The microstructure of Carbopol in water under static and flow conditions and its effect on the yield stress.
In this work, experimental observations of the microstructure of neutralized polyacrylic acid (Carbopol) in water by confocal microscopy under both static and flow conditions are presented. In the former case, a Carbopol-rich phase made by swollen particles dispersed in a water-rich continuous phase is found, so that the system will be henceforth referred to as a suspension, as long as particles are observed. The swollen particles form dendritic-like aggregates, which span the entire solution volume above a critical concentration. In such conditions, a percolated network can be formed, leading to the onset of a yield stress behavior. By separating the dispersed and continuous phase through centrifugation, we provide evidence of a miscibility gap in the phase behavior of Carbopol in water. When the Carbopol suspensions flow in a microfluidic capillary, a particle-concentrated plug core can be distinguished from a less concentrated layer corresponding to a steep velocity decrease. Confocal imaging also shows that the apparent slip found in Carbopol suspensions is due to a particle-concentrated near-wall region, where no flow is observed. Such flow-induced microstructure is responsible for the different nature of the yield stress values measured by classical rheometry and by flow velocimetry. While the yield stress measured by the former can be here related to the presence of a percolated network, the yield stress obtained from the velocity profile is due to the heterogeneous particle distribution along the capillary radius. These results provide a novel insight on the mechanisms governing yield stress in complex fluids.


A conserved Gbeta binding (GBB) sequence motif in Ste20p/PAK family protein kinases.
Serine/threonine protein kinases of the Ste20p/PAK family are highly conserved from yeast to man. These protein kinases have been implicated in the signaling from heterotrimeric G proteins to mitogen-activated protein (MAP) kinase cascades and to cytoskeletal components such as myosin-I. In the yeast Saccharomyces cerevisiae, Ste20p is involved in transmitting the mating-pheromone signal from the betagamma-subunits of a heterotrimeric G protein to a downstream MAP kinase cascade. We have previously shown that binding of the G-protein beta-subunit (Gbeta) to a short binding site in the non-catalytic carboxy-terminal region of Ste20p is essential fortransmitting the pheromone signal. In this study, we searched protein sequence databases for sequences that are similar to the Gbeta binding site in Ste20p. We identified a sequence motif with the consensus sequence S S L phi P L I/V x phi phi beta (x: any residue; phi: A, I, L, S, or T; beta: basic residues) that is solely present in members of Ste20p/PAK family protein kinases. We propose that this sequence motif, which we have designated GBB (Gbeta binding) motif, is specifically responsible for binding of Gbeta to Ste20p/PAK protein kinases in response to activation of heterotrimeric G protein coupled receptors. Thus, the GBB motif is a novel type of signaling domain that serves to link protein kinases of the Ste20p/PAK family to G protein coupled receptors.


Chromosome segregation during female meiosis in C. elegans: A tale of pushing and pulling.
The role of the kinetochore during meiotic chromosome segregation in C. elegans oocytes has been a matter of controversy. Danlasky et al. (2020. J. Cell. Biol.https://doi.org/10.1083/jcb.202005179) show that kinetochore proteins KNL-1 and KNL-3 are required for early stages of anaphase during female meiosis, suggesting a new kinetochore-based model of chromosome segregation.


Data-driven RRAM device models using Kriging interpolation.
A two-tier Kriging interpolation approach is proposed to model jump tables for resistive switches. Originally developed for mining and geostatistics, its locality of the calculation makes this approach particularly powerful for modeling electronic devices with complex behavior landscape and switching noise, like RRAM. In this paper, a first Kriging model is used to model and predict the mean in the signal, followed up by a second Kriging step used to model the standard deviation of the switching noise. We use 36 synthetic datasets covering a broad range of different mean and standard deviation Gaussian distributions to test the validity of our approach. We also show the applicability to experimental data obtained from TiOx devices and compare the predicted vs. the experimental test distributions using Kolmogorov-Smirnov and maximum mean discrepancy tests. Our results show that the proposed Kriging approach can predict both the mean and standard deviation in the switching more accurately than typical binning model. Kriging-based jump tables can be used to realistically model the behavior of RRAM and other non-volatile analog device populations and the impact of the weight dispersion in neural network simulations.


Quantitative computed tomographic study in schizophrenia: cerebral density and ventricle measures.
Twenty-seven chronic schizophrenics and nineteen controls, all male, were evaluated by computed tomography (CT) scans. Lateral, third and fourth ventricles and cerebral density numbers were measured. In the schizophrenic patients there was a significant increase in third ventricle width, Ventricular Brain Ratio (VBR) and there were significantly higher densities of white matter in the right frontal and parietal region.


Production of recombinant proteins by filamentous fungi.
The initial focus of recombinant protein production by filamentous fungi related to exploiting the extraordinary extracellular enzyme synthesis and secretion machinery of industrial strains, including Aspergillus, Trichoderma, Penicillium and Rhizopus species, was to produce single recombinant protein products. An early recognized disadvantage of filamentous fungi as hosts of recombinant proteins was their common ability to produce homologous proteases which could degrade the heterologous protein product and strategies to prevent proteolysis have met with some limited success. It was also recognized that the protein glycosylation patterns in filamentous fungi and in mammals were quite different, such that filamentous fungi are likely not to be the most suitable microbial hosts for production of recombinant human glycoproteins for therapeutic use. By combining the experience gained from production of single recombinant proteins with new scientific information being generated through genomics and proteomics research, biotechnologists are now poised to extend the biomanufacturing capabilities of recombinant filamentous fungi by enabling them to express genes encoding multiple proteins, including, for example, new biosynthetic pathways for production of new primary or secondary metabolites. It is recognized that filamentous fungi, most species of which have not yet been isolated, represent an enormously diverse source of novel biosynthetic pathways, and that the natural fungal host harboring a valuable biosynthesis pathway may often not be the most suitable organism for biomanufacture purposes. Hence it is expected that substantial effort will be directed to transforming other fungal hosts, non-fungal microbial hosts and indeed non microbial hosts to express some of these novel biosynthetic pathways. But future applications of recombinant expression of proteins will not be confined to biomanufacturing. Opportunities to exploit recombinant technology to unravel the causes of the deleterious impacts of fungi, for example as human, mammalian and plant pathogens, and then to bring forward solutions, is expected to represent a very important future focus of fungal recombinant protein technology.


Analysis of a Functional Dimer Model of Ubiquinol Cytochrome c Oxidoreductase.
Ubiquinol cytochrome c oxidoreductase (bc1 complex) serves as an important electron junction in many respiratory systems. It funnels electrons coming from NADH and ubiquinol to cytochrome c, but it is also capable of producing significant amounts of the free radical superoxide. In situ and in other experimental systems, the enzyme exists as a dimer. But until recently, it was believed to operate as a functional monomer. Here we show that a functional dimer model is capable of explaining both kinetic and superoxide production rate data. The model consists of six electronic states characterized by the number of electrons deposited on the complex. It is fully reversible and strictly adheres to the thermodynamics governing the reactions. A total of nine independent data sets were used to parameterize the model. To explain the data with a consistent set of parameters, it was necessary to incorporate intramonomer Coulombic effects between hemes bL and bH and intermonomer Coulombic effects between bL hemes. The fitted repulsion energies fall within the theoretical range of electrostatic calculations. In addition, model analysis demonstrates that the Q pool is mostly oxidized under normal physiological operation but can switch to a more reduced state when reverse electron transport conditions are in place.


Bacterial and fungal pathogens in granulomatous lesions of Chelonia mydas in a significant foraging ground off southern Brazil.
The green sea turtle Chelonia mydas inhabit near-shore areas exposed to threatening anthropogenic activities. The granulomatous lesions in these animals may indicate infectious diseases that can be associated with environmental contamination and hazards to human health. This study aimed to characterize the granulomatous inflammation associated with bacterial and fungal infection in C. mydas off Paraná state. From September 2015 to February 2019, systematic monitoring was performed by the Santos Basin Beach Monitoring Project for sea turtles'carcasses recovery, necropsy, and cause of death diagnosis. The tissue samples were fixed in buffered formalin 10% for histochemical analysis and frozen for molecular analysis to fungi detection (Internal Transcribed Spacer region of the nuclear rDNA) and bacteria detection (16S ribosomal gene). From a total of 270 C. mydas, granulomatous lesions were observed in different organs of 63 (23.3%) individuals. The histological analysis indicated lesions in 94 organs, affecting most respiratory and digestive systems. Bacteria were identified in 25 animals, including an acid-fast bacteria detected in one animal, and fungi in 24 C. mydas. The fungi species included the genus Candida (Candida zeylanoides, n = 3), Yarrowia (Yarrowia lipolytica, n = 9; Yarrowia deformans, n = 5; and Yarrowia divulgata, n = 1), and Cladosporium anthropophilum (n = 1). No species of bacteria was identified by molecular testing. All fungi species identified are saprobic, some are important to food and medical industries, but are also pathogens of humans and other animals. Therefore, long-term monitoring of these pathogens and the C. mydas health may indicate changes in environmental quality, possible zoonotic diseases, and their effects.


Phase separation at the heart of "heat" sensing.
Phytochrome B is known as a receptor for both light and temperature signals. In this issue of Molecular Cell, Chen et al. (2022) show how these two environmental signals are perceived distinctly by a single photoreceptor through liquid-liquid phase separation (LLPS).


[Vaccination against hepatitis B in health workers and other staff in Barcelona].
To analyse the results of a hepatitis B vaccination programme, in order to find the levels of acceptance of the programme and adherence to it, as well as the immunological response and the impact of age, gender and the index of corporal mass (ICM). This was a retrospective study. Primary Care. 2,055 Primary Care professionals considered at risk (43.3% of the Area total). Out of the total number of professionals at risk, 1,294 (63%) agreed to have the serological markers. The prevalence of markers of the hepatitis B virus (HBV) was 16.07% (208), which increased with age (p < 0.0001). 87% had three doses (961/1,106). 863 (89.8%) of these went through the post-vaccination controls and levels of HB antibodies above 10 IU/ml were found in 790 (91.5%). The fourth dose produced favorable results (66.7%) in individuals with HB antibodies between 10 and 100 IU/ml and unfavorable ones (3.8%) where the HB antibodies were below 10 IU/ml. The hepatitis B vaccination programme has not enjoyed total acceptance by Primary Care professionals, although a satisfactory level of adherence has been reached. Age is the variable linked most closely to the risk of a poor immunological response, though ICM and gender should not be ignored.


A hypothesis relating breathing pattern to some forms of the "adult respiratory distress syndrome".
Quantitative deficiency of surfactant in neonates results in hyaline membrane disease. Although surfactant is also required for normal gas exchange in adults, no disorders have been clearly attributable to a deficient amount of surfactant. Based on studies in our laboratories as well as on information and ideas in the literature, we suggest that a physical alteration in surfactant may lead to, or contribute to, the development of some forms of "adult" respiratory distress syndrome." In particular, we suggest that an altered breathing pattern contributes to the alveolar collapse and liver-like appearance of the lung found in certain clinical entities, i.e., pulmonary embolism and oxygen toxicity. We hypothesize that in these conditions shallow breathing leads to the aggregation of surfactant into a less functional form resulting in increased alveolar surface tension and atelectasis. The increase in surface tension would also contribute to the edema found in these conditions.


Implications of science for illicit drug use policies for adolescents in low- and middle-income countries.
Advances in neuroscience have improved our knowledge of the impact of illicit drug use on the adolescent brain. Translating this new knowledge into improved policies and programs requires the participation of public health and social sciences. This article discusses the implications of the recent advances of neurobiology for policies especially as they pertain to adolescents in low- and middle-income countries. It includes an overview of adolescent use of illicit drugs in low- and middle-income countries and calls for a move toward a transdisciplinary approach. It presents some of the challenges for research aimed at increasing our understanding of the issue and for policy.


Synthesis of sterically-crowded olefins, gem-dihaloalkenes, butatrienes, and thioketenes through the reaction of substituted bornane-2-thiones or bornane-2-selones with conventional carbenes or metal carbenoids.
Reaction of highly-substituted bornane-2-selones with a diazoalkane in the presence of either Rh2(OAc)4 or CuCl formed sterically-crowded exo-methylenic products, and similar treatment of the thiones or selones with dihalocarbenes or a propadienylidene carbene also formed dihaloalkenes, butatrienes, and thioketenes. All these reactions were assumed to proceed through a pathway involving the in situ formation and subsequent ring closure of chalcogenocarbonyl ylides.


[Verbal comprehension with objects and its comparison with the token test in children].
This study analyzes the results obtained in the child from an application of the Token Test of the De Renzi and Vignolo and compares them with those obtained from the application of a similar Test, in which objects of more familiar semantic field were employed. Normal children ranking from 4 years 0 month to 8 years 11 months were studied for this purpose.


The trend toward electronic time and attendance sheets.
One way in which savvy agencies can generate businesslike efficiencies is by using advanced electronic, telephone-based time, attendance, and data collection systems. Telephony solutions are helping agencies achieve cost and operational efficiencies, while assuring high standards of patient care.


A Race-neutral Approach to the Interpretation of Lung Function Measurements.
Rationale: The use of self-reported race and ethnicity to interpret lung function measurements has historically assumed that the observed differences in lung function between racial and ethnic groups were because of thoracic cavity size differences relative to standing height. Very few studies have considered the influence of environmental and social determinants on pulmonary function. Consequently, the use of race and ethnicity-specific reference equations may further marginalize disadvantaged populations. Objectives: To develop a race-neutral reference equation for spirometry interpretation. Methods: National Health and Nutrition Examination Survey (NHANES) III data (n = 6,984) were reanalyzed with sitting height and the Cormic index to investigate whether body proportions were better predictors of lung function than race and ethnicity. Furthermore, the original GLI (Global Lung Function Initiative) data (n = 74,185) were reanalyzed with inverse-probability weights to create race-neutral GLI global (2022) equations. Measurements and Main Results: The inclusion of sitting height slightly improved the statistical precision of reference equations compared with using standing height alone but did not explain observed differences in spirometry between the NHANES III race and ethnic groups. GLI global (2022) equations, which do not require the selection of race and ethnicity, had a similar fit to the GLI 2012 "other" equations and wider limits of normal. Conclusions: The use of a single global spirometry equation reflects the wide range of lung function observed within and between populations. Given the inherent limitations of any reference equation, the use of GLI global equations to interpret spirometry requires careful consideration of an individual's symptoms and medical history when used to make clinical, employment, and insurance decisions.


Importance of perceived naturalness for acceptance of food additives and cultured meat.
Four experiments examined some factors influencing the perceived naturalness of food products and their biasing effect on risk perception. The results of Experiment 1a showed that three food additives displaying their respective E-numbers (i.e., codes for food additives in the European Union and Switzerland) decreased perceived naturalness. Experiment 1b demonstrated that mentioning possible health effects decreased the perceived naturalness of a plant-based food additive. This experiment further showed that it would not matter for perceived naturalness whether the food was synthetic or nature-identical. Moreover, the results of Experiments 2 and 3 suggested that the same risk associated with meat consumption was much more acceptable for traditionally produced meat compared with in-vitro meat. Experiment 3 further indicated that the perceived naturalness of the meat (i.e., traditional or cultured meat) had a full mediation effect on participants' evaluation of the acceptability of the risk of colon cancer associated with the meat consumption. Even if the new production method (i.e., cultured meat) was more environmentally friendly and less harmful to animals, the perceived lack of naturalness might reduce the acceptability of the risk associated with such a product. The present study provides evidence that consumers rely on symbolic information when evaluating foods, which may lead to biased judgments and decisions.


Sources and sequelae of bacterial contamination of hematopoietic stem cell components: implications for the safety of hematotherapy and graft engineering.
It is important to compare the incidence of bacterial contamination of components collected from the peripheral blood or bone marrow (BM), as well as of components processed with or without cell selection or depletion, and to evaluate the sequelae of such contamination. Bacterial contamination rates were compared in 1380 untreated autologous peripheral blood progenitor cells (PBPCs), 291 untreated autologous BM samples, 916 monoclonal antibody (MoAb)-treated autologous and allogeneic BM samples, and in 45 autologous PBPC components from which the CD34+ cells were selected. Bacterial cultures were performed at sequential time points during the processing of MoAb-treated BM. Bacterial contamination was documented in 44 of 2632 components from 1593 patients (1.67% of components, 2.76% of patients) before cryopreservation. Although only 0.65% of untreated PBPCs were contaminated before cryopreservation, each patient was more likely to have given a contaminated PBPC component than a contaminated BM component (2.41% vs. 0%, p < 0.01). Bacterial contamination of MoAb-treated BM was greater during or after manipulation than it was before (2.33% vs. 0.77%, p < 0.05). At thawing, contamination was documented in 42 (1.97%) of 2136 components cultured. Ten (13.7%) of 73 patients who received hematopoietic progenitor cells that were contaminated before cryopreservation or at thawing developed fever or positive blood cultures within 48 hours of transfusion. Fever was associated with bacteremia in two cases, but no irreversible clinical sequelae were noted. These studies suggest that, despite careful attention to sterile procedures, low-level contamination of hematopoietic stem cell components can be introduced before or during manipulation as well as at thawing, and that standards for monitoring of the procedures for collection, processing, cryopreservation, thawing, and transfusion of hematopoietic progenitor cells are necessary.


Signal transduction by tumor necrosis factor receptors.
Tumor necrosis factor (TNF) is a key mediator in the inflammatory response which is implicated in the onset of a number of diseases. Research on TNF led to the characterization of the largest family of cytokines known until now, the TNF superfamily, which exert their biological effects through the interaction with transmembrane receptors of the TNFR superfamily. TNF itself exerts its biological effects interacting with two different receptors: TNFR1 and TNFR2. TNFR1 presents a death domain on its intracellular region. In contrast to TNFR1, TNFR2 does not have a death domain. Activation of TNFR1 implies the consecutive formation of two different TNF receptor signalling complexes. Complex I controls the expression of antiapoptotic proteins that prevent the triggering of cell death processes, whereas Complex II triggers cell death processes. TNFR2 only signals for antiapoptotic reactions. However, recent evidence indicates that TNFR2 also signals to induce TRAF2 degradation. TRAF2 is a key mediator in signal transduction of both TNFR1 and TNFR2. Thus, this novel signalling pathway has two important implications: on one hand, it represents an auto regulatory loop for TNFR2; on the other hand, when this signal is triggered TNFR1 activity is modified so that antiapoptotic pathways are inhibited and apoptotic reactions are enhanced.


Role of lncRNA LUCAT1 in cancer.
Long non-coding RNAs (lncRNAs) are RNA molecules with a transcript length of more than 200 nt and lack a protein-coding ability. They regulate gene expression by interacting with protein, RNA, and DNA. Their function is closely related to their subcellular localization. In the nucleus, lncRNAs regulate gene expression at the epigenetic and transcriptional levels, and in the cytoplasm, they regulate gene expression at the post-transcriptional and translational levels. Abnormalities in lncRNAs have been confirmed to exhibit tumor suppressor or carcinogenic effects and play an important role in the development of tumors. In particular, the lung cancer-related transcript 1 (LUCAT1) located in the antisense strand of the q14.3 region of chromosome 5 was first discovered in smoking-related lung cancer. Increasing evidence have showed that LUCAT1 is involved in breast cancer, ovarian cancer, thyroid cancer, renal cell carcinoma. It is highly expressed in liver cancer and other malignant tumors and has been confirmed to be induce various malignant tumors. It regulates tumor proliferation, invasion, and migration via various mechanisms and is related to the clinicopathological characteristics of tumor patients. Thus, LUCAT1 is a potential prognostic biological marker and therapeutic target for cancer. This article reviews its expression, function, and molecular mechanism in various malignant tumors.


Is regionally selective D2/D3 dopamine occupancy sufficient for atypical antipsychotic effect? an in vivo quantitative [123I]epidepride SPET study of amisulpride-treated patients.
Atypical antipsychotic drug treatment is clinically effective with a low risk of extrapyramidal symptoms. Explanations for the mechanism underlying this beneficial therapeutic profile of atypical over typical antipsychotic agents include 1) simultaneous antagonism of dopamine D(2) and serotonin 5-HT(2A) receptors or 2) selective action at limbic cortical dopamine D(2)-like receptors with modest striatal D(2) receptor occupancy. Amisulpride is an atypical antipsychotic drug with selective affinity for D(2)/D(3) dopamine receptors and provides a useful pharmacological model for examining these hypotheses. The authors' goal was to evaluate whether treatment with amisulpride results in "limbic selective" D(2)/D(3) receptor blockade in vivo. Five hours of dynamic single photon emission tomography data were acquired after injection of [(123)I]epidepride (approximately 150 MBq). Kinetic modeling was performed by using the simplified reference region model to obtain binding potential values. Estimates of receptor occupancy were made relative to a healthy volunteer comparison group (N=6). Eight amisulpride-treated patients (mean dose=406 mg/day) showed moderate levels of D(2)/D(3) receptor occupancy in the striatum (56%), and significantly higher levels were seen in the thalamus (78%) and temporal cortex (82%). Treatment with amisulpride results in a similar pattern of limbic cortical over striatal D(2)/D(3) receptor blockade to that of other atypical antipsychotic drugs. This finding suggests that modest striatal D(2) receptor occupancy and preferential occupancy of limbic cortical dopamine D(2)/D(3) receptors may be sufficient to explain the therapeutic efficacy and low extrapyramidal symptom profile of atypical antipsychotic drugs, without the need for 5-HT(2A) receptor antagonism.


Microglia activation by SIV-infected macrophages: alterations in morphology and cytokine secretion.
HIV infection in the brain and the resultant encephalitis affect approximately one third of individuals infected with HIV, regardless of treatment with antiretroviral drugs. Microglia are the resident phagocytic cell type in the brain, serving as a "first responder" to neuroinvasion by pathogens. The early events of the microglial response to productively infected monocyte/macrophages entering the brain can best be investigated using in vitro techniques. We hypothesized that activation of microglia would be specific to the presence of simian immunodeficiency virus (SIV)-infected macrophages as opposed to responses to macrophages in general. Purified microglia were grown and stimulated with control or SIV-infected macrophages. After 6 h, aliquots of the supernatant were analyzed for 23 cytokines using Millipore nonhuman primate-specific kit. In parallel experiments, morphologic changes and cytokine expression by individual microglia were examined by immunofluorescence. Surprisingly, the presence of macrophages was more important to the microglial response rather than whether the macrophages were infected with SIV. None of the cytokines examined were unique to co-incubation with SIV-infected macrophages compared with control macrophages, or their supernatants. Media from SIV-infected macrophages, however, did induce secretion of higher levels of IL-6 and IL-8 than the other treatments. As resident macrophages in the brain, microglia would be expected to have a strong response to infiltrate innate immune cells such as monocyte/macrophages. This response is triggered by incubation with macrophages, irrespective of whether or not they are infected with SIV, indicating a rapid, generalized immune response when infiltrating macrophages entering the brain.


Land-atmosphere coupling speeds up flash drought onset.
Flash drought is a type of drought with rapid onset and great destructiveness, which poses a serious threat to agriculture, ecosystem, and environment without sufficient early warning. The rapid onset is a unique feature that distinguishes flash drought from conventional dry conditions, but its underlying mechanism remains unclear. With the 42-years reanalysis data, we compared the differences in convective triggering potential and atmospheric humidity indices between flash drought onset and conventional dry conditions over China. We found that the dry land-atmospheric coupling can speed up flash drought onset by suppressing precipitation and increasing evapotranspiration. Results show that the increase of sensible heat transport during flash drought onset can intensify the heating of atmosphere, and enhance the lifting condensation level deficit which efficiently inhibits the convective precipitation. Meanwhile, the atmospheric drying significantly increases the evapotranspiration demand and decreases soil moisture, thus speeds up the drought onset. In this regard, the drier land surface makes the atmosphere drier through land-atmosphere coupling, and the rapid drought onset can be maintained via the positive feedback. Although the contribution of precipitation deficit averaged over China is 92 %, the evapotranspiration excess is also critical for increasing the onset speed especially over South China where the flash drought hotspot exists. With the contribution of evapotranspiration increased by about 26 %, the flash drought onset speed over China almost doubled. This study highlights the importance of dry land-atmospheric coupling for speeding up flash drought onset and provides insights for flash drought diagnosis and prediction.


Release of acetylcholine and GABA, and activity of their synthesizing enzymes in the rat pontine reticular formation.
The aim of this study was to obtain neurochemical information on the possible role of acetylcholine (ACh) and gamma-aminobutyric acid (GABA) as neurotransmitters in the pontine reticular formation (PRF). We studied the uptake of labeled choline and GABA, as well as the release of this amino acid and of ACh, in PRF slices of the rat. In addition, choline acetyltransferase, acetylcholinesterase and glutamate decarboxylase activities were assayed in PRF homogenates. The uptake of GABA was strictly Na(+)-dependent, whereas choline uptake was only partially Na(+)-dependent. The release of both ACh and GABA was stimulated by K(+)-depolarization, but only the former was Ca(2+)-dependent. Choline acetyltransferase activity in the PRF was 74% of that in the striatum, whereas acetylcholinesterase activity was considerably lower. Glutamate decarboxylase activity in the PRF was about half that observed in the striatum. These findings support the possibility that both ACh and GABA may act as neurotransmitters in the rat PRF.


Serum Cystatin C as an Inflammatory Marker in Exacerbated and Convalescent COPD Patients.
Chronic obstructive pulmonary disease (COPD) is a common chronic inflammatory disease with high morbidity and mortality rates. Cystatin C (Cys C) is a sensitive indicator for various chronic inflammatory diseases. In this study, we aimed to evaluate the role of Cys C in COPD patients comparing with the other well-known inflammatory markers. Ninety patients with acute exacerbated COPD were studied and were reassessed when convalescent. Ninety controls were matched for age, gender, body mass index, smoking index, and comorbidity. Serum Cys C was significantly increased in convalescent COPD patients compared with healthy controls and further increased in COPD patients with an acute exacerbation. Serum Cys C was positively correlated with hsCRP both in the exacerbation and convalescence periods of COPD and negatively correlated with FEV1% predicted and FEV1/FVC in the convalescent COPD patients. In conclusion, serum Cys C is a positive acute-phase reactant in COPD patients and might indicate systemic inflammation during the progression of COPD.


Diet, lipoproteins and cholesteryl ester transfer activity in hyperlipidaemic subjects.
In order to study the response of cholesteryl ester transfer activity (CETA) to alteration in diet in humans we carried out a longitudinal study in hyperlipidaemic patients. Five subjects, all hyperlipidaemic, were first given a low fat diet for 7 to 15 days and then a diet high in fat for 7 to 21 days. In four out of five patients both diets were low in energy. The plasma lipoprotein levels and CETA were measured daily. All patients responded on the low fat diet by a decrease in total cholesterol and total triglycerides. No response on the high fat diet was noticed except in the patient for whom the high fat diet was also high in energy. In all patients the changes in CETA ran parallel to changes in (VLDL + LDL) cholesterol. It is concluded that diet induced changes in (VLDL + LDL) cholesterol are accompanied by similar changes in CETA in hyperlipidaemic subjects.


The bed nucleus of the stria terminalis in the rat: regional sex differences controlled by gonadal steroids early after birth.
The effects of postnatal (on day 1 (D1) after birth) male orchidectomy and female androgenization on the bed nucleus of the stria terminalis (BNST) were studied. The volume of the medial posterior region of the BNST was greater in the control males than in the control females. Postnatal treatment reversed these differences. Sex differences were also found in the medial anterior region of the BNST where female rats always showed a greater volume than did the males. Female androgenization on D1 did not affect the volume of the BNST medial anterior region. However, D1 male orchidectomy did increase significantly the volume of this region. No sex differences were found in lateral, ventral or intermediate BNST divisions.


BamHash: a checksum program for verifying the integrity of sequence data.
Large resequencing projects require a significant amount of storage for raw sequences, as well as alignment files. Because the raw sequences are redundant once the alignment has been generated, it is possible to keep only the alignment files. We present BamHash, a checksum based method to ensure that the read pairs in FASTQ files match exactly the read pairs stored in BAM files, regardless of the ordering of reads. BamHash can be used to verify the integrity of the files stored and discover any discrepancies. Thus, BamHash can be used to determine if it is safe to delete the FASTQ files storing raw sequencing read after alignment, without the loss of data. The software is implemented in C++, GPL licensed and available at https://github.com/DecodeGenetics/BamHash email@example.com.


Myostatin is associated with the presence and development of acute-on-chronic liver failure.
Acute-on-chronic liver failure (ACLF) has been linked to different pathophysiological mechanisms, including systemic inflammation and mitochondrial dysfunction. Sarcopenia has also been proposed as a potential mechanism; myostatin is a key factor inducing sarcopenia. Therefore, this study aimed to evaluate the association of myostatin levels with the development of ACLF and mortality in patients with cirrhosis. We performed a prospective cohort study, including both outpatient and hospitalized patients with cirrhosis. Clinical, biochemical, and nutritional parameters were evaluated, and the development of acute decompensation (AD) or ACLF during follow-up was recorded. ACLF was defined according to the EASL-CLIF criteria. Receiver-operating characteristic, Kaplan-Meier and Cox regression analyses were performed. A total of 186 patients with the whole spectrum of cirrhosis were included; mean age was 53.4 ± 14 years, mean Child-Pugh score was 8 ± 2.5 and mean MELD score was 15 ± 8. There was a stepwise decrease in myostatin levels from a compensated stage to AD and ACLF. Myostatin correlated positively with nutritional markers and negatively with severity scores. The prevalence of sarcopenia was 73.6%. During follow-up, 27.9% of patients developed AD and 25.8% developed ACLF. Most episodes were grade 2-3, mainly (62.5%) precipitated by infections. The most common organ failures observed were in the liver (63.3%) and the kidney (64.6%). Receiver-operating characteristic analysis yielded <1,280 pg/ml as the best serum myostatin cut-off for the prediction of ACLF. In Kaplan-Meier curves and multivariate analysis, myostatin levels remained independently associated with the incidence of ACLF and survival. There is a progressive decrease in myostatin levels as cirrhosis progresses, demonstrating an association of sarcopenia with the development of ACLF and increased mortality. Myostatin is a muscle hormone, it is decreased in patients with muscle loss and is a marker of impaired muscle function. In this study we show that myostatin levels are decreased in patients with cirrhosis, with lower levels in patients with acute decompensation and acute-on chronic liver failure (ACLF). Low myostatin levels in cirrhosis predict the development of ACLF and mortality independently of liver disease severity and sex.


Biochemical markers of oxidative and nitrosative stress in acne vulgaris: correlation with disease activity.
Acne vulgaris is a multifactorial skin disorder of unknown etiology. Free radical-mediated reactions have been implicated but their role in eliciting this response and contributing to disease progress remains unexplored. This study was undertaken to investigate the status and contribution of oxidative/nitrosative stress in patients with acne vulgaris. Sera from 50 acne vulgaris with varying levels of disease activity (mild, moderate, and severe) according to the Global Acne Grading System (GAGS) and 40 age- and sex-matched controls were evaluated for serum levels of oxidative/nitrosative stress markers, including protein oxidation, lipid peroxidation and nitric oxide (NO), superoxide dismutase (SOD), and glutathione (GSH). Serum analysis showed significantly higher levels of carbonyl contents, malondialdehyde (MDA) and NO, in acne patients compared with healthy controls (P < 0.05). Interestingly, not only there were an increased number of subjects positive for carbonyl contents, but also the levels of these oxidants were significantly increased with the increase of the disease activity (P < 0.05). In addition, a significant correlation was observed between the levels of carbonyl contents and the GAGS scores (r = 0.341, r = 0.355, and r = 0.299, respectively). Furthermore, sera from acne patients had lower levels of SOD and GSH compared with healthy control sera. These findings support an association between oxidative/nitrosative stress and acne. The stronger response observed in serum samples from patients with higher GAGS scores suggests that markers of oxidative/nitrosative stress may be useful in evaluating the progression of acne and in elucidating the mechanisms of disease pathogenesis.


Modulation of AT1 receptor-mediated contraction of rat uterine artery by AT2 receptors.
The aim of this study was to characterize the angiotensin II receptors in isolated uterine arteries from non pregnant and pregnant rats, since it has been reported from binding studies that ovine uterine arteries contain AT2 receptors. Uterine arterial segments were obtained from virgin, non-pregnant and late pregnant (18-21 days) Sprague-Dawley rats and mounted in small vessel myographs. Concentration-response curves were constructed to angiotensin II (1 nM-10 microM) in the absence and presence of various angiotensin II receptor subtype selective compounds. These included losartan (AT1 antagonist; 1, 10 and 100 nM), PD 123319 (AT2 antagonist; 1 microM) and CGP 42112 (AT2 agonist; 1 microM). Responses to angiotensin II were measured as increases in force (mN) and expressed as a per cent of the response to a K+ depolarizing solution. Losartan (1, 10 and 100 nM) caused significant concentration-dependent rightward shifts of the angiotensin II concentration-response curve in uterine arteries from non-pregnant and pregnant rats. The pA2 values calculated from these data were 9.8 and 9.2, respectively, although the slope of the Schild plot in the non-pregnant group was less than unity. PD 123319 (1 microM) caused significant 6- and 3 fold leftward shifts of the angiotensin II concentration-response curve in uterine arteries from non-pregnant and pregnant rats, respectively. In vessels from pregnant rats, PD 123319 also significantly increased the maximum response to angiotensin II. CGP 42112 (1 microM) attenuated the response to angiotensin II of uterine arteries from non-pregnant rats. This was reflected by a 14 fold rightward shift of the angiotensin II concentration-response curve and a decrease in the maximum response. In uterine arteries from pregnant rats, CGP 42112 (1 microM) caused a 3 fold rightward shift of the angiotensin II concentration-response curve, but had no effect on the maximum response. PD 123319 (1 microM) and CGP 42112 (1 microM) had no effect on the concentration-response curves to phenylephrine (PE) of uterine arteries from non-pregnant or pregnant rats. In addition, CGP 42112 (1 nM-1 mM) had no vasodilator effect on tissues precontracted with phenylephrine. These results suggest that the contractile responses of the rat uterine artery are mediated by the AT1 receptor. Furthermore, in this vascular preparation, the AT2 receptor appears to inhibit the response mediated by the AT1 receptor, although, this is not uniform between the non-pregnant and pregnant states.


General solutions to multiple testing problems. Translation of "Sonnemann, E. (1982). Allgemeine Lösungen multipler Test probleme. EDV in Medizin und Biologie 13(4), 120-128".
The introduction of sequentially rejective multiple test procedures (Einot and Gabriel, 1975; Naik, 1975; Holm, 1977; Holm, 1979) has caused considerable progress in the theory of multiple comparisons. Emphasizing the closure of multiple tests we give a survey of the general theory and its recent results in applications. Some new applications are given including a discussion of the connection with the theory of confidence regions.


Preparing the health professional for community health.
An assessment is made of an initial experience of undergraduate and postgraduate preparation increasingly directed to priority areas in community health. It is measured against set objectives, interrelated factors and a WHO viewpoint of target areas.


Immunosuppression after liver transplantation for primary sclerosing cholangitis influences activity of inflammatory bowel disease.
Previous studies have shown conflicting results regarding the course of inflammatory bowel disease (IBD) after liver transplantation in patients with primary sclerosing cholangitis (PSC). We studied the progression of IBD in patients with PSC who have undergone liver transplantation. We also studied risk factors, including medical therapy, that could influence on IBD disease activity. In a longitudinal multicenter study, we analyzed data from the Nordic Liver Transplant Group on 439 patients with PSC who underwent liver transplantation from November 1984 through December 2006; 353 had IBD at the time of transplantation. We compared IBD activity before and after liver transplantation. Two hundred eighteen patients who had an intact colon and had undergone pretransplant and post-transplant colonoscopies were characterized further. Macroscopic colonic inflammation was more frequent after liver transplantation than before liver transplantation (153 vs 124 patients; P < .001). The degree of inflammation decreased in 37 patients (17%), was unchanged in 93 patients (43%), and increased in 88 patients (40%) (P < .001). The rate of relapse after transplantation was higher than that before transplantation (P < .001), and overall clinical IBD activity also increased (P < .001). Young age at diagnosis of IBD and dual treatment with tacrolimus and mycophenolate mofetil were significant risk factors for increased IBD activity after transplantation, whereas combination treatment with cyclosporin A and azathioprine had protective effects. Immunosuppression affects IBD activity after liver transplantation in patients with PSC; a shift from present standard maintenance treatment of tacrolimus and mycophenolate mofetil to cyclosporin A and azathioprine should be considered for these patients.


Prevalence and risk factors of gestational diabetes in the health region of Lleida: a retrospective observational cohort study.
Diabetes is a very common metabolic condition during pregnancy. The number of cases increases with age and obesity. The prevalence of pre-gestational diabetes and gestational diabetes (GD) differs between different ethnic groups. The aim of the study was to analyse the prevalence of pre-gestational diabetes and GD in the health region of Lleida. We also studied the GD risk factors during pregnancy according to the country of origin of the pregnant woman. We performed a retrospective observational cohort study among pregnant women between 2012 and 2018 in the health region of Lleida. A multivariate model was performed with the different variables analysed by calculating the regression coefficient and its 95% confidence interval (CI). In our sample of 17,177 pregnant women, we observed a prevalence of pre-gestational diabetes and GD of 8.2% and 6.5%, respectively. We found a relationship of gestational diabetes with different factors: age, with 6.8% in 30-34 year-old women and 11.3% in women over 35 (OR 1.78 and 3.29, respectively); overweight, with 8.29% (OR 1.89); and obesity, with 12.9% (OR 3.15). Finally, women from Asia and the Middle East and the Maghreb had a higher risk of diabetes, with 12.2% (OR 2.1) and 9.91% (OR 1.3), respectively, and Sub-Saharan women had a lower risk of it 6.07% (OR 0.71). GD has different risk factors, such as age, overweight, and obesity. Non-related conditions include hypothyroidism, arterial hypertension, and dyslipidaemia. Finally, pregnant women from the Maghreb, and Asia and the Middle East, are at higher risk of developing diabetes during pregnancy; meanwhile, Sub-Saharan origin is protector factor.


A genetic association study of the FXYD domain containing ion transport regulator 6 (FXYD6) gene, encoding phosphohippolin, in susceptibility to schizophrenia in a Japanese population.
The FXYD domain containing ion transport regulator 6 (FXYD6) gene is located within a region of chromosome 11 (11q23.3) that has been shown by a number of genome scans to be one of the most well-established linkages to schizophrenia. FXYD6 encodes the protein phosphohippolin, which is primarily expressed in the brain. Phosphohippolin modulates the kinetic activity of Na,K-ATPase and has long-term physiological importance in maintaining cation homeostasis. A recent study reported that FXYD6 was associated with schizophrenia in the United Kingdom samples. Applying the gene-based association concept, we carried out an association study regarding FXYD6 and schizophrenia in a Japanese population, with a sample consisting of 2026 subjects (906 schizophrenics and 1120 controls). After linkage disequilibrium analysis, 23 single nucleotide polymorphisms (SNPs) were genotyped using 5'-exonuclease allelic discrimination assay. We found a significant association of two SNPs (rs11216573; genotypic P value: 0.022 and rs555577; genotypic P value: 0.026, allelic P value: 0.011, uncorrected). Nominal P values did not survive correction for multiple testing (rs11216573; genotypic P value: 0.47 and rs555577; genotypic P value: 0.55, allelic P value: 0.24, after SNPSpD correction). No association was observed between schizophrenia patients and controls in allelic, genotypic and haplotypic analyses. Our findings suggest that FXYD6 is unlikely to be related to the development of schizophrenia in a Japanese population.


Effects of NH4F and distilled water on structure of pores in TiO2 nanotube arrays.
In this study, we report the influences of distilled water and ammonium fluoride (NH4F) on morphology of pores in honeycomb-like titanium dioxide (TiO2) nanotube arrays. We observed the structure and arrangement of pores in the TiO2 nanotube arrays based on scanning electron microscopy images and analyzed the spatial distribution of the pores using fast Fourier transform and Voronoi diagram. We studied the individual pore properties including pore diameter, wall thickness, and interpore distance and found that locally connected ordering defects decreased with increasing distilled water concentration. Furthermore, we found that the optimum conditions of well-ordered hexagonal pore arrangement were 2 and 10 vol% distilled water with 0.2 and 0.4 wt% NH4F, respectively. Throughout this study, we provide a better understanding about the roles of distilled water and NH4F in forming well-ordered nanoscale pore structure with less ordering defects in the honeycomb-like TiO2 nanotube arrays.


Increased Complications and Cost Associated With Hip Arthroplasty for Femoral Neck Fracture: Evaluation of 576,119 Medicare Patients Treated With Hip Arthroplasty.
The benefit of total hip arthroplasty (THA) for treatment of osteoarthritis (OA) and femoral neck fractures (FNFs) in the geriatric population is well established. We compare perioperative complications and cost of THA for treatment of OA to hemiarthroplasty (HA) and THA for treatment of FNF. Data from the Centers for Medicare & Medicaid Services were used to identify all patients 65 years and older undergoing primary hip arthroplasty between 2013 and 2017. Patients were divided into 3 cohorts: THA for OA (n = 326,313), HA for FNF (n = 223,811), and THA for FNF (n = 25,995). Generalized regressions were used to compare group mortality, 90-day readmission, thromboembolic events, and 90-day episode costs, controlling for age, gender, race, and comorbidities. Compared to patients treated for OA, FNF patients were older and had significantly more comorbidities (all P < .001). Even among the youngest age group (65-69 years) without comorbidities, FNF was associated with a greater risk of mortality at 90 days (THA-FNF odds ratio [OR] 9.3, HA-FNF OR 27.0, P < .001), 1 year (THA-FNF OR 7.8, HA-FNF OR 19.0, P < .001) and 5 years (THA-FNF hazard ratio 4.5, HA-FNF hazard ratio 10.0, P < .001). The average 90-day direct cost was $12,479 and $14,036 greater among THA and HA for FNF respectively compared to THA for OA (all P < .001). Among Centers for Medicare & Medicaid Services hip arthroplasty patients, those with an FNF had significantly higher rates of mortality, thromboembolic events, readmission, and greater direct cost. Reimbursement models for arthroplasty should account for the distinctly different perioperative complication and resource utilization for FNF patients.


Incorporating Colorectal Cancer Genetic Risk Assessment into Gastroenterology Practice.
Decades have passed since the underlying molecular etiologies of the most common hereditary forms of colorectal cancer (CRC), Lynch syndrome, and familial adenomatous polyposis (FAP) were first described. With the advent of next-generation sequencing (NGS) panels, the landscape of hereditary CRC testing has changed dramatically. We review available screening strategies, novel CRC predisposition genes, and challenges and opportunities in this field. Improved sensitivity and availability of NGS panel testing have greatly expanded our understanding regarding the number of CRC syndromes and their phenotypic expression. A variety of screening strategies are available to identify heritable CRC syndromes, potentially decreasing morbidity and mortality in this population. However, these screening strategies remain imperfect and present challenges regarding their implementation in clinical practice. Screening strategies include universal screening of CRC tumors for Lynch syndrome, clinical prediction algorithms, and risk assessment questionnaires. Additionally, there remains a gap in our understanding of the clinical implications of novel gene mutations of variable penetrance and unexpected NGS panel test results. Incorporation of single nucleotide polymorphisms (SNPs) may help to further refine cancer risk assessment, and the clinical introduction of RNA analysis may allow us to clarify variants of unknown significance (VUSs) and identify deep intronic mutations that would otherwise be missed. Recognition of genetic predisposition to CRC is critical for the practicing gastroenterologist. The evolving field of cancer genetics offers great challenges and opportunities for improved CRC management.


Catabolite regulation in a diauxic strain and a nondiauxic strain of Streptococcus bovis.
Streptococcus bovis JB1 utilized glucose preferentially to lactose and grew diauxically, but S. bovis 581AXY2 grew nondiauxically and used glucose preferentially only when the glucose concentration was very high (greater than 5 mM). As little as 0.1 mM glucose completely inhibited the lactose transport of JB1. The lactose transport system of 581AXY2 was at least tenfold less sensitive to glucose, and 1 mM glucose caused only a 50% inhibition of lactose transport. Both strains had phosphotransferase systems (PTSs) for glucose and lactose. The glucose PTSs were constitutive, but little lactose PTS activity was detected unless lactose was the energy source for growth. JB1 had approximately threefold more glucose PTS activity than 581AXY2 (1600 versus 600 nmol glucose (mg protein)-1(min)-1. The glucose PTS of JB1 showed normal Michaelis Menten kinetics, and the affinity constant (Ks) was 0.12 mM. The glucose PTS of 581AXY2 was atypical, and the plot of velocity versus velocity/substrate was biphasic. The low capacity system had a Ks of 0.20 mM, but the Ks of the high capacity system was greater than 6 mM. On the basis of these results, diauxic growth is dependent on the affinity of glucose enzyme II and the velocity of glucose transport.


BCR-ABL activates STAT3 via JAK and MEK pathways in human cells.
Chronic myeloid leukaemia (CML) is characterised by a progression from a chronic towards an acute phase. We previously reported that signal transducer and activator of transcription 3 (STAT3), a major oncogenic signalling protein, is the target of p210-BCR-ABL in a murine embryonic stem (ES) cell model and in primary CD34+ CML cells. This activation was associated with inhibition of differentiation in ES cells. The present study found that BCR-ABL greatly phosphorylated STAT3 Ser727 residue and, to a lesser extent, Tyr705 residue in BCR-ABL-expressing cell lines (UT7-p210, MO7E-p210, and K562) and in primary CD34+ CML cells. Using BCR-ABL mutants, it was shown that BCR-ABL tyrosine kinase activity and its Tyr177 residue were necessary for STAT3 Ser727 phosphorylation. Constitutive STAT3 Tyr705 phosphorylation was associated with constitutive phosphorylation of Janus kinase (JAK)1 and JAK2, and was inhibited by the JAK inhibitor AG490, suggesting the involvement of JAK proteins in this process. Specific MEK [mitogen-activated protein (MAP) kinase/extracellular signal-regulated kinase (ERK) kinase] inhibitors PD98056 and UO126, as well as the use of a dominant-negative form of MEK1 abrogated STAT3 Ser727 phosphorylation, suggesting involvement of MAP-Kinase/Erk pathway. Inhibition of BCR-ABL with imatinib mesylate led to a dose-dependent downregulation of total STAT3 protein and mRNA, suggesting that BCR-ABL is involved in the transcriptional regulation of STAT3. Targeting JAK, MEK and STAT3 pathways could therefore be of therapeutic value, especially in advanced stage CML.


Infectious osteitis pubis.
Osteitis pubis is a well-recognized painful inflammation involving the structures of the anterior half of the pelvic girdle, but its cause remains controversial. Biopsy and culture of the pubic bone in 3 patients with osteitis pubis after implantation of a urinary anti-incontinence device were consistent with pubic osteomyelitis which responded to antibiotic therapy. Infection was also found in almost all previously reported cases of osteitis pubis subjected to similar biopsy and culture. Bone biopsy and culture should be strongly considered before initiating frequently unsuccessful empirical therapy in patients with osteitis pubis.


Telescopic video-otoscopy using a compact home video color camera.
Our method of telescopic video-otoscopy using a telescope (Hopkins) and a compact home video camera is presented. Telescopic video-otoscopy is a most effective method of demonstrating and documenting the anatomy and pathology of the tympanic membrane, ear canal, and mastoid cavity. It is of considerable value for teaching, patient counseling, and making a permanent record. It obtains instantaneously a video print-out either in black-and-white or in color of video images of telescopic otoscopy. A simple and economical method of telescopic pneumatic otoscopy (pneumatic teleotoscopy) is also described. Telescopic video otoscopy combined with the use of a video printer is a useful addition to the clinical practice of otology.


Detection of aperiodic test patterns by pattern specific detectors revealed by subthreshold summation.
The hypothesis that the visual system detects, under certain conditions, stimulus patterns by means of filters matched to these patterns (Hauske et al. 1976) may be challenged by the argument that other coding mechanisms like spatial frequency channels, Gabor or Hermite filters mimic the behaviour of matched filters, a view supported by the finding of non-linear contrast-interrelationship functions (CIFs), as determined in superposition experiments. In this paper we argue that an overall non-linear CIF does not contradict the hypothesis of detection by a single matched filter: we find that the sensitivity functions determined in our experiments can be separated into two components reflecting (i) a bandpass filter and (ii) a filter characterized by the spectrum of the test-pattern.


[Autoantibodies and antibody-secreting cells].
Autoantibodies are a hallmark of systemic and organ-specific autoimmune diseases. They contribute both directly and indirectly to the pathogenesis of these diseases. There is now a rising interest in cells that secrete (auto)antibodies. Antibody-secreting cells are plasma blasts and plasma cells that differentiate from B cells following antigen encounter. The view held by the immunology community for decades was that (auto)antibodies are produced by short-lived cells arising from chronic (auto)antigen-mediated B cell stimulation. However, it was recently shown that plasma cells can survive in niches in the bone marrow and inflamed tissues for months to years. These long-lived plasma cells continuously secrete (auto)antibodies without the need for any additional antigen stimulation. They are resistant to immuno-suppressants and are not eliminated by B-cell depleting therapies. Depending on which antibodies are secreted, this plasma cell memory may play an important role in maintaining protective humoral immunity or in the pathogenesis of autoimmune diseases. Consequently, strategies targeting long-lived autoreactive plasma cells may provide new therapeutic options in the treatment of autoimmune diseases.


Linking centennial scale anthropogenic changes and sedimentary records as lessons for urban coastal management.
Coastal eutrophication and urban flooding are increasingly important components of global change. Although increased seawater renewal by barrier openings and channelizing are common mitigation measures in coastal lagoons worldwide, their effects on these ecosystems are not fully understood. Here, we evaluated the relationships between human interventions in the watershed, artificial connections to the sea, and the sediment burial rates in an urban coastal lagoon (Maricá lagoon, Southeastern Brazil). Sediment accretion along with nutrient and carbon burial rates were determined in two sediment cores representing the past ∼120 years (210Pb dating) and associated with anthropogenic changes as indicated by historical records and geoinformation analyses. Lagoon infilling and eutrophication, expressed by the average sediment accretion, TP, TN, and OC burial rates, respectively, increased ∼9-18, 13-15, 11-14 and 11-12-fold from the earliest (<1950) to the most recent (2000-2017) period. These multi-proxy records confirm mechanistic links between deforestation, urbanization, and untreated sewage discharges. In addition, our findings reveal artificial connections to the sea may contribute to lagoonal eutrophication and infilling, particularly when not integrated with sewage treatment and forest conservation or reforestation in the watershed. Therefore, increased seawater renewal by physical interventions commonly considered as mitigation measures may in contrast cause severe degradation in coastal lagoons, causing harmful consequences that should be not neglected when implementing management practices.


Congenital cutaneous fistula at the sternoclavicular joint - Not a dermoid fistula but the remnant of the fourth branchial (pharyngeal) cleft ?
A fourth branchial pouch remnant is well known as a pyriform sinus fistula. However, there has been no report of a fistula composed of the complete remnant of the fourth branchial apparatus. We experienced patients with a congenital lower neck cutaneous fistula which was thought to be the skin-side remnant of the fourth branchial cleft. Seven children were referred to our hospital from 2009 to 2015 for the treatment of a cutaneous fistula situated near the sternoclavicular joint. All of them were surgically resected and their pathological characteristics were examined. Clinical charts were retrospectively reviewed. In six cases, the left side was affected. All cutaneous fistulas had a small skin orifice near the sternoclavicular joint and they were situated at the anterior edge of the sternocleidomastoid muscle. Abscess formation was seen in four cases. Surgical resection was performed at the age of 6 months to 9 years. These fistulas ran deep into the subcutaneous tissue and had a blind end. Pathological examination showed that the epithelial layer was mainly composed of a stratified squamous epithelium. In two cases the epithelium was composed of ciliated columnar epithelium. Recurrence has not been observed in any of the cases. The seven cases had a common clinical feature and were a definite clinical entity. Judging from the characteristics of our cases and the previous literature, we concluded that this lower neck cutaneous fistula was most likely a congenital skin-side remnant of the fourth branchial cleft.


Weight loss reduces C-reactive protein levels in obese postmenopausal women.
C-reactive protein (CRP) has been proposed as an independent risk factor for cardiovascular disease and has been positively associated with body weight and body fatness. We examined the hypothesis that weight loss would reduce plasma CRP levels in obese postmenopausal women. In a sample of 61 obese (body mass index, 35.6 +/- 5.0 kg/m(2)), postmenopausal women (age, 56.4 +/- 5.2 years), we found that plasma CRP levels were positively associated with dual x-ray absorptiometry-measured total body fatness (r=0.36, P<0.005) and CT-measured intra-abdominal body fat area (r=0.30, P<0.02). Significant correlations were also found between plasma CRP and triglyceride levels (r=0.33, P<0.009) and glucose disposal measured by the hyperinsulinemic-euglycemic clamp technique (r=-0.29, P<0.03). Twenty-five of the 61 women tested at baseline completed a weight loss protocol. The average weight loss was 14.5 +/- 6.2 kg (-15.6%, P<0.0001), with losses of 10.4 +/- 5.4 kg fat mass (-25.0%, P<0.0001) and 2.8 +/- 1.4 kg fat-free mass (-6.0%, P<0.0001). Visceral and subcutaneous fat areas were reduced by -36.4% and -23.7%, respectively (P<0.0001). Plasma CRP levels were significantly reduced by weight loss: average -32.3%, from 3.06 (+0.69, -1.29) to 1.63 (+0.70, -0.75) microgram/mL (P<0.0001, medians and interquartile differences). Changes in body weight and in total body fat mass were both positively associated with plasma CRP level reductions. Adiposity was a significant predictor of plasma CRP in postmenopausal women on a cross-sectional basis. Moreover, caloric restriction-induced weight loss decreased plasma CRP levels. Weight loss may represent an important intervention to reduce CRP levels, which may mediate part of its cardioprotective effects in obese postmenopausal women.


Fractal model for blood flow in cardiovascular system.
Blood flow in the cardiovascular system is the central point of experimental and theoretical investigation. The objective of the study is to determine the blood flow in the cardiovascular system using Darcy's law, Reynold's number and Poiseuille's equation. A possible way of modeling of self-similar biological tree-like structure is proposed. Special attention is paid to the blood vessel system, with elaboration on a model with certain spatial arrangement of the vessels and reasonable dependence of the blood pressure on the vessels diameter such that the organism has a homogeneous oxygen supply. Flow analysis in the above systems is analyzed by invasion percolation. The blood flow in the cardiovascular system has been numerically calculated for both normal and abnormal patients. A new algorithm has been introduced to visit the blood vessels in a robust manner which avoids loops and provides us the results in a simple manner.


Do rare variant genotypes predict common variant genotypes?
The synthetic association hypothesis proposes that common genetic variants detectable in genome-wide association studies may reflect the net phenotypic effect of multiple rare polymorphisms distributed broadly within the focal gene rather than, as often assumed, the effect of common functional variants in high linkage disequilibrium with the focal marker. In a recent study, Dickson and colleagues demonstrated synthetic association in simulations and in two well-characterized, highly polymorphic human disease genes. The converse of this hypothesis is that rare variant genotypes must be correlated with common variant genotypes often enough to make the phenomenon of synthetic association possible. Here we used the exome genotype data provided for Genetic Analysis Workshop 17 to ask how often, how well, and under what conditions rare variant genotypes predict the genotypes of common variants within the same gene. We found nominal evidence of correlation between rare and common variants in 21-30% of cases examined for unrelated individuals; this rate increased to 38-44% for related individuals, underscoring the segregation that underlies synthetic association.


Central auditory processing in patients with systemic lupus erythematosus.
Systemic Lupus Erythematosus (SLE) patients can also present neuropsychiatric disorders, such as impaired memory and attention. Central auditory processing depends on a great number of skills controlled by the central nervous system. To characterize the performance of SLE patients, with and without neuropsychiatric disorders (NP), in central auditory processing tests. A prospective controlled study of Dichotic Speech and Temporal Processing Tests was carried out at a tertiary teaching Institution. Three groups were formed with 20 individuals each, totalizing sixty women with age varying from 18 to 48 years: Group I - SLE patients without neuropsychiatric disorders; Group II - SLE patients with neuropsychiatric disorders as well; and Group III - age and gender matched healthy controls. Dichotic Speech Test showed similar results for patients in Group I and for healthy controls; however, most of the patients in Group II presented impaired performance with great variability of response. SLE patients (Groups I and II) presented a significantly lower performance in Temporal Processing tests than controls. SLE patients especially those with neuropsychiatric disorders presented impaired central auditory processing, which may contribute to the memory and attention impairment.


Comprehensive Analysis of Spinal Muscular Atrophy: SMN1 Copy Number, Intragenic Mutation, and 2 + 0 Carrier Analysis by Third-Generation Sequencing.
Population-wide carrier screening for spinal muscular atrophy (SMA) is recommended by the American College of Medical Genetics and Genomics. However, the methods used currently mainly focus on SMN1 copy number and fail to identify carriers with pathogenic intragenic mutations and silent (2 + 0) carriers. We developed a method termed comprehensive analysis of SMA (CASMA) based on long-range PCR and third-generation sequencing of full-length and downstream regions of SMN1/2. The sensitivity and specificity of CASMA to detect SMA carriers with one copy of SMN1 were 100% (n = 101) and 99.2% (n = 236), respectively. CASMA confirmed three SMN1 intragenic mutations and pinpointed an inframe mutation c.661_666del to SMN2, which was misreported to SMN1 by allele-specific long-range nested PCR plus Sanger sequencing. CASMA also correctly predicted 8 of 16 samples (50%) with SMN1 duplication alleles. CASMA was expected to increase the detection rate of SMA carriers from 91% to 98% and decrease the residual risk ratio from 1:415 to 1:1868 after negative results of two SMN1 copies in the Chinese population. CASMA presents a comprehensive approach for identifying SMN1 and SMN2 copy number, intragenic mutations, and potential silent carriers that significantly reduces the residual risk ratio in SMA carrier screening and has great clinical utility.


Breast Implant-Associated Anaplastic Large Cell Lymphoma: Updates in Diagnosis and Specimen Handling.
Pathologic staging including assessment of margins is essential for the proper management of patients with breast implant-associated anaplastic large-cell lymphoma (BIA-ALCL). As most patients present with effusion, cytologic examination with immunohistochemistry and/or flow cytometry immunophenotyping are essential for diagnosis. Upon a diagnosis of BIA-ALCL, en bloc resection is recommended. When a tumor mass is not identified, a systematic approach to fixation and sampling of the capsule, followed by pathologic staging and assessment of margins, is essential. Cure is likely when lymphoma is contained within the en bloc resection and margins are negative. Incomplete resection or positive margins require a multidisciplinary team assessment for adjuvant therapy.


Novel Surgical Approach for Root Coverage Using Coronally Advanced Flap in Conjunction With Transposition of Periosteal Pedicle Graft.
Gingival recession is a complex phenomenon with multifactorial etiology. It is defined as the apical migration of the soft tissue margin beyond the cemento-enamel junction, thereby exposing the root surface. It results in the destruction of both soft and hard tissues. Three patients with buccal gingival recession defects underwent surgical treatment consisting of transposition of a periosteal pedicle in conjunction with the coronally advanced flap (CAF) technique. As the cambium layer of the periosteum has greater osteoblastic potential than the fibrous layer, this study considered juxtaposing of the cambium layer directly onto the denuded root surface. A 9-month review demonstrated satisfactory: root coverage; gain in clinical attachment, reduction in probing depth; and increase in width of keratinized gingiva with a good color match and minimal scarring. Within the limits of the study, this CAF technique, in conjunction with the cambium layer of periosteum, showed a significant amount of root coverage.


Laparoscopic reconstruction after esophageal resection for perforation: a new surgical approach.
The authors present 2 cases of esophageal perforation treated using a new 2-step approach, consisting of esophageal resection and delayed reconstruction of the digestive tract after laparoscopic preparation and transposition of the stomach. The method is characterized by the minimally invasive insertion of a gastric tube through the precardial esophageal stump for postoperative enteral nutrition, and by the use of a laparoscopic method in the reconstruction step for gastrolysis and transposition of the stomach. The benefits lie in the opportunity for enteral feeding preparatory to the reconstruction, with no need for any gastrostomy or jejunostomy, and with fewer complications and a better recovery after reconstruction surgery thanks to the use of a laparoscopic method instead of a laparotomy.


Effect of prostaglandins on skin tumorigenesis.
Concomitant administration of prostaglandins E2 (PGE2) and F2alpha (PGF2alpha) with a carcinogen, 3-methylcholanthrene (MCA) to mice for 2 months markedly enhanced the occurrence of squamous cell carcinomas. Only epidermal cell hyperplasia occurred in mice treated with MCA alone by that time. Radioactivity measurements and electron microscopic autoradiography revealed that prostaglandins stimulate DNA, RNA and protein synthesis in neoplastic cells. These findings indicate that PGE2 and PGF2alpha can act as cocarcinogens on skin tumorigenesis.


Scene-relative object motion biases depth percepts.
An important function of the visual system is to represent 3D scene structure from a sequence of 2D images projected onto the retinae. During observer translation, the relative image motion of stationary objects at different distances (motion parallax) provides potent depth information. However, if an object moves relative to the scene, this complicates the computation of depth from motion parallax since there will be an additional component of image motion related to scene-relative object motion. To correctly compute depth from motion parallax, only the component of image motion caused by self-motion should be used by the brain. Previous experimental and theoretical work on perception of depth from motion parallax has assumed that objects are stationary in the world. Thus, it is unknown whether perceived depth based on motion parallax is biased by object motion relative to the scene. Naïve human subjects viewed a virtual 3D scene consisting of a ground plane and stationary background objects, while lateral self-motion was simulated by optic flow. A target object could be either stationary or moving laterally at different velocities, and subjects were asked to judge the depth of the object relative to the plane of fixation. Subjects showed a far bias when object and observer moved in the same direction, and a near bias when object and observer moved in opposite directions. This pattern of biases is expected if subjects confound image motion due to self-motion with that due to scene-relative object motion. These biases were large when the object was viewed monocularly, and were greatly reduced, but not eliminated, when binocular disparity cues were provided. Our findings establish that scene-relative object motion can confound perceptual judgements of depth during self-motion.


Black Americans have worse stroke outcome compared with non-Hispanic whites.
We studied racial differences in post-stroke outcomes using a prospective, population-based cohort of stroke survivors as part of the Brain Attack Surveillance in Corpus Christi (BASIC) project. Neurologic (NIHSS, range of 0-42, higher scores are worse), functional (ADLs/IADLs, range 1-4, higher scores are worse), and cognitive (3MSE, range 0-100, higher scores are better) outcomes were measured 90 days after stroke. Cox proportional hazards and negative binomial linear regression models were used to examine the associations between race and 90-day all-cause mortality and NIHSS, respectively, whereas linear regression was used for ADLs/IADLs and 3MSE scores. Covariates included demographics, initial NIHSS, comorbidities, prior stroke history, tPA treatment status, pre-stroke disability, and pre-stroke cognition. The mortality model was also adjusted for DNR status. At 90 days post-stroke, Black American individuals (BAs) (n = 122) had a median (IQR) NIHSS of 2 (1,6) compared to NIHSS of 1 (0,3) in non-Hispanic White American individuals (NHWs) (n = 795). BAs had a median (IQR) ADL/IADL score of 2.41 (1.50, 3.39) compared to 2.00 (1.27, 2.95) in NHWs. BAs scored a median of 84 (75, 92) on the 3MSE compared to NHWs' score of 91.5 (83, 96). Death occurred in 23 (8%) of BAs and 268 (15%) of NHWs within 90 days among those who participated in baseline. After adjustment for covariates, functional outcomes at 90 days were worse in BAs compared to NHWs, with 15.8% (95% CI=5.2, 26.4) greater limitations in ADLs/IADLs and 43.9% (95% CI=12.0, 84.9) greater severity of stroke symptoms. Cognition at 90 days was 6.5% (95% CI=2.4, 10.6) lower in BAs compared to NHWs. BAs had a 35.4% lower (95% CI=-9.8, 61.9) hazard rate of mortality than NHWs. In this prospective, population-based community sample, BAs had worse neurologic, functional and cognitive outcomes at 90 days compared to NHWs. Future research should investigate how social determinants of health including structural racism, neighborhood factors and access to preventive and recovery services influences these racial disparities.


Ovine pineal indoles: effects of L-tryptophan or L-5-hydroxytryptophan administration.
L-5-Hydroxytryptophan (L-5-HTP) (20 or 200 mg/kg i.p.) but not L-tryptophan (500 mg/kg i.p.) loading substantially increases serum melatonin in sheep. In the present study we examined the effects of these compounds on pineal serotonin and six serotonin metabolites. L-Tryptophan failed to increase 5-hydroxytryptamine (5-HT; serotonin) or any of its metabolites despite a five-fold increase in pineal tryptophan. In contrast, L-5-HTP loading produced a marked increase in pineal 5-HT and its metabolites, including N-acetylserotonin (NAS) and melatonin, indicating that an increased synthesis of melatonin is responsible for the increased serum melatonin concentration after loading with this precursor. No change in pineal indoleamine N-acetyltransferase (NAT) activity was seen. These results are consistent with the suggestion that, during daytime in the sheep, 5-HT availability may limit the production of melatonin.


Genital bacteriology: a comparative study of premenopausal women with postmenopausal women.
Premenopausal women are reportedly at a higher risk than postmenopausal women of postoperative infection following vaginal hysterectomy. A study was designed to determine whether a relationship exists between bacterial flora and patient age that may explain the difference in the risk of postoperative infection. No statistically significant difference was found in the number or type of bacterial species isolated from the cervix or vagina of premenopausal and postmenopausal women. Postmenopausal women on a regimen of conjugated estrogens had genital flora similar to that of the other women studied.


Clinical features of pain in amyotrophic lateral sclerosis: A clinical challenge.
Pain in amyotrophic lateral sclerosis (ALS) is paradoxical in this disease of the upper and lower motor neurons. As such, it remains an underestimated and neglected clinical problem because it is poorly identified by physicians, its mechanisms are numerous and its treatments are generally not effective. Pain may be primary in the form of cramps, spasticity and neuropathy, or secondary as nociceptive pain, and may arise before the first motor symptoms. It may also lead to depression and, in all cases, affect patients' daily activities and quality of life. Given the high frequency of pain in ALS, the use of analgesic or sedative drugs is necessary and should reduce the course of the disease. Nevertheless, it is important to understand the pathophysiological mechanisms of pain in ALS, and to train physicians how to detect ALS pain early on and provide dedicated treatments. In France, the implementation of ALS centers is a positive response to the public-health problem resulting from this disorder.


The effects of waste-activated sludge pretreatment using hydrodynamic cavitation for methane production.
Disintegration of waste-activated sludge (WAS) is regarded as a prerequisite of the anaerobic digestion (AD) process to reduce sludge volume and increase methane yield. Hydrodynamic cavitation (HC), which shares a similar underlying principle with ultrasonication but is energy-efficient, was employed as a physical means to break up WAS. Compared with ultrasonic (180-3600 kJ/kg TS) and thermal methods (72,000 kJ/kg TS), HC (60-1200 kJ/kg TS) found to consume significantly low power. A synergetic effect was observed when HC was combined with alkaline treatment in which NaOH, KOH, and Ca(OH)2 were used as alkaline catalysts at pH ranging from 8 to 13. As expected, the production yield of CH4 gas increased proportionally as WAS disintegration proceeded. HC, when combined with alkaline pretreatment, was found to be a cost-effective substitute to conventional methods for WAS pretreatment.


Green tea polyphenol EGCG suppresses lung cancer cell growth through upregulating miR-210 expression caused by stabilizing HIF-1α.
(-)-Epigallocatechin-3-gallate (EGCG) has been reported to affect many cellular regulatory pathways. This study aims to determine whether EGCG could target microRNA (miRNA), one of the mechanisms for cells to achieve subtle change in multiple targets. We found that, in both human and mouse lung cancer cells in culture, EGCG specifically upregulated the expression of miR-210, a major miRNA regulated by HIF-1α. Furthermore, we found that overexpression of miR-210 led to reduced cell proliferation rate and anchorage-independent growth as well as reduced sensitivity to EGCG. On the mechanisms of miR-210 regulation by EGCG, we demonstrated that the regulation was mediated through the hypoxia-response element in miR-210 promoter. Consistently, the upregulation of miR-210 was found to be correlated with the stabilized HIF-1α in lung cancer cell lines after EGCG treatment. This EGCG-induced stabilization of HIF-1α was further shown by the stabilization of HA-tagged HIF-1α but not the P402A/P564A-mutated HIF-1α by EGCG, suggesting that EGCG targets the oxygen-dependent degradation (ODD) domain. Direct evidence was obtained by affinity binding assay showing that EGCG specifically binds HIF-1α with a K(d) = 3.47 μM. This result suggests that EGCG binding interferes with the hydroxylation of key Pro residues in the ODD domain, preventing HIF-1α from the Pro hydroxylation-dependent ubiquitination and subsequent proteosome-mediated degradation. In summary, our results demonstrated, for the first time, the elevation of miR-210 by EGCG in lung cancer cell lines and this is mediated by the stabilization of HIF-1α. This event contributes to the anticancer activity of EGCG.


EIF2AK3, encoding translation initiation factor 2-alpha kinase 3, is mutated in patients with Wolcott-Rallison syndrome.
Wolcott-Rallison syndrome (WRS) is a rare, autosomal recessive disorder characterized by permanent neonatal or early infancy insulin-dependent diabetes. Epiphyseal dysplasia, osteoporosis and growth retardation occur at a later age. Other frequent multisystemic manifestations include hepatic and renal dysfunction, mental retardation and cardiovascular abnormalities. On the basis of two consanguineous families, we mapped WRS to a region of less than 3 cM on chromosome 2p12, with maximal evidence of linkage and homozygosity at 4 microsatellite markers within an interval of approximately 1 cM. The gene encoding the eukaryotic translation initiation factor 2-alpha kinase 3 (EIF2AK3) resides in this interval; thus we explored it as a candidate. We identified distinct mutations of EIF2AK3 that segregated with the disorder in each of the families. The first mutation produces a truncated protein in which the entire catalytic domain is missing. The other changes an amino acid, located in the catalytic domain of the protein, that is highly conserved among kinases from the same subfamily. Our results provide evidence for the role of EIF2AK3 in WRS. The identification of this gene may provide insight into the understanding of the more common forms of diabetes and other pathologic manifestations of WRS.


Distribution of fluoride concentration in the rat's bone.
The present study was undertaken to determine the fluoride distribution profile in the rat femur. Male Wistar rats were divided into four groups and given water containing 0, 25, 50, and 100 ppm of fluoride, respectively, for 10 weeks. The fluoride distribution from the periosteum to the endosteum was determined in each specimen after sampling using the abrasive microsampling technique. In the outer circumferential lamellae, the concentration of fluoride was relatively high in the periosteal layer and then decreased gradually towards its interior. In the haversian and interstitial lamellae, it was lower and roughly constant through the tissue. In the inner circumferential lamellae, it rose again to reach the highest level towards the endosteal surface. Fluoride concentration throughout the cortex increased significantly with increasing intake of fluoride. These increases were especially marked at periosteal and endosteal surfaces.


Fate, transport, and source of microplastics in the headwaters of the Yangtze River on the Tibetan Plateau.
Microplastics (MPs) in the Yangtze River have been drawn increasing attention recently with most merely concentrating on the plain area. This research focuses on the source area of the Yangtze River on the Qinghai-Tibet Plateau (QTP), revealing the occurrence, drivers, sources, and exposure risks of riverine MPs in the Jinsha River (JSR) basin. The results showed that average MP abundances determined were higher in the tributaries than in the of mainstreams. According to the correlation analysis, MP abundance was consistently negatively related to pH and altitude both in water and sediment. However, MPs in two media showed a contrary relationship with river width, which could be explained by the special terrain of plateau rivers and hydrological conditions. After the tributary river flow into the mainstream, the concentration of MPs in the mainstream near the tributary side were significantly lower than that before confluence temporarily. Based on the conditional fragmentation-based model, the cumulative λ value of fibers in surface water along the river divided the JSR into three stages (upstream, midstream, and downstream). Under certain assumptions, the proportions of MPs sourced from three stages were eventually revealed, respectively. This is conducive to better understanding the plateau environmental impacts of MP distribution in the large river.


An analysis of civil aircrash statistics 1977-86 for the purposes of planning disaster exercises.
Details of 473 aircrashes throughout the world for the period 1977-1986 were obtained from the Civil Aviation Authority. 114 occurred on or near and 359 away from airfields. In 188 there were survivors and in 285 none. On or near airfields it was more common to have survivors, and away from airfields more common to have none, yet crashes with survivors were more common away from airfields. In ten years there were only 3 crashes with more than 50 seriously injured live casualties. Acted out disaster exercises with mock casualties should not have more than 50 injured casualties, of whom not more than 20 should have serious injuries (i.e. need admission to hospital). The problems of crashes with much larger casualty figures should be worked through in table-top exercises.


Difference in hypertension prevalence applying three childhood hypertension management guidelines in a national cohort study.
The European Society of Hypertension (ESH) and American Academy of Pediatrics (AAP) recently updated their childhood hypertension management guidelines. We aimed to compare the hypertension prevalence determined using the two aforementioned guidelines and Fourth Report in a national cohort study. This 4.6-year follow-up study included 4276 children who had participated in the China Health and Nutrition Study. At baseline and during a follow-up survey, hypertension was defined using the three guidelines. We calculated the pediatric hypertension prevalence in at least one survey and in both surveys as the number of participants identified as hypertensive in at least one survey or in both surveys divided by 4276, respectively. Using Mc Nemar's test, we determined that the prevalence of pediatric hypertension differed significantly according to AAP vs. ESH guidelines and Fourth Report at the baseline (8.3% vs. 5.0% and 5.0%, respectively; reference, AAP; Ps < 0.001 for AAP vs. ESH guidelines and Fourth Report) and follow-up surveys (14.5% vs. 5.0% and 6.0%, respectively; reference, AAP; both Ps < 0.001), as well as among those detected with hypertension in at least one survey (21.0% vs. 9.4% and 10.4%, respectively; reference, AAP; both Ps < 0.001) and both surveys (1.8% vs. 0.5% and 0.6%, respectively; reference, AAP; both Ps < 0.001). We obtained similar results when using the three guidelines to define childhood elevated blood pressure. Our findings confirm the higher prevalence of pediatric hypertension using AAP guideline than those using ESH guideline and Fourth Report. Consequently, childhood hypertension management guidelines should be selected and used with caution.


Evaluation of survivorship care plans in patients attending the Sydney Cancer Survivorship Centre.
The transitioning of cancer survivors from active treatment to surveillance care has been described as uncoordinated, with lack of communication between healthcare professionals. Survivorship care plans (SCP) are recommended to bridge this transitioning period and help improve coordination of care. SCP contain individualized information about a survivor's cancer diagnosis, treatment, and recommendations for managing treatment-related side effects and improving lifestyle risk factors for cancer recurrence and chronic disease. The aims of the study were to assess the delivery, usefulness, and compliance with SCP of survivors attending a multidisciplinary survivorship clinic and to determine patient suggestions regarding how to improve SCP. A total of 110 survivors were interviewed in-person or by phone regarding their SCP following a script with formalized questions. Data were analyzed quantitatively using descriptive statistics. Overall, 65% of participants (72/110) acknowledged having received a SCP and 86% found them useful. Only 11% of survivors (8/72) showed their SCP to other health professionals and about half (33/72) showed it to family/friends. Ninety percent of survivors (65/72) reported following at least one recommendation in their SCP. Survivors found SCP helpful but did not share them with other healthcare providers, which questions their usefulness in coordinating care. There were challenges with SCP delivery. Survivors reported they were compliant with SCP lifestyle recommendations. Further research is required to address the utility of SCP to other stakeholders, such as general practitioners, to determine whether they receive the SCP, if they find them helpful, and their expectations regarding SCP.


The development of a system for the reporting, classification and grading of quality failures in the clinical biochemistry laboratory.
There is no agreed system for the reporting, classification and grading of the severity of quality failures in the clinical biochemistry laboratory. A 'Quality Query' reporting system was set up to log all quality failures identified by staff and service users. Quality failures were classified into three major groups of the preanalytical, analytical and postanalytical phases with appropriate subcategories in each group. The severity of each quality failure was graded using a five-point scoring system incorporating both actual ('A') and potential ('P') score elements. The 'A' score measured the actual adverse impact of the quality failure on patient care, while the 'P' score measured the 'worst case' potential outcome that might have resulted. The system was assessed over a 19-month period. Three hundred and ninety-seven Quality Query reports were completed (0.085% of all requests). Breakdown by cause: pre-analytical phase--88.9%, analytical phase--9.6%, post-analytical phase--1.5%. The quality failure severity 'A' scores were skewed towards a low adverse impact on patient care: 72.7% allocated an 'A' score of 1 (least severe grade). The 'P' scores were skewed towards a high potential impact on patient care: 65.9% allocated a 'P' score of 5 (most severe grade). The Quality Query reporting system proved easy to integrate into routine laboratory practice. Although the great majority of quality failures had minimal adverse impact on patient care, the potential for adverse outcomes was much higher. This system generates important information on laboratory performance and helps inform risk management priorities.


[Whole-course, individualized, and standardized sequential nutrition therapy for radical resection of tongue cancer: a case report].
Surgery, radiotherapy, and chemotherapy are the main treatments for tongue cancer, but the nutritional status of patients is not considered. Nutritional treatment is often not standard or by experience. This article reports a patient with tongue cancer who underwent preoperative chemotherapy and postoperative nutrition treatment. The entire process of individualized and sequential nutrition therapy was adopted, and the nutritional status of the patient was significantly improved. This paper describes the methods of nutrition therapy and evaluation and discusses the treatment process and key points in combination with relevant literature.


Outcome of childhood bacterial meningitis on three continents.
Our objective was to quantify the differences in the outcomes from childhood bacterial meningitis (BM) and to describe the factors associated with them in different parts of the world. This study is a secondary analysis of prospectively collected data from five clinical BM trials conducted in Finland, Latin America (LatAm), and Angola between 1984 and 2017. As all data were collected uniformly, direct comparison of the series was possible. Associations between patient characteristics and death or dismal outcome-the triad of death, severe neurological sequelae, or deafness-were explored. In all, data on 2123 children with BM were analyzed. Etiology was confirmed in 95%, 83%, and 64%, in Finland, LatAm and Angola, respectively. The leading agents were Haemophilus influenzae, Streptococcus pneumoniae, and Neisseria meningitidis. Dismal outcome was the end result for 54%, 31%, and 5% of children in Angola, LatAm, and Finland, respectively. Although underweight, anemia, and tardy arrival worsened prognoses in Angola and LatAm, it was the presenting condition that was central in terms of outcome. In multivariate analysis, the factors independently associated with dismal outcome were the study site (Angola vs. Finland, OR 11.91, 95% CI 5.54-25.63, p < 0.0001 or LatAm vs. Finland, OR 9.46, 95% CI 4.35-20.61, p < 0.0001), Glasgow Coma Score < 13 (OR 4.58, 95% CI 3.31-6.32, p < 0.0001), seizures (OR 1.96, 95% CI 1.43-2.69), age < 1 year (OR 1.55, 95% CI 1.13-2.14, p = 0.007), and pneumococcal etiology (OR 1.49, 95% CI 1.08-2.06, p = 0.015). Greatly dissimilar outcomes from BM reflected the findings on admission on all three continents. Optimizing growth, preventing anemia, and prompt treatment may improve outcomes in resource poor areas.


Laser photobiomodulation does not alter clinical and histological characteristics of 4-NQO-induced oral carcinomas and leukoplakia in mice.
This study evaluated the effect of laser photobiomodulation (PBM) on oral leukoplakia and squamous cell carcinomas (OSCC) in a model of oral carcinogenesis. Forty-one C57Bl/6 female mice were distributed in control group, 4-NQO group, Laser group 1.5 J and Laser group 9 J. Oral cancer was induced on the tongue by nitroquinoline oxide (4-NQO), diluted in the water for 16 weeks. In the 18th and 19th weeks, PBM with a diode laser, 0.028 cm2 spot size, continuous emission mode, 660 nm wavelength was applied on the tongue of animals for seven sessions. Laser group 1.5 J received 30 mW power and 1.5 J energy. In the Laser group 9 J, 100 mW power, and 9 J energy were applied. In the 20th week the animals were euthanized. All animals exposed to carcinogen developed clinical and histological alterations such as leukoplakia and OSCC on the tongue. There was no significant difference among Laser groups 1.5 and 9 J and 4-NQO group (not irradiated) regarding the area of leukoplakia and carcinomas (P > 0.05) or thickness of epithelial tissue and keratin (P > 0.05). There were also no association between PBM and histologic classification of the lesions (P = 0.87), frequency of OSCC (P = 0.57), grade of tumor differentiation (P = 0.88) or depth of invasion (P = 0.45). Laser PBM, in both parameters used, does not influence on clinical and histological characteristics of oral leukoplakia and OSCC. Results suggest that PBM may be a safe treatment for adverse effects of antineoplastic therapies in patients with leukoplakia and OSCC.


A pattern formed by preferential orientation of tangential fibres in layer I of the rabbit's cerebral cortex.
1. The tangential organization of layer I has been studied in frozen sections impregnated according to a modified Liesegang method and in Bodian impregnated paraffin sections cut tangentially to the dorsal surface of the rabbit's cerebral cortex. 2. It is shown that sublamina tangentialis of layer I contains a system of parallel nerve fibres forming a distinct pattern in the tangential plane. 3. This pattern has been reconstructed for a large region of the dorsal surface of the cerebral cortex including the striate areas as well as the peristriate, parietal and precentral agranular regions and parts of the retrosplenial area. 4. In most parts of the region investigated, the tangential fibres of layer I are oriented in an antero-medial to postero-lateral direction, forming an angle of about 50 degrees with the sagittal plane. 5. Deviations from this pattern are found in the furrows formed by the lateral sulcus and the frontal impression and also in the caudal part of the retrosplenial area. In these regions, which are characterized by comparatively steep changes of the cortical relief, the fibres course in a more sagittal direction.


A binocular indirect ophthalmomicroscope (BIOM) for non-contact wide-angle vitreous surgery.
The binocular indirect ophthalmomicroscope (BIOM) incorporates the principles of indirect ophthalmoscopy in the operating microscope. When used with an image inverting system, it enables noncontact 70 degrees-90 degrees wide-angle observation of the fundus during vitreous microsurgery.