Sleep-related breathing disturbances: their pathogenesis and potential interest to the nephrologist.
For about 120 years we have been looking for the 'cause' of essential hypertension. It is possible that we have merely been wandering through its graveyard, looking at the pathogenetic mechanisms but never the actual cause? Here we pass the gravestone of increased sympathetic activity; there the gravestone of low renin activity. Here high endothelin; there low EDRF. Here high thromboxane A2; there low prostacyclin. It is possible that all these and so many other pathogenetic factors are all due to one basic defect? Is it possible that, in the dead of night while patients with EH have been sleeping, the villain has been lurking in their mouths, stuck somewhere at the back of their throats, hidden from view yet choking them hundreds of times a night. But this intermittent strangulation has not occurred silently. On the contrary, it has made its presence felt in the most irritating way, with snores, groans, grunts, gasps and frightening periods of total apnea. But we, their physicians, never asked about these symptoms, or, if we did, we never paid heed to them. This is clear from the fact that, most cases of OSA occur in association with EH yet are not diagnosed. Perhaps the next 'arousal response' should be the arousal of physicians' consciousness so that they can at long last wake up to the existence of the close connection between sleep-related breathing disorders and hypertension and breathe some new life into the treatment of two old diseases-essential hypertension and secondary hypertension. Early diagnosis and treatment of the sleep-related breathing disorders may not only make the patient feel much better, (something our antihypertensive medications do not always do), but may reduce the blood pressure and prevent the progression of renal and cardiovascular damage as well.


Motion-based, high-yielding, and fast separation of different charged organics in water.
We report a self-propelled Janus silica micromotor as a motion-based analytical method for achieving fast target separation of polyelectrolyte microcapsules, enriching different charged organics with low molecular weights in water. The self-propelled Janus silica micromotor catalytically decomposes a hydrogen peroxide fuel and moves along the direction of the catalyst face at a speed of 126.3 μm s(-1) . Biotin-functionalized Janus micromotors can specifically capture and rapidly transport streptavidin-modified polyelectrolyte multilayer capsules, which could effectively enrich and separate different charged organics in water. The interior of the polyelectrolyte multilayer microcapsules were filled with a strong charged polyelectrolyte, and thus a Donnan equilibrium is favorable between the inner solution within the capsules and the bulk solution to entrap oppositely charged organics in water. The integration of these self-propelled Janus silica micromotors and polyelectrolyte multilayer capsules into a lab-on-chip device that enables the separation and analysis of charged organics could be attractive for a diverse range of applications.


Prognostic Value of Plasma Catestatin Concentration in Patients with Heart Failure with Reduced Ejection Fraction in Two-Year Follow-Up.
The primary objective of the study was to evaluate the prognostic value of measuring plasma catestatin (CST) concentration in patients with heart failure with reduced ejection fraction (HFrEF) as a predictor of unplanned hospitalization and all-cause death independently and as a composite endpoint at 2-year follow-up. The study group includes 122 hospitalized Caucasian patients in NYHA classes II to IV. Patients who died during the 24-month follow-up period (n = 44; 36%) were significantly older on the day of enrollment, were more likely to be in a higher NYHA class, had lower TAPSE, hemoglobin concentration, hematocrit, and platelet count, higher concentrations of CST, NT-proBNP, troponin T, creatinine, and glucose, and higher red cell distribution width value and leukocyte and neutrocyte count than patients who survived the follow-up period. Plasma catestatin concentration increased with NYHA class (R = 0.58; p <0.001) and correlated significantly with blood NT-proBNP concentration (R = 0.44; p <0.001). We showed that higher plasma catestatin concentration increased the risk of all-cause death by more than five times. Plasma CST concentration is a valuable prognostic parameter in predicting death from all causes and unplanned hospitalization in patients with HFrEF.


Does abdominal obesity accelerate the effect of hypertriglyceridemia on impaired fasting glucose?
This study sought to determine whether abdominal obesity is a risk factor for impaired fasting glucose (IFG) and hypertriglyceridemia and to verify whether moderate effect of abdominal obesity on the relationship between IFG and hypertriglyceridemia in Korea. Data from the Korean National Health and Nutrition Examination Survey was used for the analysis. The study population included 5,938 subjects aged 20 year old drawn from non-diabetic participants in a health examination survey. The subjects were classified according to the presence of abdominal obesity based on waist circumference, IFG based on their fasting blood glucose level, and hypertriglyceridemia on their fasting triglyceride. The multivariate-adjusted odds ratios for the occurrence of hypertriglyceridemia were 2.91 in the abdominal obesity group as compared with the nonobesity group and 1.31 in subjects with IFG compared with the normoglycemia controls. Abdominal obesity was found to be positively moderated in the interaction between waist circumference and fasting blood sugar. The moderate effect between abdominal obesity and IFG contributes to the development of hypertriglyceridemia in Korea.


Immune regulation of transgene expression in the brain: B cells regulate an early phase of elimination of transgene expression from adenoviral vectors.
Cellular immune mechanisms that regulate viral gene expression within infected brain cells remain poorly understood. Previous work has shown that systemic immunization against adenovirus after vector delivery to the brain results in complete loss of brain cells infected by adenoviral vectors. Although T cells play an important role in this process, we demonstrate herein that B cells also significantly regulate transgene expression from the CNS. After the systemic immunization against adenovirus of animals injected via the brain with an adenoviral vector 30 days earlier, we uncovered substantial infiltration by CD19+ B cells of the area of the brain transduced by the virus. This suggests the involvement of B cells in the adaptive immune response-mediated loss of transduced cells from the brain. Confocal analysis of these brains demonstrated physical contacts between transduced brain cells and CD19+ cells. To test the hypothesis that B cells play a causal role in the loss of infected cells from the brain, we demonstrated that animals devoid of B cells were unable to eliminate transgene expression at early time points after immunization. This demonstrates that B cells play a necessary role in the loss of transgene expression at early, but not late, time points postimmunization. Thus, these data have important implications for our understanding of the role of B cells as immune effectors during the immune-mediated clearance of viral infections from the CNS, and also for understanding mechanisms operating in brain autoimmunity, as well as for the potential safety of clinical gene therapy for brain diseases.


Rothmund-Thomson syndrome. The first case with plantar keratoderma and the second with coeliac disease.
We report two unusual patients with Rothmund-Thomson syndrome (RTS), a rare genodermatosis. The first patient is a 5-year-old girl with congenital poikiloderma, photosensitivity, plantar punctate keratoderma, stunted growth and severe mental retardation. Plantar keratoderma associated with RTS has been reported only once. The second patient is a 21-year-old female presenting with rounded "moon" face, trunk obesity, coeliac disease, short stature and mild mental retardation. This is the first case of RTS associated with coeliac disease.


Simultaneous recordings of visual evoked potentials and BOLD MRI activations in response to visual motion processing.
Visual motion processing in humans was studied by simultaneous 32-channel electroencephalography (EEG) recordings of visual evoked potentials and BOLD MRI activations at 2.9 T. The paradigms compared three different random dot patterns (12 s duration) with stationary random dots (18 s) or with each other. The stimuli represented pattern reversal (500 ms switches between two stationary patterns), motion onset (200 ms of starfield motion followed by 1000 ms of stationary dots) and motion reversal (reversal of moving starfield directions every 1000 ms). Whereas motion-evoked visual potentials, and in particular the N2 component in occipito-temporal channels, were most prominent for motion onset, the most extended BOLD MRI activations and strongest signal changes in V5/MT+ were obtained in response to motion reversal. These apparently contradictory findings most likely reflect different physiological aspects of the neural activity associated with visual motion processing. For example, desynchronized activity of subpopulations of cortical neurons inside V5/MT+ is expected to attenuate visual evoked potentials in scalp recordings while continuously driving metabolic demands that lead to sustained BOLD MRI responses. The understanding of the physiological correlates and neural processes underlying either technique is fundamental to exploring fully the potential of combined EEG-MRI for studying human brain function at both high temporal and spatial resolution.


[Effect of tetracycline and oleandomycin on the indices of nonspecific resistance in aseptic inflammation under conditions of changes in the body's reactivity].
The effect of tetracycline and oleandomycin on the complement titer, lysozyme content, serum bactericidal properties and presence of specific antibiotic antibodies in the blood serum was studied. The latter were shown with the Hoigné reaction under conditions of aseptic inflammation caused against the background of latent tetanus intoxication. It was shown that tetracycline and oleandomycin used in treatment of the animals with aseptic inflammation developed at the background of latent tatanus intoxication induced an increased in the complement titer, lysozyme content and bactericidal properties of the serum. Reduction of the above indices was observed by the 15th-20th day after discontinuation of the drug use. The increase in the factors of non-specific immunity under the effect of tetracycline and oleandomycin in the animals with aseptic inflammation caused against the background of latent tetanus intoxication was accompanied by appearance in the blood serum on non-specific antibodies revealed with the Hoigné reaction. Changed reactivity because of latent tetanus intoxication was accompanied by a delay in the formation of the non-specific antibodies in the blood serum. However, later the rate of their accumulation became higher and as a result the maximum titers of the antibodies were 2-3 times higher than those in the control animals.


Rehabilitation of maxillary edentulism with implant-supported milled-bar prostheses.
Implantology has allowed more options for rehabilitation of complete and partially edentulous patients. The professional should describe all possible alternatives to the patient, addressing all the positive and negative aspects of each possibility, such as treatment time, complexity of surgical procedures, and the final cost. The patient should select the best cost-benefit relationship because fixed prostheses are often not the option of choice for the patient. The aim of this article is to present one possible treatment option for the completely edentulous patient by use of implants to support and retain a removable complete or partial prosthesis. The clinical situations were rehabilitated by the use of a milled bar screwed to the implants to support a removable prosthesis with attachments and a milled metallic groove, which provide many advantages to the patient.


Ergonomics in Radiology: Improving the Work Environment for Radiologists.
Implementation of optimal ergonomic setups of workstations and reading rooms can help to improve the overall quality of life for most radiologists by preventing repetitive stress injuries and potentially improving efficiency. It is important for radiologists to know what optimal ergonomic setups are and what works for the individual person in order to implement the best possible ergonomic setups as they may differ from person to person. These issues have become more important recently as many radiologists have been working from home and will continue to do so, at least partially, during the COVID-19 pandemic. In this paper, we aim to increase awareness of sound ergonomic principles and discuss possible options for individual optimization along with practical tips for implementation of optimal ergonomic setups.


Fibrosis Progression in Patients With Chronic Hepatitis C Virus Infection.
Fibrosis progression varies markedly in hepatitis C virus (HCV)-infected individuals. We investigated factors that influence fibrosis progression in chronic HCV infection. HCV-infected patients who underwent at least 2 liver biopsies were included in this study. Associations between fibrosis progression and epidemiologic, virologic, and disease-associated factors were analyzed using logistic regression and multistate Markov modeling. We analyzed 936 biopsy specimens obtained from 378 individuals. Mean age (±SD) at first biopsy was 48.3 ± 9.3 years, 59.3% of patients were male, 59.9% were white, and 86.7% were infected with HCV genotype 1. Fibrosis progression and cirrhosis occurred in 57.4% and 5.8%, respectively. Fibrosis progression between the first and last biopsies was associated with lower fibrosis in the first biopsy specimen (P < .001) and with the occurrence of at least 1 flare in the alanine aminotransferase (ALT) level (>200 U/L; P = .007). We found the highest fibrosis progression rate between stages 0 and 1 and the lowest between stages 2 and 3. Increased necroinflammation and higher ALT level were associated with faster progression. HCV genotype 3-infected patients were more likely to progress to cirrhosis (P < .001). Fibrosis progression in HCV is not linear but varies according to stage, with the highest progression in patients with the lowest fibrosis severity. Patients who experience flares in the ALT level are also more likely to progress.


Amyloid Precursor-Like Protein 2 deletion-induced retinal synaptopathy related to congenital stationary night blindness: structural, functional and molecular characteristics.
Amyloid precursor protein knockout mice (APP-KO) have impaired differentiation of amacrine and horizontal cells. APP is part of a gene family and its paralogue amyloid precursor-like protein 2 (APLP2) has both shared as well as distinct expression patterns to APP, including in the retina. Given the impact of APP in the retina we investigated how APLP2 expression affected the retina using APLP2 knockout mice (APLP2-KO). Using histology, morphometric analysis with noninvasive imaging technique and electron microscopy, we showed that APLP2-KO retina displayed abnormal formation of the outer synaptic layer, accompanied with greatly impaired photoreceptor ribbon synapses in adults. Moreover, APLP2-KO displayed a significant decease in ON-bipolar, rod bipolar and type 2 OFF-cone bipolar cells (36, 21 and 63 %, respectively). Reduction of the number of bipolar cells was accompanied with disrupted dendrites, reduced expression of metabotropic glutamate receptor 6 at the dendritic tips and alteration of axon terminals in the OFF laminae of the inner plexiform layer. In contrast, the APP-KO photoreceptor ribbon synapses and bipolar cells were intact. The APLP2-KO retina displayed numerous phenotypic similarities with the congenital stationary night blindness, a non-progressive retinal degeneration disease characterized by the loss of night vision. The pathological phenotypes in the APLP2-KO mouse correlated to altered transcription of genes involved in pre- and postsynatic structure/function, including CACNA1F, GRM6, TRMP1 and Gα0, and a normal scotopic a-wave electroretinogram amplitude, markedly reduced scotopic electroretinogram b-wave and modestly reduced photopic cone response. This confirmed the impaired function of the photoreceptor ribbon synapses and retinal bipolar cells, as is also observed in congenital stationary night blindness. Since congenital stationary night blindness present at birth, we extended our analysis to retinal differentiation and showed impaired differentiation of different bipolar cell subtypes and an altered temporal sequence of development from OFF to ON laminae in the inner plexiform layer. This was associated with the altered expression patterns of bipolar cell generation and differentiation factors, including MATH3, CHX10, VSX1 and OTX2. These findings demonstrate that APLP2 couples retina development and synaptic genes and present the first evidence that APLP2 expression may be linked to synaptic disease.


Genetic association of autoimmune hepatitis and human leucocyte antigen in German patients.
To report on our large German collective and updated data of 142 patients with autoimmune hepatitis (AIH) type 1. Key investigations performed were liver biopsy, serum autoantibodies as well as serum markers such as IgG and elevated transaminases. Antinuclear antigen (ANA) and smooth muscle antigen (SMA) autoantibodies characterized type 1 AIH. Type 3 (AIH) was solely characterized by the occurrence of soluble liver antigen/liver-pancreas antigen (SLA/LP) autoantibodies either with or without ANA or SMA autoantibodies. Most prevalent HLAs were A2 (68 patients, 48%), B8 (63 patients, 44%), C7 (90 patients, 63%), DR3 (49 patients, 38%), DR4 (49 patients, 38%) and DQ2 (42 patients, 30%). Compared to the Italian and North American patients, we found fewer patients with a DQ2 subtype. Furthermore, the B8-DR3-DQ2 human leucocyte antigen (HLA) was also less prominent compared to the North American patients. However, prevalences of B8, DR3, DR4, DR7, DR11 and DR13 were comparable to the Italian and North American patients. Furthermore, we report on an additional subgroup of patients with SLA/LP positive AIH. Generally, in this subgroup of patients the same HLA subtypes were favoured as the AIH type 1. Although HLA subtypes were comparable between these three collectives, the German patients were distinct from the Italian and North American patients with respect to DQ2 and from the North American patients with respect to B8-DR3-DQ2 HLA. A clinical correlation, e.g. difference in severity or treatability of AIH type 1, has yet to be determined.


Exosomes Secreted from Induced Pluripotent Stem Cell-Derived Mesenchymal Stem Cells Accelerate Skin Cell Proliferation.
Induced pluripotent stem cell (iPSC)-derived mesenchymal stem cells (iMSCs) serve as a unique source for cell therapy. We investigated whether exosomes from iMSCs promote the proliferation of human keratinocytes (HaCaT) and human dermal fibroblasts (HDFs). iPSCs were established from human Wharton's jelly MSCs and were allowed to differentiate into iMSCs. Exosomes were collected from the culture supernatant of MSCs (MSC-exo) and iMSCs (iMSC-exo), and their characteristics were investigated. Both exosome types possessed basic characteristics of exosomes and were taken up by skin cells in vitro and in vivo. A significant increase in HaCaT proliferation was observed with iMSC-exo, although both exosomes increased the viability and cell cycle progression in HaCaT and HDFs. No significant difference was observed in the closure of wound scratch and the expression of reparative genes between cells treated with the two exosome types. Both exosomes enhanced the secretion of collagen in HaCaT and HDFs; however, an increase in fibronectin level was observed only in HaCaT, and this effect was better with iMSC-exo treatment. Only iMSC-exo increased the phosphorylation of extracellular signal-regulated kinase (ERK)-1/2. Our results indicate that iMSC-exo promote the proliferation of skin cells by stimulating ERK1/2 and highlight the application of iMSCs for producing exosomes.


Density of phonon states in solid parahydrogen from inelastic neutron scattering.
We have measured the inelastic neutron scattering spectrum of solid parahydrogen (at low pressure and T=13.3 K) using the thermal original spectrometer with cylindrical analyzers spectrometer at the ISIS pulsed neutron source (UK). From the experimental spectrum we have obtained the parahydrogen density of phonon states which has been compared with the estimates available in the literature. The present determination improves substantially the previous experimental scenario from the point of view of both statistics and accuracy. The comparison with the most recent estimate obtained from a quantum mechanical simulation of the molecular dynamics calls for an improvement of the computational methods..


Radiative corrections to the polarizability of helium.
The complete alpha(3) QED correction to the helium atom polarizability is computed assuming an infinite nuclear mass and found to be equal to 0.000030666(3) a.u., with the contribution from the electric-field dependence of the Bethe logarithm amounting to 0.000000193(2) a.u. After including the alpha(2) and alpha(3) corrections for the nuclear recoil and the leading part of the alpha(4) QED correction, we find that the molar polarizability of 4He is 0.51725419(9)(4) cm(3)/mol. The first of the two error bounds is dominated by the uncertainty of alpha(4) and higher-order QED corrections and the second reflects the uncertainty of the Avogadro constant.


Organocatalytic vs. Ru-based electrochemical hydrogenation of nitrobenzene in competition with the hydrogen evolution reaction.
The electrochemical reduction of organic contaminants allows their removal from water. In this contribution, the electrocatalytic hydrogenation of nitrobenzene is studied using both oxidized carbon fibres and ruthenium nanoparticles supported on unmodified carbon fibres as catalysts. The two systems produce azoxynitrobenzene as the main product, while aniline is only observed in minor quantities. Although PhNO2 hydrogenation is the favoured reaction, the hydrogen evolution reaction (HER) competes in both systems under catalytic conditions. H2 formation occurs in larger amounts when using the Ru nanoparticle based catalyst. While similar reaction outputs were observed for both catalytic systems, DFT calculations revealed some significant differences related to distinct interactions between the catalytic material and the organic substrates or products, which could pave the way for the design of new catalytic materials.


Synaptic Specificity, Recognition Molecules, and Assembly of Neural Circuits.
Developing neurons connect in specific and stereotyped ways to form the complex circuits that underlie brain function. By comparison to earlier steps in neural development, progress has been slow in identifying the cell surface recognition molecules that mediate these synaptic choices, but new high-throughput imaging, genetic, and molecular methods are accelerating progress. Over the past decade, numerous large and small gene families have been implicated in target recognition, including members of the immunoglobulin, cadherin, and leucine-rich repeat superfamilies. We review these advances and propose ways in which combinatorial use of multifunctional recognition molecules enables the complex neuron-neuron interactions that underlie synaptic specificity.


Characteristics of patients with osteonecrosis of the jaw with oral versus intravenous bisphosphonate treatment.
This retrospective study was aimed to evaluate the clinical characteristics and treatment outcomes in patients with osteonecrosis of the jaw who were receiving oral versus intravenous (IV) bisphosphonate (BP). This retrospective study enrolled subjects who had been diagnosed with medication-related osteonecrosis of the jaw (MRONJ) during the period from July 2010 to June 2014. Information regarding the following demographic and clinical characteristics was collected: demographic data, administration route and type of BP, duration of BP medication, primary disease, number of involved sites, location of the lesion, number of surgeries, outcome of treatments, and laboratory test. All the patients were divided into oral and IV BP groups; and the between-group differences were compared. Total 278 patients were divided into two groups as per the route of BP administration. The proportion of oral BP-related MRONJ group were more dominant over IV BP group (oral BP, n = 251; IV BP, n = 27). In the IV BP group, the average dosing duration (31.4 months) was significantly shorter than that in the oral BP group (53.1 months) (P < 0.001). The average number of involved sites in the oral BP group (1.21 ± 0.48) was smaller than that in the IV BP group (1.63 ± 0.84) (P < 0.001). The average number of surgeries was higher in the IV BP group (1.65 ± 0.95) as compared to that in the oral BP group (0.98 ± 0.73) (P < 0.001). Outcome after the surgery for MRONJ after IV BP was poor than oral BP group. IV administration of BP causes greater inhibition of bone remodeling and could lead more severe inflammation. Therefore, even if the duration of IV administration of BP is shorter than that of oral BP, the extent of the lesion could be more extensive. Therefore, the result suggests that the MRONJ after IV BP for cancer patients needs to be considered as different characteristics to oral BP group for osteoporosis patents.


Comparison of plasma PARK7 and NDKA diagnostic value in acute stroke.
In this prospective case-control study we aimed to compare diagnostic value of plasma PARK7 and NDKA in early diagnosis of acute stroke and evaluate the validated diagnostic values of PARK7 and NDKA in an independent patient cohort. We then assessed the quantitative relationship between the release of these markers: stroke severity and time. Blood samples were drawn upon hospital admission and 14 days later. PARK7 and NDKA concentrations were measured using an ELISA. The expression of PARK7 (area under the curve [AUC] = 0.897) in acute stroke patients was more significant than in controls, relative to the NDKA expression (AUC = 0.462); p < 0.05. Their expressions were not related to the clinical characteristics of both groups; p > 0.05. Even though both markers cannot differentiate stroke etiologies (ischemic or hemorrhagic), plasma PARK7 has better diagnostic value than NDKA for early diagnosis of stroke. 72 plasma samples obtained from acute stroke patients and 78 plasma samples collected from non-stroke patients were analyzed in this study.


Interrelation between whole-body turnover rates of RNA and protein.
In our search for new non-invasive methods to determine metabolic and nutritional state, we have identified several specific, modified, urinary one-way catabolites of rRNA, tRNA and mRNA which permit the assessment of the whole-body turnover of these RNA classes. A comparison of the steady-state turnover of RNA and the proteins actin plus myosin (determined using urinary 3-methylhistidine) in preterm infants and adults showed that preterm infants have about 3 times higher average turnover rates per unit body weight than adults of tRNA and rRNA as well as of actin plus myosin, whereas calculated mRNA turnover was 6 times higher in preterm infants than in adults. These as well as our recent observations of RNA turnover in different mammals are compared here with data on whole-body protein turnover and basal metabolic rates (BMR) in different mammalian species including man, for which data are available. The turnover rates of tRNA, rRNA, protein and energy (BMR) can be described by the relation, turnover = const. x body mass (exp.), the extrapolated exponents being 0.69-0.78. This suggests a common underlying principle, possibly energy turnover, as cause for the coordinated whole-body turnover rates of RNA and protein in the steady state.


A model for the hierarchical structure of the human epidermal cornified cell envelope.
The epidermal cornified cell envelope (CE) is a 15 nm thick layer of highly insoluble protein that is assembled on the intracellular surface of the cell membrane during terminal differentiation, and comprises about 10% of the mass of the cornified dead layers of the tissue. The CE consists of a complex amalgam of several known proteins that are crosslinked by isodipeptide bonds formed by the action of transglutaminases, but little is known about their order of accretion during CE assembly, or how they are crosslinked. In this paper, CEs purified from human foreskin epidermis were examined by immunogold electron microscopy before and after digestion with proteases.The mass fractions of the proteins remaining in CE remnants during digestion were estimated from the amino acid compositions by mathematical modelling. Together, the data support a new model for the complex hierachical structure of the CE. The cytoplasmic surface of intact purified CEs consists of filaggrin, loricrin, SPRs and keratin intermediate filaments. The bulk of the CE consists of a mixture of loricrin (75%) and SPRs (5%). Following removal of most of these, the novel protein elafin is exposed, which contributes about 6% of CE mass. The protein material on the inner CE 'core' adjacent or attached to the lipid envelope consists of cystatin alpha (5%), involucrin (2%), keratin filaments (3%) and possibly other as yet unidentified protein(s)(2-5%). This model supports but considerably extends an earlier extant hypotheis for CE structure, and thus provides the basis for further detailed biochemical and ultra-structural studies.


Structure-specific DNA-induced conformational changes in Taq polymerase revealed by small angle neutron scattering.
The DNA polymerase I from Thermus aquaticus (Taq polymerase) performs lagging-strand DNA synthesis and DNA repair. Taq polymerase contains a polymerase domain for synthesizing a new DNA strand and a 5'-nuclease domain for cleaving RNA primers or damaged DNA strands. The extended crystal structure of Taq polymerase poses a puzzle on how this enzyme coordinates its polymerase and the nuclease activities to generate only a nick. Using contrast variation solution small angle neutron scattering, we have examined the conformational changes that occur in Taq polymerase upon binding "overlap flap" DNA, a structure-specific DNA substrate that mimics the substrate in strand replacement reactions. In solution, apoTaq polymerase has an overall expanded equilibrium conformation similar to that in the crystal structure. Upon binding to the DNA substrate, both the polymerase and the nuclease domains adopt more compact overall conformations, but these changes are not enough to bring the two active sites close enough to generate a nick. Reconstruction of the three-dimensional molecular envelope from small angle neutron scattering data shows that in the DNA-bound form, the nuclease domain is lifted up relative to its position in the non-DNA-bound form so as to be in closer contact with the thumb and palm subdomains of the polymerase domain. The results suggest that a form of structure sensing is responsible for the coordination of the polymerase and nuclease activities in nick generation. However, interactions between the polymerase and the nuclease domains can assist in the transfer of the DNA substrate from one active site to the other.


Comparison of treatment outcomes with vancomycin alone versus combination therapy in severe Clostridium difficile infection.
The recommended treatment for severe Clostridium difficile infection (CDI) is oral vancomycin alone. Combination therapy with metronidazole is only recommended in cases complicated by shock, ileus, or toxic megacolon. However, patients with severe infection are often treated with combination therapy despite a lack of data supporting this practice. To evaluate differences in outcomes for patients with severe CDI treated with oral vancomycin alone versus combination therapy. Medical records of 78 patients with severe CDI receiving either oral vancomycin alone or combination therapy for ≥ 72h were retrospectively reviewed. The primary outcome was time to clinical cure of CDI, defined as the first day of resolution of diarrhoea for ≥ 48h without development of a complication. Other endpoints included cure rates, complication rates, and recurrence rates. There was no difference in the incidence of clinical cure between monotherapy and combination therapy (57.1% vs 65.1%, P = 0.49). Median time to clinical cure was 7.0 days for the monotherapy group and 8.0 days for combination therapy (P = 0.19). After adjustment for potential confounders, the hazard ratio of the time to clinical cure for combination therapy compared with monotherapy was 0.58 (P = 0.10). There was no difference in recurrence rate or rates of individual complications between groups; however, there was a significantly higher composite complication rate in the combination therapy group. These data suggest that there is no difference in treatment outcomes between monotherapy and combination therapy for severe CDI.


Phase I Study of Carboplatin Plus Pemetrexed with Concurrent Radiotherapy for Locally Advanced Non-Squamous NSCLC (CJLSG0912).
Although concurrent chemoradiotherapy is the standard therapy for unresectable stage III non-small cell lung cancer (NSCLC), no optimal concurrent chemoradiotherapy regimen has been identified in non-squamous NSCLC. We conducted an open-label, multicenter phase I trial to assess the safety of carboplatin (CBDCA) plus pemetrexed (PEM) with concurrent thoracic radiotherapy (TRT) of 60 Gy. The primary endpoint was determination of the maximum tolerated dose. In total, 6 patients were registered during the period from February 2012 through January 2014. Dose-limiting toxicities (DLTs) were observed in 2 patients (one case each of prolonged neutropenia and pneumonitis). The overall response rate was 83.3%, and median progression-free survival was 20.1 months. Since only two DLTs were observed in the phase I cohort, we concluded that CBDCA plus PEM with concurrent TRT was feasible in Japanese patients with unresectable stage III non-squamous NSCLCs. We will recommend the dose of CBDCA area under the curve 5 plus PEM 500 mg/m2 for the next phase II trial.


Interaction of amphotericin B with cholesterol in monolayers, aqueous solutions, and phospholipid bilayers.
The interaction of amphotericin B (AmB) with cholesterol was investigated in monolayers, aqueous solutions, and phospholipid vesicles. When AmB was mixed with cholesterol, it formed a stable monolayer, implying complex formation in which the stoichiometry was primarily 1:1 AmB:cholesterol. However, the interaction of AmB with cholesterol in aqueous solutions and lipid vesicles was more complex. In aqueous solutions, cholesterol at low concentrations increased the aggregation of AmB. But higher concentrations of cholesterol caused dissociation of the aggregates of AmB due to the formation of AmB-cholesterol complexes. In lipid vesicles, the effect of cholesterol was different from that in aqueous solutions. Both in aqueous solutions and lipid vesicles, the overall dissociation of AmB molecules occurred on interaction with cholesterol. In addition, the interaction of lipid membranes with AmB-cholesterol complexes was investigated by differential scanning calorimetry. The incorporation of AmB into lipid bilayers led to broadening of the lipid transition and a slight decrease in the transition enthalpy, showing that one lipid molecule per AmB molecule was immobilized. However, the number of immobilized lipid molecule per AmB molecule increased in the coexistence of cholesterol, due to the complex formation between AmB and cholesterol.


Mortality as an adverse outcome of sarcopenia.
Sarcopenia has an important impact in elderly. Recently the European Working Group on Sarcopenia in Older People (EWGSOP) defined sarcopenia as the loss of muscle mass plus low muscle strength or low physical performance. Lack of clinical sounding outcomes (ie external validity), is one of the flaws of this algorithm. The aim of our study was to determine the association of sarcopenia and mortality in a group of Mexican elderly. A total of 345 elderly were recruited in Mexico City, and followed up for three years. The EWGSOP algorithm was integrated by: gait speed, grip strength and calf circumference. Other covariates were assessed in order to test the independent association of sarcopenia with mortality. Of the 345 subjects, 53.3% were women; with a mean age of 78.5 (SD 7) years. During the three year follow-up a total of 43 (12.4%) subjects died. Age, cognition, ADL, IADL, health self-perception, ischemic heart disease and sarcopenia were associated in the bivariate analysis with survival. Negative predictive value for sarcopenia regarding mortality was of 90%. Kaplan-Meier curves along with their respective log-rank test were significant for sarcopenia. The components of the final Cox-regression multivariate model were age, ischemic heart disease, ADL and sarcopenia. Adjusted HR for age was 3.24 (CI 95% 1.55-6.78 p 0.002), IHD 5.07 (CI 95% 1.89-13.59 p 0.001), health self-perception 5.07 (CI 95% 1.9-13.6 p 0.001), ADL 0.75 (CI 95% 0.56-0.99 p 0.048) and sarcopenia 2.39 (CI 95% 1.05-5.43 p 0.037).


Commensal relationship between a sheath-forming bacterium, Sphaerotilus natans, and a sheath-degrading bacterium, Paenibacillus sp.
Paenibacillus sp. strain TB is capable of degrading the sheath prepared from a sheathed bacterium, Sphaerotilus natans. S. natans was able to grow alone on casamino acids but strain TB was not. Cocultivation of strain TB and S. natans was examined in a medium supplemented with casamino acids as a growth substrate. The growth of strain TB was observed when the sheath was supplied to the medium or in cocultivation with S. natans. The phospholipid amount reached a maximum after 24 h of cocultivation and subsequently kept almost the same level for 96 h. The sheath amount also reached a maximum after 24 h and then gradually declined. The cell concentration of strain TB increased throughout the cocultivation. By competitive PCR targeted for amplification of a part of 16S rDNA, the abundance ratio (S. natans/strain TB) of 6.7 was obtained at 72 h. Almost no growth of strain TB was detected in a coculture with a sheath-less mutant of S. natans. The evidence allows the conclusion that strain TB grew by utilizing the intact sheath in coculture with S. natans.


Oral melanoacanthoma: a case report, a review of the literature, and a new treatment option.
Oral melanoacanthoma is a rare condition that presents as a pigmented, painful lesion, most commonly on the buccal mucosa. Argon plasma coagulation is a new treatment option for benign oral lesions and is hypothesized to be efficacious for this rare mucosal disorder. Treatment of a case and a review of the English-language literature were performed. One patient received a diagnosis of oral melanoacanthoma, and argon plasma coagulation treatment resulted in ablation of the lesion with excellent mucosal healing. A review of the literature demonstrated that this lesion is most commonly associated with black (90.9%), adult female (69.7%) patients and is most commonly located on the buccal mucosa (64.7%). Oral melanoacanthoma is a rare, benign mucosal lesion that may require surgical intervention for symptomatic relief. Argon plasma coagulation is a relatively safe and effective means of treating this lesion. Argon plasma coagulation treatment may be expanded to include other benign, superficial lesions of the oral mucosa.


Detection of novel papillomaviruses in canine mucosal, cutaneous and in situ squamous cell carcinomas.
Papillomavirus (PV) DNA is frequently uncovered in samples of human skin squamous cell carcinomas (SCC). However, the role of these viruses in the development of such cancers in canine species remains controversial. While approximately 100 human PVs are known, only one single canine oral PV (COPV) has been identified and studied extensively. Therefore, we applied a narrow-range polymerase chain reaction (PCR) suitable for the detection of classical canine and feline PVs, as well as a broad-range PCR, which has been used for the detection of various novel PVs in humans, in order to analyse 42 paraffin-embedded samples, representing three different forms of canine SCCs. Ten samples of skin tissues with various non-neoplastic conditions served as controls. While none of the negative controls reacted positively, PV DNA was discovered in 21% of the tested SCC samples. Interestingly, the classical COPV was amplified from only one sample, while the other positive cases were associated with a variety of thus far unknown PVs. This study suggests that a fraction of canine SCC is infected with PVs and that a genetic variety of canine PVs exists. Therefore, these results will facilitate the future study of the role of PVs in the development of canine skin cancers.


Pure red cell aplasia--evidence for an inhibitory action of the bone marrow adherent cell layer.
Evidence is presented for an inhibitory action of the bone marrow adherent cell layer on erythropoiesis in a case of pure red cell aplasia. Cultures of the patient's bone marrow with autologous and normal plasma showed normal numbers of CFU-C, but total absence of BFU-E. There was no inhibition of BFU-E when normal bone marrow was cultured with the patient's plasma. T-cell depletion of the patient's bone marrow did not affect these results, but after removal of the adherent cells, normal numbers of BFU-E were cultured. These observations suggest that the adherent cells, which are predominantly macrophages, were responsible for the inhibitory action on erythropoiesis.


Pregnant women quit smoking; what about fathers? Survey study in Bursa Region, Turkey.
To evaluate maternal and paternal smoking habits during pregnancy and determine their correlation with pregnancy complications and newborn status. The study included 499 pregnant women who delivered at the Department of Obstetrics and Gynecology in Uludag University School of Medicine, over a period of one year. Women were interviewed about their smoking habits before and during pregnancy. They were also asked about the smoking habits of their spouses. The relationship between smoking habits and pregnancy complications and newborn status was researched. The outcomes measured included pregnancy complications, gestational age at the onset of labor, Apgar scores during labor, and fetal birth weight and height. The percentage of maternal smoking before pregnancy was 26.5% (n=132) and decreased to 9.8% (n=49) at the end of pregnancy, with 52.5% (n=262) of the fathers who continued to smoke at home during their wife's pregnancy. Low birth weight and preterm delivery rate were significantly higher in maternal (n=15 [30.6%], and n=12 [24.5%], respectively) and paternal smoking groups (n=52 [22.4%] and n=54 [23.3%], respectively). Paternal smoking had no effect on intrauterine growth retardation (n=10 [4.3%]) and prenatal death (n=4 [1.7%]), although maternal smoking had such an effect (n=7 [14.3%] and n=3 [6.1%], respectively). Maternal smoking is a major risk factor for preterm delivery, low birth weight, intrauterine growth retardation, and intrauterine death, but paternal smoking also carries risk for the fetus. During perinatal care, we should educate the expectant parents about the side effects, not only of maternal, but also of paternal smoking.


Horizontal transfer of OC1 transposons in the Tasmanian devil.
There is growing recognition that horizontal DNA transfer, a process known to be common in prokaryotes, is also a significant source of genomic variation in eukaryotes. Horizontal transfer of transposable elements (HTT) may be especially prevalent in eukaryotes given the inherent mobility, widespread occurrence, and prolific abundance of these elements in many eukaryotic genomes. Here, we provide evidence for a new case of HTT of the transposon family OposCharlie1 (OC1) in the Tasmanian devil, Sarcophilus harrisii. Bioinformatic analyses of OC1 sequences in the Tasmanian devil genome suggest that this transposon infiltrated the common ancestor of the Dasyuridae family ~17 million years ago. This estimate is corroborated by a PCR-based screen for the presence/absence of this family in Tasmanian devils and closely-related species. This case of HTT is the first to be reported in dasyurids. It brings the number of animal lineages independently invaded by OC1 to 12, and adds a fourth continent to the pandemic-like pattern of invasion of this transposon. In the context of these data, we discuss the evolutionary history of this transposon family and its potential impact on the diversification of marsupials.


SNAP25 and GAP-43 behave differently in decentralized rat superior cervical ganglia.
The behaviour of synaptosome associated protein of mol. wt 25 kDa (SNAP25) in decentralized rat superior cervical ganglia (SCG) was investigated in order to observe its possible involvement in adrenergic postganglionic neuronal plasticity. Immunofluorescence and immunoblot results showed that the protein was increased in the nerve terminals in irides 8 days after operation. The intra-ganglionic nerve terminals and nerve fibres differed in their content of GAP-43 and SNAP25: GAP-43, which could not be observed at 1 day, appeared at 3 days after cutting the cervical sympathetic trunk, whilst SNAP25-immunoreactive material was still undetectable at this time. Immunoblot data also showed that SNAP25 did not reach control levels at 3 and 8 days after decentralization, in contrast to GAP-43. This observation may imply that SNAP25 is rapidly transported to its functional destinations immediately after synthesis and is possibly mainly involved in the remodelling of long projection pathways.


Trigeminal trophic syndrome: an important simulator of discoid cutaneous lupus erythematosus - a case series.
Trigeminal trophic syndrome occurs secondary to trigeminal nerve injury, leading to anaesthesia and paraesthesia, with consequent vigorous facial skin manipulation and lesion production, simulating other facial diseases such as ulcerative discoid lupus erythematosus, tumours and other artificially produced lesions. Ulceration and destruction of the ala nasi is a typical feature besides scratching end excoriations in the cutaneous segment affected. In this series, we present the features of five patients with trigeminal trophic syndrome, highlighting possible confusion with cutaneous lupus. Differential diagnoses, including discoid lupus erythematosus, are discussed, as well as possible treatment modalities.


A STE12 homologue of the homothallic ascomycete Sordaria macrospora interacts with the MADS box protein MCM1 and is required for ascosporogenesis.
The MADS box protein MCM1 controls diverse developmental processes and is essential for fruiting body formation in the homothallic ascomycete Sordaria macrospora. MADS box proteins derive their regulatory specificity from a wide range of different protein interactions. We have recently shown that the S. macrospora MCM1 is able to interact with the alpha-domain mating-type protein SMTA-1. To further evaluate the functional roles of MCM1, we used the yeast two-hybrid approach to identify MCM1-interacting proteins. From this screen, we isolated a protein with a putative N-terminal homeodomain and C-terminal C2/H2-Zn2+ finger domains. The protein is a member of the highly conserved fungal STE12 transcription factor family of proteins and was therefore termed STE12. Furthermore, we demonstrate by means of two-hybrid and far western analysis that in addition to MCM1, the S. macrospora STE12 protein is able to interact with the mating-type protein SMTA-1. Unlike the situation in the closely related heterothallic ascomycete Neurospora crassa, deletion (Delta) of the ste12 gene in S. macrospora neither affects vegetative growth nor fruiting body formation. However, ascus and ascospore development are highly impaired by the Deltaste12 mutation. Our data provide another example of the functional divergence within the fungal STE12 transcription factor family.


[Arctic and southern freshwater pearl mussel Margaritifera margaritifera with long and short life span as a model system for testing longevity mechanisms].
The freshwater pearl mussel (Margaritifera margartifera) is one of the longest lived animals, attaining ages in excess of 150 years in polar climates. Because of its long life, the species may be useful for studying genetic and physiological mechanisms contributing to longevity. An ongoing study is comparing 6 southern populations in Spain, with maximum recorded ages of 28-40 years, to 3 Arctic populations in northwest Russia, with maximum ages of 114-190 years. Within Arctic populations, 40% of mussels live more than 100 years in rivers that are pristine. Possible evolutionary significance of northern longevity is an adaptation to severe cold and unstable environments in high gradient rivers. During winter, mussels have a near-famine existence during the Polar Night, and experience some shell damage from ice formation and flows. In summer, periodic droughts result in exposure and desiccation. In response to adversity, pearl mussels have acquired effective mechanisms for shell reparation and tissue healing and regeneration. Northern populations have low metabolic rates, reducing energy expenditure for growth under normal as well as extreme conditions. However, this species is capable of increasing metabolic rate for tissue regeneration and self-healing. The physiological adaptations to sustain longevity may provide useful clues to impedence of the aging process.


Altruism or nationalism? Exploring global discourses of medical school regulation.
Although medical school regulation is ubiquitous, the extent to which it should be based on global principles is unclear. In 2010, the Educational Commission for Foreign Medical Graduates (ECFMG) announced that from 2023, overseas doctors would only be eligible for certification to practise in the United States if they had graduated from a medical school that was accredited by a 'recognised' agency. This policy empowered the World Federation for Medical Education (WFME) to create a recognition programme for regulatory agencies around the world, despite a lack of empirical evidence to support medical school regulation. This study employs critical discourse analysis, drawing on the theoretical perspectives of Michel Foucault and Edward Said, to identify discourses that enabled this 'globalising' policy decision to take place. The dataset includes a series of 250 documents gathered around three key events: the Edinburgh declaration by WFME in 1988, the first set of global standards for medical schools by WFME in 2003 and the ECFMG ruling about medical school accreditation in 2010. Two discourses, endorsement and modernisation, were dominant throughout this entire period and framed the move to globalise medical school regulation in terms of altruism and improving medical education worldwide. A discourse of resistance was present in the earlier period of this study but faded away as WFME aligned itself with ECFMG after 2010. Two further discourses, protection and control, emerged in the later period of this study and framed the ECFMG ruling in terms of nationalism and protecting American interests. This study proposes a new conceptualisation of the relationship between ECFMG and WFME in light of the apparently contradictory policy motivations of altruism and nationalism. It goes on to consider the implications of this association for the legitimacy of WFME as an organisation that represents all of the world's medical schools.


FDG-PET imaging in the management of non-small-cell lung cancer.
Lung cancer is currently the leading cause of cancer-related death in both men and women in most Western countries. Tumour stage is the strongest prognostic factor and the most important parameter guiding treatment decision making. Metabolic positron emission tomography imaging with fluorodeoxyglucose (FDG-PET) has consistently proved superior to conventional imaging for staging of non-small-cell lung cancer and provides information of greater prognostic significance than can be obtained using conventional approaches. FDG-PET has been approved in the USA, Germany and the UK as a basic and invaluable tool in the management of lung cancer.


Intake of Animal Protein Blend Plus Carbohydrate Improves Body Composition With no Impact on Performance in Endurance Athletes.
The impact of animal protein blend supplements in endurance athletes is scarcely researched. The authors investigated the effect of ingesting an admixture providing orange juice and protein (PRO) from beef and whey versus carbohydrate alone on body composition and performance over a 10-week training period in male endurance athletes. Participants were randomly assigned to a protein (CHO + PRO, n = 15) or a nonprotein isoenergetic carbohydrate (CHO, n = 15) group. Twenty grams of supplement mixed with orange juice was ingested postworkout or before breakfast on nontraining days. Measurements were performed pre- and postintervention on body composition (by dual-energy X-ray absorptiometry), peak oxygen consumption (V˙O2peak), and maximal aerobic speed. Twenty-five participants (CHO + PRO, n = 12; CHO, n = 13) completed the study. Only the CHO + PRO group significantly (p < .05) reduced whole-body fat (mean ± SD) (-1.02 ± 0.6 kg), total trunk fat (-0.81 ± 0.9 kg), and increased total lower body lean mass (+0.52 ± 0.7 kg), showing close to statistically significant increases of whole-body lean mass (+0.57 ± 0.8 kg, p = .055). Both groups reduced (p < .05) visceral fat (CHO + PRO, -0.03 ± 0.1 kg; CHO, -0.03 ± 0.5 kg) and improved the speed at maximal aerobic speed (CHO + PRO, +0.56 ± 0.5 km/hr; CHO, +0.35 ± 0.5 km/hr). Although consuming animal protein blend mixed with orange juice over 10 weeks helped to reduce fat mass and to increase lean mass, no additional performance benefits in endurance runners were observed.


(T2AG3)n telomeric sequence hybridization indicating centric fusion rearrangements in the karyotype of the rodent oryzomys subflavus.
Chromosome preparations of 30 specimens of Oryzomys subflavus trapped in eight Brazilian localities were C-, and G-banded and analyzed by fluorescence in situ hybridization (FISH). Two karyotypes were found, 2n = 50/FN = 64, at three coastal localities of the Atlantic Forest domain, and 2n = 58/FN = 70 at two sites located in the Cerrado biome, Brazil Central. Two fluorescence in situ hybridization (FISH) patterns of the telomeric sequence (T2AG3)n were observed: in both karyotypes the probes hybridized to the telomeres of all chromosomes and also a hybridization signal in the centromeric regions of two autosome pairs was seen in the 2n = 50 karyotype. These results, together with the occurrence of other diploid numbers described in the literature, suggest that 0. subflavus is a complex species, bearing fusion/fission rearrangements proper to the different biomes which it inhabits.


DELFOS-drug efficacy leveraging forked and specialized networks-benchmarking scRNA-seq data in multi-omics-based prediction of cancer sensitivity.
Cancer is currently one of the most notorious diseases, with over 1 million deaths in the European Union alone in 2022. As each tumor can be composed of diverse cell types with distinct genotypes, cancer cells can acquire resistance to different compounds. Moreover, anticancer drugs can display severe side effects, compromising patient well-being. Therefore, novel strategies for identifying the optimal set of compounds to treat each tumor have become an important research topic in recent decades. To address this challenge, we developed a novel drug response prediction algorithm called Drug Efficacy Leveraging Forked and Specialized networks (DELFOS). Our model learns from multi-omics data from over 65 cancer cell lines, as well as structural data from over 200 compounds, for the prediction of drug sensitivity. We also evaluated the benefits of incorporating single-cell expression data to predict drug response. DELFOS was validated using datasets with unseen cell lines or drugs and compared with other state-of-the-art algorithms, achieving a high prediction performance on several correlation and error metrics. Overall, DELFOS can effectively leverage multi-omics data for the prediction of drug responses in thousands of drug-cell line pairs. The DELFOS pipeline and associated data are available at github.com/MoreiraLAB/delfos.


Irrigation scheduling for potatoes (Solanum tuberosum L.) under drip irrigation in an arid region using AquaCrop model.
Potato is one of the key food crops and China is the largest potato producer in the world. However water scarcity is the major constraint to increase the productivity of potato in the arid regions such as Ningxia in northwest China where this crop is extensively cultivated. The overall objective of this study was to optimize the irrigation for potato cultivated under the drip irrigation. To do this, the AquaCrop model was calibrated and validated using the data obtained from two years of field experiment. Then, the calibrated crop model was used to simulate growth and tuber yield of potato in response to 30 different irrigation schemes under two different irrigation scenarios. The crop model evaluation parameters namely, the root mean square error (RMSE), the index of agreement (d), the normalized root mean square error (NRMSE) and the coefficient of determination (R2) showed that the AquaCrop model could simulate the growth and yield of potato under the drip irrigation with different irrigation treatments with reasonable accuracy. Furthermore, yield of potato has increased with increasing amount of total irrigation under drip irrigation; however, yield begins to decline when the amount of total irrigation exceeds 2500 m3 ha-1. The study also found that the optimum irrigation schedule for potato was 20 mm of irrigation quota at 7 days of irrigation cycle (i.e., 1800 m3 ha-1 or 180 mm of total irrigation). The above irrigation scheduling has achieved 46.77 t ha-1 of tuber yield with 15.74 kg m-3 of water use efficiency. These findings may be evaluated in potato cultivation across different climate and soil conditions for wide applicability at different arid regions of the world.


Fecal calprotectin levels used as a noninvasive method for screening for chronic gastritis in pediatric patients. A descriptive study.
Gastritis consists of inflammation of the gastric mucosa and is one of the main causes of dyspeptic symptoms in children. To investigate the presence of inflammation by evaluating fecal calprotectin (FC) in children diagnosed with chronic gastritis. Descriptive study in Pediatric Gastroenterology Department of Ondokuz Mayis University Hospital in Turkey. Between January 2016 and July 2018, FC levels were compared retrospectively in children with chronic gastritis (histopathology-based diagnosis), patients with inflammatory bowel disease (IBD) and healthy children. A total of 67 chronic gastritis patients (61.2% girls) with a mean age of 13.09 ± 3.5 years were evaluated. The mean FC levels were 153.4 μg/g in the chronic gastritis group, 589.7 μg/g in the IBD group and 43.8 μg/g in the healthy group. These levels were higher in chronic gastritis patients than in healthy individuals (P = 0.001) and higher in IBD patients than in the other two groups (P < 0.001). The FC level in the patients with chronic active gastritis (156.3 μg/g) was higher than in those with chronic inactive gastritis (150.95 μg/g) (P = 0.011). Among the patients with chronic active gastritis, the FC level was significantly higher in Helicobacter pylori-positive individuals than in negative individuals (P = 0.031). We confirmed the association between increased FC and chronic gastritis. Elevated FC levels may be seen in patients with chronic active gastritis. In order to be able to use FC as a screening tool for chronic gastritis, further studies in a larger study group are needed.


Significant impact of the MTHFR polymorphisms and haplotypes on male infertility risk.
Methylenetetrahydrofolate reductase (MTHFR) converts 5,10-methylene tetrahydrofolate to 5-methyl tetrahydrofolate and affects the activity of cellular cycles participating in nucleotide synthesis, DNA repair, genome stability, maintenance of methyl pool, and gene regulation. Genetically compromised MTHFR activity has been suggested to affect male fertility. The objective of the present study was to find the impact on infertility risk of c.203G>A, c.1298A>C, and c.1793G>A polymorphisms in the MTHFR gene. PCR-RFLP and DNA sequencing were used to genotype the common SNPs in the MTHFR gene in 630 infertile and 250 fertile males. Chi-square test was applied for statistical comparison of genotype data. Linkage disequilibrium between the SNPs and the frequency of common haplotypes were assessed using Haploview software. Biochemical levels of total homocysteine (tHcy) and folic acid were measured. Meta-analysis on c.1298A>C polymorphism was performed using data from ten studies, comprising 2734 cases and 2737 controls. c.203G>A and c.1298A>C were found to be unrelated to infertility risk. c.1793G>A was protective against infertility (P = 0.0008). c.677C>T and c.1793G>A were in significant LD (D' = 0.9). Folic acid and tHcy level did not correlate with male infertility. Pooled estimate on c.1298A>C data from all published studies including our data showed no association of this polymorphism with male infertility (Odds ratio = 1.035, P = 0.56), azoospermia (Odds ratio = 0.97, P = 0.74), or oligoasthenoteratozoospermia (Odds ratio = 0.92, p = 0.29). Eight haplotypes with more than 1% frequency were detected, of which CCGA was protective against infertility (p = 0.02), but the significance of the latter was not seen after applying Bonferroni correction. Among MTHFR polymorphisms, c.203G>A and c.1298A>C do not affect infertility risk and c.1793G>A is protective against infertility. Haplotype analysis suggested that risk factors on the MTHFR locus do not extend too long on the DNA string.


T-cell activation through the antigen receptor. Part 1: signaling components, signaling pathways, and signal integration at the T-cell antigen receptor synapse.
Part 1 of this review will highlight the basic components and signaling pathways by which the T-cell antigen receptor (TCR) activates mature extrathymic T cells. TCR signaling commences with an early wave of protein tyrosine kinase activation, which is mediated by the Src kinases Lck and Fyn, the 70-kd zeta-associated protein kinase, and members of the Tec kinase family. This early wave of protein tyrosine phosphorylation leads to the activation of downstream signaling pathways, including an increase in intracellular free calcium, protein kinase C, nuclear factor kappaB and Ras-mitogen-activated protein kinase activation. These pathways activate transcription factors, such as activator protein 1, nuclear factor of activated T cells, and Rel proteins, which ultimately lead to the expression of genes that control cellular proliferation, differentiation, anergy, or apoptosis. This review also describes how costimulatory receptors assist in signal transduction and assembly of macromolecular complexes at the TCR contact site with the antigen-presenting cell, also known as the immune synapse. These basic concepts of TCR signal transduction will be used in part 2 to explain how T-cell function can be altered by therapeutic targeting of TCR signaling components, as well as to explain modification of TCR signaling during T(H)1/T(H)2 differentiation, tolerance, and immune senescence.


Apelin ameliorates TNF-α-induced reduction of glycogen synthesis in the hepatocytes through G protein-coupled receptor APJ.
Apelin, a novel adipokine, is the specific endogenous ligand of G protein-coupled receptor APJ. Consistent with its putative role as an adipokine, apelin has been linked to states of insulin resistance. However, the function of apelin in hepatic insulin resistance, a vital part of insulin resistance, and its underlying mechanisms still remains unclear. Here we define the impacts of apelin on TNF-α-induced reduction of glycogen synthesis in the hepatocytes. Our studies indicate that apelin reversed TNF-α-induced reduction of glycogen synthesis in HepG2 cells, mouse primary hepatocytes and liver tissues of C57BL/6J mice by improving JNK-IRS1-AKT-GSK pathway. Moreover, Western blot revealed that APJ, but not apelin, expressed in the hepatocytes and liver tissues of mice. We found that F13A, a competitive antagonist for G protein-coupled receptor APJ, suppressed the effects of apelin on TNF-α-induced reduction of glycogen synthesis in the hepatocytes, suggesting APJ is involved in the function of apelin. In conclusion, we show novel evidence suggesting that apelin ameliorates TNF-α-induced reduction of glycogen synthesis in the hepatocytes through G protein-coupled receptor APJ. Apelin appears as a beneficial adipokine with anti-insulin resistance properties, and thus as a promising therapeutic target in metabolic disorders.


[Trans-septal catheterization. Technic and indications].
We report our experience with transseptal catheterization of the left side of the heart via the right femoral vein. This technique was attempted in 50 patients undergoing left heart catheterization for hemodynamic evaluation of aortic valve stenosis (15 patients) and prosthetic valves (35 patients). The importance of some manoeuvres, especially within the right atrium, to avoid some of the most usual complications, like cardiac or aortic perforations, intramyocardial injection of contrast medium, and embolization of left atrial masses, is underlined.


Effects of dobutamine on isovolumic and ejection phase indices of cardiac contractility in conscious healthy dogs.
The aim of this study was to determine cardiac contractility using indices derived from cardiac catheterisation in conscious healthy dogs during dobutamine infusion. Eight dogs were studied. An ECG was recorded together with left ventricular pressure and volume which were measured using a conductance catheter with an integrated microtip pressure sensor. Eight indices of left ventricular systolic performance were derived from these records. Measurements were realised under basal conditions and during an incremental dobutamine challenge. The maximal rate of rise in ventricular pressure (max dP/dt), max dP/dt divided by the developed pressure and the mean systolic ejection rate were the most sensitive indices to detect dobutamine induced changes in contractility with maximal percentage changes of 122+/-11 per cent, 130+/-7 per cent and 102+/-24 per cent respectively. Ejection fraction increased significantly during dobutamine infusion (maximal percentage change of 43+/-9 per cent) whereas the pre-ejection period (PEP) and the left ventricular ejection time (LVET) decreased significantly (maximal percentage change of -41+/-2 per cent and -28+/-3 per cent respectively). All these six indices were significantly correlated with each other. Conversely, the ratio PEP/LVET and the LVET corrected for heart rate dependency showed a maximal percentage change of only -10+/-1 per cent and -16+/-7 per cent, respectively, during the dobutamine infusion and were not significantly correlated with the other contractility indices. This study demonstrated the feasibility of the conductance method to determine cardiac contractility in conscious healthy dogs submitted to a pharmacological stress testing and provides control values for eight indices of left ventricular contractility during dobutamine infusion at increasing dosages.


Promoting Patient Safety Through Effective Health Information Technology Risk Management.
The potential for health information technology (IT) to improve health care delivery has been appreciated for decades, but "digitizing" health care can also introduce new risks and even harm. As the use of health IT has grown, these risks have become more apparent. The authors of this report evaluated the efforts of 11 hospitals and ambulatory practices to use an improvement strategy and tools developed to promote safe use of health IT and to diagnose, monitor, and mitigate health IT-related safety risks. Through interviews, the authors discovered that some health care organizations (especially hospitals) with expertise in process improvement were able to identify and begin to mitigate health IT-related safety risks, but in most others, awareness of these risks was limited (especially in ambulatory practices). The authors concluded that better tools like the recently released Safety Assurance Factors for EHR Resilience (SAFER) Guides are needed to help organizations optimize the safe use of health IT. However, health care organizations will require a better understanding of the safety risks posed by electronic health record (EHR) use to take full advantage of the SAFER Guides. There may also be a need for additional tools and metrics (and further usability studies of existing tools and metrics) to better support the needs of health care organizations as they increasingly rely on health IT to improve the quality and safety of patient care.


In vivo transcription from multiple spacer rRNA gene promoters during early development and evolution of the intergenic spacer in the brine shrimp Artemia.
The control of ribosomal RNA (rRNA) gene expression during development can be productively studied by examination of the relationship between promoter structure and function as well as the processing of primary transcripts. Toward this end total cell RNA was extracted from embryos at various stages and probed with cloned rRNA genes using the "dot blot" method. This exercise showed that rRNA gene expression is a stage-specific process and is thus under developmental control. S1 nuclease protection experiments localized fourteen different upstream DNA sites encoding 5'-termini of pre-rRNAs during this synthetic phase of development. There is no indication of any spacer fail-safe terminator function. The S1 approach contributed to the sequencing of several of the sites. Comparative sequence alignments reveal short conserved regions in DNAs corresponding to these sites, which are shown to fall into two structural classes. Sites 3, 4, 6 and 9 are proposed to function in transcription initiation and are found to have the consensus sequence 5'...T-A-T-A-T-Pu-Pu-Pu-G-Pu-Pu-G-T-C-A 3'. Sites 1, 2, 5 and 8 which are proposed to function in 5'-processing have the consensus sequence; 5'...Pu-G-T-Pu-T-T-G 3'. These short sequence conserved regions are hypothesized to serve as recognition signals for proteins within the rDNA transcription initiation complex and for 5'-processing enzymes, respectively. Sequencing of the intergenic spacer region from which a model for spacer evolution is derived shows that tandem ca 600 bp subrepeats explain much of the multiplicity observed within control sites.


Prevalence and Histopathologic Study of Lernaea cyprinacea in Two Species of Ornamental Fish (Poecilia latipinna and Xiphophorus helleri) in Kerman, South-East Iran.
Lernaeids are crustacean parasites that are globally distributed among freshwater and marine fish. Approximately 110 species of Lernaeids have been divided into 14 genera. The most common species of Lernaeids is Lernaea cyprinacea, which has been transmitted to ornamental fish worldwide. The economic importance of L. cyprinacea is increasing because of the epidemic caused by the parasite in most of the ornamental fish breeding centers in different parts of the world. The parasite affects its host's health, decreases growth rate, and causes abnormal metabolic activity. Accumulation of these parasites in some parts of the body causes painful points and has harmful outcomes for the functioning and survival of the host. The present study was conducted to examine the prevalence of L. cyprinacea among ornamental fish within 1 year from September-October 2011 to September-October 2012. In total, 3520 fish [3380 mollies (Poecilia latipinna) and 140 swordtails (Xiphophorus helleri)] were collected from 10 fish maintenance and breeding centers in Kerman, Iran. Of 3520 fish, only 186 fish (5.3%) were infected with L. cyprinacea, and the remaining fish (94.7%) were not infected. The swordtails (X. helleri) and mollies (P. latipinna) showed the highest (10.7%) and the lowest (5.1%) level of infection, respectively. In other words, there was a significant correlation between species of fish and L. cyprinacea infection (p<0.05). The highest prevalence (39.4%) and the lowest prevalence (0%) of L. cyprinacea were observed during summer and winter, respectively, which can be attributed to the temperature difference between the two seasons. Also, the histopathologic examination of sections revealed some lesions in the epidermis, dermis, and muscles. Considering the existing L. cyprinacea infection in ornamental fish reproduction and breeding centers in Kerman, public knowledge should increase through management methods; physical and chemical treatments should also be applied to inform the public regarding the risk of infection and other internal diseases that may be associated with ornamental fish.


Glucagon and plasma catecholamines during beta-receptor blockade in exercising man.
Seven men ran at 60% of individual maximal oxygen uptake to exhaustion during beta-adrenergic blockade with propranolol (P), during lipolytic blockade with nicotinic acid (N), or without drugs (C). The total work times (83 +/- 9 (P), 122 +/- 8 (N), 166 +/- 10 (C) min, mean and SE) differed significantly. Epinephrine rose progressively above preexercise levels (0.06 +/- 0.01 ng/ml); at exhaustion concentrations in P experiments (2.15 +/- 0.41) were larger than in N (1.08 +/- 0.31) and C (0.72 +/- 0.28) experiments. Norepinephrine increased consistently while insulin decreased. After an initial decrease glucagon concentrations increased progressively in parallel with declining plasma glucose and were at exhaustion always three times preexercise values. Thus beta-adrenergic blockade did not diminish the glucagon response. Nor was this response increased when alpha-receptor stimulation in P experiments was intensified. Carbohydrate combustion was smaller and NEFA and glycerol concentrations in serum larger during C experiments. Alanine concentrations were never raised at exhaustion. Accordingly, neither stimulation of adrenergic receptors nor NEFA and alanine concentrations are major determinants for the exercise-induced glucagon secretion in man. It is suggested that decreased glucose availability enhances the secretion of glucagon and epinephrine during prolonged exercise.


A spectral sampling algorithm in dynamic causal modelling for resting-state fMRI.
Resting-state functional magnetic resonance imaging (rs-fMRI) is widely utilized to study the directed influences among neural populations which were called effective connectivity (EC), and the spectral dynamic causal modelling (spDCM) is the state-of-the-art framework to identify them. However, spDCM used variational Laplace to approximate the posterior density by maximizing the free energy, which might underestimate the variability of posterior density and get locked to the local minima. A spectral sampling algorithm (SS-DCM) was proposed to improve the estimation accuracy of the dynamic causal model for rs-fMRI. In SS-DCM, a naïve Bayesian model was constructed in the spectral domain, which described the probabilistic relationship between the sampled parameters and cross spectra of the observed blood oxygen level-dependent signals, and the parameters were sampled using randomly walked Markov Chain Monto Carlo scheme. The root mean square errors of the estimation of EC and hemodynamic parameters of SS-DCM, spDCM and generalized filter scheme were compared in the synthetic data, and SS-DCM was the most accurate and stable. A comparative evaluation using empirical rs-fMRI data was performed to study the EC pattern of the default mode network and compare the accuracy of classification between typically developed subjects and inattentive attention deficit and hyperactivity disorder patients. The results showed high consistency of positivity and negativity of EC between spDCM and SS-DCM, and SS-DCM also provided higher classification accuracy. It is highlighted that SS-DCM improves the accuracy of the estimation of EC and provides accurate information of discrepancies between diseased and healthy subjects using rs-fMRI.


Three new naphthalenyl glycosides from the root bark of Juglans cathayensis.
Phytochemical investigations of the root bark of Juglans cathayensis DODE. led to the isolation of three new naphthalenyl glycosides, Jugnaphthalenoside A-C (1-3). Their structures were elucidated on the basis of extensive analysis of spectroscopic data. The cytotoxicities of the three new compounds were also evaluated.


Oxalate excretion during the first 7 weeks in very-low-birth-weight infants.
To determine reference values, we studied urinary excretion of oxalate prospectively and longitudinally in a cohort of 23 very-low-birth-weight (VLBW) infants. The urinary oxalate concentrations were evaluated in 24-hour urine samples by the oxalate oxidase method. Urine samples were obtained at 1, 2-3, 4-5 and 6-7 weeks of age. The median oxalate amount was 24 mumol/kg body weight/day with a 10th-90th percentile range of 16-45 in the 1st week. Oxalate excretion was highest in 2- to 3-week-old infants (median: 35; percentile range: 26-56 mumol/kg body weight/day). In the 4th-5th week, the median was 24 (percentile range: 15-47) mumol/kg body weight/day and in weeks 6-7 also 24 (percentile range: 10-36) mumol/ kg body weight/day. Also, the urinary oxalate concentration as well as the oxalate-creatinine ratio showed increased values in the first 3 weeks of life and decreased values afterwards. In a multivariate analysis, nutrition or gestational age did not affect the urinary oxalate concentration, the daily amount excreted or the oxalate-creatinine ratio. The investigated parameters (oxalate amount and oxalate-creatinine ratio in urine) were significantly age dependent). The data show that urinary oxalate excretion in VLBW infants approaches levels that are in the same range as those of patients with urolithiasis. Thus the risk of nephrocalcinosis in VLBW infants may be increased.


Effects of duration of capture and sample handling on critical care blood analytes in free-ranging bottlenose dolphins.
To determine effects of duration of capture and sample-handling procedures on blood analytes in free-ranging bottlenose dolphins. Cross-sectional study. 154 free-ranging bottlenose dolphins of various ages and both sexes. Blood samples were drawn from each dolphin within 10 minutes of capture and before release and analyzed by use of a portable analyzer with a single-use 8-analyte disposable cartridge. Analyte values were compared according to duration between sample acquisition and analysis (time to run [TTR]) and duration between net encirclement and sample acquisition (time to bleed [TTB]). Neither TTB nor TTR significantly affected sodium or chloride concentration. Potassium concentration was not significantly affected by TTR, whereas the effect of TTB was significant. Glucose, total CO(2), HCO(3), Hct, and base excess of extracellular fluid values were significantly affected by TTR. Increased TTB resulted in significantly increased total CO(2), HCO(3), and base excess when TTR was kept within 10 minutes. The effect of TTB on certain acid-base and electrolyte values was readily measured in free-ranging bottlenose dolphins, and such values may provide a reference range for those variables.


Can lumbar paraspinal muscle/fat ratio and spinopelvic parameters predict short-term outcomes after decompressive surgeries in lumbar disc herniation and lumbar spinal stenosis?
We aimed to investigate whether the lumbar paraspinal muscle/fat ratio influences the outcomes of patients who had simple decompressive surgeries for lumbar disc herniation (LDH) or lumbar spinal stenosis. We also wanted to see if the spinopelvic parameters change with surgery and whether this change influences the outcomes. This was a prospective study on patients with lumbar spinal stenosis (20 patients) and LDH (20 patients) who underwent simple discectomy or decompressive surgery between November 2021 and May 2022. Visual Analog Scale (VAS) for back and leg pain, Oswestry Disability Index, and Japanese Orthopedic Association (JOA) score were performed before and 3 months after surgery. Spinopelvic parameters were measured on whole spine radiographs before and 3 months after surgery. On axial magnetic resonance images, paraspinal muscle volume and muscle/fat ratios were calculated. All data were statistically analyzed with SPSS program. There was a significant improvement in VAS, Oswestry, and JOA scores after surgery. We observed that more preoperative paraspinal muscle mass was positively correlated with lumbar lordosis (LL) and negatively correlated with sagittal vertical axis (SVA), VAS leg scores, and Oswestry scores. Furthermore, we observed a positive correlation between preoperative SVA and VAS leg scores. Despite limited number of patients, and shorter follow-ups, this prospective study demonstrates a correlation among the lumbar paraspinal muscle/fat ratio, preoperative/postoperative spinopelvic parameters, and surgical outcomes. Increased paraspinal muscle ratio was correlated with lower SVA values and increased LL; lower VAS leg scores; higher Oswestry scores which reflects better surgical outcomes.


Enhanced efficacy of an AAV vector encoding chimeric, highly secreted acid alpha-glucosidase in glycogen storage disease type II.
Glycogen storage disease type II (GSD-II; Pompe disease; MIM 232300) is an inherited muscular dystrophy caused by deficiency in the activity of the lysosomal enzyme acid alpha-glucosidase (GAA). We hypothesized that chimeric GAA containing an alternative signal peptide could increase the secretion of GAA from transduced cells and enhance the receptor-mediated uptake of GAA in striated muscle. The relative secretion of chimeric GAA from transfected 293 cells increased up to 26-fold. Receptor-mediated uptake of secreted, chimeric GAA corrected cultured GSD-II patient cells. High-level hGAA was sustained in the plasma of GSD-II mice for 24 weeks following administration of an AAV2/8 vector encoding chimeric GAA; furthermore, GAA activity was increased and glycogen content was significantly reduced in striated muscle and in the brain. Administration of only 1 x 10(10) vector particles increased GAA activity in the heart and diaphragm for >18 weeks, whereas 3 x 10(10) vector particles increased GAA activity and reduced glycogen content in the heart, diaphragm, and quadriceps. Furthermore, an AAV2/2 vector encoding chimeric GAA produced secreted hGAA for >12 weeks in the majority of treated GSD-II mice. Thus, chimeric, highly secreted GAA enhanced the efficacy of AAV vector-mediated gene therapy in GSD-II mice.


Wetting of nanopatterned grooved surfaces.
The wetting by perfluoromethylcyclohexane of a well-defined silicon grating with a channel width of 16 nm has been studied using transmission small angle x-ray scattering. Prefilling, capillary filling, and postfilling wetting regimes have been identified. A detailed comparison of the data with theory reveals the importance of long-ranged substrate-fluid and fluid-fluid interactions for determining the wetting behavior on these length scales, especially at the onset of capillary condensation and in the prefilling regime.


Wild-type levels of the mouse Forkhead Box f1 gene are essential for lung repair.
The Forkhead Box (Fox) family of transcription factors plays important roles in regulating expression of genes involved in cellular proliferation and differentiation. In a previous study, we showed that newborn foxf1(+/-) mice with diminished Foxf1 levels exhibited abnormal formation of pulmonary alveoli and capillaries and died postnatally. Interestingly, surviving newborn foxf1(+/-) mice exhibited increased pulmonary Foxf1 levels and normal adult lung morphology, suggesting that wild-type Foxf1 levels are required for lung development and function. The present study was conducted to determine whether adult foxf1(+/-) mice were able to undergo lung repair similar to that observed in wild-type mice. We demonstrated that adult foxf1(+/-) mice died from severe lung hemorrhage after butylated hydroxytoluene (BHT) lung injury and that this phenotype was associated with a 10-fold decrease in pulmonary Foxf1 expression and increased alveolar endothelial cell apoptosis that disrupted capillary integrity. Furthermore, BHT-induced lung hemorrhage of adult foxf1(+/-) mice was associated with a drastic reduction in expression of the Flk-1, bone morphogenetic protein-4, surfactant protein B, platelet endothelial cell adhesion molecule, and vascular endothelial cadherin genes, whereas the expression of these genes was either transiently diminished or increased in wild-type lungs after BHT injury. Because these proteins are critical for lung morphogenesis and endothelial homeostasis, their decreased mRNA levels are likely contributing to BHT-induced lung hemorrhage in foxf1(+/-) mice. Collectively, our data suggest that sustained expression of Foxf1 is essential for normal lung repair and endothelial cell survival in response to pulmonary cell injury.


Clinical utility of an LC-MS/MS seizure panel for common drugs involved in drug-induced seizures.
Approximately 6% of new-onset seizures are drug-related, but there is currently no reliable way to determine if a seizure is drug-induced. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) is a powerful tool that allows simultaneous detection of numerous analytes of diverse chemical nature in patient samples. This allows a single analysis to incorporate many compounds relevant to a particular clinical presentation, such as suspected drug-induced seizures. We investigated whether results from a seizure panel using LC-MS/MS could affect patient care. We developed a semiquantitative LC-MS/MS assay to detect 12 chemically diverse drugs implicated in drug-related seizures. We collected leftover serum and plasma samples from patients who had seized, performed solid-phase extraction, and analyzed the samples using a hybrid triple quadrupole/linear ion trap mass spectrometer. After assembling a team of medical and toxicology experts, we developed and used a scoring system to determine whether the results of the seizure panel would have affected patient treatment in each case where a drug was detected. In an analysis of 157 samples from patients who seized, 17 (11%) were found to be positive for a drug on the seizure panel. The team of experts determined that the test results probably or definitely would have affected treatment in 7 (41%) of these cases. A test that detects the presence of drugs implicated in drug-induced seizures can help physicians determine if an unexplained seizure is drug-related and thus potentially better direct patient care. Additionally, LC-MS/MS is an effective tool for answering clinically driven questions.


Inhibition difficulties in preterm children: Developmental delay or persistent deficit?
Among executive functions (EFs), research has highlighted specific inhibition difficulties in preterm children. The present paper reviews and classifies the studies that assessed response inhibition and interference control abilities in preterm children and adolescents aged 3 to 16 years. Most behavioral studies agree on a developmental delay at early school age in inhibition abilities and a catch-up before adolescence, with lesser response inhibition difficulties at pre-adolescence. However, persisting interference control difficulties have been reported into early adulthood. These results are discussed, along with functional magnetic resonance imaging (fMRI) findings. Finally, this paper outlines methodological issues that need to be overcome in order to define the developmental trajectory of inhibition abilities in the preterm population.


Role of tight junctions in signal transduction: an update.
Tight junctions (TJs), which are the most apically located of the intercellular junctional complexes, have a barrier function and a fence function. Recent studies show that they also participate in signal transduction mechanisms. TJs are modulated by intracellular signaling pathways including protein kinase C, mitogen-activated protein kinase, and NF-ϰB, to affect the epithelial barrier function in response to diverse stimuli. TJs are also regulated by various cytokines, growth factors, and hormones via signaling pathways. To investigate the regulation of TJ molecules via signaling pathways in human epithelial cells under normal and pathological conditions, we established a novel model of human telomerase reverse transcriptase-transfected human epithelial cells. In this review, we describe the recent progress in our understanding of the role of TJs for signal transduction under normal conditions in upper airway epithelium, pancreatic duct epithelial cells, hepatocytes, and endometrial epithelial cells, and in pathological conditions including cancer and infection.


Primed IN situ labelling (PRINS) as a rational procedure for identification of marker chromosomes using a panel of primers differentially tagging the human chromosomes.
PRimed IN Situ labelling (PRINS) is a highly specific and sensitive technique for detecting DNA sequences on human chromosomes in situ. PRINS is currently being introduced for research and routine analysis in clinical and cancer genetics. In this paper, we report a rational PRINS procedure for the rapid identification of marker chromosomes. Using this method it is possible to test a sample from a patient with up to eight different primers simultaneously on one slide. We have synthesized oligonucleotide primers that can differentially tag the human chromosomes, and with the protocol presented in this report we are able to identify the chromosomal origin of a marker chromosome within 2 hours.


Eating disorder not otherwise specified: the view from a tertiary care treatment center.
This study sought to characterize a large number of adult outpatients diagnosed with eating disorder not otherwise specified (EDNOS). The sample consisted of 1,449 patients who were classified as anorexia nervosa (AN), bulimia nervosa (BN), or assigned to one of six EDNOS categories. Eating disorder groups were compared on demographic features, symptom frequencies, and psychological functioning. Forty percent of the sample was categorized as EDNOS. A subgroup of purging only patients closely resembled the BN purging subtype. Although EDNOS subthreshold BN patients reported less psychopathology than full syndrome BN they, nevertheless, displayed clinical levels of disturbance. Patients who binge-eat once a week demonstrate a profile of psychological functioning similar to those who binge eat twice a week. Consistent with previous research, in this sample there were subgroups embedded in the EDNOS category that both share similarities with and differ from full syndrome BN.


Prevention of Plasmodium falciparum malaria by Fansimef and Lariam in the northeastern part of Thailand.
Two studies were conduct in Thailand in order to find appropriate falciparum malaria prophylactic drug regimens. The first study was done during June - September 1987 with 363 soldiers who received Fansimef (MSP) 1 tab/week (group 1), 337 soldiers who received MSP 1 tab/2 week (group 2) and 165 soldiers who received chloroquine 300 mg base weekly plus Fansidar 1 tab/week (group 3). At the end of the study there were 9 and 13 falciparum malaria episodes in groups 1 and 2, respectively, with incidence rates of 0.8 and 1.8 cases/100 person-months (P-M). In group 3, the corresponding values were 30 episodes and an incidence of 7.2/100 P-M. For the second study which lasted from October 1987 - January 1988 in the same area, 498 soldiers were given Fansimef 1/2 tab/week (group 4), 499 soldiers were given Lariam 1/2 tab/week (group 5) and 247 soldiers were given chloroquine plus Fansidar (group 6). Thirty malaria episodes were found in group 4, for an incidence of 2.0/100 P-M. In group 5, 23 episodes were found, for an incidence of 1.6/100 P-M. In group 6, 74 episodes occurred, ie an incidence of 12.2/100 P-M. The incidence rates of malaria among Fansimef 1 tab weekly, Fansimef half dose weekly or Lariam half dose weekly were not significantly different but were different from chloroquine plus Fansidar groups. Adverse events in each group were mild.


Isolation of DNTNP, which encodes a potential nuclear protein that is expressed in the developing, dorsal neural tube.
We have performed a screen to identify genes expressed in a functionally significant anatomic region of the vertebrate dorsal neural tube, the dorsomedial roof of the third ventricle (DMRTV). The DMRTV includes the primordia of a series of circumventricular organs. The screen searched for genes preferentially expressed in the DMRTV of stage 18-25 chicken embryos, relative to their telencephala and ventral diencephalon. Through this screen, we have cloned a series of genes strongly expressed in the dorsal but not ventral neural tube. We describe here the first of these genes, DNTNP (dorsal neural tube nuclear protein). DNTNP is highly expressed in the dorsal regions of the diencephalon, the midbrain, the hindbrain, and the spinal neural tube in the chicken stage 18 embryo. Expression is also observed in the telencephalon, the branchial arches, the heart, and somites, but is absent from the presomitic mesoderm. The amino acid sequence of DNTNP reveals that it belongs to an uncharacterized protein family with at least two additional members. All the members of this family possess a basic region reminiscent of a nuclear localization signal (NLS). We demonstrate that the putative NLS of DNTNP can indeed direct nuclear localization of green fluorescent protein (GFP). The dorsal localization of DNTNP in the early embryonic central nervous system suggests roles for this molecule in specifying dorsal cell fates within the neural tube.


[A tricho-odonto-onychial subtype of ectodermal dysplasia].
We report on a case of " uncombable hair syndrome" combined with additional hair changes ( peripilar casts), periodic shedding of nails, abnormality of teeth, dysplasia of the nipples , Morbus Scheuermann, and atopic disorders with specific IgE sensibilisation . Pili trianguli et canaliculi as well as peripilar casts were electron-microscopically examined. The presented case might be interpreted as a special tricho-odonto- onychial subtype of ectodermal dysplasia.


Increased serum levels of interleukin-8 in patients with tension-type headache.
The pathophysiology of tension-type headache is not well understood. Increased peripheral levels of pro-inflammatory cytokines may act as mediators of several chronic pain disorders. The aim of the present study was to investigate the peripheral levels of chemokines in patients with tension-type headache. This was a cross sectional study evaluating serum levels of chemokines in age and sex-matched tension-type headache patients, ictally and interictally, and control participants. Beck Depression and Anxiety Inventories were recorded. Serum levels of monocyte chemoattractant protein-1, macrophage inflammatory protein 1α, regulated on activation, normal T cell expressed and secreted, eotaxin, eotaxin-2, interleukin-8, interferon gamma induced protein-10 were measured by enzyme-linked immunosorbent assay. A total of 96 participants (48 tension-type headache, 48 controls) were included. Interleukin-8 levels were significantly increased in patients with tension-type headache when compared to controls (413.8 (123.4-1756.3) and 329 (107.8-955.6), respectively, P = 0.025). Anxiety and depression scores were higher in patients with tension-type headache but interleukin-8 increase in tension-type headache patients persisted after controlling for anxiety and depression symptoms. Patients with headache at the time of assessment had increased monocyte chemoattractant protein-1 levels when compared with patients without headache (2809.3 (1101-6122.2) and 1630.2 (669.3-31056.8), respectively P = 0.026). Patients with episodic and chronic tension-type headache had no significant differences in serum chemokines levels. Interleukin-8 was increased in tension-type headache and monocyte chemoattractant protein-1 was higher in tension-type headache patients with headache, suggesting that pro-inflammatory mechanisms may participate in tension-type headache pathophysiology.


Biocompatible Alginate Film Crosslinked with Ca2+ and Zn2+ Possesses Antibacterial, Antiviral, and Anticancer Activities.
Alginate is a highly promising biopolymer due to its non-toxic and biodegradable properties. Alginate hydrogels are often fabricated by cross-linking sodium alginate with calcium cations and can be engineered with highly desirable enhanced physical and biological properties for biomedical applications. This study reports on the anticancer, antiviral, antibacterial, in vitro, and in vivo toxicity, water absorption, and compound release properties of an alginate hydrogel crosslinked with calcium and different amounts of zinc cations. The results showed that the calcium alginate hydrogel film crosslinked with the highest amount of zinc showed similar water sorption properties to those of calcium alginate and released a suitable amount of zinc to provide anticancer activity against melanoma and colon cancer cells and has antibacterial properties against methicillin-resistant Staphylococcus epidermidis and antiviral activity against enveloped and non-enveloped viruses. This film is non-toxic in both in vitro in keratinocyte HaCaT cells and in vivo in the Caenorhabditis elegans model, which renders it especially promising for biomedical applications.