The effects of pre- and perinatal undernutrition on the succinic dehydrogenase content of muscle fibres from fast and slow rat muscles.
Male rats were subjected to early undernutrition by limiting the mothers' food supply by 50% during pregnancy and lactation. At age 36 weeks, quantitative cytochemical determinations of succinic dehydrogenase activity were made in muscle fibres from the anterior tibialis and soleus muscles. Marked decreases were found in the former muscle but relatively little decrease was seen in the latter. This response of the muscles to early undernutrition was discussed with reference to other studies on pre and post-natal starvation.


[Congenital dermatofibrosarcoma protuberans: a case report].
Dermatofibrosarcoma protuberans is a rare low-grade fibrohistiocytic tumor with onset normally at ages between 20 and 50 years. It presents as a violaceous plaque or macule with an appearance suggestive of vascular lesion, on which nodular lesions appear later. Histological diagnosis is based on the presence of a spindle-cell tumor arranged in small bundles in a characteristic cartwheel pattern. The local recurrence rate is high but metastases are rare. The treatment is surgical resection with wide margins. The tumor rarely affects children under 16 years of age and it is even less common at birth--only 27 congenital cases have been described in the literature. We describe the case of a 10-year-old boy with dermatofibrosarcoma protuberans present since birth and currently without signs of recurrence.


Selective binding to AT sequences in DNA by an acridine-linked peptide containing the SPKK motif.
The sequence selectivity of binding to DNA by an acridine-linked peptide ligand has been investigated by means of footprinting methodologies. The ligand conjugates an anilino-acridine intercalating chromophore with the potentially minor groove binder octapeptide SPKKSPKK. This basic peptide corresponds to a highly conserved DNA recognition motif found in histone H1 and several other nonhistone proteins. Three complementary techniques using DNase I, hydroxyl radicals and osmium tetroxide as sequencing probes have been employed to evaluate both the sequence specificity of binding and the drug-induced conformational changes in DNA. The results converge to demonstrate the AT-selectivity and support a model in which the peptide moiety lies in the minor groove. DNA-binding sites of the conjugate are restricted to a few alternating AT-sequences proximal to GC-rich regions. Binding to homooligomeric runs of A and T is clearly disfavoured by the hybrid whereas such sequences represent preferred binding sites for the unsubstituted basic peptide. These differences reflect the influence of the anilino-acridine chromophore, which evidently contributes to the DNA recognition process allowing the peptide only to contact defined DNA sequences.


Positional calibration of an ultrasound image-guided robotic breast biopsy system.
Precision biopsy of small lesions is essential in providing high-quality patient diagnosis and management. Localization depends on high-quality imaging. We have developed a dedicated, fully automatic volume breast ultrasound (US) imaging system for early breast cancer detection. This work focuses on development of an image-guided robotic biopsy system that is integrated with the volume breast US system for performing minimally invasive breast biopsies. The objective of this work was to assess the positional accuracy of the robotic system for breast biopsy. We have adapted a compact robotic arm for performing breast biopsy. The arm incorporates a force torque sensor and is modified to accommodate breast biopsy sampling needles mounted on the robot end effector. Volume breast US images are used as input to a targeting algorithm that provides the physician with control of biopsy device guidance and trajectory optimization. In this work, the positional accuracy was evaluated using (1) a light-emitting diode (LED) mounted on the end effector and (2) a LED mounted on the end of a biopsy needle, each of which was imaged for each robot controller position as part of mapping the positional accuracy throughout a volume that would contain the breast. We measured the error in each location and the cumulative error. Robotic device performance over the volume provided mean accuracy ± SD of 0.76 ± 0.13 mm (end effector) and 0.55 ± 0.13 mm (needle sample location), sufficient for a targeting accuracy within ±1 mm, which is suitable for clinical use. Depth positioning error also was small: 0.38 ± 0.03 mm. Reproducibility was excellent with less than 0.5% variation. Overall accuracy and reproducibility of the compact robotic device were excellent, well within clinical biopsy performance requirements. Volume breast US data provide high-quality input to a biopsy sampling algorithm under physician control. Robotic devices may provide more precise device placement, assisting physicians with biopsy procedures.


TT virus infection among renal transplant recipients.
To clarify the prevalence of TT virus (TTV) infection in renal transplant recipients and to estimate the role of TTV in patients with post-transplant liver function abnormalities, TTV-DNA of 47 renal transplant recipients was screened by polymerase chain reaction (PCR) according to a method described by Okamoto et al. before and after the renal transplantation. One of them was positive for hepatitis B surface antigen (HBsAg), one was positive for anti-hepatitis C virus (HCV) and other 45 were negative for both HBsAg and anti-HCV. TTV-DNA was detected in 22 of 47 patients before renal transplantation, and nine became positive after transplantation. All 47 patients showed a normal level of ALT before transplantation. Three of nine (33%) who became positive for TTV-DNA after transplantation and three of 16 (19%) who were negative for TTV-DNA before and after transplantation showed transient elevation of ALT. These results indicate that TTV was highly prevalent among renal transplant recipients, but a clear association between TTV and post-transplant liver function abnormality was not found.


Pharmacokinetics of amikacin in African gray parrots.
Amikacin sulfate was administered to African gray parrots at 3 dosages (5, 10, and 20 mg/kg) via 2 routes (IV and IM). The elimination half-time was approximately 1 hour (range, 0.9 to 1.34 hour). The apparent bioavailability of IM administered drug was 61 to 106% and was not dose-related.


Hegemonic structure of basic, clinical and patented knowledge on Ebola research: a US army reductionist initiative.
Ebola hemorrhagic fever (Ebola) is still a highly lethal infectious disease long affecting mainly neglected populations in sub-Saharan Africa. Moreover, this disease is now considered a potential worldwide threat. In this paper, we present an approach to understand how the basic, clinical and patent knowledge on Ebola is organized and intercommunicated and what leading factor could be shaping the evolution of the knowledge translation process for this disease. A combination of citation network analysis; analysis of Medical heading Subject (MeSH) and Gene Ontology (GO) terms, and quantitative content analysis for patents and scientific literature, aimed to map the organization of Ebola research was carried out. We found six putative research fronts (i.e. clusters of high interconnected papers). Three research fronts are basic research on Ebola virus structural proteins: glycoprotein, VP40 and VP35, respectively. There is a fourth research front of basic research papers on pathogenesis, which is the organizing hub of Ebola research. A fifth research front is pre-clinical research focused on vaccines and glycoproteins. Finally, a clinical-epidemiology research front related to the disease outbreaks was identified. The network structure of patent families shows that the dominant design is the use of Ebola virus proteins as targets of vaccines and other immunological treatments. Therefore, patents network organization resembles the organization of the scientific literature. Specifically, the knowledge on Ebola would flow from higher (clinical-epidemiology) to intermediated (cellular-tissular pathogenesis) to lower (molecular interactions) levels of organization. Our results suggest a strong reductionist approach for Ebola research probably influenced by the lethality of the disease. On the other hand, the ownership profile of the patent families network and the main researches relationship with the United State Army suggest a strong involvement of this military institution in Ebola research.


Partitioning and bioaccumulation of cadmium in artificial sediment systems: application of a stable isotope tracer technique.
The utility of stable isotope tracers for investigating the relationship between cadmium (Cd) partitioning in artificial sediment-water systems and Cd accumulation in a benthic detritivore (Asellus racovitzai, Isopoda) was explored. In the laboratory, Cd isotopes were applied to synthetic sediment and isotope concentrations were measured in sediment, overlying water and exposed asellids over a 10-day period. Isotope ratios measured in sediment and water were compared to ratios measured in asellids to determine whether Cd partitioning could predict metal bioaccumulation. Two different parameters which might affect Cd partitioning between the sediment and overlying water compartments were investigated: the chemical form in which Cd was added to systems, and the organic matter content of the sediment. To test the effect of chemical form on Cd partitioning, three isotopes of cadmium were individually applied to formulated sediment in varying combinations of 113Cd(NO3)2, 112Cd-humic acid (HA) 114CdSO4. The results demonstrated that chemical form did not influence partitioning, as the Cd isotope that was applied to sediment in the nitrate form exhibited similar partitioning between sediment and overlying water as the isotope that was applied in the sulfate or HA form. However, Cd isotope concentrations in overlying water were strongly related to the pattern of isotope accumulation in asellids suggesting that overlying water concentrations determined Cd bioaccumulation. In contrast, when the organic matter content of sediment was increased through the addition of Sphagnum peat moss, total Cd concentrations in overlying water and tissue were low, and there was no relationship between Cd-isotope concentrations in tissue and water. These results indicate that Cd accumulation occurred primarily from water, and factors that increase metal partitioning to sediment, such as increased sediment organic matter content, decrease Cd accumulation in asellids. The stable isotope tracer method described herein appears to be a useful technique for investigating the relationship between metal partitioning and bioaccumulation in simple sediment systems, but could also be extended to more complex systems, and used with different metals that have multiple stable isotopes.


Phylogeography of ground tit (Pseudopodoces humilis) based on mtDNA: evidence of past fragmentation on the Tibetan Plateau.
Pseudopodoces humilis, a long misclassified terrestrial tit, is the only species of parid whose distribution is limited to treeless terrain and endemic to the Tibetan Plateau. We revealed the phylogeographic structure of the species by using mitochondrial control region, as well as comparing morphological characters. The distinct geographic distributions of two major clades suggest spatial and temporal separations that coincide with important climatic and paleogeographic changes following the uplift of the Tibetan Plateau. Population expansion was inferred for the population at the platform of the Plateau 0.17 million years before present (Ma B.P.), and restricted gene flow with isolation by distance was detected within this region, congruent with expansion occurring after the extensive glacial period. A significant decrease in body size with decreasing altitude was found, possibly indicating selection for larger-sized birds at higher altitude.


Further terpenoids from the Chloranthaceae plant Chloranthus multistachys and their anti-neuroinflammatory activities.
Three labdane-type [multisins A-C (1-3)], two guaiane-type [multisins D (4) and E (5)], and one eudesmane-type [multisin F (6)] previously undescribed terpenoids, together with 14 mono- (7-20) and seven dimeric- (21-27) known terpenoids, were isolated from the 90% MeOH extract of the whole plant of Chloranthus multistachys. Their structures and absolute configurations were determined by extensive spectroscopic methods and electronic circular dichroism (ECD) calculations. Compounds 4 and 5 are rare trinor-sesquiterpenes with a de-isopropyl guaiane skeleton, whereas compound 6 is a rearranged dinor-eudesmene featuring an uncommon octahydro-1H-indene ring system. Among the isolates, the dimeric lindenane sesquiterpenoid shizukaol C (25) exhibited the most potent (IC50 = 8.04 μM) anti-neuroinflammatory activity by inhibiting the nitric oxide (NO) production in lipopolysaccharide (LPS)-stimulated murine BV-2 microglial cells.


Positive Association Between Adipose Tissue and Bone Stiffness.
Obesity is often considered to have a protective effect against osteoporosis. On the other hand, several recent studies suggest that adipose tissue may have detrimental effects on bone quality. We therefore aimed to investigate the associations between body mass index (BMI), waist circumference (WC), visceral adipose tissue (VAT) or abdominal subcutaneous adipose tissue (SAT), and bone stiffness. The study involved 2685 German adults aged 20-79 years, who participated in either the second follow-up of the population-based Study of Health in Pomerania (SHIP-2) or the baseline examination of the SHIP-Trend cohort. VAT and abdominal SAT were quantified by magnetic resonance imaging. Bone stiffness was assessed by quantitative ultrasound (QUS) at the heel (Achilles InSight, GE Healthcare). The individual risk for osteoporotic fractures was determined based on the QUS-derived stiffness index and classified in low, medium, and high risk. Linear regression models, adjusted for sex, age, physical activity, smoking status, risky alcohol consumption, diabetes, and height (in models with VAT or abdominal SAT as exposure), revealed positive associations between BMI, WC, VAT or abdominal SAT, and the QUS variables broadband-ultrasound attenuation or stiffness index. Moreover, BMI was positively associated with speed of sound. Our study shows that all anthropometric measures including BMI and, WC as well as abdominal fat volume are positively associated with bone stiffness in the general population. As potential predictors of bone stiffness, VAT and abdominal SAT are not superior to easily available measures like BMI or WC.


Different carbohydrate exposures and weight gain-results from a pooled analysis of three population-based studies.
The role of carbohydrate quantity and quality in weight gain remains unsolved, and research on carbohydrate subcategories is scarce. We examined total carbohydrates, dietary fiber, total sugar, and sucrose intake in relation to the risk of weight gain in Finnish adults. Our data comprised 8327 adults aged 25-70 years in three population-based prospective cohorts. Diet was assessed by a validated food frequency questionnaire and nutrient intakes were calculated utilizing the Finnish Food Composition Database. Anthropometric measurements were collected according to standard protocols. Two-staged pooling was applied to derive relative risks across cohorts for weight gain of at least 5% by exposure variable intake quintiles in a 7-year follow-up. Linear trends were examined based on a Wald test. No association was observed between intakes of total carbohydrate, dietary fiber, total sugar or sucrose and the risk of weight gain of at least 5%. Yet, total sugar intake had a borderline protective association with the risk of weight gain in participants with obesity (RR 0.63; 95% CI 0.40-1.00 for highest vs. lowest quintile) and sucrose intake in participants with ≥10% decrease in carbohydrate intake during the follow-up (RR 0.78; 95% CI 0.61-1.00) after adjustments for sex, age, baseline weight, education, smoking, physical activity, and energy intake. Further adjustment for fruit consumption strengthened the associations. Our findings do not support an association between carbohydrate intake and weight gain. However, the results suggested that concurrent changes in carbohydrate intake might be an important determinant of weight change and should be further examined in future studies.


The Emerging Role of Automation, Measurement Standardization, and Artificial Intelligence in Foot and Ankle Imaging: An Update.
In the past few years, advances in clinical imaging in the realm of foot and ankle have been consequential and game changing. Improvements in the hardware aspects, together with the development of computer-assisted interpretation and intervention tools, have led to a noticeable improvement in the quality of health care for foot and ankle patients. Focusing on the mainstay imaging tools, including radiographs, computed tomography scans, and ultrasound, in this review study, the authors explored the literature for reports on the new achievements in improving the quality, accuracy, accessibility, and affordability of clinical imaging in foot and ankle.


Effect of Resistance Exercises on Function and Pain in Fibromyalgia: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.
This review aimed to compare the effectiveness of resistance exercise with that of other exercises in functional improvement and pain control in patients with FM. PubMed, Embase, Scopus, and Cochrane databases were searched for studies published from their inception until March 2023. The following medical search heading terms were used: "resistance OR strength OR strengthening" AND "fibromyalgia". The analysis was performed using the statistical package Review Manager, version 5.4.1. This study reviewed 11 randomized controlled trials involving 530 patients. In comparison with no intervention, resistance exercise reduced the FIQ total score, pain score, tender points, and depression and improved physical function. Compared with flexibility exercise, resistance exercise reduced the FIQ total score. Compared with aerobic exercise, resistance exercise shows similar effects on pain control, reduction of tender points and improvement of physical function. Compared with other exercises, resistance exercise demonstrated a more favorable effect on the FIQ total score, and the effects on pain control, tender points, physical function, and depression were comparable. Thus, resistance exercise exhibits comparable or superior effects when compared with other interventions and more precise research is needed to confirm this conclusion.


Processing speed and executive functions in cognitive aging: how to disentangle their mutual relationship?
The processing-speedtheory and the prefrontal-executivetheory are competing theories of cognitive aging. Here we used a theoretically and methodologically-driven framework to investigate the relationships among measures classically used to assess these two theoretical constructs. Twenty-eight young adults (18-32 years) and 39 healthy older adults (65-80 years) performed a battery of nine neuropsychological and experimental tasks assessing three executive function (EF) components: Inhibition, Updating, and Shifting. Rate of information processing was evaluated via three different experimental and psychometric tests. Partial correlations analyses suggested that 2-Choice Reaction Time (CRT) performance is a more pure measure of processing speed than Digit Symbol Substitution Test (DSST) performance in the elderly. Hierarchical regression analyses showed that, although measures of processing speed and EF components share mutual variance, each measure was independently affected by chronological age. The unique adverse effect of age was more important for processing speed than for EF. The processing-speed theory and the prefrontal-executive theory of cognitive aging were shown not to be mutually exclusive but share mutual variance. This implies the need to control for their mutual relationship before examining their unique potential role in the explanation of age-related cognitive declines. Caution has still to be taken concerning the tasks used to evaluate these theoretical constructs.


Recurrence of clinically significant hepatitis A following liver transplantation for fulminant hepatitis A.
We report hepatitis A virus (HAV) infection of a liver allograft following transplantation for fulminant liver failure due to HAV infection. This rare condition has been described in only three patients to date. After liver transplantation allograft function was good, but starting 80 days after transplantation, episodes of acute graft dysfunction were observed. To elucidate the reason for acute hepatic dysfunction a large number of differential diagnoses were tested. HAV RNA was undetectable for more than 80 days after transplantation. Detection of genomic HAV RNA by RT-PCR in serum and stool at the time of graft dysfunction led to the diagnosis of recurrent HAV infection. We suggest that the risk of HAV reinfection after liver transplantation may be far higher than expected as results may be misinterpreted as rejection episodes.


Usage of U7 snRNA in gene therapy of hemoglobin S disorder - is it feasible?
Hemoglobin (Hb) S disorder [beta6(A3)Glu-->Val, GAG-->GTG] is an important hemoglobinopathy with the highest endemicity in Africa. Here, the author performs a basic bioinformatics gene ontology study to assess the effect of co-expression between nucleic acid sequence for human Hb S beta globin chain and U7.623. According to this study, the analytical results show that fully recovery of hemoglobin in both function and biological process can be got. Here, the author proposed that U7 snRNA might be a probable tool for treatment by gene therapy approach in Hb S disorder.


Applying patient-reported outcome methodology to capture patient-reported health data: Report from an NIH Collaboratory roundtable.
Patient-reported health data provide information for pragmatic clinical trials that may not be readily available from electronic health records or administrative claims data. In this report, we present key considerations for collecting patient-reported health information in pragmatic clinical trials, which are informed by best practices from patient-reported outcome research. We focus on question design and administration via electronic data collection platforms with respect to 3 types of patient-reported health data: medication use, utilization of health care services, and comorbid conditions. We summarize key scientific literature on the accuracy of these patient-reported data compared with electronic health record data. We discuss question design in detail, specifically defining the concept to be measured, patient understanding of the concept, recall periods of the question, and patient willingness to report. In addition, we discuss approaches for question administration and data collection platforms, which are key aspects of successful patient-reported data collection.


An on-chip photonic deep neural network for image classification.
Deep neural networks with applications from computer vision to medical diagnosis1-5 are commonly implemented using clock-based processors6-14, in which computation speed is mainly limited by the clock frequency and the memory access time. In the optical domain, despite advances in photonic computation15-17, the lack of scalable on-chip optical non-linearity and the loss of photonic devices limit the scalability of optical deep networks. Here we report an integrated end-to-end photonic deep neural network (PDNN) that performs sub-nanosecond image classification through direct processing of the optical waves impinging on the on-chip pixel array as they propagate through layers of neurons. In each neuron, linear computation is performed optically and the non-linear activation function is realized opto-electronically, allowing a classification time of under 570 ps, which is comparable with a single clock cycle of state-of-the-art digital platforms. A uniformly distributed supply light provides the same per-neuron optical output range, allowing scalability to large-scale PDNNs. Two-class and four-class classification of handwritten letters with accuracies higher than 93.8% and 89.8%, respectively, is demonstrated. Direct, clock-less processing of optical data eliminates analogue-to-digital conversion and the requirement for a large memory module, allowing faster and more energy efficient neural networks for the next generations of deep learning systems.


Predictors of serum chlorinated pesticide concentrations among prepubertal Russian boys.
Few studies have evaluated predictors of childhood exposure to organochlorine pesticides (OCPs), a class of lipophilic persistent chemicals. Our goal was to identify predictors of serum OCP concentrations-hexachlorobenzene (HCB), β-hexachlorocyclohexane (β-HCH), and p,p-dichlorodiphenyldichloroethylene (p,p´-DDE)-among boys in Chapaevsk, Russia. Between 2003 and 2005, 499 boys 8-9 years of age were recruited in a prospective cohort. The initial study visit included a physical examination; blood collection; health, lifestyle, and food-frequency questionnaires; and determination of residential distance from a local factory complex that produced HCB and β-HCH. Fasting serum samples were analyzed for OCPs at the U.S. Centers for Disease Control and Prevention. General linear regression models were used to identify predictors of the boys' serum HCB, β-HCH, and p,p´-DDE concentrations. Among 355 boys with OCP measurements, median serum HCB, β-HCH, and p,p´-DDE concentrations were 158, 167, and 284 ng/g lipid, respectively. Lower body mass index, longer breastfeeding duration, and local dairy consumption were associated with higher concentrations of OCPs. Boys who lived < 2 km from the factory complex had 64% (95% CI: 37, 96) and 57% (95% CI: 32, 87) higher mean HCB and β-HCH concentrations, respectively, than boys who lived ≥ 5 km away. Living > 3 years in Chapaevsk predicted higher β-HCH concentrations, and having parents who lacked a high school education predicted higher p,p´-DDE concentrations. Among this cohort of prepubertal Russian boys, predictors of serum OCPs included consumption of local dairy products, longer local residence, and residential proximity to the local factory complex.


Cardio-protective effects of a dioxidovanadium(V) complex in male sprague-dawley rats with streptozotocin-induced diabetes.
Cardiovascular complications are among the leading causes of morbidity and mortality in diabetes mellitus (DM). Despite the anti-hyperglycemic effects of various anti-diabetic therapeutic agents like insulin, some of these drugs are implicated in precipitating cardiovascular dysfunction. There is therefore an imperative need to seek alternative drugs that may ameliorate these complications. Accordingly, the aim of the study was to investigate the effects of a dioxidovanadium (V) complex, cis-[VO2(obz)py]) on selected cardiovascular function markers in STZ-induced diabetic rats. The vanadium complex (40 mg kg) was administered orally twice every 3rd day 5 weeks, non-diabetic and diabetic control groups received distilled water whereas the insulin group received subcutaneous insulin injections twice daily for 5 weeks. Blood glucose concentrations, mean arterial pressure (MAP), heart rate, triglycerides (TG) and total cholesterol concentrations were monitored weekly for 5 weeks. Rats were then euthanised and blood and hearts were collected for biochemical analysis. There was a significant decrease in blood glucose, triglycerides, cholesterol concentrations as well as blood pressure of vanadium treated rats compared to the untreated diabetic animals. Vanadium treatment also attenuated cardiac oxidative stress and decreased the expression of transforming growth factor β1 (TGFβ1) and Smad7. Lastly, the administration of the vanadium complex significantly decreased C reactive protein (CRP) and cardiotropin 1(CT-1) concentrations in the plasma and heart tissues. The administration of the dioxidovanadium(V) complex to diabetic rats culminated into cardio-protective effects. Taken together, these observations suggest that this metal complex exhibit a significant potential as an alternative therapeutic drug for DM management.


Effect of crystalline phase assemblage on reliability of 3Y-TZP.
Strengthening mechanisms of zirconia ceramics stabilized with 3 mol% yttria (3Y-TZP) are complex and dictated by the crystalline phase assemblage. Although their clinical performance for dental restorations has been excellent, there is evidence that framework fractures do occur and have been underreported. Meanwhile, the relationship between phase assemblage and reliability of 3Y-TZP is not properly understood. The purpose of this in vitro study was to elucidate the relationship between crystalline phase assemblage and the reliability of 3Y-TZP and to calculate the associated probabilities of survival. Disks of 3Y-TZP were prepared from cylindrical blanks and randomly assigned to 12 experimental groups (n=20 per group). Different crystalline phase assemblages were produced by either varying the sintering temperature from 1350 °C to 1600 °C and/or treating the surface by airborne-particle abrasion with 50-mm alumina particles at a pressure of 0.2 MPa for 1 minute with or without subsequent heat treatment. Crystalline phases were analyzed by standard and grazing incidence X-ray diffraction (GIXRD). The relationship between phase assemblage and reliability was determined by measuring the biaxial flexural strength (BFS) according to ISO standard 6872 and by using Weibull statistics to calculate the Weibull modulus (m), probability of survival, and maximum allowable stresses. XRD results were analyzed by ANOVA to detect statistically significant differences between groups. Adjustment for all pairwise group comparisons was made using the Tukey method (α=.05). Standard incidence XRD confirmed the presence of a small amount of cubic phase after sintering at 1350 °C. A cubic-derived nontransformable tetragonal t'-phase was observed at sintering temperatures of 1450 °C and above, the amount of which increased linearly. GIXRD revealed that airborne-particle abraded groups sintered at 1350 °C and 1600 °C had the highest variability in monoclinic phase fraction as a function of depth. These groups were also associated with the lowest reliability. Groups as-sintered at 1350 °C and 1600 °C had the lowest modulus (m=8.1 [0.5] and 7.0 [0.8], respectively) and probability of survival (Ps) for a maximum allowable stress of 700 MPa, while treated groups sintered at 1450 °C and 1550 °C were associated with the highest modulus (from 15.0 [1.4] to 20.9 [1.4]) and Ps (≥0.9999). The lower strength and reliability of groups sintered at 1600 °C was consistent with the presence of a significant amount of nontransformable t'-phase. The pattern of BFS results indicated that ferro-elastic domain switching was a dominant strengthening mechanism in 3Y-TZP. The present study first reported on the detrimental effect of the cubic-derived nontransformable t'-phase on the mechanical properties of 3Y-TZP. It was demonstrated that phase assemblage determined reliability and was directly linked to the probability of survival.


Metaproteomics of cellulose methanisation under thermophilic conditions reveals a surprisingly high proteolytic activity.
Cellulose is the most abundant biopolymer on Earth. Optimising energy recovery from this renewable but recalcitrant material is a key issue. The metaproteome expressed by thermophilic communities during cellulose anaerobic digestion was investigated in microcosms. By multiplying the analytical replicates (65 protein fractions analysed by MS/MS) and relying solely on public protein databases, more than 500 non-redundant protein functions were identified. The taxonomic community structure as inferred from the metaproteomic data set was in good overall agreement with 16S rRNA gene tag pyrosequencing and fluorescent in situ hybridisation analyses. Numerous functions related to cellulose and hemicellulose hydrolysis and fermentation catalysed by bacteria related to Caldicellulosiruptor spp. and Clostridium thermocellum were retrieved, indicating their key role in the cellulose-degradation process and also suggesting their complementary action. Despite the abundance of acetate as a major fermentation product, key methanogenesis enzymes from the acetoclastic pathway were not detected. In contrast, enzymes from the hydrogenotrophic pathway affiliated to Methanothermobacter were almost exclusively identified for methanogenesis, suggesting a syntrophic acetate oxidation process coupled to hydrogenotrophic methanogenesis. Isotopic analyses confirmed the high dominance of the hydrogenotrophic methanogenesis. Very surprising was the identification of an abundant proteolytic activity from Coprothermobacter proteolyticus strains, probably acting as scavenger and/or predator performing proteolysis and fermentation. Metaproteomics thus appeared as an efficient tool to unravel and characterise metabolic networks as well as ecological interactions during methanisation bioprocesses. More generally, metaproteomics provides direct functional insights at a limited cost, and its attractiveness should increase in the future as sequence databases are growing exponentially.


Evaluation of in vitro free radical scavenging potential of Streptomyces sp. AM-S1 culture filtrate.
The present study was carried out to determine the free radical scavenging potential of culture filtrate of Streptomyces sp. AM-S1. Antioxidant activity of culture filtrate, lyophilized culture filtrate and ethyl acetate extract of Streptomyces sp. AM-S1 was determined by various in vitro assays such as ferric reducing power assay, phosphomolybdenum reduction, DPPH and ABTS radical scavenging activities. The results revealed that the culture filtrate of Streptomyces sp. AM-S1 effectively scavenged DPPH (IC50 90.2 μl/ml) and ABTS (IC50 13.2 μl/ml) radicals in a concentration dependent manner. In all the assays, ethyl acetate extract registered higher antioxidant activity when compared with the lyophilized culture filtrate (LCF). In addition, ethyl acetate extract (1123.4 μmole Fe(II)/mg extract) exhibited higher ferric reducing activity than the standard BHA (814.4 μmole Fe(II)/mg extract). Further works are needed on the isolation and identification of antioxidant molecules from the ethyl acetate extract of Streptomyces sp. AM-S1 culture filtrate.


GOLPH3 inhibition reverses oxaliplatin resistance of colon cancer cells via suppression of PI3K/AKT/mTOR pathway.
To explore whether GOLPH3 regulated oxaliplatin (L-OHP) resistance of colon cancer cells via PI3K/AKT/mTOR pathway. HCT116/L-OHP cells were divided into Blank, Control/GOLPH3 shRNA, BEZ235 (a PI3K/AKT/mTOR inhibitor), and GOLPH3 + BEZ235 groups followed by the detection with MTT, soft agar colony formation, flow cytometry and TUNEL assays. Mice bearing HCT116/L-OHP xenografts were randomized into Control, L-OHP, NC/GOLPH3 shRNA, L-OHP + NC/GOLPH3 shRNA groups. The expressions of Ki67, Caspase-3, and PI3K/AKT/mTOR pathway proteins were examined by immunohistochemistry. HCT116/L-OHP cells had increased GOLPH3 expression compared to HCT116 cells, which positively regulated PI3K/AKT/mTOR pathway in HCT116/L-OHP cells. BEZ235 declined IC50 of HCT116/L-OHP cells to L-OHP, decreased the expressions of ABCB1, ABCC1, ABCG2, ATP7A, ATP7B, MATE1, p-gp, MRP1 and BCRP, induced cell apoptosis, reduced cell proliferation, and arrested cells at G0/G1, which was reversed by GOLPH3 overexpression. L-OHP and GOLPH3 shRNA decreased tumor volume and reduced expression of Ki67 in tumor tissues with the increased Caspase-3. Meanwhile, the combined treatment had the better treatment effect. GOLPH3 inhibition reduced proliferation and promoted apoptosis of HCT116/L-OHP cells, and also reversed the L-OHP resistance of HCT116/L-OHP, which may be associated with the suppression of P13K/AKT/mTOR pathway.


The horizontal sacrum as an indicator of the tethered spinal cord in spina bifida aperta and occulta.
The authors report on symptomatic patients with myelomeningocele (MMC) and lipomyelomeningocele (LMMC) who were found to have changes in their lumbosacral angle (LSA) corresponding to the onset of symptoms indicative of a tethered spinal cord. The authors review data obtained in these two cohorts of patients and compare the LSAs measured in the perinatal period with those seen when the patients presented with symptoms of a tethered spinal cord. Children with LMMC, roughly one third of studied cases, were symptomatic due to a tethered spinal cord at their most recent follow-up. In children in whom the MMC was the closed form at birth, 20 of 30 had symptoms that could be indicative of a tethered spinal cord at their most recent follow-up. The LSA was altered in both groups with symptoms. Signs and symptoms indicative of a tethered spinal cord appear to correspond to increases in the LSA.


Impacts of Technology Use on the Workload of Registered Nurses: A Scoping Review.
Technology is an integral part of healthcare. With the rapid development of technological innovations that inform and support nurses, it is important to assess how these technologies may affect their workload particularly in rural contexts, where the workforce and supports may be limited. This literature review guided by Arksey and O'Malley's scoping review framework describes the breadth of technologies which impact on nurses' workload. Five databases (PubMed, CINAHL, PsycInfo, Web of Science, Business Source Complete) were searched. Thirty-five articles met the inclusion criteria. A data matrix was used to organize the findings. The technology interventions described in the articles covered diverse topics including: Cognitive care technologies; Healthcare providers' technologies; Communication technologies; E-learning technologies; and Assistive technologies and were categorized as: Digital Information Solutions; Digital Education; Mobile Applications; Virtual Communication; Assistive Devices; and Disease diagnoses groups based on the common features. Technology can play an important role to support nurses working in rural areas, however, not all technologies have the same impact. While some technologies showed evidence to positively impact nursing workload, this was not universal. Technology solutions should be considered on a contextual basis and thought should be given when selecting technologies to support nursing workload.


Efficacy and safety of ossein-hydroxyapatite complex versus calcium carbonate to prevent bone loss.
Objective: This study aimed to compare the efficacy and safety of ossein-hydroxyapatite complex (OHC) versus calcium carbonate (CC) for preventing bone loss during perimenopause in current clinical practice.Methods: The prospective, comparative, non-randomized, open-label study included 851 perimenopausal women with basal bone mineral density (BMD) T-score ≥-2 standard deviations (SDs). Participants received either OHC (712 mg calcium/day) or CC (1000 mg calcium/day) over 3 years. BMD was evaluated by dual-energy X-ray absorptiometry at the lumbar spine (L2-L4) at baseline and after 18 and 36 months of follow-up. Adverse drug reactions (ADRs) were also recorded.Results: In women receiving OHC, BMD at the L2-L4 site remained stable over the 3-year follow-up period (mean [SD] change 0.00 [0.11] g/cm2). BMD in the CC arm decreased -3.1% (mean [SD] - 0.03 [0.11] g/cm2). Between-group differences were statistically significant (p < 0.001) and favored OHC. ADRs were more frequent in the CC group (7.7% vs. 2.7% in the OHC group; p = 0.001), affecting primarily the gastrointestinal system.Conclusion: OHC showed greater efficacy and tolerability than CC for bone loss prevention in perimenopausal women in real-world practice. As the daily dose of calcium was higher in the CC group, the differences might be linked to the ossein compound in OHC.


Tristetraprolin mediates the anti-proliferative effects of metformin in breast cancer cells.
Metformin, which is a drug commonly prescribed to treat type 2 diabetes, has anti-proliferative effects in cancer cells; however, the molecular mechanisms underlying this effect remain largely unknown. The aim is to investigate the role of tristetraprolin (TTP), an AU-rich element-binding protein, in anti-proliferative effects of metformin in cancer cells. p53 wild-type and p53 mutant breast cancer cells were treated with metformin, and expression of TTP and c-Myc was analyzed by semi-quantitative RT-PCR, Western blots, and promoter activity assay. Breast cancer cells were transfected with siRNA against TTP to inhibit TTP expression or c-Myc and, after metformin treatment, analyzed for cell proliferation by MTS assay. Metformin induces the expression of tristetraprolin (TTP) in breast cancer cells in a p53-independent manner. Importantly, inhibition of TTP abrogated the anti-proliferation effect of metformin. We observed that metformin decreased c-Myc levels, and ectopic expression of c-Myc blocked the effect of metformin on TTP expression and cell proliferation. Our data indicate that metformin induces TTP expression by reducing the expression of c-Myc, suggesting a new model whereby TTP acts as a mediator of metformin's anti-proliferative activity in cancer cells.


Cost-effectiveness of professional and mechanical oral care for preventing pneumonia in nursing home residents.
Pneumonia is common in nursing home residents and is a leading cause of hospitalization and death. Nursing home residents with cerebrovascular diseases and impaired consciousness are at high risk of aspiration pneumonia. Professional and mechanical oral care by dentists and hygienists in addition to daily oral care by caregivers was shown to be effective in preventing pneumonia in nursing home residents. However, professional and mechanical oral care has not been widely provided in Japan, while daily oral care by caregivers has been widely provided as a basic service in nursing homes. This study aimed to evaluate the cost-effectiveness of providing professional and mechanical oral care for preventing pneumonia in nursing home residents. Using a decision tree and Markov modeling, we conducted a cost-effectiveness analysis from the payer's perspective (social insurers and patients) in Japan. The incremental cost-effectiveness ratio for professional and mechanical oral care compared with daily oral care only was calculated as 4,079,313 Japanese yen (¥; 33,994 United States dollars [US$], US$1 = ¥120) per quality-adjusted life year. Using the official value of social willingness to pay for a one-quality-adjusted life year gain in Japan of ¥5 million (US$41,667) as the threshold to judge cost-effectiveness, providing professional and mechanical oral care is cost-effective. Our results suggest professional and mechanical oral care for preventing pneumonia in nursing home residents could be justifiable as efficient use of finite healthcare resources. The results have implications for oral care in nursing homes both in Japan and worldwide.


The importance of human glandular kallikrein and its correlation with different prostate specific antigen serum forms in the detection of prostate carcinoma.
Human glandular kallikrein (hK2), the prostate specific antigen (PSA) close homologue, possesses approximately 80% structure identity with PSA. The identification of PSA was an important step in the detection of prostate carcinoma (PCa). Thus, hK2 measurement in the serum has the potential to become another important diagnostic test for PCa. In the current study, the authors measured the serum concentrations of the hK2 with "in-house" immunofluorometric assays in different patient groups. The correlation between serum hK2 and different PSA forms was investigated. The prospectively collected serum samples were obtained preoperatively on admission from 311 consecutive male patients. Sixteen patients did not fulfill inclusion criteria; the remaining patients were divided into four groups (Groups I-III confirmed histologically): Group I: patients with PCa (n = 56); Group II: patients with benign prostatic hyperplasia (BPH) (n = 163); Group III: patients with BPH with a chronic in-dwelling catheter (BPH cat) (n = 44); and Group IV-control group (n = 32). The patients in Group IV had urolithiasis, varicocele, or kidney or bladder tumors). An experimental immunofluorometric assay with an analytic sensitivity of 0.01 ng/mL and a functional sensitivity of 0.05 ng/mL was used to determine serum hK2 concentrations. Total PSA, free PSA, and PSA complexed to alpha-1-antichymotrypsin (PSA-ACT) also were measured. hK2 concentrations equal to or above the functional sensitivity limit were correlated with each of these PSA serum forms. Free to total PSA, hK2 to total PSA, and hK2 to free PSA ratios were calculated and compared in different patient groups. The hK2 concentrations were equal to or above the functional sensitivity limit in 179 of 311 samples (57.6%). In these samples, hK2 correlated best with free PSA (correlation coefficient [r] = 0.79) and correlated well with total PSA (r = 0.72) and PSA-ACT (r = 0.74). Similar correlations also could be observed when each clinical group was analyzed separately. The median proportion of hK2 in relation to total PSA was 2.1%, 1.8%, and 1.4%, respectively, for PCa, BPH, and BPH cat patients. Both the free to total PSA ratio and the hK2 to free PSA ratio discriminated well between PCa and BPH patients. Within the range of total PSA of 4-10 ng/mL (PCa [n = 11] and BPH [n = 41]) the hK2 to free PSA ratio had a specificity of 63.4% and 90.9% sensitivity (area under the receiver operating characteristic [ROC] curve = 0.85) whereas the free to total PSA ratio had a 34.1% specificity at the same sensitivity level (area under ROC curve = 0.74). The hK2 serum level correlates well with all PSA serum forms in all clearly defined clinical groups. The preliminary finding that the hK2 to free PSA ratio appeared to improve the detection of PCa compared with the free to total PSA ratio in patients with total PSA within a 4-10 ng/mL range is of clinical interest. Combining human serine proteases in the multivariate regression analysis will be a tool to improve cancer detection. Further investigations with more sensitive hK2 assays and in larger patient populations are needed to confirm this finding.


AIDS and SLE: a reverse process of the same disease.
Acquired immunodeficiency syndrome (AIDS) and systemic lupus erythematosus (SLE) are two diseases with striking similarities as well as contrasting differences. There is evidence that AIDS and SLE have the same or similar viruses as their etiologic agent. Genetic, clinical and immunological studies suggest that the two diseases are the same, with their only difference being the stimulatory effects of the AIDS virus on cortisol production versus the inhibitory effects of the proposed SLE virus on cortisol production. Possible mechanisms of the disease process for both AIDS and SLE are discussed, as well as proposed treatments for AIDS, including the use of procainamide and ascorbic acid.


Femtosecond laser nanosurgery of sub-cellular structures in HeLa cells by employing Third Harmonic Generation imaging modality as diagnostic tool.
Femtosecond laser assisted nanosurgery of microscopic biological specimens is a relatively new technique which allows the selective disruption of sub-cellular structures without causing any undesirable damage to the surrounding regions. The targeted structures have to be stained in order to be clearly visualized for the nanosurgery procedure. However, the validation of the final nanosurgery result is difficult, since the targeted structure could be simply photobleached rather than selectively destroyed. This fact comprises a main drawback of this technique. In our study we employed a multimodal system which integrates non-linear imaging modalities with nanosurgery capabilities, for the selective disruption of sub-cellular structures in HeLa cancer cells. Third Harmonic Generation (THG) imaging modality was used as a tool for the identification of structures that were subjected to nanosurgery experiments. No staining of the biological samples was required, since THG is an intrinsic property of matter. Furthermore, cells' viability after nanosurgery processing was verified via Two Photon Excitation Fluorescence (TPEF) measurements.


Supernormal responses to premature stimulation in Ca-dependent action potentials.
The responses of Ca-dependent action potentials to premature stimulation were studied in the isolated canine ventricular muscle. When very premature stimuli were applied, supernormally augmented responses with propagation occurred, while responses with long preceding intervals were small and not conducted.


Modular DNA strand-displacement controllers for directing material expansion.
Soft materials that swell or change shape in response to external stimuli show extensive promise in regenerative medicine, targeted therapeutics, and soft robotics. Generally, a stimulus for shape change must interact directly with the material, limiting the types of stimuli that may be used and necessitating high stimulus concentrations. Here, we show how DNA strand-displacement controllers within hydrogels can mediate size change by interpreting, amplifying, and integrating stimuli and releasing signals that direct the response. These controllers tune the time scale and degree of DNA-crosslinked hydrogel swelling and can actuate dramatic material size change in response to <100 nM of a specific biomolecular input. Controllers can also direct swelling in response to small molecules or perform logic. The integration of these stimuli-responsive materials with biomolecular circuits is a major step towards autonomous soft robotic systems in which sensing and actuation are implemented by biomolecular reaction networks.


Hormonal stimulation of mitochondrial glutaminase. Effects of vasopressin, angiotensin II, adrenaline and glucagon.
Adrenaline (through alpha 1-adrenoceptors), vasopressin and angiotensin II stimulate mitochondrial glutaminase activity. This stimulation probably contributes to the ureogenic effect of these hormones. The activity of the enzyme is sensitive to Ca2+ depletion. A role of Ca2+ in hormonal modulation of glutaminase activity is suggested.


Late hypoglossal nerve palsy following fracture of the occipital condyle.
Fracture of the occipital condyle is a rare problem that can easily be overlooked. We report a patient with occipital condyle fracture who was neurologically intact on admission, and who developed hypoglossal nerve palsy in the late posttraumatic period. The diagnosis was facilitated by the aid of computed tomography.


Effects of single and repeated electroconvulsive shock on local cerebral glucose utilization in the conscious rat.
Local rates of cerebral glucose utilization (LCGU) were determined in adult rats submitted to electroconvulsive shock (ECS) treatment. One group of rats (n = 5) received a single ECS, a second group (n = 5) was treated once daily for 7 days. A third group (n = 5) of unshocked rats served as control. LCGU measurements were performed one day after either the single or the last ECS. Following a single ECS, most of the 45 brain regions examined exhibited lower rates of LCGU than controls, in contrast after repeated ECS treatment the metabolic activity results increased in segments of the hippocampus. The results indicate that repeated ECS treatment selectively increases metabolic rates within the hippocampus, a structure of the limbic system thought to be related to affective disorders and memory.


Long-term exposure to ambient air pollution is associated with an increased incidence and mortality of acute respiratory distress syndrome in a large French region.
Air pollution exposure is suspected to alter both the incidence and mortality in acute respiratory distress syndrome (ARDS). The impact of chronic air pollutant exposure on the incidence and mortality of ARDS from various aetiologies in Europe remains unknown. The main objective of this study was to evaluate the incidence of ARDS in a large European region, 90-day mortality being the main secondary outcome. The study was performed in the Provence-Alpes-Cote-d'Azur (PACA) region. Nitrogen dioxide (NO2), particulate matter (PM2.5 and PM10) and ozone (O3) were measured. The Programme de Médicalisation des Systèmes d'Information (PMSI), which captures all patient hospital stays in France, was used to identify adults coded as ARDS in an intensive care unit. From 2016 to 2018, 4733 adults with ARDS treated in intensive care units were analysed. The incidence rate ratios for 1-year average exposure to PM2.5 and PM10 were 1.207 ([95% confidence interval (95% CI), 1.145-1.390]; P < 0.01) and 1.168 (95% CI, 1.083-1.259; P < 0.001), respectively. The same trend was observed for both 2- and 3-year exposures, while only chronic 1- and 2-year exposure NO2 exposures were related to a higher incidence of ARDS. Increased PM2.5 exposure was associated with a higher 90-day mortality for both 1- and 3-year exposures (OR 1.096 (95% CI, 1.001-1.201) and 1.078 (95% CI, 1.009-1.152), respectively). O3 was not associated with either of incidence nor mortality. While chronic exposure to NO2, PM2.5, and PM10 was associated with an increased ARDS incidence and a higher mortality rate (for PM2.5) in those patients presenting with ARDS, further research on this topic is required.


High miR-21 expression in breast cancer associated with poor disease-free survival in early stage disease and high TGF-beta1.
MicroRNA-21 (miR-21) is considered an onco-microRNA given its abilities to suppress the actions of several tumor suppressor genes and to promote tumor cell growth, invasion and metastasis. Recently, transforming growth factor-beta (TGF-beta) is found to up-regulate the expression of miR-21, and elevated miR-21 expression is seen frequently in breast cancer. To evaluate the effect of miR-21 on disease progression and its association with TGF-beta, we analyzed miR-21 expression in breast cancer. Fresh tumor samples were collected during surgery from 344 patients diagnosed with primary breast cancer. The expression of miR-21 in tumor samples was measured with a TaqMan microRNA assay using U6 as reference. Levels of miR-21 expression by disease stage, tumor grade, histology, hormone receptor status and lymph node involvement were compared. Cox proportional hazards regression analysis was performed to assess the association of miR-21 expression with disease-free and overall survival. The study results showed that the expression of miR-21 was detected in all tumor samples with substantial variation. High miR-21 expression was associated with features of aggressive disease, including high tumor grade, negative hormone receptor status, and ductal carcinoma. High miR-21 was also positively correlated with TGF-beta1. No associations were found between patient survival and miR-21 expression among all patients, but high miR-21 was associated with poor disease-free survival in early stage patients (HR = 2.08, 95% CI: 1.08-4.00) despite no value for prognosis. The study supports the notion that miR-21 is an onco-microRNA for breast cancer. Elevated miR-21 expression may facilitate tumor progression, and TGF-beta may up-regulate its expression.


Determination of PCBs and chlorinated hydrocarbons in marine mammal tissues.
Selected tissues (blubber, liver, kidney and muscle) from marine mammals, which were collected as part of the Alaska Marine Mammal Tissue Archival Project (AMMTAP), were analyzed for polychlorinated biphenyl (PCB) congeners and chlorinated pesticides. Concentrations of these compounds in the different tissues were compared and blubber was selected as the primary tissue for organic contaminant analyses for the AMMTAP based on higher levels (1-2 orders of magnitude) in this tissue compared to liver, kidney and muscle. Concentrations for 15 PCB congeners and 12 chlorinated pesticides are reported for 10 different animals of three species (northern fur seal, ringed seal and belukha whale) from five different sites.


The metastasis gene osteopontin: a candidate target for cancer therapy.
Malignant tumors are characterized by dysregulated growth control, overcoming of replicative senescence, and metastasis formation. Current therapeutic regimens mostly exert their effects through inhibition of cell cycle progression, leaving two major components of transformation untouched. The cytokine osteopontin is essential for the dissemination of various cancers. Past research has implied several modes in which osteopontin and its main receptors on tumor cells can be suppressed. Osteopontin expression is inhibitable on the levels of gene transcription and the RNA message, and the osteopontin protein can be blocked with antibodies or synthetic peptides. The osteopontin receptor CD44 has been targeted by diverse therapeutic strategies, including cytotoxic and immunotherapeutic approaches. The receptor integrin alpha(V)beta(3) contributes not only to tumor cell dissemination, but also to angiogenesis and osteolysis in bone metastases. Small molecule inhibitors of this receptor are under study as drug candidates. Because receptors and cytokine ligands that mediate metastasis formation are sparsely expressed in the adult healthy organism and are more readily reached by pharmaceuticals than intracellular drug targets they may represent a particularly suitable focus for therapeutic intervention.


Expanding indications for thrombolytic therapy in acute myocardial infarction. How late is too late, and how early is early: the clinician's view of the first 100 minutes.
Proper understanding of the pathologic process of a ruptured plaque followed by thrombus formation, with acute assessment of the deranged pathophysiology of the coronary circulation as a sequel, remains the basis for rational therapy of cardiac ischemia. With the advent of better thrombolytic regimens, improved direct reperfusion via angioplasty, and streamlined recognition/admission procedures, therapeutic strategies for dealing with acute myocardial infarction have once more turned to the options for early therapy. From recent studies of out-of-hospital thrombolysis or immediate percutaneous transluminal coronary angioplasty, the position is reinforced that "early" means the first 100 minutes. It is hoped that the large Global Utilization of Streptokinase and t-PA for Occluded Arteries (GUSTO) study, which specifically analyses the effect of early reperfusion by optimal alteplase and actilyse (recombinant tissue-type plasminogen activator [rt-PA]) versus streptokinase regimens will confirm this essential concept once and for all. Thus, when appropriate therapy--depending in the local availability of facilities--is promptly given, further reductions in myocardial infarction size and ventricular dysfunction can be achieved, resulting in mortality rates < 5%, at substantial savings in ever more expensive healthcare resources. "Early is < 100 minutes; later may be too late or too costly."


3,3-Dimethyl-2-benzofuran-1(3H)-one.
In the title compound, C(10)H(10)O(2), all the non-H atoms except the methyl C atoms lie on a crystallographic mirror plane. In the crystal, C-H⋯O hydrogen bonds link the mol-ecules into zigzag chains running parallel to [100]. Weak π-π stacking inter-actions between the benzene rings [centroid-centroid distance = 3.9817 (5) Å] link the chains in the [010] direction.


A waterborne outbreak with a single clone of Campylobacter jejuni in the Danish town of Køge in May 2010.
In Denmark, large-scale waterborne outbreaks are rare. This report describes the investigation of an outbreak that occurred in the town of Køge in May 2010. The epidemiological investigation consisted of hypothesis generating telephone interviews, followed by a cohort study among approximately 20,000 residents using an online questionnaire. Odds ratios were calculated for exposures including the number of glasses of tap water consumed. Geographical spreading was assessed using a geographical information system. The microbiological investigation included cultures of stool samples and flagellin-typing. In the environmental investigation, water samples were tested for Escherichia coli and coliform counts and for DNA of Campylobacter, Enterococcus, and Bacteroides. During the outbreak investigation a water boiling order was enforced, as tap water was considered a potential source. Of 45 patients with laboratory confirmed Campylobacter infection in the municipality of Køge in May, 43 lived in the area covered by the central water supply. Of 61 patients with laboratory confirmed Campylobacter jejuni by 8 June, 50 shared a common flagellin gene type--flaA type 36 (82%). The epidemic curve from the cohort study showed a wave of diarrhoea onset from 14 to 20 May (n = 176). Among these patients, the development of diarrhoea was associated with drinking tap water with a dose-response pattern (linear increase by 2 glasses: odds ratio 1.40, 95% confidence interval 1.16-1.70). No bacterial DNA was found in water samples. These findings indicated a point source contamination of tap water with a single clone of C. jejuni which likely occurred on 12-13 May. The water boiling order was lifted on 18 June.


The effects of cardiopulmonary bypass and profound hypothermic circulatory arrest on anterior fontanel pressure in infants.
The Ladd transducer was used to measure anterior fontanel pressure in 23 infants undergoing cardiopulmonary bypass and profound hypothermic circulatory arrest for surgical correction of congenital heart disease. Mean (+/- SD) minimum oesophageal and rectal temperatures of 11.3 +/- 1.5 degrees C and 18.1 +/- 2.2 degrees C respectively were achieved with a mean duration of arrest of 53.4 +/- 13.9 minutes. During reperfusion cardiopulmonary bypass after circulatory arrest, mean anterior fontanel pressure (18.3 +/- 6.4 mmHg) increased above baseline pre-bypass values (10.6 +/- 2.9 mmHg) (p less than 0.005). Mean arterial blood pressure decreased significantly from pre-bypass values (57.0 +/- 11.8 mmHg) during both cooling (38.8 +/- 8.4 mmHg) and rewarming cardiopulmonary bypass (45.8 +/- 8.9 mmHg) (p less than 0.005). These changes were associated with a significant decrease in cerebral perfusion pressure during cooling (27.3 +/- 11.0 mmHg) and rewarming cardiopulmonary bypass (27.5 +/- 10.6 mmHg), compared with baseline pre-bypass values (46.5 +/- 12.3 mmHg) (p less than 0.005). The data demonstrate significant but transient decreases in cerebral perfusion pressure during cooling and rewarming bypass.


Comparison between the mechanisms of Clearfield ® wheat and Lolium rigidum multiple resistant to acetyl CoA carboxylase and acetolactate synthase inhibitors.
Clearfield® wheat (Triticum aestivum) have helped eliminate the toughest grasses and broadleaf weeds in Spain since 2005. This crop production system includes other tolerant cultivars to the application of imidazolinone (IMI) herbicides. However, the continuous use and off-label rates of IMI herbicides can contribute to the development of resistance in Lolium rigidum and other weed species. In this research, the main objectives were to study the resistance mechanisms to acetolactate synthase (ALS) and acetyl coenzyme A carboxylase (ACCase) inhibitors in a L. rigidum accession (LrR) from a Clearfield® wheat field, with a long history rotating these IMI-tolerant crops and compare them with those present in the IMI-tolerant wheat. The resistance to ACCase inhibitors in LrR was due to point mutations (Ile1781Leu plus Asp2078Gly) of the target site gene plus an enhanced herbicide metabolism (EHM), on the other hand, in wheat accessions was due only by EHM. Mechanisms involved in the resistance to ALS inhibitors were both point mutations of the target gene and EHM in the IMI-tolerant wheat, while only evidence of mutation (Trp574Leu) was found in the multiple herbicide resistant L. rigidum accession. This research demonstrates that if crop rotation is not accompanied by the use of alternative sites of action in herbicide-tolerant crops, resistant weeds to herbicide to which crops are tolerant, can easily be selected. Moreover, repeated and inappropriate use of Clearfield® crops and herbicide rotations can lead to the evolution of multiple resistant weeds, as shown in this study, and have also inestimable environmental impacts.


Regional cerebral glucose metabolism in man during wakefulness, sleep, and dreaming.
Regional cerebral glucose metabolism was measured by positron emission tomography in 4 healthy male volunteers, both during wakefulness and sleep, using the 2-deoxy-D-[2-18F]glucose method. While 3 of the subjects did not report dreaming and, during sleep stages I-IV of variable duration, exhibited a non-selective decrease in metabolic rates averaging 12.6 +/- 4.73% (mean +/- S.D.) for the entire brain, the fourth volunteer who experienced an extended nightmare during his sleep examination showed a generalized increase in cerebral glucose utilization ranging from 2.1% in lentiform nucleus to 30.0% in the superior frontal cortex, with a weighted whole brain average of 16.4%. These findings suggest that energy metabolism in the human brain is generally depressed during slow-wave sleep as opposed to a--possibly differential--activation during dreaming.


Maternal perception of sound-provoked fetal movements in low-risk pregnancies during the third trimester.
Maternal perception of fetal movements after vibroacoustic stimulation (Servox) was studied longitudinally on 456 occasions in 90 low-risk pregnancies after 28 weeks gestation until delivery. A positive response to sound stimulation, recorded as a fetal movement by the mother, occurred on 444 (97%) occasions. Of the 12 negative responses eight occurred before 33 weeks showing a positive correlation with decreasing maturity. All the pregnancies had good outcomes. The low rate of false-positive tests (3%) adds support to the suggestion that this rapid test could play a role in the assessment of fetal well-being.


Evidence for the involvement of vicinal sulfhydryl groups in insulin-activated hexose transport by 3T3-L1 adipocytes.
Following the differentiation of 3T3-L1 preadipocytes insulin acutely activates the rate of 2-deoxy-[1-14C]glucose uptake in the mature 3T3-L1 adipocyte by 15- to 20-fold. Phenylarsine oxide, a trivalent arsenical that forms stable ring complexes with vicinal dithiols, prevents insulin-activated hexose uptake in a concentration-dependent manner (Ki = 7 microM) but has no inhibitory effect on basal hexose uptake. 2,3-Dimercaptopropanol at a level nearly stoichiometric to that of phenylarsine oxide prevents or rapidly reverses the inhibition of hexose uptake; 2-mercaptoethanol, even in high stoichiometric excess over the arsenical, does not reverse inhibition of hexose uptake. When phenylarsine oxide is added after adipocytes have been fully activated by insulin, 2-deoxy-[1-14C]glucose uptake rate decays slowly at a rate corresponding to that caused by the withdrawal of insulin (t1/2 = 10 min). Using the same conditions under which phenylarsine oxide blocked activation, the Km for deoxyglucose uptake, the rate at which 125I-insulin became cell-associated, and the 125I-insulin binding isotherm for solubilized insulin receptor were not affected by phenylarsine oxide. These results support the transporter translocation model for insulin-activated hexose transport and implicate vicinal sulfhydryl groups in a post-insulin binding event essential for the translocation of glucose transporters to the plasma membrane.


A rare case of supraclinoid internal carotid artery (ICA) fenestration in combination with duplication of the middle cerebral artery (MCA) originating from the ICA fenestration and an associated aneurysm.
Fenestrations and duplications of the cervical and intracranial arteries are rare anatomic variants, reported to be associated with aneurysms or other vascular anomalies. We here present a patient with a supraclinoid ICA fenestration in combination with a duplication of the MCA originating from the ICA fenestration and an associated aneurysm.


The nose between ethics and aesthetics: Sushruta's legacy.
The aim of this article is to determine the origin of interest in rhinoplasty in ancient India, as well as to discuss the ethical and aesthetic implications of the nose in human history. Literature review. Articles on history of medical ethics and rhinoplastic surgery were reviewed. Sushruta is considered "the father of plastic surgery," and ancient India a cradle of rhinoplastic method called "the Indian method." Origin of interest in and need for rhinoplasty is deeply rooted in ancient Indian society due to the practice of nose mutilations as a form of public punishment for immoral conduct. The nose, once symbol of morality expressed through physical integrity, today becomes an important factor of human beauty. Rhinoplastic surgery is, both then and now, deeply pervaded with both ethics and aesthetics.


Reducing stimulus overselectivity in autistic children.
It has been repeatedly reported that when presented with a discrimination task involving multiple cues, autistic children, as compared to normal children, tend to respond on the basis of only a restricted portion of the component cues. This phenomenon has been called "stimulus overselectivity" and has been implicated as a possible basis for some of the pronounced behavioral deficits charactertistic of autism. Examination of the results of several previous studies suggests that the overselectivity effect might be reduced with repeated exposure to testing. However, since the previous studies were not designed to test this hypothesis, no conclusions were drawn regarding variables influencing the reduction of the overselectivity phenomenon. The present investigation was therefore conducted to determine if stimulus overselectivity in autistic children is changed as a function of repeated exposure to testing. Nineteen autistic children were trained on a discrimination task with a cue complex composed of two visual cues. After the children reached criterion on the task, they were exposed to a testing phase with probe trials where the cue components were presented singly. The results indicated that 16 of the children initially showed overselectivity and 3 responded to both cues. Of the 16 children who showed overselectivity, 13 decreased their level of overselectivity with continued testing. These results are discussed in relation to variables in the testing procedure itself and to the literature on selective attention.


[Study on relationship between bent angles of dental fiber reinforced composites posts and their flexural properties].
To develop a new type of fiber reinforced composites (FRC) posts with optimal bent angles. Three kinds of experimental bent posts were made with bent angle of 5 degrees, 10 degrees, and 15 degrees respectively. The flexural strength of all FRC posts was tested with a 3-point bending test. The flexural strength of the posts with 15 degrees was significantly lower than that of 5 degrees and 10 degrees post groups and prefabricated straight group (P < 0.05). There was no significant difference in flexural strength within other groups (P > 0.05). The experimental FRC posts with bent angles of 0 degrees, 5 degrees, 10 degrees can be accepted clinically.


The "dermal cage": Inferiorly based dermal flap technique for breast reconstruction after mastectomy.
"Direct to implant," "one-stage," or "immediate" breast reconstruction procedures have become extremely popular in the last decade. The additional task of covering the lower pole of the prosthetic implant for stability can be achieved by one of two principal methods: either the use of acellular dermal matrix (ADM) or alternatively by the use of autologous dermis (inferiorly based dermal flap). In 2013, we published a modification of the inferior pedicle technique for reduction mammaplasty with the principal goal of making a strong, durable, and internalized ``dermal cage'' fixed to the chest wall to support the remaining breast tissue and to prevent the long-term descent of the breast tissue through the effects of gravity. At that time, we started to use the same technique in breast reconstruction for selected cases who required skin or nipple-sparing mastectomy with reduction of the skin envelope, not just to cover the lateroinferior pole of breast implants as an alternative to ADM but primarily for functional support and suspension with fixation of the implant on the chest wall, shaping the reconstructed breast with the aim of preventing lateral displacement. In this article, we present the method and rationale of our "dermal cage" technique explaining differences between previously published modifications by other authors of the inferior dermal pedicle.


Prodromal symptoms as unfamiliar feelings: Experiences of Iranian myocardial infarction patients.
Patients affected by myocardial infarction (MI) report prodromal symptoms before heart attack. Deep understanding of these symptoms can increase the likelihood of early recognition and treatment of coronary heart disease (CHD). The purpose of this study was to describe the prodromal symptoms of MI experienced by Iranian adults. In this qualitative conventional content analysis, data was collected through an in-depth semi-structured interview with 14 men and women (aged 40-82 years). The patients were interviewed at the hospital 2 or 3 days after hospitalization due to MI. MAXQDA software was used for data analysis. Data analysis led to the emergence of the 4 categories of 'Misperception of the symptoms', 'Reactions to the symptoms', 'Heart disease knowledge deficit', and 'Ideas and beliefs about heart disease'. The participants had not recognized the prodromal symptoms of MI and they attributed their symptoms to non-cardiac causes. They did not consider themselves at risk of heart disease, so they did not seek health services. The participants were unaware of their prodromal symptoms. Clinicians should be attentive that men and women at risk of MI may experience a range of unfamiliar and vague prodromal symptoms, so they must give greater attention to their narratives. A greater understanding of the prodromal symptoms experienced may lead to a more truthful and timely interpretation of their symptoms and earlier detection by physicians.


A weighted accumulation test for associating rare genetic variation with quantitative phenotypes.
Currently there is a great deal of interest in developing methods for testing the role that rare variation plays in disease development. Here we propose a weighted association test that accumulates genetic variation across a signaling pathway. We evaluate our approach by analyzing simulated phenotype data from an exome sequencing study of 697 unrelated individuals from the Genetic Analysis Workshop 17 (GAW17) data set. Although our weighted approach identifies several interesting pathways associated with phenotype Q1, so does an alternative unweighted accumulation approach. Such a result is not unexpected because there is no systematic relationship between the allele frequency of a variant and its effect on phenotype in the GAW17 simulation model.


Removal of arsenic from aqueous environments by native and chemically modified biomass of Aspergillus niger and Neosartorya fischeri.
Arsenic removal from aqueous solutions by biomass of two fungal strains, Aspergillus niger and Neosartorya fischeri, was assessed. The biosorption capacity of fungal biomass was studied within the As(V) concentration range of approximately 0.2 to 5.0 mg L(-1) at two different pH values (pH 5 and 7). With increasing initial arsenic concentration, the biosorption capacity of both fungal strains increased almost linearly and achieved the sorption capacity of 0.317 and 0.124 mg g(-1) for biomass of N. fischeri and A. niger, respectively. The effect of biomass treatment with FeCl3 and HCI on As(III) and As(V) uptake was also studied. The optimum biosorption pH as well as the effect ofbiomass treatment was found to be dependent on the fungal strain used. Treatment with FeCl3 and HCl did not result in any significant increase in arsenic uptake. To the contrary, treatment with ferric oxyhydroxide was found to be very effective and virtually 100% of the arsenic was removed from the samples of contaminated natural water.


A Mouse Model of Oral Sensitization to Hen's Egg White.
Egg allergy is one of the most common food allergies in children, being the most important allergenic proteins found in the egg white (EW). Allergy to EW shows a complex phenotype that involves a multifaceted reaction that can only be assessed in vivo. Although other routes of sensitization have been described, oral exposure to food antigens is one of the most suitable in humans. In mice, oral administration of allergenic proteins results in the development of tolerance, and the use of adjuvants, such as cholera toxin (CT), is required to promote Th2-biased immune responses over tolerogenic responses. In this regard, among the mouse strains that readily display Th2 responses, Balb/c has been widely used. Here, we describe a frequently used protocol of oral EW sensitization by using CT as an adjuvant and we explain in detail the methods that we have developed to analyze the sensitizing and eliciting capacity of EW proteins including evaluation of signs, measurement of serum levels of specific immunoglobulins, mast cell degranulation, cytokine secretion profile of allergen-reactive T cells, phenotyping of mesenteric lymph node- and spleen-derived dendritic and T cells by flow cytometry, and quantification of intestinal gene expression.


Comparison of basal and noradrenaline stimulated methylation of chloroform-extractable products in synaptosomal preparations from the rat brain.
Noradrenaline addition increases (S-adenosyl-L-methionine)-methylation of chloroform extractable products in the rat brain synaptosomal preparation. The characteristics of this methylation (MgCl2 dependence, S-adenosyl-L-methionine concentration dependence) are different from those of phosphatidylethanolamine methylase. The greatest increase was induced by noradrenaline in the 10(-4) M concentration range; preincubation of noradrenaline with the membranes, before S-adenosyl-L-methionine addition, was necessary. The TLC analysis of chloroform extractable products showed that: methylation of phosphatidylethanolamine derivatives was increased and the production of another unknown product (corresponding to that described by Wazer et al., Life Sci. 32, 2535, 1983) was more enhanced.


Author Correction: Integrating microarray-based spatial transcriptomics and single-cell RNA-seq reveals tissue architecture in pancreatic ductal adenocarcinomas.
A Correction to this paper has been published: https://doi.org/10.1038/s41587-019-0392-8.


Metal-Organic Framework-Polyacrylonitrile Composite Beads for Xenon Capture.
Mechanically robust forms of HKUST-1 metal-organic frameworks (MOFs) were fabricated by embedding the MOF crystals in a passive polyacrylonitrile (PAN) matrix at different MOF loadings of 10-90 mass %. PAN is highly porous and acts as a scaffold that holds the active MOF adsorbent in place. These MOF-PAN composites were then evaluated for capturing Xe. Data presented herein show that the PAN matrix does not notably interfere with the Xe capture process, where the Xe capacities scale somewhat linearly with the increase in MOF loadings within the composites. Also, γ radiation exposures to the composites revealed that they are highly tolerant to these types of radiation fields.


Absence of the ductus venosus: report of 10 new cases and review of the literature.
To assess the clinical significance of the absence of the ductus venosus. A retrospective study with a review of the literature. The archives of our ultrasound laboratory and the English literature were searched for cases with a prenatal diagnosis of absence of the fetal ductus venosus. Between 1985 and 2000, 10 fetuses were diagnosed in our center as having absence of the ductus venosus. The review of the literature revealed 23 cases. Three main patterns of abnormal venous circulation were documented: (1) umbilical vein bypassing the liver and connecting directly to the right atrium (46%); (2) umbilical vein bypassing the liver and connecting to the inferior vena cava mostly through one of the iliac veins (25%); (3) umbilical vein connecting to the portal circulation without giving rise to the ductus venosus (21%). Major anomalies, including chromosomal aberrations, were found in 8/33 (24%) cases. Hydrops developed in 11/33 (33%) cases. Twenty fetuses with isolated absence of the ductus venosus were delivered, and 5 (20%) died. The portal vein was found to be absent in half of the infants examined after birth. Our results and the review of literature suggest that absence of the ductus venosus is associated with a high incidence of fetal anomalies and adverse outcomes, including associated malformations, chromosomal aberrations, in utero heart failure and absence of the portal vein. Heart failure and absence of the portal vein seem particularly frequent when absence of the ductus venosus is associated with a connection of the umbilical vein to either the inferior vena cava or the right atrium.


Allergen-specific immunotherapy: update on immunological mechanisms.
Immunotherapy selectively modulates the allergen-specific immune response. It involves the gradual administration of increasing amounts of allergen for the purpose of inducing protective immunological changes and it is the only curative approach for specific type I allergy. Description of the allergic inflammation.- Comprehension of the early cellular changes after specific immunotherapy has been initiated. Exposure of the mechanisms involved in tolerance induction by regulatory T cells (Treg) with the inhibition of the Th2 responses. Comprehension of IL-10 and transforming growth factor (TGF- ) roles. Explanation of specific IgE, IgG and IgA changes. Description of the suppression of inflammatory responses during immunotherapy.


Capsaicin stimulates glucose uptake in C2C12 muscle cells via the reactive oxygen species (ROS)/AMPK/p38 MAPK pathway.
Capsaicin has been reported to regulate blood glucose levels and to ameliorate insulin resistance in obese mice. This study demonstrates that capsaicin increases glucose uptake directly by activating AMP-activated protein kinase (AMPK) in C2C12 muscle cells, which manifested as an attenuation of glucose uptake when compound C, an AMPK inhibitor, was co-administered with capsaicin. However, the insulin signaling molecules insulin receptor substrate-1 (IRS-1) and Akt were not affected by capsaicin. Additional results showed that p38 mitogen-activated protein kinase (MAPK) is also involved in capsaicin-induced glucose transport downstream of AMPK because capsaicin increased p38 MAPK phosphorylation significantly and its specific inhibitor SB203580 inhibited capsaicin-mediated glucose uptake. Treatment with an AMPK inhibitor reduced p38 MAPK phosphorylation, but the p38 MAPK inhibitor had no effect on AMPK. Capsaicin stimulated ROS generation in C2C12 muscle cells, and when ROS were captured using the nonspecific antioxidant NAC, the increase in both capsaicin-induced AMPK phosphorylation and capsaicin-induced glucose uptake was attenuated, suggesting that ROS function as an upstream activator of AMPK. Taken together, these results suggest that capsaicin, independent of insulin, increases glucose uptake via ROS generation and consequent AMPK and p38 MAPK activations.


Multimodal imaging of the tricuspid valve: normal appearance and pathological entities.
The tricuspid valve, which is the atrioventricular valve attached to the morphological right ventricle, is affected by a wide range of pathological processes. Tricuspid valve diseases are now increasingly recognized as a significant cause of morbidity and mortality. Echocardiography is the most widely available and, hence, the first-line imaging modality used in the evaluation of tricuspid valve disorders; however, CT and MRI are also increasingly used for further evaluation and characterization of these entities. In this article, we first review the normal anatomy and embryology of the tricuspid valve, followed by a discussion of the role of multiple imaging modalities in the evaluation of tricuspid valve abnormalities. We then review and illustrate the imaging appearance of several congenital and acquired tricuspid valve abnormalities. Main Messages • Tricuspid valve diseases have a significant impact on morbidity and mortality. • CT and MRI are increasingly used in the evaluation of tricuspid disorders. • CT and MRI help in diagnosis, functional evaluation, pre-surgical planning and post-surgical follow-up. • The most common cause of tricuspid regurgitation is functional.


How do we define the policy impact of public health research? A systematic review.
In order to understand and measure the policy impact of research we need a definition of research impact that is suited to the task. This article systematically reviewed both peer-reviewed and grey literature for definitions of research impact to develop a definition of research impact that can be used to investigate how public health research influences policy. Keyword searches of the electronic databases Web of Science, ProQuest, PubMed, EMBASE, CINAHL, Informit, PsycINFO, The Cochrane Database of Systematic Reviews and Google Scholar were conducted between August 2015 and April 2016. Keywords included 'definition' and 'policy' and 'research impact' or 'research evidence'. The search terms 'health', public health' or 'mental health' and 'knowledge transfer' or 'research translation' were used to focus the search on relevant health discipline approaches. Studies included in the review described processes, theories or frameworks associated with public health, health services or mental health policy. We identified 108 definitions in 83 publications. The key findings were that literature on research impact is growing, but only 23% of peer-reviewed publications on the topic explicitly defined the term and that the majority (76%) of definitions were derived from research organisations and funding institutions. We identified four main types of definition, namely (1) definitions that conceptualise research impacts in terms of positive changes or effects that evidence can bring about when transferred into policies (example Research Excellence Framework definition), (2) definitions that interpret research impacts as measurable outcomes (Research Councils UK), and (3) bibliometric and (4) use-based definitions. We identified four constructs underpinning these definitions that related to concepts of contribution, change, avenues and levels of impact. The dominance of bureaucratic definitions, the tendency to discuss but not define the concept of research impact, and the heterogeneity of definitions confirm the need for conceptual clarity in this area. We propose a working definition of research impact that can be used in a range of health policy contexts.


Hierarchical NiMn/NiMn-LDH/ppy-C induced by a novel phase-transformation activation process for long-life supercapacitor.
For micron-sized nickel-based hydroxides sheets, the reaction and migration of anions/water molecules in the inner region tends to lag behind those along the edge, which can cause structure mismatch and capacity degradation during cycles. Nanosizing and structure design is a feasible solution to shorten the ion/electron path and improve the reaction homogeneity. Herein, this study reports a novel three-stage strategy (self-assembly of NiMn-LDH/ppy-C - reduction to NiMn/ppy-C - in situ phase transformation into NiMn/NiMn-LDH/ppy-C) to reduce the sheet size of NiMn-LDH to nanometer. Triggered by electrochemical activation, NiMn-LDH nanosheets can hereby easily and orderly grow on the exposed active (111) crystal plane of Ni to establish NiMn-LDH/NiMn heterostructure around ppy-C. Importantly, nanosizing and hierarchical structure play a synergistic role to maintain structural integrity and to promote the electron/mass transfer kinetics. The NiMn/NiMn-LDH/ppy-C composite delivers superior cycling stability with almost no decay of capacity retention after 40,000 cycles at 5 A g-1. Our hierarchical morphology modulation provides an ingenious, efficient way to boost the performance of Ni-based layered hydroxide materials.


The impact of post-operative opioid guidelines on prescribing behaviors in the pediatric population.
Opioid misuse continues to be a major source of morbidity and mortality in the US, in both the adult and pediatric populations. Post-operative opioid prescriptions are often the first exposure children have to opioids and increases their risk of chronic use. There is significant variation in the number of opioids following identical procedures and measures have been taken within the adult population to limit this. However, specific post-operative opioid prescription guidelines are not present in the pediatric population. Seven common pediatric surgery procedures were selected for inclusion. The recommended number of opioid doses following each procedure was determined by a multi-disciplinary expert panel. All surgery residents were sent an initial survey to determine the number of opioids they would prescribe for each procedure. They were then shown the guidelines and the survey repeated to determine changes in response. 35 and 27 general surgery residents took part in and pre- and post-educational surveys respectively. In all procedures, there was a decrease in the mean number of post-operative opioids prescribed. In addition, there was an increase in the number of residents who prescribed within the guidelines and a decrease in the number who overprescribed post-operative opioids. Pediatric postoperative opioid prescribing guidelines derived from expert opinion increase resident compliance with appropriate dosing; this has the potential to decrease the classic problem of general surgery residents accustomed to treating adults overprescribing opioids to children. These results are promising, and we aim to expand on this work and incorporate these guidelines into our clinical practice. III/IV.


[Medical therapy of gastroesophageal reflux. Evaluation of the activity of clebopride by continuous intraluminal pH measurement].
Seven female and three male outpatients (mean age 45, range 37-54), suffering from gastroesophageal reflux underwent therapy with clebopride, a new selective antidopaminergic agent. Before and after treatment (1 mg b.i.d. for ten days) 24 h-continuous monitoring of esophageal pH was done. Clebopride significantly lowered the number and the extension of gastroesophageal acid refluxes.


An unusual presentation of meningococcal meningitis--timely recognition can save lives!
Meningococcal meningitis has been known to have a high fatality rate. A high degree of suspicion is required for early recognition and timely intervention. In this report, a case of a young male is presented who came to the emergency department with predominately lower gastrointestinal symptoms but was diagnosed with meningococcal meningitis and managed accordingly.


[Endovascular treatment of carotid stenosis: an experience in the Hospital Universitario Central de Asturias].
Carotid stenosis accounts for about 25% of all ischaemic cerebrovascular events. Carotid angioplasty and stenting (CAS) is a minimally invasive procedure used as an alternative to carotid endarterectomy, especially in high surgical risk patients. To analyse the effectiveness and safety of the endovascular treatment of carotid stenosis in the Hospital Universitario Central de Asturias. The study consisted in a retrospective analysis of the carotid stenoses treated by means of CAS between February 2005 and April 2010, and the following information was recorded: demographic data, clinical diagnosis, indication of treatment, time between the onset of symptoms and beginning of treatment, angiographic findings, complications and long-term follow-up (including the rate of restenosis). Altogether 121 patients were treated (77.8% males and 22.2% females), with a mean age of 70.8 ± 10.7 years. The main vascular risk factors were arterial hypertension (65.3%), smoking (61.2%) and dyslipidaemia (42.1%). In 86% of cases the stenoses were symptomatic and in the remaining 14% they were asymptomatic. In 60.3% of cases they were stenoses > 70%, in 30.6% they were preocclusive stenoses and in 9.1% they were recanalisations of unstable carotid occlusions. The mean treatment time was 17.0 ± 8.3 days after the ischaemic event. The residual stenosis was less than 30% in all cases. The morbidity and mortality rate at 30 days was 4.1% and the rate of restenosis throughout a mean follow-up of 31.2 ± 10.8 months was 2.4%. In our hospital CAS is considered an effective and safe technique, with a rate of complications that is within the parameters that justify its indication.


Chemically acidified, live and heat-inactivated fermented dairy yoghurt show distinct bioactive peptides, free amino acids and small compounds profiles.
Previous studies found variations in the health-promoting effects of consuming different dairy products. This study aims at investigating the chemical composition of microbial fermented yogurt, chemically acidified yogurt and whole milk to understand the differences in the effects these products exert on human health. For this purpose, peptides and small compounds present in the products were examined using a combination of liquid chromatography mass spectrometry and nuclear magnetic resonance spectroscopic techniques. Results revealed that each product had its own characteristic peptide, free amino acid and small compound profile, and database search for bioactivity disclosed that fermented yogurt manufactured using a starter culture is associated with a higher bioactivity potential than chemically acidified yogurt or whole milk. Additional cold storage (14 days) further enhances the bioactivity potential of fermented yogurt while heat-inactivation, ensuring long shelf-life, modulates the proteins available for proteolysis and thereby the peptide profile generated.


Endovascular treatment in patients with middle cerebral artery occlusion of different aetiologies.
The purpose of this study was to evaluate differences in endovascular treatment (EVT) outcomes in M1 segment middle cerebral artery occlusion (MCAO) patients with different pathologic subtypes. Patients with MCAO who received EVT from July 2014 to December 2020 were categorized into three groups: embolism without internal carotid artery steno-occlusion (MCAO-E), in situ atherosclerotic thrombosis (MCAO-AS) and embolism from tandem ICA steno-occlusion (MCAO-T). Baseline characteristics, EVT-related factors and clinical outcomes were compared between groups. Multivariable regression analyses were performed to evaluate the relationship between aetiologic classification and outcomes at 90 days after stroke. Among eligible patients (n = 220), MCAO-E (n = 129, 58.6%) was the most common aetiology, followed by MCAO-AS (n = 47, 21.4%) and MCAO-T (n = 44, 20.0%). Patients with MCAO-E were significantly older but had a lower rate of dyslipidaemia and smoking history than those with MCAO-AS. Although patients with MCAO-AS and MCAO-T more often required rescue balloon angioplasty and stenting (p < 0.001), no significant difference in the rate of final recanalization was found. Patients in the MCAO-AS group obtained better functional outcomes (90-day modified Rankin Scale score, 0-2) (p = 0.002) and lower mortality than in the MCAO-E group (p = 0.009). On multivariable logistic regression, we failed to find that stroke subtype was an independent predictor of functional outcomes and mortality. Patients with acute MCA M1 occlusion stroke due to different pathogeneses had comparable successful recanalization rates and functional independence at 90 days. The optimal management for MCAO patients with different aetiologies requires further research.