Interleukin 27 induces differentiation of neural C6-precursor cells into astrocytes.
Interleukin 6 (IL6)-type cytokines are major regulators of inflammation and thereby contribute to the neuropathology and pathophysiology associated with inflammation of the central nervous system (CNS). Furthermore, astrocyte development which is a key process in the development of the CNS is also controlled by cytokines of the IL6-family. Interleukin 27 (IL27) is a recently identified member of this family and has been implicated in the inhibition of TH17 T-cell-responses. Here we show that IL27 and the HHV8 encoded viral IL6 (vIL6) induce C6 glioma cells to differentiate into an astrocyte-like state. Cytokine stimulation led to STAT-factor phosphorylation and consequently to protein expression of the astrocyte marker glial fibrillary acidic protein (GFAP). These data could be confirmed by GFAP-immunostaining of stimulated cells. Taken together, IL27 and vIL6 can be considered as new astrocyte-inducing cytokines of the brain.


[Children's mental health: the role of screen time, parenting behavior, and parenting stress-a secondary data analysis of KiGGS and BELLA data].
Previous studies established a link between high screen time and mental health problems in childhood. The role of possible influencing factors is currently unclear. This study aims at testing correlations among mental health problems, high screen time, parenting stress, and inconsistent and positive parenting behavior. This study is based on data from the KiGGS and BELLA studies. For the present study, data from preschool children (age: 3-5 years, N = 417) and school children (age: 7-13 years, N = 239) were analyzed. Binary-logistic regressions were carried out to test for correlations between high screen time and children's mental health problems in cross-sectional and longitudinal analyses. Socioeconomic status, the child's gender, the parent's gender, parenting stress, and inconsistent and positive parenting behavior were used as control variables. In the cross-sectional analysis, mental health problems in preschool children were associated with high screen time (OR = 3.02; p = 0.003), parenting stress (OR = 17.00; p < 0.001), and positive parenting behavior (OR = 0.24; p < 0.001). In the longitudinal analysis, mental health problems in school children were associated with parenting stress (OR = 4.04; p < 0.001). Socioeconomic status and the child's and parent's gender were at no point associated with mental health problems. The sole existence of high screen time cannot explain mental health problems in children. Parental variables seem to be critical for children's mental health and should be considered in a holistic apporach on children's mental health in terms of strengthening parental competencies.


Trends and Race/Ethnic Disparities in Diabetes-Related Hospital Use in Medicaid Enrollees: Analyses of Serial Cross-sectional State Data, 2008-2017.
Race/ethnic disparities in preventable diabetes-specific hospital care may exist among adults with diabetes who have Medicaid coverage. To examine race/ethnic disparities in utilization of preventable hospital care by adult Medicaid enrollees with diabetes across nine states over time. Using serial cross-sectional state discharge records for emergency department (ED) visits and inpatient (IP) hospitalizations from the Healthcare Cost and Utilization Project, we quantified race/ethnicity-specific, state-year preventable diabetes-specific hospital utilization. Non-Hispanic Black, non-Hispanic White, and Hispanic adult Medicaid enrollees aged 18-64 with a diabetes diagnosis (excluding gestational or secondary diabetes) who were discharged from hospital care in Arizona, Iowa, Kentucky, Florida, Maryland, New Jersey, New York, North Carolina, and Utah for the years 2008, 2011, 2014, and 2017. Non-Hispanic Black-over-White and Hispanic-over-White rate ratios constructed using age- standardized state-year, race/ethnicity-specific ED, and IP diabetes-specific utilization rates. The ratio of Black-over-White ED utilization rates for preventable diabetes-specific hospital care increased across the 9 states in our sample from 1.4 (CI 95, 1.31-1.50) in 2008 to 1.73 (CI 95, 1.68-1.78) in 2017. The cross-year-state average non-Hispanic Black-over-White IP rate ratio was 1.46 (CI 95, 1.42-1.50), reflecting increases in some states and decreases in others. The across-state-year average Hispanic-over-White rate ratio for ED utilization was 0.67 (CI 95, 0.63-0.71). The across-state-year average Hispanic-over-White IP hospitalization rate ratio was 0.72 (CI 95, 0.69-0.75). Hospital utilization by non-Hispanic Black Medicaid enrollees with diabetes was consistently greater and often increased relative to utilization by White enrollees within state programs between 2008 and 2017. Hispanic enrollee hospital utilization was either lower or indistinguishable relative to White enrollee hospital utilization in most states, but Hispanic utilization increased faster than White utilization in some states. Among broader patterns, there is heterogeneity in the magnitude of race/ethnic disparities in hospital utilization trends across states.


Intraspinal implantation of hNT neurons into SOD1 mice with apparent motor deficit.
The aim of this study was to determine the effect of hNT neuron transplants on motor neuron function in SOD1 (G93A) mice when motor deficits were already apparent. The hNT neurons were implanted into L(4)-L(5) segments of the ventral horn spinal cord of mice at 15-16 weeks of age: either G93A mice, transgenic mice carrying the normal allele for human SOD1 gene (hTg), or control wild type mice (wt). Behavioral tests (rotorod, beam balance, extension reflex, footprint) were performed prior to transplantation and at weekly intervals afterwards. HNT neuron transplantation in the SOD1 mice delayed disease progression for 3-4 weeks, although lifespan was not affected. These results suggest that hNT neuron transplantation may be a promising therapeutic strategy for ALS in the later phase of the neurodegeneration.


Adenine-Driven Structural Switch from a Two- to Three-Quartet DNA G-Quadruplex.
A G-rich sequence found in the regulatory region of the RANKL gene, which is associated with homeostasis of bone metabolism, folds into a two-quartet basket-type G-quadruplex stabilized by A⋅G⋅A and G⋅G⋅G base-triads. Perusal of local structural features together with G/A-to-T modifications uncovered the critical role of A5 for the formation of a distinct antiparallel two-quartet topology and not the three-quartet topology that would be expected based on the sequence with four GGG-tracts alone. The structural changes induced by the A5-to-T5 modification include a switch in orientation and relative positions of G-strands that together with anti to syn reorientation of G12 provide insights into the complexity of the interactions that influence the folding of G-rich DNA. Understanding the impact of loop residues on the stability and formation of G-quadruplexes advances our knowledge and ability to predict structures adopted by G-rich sequences, which are involved in regulatory mechanisms in the cell, and may also facilitate drug design.


Aluminium complexes with thio-phosphorus ligands: syntheses and characterisations of [Al(2)(CyPS(3))(2)(CyPHS(2))(2)] and [Al(S(2)PPh(2))(3)].
The novel aluminium complexes [Al(2)(CyPS(3))(2)(CyPHS(2))(2)] and [Al(S(2)PPh(2))(3)] have been prepared as potential models for alumino-thiophosphonate based materials; [Al(2)(CyPS(3))(2)(CyPHS(2))(2)] is the first example of a primary dithiophosphinate to be characterised in the solid state.


Correlation between standardized uptake value of 18F-FDG PET/CT and conductivity with pathologic prognostic factors in breast cancer.
We investigated the correlation between standardized uptake value (SUV) of 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT) and conductivity parameters in breast cancer and explored the feasibility of conductivity as an imaging biomarker. Both SUV and conductivity have the potential to reflect the tumors' heterogeneous characteristics, but their correlations have not been investigated until now. Forty four women diagnosed with breast cancer who underwent breast MRI and 18F-FDG PET/CT at the time of diagnosis were included. Among them, 17 women received neoadjuvant chemotherapy followed by surgery and 27 women underwent upfront surgery. For conductivity parameters, maximum and mean values of the tumor region-of-interests were examined. For SUV parameters, SUVmax, SUVmean, and SUVpeak of the tumor region-of-interests were examined. Correlations between conductivity and SUV were evaluated, and among them, the highest correlation was observed between mean conductivity and SUVpeak (Spearman's correlation coefficient = 0.381). In a subgroup analysis for 27 women with upfront surgery, tumors with lymphovascular invasion (LVI) showed higher mean conductivity than those without LVI (median: 0.49 S/m vs 0.06 S/m, p < 0.001). In conclusion, our study shows a low positive correlation between SUVpeak and mean conductivity in breast cancer. Furthermore, conductivity showed a potential to noninvasively predict LVI status.


Palindromic repetitive DNA elements with coding potential in Methanocaldococcus jannaschii.
We have identified 141 novel palindromic repetitive elements in the genome of euryarchaeon Methanocaldococcus jannaschii. The total length of these elements is 14.3kb, which corresponds to 0.9% of the total genomic sequence and 6.3% of all extragenic regions. The elements can be divided into three groups (MJRE1-3) based on the sequence similarity. The low sequence identity within each of the groups suggests rather old origin of these elements in M. jannaschii. Three MJRE2 elements were located within the protein coding regions without disrupting the coding potential of the host genes, indicating that insertion of repeats might be a widespread mechanism to enhance sequence diversity in coding regions.


Vaccines against enterotoxigenic bacterial pathogens based on hybrid Salmonella that express heterologous antigens.
In this report, we examine two aspects in the development of a vaccine against enterotoxigenic bacterial pathogens based on hybrid Salmonella that express heterologous antigens. First, we describe the construction of a non-toxic fusion peptide for immunization against Escherichia coli that produce heat-labile (LT) and heat-stable (ST) enterotoxins. For that construction, the 5' terminus of the gene coding for ST was fused to the 3' terminus of the gene coding for the binding subunit of LT(LT-B). The ST gene was constructed synthetically with appropriate restriction sites to permit in-frame, downstream insertion. Maximum expression of ST antigenicity was obtained when a seven-amino-acid proline-containing linker was included between the LT-B and ST moieties. The purified LT-B/ST fusion peptide consisted of a single polypeptide chain with an apparent molecular weight of 18,000. The LT-B/ST fusion peptide was non-toxic and immunologic determinants of both LT and ST were recognized by antibodies directed against the native toxins. Animals immunized with either crude or purified preparations containing the hybrid molecule produced antibodies that were able to recognize native toxin in vitro. Significantly, these antibodies were able to neutralize the biological activity of native ST. The second aspect reported here examines a mechanism for stabilizing expression of heterologous antigens in attenuated Salmonella mutants by integration of the heterologous gene (LT-B) into the chromosome of the carrier. A comparative in vitro study of the levels of expression of LT-B between the cointegrate strain and an isogenic strain carrying the LT-B gene on a multicopy plasmid demonstrated that the initial levels of expression of both strains is similar, that the plasmid-carrying strain loses the ability to express the heterologous antigen very quickly and that the cointegrate continues to maintain and express the antigen without the requirement for a stabilizing antibiotic.


Exogenous and endogenous dsRNAs perceived by plant Dicer-like 4 protein in the RNAi-depleted cellular context.
In plants, RNase III Dicer-like proteins (DCLs) act as sensors of dsRNAs and process them into short 21- to 24-nucleotide (nt) (s)RNAs. Plant DCL4 is involved in the biogenesis of either functional endogenous or exogenous (i.e. viral) short interfering (si)RNAs, thus playing crucial antiviral roles. In this study we expressed plant DCL4 in Saccharomyces cerevisiae, an RNAi-depleted organism, in which we could highlight the role of dicing as neither Argonautes nor RNA-dependent RNA polymerase is present. We have therefore tested the DCL4 functionality in processing exogenous dsRNA-like substrates, such as a replicase-assisted viral replicon defective-interfering RNA and RNA hairpin substrates, or endogenous antisense transcripts. DCL4 was shown to be functional in processing dsRNA-like molecules in vitro and in vivo into 21- and 22-nt sRNAs. Conversely, DCL4 did not efficiently process a replicase-assisted viral replicon in vivo, providing evidence that viral RNAs are not accessible to DCL4 in membranes associated in active replication. Worthy of note, in yeast cells expressing DCL4, 21- and 22-nt sRNAs are associated with endogenous loci. We provide new keys to interpret what was studied so far on antiviral DCL4 in the host system. The results all together confirm the role of sense/antisense RNA-based regulation of gene expression, expanding the sense/antisense atlas of S. cerevisiae. The results described herein show that S. cerevisiae can provide insights into the functionality of plant dicers and extend the S. cerevisiae tool to new biotechnological applications.


Gap junctions coupling photoreceptor axons in the first optic ganglion of the fly.
The first optic ganglion of the fly, the lamina ganglionaris, was investigated with the transmission electron microscope for the purpose of demonstrating possible electronic junctions. Within a cartridge, the six short receptor cell axons R1--R6 are extensively coupled by symmetrical gap junctions. This is mainly seen in the distal third of the first synaptic region where none or only a few lateral branches of the centrally lying L-fibres (L1, L2) penetrate the ring of six short receptor fibre endings. Gap junctions as found between R1--R6 are distinguished morphologically from chemically-mediated synapses by the closely apposed cell membranes. They exhibit only a 2--4 nm extracellular cleft. Unlike the chemical synapse the gap junction in the neuropile of the fly appears structurally symmetrical. No such gap junctions are found either between R-fibres and glial cells, interneurons and glial cells, between glial cells and between interneurones themselves, nor between the parallel long receptor axons R7/8, which bypass the lamina outside the cartridge. In accordance with electrophysiological data, it can now be argued that the six short receptor axons R1--R6 are electrically interconnected by symmetrical gap junctions.


Effects of galanin on dopamine release in the central nervous system of normotensive and spontaneously hypertensive rats.
Galanin is a 29-amino acid peptide and widely distributed in the brain, although its significance in the control of neural activities is undefined. In the present study, we describe the effects of galanin on the electrically evoked release of dopamine in the rat central nervous system. In addition, to elucidate a possible role of galanin in the regulation of dopaminergic transmission in hypertension, we examined whether the effect of galanin on dopamine release might be altered in the central nervous system of spontaneously hypertensive rats (SHR). Galanin (1 x 10(-8) to 1 x 10(-7) mol/L) inhibited the stimulation (1 Hz)-evoked [3H]dopamine release by a comparable amount in striatal slices of Sprague-Dawley rats, although the basal release of dopamine was not affected by the peptide. In the striatum of SHR, the electrical stimulation (1 Hz)-evoked [3H]dopamine release was significantly smaller than in the striatum of Wistar-Kyoto (WKY) rats. However, the inhibitory effect of galanin on the stimulation-evoked [3H]dopamine release was significantly more pronounced in SHR than in WKY rats. These results show that galanin significantly reduced the release of dopamine in rat striatum. Furthermore, the greater inhibitory effect of galanin on dopamine release in SHR suggests that galanin might actively participate in the regulation of dopaminergic nerve activity in hypertension.


beta-catenin/Tcf signaling in squamous differentiation of porcine airway epithelial cells.
For a preliminary study of the role of beta-catenin/Tcf signaling in squamous differentiation of airway (tracheobronchial) epithelial cells, a stable mutant of beta-catenin was transfected into primarily cultured porcine airway epithelial cells. Western blotting revealed that exogenous protein was observed in large quantity in cytoplasm and nucleus. When co-transfected with Tcf luciferase reporter plasmids, beta-catenin mutant increased the reporter's transcriptional activities. However, mRNA expression of a squamous differentiation marker, small proline-rich protein (SPRP), was not elevated, as shown by reverse transcription-polymerase chain reaction. These findings suggest that beta-catenin/Tcf signaling may not be directly involved in the squamous differentiation of porcine airway epithelial cells.


Theoretical Study of the Local Surface Plasmon Resonance Properties of Silver Nanosphere Clusters.
The local surface plasmon resonance properties in systems consisting of silver nanosphere clusters are studied by Green's function. The extinction, absorption, and scattering efficiencies band of two, three, and more silver nanospheres clusters are discussed in detail. The clusters show new types of the local surface plasmon resonances compared with single silver nanosphere. Our results suggest that the resonances depend strongly on individual particles' characteristics such as their shapes, gap distances, directions and polarizations of incident light waves, and the number of clusters. The spectrum shows that equilateral triangle nanospheres has a good absorption peak, while the better red-shifted with three aligned nanospheres. In addition, the distributions of electric field intensity for three and four touched silver nanospheres are also investigated. The study is useful to broaden the application scope of Raman spectroscopy and nanooptics.


A linear systems model of the hydrothermal isometric tension test for assessing collagenous tissue quality.
Collagen is the most abundant structural protein in the animal kingdom. Its thermal and thermomechanical properties are often measured using differential scanning calorimetry (DSC) and hydrothermal isometric tension (HIT) tests, respectively. In living tissues, not all collagenous structures (molecules, fibrils, etc.) have the same "quality," and the heterogeneity among these structures in specific tissues increases with remodeling, aging, and/or disease states. In this paper, first, a peak-fitting analysis is carried out to separate and distinguish the sequential denaturation events in a DSC endotherm, which presumably stem from heterogeneity in the collagen fibrils. The fitting analysis uses one of two functions: a Gaussian function or a function proposed by Miles. The individual endotherms were then convolved with a physics-based parametric function, J(T), proposed by the authors, to model the development of the isometric tension in two stages: 1) tension development due to a sudden increase in conformational entropy as each collagen packet denatures, and 2) additional isometric tension development due to increasing temperature, consistent with rubber thermo-elasticity. The proposed function parameters were then found by fitting to actual HIT curves using a global optimization technique. This model provides a decoupling of the effects of denaturation kinetics and collagen network connectivity and therefore an improved interpretation of HIT test results during the temperature ramp from ambient temperature to 90 °C. The simple model outputs are two parameters, α and β, that have physical meaning and aid in assessing collagenous tissue quality in terms of connectivity and integrity.


Ferrets develop fatal influenza after inhaling small particle aerosols of highly pathogenic avian influenza virus A/Vietnam/1203/2004 (H5N1).
There is limited knowledge about the potential routes for H5N1 influenza virus transmission to and between humans, and it is not clear whether humans can be infected through inhalation of aerosolized H5N1 virus particles. Ferrets are often used as a animal model for humans in influenza pathogenicity and transmissibility studies. In this manuscript, a nose-only bioaerosol inhalation exposure system that was recently developed and validated was used in an inhalation exposure study of aerosolized A/Vietnam/1203/2004 (H5N1) virus in ferrets. The clinical spectrum of influenza resulting from exposure to A/Vietnam/1203/2004 (H5N1) through intranasal verses inhalation routes was analyzed. Ferrets were successfully infected through intranasal instillation or through inhalation of small particle aerosols with four different doses of Influenza virus A/Vietnam/1203/2004 (H5N1). The animals developed severe influenza encephalomyelitis following intranasal or inhalation exposure to 10¹, 10², 10³, or 10⁴ infectious virus particles per ferret. Aerosolized Influenza virus A/Vietnam/1203/2004 (H5N1) is highly infectious and lethal in ferrets. Clinical signs appeared earlier in animals infected through inhalation of aerosolized virus compared to those infected through intranasal instillation.


[Measurement of the isometric dorsiflexion and plantar flexion force in the ankle joint].
This article describes an easy to use test equipment for measuring the isometric force in the ankle joints in dorsiflexion and plantar flexion. The combination of the test equipment for measuring the voluntary maximal isometric muscle force in the ankle joint, the surface electromyograms and the motion analysis of the measured leg allow an objective comparison of the strength of the muscular force between the left and right leg. It might be also used as a control setup during rehabilitation after surgical treatment or injuries.


Ciprofloxacin salt and salt co-crystal with di-hydroxy-benzoic acids.
The crystal structure of two multi-component crystals of ciprofloxacin [systematic name: 1-cyclo-propyl-6-fluoro-4-oxo-7-(piperazin-1-yl)quinoline-3-carb--oxy-lic acid], a fluoro-quinolone anti-biotic, namely, ciprofloxacin 2,6-di-hydroxy-benzoate salt, C17H19FN3O3 +·C7H5O4 -, (I), and ciprofloxacin hydro-chloride-3,5-di-hydroxy-benzoic-water (1/1/1), C17H19FN3O3 +·Cl-·C7H6O4·H2O, (II), were determined. In (I) and (II), the ciprofloxacin cations are connected via head-to-tail N-H⋯O hydrogen bonding. Both structures show an alternating layered arrangement between ciprofloxacin and di-hydroxy-benzoic acid.


Conformational changes in pH2-treated human interferon-alpha 2 detected with monoclonal antibodies.
Monoclonal antibodies allowed to demonstrate the existence of alternative antigenic forms of the same molecule as of human interferon (IFN)-alpha 2. Exposure of recombinant IFN to pH 2, although not affecting its bioactivity, induced structural modulation of molecular surface. The antigenic structure of IFN-alpha 2 appeared to be built of the acid-stable and acid-labile epitopes. In general, the acid-stable sites determined subtype-specific antigenic properties of the protein, whereas the acid-labile determinants were responsible for antigenic characteristics shared by some other human IFNs. Acidification of IFN-alpha 2 to pH 2 for at least 1-2 h resulted in simultaneous structural rearrangement of all acid-labile sites.


Conventional and assisted suicide in Switzerland: Insights into a divergent development based on cancer-associated self-initiated deaths.
We tested the hypothesis of supporters of assisted dying that assisted suicide (AS) might be able to prevent cases of conventional suicide (CS). By using data from the Federal Statistical Office, we analyzed the long-term development of 30,756 self-initiated deaths in Switzerland over a 20-year period (1999-2018; CS: n = 22,018, AS: n = 8738), focusing on people suffering from cancer who died from AS or CS. While cancer was the most often listed principal disease for AS (n = 3580, 41.0% of AS cases), cancer was listed in only a small minority of CS cases (n = 832, 3.8% of CS cases). There was a significant increase in the absolute number of cancer-associated AS cases: comparing four 5-year periods, there was approximately a doubling of cases every 5 years (1999-2003: n = 228 vs.2004-2008: n = 474, +108% compared with the previous period; 2009-2013: n = 920, +94%; 2014-2018: n = 1958, +113%). The ratio of cancer-associated AS in relationship with all cancer-associated deaths increased over time to 2.3% in the last observation period (2014-2018). In parallel, the numbers of cancer-associated CS showed a downward trend only at the beginning of the observation period (1999-2003, n = 240 vs. 2004-2008, n = 199, -17%). Thereafter, the number of cases remained stable in the subsequent 5-year period (2009-2013, n = 187, -6%), and increased again toward the most recent period (2014-2018, n = 206, +10%). The assumption that, with the increasingly accessible option of AS for patients with cancer, CS suicide will become "superfluous" cannot be confirmed. There are strong reasons indicating that situations and circumstances of cancer-associated CS are different from those for cancer-associated AS.


Severe Clostridioides difficile Infection in the Intensive Care Unit-Medical and Surgical Management.
Clostridioides difficile remains a major cause of morbidity and mortality in the intensive care unit, and therefore, C difficile guidelines are frequently being updated. Currently, fidaxomicin is the suggested treatment of initial and recurrent infection. Oral vancomycin is an acceptable alternative, followed by rifaximin and fecal microbiota transplantation. Bezlotoxumab is suggested in recurrent cases within 6 months. If patients fail to improve within 3 to 5 days of therapy, especially in patients who have had nasogastric tubes or emergent surgery, fulminant colitis is possible and surgical consultation should be considered for total colectomy.


Optimized Management of Cardio-Renal-Metabolic (CRM) Conditions in Patients With T2D.
Describe cardio-renal-metabolic (CRM) conditions and their impact on health and patient-centered outcomes. Recognize current gaps in screening, risk factor management, and utilization of guideline-directed therapies in patients with CRM conditions. Select appropriate guideline-directed therapies for patients with type 2 diabetes, atherosclerotic cardiovascular disease, heart failure, and/or chronic kidney disease based on current guidelines and clinical evidence. Recognize the importance of multidisciplinary care when managing patients with CRM conditions.


Development and characterization of novel alginate-based hydrogels as vehicles for bone substitutes.
In this work three different hydrogels were developed to associate, as vehicles, with the synthetic bone substitute GR-HAP. One based on an alginate matrix (Alg); a second on a mixture of alginate and chitosan (Alg/Ch); and a third on alginate and hyaluronate (Alg/HA), using Ca(2+) ions as cross-linking agents. The hydrogels, as well as the respective injectable bone substitutes (IBSs), were fully characterized from the physical-chemical point of view. Weight change studies proved that all hydrogels were able to swell and degrade within 72 h at pH 7.4 and 4.0, being Alg/HA the hydrogel with the highest degradation rate (80%). Rheology studies demonstrated that all hydrogels are non-Newtonian viscoelastic fluids, and injectability tests showed that IBSs presented low maximum extrusion forces, as well as quite stable average forces. In conclusion, the studied hydrogels present the necessary features to be successfully used as vehicles of GR-HAP, particularly the hydrogel Alg/HA.


Comparison of snoring sounds between natural and drug-induced sleep recorded using a smartphone.
Snoring is an important clinical feature of obstructive sleep apnea (OSA), and recent studies suggest that the acoustic quality of snoring sounds is markedly different in drug-induced sleep compared with natural sleep. However, considering differences in sound recording methods and analysis parameters, further studies are required. This study explored whether acoustic analysis of drug-induced sleep is useful as a screening test that reflects the characteristics of natural sleep in snoring patients. The snoring sounds of 30 male subjects (mean age=41.8years) were recorded using a smartphone during natural and induced sleep, with the site of vibration noted during drug-induced sleep endoscopy (DISE); then, we compared the sound intensity (dB), formant frequencies, and spectrograms of snoring sounds. Regarding the intensity of snoring sounds, there were minor differences within the retrolingual level obstruction group, but there was no significant difference between natural and induced sleep at either obstruction site. There was no significant difference in the F1 and F2 formant frequencies of snoring sounds between natural sleep and induced sleep at either obstruction site. Compared with natural sleep, induced sleep was slightly more irregular, with a stronger intensity on the spectrogram, but the spectrograms showed the same pattern at both obstruction sites. Although further studies are required, the spectrograms and formant frequencies of the snoring sounds of induced sleep did not differ significantly from those of natural sleep, and may be used as a screening test that reflects the characteristics of natural sleep according to the obstruction site.


Nucleosomes, DNA-binding proteins, and DNA sequence modulate retroviral integration target site selection.
Integration of retroviral DNA can serve as a paradigm for cellular functions that are affected by the packaging of DNA into chromatin. We have used a novel polymerase chain reaction-based assay to survey DNA and chromatin for the precise distribution of many integration sites. Integration into naked DNA targets is non-uniform, implying a nucleotide sequence bias. In chromatin, integration occurs preferentially at positions where the major groove is on the exposed face of the nucleosomal DNA helix, generating a 10 bp periodic spacing of preferred sites. Chromatin assembly enhances the reactivity of many sites, so that integration occurs most frequently at sites in nucleosomal, rather than nucleosome-free, regions of minichromosomes. In contrast, integration is prevented in a region occupied by a site-specific DNA-binding protein. Comparisons of integration events mediated by viral nucleoprotein complexes or by two different retroviral integrases show that the integration machinery also affects target site selection.


The effect of the DNA-suppressing factor (DSF) on host DNA synthesis in synchronized cell cultures.
Purified host DNA-suppressing factor (DSF) produced into culture fluid of HeLa C-9 cells infected with measles virus inhibited cellular DNA synthesis in HeLa cells. When purified DSF was added into cultures of synchronous HeLa cells at the early G1-phase, cellular DNA synthesis was irreversibly inhibited. However, DSF did not affect the stability of native double-stranded DNA nor the chain-elongation of single-stranded DNA in cells of the S-phase.


Reproducibility of Dynamic Contrast-Enhanced MRI in Renal Cell Carcinoma: A Prospective Analysis on Intra- and Interobserver and Scan-Rescan Performance of Pharmacokinetic Parameters.
The objective of this study was to investigate the intra- and interobserver as well as scan-rescan reproducibility of quantitative parameters of renal cell carcinomas (RCCs) with dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI). A total of 21 patients with clear cell RCCs (17 men, 4 woman; age 37-69 years, mean age 54.6 years, mean size, 5.0 ± 2.2 cm) were prospectively recruited from September 2012 to November 2012. Patients underwent paired DCE-MRI studies on a 3.0 T MR system with an interval of 48 to 72 hours. The extended-Tofts model and population-based arterial input function were used to calculate kinetic parameters. Three observers defined the 2-dimensional whole-tumor region of interest at the slice with the maximum diameter of the RCC. Intraobserver and scan-rescan differences were assessed using paired t tests, whereas interobserver differences using two-way analysis of variance. Intra- and interobserver reproducibility and scan-rescan reproducibility were evaluated using within-subject coefficient of variation (wCoV) and intraclass correlation coefficient (ICC). There were no significant intra-, interobserver, or scan-rescan differences in parameters (all P > 0.05). All ICCs for intra- and interobserver agreements were >0.75 (P < 0.05), whereas the scan-rescan agreement was moderate to good; V(e) (0.764, 95% confidence interval [CI]: 0.378-0.925) and K(ep) (0.906, 95% CI: 0.710-0.972) had higher ICC than K(trans) (0.686; 95% CI: 0.212-0.898) and V(p) (0.657; 95% CI: 0.164-0.888). In intra- and interobserver variability analyses, all parameters except V(p) had low wCoV values. K(trans) and V(e) had slightly lower intraobserver wCoV (1.2% and 0.9%) compared with K(ep) (3.7%), whereas all 3 of these parameters had similar interobserver wCoV values (2.5%, 3.1%, and 2.9%, respectively). Regarding scan-rescan variability, K(trans) and K(ep) showed slightly higher variation (15.6% and 15.4%) than V(e) (10.1%). V(p) had the largest wCoV in all variability analyses (all >30%). DCE-MRI demonstrated good intra- and interobserver reproducibility and moderate to good scan-rescan performance in the assessment of RCC using K(trans), K(ep), and V(e) as parameters under noncontinuous scanning mode. V(p) showed poor reproducibility, and thus may not be suitable for this scanning protocol.


The specific binding of estradiol to the nuclear matrix.
Recent studies on the eukaryotic nucleus have described the presence of a structural component termed the nuclear matrix, that appears to be involved in nucleic acid synthesis. This study will present evidence that the nuclear matrix of both the rat uterus and chick liver contains specific, high affinity, saturable estradiol binding sites.


Ligandinuria in nephrotoxic acute tubular necrosis.
Ligandin (GSH-S-transferase B), an abundant intracellular soluble protein in rat proximal tubules, hepatocytes, and small intestinal mucosal cells, is believed to be a component of an organic anion transport system. Its presence in urine was determined immunologically and catalytically in adult, female, Sprague-Dawley rats that were given mercuric chloride or potassium dichromate. These nephrotoxic agents produce severe renal failure, with epithelial necrosis in the proximal tubule. Mercuric chloride perferentially injures the terminal part of the proximal tubule, while potassium dichromate damages more proximal segments. Ligandinuria was consistently detected immunologically and catalytically from 6 to 24 hr following injection of mercuric chloride. Potassium dichromate administration did not result in immunologically detectable liganduria; however, GSH-S-transferase activity, which provides a more sensitive assay, was frequently detected. The findings are consistent with immunofluorescent localization of ligandin in the proximal tubule. Immunologic or enzymatic measurement of ligandin in urine may provide a sensitive index of acute injury to the proximal tubule.


Trypan blue injection into the capsular bag during phacoemulsification: initial postoperative posterior capsule opacification results.
To study the effect of injecting trypan blue 0.1% into the capsular bag on posterior capsule opacification (PCO) in eyes having phacoemulsification with foldable intraocular lens (IOL) implantation. Department of Ophthalmology, SMS Medical College & Hospital, Jaipur, India. Comparative case series. Eyes having phacoemulsification were randomized to have 0.2 mL of trypan blue 0.1% injected subcapsularly at 2 sites 180 degrees apart after cortical-cleaving hydrodissection (trypan blue group) or 0.2 mL of a balanced salt solution injected in a similar fashion (control group). Six- and 12-month postoperative PCO was analyzed by a masked examiner using public-domain open-source software (ImageJ) on digital retroillumination images. The PCO score Σ[% area × PCO grade (0 to 4)] was compared between the groups using the paired t test. The trypan blue group comprised 150 eyes and the control group, 150 eyes. The mean patient age was 62.79 years ± 8.89 (SD) and 63.69 ± 9.20 years, respectively. After applying exclusion criteria, the mean PCO scores at 6 months and 12 months were 0.10 and 0.15, respectively, in the trypan blue group (102 eyes) and 0.21 and 0.25, respectively, in the control group (103 eyes). The difference was statistically significant at 6 months (P=.042) and 12 months (P=.0227). Two eyes in the trypan blue group and 6 eyes in the control group required laser capsulotomy. Intraoperative injection of trypan blue 0.1% into the capsular bag reduced PCO after phacoemulsification with foldable hydrophilic acrylic IOL implantation.


Pediatric epilepsy surgery.
Whereas there is no specific neurosurgical technique in pediatric epilepsy, the frequency of each type of surgery is very different from epilepsy surgery applied in adults, and reflects the underlying etiologies, which are much more diverse in children, with malformations of cortical development and tumors as the prevailing etiologies. Extensive resective or disconnective procedures for extratemporal epilepsy are more frequently performed in infants and younger children, whereas temporo-mesial resection is by far the most common surgical treatment for adults with epilepsy. More recently, less invasive techniques in children with an extensive epileptogenic zone, such as multilobar disconnection, hemispherotomy and other functional hemispherectomy variants, have been introduced in order to reduce duration of surgery, perioperative morbidity and length of hospital stay. Likewise, minimally invasive techniques are utilized, such as the endoscopic disconnection of hypothalamic hamartomas for gelastic epilepsy. This development has been encouraged with the introduction of image-guided navigation systems for the preoperative planning and during surgery. Historically, epilepsy surgery for children has been established much later than for adults. Apart from the particular aspects in perioperative management of younger infants, surgery-related morbidity as well as seizure outcome is in general similar to those in adults, depending rather on each type of surgery.


Integrated generation of solid fuel and biogas from green cut material from landscape conservation and private households.
Green cut material is a potential source of renewable energy which is not fully exploited through conventional energy recovery systems. A new energy conversion process, the integrated generation of solid fuel and biogas from biomass (IFBB), which includes mechanical separation after hydro-thermal conditioning, was investigated. Ash softening temperature and lower heating value of the solid fuel were increased through the IFFB process in comparison to the untreated raw material. The net energy yield of IFBB at 40 °C conditioning temperature ranged between 1.96 and 2.85 kWh kg(-1) dry matter (DM) and for the direct combustion between 1.75 and 2.65 kWh kg(-1) DM. Conversion efficiencies for the IFBB system were 0.42-0.68 and for direct combustion 0.42-0.63. The IFBB system produces storable energy from material which is nowadays not used for energy conversion.


Cytochalasin E enhances the protein kinase C-dependent process of secretion.
Platelet dense body secretion, monitored as released serotonin, when induced by 20 nM tetradecanoylphorbol acetate was enhanced by 10 microM cytochalasin E even in the absence of external calcium ions and aggregation. Secretion induced by 500 nM A23187 in the presence of 15 microM indomethacin was not changed by cytochalasin but the synergy between A23187 and phorbol ester was enhanced. Therefore, protein kinase C-mediated secretion is not dependent on filipodal development, granule centralization, external calcium ion concentration or aggregation but is enhanced selectively by cytochalasin. Because the synergy between kinase C and A23187 is very rapid, the rate determining step in the slow secretion induced by phorbol ester alone appears to be the step accelerated by a rise in cytosolic Ca2+ concentration.


A family with autosomal dominant polycystic kidney disease not linked to chromosome 16p13.3.
A family of Sicilian origin with autosomal dominant polycystic kidney disease (APKD) has been shown to be unlinked to chromosome 16 markers. LOD scores for the polymorphic markers 3'HVR and SM7 flanking the PKD 1 locus, were -1.4 and -2.33 respectively, and theta max was 0.5 for each marker. The clinical phenotype of this family is consistent with that of the other non-linked families with APKD reported in the literature, all outside the United Kingdom, which have a milder progression than those linked to 16p13.3. Assuming that a clinic population represents the most severe forms of a disease and non PKD-1 is a less aggressive phenotype, the degree of genetic heterogeneity for APKD in the population may well be much greater than at present suggested.


Additive value of lung ultrasound to clinical parameters for prognosticating COVID-19.
The inclusion of LUS with simple, point-of-care clinical parameters have potential to improve COVID-19 prognostication above that from standard clinical care delivery. https://bit.ly/3InePYK.


Measurement of clavicular length and shortening after a midshaft clavicular fracture: Spatial digitization versus planar roentgen photogrammetry.
Clavicular shortening after fracture is deemed prognostic for clinical outcome and is therefore generally assessed on radiographs. It is used for clinical decision making regarding operative or non-operative treatment in the first 2weeks after trauma, although the reliability and accuracy of the measurements are unclear. This study aimed to assess the reliability of roentgen photogrammetry (2D) of clavicular length and shortening, and to compare these with 3D-spatial digitization measurements, obtained with an electromagnetic recording system (Flock of Birds). Thirty-two participants with a consolidated non-operatively treated two or multi-fragmented dislocated midshaft clavicular fracture were analysed. Two observers measured clavicular lengths and absolute and proportional clavicular shortening on radiographs taken before and after fracture consolidation. The clavicular lengths were also measured with spatial digitization. Inter-observer agreement on the radiographic measurements was assessed using the Intraclass Correlation Coefficient (ICC). Agreement between the radiographic and spatial digitization measurements was assessed using a Bland-Altman plot. The inter-observer agreement on clavicular length, and absolute and proportional shortening on trauma radiographs was almost perfect (ICC>0.90), but moderate for absolute shortening after consolidation (ICC=0.45). The Bland-Altman plot compared measurements of length on AP panorama radiographs with spatial digitization and showed that planar roentgen photogrammetry resulted in up to 37mm longer and 34mm shorter measurements than spatial digitization. Measurements of clavicular length on radiographs are highly reliable between observers, but may not reflect the actual length and shortening of the clavicle when compared to length measurements with spatial digitization. We recommend to use proportional shortening when measuring clavicular length or shortening on radiographs for clinical decision making.


Mycobacterium paratuberculosis and autism: is this a trigger?
Autism is a heterogeneous group of life-long neurologic problems that begin in childhood. Success in efforts to understand and treat autism has been mostly elusive. The role of autoimmunity in autism has gained recognition both for associated systemic autoimmune disease and the presence of brain autoantibodies in autistic children and their family members. There is an acknowledged genetic susceptibility to autism--most notably allotypes of complement C4. C4 defects are associated with several autoimmune diseases and also confer susceptibility to mycobacterial infections. Mycobacterium avium ss. paratuberculosis (MAP) causes an enteric inflammatory disease in ruminant animals (Johne's disease) and is the putative cause of the very similar Crohn's disease in humans. Humans are widely exposed to MAP in food and water. MAP has been also linked to ulcerative colitis, irritable bowel syndrome, sarcoidosis, Blau syndrome, autoimmune (Type 1) diabetes, Hashimoto's thyroiditis and multiple sclerosis. Environmental agents are thought to trigger autism in the genetically at risk. Molecular mimicry is the proposed mechanism by which MAP is thought to trigger autoantibodies. Autoantibodies to brain myelin basic protein (MBP) is a common feature of autism. This article considers the subset of autoimmunity-related autism patients and postulates that MAP, through molecular mimicry to its heat shock protein HSP65, triggers autism by stimulating antibodies that cross react with myelin basic protein (MBP).


[Differentialdiagnostic problems in fibrosarcoma of the foot (author's transl)].
3 cases of fibrosarcoma of the foot are presented. Despite a history of pain up to several years the first radiological examination did not reveal any signs of a malignant tumor. X-rays taken 1/2 to one year later showed a localized osteolytic process. Then the diagnosis was established by biopsy. Consecutive x-rays and timing for a biopsy are discussed.


One-pot solvothermal synthesis of graphene-supported TiO2 (B) nanosheets with enhanced lithium storage properties.
A facile process was developed for the synthesis of graphene-supported TiO2 (B) nanosheets (GTBN) composite based on the hydrothermal treatment titanium (III) chloride and graphene oxide in an ethylene glycol. The morphology and microstructure of the composites were examined by X-ray diffraction, X-ray photoelectron spectroscopy, transmission electron microscopy, and Raman spectroscopy. The obtained GTBN show a high thermal stability and the phase transformation of TiO2 (B) to anatase can be prevented by graphene after pyrolysis of GTBN at 350°C for 2h. Furthermore, GTBN exhibited high rate performance and stability of lithium ion batteries, due to the enhanced conductivity of the electrode and accommodation to volume/strain changes during lithium insertion-extraction.


Late left ventricular color M-mode Doppler in the assessment of diastolic dysfunction in patients with dilated cardiomyopathy.
The ratio of early (Ep) to late (Ap) color M-mode Doppler flow propagation through the left ventricle helps in the differentiation between normal and pseudonormal (PSN) filling pattern in patients with preserved systolic function. We studied the value of this index in the assessment of diastolic dysfunction for patients with reduced left ventricular systolic function. We studied 80 patients with nonischemic dilated cardiomyopathy and 50 control subjects. According to echocardiography 53 patients had abnormal relaxation and 27 had PSN pattern. Patients had reduced Ep (P < .001) and Ep/Ap ratio (P < .001) and increased Ap (P = .001) compared to controls. Binary logistic regression analysis showed that Ep followed by Ep/Ap ratio (both P < .001) were the best determinants for the discrimination of PSN from normal filling pattern. Ep/Ap ratio, this novel echo-index, increases the diagnostic accuracy of color M-mode Doppler in discriminating normal from PSN filling pattern in patients with left ventricular systolic dysfunction.


S-100 protein-immunoreactive cells in the bovine ovary.
The present study deals with an immunohistochemical localization of S-100 protein in the bovine ovary. Immunoreactivity for S-100 was observed in various types of cells, as well as in cells of the nervous system. The endothelial cells of arterial vessels, blood capillaries, and lymph vessels; the epithelial cells of ovarian cysts; and the oocytes of normal and atretic follicles showed an S-100 protein positivity. The immunoreactivity also was found in the epithelial cells of the rete ovarii. No cells other than these showed immunoreactivity to the anti-S-100 serum. S-100 protein can be a useful marker for providing information on ovarian function.


New Therapeutic Strategies Are Associated With a Significant Decrease in Colectomy Rate in Pediatric Ulcerative Colitis.
We evaluated the impact of immunosuppressants (IS) and antitumor necrosis factor (TNF) introduction on long-term outcomes of ulcerative colitis (UC) in a large population-based pediatric-onset cohort. All patients included in the EPIMAD registry with a diagnosis of UC made before the age of 17 years between 1988 and 2011 were followed up retrospectively until 2013. Medication exposure and disease outcomes were compared between 3 diagnostic periods: 1988 to 1993 (period [P] 1; pre-IS era), 1994 to 2000 (P2; pre-anti-TNF era), and 2001 to 2011 (P3; anti-TNF era). A total of 337 patients (female, 57%) diagnosed with UC were followed up during a median duration of 7.2 years (interquartile range 3.8-13.0). The IS and anti-TNF exposure rates at 5 years increased over time from 7.8% (P1) to 63.8% (P3) and from 0% (P1) to 37.2% (P3), respectively. In parallel, the risk of colectomy at 5 years decreased significantly over time (P1, 17%; P2, 19%; and P3, 9%; P = 0.045, P -trend = 0.027) and between the pre-anti-TNF era (P1 + P2, 18%) and the anti-TNF era (P3, 9%) ( P = 0.013). The risk of disease extension at 5 years remained stable over time (P1, 36%, P2, 32%, and P3, 34%; P = 0.31, P -trend = 0.52) and between the pre-anti-TNF era (P1 + P2, 34%) and the anti-TNF era (P3, 34%) ( P = 0.92). The risk of flare-related hospitalization at 5 years significantly increased over time (P1, 16%; P2, 27%; P3, 42%; P = 0.0012, P -trend = 0.0006) and between the pre-anti-TNF era (P1 + P2, 23%) and the anti-TNF era (P3, 42%) ( P = 0.0004). In parallel with the increased use of IS and anti-TNF, an important decline in the risk of colectomy in pediatric-onset UC was observed at the population level.


Association between non-invasive liver fibrosis scores and occurrence of health adverse outcomes in older people.
The relation between liver fibrosis scores and health outcomes in older people has been barely investigated. We aimed to evaluate the association of four liver fibrosis scores (fibrosis-4 -FIB-4-, NAFLD fibrosis score -NFS-, BARD and aspartate aminotransferase/alanine aminotransferase ratio -AST/ALT-) with mortality and incident disability at 6 years in an older population. We studied 962 individuals aged ≥65 (mean age 74.4; female 55.5%) with a mean follow-up of 95.7 months, enrolled in the InCHIANTI study. The relationship between liver fibrosis scores and mortality and disability was assessed through Cox and log-binomial regressions. NFS and FIB-4 were associated with higher overall (aHR ranging 1.38-1.78 for intermediate risk of fibrosis and 1.60-2.02 for high risk) and cardiovascular (aHR ranging 1.76-2.90 for intermediate and 2.22-2.42 for high risk) mortality. AST/ALT and BARD were only associated with overall mortality. Only NFS and FIB-4 high risk classes were associated with incident disability (aRR ranging 1.93-2.76). Despite poor sensitivity, all scores showed high specificity (ranging 0.88-0.95). Higher risk of liver fibrosis is associated with higher risk of poor health outcomes. Liver fibrosis scores may help to stratify the risk and, mainly, identify elderly patients with favorable prognosis.


Insights into glucocorticoid responses derived from omics studies.
Glucocorticoid drugs are commonly used in the treatment of several conditions, including autoimmune diseases, asthma and cancer. Despite their widespread use and knowledge of biological pathways via which they act, much remains to be learned about the cell type-specific mechanisms of glucocorticoid action and the reasons why patients respond differently to them. In recent years, human and in vitro studies have addressed these questions with genomics, transcriptomics and other omics approaches. Here, we summarize key insights derived from omics studies of glucocorticoid response, and we identify existing knowledge gaps related to mechanisms of glucocorticoid action that future studies can address.


Methyl 2-naphthoates with anti-inflammatory activity from Morinda officinalis.
Chemical fractionation of the EtOH extract of the roots of a traditional Chinese herb, Morinda officinalis, afforded an array of methyl 2-naphthoate derivatives (1-9) including four pairs of enantiomers (1-4), two pimarane diterpenes and two ursane triterpenoids. Among them, eight compounds (1a/1b-3a/3b, 11 and 13) were reported in the current work for the first time. The structures of the new compounds, including their absolute configurations, were defined by spectroscopic analyses in combination with quantum chemical electronic circular dichroism (ECD) and gauge-independent atomic orbital (GIAO) NMR calculations. All the isolates were evaluated for their inhibitory effect on nitric oxide (NO) production induced by lipopolysaccharide (LPS) in murine RAW264.7 macrophage cells, and the enantiomers 1a and 3b exhibited moderate activity with IC50 values of 41.9 and 26.2 μM. Meanwhile, compound 3b also dose-dependently inhibited the secretion of two pro-inflammatory cytokines TNF-α and IL-6 in the same cell model.


Infection by human polyomaviruses JCPyV and BKPyV in blood donors of Argentina.
A spectrum of blood-borne infectious agents may be transmitted through transfusion of blood components from asymptomatic donors. Despite the persistence of polyomaviruses in blood cells, no studies have been conducted in Argentina to assess the risk of transfusion infection. We investigated BKPyV and JCPyV in 720 blood donors, using polymerase chain reaction (PCR) for a region of T antigen common to both viruses. Positive T-antigen samples were subjected to two additional PCR assays targeting the VP1 region. Viral genotypes were characterized by phylogenetic analysis. Polyomaviruses were detected in 1.25% (9/720) of the blood samples selected; JCPyV was identified in 0.97% (7/720) and BKPyV in 0.28% (2/720) of them. Phylogenetic analysis showed that the JCPyV sequences clustered with 2A genotype and Ia of BKPyV. This study describes for the first time the prevalence of polyomavirus DNA in blood donors of Córdoba, Argentina. The polyomavirus DNAemia in healthy populations suggests that those viruses are present in blood components eligible for transfusion. Therefore, the epidemiological surveillance of polyomavirus in blood banks might be incorporated into haemovigilance programmes, to determine the infectious risk and implement newer interventions to ensure the safety of blood supplies, if required.


Type 2 diabetes in young adults in Central Auckland: demography and complications.
Type 2 diabetes (T2D) in young adults is associated with a high risk of diabetes complications. To investigated the demography and the emergence of complications of young adults with T2D in the central Auckland region where there has been substantial immigration. In total, 310 young adults with T2D (<40 years) were registered with the Auckland Diabetes Centre in 2015. We documented demographic, anthropometric and metabolic variables and prevalence and the emergence of complications. Three demographic groups accounted for 243 participants (78%): 135 (44%) were migrants of Asian or Pacific Island origin, diagnosed a median 9 years after migration at a mean age of 28 ± 6 years; 88 (29%) were New Zealand-born Pāsifika descent, with a high prevalence of morbid obesity and 37 (12%) had major mental illness or intellectual disability. At diagnosis, the median HbA1c was 80 mmol/mol, and in 28%, it was ≥100 mmol/mol. A median 6 years after diagnosis, 56% had some degree of retinopathy, with the prevalence related both to the duration of diabetes and glycaemic control (P = 0.001). Forty-four percent of subjects had abnormal albuminuria at diagnosis (12% with macroalbuminuria). Increased albuminuria was strongly associated with obesity (P = 0.002). The development of CKD stages 4-5 was related both to the severity of retinopathy and degree of albuminuria at diagnosis (P = 0.0001). Major cardiovascular events were related to the severity of retinopathy at diagnosis (P = 0.0001). New migrants, New Zealand-born Pāsifika and patients with mental illness or an intellectual disability comprise the bulk of young onset T2D. The disease is aggressive, and by the age of 40, patients are already developing advanced complications.


Actin polymerization: riding the wave.
WAVE/SCAR has long been known to activate the actin-nucleating Arp2/3 complex in a Rac-dependent manner. Recent biochemical and genetic studies have revealed important roles for four WAVE-associated proteins in regulating WAVE function.


A flow rate monitor for a variety of physiological preparations, including in vitro brain slices.
A flow rate monitor system for constant perfusion of media for maintaining physiological preparations, particularly in vitro brain slices, is described. The system consists of 3 components: the counter with a drip rate meter and alarm; a drop sensor; and a remote DC power supply. It provides accurate and immediate readout of flow rate in drops per minute and it provides an audio warning if the drip rate falls below a level set by the investigator.


Assessing predictors for new post translational modification sites: A case study on hydroxylation.
Post-translational modification (PTM) sites have become popular for predictor development. However, with the exception of phosphorylation and a handful of other examples, PTMs suffer from a limited number of available training examples and sparsity in protein sequences. Here, proline hydroxylation is taken as an example to compare different methods and evaluate their performance on new experimentally determined sites. As a guide for effective experimental design, predictors require both high specificity and sensitivity. However, the self-reported performance may often not be indicative of prediction quality and detection of new sites is not guaranteed. We have benchmarked seven published hydroxylation site predictors on two newly constructed independent datasets. The self-reported performance is found to widely overestimate the real accuracy measured on independent datasets. No predictor performs better than random on new examples, indicating the refined models do not sufficiently generalize to detect new sites. The number of false positives is high and precision low, in particular for non-collagen proteins whose motifs are not conserved. As hydroxylation site predictors do not generalize for new data, caution is advised when using PTM predictors in the absence of independent evaluations, in particular for highly specific sites involved in signalling.


Intercoronary collateral flow detected by Doppler colour flow mapping is an additional diagnostic sign in children with anomalous origin of the left coronary artery from the pulmonary artery.
Intercoronary collateral flow within septal collaterals was detected by colour-coded Doppler echocardiography in three children with anomalous origin of the left coronary artery from the pulmonary artery. In each of the three patients angiography confirmed the presence of septal collaterals.


3-D Image-guided diffuse optical tomography using boundary element method and MPI implementation.
Boundary elements provide an attractive method for image-guided multi-modality near infrared spectroscopy in three dimensions using only surface discretization. This method operates under the assumption that the underlying tissue contains piece-wise constant domains whose boundaries are known a priori from an alternative imaging modality such as MRI or microCT. This significantly simplifies the meshing process providing both speed-up and accuracy in the forward solution. Challenges with this method are in solving dense matrices, and working with complex heterogeneous domains. Solutions to these problems are presented here, with applications in breast cancer imaging and small - animal molecular imaging.


Influence of C/N ratios on treatment performance and biomass production during co-culture of microalgae and activated sludge.
Novel phycosphere associated bacteria processes are being regarded as a potential and cost-effective strategy for controlling anthropogenic contaminants in wastewater treatment. However, the underlying concern with the process is its vulnerability to improper organic or nutrient intake. This study established a synergistic interaction between microalgae and activated sludge in a three-photobioreactor system (without external aeration) to understand how pollutants could be mitigated whilst simultaneously yielding biomass under different C/N ratios of 1:1, 5:1 and 10:1. The result showed that the superior biomass productivity was facilitated at a C/N ratio of 5:1 (106 mg L-1 d-1), and the high degradation rate constants (kCOD = 0.25 d-1, kTN = 0.29 d-1, kTP = 0.35 d-1) was approximated using a first-order kinetic model. The removal of pollutants was remarkably high, exceeding 90% (COD), 93% (TN), and 96% (TP). Nevertheless, the C/N ratio of 1:1 resulted in a threefold drop in biomass-specific growth rate (μ = 0.07 d-1). Microalgal assimilation, followed by bacterial denitrification, is the major pathway of removing total nitrogen when the C/N ratio exceeds 5:1. Activated sludge plays an important role in improving microalgae tolerance to high concentration of ammonia nitrogen and boosting nitrification (light phase) and denitrification (dark phase). The use of phycosphere associated bacteria could be a promising strategy for controlling nutrients pollution and other environmental considerations in wastewater.


Comparison of costs of different anaesthetic techniques.
The costs of anaesthetic drugs, intravenous agents as well as gases, were studied for different anaesthetic techniques in a medium-sized operative procedure, cholecystectomy. Three anaesthetic breathing systems were used: a non-rebreathing system, a circle absorber system with medium fresh gas flows of 3-6 l/min, and a low-flow circle system. Anaesthesia without volatile inhalation agents used with a low-flow technique was the least expensive, and anaesthesia with isoflurane in a non-rebreathing system was the most expensive. The costs of anaesthesia without volatile inhalation agents in a non-rebreathing system, enflurane anaesthesia in a circle system with medium fresh gas flows, and isoflurane anaesthesia with low-flow technique were similar.


Benefits of Mediterranean and Japanese diets among Nurses: a Scoping literature review.
The present study aimed at all the benefits induced by taking the Mediterranean or Japanese diet among nurses and whether any beneficial differences in intakes between the two diets were considered. The author searched PubMed and Embase databases for medical subheadings terms and free full text referring to "Diet," "Mediterranean," "Japanese," and "Nurses" before 31st December 2022. A total of 14 studies were included in this scoping review, which better underlined all the benefits implicated in the Mediterranean or Japanese diets assumption and also if there were any differences between the two diets. These eating behaviors were exclusively investigated among nurses. The nursing profession has always been considered the most stressful healthcare activity. However, some important concerns in the regular lifestyle, such as eating and physical activity, might help to live better.


Saccharomyces uvarum isolated from patagonian ciders shows excellent fermentative performance for low temperature cidermaking.
Saccharomyces uvarum has been recovered from natural habitats and traditionally fermented beverages (apple chicha) in Patagonia. However, this species has never been obtained from industrially relevant beverages like wine or cider in the same region. In this work, different strains belonging to the cryotolerant species S. uvarum were recovered from spontaneous cider fermentations carried out at low temperature in Red Delicious apple must. The strain S. uvarum NPCC1420 obtained from this cider and selected for its physiological and technological features, evidenced a better adaptation to the cidermaking process than a previously selected strain obtained from a less industrialized product called apple chicha. Some differences, like a higher ethanol and sulphite tolerance, seemed to be associated with differential domestication pressures suffered by each different strain. Moreover, the most important fermentative features of the strain NPCC1420 were a higher competition capacity than the strain NPCC1314 in non-sterile apple must, as well as significantly higher amounts of glycerol, 2-phenylethanol and 2-phenylethyl acetate than the strain isolated from apple chicha.


Chilly climate perceived by female engineering undergraduates: an exploratory study using concept mapping.
Women still being a minority in engineering majors, they are reported to face discriminatory treatment in a collegiate environment. "Chilly climate," referring to such a sexist environment, may have a negative impact on women's mental health, academics, and careers. But, what exactly is it that female students in engineering perceive as chilly, and how chilly is it? This study aimed to explore the chilly campus climate perceived by female undergraduate engineering students in South Korea using the concept mapping method. Semi-structured interviews were conducted with 13 participants enrolled for more than four semesters at four-year coeducational universities. After extracting 52 representative statements, the participants were asked to classify them according to content similarity and rate the influence of each statement on their perception of the chilly climate. For concept mapping analysis, multidimensional scaling analysis (ALSCAL), hierarchical cluster analysis (Ward's method), and non-hierarchical cluster analysis (K-means method) were performed. Fifty-two statements were extracted under the following four clusters: (i) "Exclusion and alienation inherent in the culture (Cluster 1)," (ii) "Sexual objectification and lack of gender sensitivity (Cluster 2)," (iii) "Male-centered academic situations (Cluster 3)," and (iv) "Prejudice and generalization (Cluster 4)." A concept map was two-dimensional: an X-axis named "context dimension," with "task: academic" and "non-task: social" at both ends, and a Y-axis named "sexism dimension", having "explicit" and "implicit" at both ends. The order of higher scores in the influence rating is as follows: Cluster 2, Cluster 3, Cluster 1, and Cluster 4. This study is significant because it conceptualizes the subjective experience of minorities in a collegiate environment and provides influence rating results for prioritized measures. The findings will be helpful in formulating educational policies, psychological counseling, and social advocacy activities. Future research should target larger populations, and cover more diverse cultures, majors, and age groups.


[New perspectives in the approach to central retinal vein occlusion].
The COPERNICUS and GALILEO trials were designed to evaluate the safety and efficacy of intravitreal injection of 2mg of aflibercept in the treatment of macular edema secondary to central retinal vein occlusion. Two phase III randomized, double-masked trials: COPERNICUS in North America (188 patients) and galileo in Europe and Asia (177 patients). In COPERNICUS, the patients in the treatment group received monthly injections of 2mg aflibercept for 6 months and later continued with strict PRN treatment with monthly follow-up every 6 months and with a minimum of 3-monthly follow up for 1 year. Patients in the placebo group could receive treatment after the sixth month, with similar treatment regimens and follow-up to the treatment group. In contrast, in galileo, the placebo group received no PRN treatment until 1 year of follow-up and during the first 6 months, followup visits were bi-monthly. The treatment group in COPERNICUS showed a mean improvement of 13 letters versus the placebo group (1.5 letters) at week 100 of follow-up. In galileo, the mean best corrected visual acuity at 76 weeks were 13.7 and 6.6 in the treatment and placebo groups, respectively. Early treatment with intravitreal afliberceptin achieves better results than when treatment is delayed by 6 months or 1 year. The visual benefits obtained with the drug are affected by the reduction in the frequency of monitoring during follow-up.


Regulation of the thermal sensitivity of hydroxypropyl cellulose by poly(N-isopropylacryamide) side chains.
Hydroxyproyl cellulose graft poly(N-isopropylacryamide) (HPC-g-PNIPAm) copolymers were synthesized by single-electron transfer living radical polymerization (SET-LRP) in water and THF mixture solvent and characterized. The controllability and polymerization rate of SET-LRP can be adjusted by the water/THF ratio in the mixture solvent. The monomer conversion rate is relatively low in the solvent with low water content. The thermal responsive property of HPC-g-PNIPAm copolymers in aqueous solution depends on the length of the graft chains. The relatively short PNIPAm side chains (<150 repeat units) can effectively regulate the low critical solution temperature (LCST) of the HPC-g-PNIPAm copolymers in aqueous solution due to the hydrophilic properties of the short PNIPAm chains. This work provides an approach for the regulation of the LCST to body temperature region by graft copolymerization.


Identifying the psychosocial predictors of ultraviolet exposure to the face in patients with xeroderma pigmentosum: a study of the behavioural factors affecting clinical outcomes in this genetic disease.
For patients with xeroderma pigmentosum (XP), the main means of preventing skin and eye cancers is extreme protection against ultraviolet radiation (UVR), particularly for the face. We have recently developed a methodology for objectively measuring photoprotection behaviour ('UVR dose to facial skin') and have found that the degree of photoprotection varies greatly between patients with XP. We have previously identified factors affecting photoprotection behaviour in XP using a subjective measure of photoprotection. Here, we have used this objective methodology to identify the factors which determine photoprotection behaviour in XP. We studied 29 psychological, social, demographic and clinical variables in 36 patients with XP. We have previously objectively measured UVR protection (by measuring the dose of UVR reaching the skin of the face over a 3-week period) in these patients. Here, we use linear mixed-effects model analysis to identify the factors which lead to the differences in degree of photoprotection observed in these patients. Psychosocial factors accounted for as much of the interindividual variation in photoprotection behaviour (29%) as demographic and clinical factors (24%). Psychosocial factors significantly associated with worse UVR protection included: automaticity of the behaviours, and a group of beliefs and perceptions about XP and photoprotection known to associate with poor treatment adherence in other diseases. We have identified factors contributing to poor photoprotection in XP. Identifying these potentially reversible psychosocial features has enabled us to design an intervention to improve photoprotection in patients with XP, aiming to prevent skin and eye cancers in these patients.


QT dispersion and viable myocardium in patients with prior myocardial infarction and severe left ventricular dysfunction.
QT dispersion (QTd) has been found to correlate to the amount of viable myocardium in patients with Q-wave myocardial infarction and well-preserved LV function. However, this relationship is unknown in patients with severe left ventricular dysfunction. Thirty-four patients with prior large myocardial infarction and severe left ventricular dysfunction underwent Tc-99m sestamibi single photon emission cardiac tomography (SPECT) and F-18 fluorodeoxyglucose (FDG) SPECT. Viability was defined as a defect relative count density (DCD) of at least 20% greater on FDG SPECT. QTd, corrected QT dispersion (QTcd), and QT coefficient of variation (cv) in patients with viable myocardium was compared to those without viable myocardium in the infarct area. Thirteen patients were excluded from analysis for poor FDG images or inadequate ECG tracings. Of the remaining patients, 10 (48%) were found to have viability on FDG SPECT. QTd, QTcd, and QTcv in patients with viability were: 58 +/- 22 ms, 61 +/- 23 ms, and 4.81 +/- 1.76%, respectively, which did not differ significantly from those in patients without viability (QTd = 56 +/- 14 ms, QTcd = 70 +/- 16 ms and Qtcv = 5.06 +/- 1.20% [P = NS]). Moreover, neither FDG defect size, nor LVEF correlated with QTd. This study indicates no relationship between QTd and viability in patients with myocardial infarction and severe left ventricular dysfunction.


Outpatient management of vascular access devices in children receiving radiotherapy: complications and morbidity.
When treating children with cancer, long-term venous access is critical. This is especially true in the context of children receiving daily radiation therapy (RT) under general anesthesia. We have previously reported <0.1% risk of complications in complications in over 4,040 pediatric treatments under general anesthesia in our outpatient facility. Here, we present our experience with venous catheter access techniques in children receiving daily proton RT. After Institutional Review Board approval, we reviewed our center's records between September 9, 2004 and October 23, 2012 with respect to complications and morbidity of indwelling catheters in our pediatric patients. Vascular access device (VAD) types included: 110 patients with indwelling port-a-cath (PAC), 34 PICC line devices, and 34 central venous catheter (CVC) devices in 170 patients. Median catheter life during RT was 43 days (range 1-86 days) with a total of 7,169 total catheter days while patients received RT. A 14% PAC complication rate included negative blood return (6.3%) and infection (3.6%). Complication rates for PICC and CVC access devices were 38% and 20.5%, respectively (χ(2) P = 0.007 when compared with PAC). Most frequent complications for PICC lines were no blood return (11.7%), and infection or occlusion (8.8% each). CVC complications were breakage (8.8%) and infection (8.8%). Access device replacement rates were 3.6% (PAC), 14.7% (PICC), and 8.8% (CVC). In the outpatient delivery of RT to children, indwelling ports provide greater convenience, less likelihood of infection or complication, and greater durability than PICC or CVC devices.


Prediction of the clinical and naming status after anterior temporal lobe resection in patients with epilepsy.
By assessing the cognitive capital, neuropsychological evaluation (NPE) plays a vital role in the perioperative workup of patients with refractory focal epilepsy. In this retrospective study, we used cutting-edge statistical approaches to examine a group of 47 patients with refractory temporal lobe epilepsy (TLE), who underwent standard anterior temporal lobectomy (ATL). Our objective was to determine whether NPE may represent a robust predictor of the postoperative status, two years after surgery. Specifically, based on pre- and postsurgical neuropsychological data, we estimated the sensitivity of cognitive indicators to predict and to disentangle phenotypes associated with more or less favorable outcomes. Engel (ENG) scores were used to assess clinical outcome, and picture naming (NAM) performance to estimate naming status. Two methods were applied: (a) machine learning (ML) to explore cognitive sensitivity to postoperative outcomes; and (b) graph theory (GT) to assess network properties reflecting favorable vs. less favorable phenotypes after surgery. Specific neuropsychological indices assessing language, memory, and executive functions can globally predict outcomes. Interestingly, preoperative cognitive networks associated with poor postsurgical outcome already exhibit an atypical, highly modular and less densely interconnected configuration. We provide statistical and clinical tools to anticipate the condition after surgery and achieve a more personalized clinical management. Our results also shed light on possible mechanisms put in place for cognitive adaptation after acute injury of central nervous system in relation with surgery.


[Influence of massive blood transfusion and traumatic brain injury on TIMP‑1 and MMP‑9 serum levels in polytraumatized patients].
The morbidity and mortality of polytrauma patients are substantially influenced by the extent of the posttraumatic inflammatory reaction. Studies have shown that TIMP‑1 and MMP‑9 play a major role in posttraumatic immune disorder in genome-wide mRNA microarray analyses. Furthermore, both showed differential gene expression profiles depending on the clinical parameters massive blood transfusion and traumatic brain injury. The aim of this study was to evaluate TIMP‑1 and MMP‑9 serum concentrations in polytraumatized patients depending on the clinical parameters massive blood transfusion and traumatic brain injury in the early posttraumatic phase. Polytrauma patients (≥18 years) with an "Injury Severity Score" (ISS) ≥ 16 points were enrolled in this prospective study. Serum levels of TIMP‑1 and MMP‑9 were quantified (at 0 h, 6 h, 12 h, 24 h, 48 h and 72 h) using an enzyme-linked immunosorbent assay (ELISA). Groups were divided according to the clinical parameter massive blood transfusion (≥10 red blood cell units [RBC units] in the first 24-hour posttrauma) and traumatic brain injury (CCT postive [cranial computed tomography]). Following massive blood transfusion (n = 21; 50 ± 15.7 years; ISS 39 ± 12.8 points) patients showed overall significantly increased TIMP‑1 levels (p = 0.003) and significantly higher TIMP‑1 values after 12-72 h. Traumatic brain injury patients (n = 28; 44 ± 19 years; ISS 42 ± 10 points) showed significantly higher MMP‑9 levels (p = 0.049) in the posttraumatic period. Polytraumatized patients who received massive blood transfusions following major trauma showed significantly higher TIMP‑1 levels than patients who did not receive massive transfusions. This seems to be an expression of a massively excessive inflammatory reaction and therefore represents a substantial factor in the pathogenesis of severe posttraumatic immune dysfunction in this collective. Furthermore, the significant increase in MMP‑9 with accompanying traumatic brain injury reflects the pivotal role of matrix metalloproteinases in the pathophysiology of traumatic brain injury.


Urinary bladder mucosal responses to ischemia.
The objectives of this study were to examine the expression of various cellular proteins within the urothelium (UT) and lamina propria (LP) following chronic bladder ischemia in the rat urinary bladder. Urinary bladders were removed from adult Sprague-Dawley rats 8 weeks after creation of bladder ischemia and from sham controls. Immunocytochemistry was used to examine distribution of LP-vimentin-immunoreactive (IR) cells and connexins (Cx26; Cx43), and western immunoblotting or ELISA for proteins involved in UT barrier and sensory functions. Ischemia was associated with a significant increase in LP-vimentin-IR cells and increased expression of the gap junction proteins Cx26 and Cx43 within the bladder UT as compared to sham control. Ischemia also resulted in an increased (p < 0.05) expression level of the junctional marker (ZO-1) and non-significantly increased expressions of the trophic factor nerve growth factor as well as norepinephrine. Our findings reveal that chronic ischemia alters a number of proteins within the UT and underlying LP. These proteins are involved in barrier function, remodeling, repair as well as intercellular communication. The increased expression of LP-vimentin-IR cells suggests that changes in cell-cell interactions could play a role in ischemia-induced changes in bladder activity.


Xenopus research: metamorphosed by genetics and genomics.
Research using Xenopus takes advantage of large, abundant eggs and readily manipulated embryos in addition to conserved cellular, developmental and genomic organization with mammals. Research on Xenopus has defined key principles of gene regulation and signal transduction, embryonic induction, morphogenesis and patterning as well as cell cycle regulation. Genomic and genetic advances in this system, including the development of Xenopus tropicalis as a genetically tractable complement to the widely used Xenopus laevis, capitalize on the classical strengths and wealth of achievements. These attributes provide the tools to tackle the complex biological problems of the new century, including cellular reprogramming, organogenesis, regeneration, gene regulatory networks and protein interactions controlling growth and development, all of which provide insights into a multitude of human diseases and their potential treatments.


'Barn allergy': asthma and rhinitis due to storage mites.
The differential diagnosis of asthma in farm workers is between a type I hypersensitivity to a pollen or dust allergen and a type III hypersensitivity to mould antigens. We describe asthma and rhinitis, and not farmer's lung, in a farming population due to the non-pyroglyphid grain storage mite. Before a diagnosis of farmers' lung due to mouldy hay is made in any patient whether or not precipitins to Micropolyspora faeni are present, skin tests for storage mite should be made. If these are positive a diagnosis of 'barn allergy' should be considered and a trial of sodium cromoglycate be given.


Polar Ejection Forces Promote the Conversion from Lateral to End-on Kinetochore-Microtubule Attachments on Mono-oriented Chromosomes.
Chromosome bi-orientation occurs after conversion of initial lateral attachments between kinetochores and spindle microtubules into stable end-on attachments near the cell equator. After bi-orientation, chromosomes experience tension from spindle forces, which plays a key role in the stabilization of correct kinetochore-microtubule attachments. However, how end-on kinetochore-microtubule attachments are first stabilized in the absence of tension remains a key unanswered question. To address this, we generated Drosophila S2 cells undergoing mitosis with unreplicated genomes (SMUGs). SMUGs retained single condensed chromatids that attached laterally to spindle microtubules. Over time, laterally attached kinetochores converted into end-on attachments and experienced intra-kinetochore stretch/structural deformation, and SMUGs eventually exited a delayed mitosis with mono-oriented chromosomes after satisfying the spindle-assembly checkpoint (SAC). Polar ejection forces (PEFs) generated by Chromokinesins promoted the conversion from lateral to end-on kinetochore-microtubule attachments that satisfied the SAC in SMUGs. Thus, PEFs convert lateral to stable end-on kinetochore-microtubule attachments, independently of chromosome bi-orientation.


Alanine racemase from the acidophile Acetobacter aceti.
Acetobacter aceti converts ethanol to acetic acid, and survives acetic acid exposure by tolerating cytoplasmic acidification. Alanine racemase (Alr) is a pyridoxal 5' phosphate (PLP) -dependent enzyme that catalyzes the interconversion of the d- and l-isomers of alanine and has a basic pH optimum. Since d-alanine is essential for peptidoglycan biosynthesis, Alr must somehow function in the acidic cytoplasm of A. aceti. We report the partial purification of native A. aceti Alr (AaAlr) and evidence that it is a rather stable enzyme. The C-terminus of AaAlr has a strong resemblance to the ssrA-encoded protein degradation signal, which thwarted initial protein expression experiments. High-activity AaAlr forms lacking a protease recognition sequence were expressed in Escherichia coli and purified. Biophysical and enzymological experiments confirm that AaAlr is intrinsically acid-resistant, yet has the catalytic properties of an ordinary Alr.


Optimized Training in the Use of Endoscopic Closure Devices.
Successful closure of gastrointestinal defects is one of the most important goals for therapeutic endoscopy. Historically, surgical repair was the mainstay of treatment for any gastrointestinal defect; however, surgery is associated with high morbidity and mortality. Endoscopic management of gastrointestinal defects has developed rapidly in recent years and has become more effective, reducing the morbidity and mortality rates, and avoiding surgical interventions. Appropriate use of endoscopic techniques requires extensive knowledge of the devices and their advantages and limitations during practical applications.


Influence of fellowship educational experience on practice patterns for adrenalectomy: A survey of recent AAES fellowship graduates.
Current practice patterns for adrenalectomy among endocrine surgeons is a limited area of study. Here we survey relatively junior endocrine surgeons regarding educational experiences in adrenalectomy and correlate these with current practice. An electronic survey was sent to recent AAES-accredited fellowships graduates (2014-2019), querying adrenalectomy volume and approaches during fellowship and current practice patterns. Most graduates (63.2%) performed >20 adrenalectomies in fellowship. Exposure was greatest to open (94.1%) and laparoscopic transabdominal (92.6%) adrenalectomy, followed by retroperitoneoscopic (86.7%). The majority (73.5%) of respondents stated their current practice patterns are the same as their exposure during training. Preoperative diagnosis, side of lesion, and patient comorbidities were all ranked as significant predictors affecting choice of approach (p < 0.001). The large majority of AAES fellowship graduates receive high-volume adrenalectomy experience in several approaches. The technique to which a trainee was exposed to most frequently was the greatest predictor for preferential approach in current practice.


Impact of Gastroesophageal Reflux Disease on Mucosal Immunity and Atopic Disorders.
Atopic disorders and gastroesophageal reflux disease (GERD) are some of the most common medical conditions treated by primary care physicians and specialists alike. The observation that atopic disorders, like asthma, allergic rhinitis and sinusitis, food allergies, atopic dermatitis, contact dermatitis, and eosinophilic esophagitis are common comorbidities in patients with GERD raises the question of the nature of the relationship that may exist between GERD and atopic disorders. In this article, we review the pathophysiology of GERD, its effect on the immune system, the effect of acid-blocking medications on allergic responses, as well as several common atopic conditions that have been associated with GERD including asthma, chronic rhinosinusitis (CRS), allergic rhinitis (AR), atopic dermatitis (AD), contact dermatitis (CD), food allergies, proton pump inhibitor (PPI)-responsive esophageal eosinophilia (PPI-REE), and eosinophilic esophagitis (EoE). In each condition, the evidence of a causal link is not definitive. Although the relationship between asthma and GERD remains controversial, evidence suggests that a subset of asthma patients with documented GERD may experience improved asthma control following appropriate treatment of GERD. The relationship of GERD to allergic rhinitis and chronic sinusitis is weak; however, studies support the concept that treatment of frequent episodes of GERD can have a positive effect on rhinitis and sinusitis overall. The relationship between allergic sensitization and GERD is likely bidirectional. GERD may induce changes in the mucosal immune system that may favor the development of food allergy and allergic sensitization to aeroallergens; however, the underlying mechanisms have not been established.


[Clinico-roentgenological and scintigraphic parallels in aseptic femur head necrosis in patients with rheumatoid arthritis].
A clinicoroentgenological study was performed in 35 rheumatoid arthritic patients (of them 24 with aseptic necrosis of the femoral heads and 11 without clinicoroentgenological signs of the hip joint involvement). Aseptic necrosis, stage II, was roentgenologically defined in 12 femoral heads, stage III in 23. An analysis of the results of the scintigraphic study showed that the RP absorption ratio in the rheumatoid arthritic patients with aseptic necrosis was significantly higher than that in the control group. Significant scintigraphic differences between stage II and III of aseptic necrosis were also revealed (the ratio of 99mTc absorption was 2.79 +/- 0.156 and 4.08 +/- 0.22, respectively).


Calcium phosphate transfection optimization for serum-free suspension culture.
Aim of this study was to identify optimal conditions for suspension transfection in the absence of serum. Transfection parameters for suspension culture can be very different to ones in adherent cells. Most transfection protocols have been developed and optimizedfor adherent culture. Using green fluorescent protein (GFP) as reporter, FCS was eliminated from the transfection process by altering critical parameters and by substituting serum with albumin. Using standard phosphate and calcium concentrations for transfection in the absence of serum resulted in titers of only 1% of those observed in the presence of serum. A reduction of the calcium concentration from 250 mM to 100 mM, yielded a 25-fold increase in the expression of the recombinant protein compared to the serum-free standard conditions. Altering the phosphate concentration, 1.4 mM in the transfection buffer, did not improve the protein expression. Interestingly, reduction of DNA quantity by half to a concentration of 0.5 μg per milliliter of culture volume resulted in a two-fold increase of protein production. Addition of albumin to serum-free medium protected the cells against the toxicity of the calcium phosphate transfection particles (CaPi) yielding higher protein expression. All the experiments were executed in a shaken multi-well system, allowing high multiplicity parameter screening to speed up optimizations. The culture system is inexpensive, simple and efficient, minimizing costs for labor and consumables.


Signal transduction by interleukin 2 in human T cells: activation of tyrosine and ribosomal S6 kinases and cell-cycle regulatory genes.
The early events of signal transduction associated with interleukin-2 (IL-2) binding to its receptor were examined using a human IL-2 dependent T-cell line, Kit225. Cell cycle analysis showed that 90% of Kit225 cells were in the G0/G1 phase after a 72-hr incubation in the absence of exogenous IL-2. At this point, stimulation of the cells with IL-2 resulted in the rapid initiation of RNA and DNA synthesis by 9 and 20 hr, respectively. Within 5 min after addition of IL-2, rapid activation of tyrosine and ribosomal S6 kinases was detected. Addition of IL-2 also increased mRNA levels for c-fos, c-myc, IL-2 receptor alpha, and IL-2 receptor beta chain. These events increased in the absence of detectable changes in free cytosolic [Ca2+]i, inositol phosphate metabolism, or the activity of several kinases including cAMP-dependent protein kinase, Ca2+/calmodulin-dependent protein kinase, or protein kinase C. These findings demonstrate that the signals triggered by IL-2 binding to its receptors are quickly transduced into the nucleus with increased mRNA transcription of activation-associated genes. Furthermore, the data indicate that tyrosine and ribosomal S6 kinases may be important for IL-2-induced cell growth.


A "turn-on" fluorescent probe for hypochlorous acid: convenient synthesis, good sensing performance, and a new design strategy by the removal of C=N isomerization.
A new design strategy for the development of fluorescent turn-on chemodosimeters toward OCl(-) was proposed by the removal, but not the general inhibition, of the C=N isomerization. Accordingly, Flu-1 was prepared, which, as shown in the fluorescent picture, exhibited the off-on response for OCl(-), sensitively and selectively.


The toxic effect of double-stranded RNA for interferon-treated L cells: studies on membrane transport and with cell-free systems.
We have tested two possible explanations for the toxic effects observed in L cells treated with interferon followed by poly(rI).poly(rC), namely (1) that the toxicity was preceded by and due to a change in membrane permeability which could be monitored by measurement of ion fluxes, or (2) that the toxicity was due to the action of the inhibitors of protein synthesis which are known to be formed when extracts from interferon-treated cells are treated with poly(rI).poly(rC) in vitro. Neither explanation was found to be correct.


Gallbladder carcinoma with ultrasonographically intact outer hyperechoic layer: A sign of a favorable outcome.
Thirty-one of 40 patients with gallbladder carcinoma whom we treated from December 1983 through June 1999 underwent resection of cancers extending from the mucosa (m) (pTis-pT1a) to the subserosa (ss) (pT2). The patients were classified into five groups according to the layered-structure of the gallbladder wall and the internal echo of tumors visualized in ultrasound images. Group A included pedunculated polyps with round margins, homogeneous hypoechoic internal echoes, and intact outer hyperechoic layers; group B, broad-based lesions with homogeneous hypoechoic internal echoes and intact outer hyperechoic layers; group C, broad-based lesions with intact outer hyperechoic layers and more heterogeneous hypoechoic internal echoes in their centers than those in the marginal lesions; group D, broad-based lesions with irregularity and/or thinning of outer hyperechoic layers; and group E, tumors that could not be evaluated. The ultrasonograms and histopathologic findings of groups A through D were compared, and the surgical techniques used in each group were examined. Outcomes achieved by groups A through C, with their intact outer hyperechoic layers, were compared with those achieved by groups D and E.The six tumors in group A were all well-differentiated adenocarcinomas confined to the mucosa (pTis), and simple cholecystectomy was considered appropriate. The eight tumors in group B comprised three cases of m (pTis-pT1a) cancer, two cases of cancer invading the muscularis propria (mp) (pT1b), and three cases of cancer minutely scattered in the infiltrating subserosal fibrous layer (ss fibrous layer) (pT2). Accordingly, because of the difficulty of determining depth of invasion, resection of the liver bed was considered appropriate in group B. Histopathologic examination of group C showed that the tumors had invaded the ss fibrous layer (pT2) in all six patients. Although the ss fat layer had not been invaded, metastasis to the lymph nodes of the cystic duct (30%) had occurred, suggesting that a favorable outcome could be expected if the patient underwent resection of the liver bed and lymphadenectomy of the cystic duct, pericholedochal, hilar, peripancreatic, periportal, common hepatic, and proper hepatic lymph nodes. Group D comprised two patients with cancers that had invaded the ss fat layer (pT2). All nine tumors in group E were ss (pT2) cancers. The 5-year survival rate was 100 percent in groups A, B, and C; 50 percent in group D, and 45 percent in group E. Five-year survival rates were significantly lower in groups D and E than in groups A, B, and C, in which the outer hyperechoic layer remained intact (p<0.01).Gallbladder carcinomas with intact outer hyperechoic layers were classified into three groups (groups A, B, and C), in which depth of invasion ranged from m (pTis-pT1a) to the ss fibrous layer (pT2). These three groups were associated with favorable outcomes, although different surgical techniques were required for each group. An intact outer hyperechoic layer in the ultrasonogram is a predictor of a favorable outcome in patients with gallbladder carcinoma.


Problems associated with ultraviolet dosimetry in the photochemotherapy of psoriasis.
A hypothetical action spectrum for the regression of lesions in photochemotherapy of psoriasis is proposed. An ideal detector should have a wavelength response which matches this action spectrum but this is generally not the case with commercially available photometers. The problems that may arise by indiscriminate use of such detectors are discussed, together with a suggested solution.


[Effect of substance P on blood pressure in rats, with and without hypokinetic stress].
The effect of substance P (SP) on blood pressure was studied in normotensive rats and in rats with hypokinesia-induced hypertension. To characterize the SP effect, the influence on the blood pressure value, intra-individual variation and interindividual changes was investigated. Whereas SP corrected the hypokinesia-induced changes (increased blood pressure, increase in the intra-individual blood pressure variations) in the stressed animals, no SP effect was observed in the normotensive control rats. These findings are discussed with a view to the assumed ability of SP to act as a regulatory peptide (regulide).