrast, the Simon effect was significantly increased for the hands-close condition when the Simon task consisted of a low-level perceptual feature discrimination (i.e., color task, Exp. 2). The obtained task-processing specificity provides further evidence that a highly flexible system underlies hand posture effects on stimulus processing.


Characterization of a myosin VII MyTH/FERM domain.
A group of closely related myosins is characterized by the presence of at least one MyTH/FERM (myosin tail homology; band 4.1, ezrin, radixin, moesin) domain in their C-terminal tails. This domain interacts with a variety of binding partners, and mutations in either the MyTH4 or the FERM domain of myosin VII and myosin XV result in deafness, highlighting the functional importance of each domain. The N-terminal MyTH/FERM region of Dictyostelium myosin VII (M7) has been isolated as a first step toward gaining insight into the function of this domain and its interaction with binding partners. The M7 MyTH4/FERM domain (MF1) binds to both actin and microtubules in vitro, with dissociation constants of 13.7 and 1.7 μM, respectively. Gel filtration and UV spectroscopy reveal that MF1 exists as a monomer in solution and forms a well-folded, compact conformation with a high degree of secondary structure. These results indicate that MF1 forms an integrated structural domain that serves to couple actin filaments and microtubules in specific regions of the cytoskeleton.


An overview of the management of diabetes from pre-conception, during pregnancy and in the postnatal period.
Diabetes is one of the most common medical conditions complicating pregnancy. Both pre-existing diabetes and gestational diabetes are associated with increased risks to the mother and fetus. These risks can be reduced by improving pre-conception and antenatal care. Pre-conception planning and care is important to ensure women are taking high dose folic acid, to optimise glucose control, to review medications and to screen for and manage any complications. All women with either pre-existing diabetes or gestational diabetes should be reviewed by the antenatal team every 1-2 weeks throughout pregnancy. This is to optimise glucose control and to monitor fetal growth and development. Women with diabetes in pregnancy should receive an individualised care plan for delivery. The exact timing of delivery will depend on maternal glucose control, fetal growth and any other complications. Women diagnosed with gestational diabetes in pregnancy are at high risk of developing both gestational diabetes and type 2 diabetes in the future. After delivery, they should be offered a fasting plasma glucose at 6 weeks or a glycated haemoglobin (HbA1c) at 13 weeks to ensure that the gestational diabetes has resolved and an annual HbA1c.


In vitro and in vivo modulation of the equine immune response by parapoxvirus ovis.
While immune modulators are used routinely in equine medicine, their mechanism of action is not always known. To determine the effect of a commercial preparation of inactivated parapoxvirus ovis (Orf virus; PPVO) on cytokine gene expression by equine peripheral blood mononuclear cells (PBMC) both in vitro and in vivo. PBMC were prepared from 6 mixed-breed yearlings and cultured in vitro with PPVO with or without Concanavalin A (Con A) for 24 h. Effects on the expression of IFNalpha, IFNbeta IFNgamma, TNFalpha and IL-18 were analysed by real time quantitative PCR (RT-PCR). In addition, 12 yearling horses were treated with PPVO and whole blood RNA samples were prepared at regular intervals to assess effects on in vivo cytokine gene expression. Six of those yearlings were later treated with saline and served as treatment controls. Nine additional yearlings were injected intradermally with a single dose and their injection sites biopsied at 24 and 48 h for cytokine expression. In vitro culture of PBMC with PPVO led to a significant increase in IFNalpha and IFNbeta gene expression compared to mock-stimulated cultures. In addition, expression of IFNgamma and TNFalpha was significantly higher in PBMC stimulated with PPVO and Con A, than those stimulated with Con A alone. No changes were observed in IL-18 gene expression in vitro. Treatment of horses with a 3-dose regimen of PPVO resulted in elevation of IFNgamma gene expression, which was detected 24 h after the first dose and declined thereafter. Intradermal inoculation led to increased expression of IFNgamma along with IFNbeta, IL-15 and IL-18. Together these results indicate that PPVO stimulated IFNgamma production both in vitro and in vivo. Increased cytokine expression could account for its immunomodulatory activity. The absence of adverse reactions and clear indications of increased expression of cytokine gene expression supports previous clinical uses for this immune modulator in those situations when increased expression of IFNgamma is warranted.


A Nucleic Acid-Based Orthopoxvirus Vaccine Targeting the Vaccinia Virus L1, A27, B5, and A33 Proteins Protects Rabbits against Lethal Rabbitpox Virus Aerosol Challenge.
In the age of COVID, nucleic acid vaccines have garnered much attention, at least in part, because of the simplicity of construction, production, and flexibility to adjust and adapt to an evolving outbreak. Orthopoxviruses remain a threat on multiple fronts, especially as emerging zoonoses. In response, we developed a DNA vaccine, termed 4pox, that protected nonhuman primates against monkeypox virus (MPXV)-induced severe disease. Here, we examined the protective efficacy of the 4pox DNA vaccine delivered by intramuscular (i.m.) electroporation (EP) in rabbits challenged with aerosolized rabbitpox virus (RPXV), a model that recapitulates the respiratory route of exposure and low dose associated with natural smallpox exposure in humans. We found that 4pox-vaccinated rabbits developed immunogen-specific antibodies, including neutralizing antibodies, and did not develop any clinical disease, indicating protection against aerosolized RPXV. In contrast, unvaccinated animals developed significant signs of disease, including lesions, and were euthanized. These findings demonstrate that an unformulated, nonadjuvanted DNA vaccine delivered i.m. can protect against an aerosol exposure. IMPORTANCE The eradication of smallpox and subsequent cessation of vaccination have left a majority of the population susceptible to variola virus or other emerging poxviruses. This is exemplified by human monkeypox, as evidenced by the increase in reported endemic and imported cases over the past decades. Therefore, a malleable vaccine technology that can be mass produced and does not require complex conditions for distribution and storage is sought. Herein, we show that a DNA vaccine, in the absence of a specialized formulation or adjuvant, can protect against a lethal aerosol insult of rabbitpox virus.


Modulation of Naturally Occurring Linear Dipeptide Chirality to Reduce the Affinity for Oligopeptide Transporter 1 and Increase Intestinal Stability for an Enhanced Colon-Targeting Effect in the Treatment of Inflammatory Bowel Disease: An Application of trans-4-l-Hydroxyprolyl-l-serine.
The naturally occurring linear dipeptide JBP923 (trans-4-l-Hyp-l-Ser, HS-tLL) with anti-inflammatory effects showed potential for the treatment of inflammatory bowel disease (IBD). However, colon-specific delivery after oral administration is still a challenge because its absorption is mediated by oligopeptide transporter 1 (PEPT1) in the upper small intestine and because of its instability in the gastrointestinal tract. Therefore, we aimed to enhance the colon-targeting efficiency by modulating HS-tLL chirality to synthesize eight enantiomers. Among these enantiomers, trans-4-d-Hyp-d-Ser, cis-4-l-Hyp-d-Ser, cis-4-d-Hyp-l-Ser, and cis-4-d-Hyp-d-Ser did not work as substrates of PEPT1 and were stable in the gastrointestinal tract, resulting in enhanced colonic accumulation through the paracellular pathway due to the loose tight junctions in IBD. Interestingly, cis-4-d-Hyp-d-Ser exerted the most potent therapeutic effect on IBD. Our findings revealed the impact of chirality on the colonic accumulation of the linear dipeptide, providing strategies for the colon-targeted delivery of the linear dipeptide for the treatment of IBD.


Cloud images from the pioneer venus orbiter.
Ultraviolet images of Venus over a 3-month period show marked evolution of the planetary scale features in the cloud patterns. The dark horizontal Y feature recurs quasi-periodically, at intervals of about 4 days, but it has also been absent for periods of several weeks. Bow-shaped features observed in Pioneer Venus images are farther upstream from the subsolar point than those in Mariner 10 images.


Cutaneous nociceptive facilitation of Ib heteronymous pathways to lower limb motoneurones in humans.
The effects of tonic pain stimulation on heteronymous Ib pathways from the gastrocnemius medialis (GM) to the soleus (Sol) and to the quadriceps (Q) muscles were investigated in four healthy human subjects. Tonic pain stimulation was performed by subcutaneous injection of 0.5 mg levo-ascorbic acid or vitamin C (L-LAS) in a volume of 0.5 ml on the dorsal surface of the ipsilateral foot. The mean curve of L-AS-induced pain sensation showed a steep rising phase reaching maximum intensity at 2-3 min, followed by a slow decay phase lasting about 15-20 min. Between about 5 and 20 min after injection, there was evidence of pure pain stimulation due to chemical activation of free nerve endings. During this interval, significant potentiation of Ib inhibition from GM to both Sol and Q motoneurones was observed. The time-course of these Ib heteronymous changes paralleled that of subjective pain sensation. These findings demonstrate that nociceptive discharge modifies the gain of Ib heteronymous effects in humans. Since the man function of these Ib pathways is to coordinate activity of muscles operating at different joints, it is suggested that nociceptive input may change muscle synergies by selecting specific subpopulations of Ib interneurones, thus contributing to establish appropriate adaptive motor strategies.


Necessity of Antibiotics following Simple Exodontia.
Introduction. The aim of our study is to assess the need for postoperative antibiotics following simple exodontia and determine its role in minimizing patient discomfort and postoperative complications. Material and Methods. All the patients undergoing simple extractions were grouped into two categories: Group 1, patients receiving antibiotics, and Group 2, patients receiving no antibiotics. Patients were recalled on the sixth day to assess postoperative complications. On recall, patients were evaluated for signs of persistent inflammation and signs of dry socket. Presence of persistent inflammation and/or suppuration on the 6th day was considered as wound infection. Results. A total of 146 patients were included in this study. Out of the total sample, 134 (91.8%) presented with no postoperative complications and 12 (8.2%) had postoperative complications, out of which 11 (7.5%) patients presented with dry socket (alveolar osteitis), 5 (3.4%) in the antibiotic group and 6 (4.1%) in the nonantibiotic group. Only 1 patient (0.7%) was reported with infection of the extraction socket in the nonantibiotic group, whereas no case of infection was found in the antibiotic group. Conclusion. Antibiotics are not required after simple extractions in patients who are not medically comprised nor do they have any role in preventing postoperative complications.


Genome-wide association study of six quality traits reveals the association of the TaRPP13L1 gene with flour colour in Chinese bread wheat.
Flour colour, kernel hardness, grain protein content and wet gluten content are important quality properties that determine end use in bread wheat. Here, a wheat 90K genotyping assay was used for a genome-wide association study (GWAS) of the six quality-related traits in Chinese wheat cultivars in eight environments over four years. A total of 846 significant single nucleotide polymorphisms (SNPs) were identified, explaining approximately 30% of the phenotypic variation on average, and 103 multienvironment-significant SNPs were detected in more than four environments. Quantitative trait loci (QTL) mapping in the biparent population confirmed some important SNP loci. Moreover, it was determined that some important genes were associated with the six quality traits, including some known functional genes and annotated unknown functional genes. Of the annotated unknown functional genes, it was verified that TaRPP13L1 was associated with flour colour. Wheat cultivars or lines with TaRPP13L1-B1a showed extremely significantly higher flour redness and lower yellowness than those with TaRPP13L1-B1b in the Chinese wheat natural population and the doubled haploid (DH) population. Two tetraploid wheat lines with premature stop codons of the TaRPP13L1 gene mutagenized by ethyl methanesulfonate (EMS) showed extremely significantly higher flour redness and lower yellowness than wild type. Our data suggest that the TaRPP13L1 gene plays an important role in modulating wheat flour colour. This study provides useful information for further dissection of the genetic basis of flour colour and also provides valuable genes or genetic loci for marker-assisted selection to improve the process of breeding quality wheat in China.


Fuzzy set analyses of genetic determinants of health and disability status.
Analyses of complex genotype-phenotype relations require new statistical procedures because of the potentially high dimensionability of those relations which are expressed with both measurement error and stochasticity in the correlation function. We propose modifying a multivariate procedure called grade of membership (GoM) analysis to deal with the special problems of such analyses. In doing so, we make clear some special features of the GoM model for multivariate analysis of high dimensional, discrete data. This is illustrated for apolipoprotein E (APOE) assessments made on 1805 people in the 1999 National Long Term Care Survey. A number of interesting relations with APOE polymorphism were found where disability profiles were more predictive than specific diagnoses because they implicitly contained information on chronicity and severity of disease processes.


Once and again: retinoic acid signaling in the developing and regenerating olfactory pathway.
Retinoic acid (RA), a member of the steroid/thyroid superfamily of signaling molecules, is an essential regulator of morphogenesis, differentiation, and regeneration in the mammalian olfactory pathway. RA-mediated teratogenesis dramatically alters olfactory pathway development, presumably by disrupting retinoid-mediated inductive signaling that influences initial olfactory epithelium (OE) and bulb (OB) morphogenesis. Subsequently, RA modulates the genesis, growth, or stability of subsets of OE cells and OB interneurons. RA receptors, cofactors, and synthetic enzymes are expressed in the OE, OB, and anterior subventricular zone (SVZ), the site of neural precursors that generate new OB interneurons throughout adulthood. Their expression apparently accommodates RA signaling in OE cells, OB interneurons, and slowly dividing SVZ neural precursors. Deficiency of vitamin A, the dietary metabolic RA precursor, leads to cytological changes in the OE, as well as olfactory sensory deficits. Vitamin A therapy in animals with olfactory system damage can accelerate functional recovery. RA-related pathology as well as its potential therapeutic activity may reflect endogenous retinoid regulation of neuronal differentiation, stability, or regeneration in the olfactory pathway from embryogenesis through adulthood. These influences may be in register with retinoid effects on immune responses, metabolism, and modulation of food intake.


Simulation of pH-Dependent Conformational Transitions in Membrane Proteins: The CLC-ec1 Cl-/H+ Antiporter.
Intracellular transport of chloride by members of the CLC transporter family involves a coupled exchange between a Cl- anion and a proton (H+), which makes the transport function dependent on ambient pH. Transport activity peaks at pH 4.5 and stalls at neutral pH. However, a structure of the WT protein at acidic pH is not available, making it difficult to assess the global conformational rearrangements that support a pH-dependent gating mechanism. To enable modeling of the CLC-ec1 dimer at acidic pH, we have applied molecular dynamics simulations (MD) featuring a new force field modification scheme-termed an Equilibrium constant pH approach (ECpH). The ECpH method utilizes linear interpolation between the force field parameters of protonated and deprotonated states of titratable residues to achieve a representation of pH-dependence in a narrow range of physiological pH values. Simulations of the CLC-ec1 dimer at neutral and acidic pH comparing ECpH-MD to canonical MD, in which the pH-dependent protonation is represented by a binary scheme, substantiates the better agreement of the conformational changes and the final model with experimental data from NMR, cross-link and AFM studies, and reveals structural elements that support the gate-opening at pH 4.5, including the key glutamates Gluin and Gluex.


[Role of androgen in the elderly. Cardiovascular disease and androgen].
Hypercholesterolemia, which is well known one of the important risk factor for cardiovascular disease, is more prevalence in women than men. However, cardiovascular disease is more prevalence in men than women. It is possible that men have more frequently hypertension and glucose intolerance than women. These may affect the sex difference in the cardiovascular disease prevalence quite a few. The feature of risk factors for cardiovascular disease may be affected by both sex hormone and sex related genes. To clarify the role of sex hormone and sex related genes in the risk factor for atherosclerosis will be very important to reduce the atherosclerosis developments in human.


Balloon pulmonary valvuloplasty in tetralogy of Fallot: effects on growth of pulmonary annulus and transannular patch.
Balloon pulmonary valvuloplasty and its benefit on the growth of pulmonary annulus and pulmonary artery in tetralogy of Fallot (TOF) patients remains controversial. The purpose ofthe present study was to determine the growth of pulmonary valve annulus and pulmonary artery and to evaluate the need of transannular patch during total surgical correction in patients with tetralogy of Fallot (TOF) after balloon pulmonary valvuloplasty. Fifty-one severely hypoxic TOF patients, who underwent balloon dilatation ofpulmonary valve, were included in the present study. The clinical outcomes, oxygen saturation, and echocardiographic parameters before and after balloon dilatation were analyzed. There were 33 males and 18females. The mean age was 3 years 5 months old (range, I month-15 years 8 months old). The mean oxygen saturation increasedfrom 73.9 +/- 9.1 to 84.8 +/- 6.7% immediately after the procedure (p-value < 0.05). There was no serious procedural-related complication. At the mean follow-up period of 2 years and 4 months, the mean Z-score of pulmonary annulus size increased from -2.56 SD to -1.87 SD (p-value < 0.05) and the right pulmonary artery size from -0.29 SD to + 0.46 SD (p-value < 0.05). Thirty-seven patients (66.1%) underwent corrective surgery. Pulmonary transannular patch was performed in 11 of37 patients (29.7%). Pulmonary valve dilatation in patients with TOF is safe. It promotes the growth ofthe pulmonary valve annulus and pulmonary artery and may decrease the need of transannular patch at the time of surgical correction.


Hydronephrosis in the course of ureteropelvic junction obstruction: An underestimated problem? Current opinions on the pathogenesis, diagnosis and treatment.
Ureteropelvic junction obstruction (UPJO) causes a reduction in the urine flow from the renal pelvis into the ureter. Untreated UPJO may cause hydronephrosis, chronic infection or urolithiasis and will often result in progressive deterioration of renal function. Most cases of UPJO are congenital; however, the disease can be clinically silent until adulthood. Other causes, both intrinsic and extrinsic, are acquired and include urolithiasis, post-operative/inflammatory/ischemic stricture, fibroepithelial polyps, adhesions and malignancy. In the past, the most frequent symptom of UPJO in neonates and infants was a palpable flank mass. Nowadays, thanks to the widespread use of maternal and prenatal ultrasound examinations, asymptomatic hydronephrosis is diagnosed very early. In adults and older children symptoms may include intermittent abdominal or flank pain, nausea, vomiting and hematuria. In addition to high specificity and sensitivity in detecting UPJO, modern technologically advanced equipment such as ultrasound, magnetic resonance imaging and computed tomography provides a lot of information about the function of the affected kidney and the anatomy of the surrounding tissues. Treatment options for UPJO include a wide spectrum of approaches, from active surveillance or minimally invasive endourologic techniques to open, laparoscopic or robotic pyeloplasty. The main goal of therapy is to relieve symptoms and maintain or improve renal function, but it is difficult to define treatment success after UPJO therapy.


The oral health of adults in NSW, 2004-06.
The 2004-06 National Survey of Adult Oral Health was Australia's second oral examination survey of a nationally representative sample of adults. The aim of this paper is to provide a brief overview of oral health in the NSW adult population from the findings of the survey. A three-stage, stratified, clustered sampling design was used to select NSW residents aged 15 years and over. Self-reported information about oral health was obtained through telephone interviews. People with natural teeth were offered clinical examinations. 3630 people were interviewed and 1099 underwent a clinical examination. Only 5.5% of the study population were edentulous (all natural teeth missing) compared with the national estimate of 6.4%. The Decayed, Missing, Filled Teeth (DMFT) caries severity index was 12.8, equal to that of the Australian population; prevalence of untreated decay was 27.1%, which was not significantly different to the national estimate of 25.5%. Some 60.3% of the NSW survey sample had visited a dentist within the last 12 months (nationally 59.4%) and 56.8% visited for a check-up (56.2% nationally). Oral health, use of dental services and perceptions of need varied significantly by geographic location, private insurance patronage and eligibility for public dental care. The oral health of the NSW adult population and patterns of dental care are similar to that estimated nationally. The prevalence and severity of dental diseases and oral health behaviours are influenced by social and geographic factors.


The Effects of a Digital Well-being Intervention on Older Adults: Retrospective Analysis of Real-world User Data.
Digital interventions have been shown to be effective for a variety of mental health disorders and problems. However, few studies have examined the effects of digital interventions in older adults; therefore, little is known about how older adults engage with or benefit from these interventions. Given that adoption rates for technology among people aged ≥65 years remain substantially lower than in the general population and that approximately 20% of older adults are affected by mental health disorders, research exploring whether older adults will use and benefit from digital interventions is needed. This study aimed to examine the extent to which older adults engaged with a digital well-being intervention (Happify) and whether engaging with this program led to improvements in both subjective well-being and anxiety symptoms. In this retrospective analysis, we analyzed data from 375 real-world Happify users aged ≥65 years who signed up for the platform between January 1, 2019, and December 23, 2021. Changes in well-being and anxiety symptoms across 42 to 182 days were assessed using responses to the in-app assessment, which users were prompted to take every 2 weeks, and were compared among users who engaged with the program at the recommended level (ie, 2 or more activities per week) or below the recommended level. In all, 30% (113/375) of the sample engaged with the platform at the recommended level (ie, completed an average of 2 or more activities per week), and overall, users completed an average of 43.35 (SD 87.80) activities, ranging from 1 to 786, between their first and last assessment. Users were also active on the platform for an average of 19.36 (SD 27.16) days, ranging from 1 to 152 days. Moreover, older adults who engaged at the recommended level experienced significantly greater improvements in subjective well-being (P=.002) and anxiety symptoms (P<.001) relative to those who completed fewer activities. These data provide preliminary evidence that older adults engage with and benefit from digital well-being interventions. We believe that these findings highlight the importance of considering older adult populations in digital health research. More research is needed to understand potential barriers to using digital interventions among older adults and whether digital interventions should be modified to account for this population's particular needs (eg, ensuring that the intervention is accessible using a variety of devices). However, these results are an important step in demonstrating the feasibility of such interventions in a population that is assumed to be less inclined toward digital approaches.


Smoking among young children in Hong Kong: influence of parental smoking.
This paper is a report of a study comparing children with smoking parents and those with non-smoking parents, in terms of knowledge and attitude towards smoking and the influence of parents and peers on smoking initiation. Adolescence is a developmental stage when smoking habits are likely to start. Adolescents are most influenced by the smoking habits of their parents and friends. A cross-section study was conducted with students aged 13-15 years in two schools in 2008, using a questionnaire that collected information on the smoking habits of their parents and peers, knowledge and attitude towards smoking, initiation and inclination towards smoking. Chi-square tests and binary logistic regression were used to analyse the data. A total of 257 of 575 (44·7%) students had smoking parent(s), and 25·4% reported having peers who smoked. Children with non-smoking parents were more likely than those with smoking parents to consider 'smoking as disgusting' (67·3% vs. 45·9%), and to know that 'smoking is addictive' (80·5% vs. 70·4%) and 'harmful to health' (81·8% vs. 67·7%). More of those with smoking parents had tried smoking than those with non-smoking parents (13·2% vs. 3·8%). Preventive programmes should involve smoking parents to increase their awareness of the impact their smoking has on their children. Interventions should include problem-solving skills for children to deal with daily stresses and thus eradicate the potential risk of smoking initiation.


The C-reactive protein/albumin ratio predicts long-term outcomes of patients with operable non-small cell lung cancer.
To investigate the association between C-reactive protein/albumin ratio (CAR), an inflammation-based prognostic score, and clinicopathological factors, as well as its association with long-term outcomes in patients with operable non-small cell lung cancer (NSCLC). A total of 617 operable NSCLC patients were retrospectively evaluated and the data of preoperative serum CRP and serum albumin was collected. The correlation between the CAR and clinicopathological factors was analyzed using the chi-square test. A Cox proportional hazards regression model was performed to evaluate the association between the CAR and outcome. The CAR was significantly related to sex, smoking status, BMI, histology type and clinical stage (p ≤ 0.05). The patients with characteristic of male, smoker, BMI under 18.5, squamous cell carcinoma or clinical stage III had a high level of CAR. Additionally, elevated CAR indicated a worse outcome, and the patients with higher CAR had 2.02-fold risk for disease progression (95% CI 1.48-2.74, p < 0.001) and 2.61-fold risk for death (95 % CI 2.02-3.37, p < 0.001). Multivariate analyses showed the similar results after adjusted by clinicopathological factors and another four inflammation-based prognostic scores. The CAR is a potential independent predictor for disease progression and death in patients with operable NSCLC.


Bereavement After Patient Deaths Among Chinese Physicians and Nurses: A Qualitative Description Study.
In order to achieve an in-depth understanding of professional caregivers' experiences of bereavement after patient deaths in Mainland China, qualitative description was employed. 24 physicians and nurses from hospitals in Nanjing, China, participated in one-to-one, semi-structured interviews. Thematic analysis was adopted for data analysis. Five themes were generated: the nature of professional bereavement experiences, the meaning of patient deaths, immediate bereavement reactions, long-term changes, and coping strategies. Each theme included personal and professional dimensions. Professional bereavement experiences in Mainland China were found to be influenced by workplace violence against professional caregivers, traditional Chinese medical ethics, the strong death taboo, and inadequacies of the healthcare system. Professional bereavement experiences are meaning-driven, comprehensive, and usually disenfranchised. They involve multidimensional reactions and have both short-term and long-lasting, both event-specific and accumulated impacts. Cultural and systemic factors could shape professional bereavement experiences.


An electroencephalography (EEG) study of short-term electromyography (EMG) biofeedback training in patients with myofascial pain syndrome in the upper trapezius.
[Purpose] In the present study, electroencephalography was used to explore neural activity related to electromyography biofeedback training, focusing on pain perception before and after electromyography biofeedback. [Participants and Methods] Twenty-seven participants (female=23; mean age: 28.85 ± 4.99 years) with mild-to-moderate myofascial pain syndrome in the upper trapezius were recruited for this study. All participants underwent electroencephalography recording before, during, and after (0 and 15 min) electromyography biofeedback training. Quantitative electroencephalography analysis was performed to obtain the absolute power of the four main frequency bands. Pain scores before and after electromyography biofeedback were also evaluated by subjective rating. [Results] Electromyography biofeedback increased alpha power and decreased delta power 15 minutes after training, suggestive of relaxation. However, although a tendency for scores to decrease was observed, no significant improvements in pain scores were observed following the intervention. Such results may be due to the short duration of the biofeedback session and the subjective nature of pain assessments. [Conclusion] Despite no obvious changes in pain perception, brief electromyography biofeedback training may induce relaxation in patients with myofascial pain syndrome of the upper trapezius muscle.


Hyperactivation of Posterior Default Mode Network During Self-Referential Processing in Children at Familial High-Risk for Psychosis.
Patients with schizophrenia spectrum disorders show disturbances in self-referential processing and associated neural circuits including the default mode network (DMN). These disturbances may precede the onset of psychosis and may underlie early social and emotional problems. In this study, we examined self-referential processing in a group of children (7-12 years) at familial high risk (FHR) for psychosis (N = 17), compared to an age and sex-matched group of healthy control (HC) children (N = 20). The participants were presented with a list of adjectives and asked to indicate whether or not the adjectives described them (self-reference condition) and whether the adjectives described a good or bad trait (semantic condition). Three participants were excluded due to chance-level performance on the semantic task, leaving N = 15 FHR and N = 19 HC for final analysis. Functional MRI (fMRI) was used to measure brain activation during self-referential vs. semantic processing. Internalizing and externalizing problems were assessed with the Child Behavior Checklist (CBCL). Evaluating main effects of task (self > semantic) showed activation of medial prefrontal cortex in HC and precuneus/posterior cingulate cortex (PCC) in FHR. Group-comparison yielded significant results for the FHR > HC contrast, showing two clusters of hyperactivation in precuneus/ PCC (p = 0.004) and anterior cerebellum / temporo-occipital cortex (p = 0.009). Greater precuneus/PCC activation was found to correlate with greater CBCL internalizing (r = 0.60, p = 0.032) and total (r = 0.69, p = 0.009) problems. In all, this study shows hyperactivity of posterior DMN during self-referential processing in pre-adolescent FHR children. This finding posits DMN-related disturbances in self-processing as a developmental brain abnormality associated with familial risk factors that predates not just psychosis, but also the prodromal stage. Moreover, our results suggest that early disturbances in self-referential processing may be related to internalizing problems in at-risk children.


Overview of high-resolution infrared measurement and analysis for atmospheric monitoring of halocarbons.
The current state of the art in recording and analyzing rotationally resolved vibration-rotation bands of atmospheric pollutant halocarbon species is reviewed. It is shown that in order to obtain molecular constants of sufficient accuracy to simulate the vibration-rotation structure over the range of atmospheric temperatures, it is necessary to obtain spectra at a range of temperatures using static cooling cells, supersonic jet expansions, and collisional cooling devices; employ sophisticated pattern recognition and analysis software; assign and fit spectral perturbations; and use spectral simulation and digital spectral subtraction (SASSI) to further simplify spectral bands for analysis. To demonstrate the techniques, an analysis of the ν(5) band of CH(37)ClF(2) in natural abundance is presented.


Hypertensive encephalopathy with reversible brainstem edema.
Presented here is a 36-year-old male with arterial hypertension who developed brainstem edema and intracranial hemorrhage. Magnetic resonance scan revealed diffuse brainstem hyperintensity in T2-weighted and fluid-attenuated inversion-recovery images, with an increase in apparent diffusion coefficient values. After a reduction in blood pressure, rapid resolution of the brainstem edema was observed on follow-up. The patient's condition was thus interpreted as hypertensive brainstem encephalopathy. While many consider this a vasogenic phenomenon, induced by sudden, severe hypertension, the precise mechanism remains unclear. Prompt recognition and aggressive antihypertensive treatment in such patients are essential to prevent permanent or life-threatening neurologic injury.


Chiral capillary electrophoresis-mass spectrometry: modes and applications.
A review is presented to highlight several approaches for coupling capillary electrophoresis (CE) and electrospray ionization-mass spectrometry (ESI-MS) for analysis of chiral compounds. A short discussion of commercially available CE-MS instruments and interface design is followed by a detail review on various modes of chiral CE-MS. In general, for each CE-MS mode, the capabilities, applications and limitations for chiral analysis have been pointed out. The first mode, chiral capillary zone electrophoresis-mass spectrometry (CZE-MS) in which neutral derivatized cyclodextrins (CDs) are used is possible using either column coupling with voltage switching or a partial-filling technique (PFT). However, some applications of direct coupling of CZE-MS mode are also reported. The second mode is a chiral electrokinetic chromatography-mass spectrometry (EKC-MS) in which a charged chiral selector such as a sulfated beta-CD or a vancomycin could be conveniently employed. This is because these chiral selectors have a significantly higher countercurrent electrophoretic mobility which prevents the entrance of these selectors into the mass spectrometer. The combination of counter-migration and PFT demonstrates that this synergism could be successfully applied to chiral analysis of a broader range of compounds. It is well-known that the on-line coupling of micellar electrokinetic chromatography to mass spectrometry (MEKC-MS) is problematic because the high surface activity and nonvolatile nature of conventional surfactant molecules lower the electrospray ionization efficiency. However, a recent report demonstrates that this hyphenation is now possible with the use of molecular micelles. Various MEKC-ESI-MS parameters that can be used to optimize both chiral resolution and ESI response are discussed. Finally, two recent examples that demonstrate the feasibility of using either open-tubular or packed chiral CEC with MS are reviewed. This survey will attempt to cover the state-of-the-art on various modes of CE-MS from 1998 up to 2002.


Targeting essential genes of Nosema for the diagnosis of pebrine disease in silkworms.
Pebrine is one of the devastating diseases mostly caused by notorious Nosema - a microsporidian infecting silkworms. Identification of novel genes associated with the pathogen plays a key role in developing a reliable diagnostic tool for the detection of disease. Targeting potential biomarkers will help in developing strategies for fast and efficient control measures, which can prevent the spread of infection. This study was to identify genes present commonly in Nosema such as Nosema bombycis, Nosema mylitta, Nosema assamensis and Nosema ricini infecting Indian silkworms in order to find potential gene markers for early pebrine disease diagnosis. Real time PCR was used to validate the genes active early during the infection cycle, confirming the expression of genes and their order of expression. 16S rRNA and β-tubulin were found to be expressed early in infection followed by PTP1 and PTP2, PTP3, SWP5 and MetAP2 genes. These identified molecular markers can be used in addition to conventional gene primers which are traditionally used for the detection of pebrine.


Solvothermal synthesis of nanoporous polymer chalk for painting superhydrophobic surfaces.
Reported here is a facile synthesis of nanoporous polymer chalk for painting superhydrophobic surfaces. Taking this nanoporous polymer as a media, superhydrophobicity is rapidly imparted onto three typical kinds of substrates, including paper, transparent polydimethylsiloxane (PDMS), and finger skin. Quantitative characterization showed that the adhesion between the water droplet and polymer-coated substrates decreased significantly compared to that on the original surface, further indicating the effective wetting mode transformation. The nanoporous polymer coating would open a new door for facile, rapid, safe, and larger scale fabrication of superhydrophobic surfaces on general substrates.


The tropical African tribes Poreuomenini, Zeuneriini and Morgeniini with the description of a new genus (Orthoptera: Tettigoniidae: Phaneropterinae).
Species currently considered belonging to the tribe Poreuomenini Brunner von Wattenwyl, 1878 are here separated; only Poreuomena Brunner von Wattenwyl, 1878 and Cestromoecha Karsch, 1893 remain in the tribe Poreuomenini, while Zeuneria Karsch, 1889 and Gravenreuthia Karsch, 1892 are transferred to the new tribe Zeuneriini Karsch, 1890. Morgenia Karsch, 1890 and Mangomaloba Sjöstedt, 1902 are moved to the new tribe Morgeniini Karsch, 1890. The new genus and species Paraporeuomena signata is described from the Tri National Sangha (TNS) (Central African Republic) and tentatively considered belonging to the tribe Poreuomenini. Its general aspect is hardly similar to that of the genus Poreuomena Brunner von Wattenwyl, 1878, but it differs remarkably in the shape of eyes, that are oval and elongate, in the presence of subocular grooves, of spines on genicular lobes of femora, and of ventral spines on fore and mid legs. Differently from Poreuomena the last tergite is not modified.


EP4 and EP2 receptor subtypes involved in colonic secretion in rat.
The study was designed to determine the prostaglandin EP receptor subtypes functionally involved in electrogenic ion secretion in rat colon. With 30 rats, measurements of short circuit current (SCC) and slope conductance were obtained by Ussing chamber technique. Prostaglandin E2 (PGE(2)) and other EP receptor selective agonists were employed on stripped rat colon pre-treated with indomethacin and theophylline. Receptor-specific agonists were butaprost (EP(2)), sulprostone (EP(1) and EP(3)) and PGE(1) alcohol (OH-PGE(1)) (EP(4)). GW627368X was used as a specific EP(4) receptor antagonist. Forskolin-induced SCC was used as a control of tissue viability. The mean basal SCC was 24.5 +/- 0.9 microA/cm(2) (range 9.8-45.1), and mean basal slope conductance was 23.7 +/- 6.1 mS/cm(2) (range 9.7-39.8). The basal SCC decreased after pre-treatment with indomethacin and increased after pre-treatment with theophylline. PGE(2), butaprost and OH-PGE(1) stimulated maximal increase in SCC (55.8 +/- 4.1, 43.9 +/- 3.8 and 93.9 +/- 2.7 microA/cm(2), respectively), while sulprostone had no apparent effects. GW627368X eliminated OH-PGE(1)-induced SCC and partially PGE(2)-induced SCC, leaving butaprost-induced SCC almost unperturbed. Bumetanide, 20 microM, inhibited between 40% and 80% of the agonist-induced changes in SCC. In conclusion, compilation of the results on induced SCC by subtype specific receptor agonists for EP receptors and the pattern of induced SCCs inhibited by GW627368X indicate the EP(4) receptor subtype as the major mediator of PGE(2)-induced electrogenic ion secretion with a lesser induction through the EP(2) receptor subtype.


Serum growth factors in patients with pancreatic cancer.
The aims of this study were (1) to assess possible variations in the serum levels of epidermal growth factor (EGF), insulin-like growth factor I (IGF I) and somatostatin in patients with pancreatic cancer as compared to other pancreatic or extrapancreatic diseases and (2) to ascertain the role of these substances in tumour growth and spread. 35 patients with pancreatic cancer were compared to 15 patients with chronic pancreatitis, 15 with benign hepatobiliary diseases, 23 with benign or malignant gastro-intestinal diseases and 22 control subjects. Increased EGF and IGF I serum levels were found in 10% of patients with pancreatic cancer. Somatostatin levels were increased in 8/16 (50%) patients with pancreatic cancer. No correlation was found between EGF, IGF I or somatostatin and tumour size or stage. In pancreatic cancer somatostatin serum levels were correlated with total bilirubin (p < 0.04), while EGF and IGF I were inversely correlated with fasting serum glucose levels (p < 0.05). In conclusion, (1) the serum levels of EGF, IGF I and somatostatin were not related to tumour size and clinical stage of pancreatic cancer, (2) the serum levels EGF and IGF I may be related to altered glucose metabolism, and (3) liver impairment can influence somatostatin serum levels.


Pattern of Substance Use: Study in a De-addiction Clinic.
Substance use disorders have become a major public health problem in Bangladesh. We sought to assess the pattern of substance use and related factors among hospitalized patients. This was a descriptive study that included 105 patients. All patients who were admitted to a private drug de-addiction clinic in Dhaka, Bangladesh, between 1 July and 31 December 2013 and diagnosed with substance use disorder were enrolled in the study. Data was collected via face-to-face interviews using a semi-structured questionnaire and the information was complemented by the case-notes. Almost all (90.5%) respondents were male and were poly-substance users (91.4%). The mean age of respondents was 28.8±8.0 years. Most (27.6%) respondents used three types of substances. Smoking or inhalation was the route used by most (90.5%) respondents. More than three-fourths (81.0%) of respondents used nicotine. Among the other substances, the majority (79.0%) used opioids, followed by cannabinoids (55.2%), and alcohol (41.0%). Curiosity, peer pressure, and for fun were identified as the common reasons for initiating substance use. A high proportion of poly-substance use was found in the study population. Our findings could help in the management and development of prevention strategies for substance use in Bangladesh.


What are the real risks of sport-related concussion, and are they modifiable?
Over the past two decades, the management of sport-related concussion has been the topic of increased attention in the scientific literature and in the popular media. Despite a proliferation of competing guidelines for concussion management, the widespread use of neuropsychological "baseline" testing designed to monitor postinjury recovery, and several prospective controlled studies of the natural history of concussion, there has been virtually no attempt to quantify the risks associated with sport-related concussion or to determine whether these risks are modifiable via management strategies. Using American football as a model, the short- and long-term risks of sport-related concussion are reviewed. It is concluded that serious short-term consequences of sport-related concussion are extremely rare and unlikely to be significantly modified via management strategies that rely on baseline testing. Other less serious short-term adverse outcomes are also quite rare, transient, and not likely to be altered by specific management guidelines. The long-term consequences of multiple sport-related head trauma remain unclear but are potentially of greater public health concern and should be the focus of increased research. Based on available evidence, there is little rationale for the use of rigid strategies or guidelines in the place of individual clinical decision-making in the management of these injuries.


Clinical characterization, linkage analysis, and PRPC8 mutation analysis of a family with autosomal dominant retinitis pigmentosa type 13 (RP13).
A Dutch family with autosomal dominant retinitis pigmentosa (adRP) displayed a phenotype characterized by an early age of onset, a diffuse loss of rod and cone sensitivity, and constricted visual fields (type I). One male showed a mild progression of the disease. Linkage analysis showed cosegregation of the genetic defect with markers from chromosome 17p13.1-p13.3, a region overlapping the RP13 locus. The critical interval of the RP locus as defined in this family was flanked by D17S926 and D17S786, with a maximal lod score of 4.2 (theta = 0.00) for marker D17S1529. Soon after the mapping of the underlying defect to the 17p13 region, a missense mutation (6970G>A; R2310K) was identified in exon 42 of the splicing factor gene PRPC8 in one patient of this family. Diagnostic restriction enzyme digestion of exon 42 amplified from genomic DNA of all family members revealed that the R2310K mutation segregated fully with the disease. The type I phenotype observed in this family is similar to that described for three other RP13 families with mutations in PRPC8.


Modulation by retinoic acid of insulin-like growth factor (IGF) and IGF binding protein expression in human SK-N-SH neuroblastoma cells.
Growth in neuroblastoma cells is regulated by insulin-like growth factors (IGFs) whose action is modulated by IGF binding proteins (IGFBPs). In this study, SK-N-SH neuroblastoma cells were shown to produce IGF-II, IGFBP-2, IGFBP-4 and small quantities of IGFBP-6. We have studied the effects of a natural morphogen, retinoic acid (RA), on growth and IGFBP expression in these cells. In all experiments, cells were cultured in serum-free medium and treated with 1 mumol/l RA for 12 h. Cell number increased by almost 50% during the first 24 h after the beginning of treatment. This stimulation was inhibited by 80% or more in the presence of the anti-type 1 IGF receptor antibody alpha-IR3 and anti-IGF-II antibody. The IGF-II concentrations in the culture media, measured after acidic gel filtration, increased about 1.5-fold and Northern blotting showed a concomitant increase in IGF-II mRNA levels. The mitogenic effect of RA therefore reflects its stimulation of IGF-II production. The availability of IGF-II to the cells may also be enhanced because of the proteolysis of IGFBP-2 to which it is bound. After this initial phase, proliferation ceased despite continued IGF-II production between 24 and 72 h. Both IGFBP-2 and IGFBP-4 production decreased, whereas that of IGFBP-6 increased. These changes appeared both in the protein quantities and in their mRNAs. Insulin-like growth factor binding protein 6 has a strong affinity for IGF-II, 5-10 times that of IGFBP-2 and at least 10 times that of the type I IGF receptor, and the arrested proliferation may result, at least in part, from sequestration by IGFBP-6 of the IGF-II secreted.


The use of benazepril in hypertensive patients age 55 and over.
Benazepril, a newer angiotensin-converting enzyme inhibitor, has been evaluated for the treatment of mild to moderate hypertension in patients 55 years of age and older. The results of the clinical trials conducted to date indicate that benazepril provides effective antihypertensive therapy in this population, with efficacy comparable to that demonstrated in younger patients. Benazepril does not produce precipitous decreases in diastolic blood pressure following the initial dose, and is well tolerated by the elderly. It has a safety profile similar to that of placebo and generally better than that of hydrochlorothiazide.


Duobinary pulse shaping for frequency chirp enabled complex modulation.
The frequency chirp of optical direct modulation (DM) used to be a performance barrier of optical transmission system, because it broadens the signal optical spectrum, which becomes more susceptible to chromatic dispersion induced inter-symbol interference (ISI). However, by considering the chirp as frequency modulation, the single DM simultaneously generates a 2-D signal containing the intensity and phase (namely, the time integral of frequency). This complex modulation concept significantly increases the optical signal to noise ratio (OSNR) sensitivity of DM systems. This Letter studies the duobinary pulse shaping (DB-PS) for chirp enabled DM and its impact on the optical bandwidth and system OSNR sensitivity. DB-PS relieves the bandwidth requirement, at the sacrifice of system OSNR sensitivity. As DB-PS induces a controlled ISI, the receiver requires one more tap for maximum likelihood sequence estimation (MLSE). We verify this modified MLSE with a 10-Gbaud duobinary PAM-4 transmission experiment.


Contamination and health risk assessment of lead, arsenic, cadmium, and aluminum from a total diet study of Jilin Province, China.
Lead (Pb), arsenic (As), cadmium (Cd) and aluminum (Al) are the four most common heavy metals and can cause serious harm to human health. To evaluate contamination levels and associated safety issues of the four common heavy metals of the residents in Jilin Province, China, a total diet study (TDS) method was used. Concentration and consumption data of the four heavy metals were collected from the fifth Chinese TDS of Jilin province. In total, 12 food groups were studied and two regions were selected for comparison. According to the results, the mean concentration of lead, arsenic, cadmium, and aluminum was 0.0189, 0.0691, 0.0085, and 9.309 mg/kg, respectively. Aluminum in deep-fried dough sticks exceeded the national limit standard. Pollution of the Songhua River Basin is not very different from that of other areas. The average consumer exposure to the four heavy metals in the 2 to 6-year-old group was the highest among all age-groups. Potatoes and their products were the primary sources of dietary exposure to lead. Aquatic products and their related commodities had the highest contribution to arsenic exposure. Vegetables and vegetable products were the main sources of dietary exposure to cadmium. The highest contributor to aluminum in the diet was from cereals and cereal products. In general, there might be some potential risks to the 2 to 6-year-old population due to exposure to lead and aluminum. Contamination of aluminum in cereals and cereal products needs further consideration.


Prevalence of low serum vitamin B12 in Mexican children and women: results from the first National Nutrition Survey (1999) as a basis for interventions and progress.
Serum samples from the 1999 Mexico National Nutrition Survey (NNS) were analyzed to determine the prevalence of low serum B12 concentrations, identify factors related with low values including B12 intake, and importantly, to provide a baseline for monitoring progress in reducing deficiency. Samples for B12 were available from 488 children and 464 women, a sub-sample of the nationally representative 1999 NNS. The national overall prevalence of low (<200 pg/mL) and marginal (200 to 300 pg/mL) serum B12 was 25.6% and 21.0%, respectively. Adolescent girls had the lowest serum B12 concentrations (325 ± 308 pg/mL) and the prevalence of deficiency was 40% in pregnant women even using a lower cut-point (<135 pg/mL). Residents of rural areas and the South, population groups with poorest socioeconomic status, and illiterate and indigenous women had the lowest serum B12 Children and women who met dietary recommendations for B12 intake had higher serum B12 than those who did not. Overall 45.9% of intakes fell below the Estimated Adequate Requirement. Dietary B12 intake of children and women was directly correlated with serum B12 (r = 0.18, p < 0.001 and r = 0.11, p = 0.0304). The prevalence of marginal and deficient B12 status in 1999 was much higher than the most recently published national data suggesting the success of national policies to improve micronutrient status.


Built for speed, not for comfort. Darwinian theory and human culture.
Darwin believed that his theory of evolution would stand or fall on its ability to account for human behavior. No species could be an exception to his theory without imperiling the whole edifice. The ideas in the Descent of Man were widely discussed by his contemporaries although they were far from being the only evolutionary theories current in the late nineteenth century. Darwin's specific evolutionary ideas and those of his main followers had very little impact on the social sciences as they emerged as separate disciplines in the early Twentieth Century. Not until the late twentieth century were concerted, sophisticated efforts made to apply Darwinian theory to human behavior. Why such a long delay? We argue that Darwin's theory was rather modern in respects that conflicted with Victorian sensibilities and that he and his few close followers failed to influence any of the social sciences. The late Twentieth Century work takes up almost exactly where James Baldwin left off at the turn of the century.


Temporal trends in the prevalence and characteristics of hypouricaemia: a descriptive study of medical check-up and administrative claims data.
We aimed to describe temporal trends in the prevalence and characteristics of hypouricaemia. We analysed medical check-up and administrative claims data to calculate hypouricaemia prevalence from 2009 to 2019. Then, using data from 2018 to 2019, we compared the characteristics of individuals with and without hypouricaemia. We also compared the characteristics of those with lower (serum uric acid [sUA] ≤ 1.0 mg/dL) and higher (1.0 mg/dL < sUA ≤ 2.0 mg/dL) hypouricaemia. In total, 1,600,290 subjects underwent medical check-ups. The age-adjusted prevalence of hypouricaemia remained stable at 0.2% overall (men, 0.1%; women, 0.4%). We identified 1704 subjects with hypouricaemia (598 men and 1106 women) among 796,508 subjects and studied their characteristics. The proportion of most pre-existing diseases, including urinary stones, was lower in those with hypouricaemia than in those without hypouricaemia. Cardio-metabolic diseases and Parkinson's disease were more frequent in men with hypouricaemia than those without hypouricaemia. Women with hypouricaemia tended to have healthier characteristics. Hypertension and dyslipidaemia were more common in the lower hypouricaemia group than in the higher hypouricaemia group. The age-adjusted prevalence of hypouricaemia remained stable over 10 years. The characteristics of hypouricaemia subjects appear to differ between the sexes and between lower and higher hypouricaemia groups. Key Points • The prevalence of hypouricaemia remained almost unchanged over 10 years. • Cardio-metabolic diseases and Parkinson's disease were more frequent in men with hypouricaemia than in those without hypouricaemia. • Subjects with extremely low serum urate (sUA ≤ 1.0 mg/dL) appeared to have higher cardio-metabolic disease risks. • Routine checks of sUA could be useful in screening or predicting these conditions.


[The impact of the prevention of cerebral toxoplasmosis].
In France, where 70% of adults are latently infected by toxoplasma, from 20% to 40% of patients with AIDS developed toxoplasmic encephalitis until recently. The prophylactic use of drugs which are active against pneumocystis and toxoplasma has proven to be efficient. These drugs are trimethoprim-sulfamethoxazole or dapsone-pyrimethamine. With the extent of these primary prophylaxis, there is a decrease of risk of toxoplasma encephalitis; thus the rate of toxoplasma encephalitis among opportunistic infections has fallen off from 19% of the patients in 1988 to 6% in 1994, in the department of infectious diseases of the Pitié-Salpêtrière hospital. However, toxoplasmic abscesses occurring despite the prophylaxis are frequently slow growing lesions which can become huge with a moderate mass effect, mimicking the pattern of primary cerebral lymphoma. The rule of antitoxoplasmic trial treatment must be strictly followed, even under prophylaxis.


Low-affinity receptors for tumour necrosis factor-alpha, interferon-gamma and granulocyte-macrophage colony-stimulating factor are expressed on human placental syncytiotrophoblast.
Scatchard binding analysis has been employed to characterize expression of low-affinity receptors for tumour necrosis factor-alpha (TNF-alpha), interferon-gamma (IFN-gamma) and granulocyte-macrophage colony-stimulating factor (GM-CSF) by isolated human placental syncytiotrophoblast microvillous plasma membrane (StMPM) vesicles. Trophoblastic receptors for the c-kit ligand (stem cell factor) could not be identified using the same methods. No high-affinity receptors could be detected for GM-CSF or IFN-gamma, but a minority of high-affinity TNF-alpha receptors were identified. Cross-inhibition studies indicated the low-affinity receptors to be specific for each cytokine rather than to be non-specific cytokine-binding factors. Only relatively high-affinity receptors for TNF-alpha and IFN-gamma could be detected on the BeWo human choriocarcinoma cytotrophoblast cell line, whereas receptor affinity for GM-CSF was similar to that on syncytiotrophoblast. Immunohistochemical staining has confirmed expression of IFN-gamma receptor by syncytiotrophoblast: in contrast, staining for the established TNF-R1 and TNF-R2 receptors was associated mainly with placental vascular endothelium. These low-affinity cytokine receptors could reflect unique biological responses of foetal syncytiotrophoblast in the presence of local concentrations of maternal cytokine.


Severe hypoglycemia in an elderly patient treated with metformin.
The following case of severe hypoglycemia was reported during a systematic evaluation of hospital admissions caused by adverse drug reactions (supported by BfArM). A 79-year-old diabetic woman was admitted to hospital in a stuporous and unresponsive state. The initial physical examination revealed no other abnormal findings. Serum blood glucose was found to be 2.0 mmol/l and HbA1c was 4.6%. The patient had been started on antidiabetic therapy with metformin 2 months earlier. Treatment with other drugs being taken at that time, an ACE inhibitor, an NSAID and nitrofurantoin, remained unchanged. DIAGNOSIS, TREATMENT AND FOLLOW-UP: Laboratory tests excluded lactic acidosis and renal insufficiency. Cerebral computed tomography findings were normal. The patient improved dramatically following administration of glucose. Other laboratory findings confirmed the diagnosis of hypoglycemia. Blood glucose concentrations ranged between 4.0 and 10.0 mmol/l in the subsequent days and the patient could be discharged in full health. Drug-induced hypoglycemia is possible even in diabetics not receiving insulin or oral antidiabetic agents increasing insulin secretion. The risk of drug-induced hypoglycemia should be particularly considered when drugs containing blood glucose-lowering components are combined. Metformin does not usually cause hypoglycemia when administered as monotherapy. We suspected that hypoglycemia in this patient was caused by additional blood glucose-lowering effects of the ACE inhibitor and the NSAID possibly combined with a suboptimal nutrition. The indications for metformin administration undergo critical scrutiny.


Next-Generation Sequencing and the Return of Results.
The impact of next-generation sequencing (NGS) on the issue of return of results is defying clear policy guidance and creating international confusion. Limiting ourselves to the return of results revealed by NGS (including incidental findings) in adults, children, family members of deceased individuals, and population studies, we describe and contrast emerging policy positions in Europe, Canada, and the United States. Until there are clear, scientific, and professional standards and practical policy, both researchers and clinicians cannot be faulted for being either hesitant or pressured to return NGS results.


Transperineal repair of persistent rectovaginal fistulas using an acellular cadaveric dermal graft (AlloDerm).
A number of surgical techniques have been described to treat rectovaginal fistulas. Recurrent or persistent fistulas after previous repair can be particularly difficult to treat. We report a novel technique used to successfully repair rectovaginal fistulas after failed mucosal advancement flap procedures using a transperineal-layered closure with an interposed graft of acellular cadaveric dermis (Alloderm).


Chronic kidney disease: implications for the perioperative period.
End-stage renal disease (ESRD) and chronic kidney disease (CKD) are increasing health problems worldwide. In the US alone, an estimated 26 million people suffer from some form of CKD. In countries such as India and Pakistan, the prevalence of CKD is also rapidly rising. The presence of CKD is associated with increased perioperative morbidity and mortality, even when adjusted for other variables such as hypertension or diabetes. Frequently, CKD is under diagnosed, so patients and physicians are often unaware of the impaired renal function. Renal dysfunction as a predictor of perioperative outcomes is discussed together with therapeutic interventions aimed at the protection of renal function. Better interventions and diagnostic tools, such as cystatin C, are needed to further improve perioperative morbidity and mortality in patients with CKD.


[Acute craniocerebral trauma in childhood--early use of MRI].
The purpose of the study was to evaluate the present diagnostic potential of MRI in early stage head trauma und possibly to replace CT studies in children. FLAIR-techniques consequently applied as "scout sequences" provided reliable identification of traumatic intra- and extracranial lesions yet during the first measurement in all 24 cases. Follow-up scan confirmed the initial results. The reliability of MRI in acute pediatric head trauma is underlined by the fact that CT scans were no longer necessary within in the last three years. Therefore the imaging algorithm of acute head trauma in children has changed in our institution: medium and high risk patients undergo MRI, in young infants we do US first. HR-CT is reserved for lesions of the visceral cranium. X rays are out.


Mechanism of action of nucleotide excision repair machinery.
Nucleotide excision repair (NER) is a versatile DNA repair pathway essential for the removal of a broad spectrum of structurally diverse DNA lesions arising from a variety of sources, including UV irradiation and environmental toxins. Although the core factors and basic stages involved in NER have been identified, the mechanisms of the NER machinery are not well understood. This review summarizes our current understanding of the mechanisms and order of assembly in the core global genome (GG-NER) pathway.


[Practice guideline 'Brain metastases' (revision)].
Improved survival of cancer patients results in an increase in the incidence of brain metastases. In addition, asymptomatic brain metastases are more often detected as a consequence of active screening. In patients with cancer and new neurological symptoms, MRI of the brain is indicated to assess the presence and number of brain metastases. Decisions concerning treatment of brain metastases should take place within a multidisciplinary team. Treatment is in the first instance focused on improvement or preservation of neurological functioning. The main treatment options for patients with brain metastases are whole brain radiotherapy, stereotactic radiosurgery/radiotherapy, and neurosurgical resection. The choice of treatment depends on the number and the location of the brain metastases, the general and neurological condition of the patient, the extent of extracranial tumour activity, and the expected results of treatment. The revised guideline supports the policy of whole brain radiotherapy not being the standard treatment following stereotactic radiosurgery or radiotherapy. In the case of complete resection, confirmed using early postoperative MRI, whole brain radiotherapy does not add to survival benefit, while patients may suffer from radiation-induced toxicity.


Use of implantable intraperitoneal diffusion chambers to study Bordetella pertussis pathogenesis: growth and toxin production in vivo.
A new animal model for Bordetella pertussis infection is described. The system utilizes small chambers bounded by 0.22-micron filter membranes. The chambers are inoculated with B. pertussis, sealed, and surgically implanted into the peritoneal cavity of mice. The chamber system allows dynamic interchange of soluble host and bacterial factors, but not cells. We have used this system to study the growth of various clinical isolates and vaccine strains of B. pertussis, including an isogenic virulent/avirulent pair. All virulent strains tested grew well and had remarkably similar growth kinetics. We monitored cellular and humoral host responses, including the response to pertussis toxin. Antitoxin appeared 21-37 days after implantation of the chambers. The model allows us to dissociate the ability of an organism to grow in vivo from other properties (e.g., attachment and toxin production) that may be involved in pathogenesis.


Evidence for the regulation of phytochrome-mediated processes in bean roots by the neurohumor, acetylcholine.
Using pharmacological and chromatographic techniques, it was shown that acetylcholine was present in all organs of both light- and dark-grown mung bean seedings (Phaseolus aureus). The highest concentrations were found in tissues containing active growing points: buds and secondary roots. Within 4 minutes, red light caused an increase in the efflux of acetylcholine from secondary root tips as well as a significant increase in the endogenous titer. Four minutes of subsequent far red light reduced the latter to a level comparable to that in the dark.Acetylcholine, given for 4 minutes in the dark, was able to substitute for red light in reducing the formation of secondary roots, inducing increased H(+) efflux, and causing the root tips to adhere to a negatively charged glass surface. Acetylcholine-esterase and atropine inhibited the latter phenomenon, whereas eserine inhibited the far red-induced release from glass. THESE AND OTHER DATA SUPPORT THE CONCLUSION THAT ACETYLCHOLINE FUNCTIONS IN MUNG BEAN ROOTS AS IT DOES IN ANIMAL SYSTEMS: by mediating changes in ion flux across cell membranes. It also seems probable that acetylcholine acts as a local hormone which regulates these phytochrome-mediated phenomena.


Ocrelizumab in Multiple Sclerosis: A Real-World Study From Spain.
Objectives: The aim of this study was to describe the tolerability, safety, and effectiveness of ocrelizumab for primary progressive multiple sclerosis (PPMS) and relapsing multiple sclerosis (RMS) in a clinical practice setting. Methods: In this retrospective observational study, we analyzed clinical and MRI data in all patients with PPMS and RMS who had received at least one infusion of ocrelizumab in two health areas in south-eastern Spain. Patients involved in any ocrelizumab trial and those patients with a follow-up shorter than 6 months were excluded. Results: The cohort included 70 patients (42 women) who had received ocrelizumab; 30% had PPMS and 70%, RMS. At baseline, patients' mean age was 47.1 years in the PPMS group and 39.2 years in the RMS group, while the median EDSS was 3.0 and 2.5, respectively. Median follow-up was 13.6 months. The median number of treatment cycles was three. Most patients remained free from clinical and MRI activity after ocrelizumab initiation. Baseline MRI showed T1 Gd-enhancing lesions in 57% of the patients; by the first MRI control at 4-6 months, all patients except one were free of T1 Gd-enhancing lesions (69/70, 98.6% P < 0.001). The proportion of patients with NEDA was 94% in the group of RMS patients who were followed for at least 1 year. Ocrelizumab was generally well-tolerated; the most common adverse events were infusion-related reactions and infections, none of which were serious. Conclusions: Our real-world study supports the tolerability, safety, and effectiveness of ocrelizumab in clinical practice.


Interpreting changes in the economic status of the elderly, 1949-1979.
"This paper analyzes changes in the economic well-being of the elderly using data from the [U.S.] Decennial Censuses of 1950 through 1980. We find that the economic status of each elderly cohort is higher on average than that of the preceding cohort. Certain events associated with age--retirement for both men and women and widowhood for women--are associated with declining incomes. Controlling for sex, labor force participation, and marital status, however, the economic well-being of elderly cohorts generally increases with age."


Lipases and carboxylesterases: possible roles in the hepatic utilization of vitamin A.
The formation and hydrolysis of retinyl esters are key processes in the metabolism of the fat-soluble micronutrient vitamin A. Long-chain acyl esters of retinol are the major chemical form of vitamin A (retinoid) stored in the body. Although retinyl esters are found in a variety of tissues and cell types, most of the total body retinoid is accounted for by the retinyl esters stored in the liver. Thus, these esters represent the major endogenous source of retinoid that can be delivered to peripheral tissues for conversion to biologically active forms. This paper summarizes the current state of our knowledge about the identity, function and regulation of the hepatic enzymes that are potentially involved in catalyzing the hydrolysis of retinyl esters. These enzymes include several known and characterized lipases and carboxylesterases.