Translumbar treatment of type II endoleaks after endovascular repair of abdominal aortic aneurysm.
The modality of treatment and the appropriate time point to treat type II endoleaks after endovascular repair of abdominal aortic aneurysms (EVAR) remain controversial issues. The purpose of the present study was to assess the efficacy of translumbar embolization of type II endoleaks after endovascular repair of aortic aneurysm repair. Eighty-four consecutive patients after EVAR were analyzed for the onset of type II endoleaks. Of these, five patients had experienced translumbar embolization after ineffective intraartrial approach to exclude the endoleak. A combination of several liquid embolic agents was used as sealant. Post-procedural contrast-enhanced ultrasound (CEUS) was used to document the outcome of the embolization. Translumbar embolization was successful in four patients. Complete sealing of the nidus was seen on CEUS 24 h after the procedure. In one patient with a duplication of the inferior vena cava, the procedure was aborted because an additional type Ib endoleak was found. The procedure was well tolerated by all patients. The translumbar approach to treat growing aneurysm sacs in patients with persistent type II endoleaks is safe and well tolerated. The immediate post-interventional outcome as documented on CEUS is promising. Long-term follow-ups are yet to be performed.


Block Copolymer-based Photonic Pigments: Towards Structural Non-iridescent Brilliant Coloration.
Creating color through the self-assembly of specific building blocks to fabricate photonic morphologies is a promising and intriguing approach to reproducing the flamboyant visual effects and dynamic properties observed in the natural world. However, the complexity and lack of robustness in the manufacture of these nanostructured materials hinder their technical exploitation on a large scale. To overcome such limitations, here we present a novel methodology to create bioinspired photonic pigments as dispersed and micrometer-scale particles based on highly ordered concentric lamellar microspheres made of block copolymers. First, we introduce the fabrication protocol and the advantages of this approach compared to the traditional colloidal self-assembly. Then, we discuss some possible future research directions focused on developing hybrid organic-inorganic photonic pigments with enhanced dielectric contrast, reduced scattering, and specific functionalities. Finally, we speculate on possible applications for these structures that go beyond their use as simple photonic pigments.


Impact of Natural Compounds on Neurodegenerative Disorders: From Preclinical to Pharmacotherapeutics.
Among the major neurodegenerative disorders (NDDs), Alzheimer's disease (AD) and Parkinson's disease (PD), are a huge socioeconomic burden. Over many centuries, people have sought a cure for NDDs from the natural herbals. Many medicinal plants and their secondary metabolites are reported with the ability to alleviate the symptoms of NDDs. The major mechanisms identified, through which phytochemicals exert their neuroprotective effects and potential maintenance of neurological health in ageing, include antioxidant, anti-inflammatory, antithrombotic, antiapoptotic, acetylcholinesterase and monoamine oxidase inhibition and neurotrophic activities. This article review the mechanisms of action of some of the major herbal products with potential in the treatment of NDDs according to their molecular targets, as well as their regional sources (Asia, America and Africa). A number of studies demonstrated the beneficial properties of plant extracts or their bioactive compounds against NDDs. Herbal products may potentially offer new treatment options for patients with NDDs, which is a cheaper and culturally suitable alternative to conventional therapies for millions of people in the world with age-related NDDs.


Occurrence of and Factors Associated With the Presence of Aflatoxin M1 in Breast Milk of Mothers in Fethiye, Turkey.
Aflatoxins comprise a group of mycotoxins that are found in the environment. Exposure to aflatoxins has been reported to cause serious health problems in humans. Since aflatoxin M1 (AFM1) is secreted in breast milk, the exposure of infants to this toxin is an important concern. The aim of this study was to determine the prevalence, levels of, and factors associated with the presence of AFM1 in breast milk of mothers in Fethiye, Turkey. Breast milk samples were taken from 100 mothers who had given birth over the period of October-November 2017. The AFM1 content of the samples was determined via enzyme-linked immunosorbent assay. The lowest limit for milk samples in the Ridascreen® AFM1 commercial test kit is 5 ng/L. Because of this, AFM1 levels below 5 ng/L in the breast milk samples were assessed as negative. Of the breast milk samples tested, 53 were positive. The average AFM1 amount in the positive samples was 6.36 ng/L (ppt; range 5.10-8.31 ng/L). Mothers who were housewives, lived in damp, humid houses, or ate spices or dried fruits and vegetables had significantly greater prevalence of AFM1 in their breast milk than those who were employed, did not report dampness or mold in the home, or did not eat spices or dried fruits and vegetables. AFM1 in breast milk could be an important risk factor for infant health. Informing the public about food safety could reduce the amount of AFM1 being transferred into breast milk via food channels.


Quality Social Connection as an Active Ingredient in Digital Interventions for Young People With Depression and Anxiety: Systematic Scoping Review and Meta-analysis.
Disrupted social connections may negatively affect youth mental health. In contrast, sustained quality social connections (QSCs) can improve mental health outcomes. However, few studies have examined how these quality connections affect depression and anxiety outcomes within digital interventions, and conceptualization is limited. The aim of this study is to conceptualize, appraise, and synthesize evidence on QSC within digital interventions (D-QSC) and the impact on depression and anxiety outcomes for young people aged 14-24 years. A systematic scoping review and meta-analysis was conducted using the Joanna Briggs Institute methodological frameworks and guided by experts with lived experience. Reporting was guided by the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses). The MEDLINE, Embase, PsycINFO, and CINAHL databases were searched against a comprehensive combination of key concepts on June 24, 2020. The search concepts included young people, digital intervention, depression, anxiety, and social connection. Google was also searched. A reviewer independently screened abstracts and titles and full text, and 9.99% (388/3882) of these were screened by a second reviewer. A narrative synthesis was used to structure the findings on indicators of D-QSC and mechanisms that facilitate the connection. Indicators of D-QSC from the included studies were synthesized to produce a conceptual framework. Of the 5715 publications identified, 42 (0.73%) were included. Among the included studies, there were 23,319 participants. Indicators that D-QSC was present varied and included relatedness, having a sense of belonging, and connecting to similar people. However, despite the variation, most of the indicators were associated with improved outcomes for depression and anxiety. Negative interactions, loneliness, and feeling ignored indicated that D-QSC was not present. In 24% (10/42) of the applicable studies, a meta-analysis showed a significant decrease in depression (-25.6%, 95% CI -0.352 to -0.160; P<.001) and anxiety (-15.1%, 95% CI -0.251 to -0.051; P=.003) after a D-QSC. Digital mechanisms that helped create a quality connection included anonymity, confidentiality, and peer support. In contrast, mechanisms that hindered the connection included disconnection from the real world and inability to see body language. Data synthesis also identified a 5-component conceptual framework of D-QSC that included rapport, identity and commonality, valued interpersonal dynamic, engagement, and responded to and accepted. D-QSC is an important and underconsidered component for youth depression and anxiety outcomes. Researchers and developers should consider targeting improved QSC between clinicians and young people within digital interventions for depression. Future research should build on our framework to further examine relationships among individual attributes of QSC, various digital interventions, and different populations.


A highly selective conversion of toxic nitrobenzene to nontoxic aminobenzene by Cu2O/Bi/Bi2MoO6.
Cu2O/Bi/Bi2MoO6, a ternary catalyst, was expertly prepared using an in situ catalytic reduction reaction. All synthetic materials were carefully researched by high-resolution transmission electron microscopy (HRTEM), powder X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS), and ultraviolet-visible diffuse reflection spectra (UV-vis DRS). The elemental Bi was generated from Bi2MoO6 (BM) after a circular reduction catalysis process of 4-nitrophenol (4-NP) and evenly dispersed in the surface of the leaves of BM flower-like spheres, which was simultaneously coated with Cu2O. The multiphase samples achieved highly effective catalytic activity (10 053.6 min-1 g-1) for the conversion of the highly toxic 4-NP to the less toxic aminobenzene, compared to the single phase Cu2O and BM nanoparticles. Moreover, the excellent reusable stability of the compositing samples was confirmed by executing successive recycling experiments. It was proposed that the Bi3+/Bi0 pairs were the key active species which were produced via prompt reduction and oxidation with the help of Cu2O. The active interfacial contact between copper oxide/metallic Bi/BM (Cu2O/Bi/BM) in the designed sandwich structure facilitated the production and maintained the balance of Bi3+/Bi0 pairs, contributing to the enhanced activity and excellent stability.


Genotype-phenotype correlations for pancreatic cancer risk in Dutch melanoma families with pathogenic CDKN2A variants.
Pathogenic variants in the CDKN2A gene are generally associated with the development of melanoma and pancreatic ductal adenocarcinoma (PDAC), but specific genotype-phenotype correlations might exist and the extent of PDAC risk is not well established for many variants. Using the Dutch national familial melanoma database, we identified all families with a pathogenic CDKN2A variant and investigated the occurrence of PDAC within these families. We also estimated the standardised incidence ratio and lifetime PDAC risk for carriers of a highly prevalent variant in these families. We identified 172 families in which 649 individuals carried 15 different pathogenic variants. The most prevalent variant was the founder mutation c.225_243del (p16-Leiden, 484 proven carriers). Second most prevalent was c.67G>C (55 proven carriers). PDAC developed in 95 of 163 families (58%, including 373 of 629 proven carriers) harbouring a variant with an effect on the p16INK4a protein, whereas PDAC did not occur in the 9 families (20 proven carriers) with a variant affecting only p14ARF. In the c.67G>C families, PDAC occurred in 12 of the 251 (5%) persons at risk. The standardised incidence ratio was 19.1 (95% CI 8.3 to 33.6) and the cumulative PDAC incidence at age 75 years (lifetime risk) was 19% (95% CI 7.5% to 30.1%). Our results support the notion that pathogenic CDKN2A variants affecting the p16INK4a protein, including c.67G>C, are associated with increased PDAC risk and carriers of such variants should be offered pancreatic cancer surveillance. There is no clinical evidence that impairment of only the p14ARF protein leads to an increased PDAC risk.


The tetracycline: Mg2+ complex: a molecular mechanics force field.
Tetracycline (Tc) is an important antibiotic, which binds specifically to the ribosome and several proteins, in the form of a Tc-:Mg2+ complex. To model Tc:protein and Tc:RNA interactions, we have developed a molecular mechanics force field model of Tc, which is consistent with the CHARMM force field for proteins and nucleic acids. We used structures from the Cambridge Crystallographic Data Base to identify the main Tc conformations that are likely to be present in solution and in biomolecular complexes. A conformational search was also done, using the MM3 force field to perform simulated annealing of Tc. Several resulting, low-energy structures were optimized with an ab initio model and used in developing the new Tc force field. Atomic charges and Lennard-Jones parameters were derived from a supermolecule ab initio approach. We considered the ab initio energies and geometries of a probe water molecule interacting with Tc at 36 different positions. We considered both a neutral and a zwitterionic Tc form, with and without bound Mg2+. The final rms deviation between the ab initio and force field energies, averaged over all forms, was just 0.35 kcal/mol. The model also reproduces the ab initio geometry and flexibility of Tc. As further tests, we did simulations of a Tc crystal, of Tc:Mg2+ and Tc:Ca2+ complexes in aqueous solution, and of a solvated complex between Tc:Mg2+ and the Tet repressor protein (TetR). With slight, ad hoc adjustments, the model can reproduce the experimental, relative, Tc binding affinities of Mg2+ and Ca2+. It performs well for the structure and fluctuations of the Tc:Mg2+:TetR complex. The model should therefore be suitable to investigate the interactions of Tc with proteins and RNA. It provides a starting point to parameterize other compounds in the large Tc family.


Enhancing EEG-based cross-day mental workload classification using periodic component of power spectrum.
Objective. The day-to-day variability of electroencephalogram (EEG) poses a significant challenge to decode human brain activity in EEG-based passive brain-computer interfaces (pBCIs). Conventionally, a time-consuming calibration process is required to collect data from users on a new day to ensure the performance of the machine learning-based decoding model, which hinders the application of pBCIs to monitor mental workload (MWL) states in real-world settings.Approach. This study investigated the day-to-day stability of the raw power spectral density (PSD) and their periodic and aperiodic components decomposed by the Fitting Oscillations and One-Over-F algorithm. In addition, we validated the feasibility of using periodic components to improve cross-day MWL classification performance.Main results. Compared to the raw PSD (69.9% ± 18.5%) and the aperiodic component (69.4% ± 19.2%), the periodic component had better day-to-day stability and significantly higher cross-day classification accuracy (84.2% ± 11.0%).Significance. These findings indicate that periodic components of EEG have the potential to be applied in decoding brain states for more robust pBCIs.


Persistent antinuclear antibodies in children without identifiable inflammatory rheumatic or autoimmune disease.
One hundred eight children with musculoskeletal pain considered not to be due to an autoimmune or inflammatory disease had an antinuclear antibody (ANA) test performed. Twenty-four of these children were ANA positive on HEp-2 cell substrate at a screening serum dilution of 1:20. A positive ANA test persisted in 21 of 24 of the patients over a mean time period of 38 months (range 1 to 103 months). No sera from any patient at initial evaluation had anti-DNA antibodies by radioimmunoassay or by indirect immunofluorescence on Crithidia luciliae. One patient recently developed elevated anti-DNA (radioimmunoassay) antibodies but still has a negative assay on C luciliae. Four patients had antibodies to core histones by immunoblotting. None had antibodies to Sm, RNP, Ro (SS-A), or La (SS-B) by counterimmunoelectrophoresis. No patient developed an overt inflammatory or autoimmune disease during a mean follow-up period of 61 months (range 13 to 138 months). A child with musculoskeletal pain and a positive test for ANA, but with no clinical evidence at presentation of inflammatory or autoimmune disease, is at low risk of imminently developing such a disease.


Concomitant 5-FU, hydroxyurea and cisplatin with external beam radiation therapy for locally advanced pancreatic cancer.
The aim of the study was to determine the efficacy and toxicity of alternate week concurrent 5-fluorouracil, hydroxyurea, and cisplatin with radiotherapy for locally advanced pancreatic adenocarcinoma. Patients received 5-fluorouracil, hydroxyurea and cisplatin with radiotherapy on an alternate week basis. Chemoradiotherapy was given day 1-5, and no therapy given day 6-14 for each 14 day cycle. Chemotherapy doses were as follows: hydroxyurea 1 mg every 12 h starting day 0, 5-fluorouracil 800 mg/m(2)/day for 5 days starting day 1, and cisplatin 20 mg/m(2) daily for 5 days every other cycle. A radiation dose of 6000 cGy was prescribed. Acute toxicities were monitored and therapy modified for hematologic toxicity. Nine patients enrolled, however eight were evaluable; one patient expired prior to therapy. The median radiation dose delivered was 5540 cGy. Sixty-three percent required a chemotherapy dose reduction. Fifty percent achieved local control by radiographic imaging after completion of therapy. Median survival was 12 months. Acute toxicity included: 38% grade 2-3 nausea, 37% grade 2-3 vomiting, 63% grade 2-3 mucositis, 63% grade 2-3 neutropenia, and 88% grade 3-4 thrombocytopenia. Other sequelae included hand-foot syndrome, deep venous thrombosis, hearing loss, seizures, and anorexia. Patients achieved the same median survival as compared to other reported studies of radiation therapy with single agent 5-fluorouracil. We do not recommend this protocol due to the significant toxicity. Future studies to incorporate conformal radiation therapy with more active, less toxic chemotherapeutic agents should be investigated.


Transient response and time evolution of 2-D solutions in a coherent optical processor with feedback.
The transient response of a coherent optical processor with feedback has been experimentally studied over the time period from the moment light first enters the system to when steady state operation is established. To facilitate this transient response study, a Blumlein-driven electrooptic gate was constructed to provide a square diagnostic pulse with nanosecond scale rise and fall time, as the characteristic circulation time through the processor is in the 10-nsec regime. Light at several discrete points of the 2-D output was measured with high-speed avalanche photodiodes and displayed on a fast oscilloscope. This technique is compared to previous work in which the entire 2-D optical output as a function of time was also obtained by incorporating a linear phase shifting wedge inside the optical processor at one of the Fourier transform locations. Spatial separation of the successive 2-D outputs then correspond to sequential circulation inside the Fabry-Perot. These experimental studies reveal interesting phenomena related to the evolution of an optically computed solution to a partial differential equation due to (a) consecutive additions of the feedback cycles, (b) feedback polarity, and (c) the processing or filtering functions inside the confocal Fabry-Perot. The time-dependent evolution can be utilized to add a third dimension of time to optical solution of 3-D partial differential equations.


[Effect of adaptation to the altitude hypoxia on catecholamine metabolism in rats with spontaneous hereditary hypertension].
An increase in the noradrenaline concentration in the myocardium and vas deferens was revealed in 11- and 15-week-old spontaneous hypertensive rats (SHR), this increase being less marked in 15-week-old SHR. On the contrary, catecholamine metabolic changes in the adrenals were more pronounced in 15-week-old SHR and consisted in an appreciable reduction of the content of noradrenaline and adrenalin. The concentration of noradrenaline was inversely proportional to the magnitude of arterial pressure. Adaptation to the daily 6-hour action of hypoxia (5000 m above sea level) by the 4th day prevents the development of hypertension in SHR and related changes in catecholamine metabolism in the adrenals.


A pipeline for automated analysis of flow cytometry data: preliminary results on lymphoma sub-type diagnosis.
Flow cytometry (FCM) is widely used in health research and is a technique to measure cell properties such as phenotype, cytokine expression, etc., for up to millions of cells from a sample. FCM data analysis is a highly tedious, subjective and manually time-consuming (to the level of impracticality for some data) process that is based on intuition rather than standardized statistical inference. This study proposes a pipeline for automatic analysis of FCM data. The proposed pipeline identifies biomarkers that correlate with physiological/pathological conditions and classifies the samples to specific pathological/physiological entities. The pipeline utilizes a model-based clustering approach to identify cell populations that share similar biological functions. Support vector machine (SVM) and random forest (RF) classifiers were then used to classify the samples and identify biomarkers associated with disease status. The performance of the proposed data analysis pipeline has been evaluated on lymphoma patients. Preliminary results show more than 90% accuracy in differentiating between some sub-types of lymphoma. The proposed pipeline also finds biologically meaningful biomarkers that differ between lymphoma subtypes.


Airline pilot medical disability: a comparison between three airlines with different approaches to medical monitoring.
To study the impact of airline medical departments on pilot disability, three major U.S. airlines, nominally airlines A, B, and C, were chosen because they had distinctly different medical programs. Airline A provided essentially no medical review. Airline B performed preemployment screening and assessment of individual disability claims, along with an irregular pilot review. Airline C provided basically the same services as airline B but also screened pilots annually. The total cohort comprised 12,866 pilots providing 79,797 person-years of experience. Between 1 January 1975 and 31 December 1982, medical losses in all three airlines increased rapidly after pilots reached the age of 45 years, with cardiovascular disease responsible for approximately 50% of the losses. For pilots 45 years old or older, the age-specific disability rates in airline A were significantly higher than those in airlines B and C; rates for airlines B and C were not significantly different. The data suggest that airlines with active medical departments have lower pilot medical disability rates than do airlines without such departments. Data also suggest that preemployment screening and assessment of individual disability claims are more important determinants of long-term disability rates than are regular (annual) pilot health reviews.


Imprint of human cytomegalovirus infection on the NK cell receptor repertoire.
Expression of the activating CD94/NKG2C killer lectin-like receptor (KLR) specific for HLA-E was analyzed in peripheral blood lymphocytes (PBLs) from healthy adult blood donors; the expression of other natural killer (NK) cell receptors (ie, CD94/NKG2A, KIR, CD85j, CD161, NKp46, NKp30, and NKG2D) was also studied. Human cytomegalovirus (HCMV) infection as well as the HLA-E and killer immunoglobulin-like receptor (KIR) genotypes were considered as potentially relevant variables associated with CD94/NKG2C expression. The proportion of NKG2C(+) lymphocytes varied within a wide range (<0.1% to 22.1%), and a significant correlation (r = 0.83; P < .001) between NKG2C(+) NK and T cells was noticed. The HLA-E genotype and the number of activating KIR genes of the donors were not significantly related to the percentage of NKG2C(+) lymphocytes. By contrast, a positive serology for HCMV, but not for other herpesviruses (ie, Epstein-Barr and herpes simplex), turned out to be strongly associated (P < .001) with increased proportions of NKG2C(+) NK and T cells. Remarkably, the CD94/NKG2C(+) population expressed lower levels of natural cytotoxicity receptors (NCRs) (ie, NKp30, NKp46) and included higher proportions of KIR(+) and CD85j(+) cells than CD94/NKG2A(+) cells. Altogether, these data support that HCMV infection selectively shapes the natural killer cell receptor (NKR) repertoire of NK and T cells from healthy carrier individuals.


Residual cyclic nucleotide associated with tissues after exposure to aqueous buffer analogous to that used in immunocytochemistry.
A question concerning cyclic nucleotide immunocytochemical localization has been how much nucleotide remains associated with the tissue section. To answer that question cryostat sections of goldfish eye and mouse spleen, liver and lung were mounted on microscope slides and air dried. Following fixation by a variety of procedures employing heat, paraformaldehyde, glutaraldehyde, acetone, or ethanol, the sections were exposed to buffer (20 microM NaHPO4, 154 microM NaCl, pH 6.1) for 4 hours. The tissues were then scraped from the slides into 0.4N Perchloric Acid and cAMP and cGMP extracted and measured. The results show that fractions of both nucleotides are retained during buffer exposure. However, the amount retained varied with the: i) neucleotide, ii) fixation procedure, and iii) tissue type. Cyclic GMP retention was consistently higher (20-70%) than cAMP (6-30%). Glutaraldehyde was consistently more efficient in fixing cAMP, while cGMP retention was more variable with different fixation procedures. Tissue variability is seen in the example that spleen and liver retained more cGmp (71.4 and 70.6% respectively) than lung and eye (22.8 and 37.7% respectively). Maximum nucleotide loss occured during the first 5-30 minutes of buffer exposure with no additional loss accuring after another 20 hours. Collectively, these results demonstrate that cyclic nucleotides are retained during immunocytochemical staining procedures but that the degree of retention is dependent on several variables.


The Monsanto Papers: Poisoning the scientific well.
Examination of de-classified Monsanto documents from litigation in order to expose the impact of the company's efforts to influence the reporting of scientific studies related to the safety of the herbicide, glyphosate. A set of 141 recently de-classified documents, made public during the course of pending toxic tort litigation, In Re Roundup Products Liability Litigation were examined. The documents reveal Monsanto-sponsored ghostwriting of articles published in toxicology journals and the lay media, interference in the peer review process, behind-the-scenes influence on retraction and the creation of a so-called academic website as a front for the defense of Monsanto products. The use of third-party academics in the corporate defense of glyhphosate reveals that this practice extends beyond the corruption of medicine and persists in spite of efforts to enforce transparency in industry manipulation.


Three-dimensional bioprinted glioblastoma microenvironments model cellular dependencies and immune interactions.
Brain tumors are dynamic complex ecosystems with multiple cell types. To model the brain tumor microenvironment in a reproducible and scalable system, we developed a rapid three-dimensional (3D) bioprinting method to construct clinically relevant biomimetic tissue models. In recurrent glioblastoma, macrophages/microglia prominently contribute to the tumor mass. To parse the function of macrophages in 3D, we compared the growth of glioblastoma stem cells (GSCs) alone or with astrocytes and neural precursor cells in a hyaluronic acid-rich hydrogel, with or without macrophage. Bioprinted constructs integrating macrophage recapitulate patient-derived transcriptional profiles predictive of patient survival, maintenance of stemness, invasion, and drug resistance. Whole-genome CRISPR screening with bioprinted complex systems identified unique molecular dependencies in GSCs, relative to sphere culture. Multicellular bioprinted models serve as a scalable and physiologic platform to interrogate drug sensitivity, cellular crosstalk, invasion, context-specific functional dependencies, as well as immunologic interactions in a species-matched neural environment.


Mortality from dementia in Norway, 1969-83.
From 1969 to the end of 1983 in Norway, dementia was coded as the underlying cause of death from 2058 death certificates, and as a contributory cause from 19,459. This is 3.56% of the total number of deaths. It seems that a considerable proportion of dementia cases are noted on death certificates in Norway. Death rates based on dementia as the underlying cause of death have increased with time, but when including contributory causes, rates have declined. The data may be useful in epidemiological studies, eg, to search for aetiological clues for Alzheimer's disease. Due to the inclusion of contributory causes of death in the registers and to the high number of dementia cases noted on death certificates, Norwegian mortality data on dementia are probably of better quality than in most other countries.


Linked-color imaging combined with the NICE classification system for optical diagnosis of colon polyps: new image-enhanced endoscopic technology for pathological prediction.
Linked-color imaging (LCI) is a recently developed system used in endoscopy. It creates clear and bright endoscopic images using short-wavelength, narrow-band laser light combined with white laser light. The illuminating light and signal processing emphasize slight color differences in abnormal regions that approximate the normal color of the mucosa. As a result, regions initially appearing red become a deeper shade of red, while regions originally appearing white become brighter, yet with natural tones. This process facilitates recognition of slight differences in the color of the mucosa and clarifies the boundaries of the mucosal pit. To determine whether LCI of the colon can improve the correlation between endoscopic findings and pathological diagnosis. Consecutive patients who underwent colonoscopy requiring polypectomy or removal by biopsy forceps if possible were recruited. Probable polyp histology was assessed by two endoscopists using the Narrow-band imaging International Colorectal Endoscopic (NICE) classification and LCI data. All detected polyps were sent to the pathology department for pathological diagnosis by two pathologists. In total, 94 polyps were found in 43 patients. The sensitivity, specificity, positive predictive value, and negative predictive value for neoplastic lesion prediction (NICE type2/3) were 96.5%, 83.8%, 90.2%, and 93.9%, respectively. LCI combined with the NICE classification system is a powerful tool for predicting probable histology of colon polyps.


Ibrutinib for patients with relapsed or refractory chronic lymphocytic leukaemia with 17p deletion (RESONATE-17): a phase 2, open-label, multicentre study.
The TP53 gene, encoding tumour suppressor protein p53, is located on the short arm of chromosome 17 (17p). Patients with 17p deletion (del17p) chronic lymphocytic leukaemia have poor responses and survival after chemoimmunotherapy. We assessed the activity and safety of ibrutinib, an oral covalent inhibitor of Bruton's tyrosine kinase, in relapsed or refractory patients with del17p chronic lymphocytic leukaemia or small lymphocytic lymphoma. We did a multicentre, international, open-label, single-arm study at 40 sites in the USA, Canada, Europe, Australia, and New Zealand. Patients (age ≥18 years) with previously treated del17p chronic lymphocytic leukaemia or small lymphocytic lymphoma received oral ibrutinib 420 mg once daily until progressive disease or unacceptable toxicity. The primary endpoint was overall response in the all-treated population per International Workshop on Chronic Lymphocytic Leukaemia 2008 response criteria modified for treatment-related lymphocytosis. Preplanned exploratory analyses were progression-free survival, overall survival, sustained haematological improvement, and immunological improvement. Patient enrolment is complete, but follow-up is ongoing. Treatment discontinuation owing to adverse events, unacceptable toxicity, or death were collected as a single combined category. This study is registered with ClinicalTrials.gov, number NCT01744691. Between Jan 29, 2013, and June 19, 2013, 145 patients were enrolled. The all-treated population consisted of 144 patients with del17p chronic lymphocytic leukaemia or small lymphocytic lymphoma who received at least one dose of study drug, with a median age of 64 years (IQR 57-72) and a median of two previous treatments (IQR 1-3). At the prespecified primary analysis after a median follow-up of 11·5 months (IQR 11·1-13·8), 92 (64%, 95% CI 56-71) of 144 patients had an overall response according to independent review committee assessment; 119 patients (83%, 95% CI 76-88) had an overall response according to investigator assessment. In an extended analysis with median follow-up of 27·6 months (IQR 14·6-27·7), the investigator-assessed overall response was reported in 120 patients (83%, 95% CI 76-89). 24-month progression-free survival was 63% (95% CI 54-70) and 24-month overall survival was 75% (67-81). Sustained haematological improvement was noted in 72 (79%) of 91 patients with any baseline cytopenia. No clinically relevant changes were noted from baseline to 6 months or 24 months in IgA (median 0·4 g/L at baseline, 0·6 g/L at 6 months, and 0·7 g/L at 24 months), IgG (5·0 g/L, 5·3 g/L, and 4·9 g/L), or IgM (0·3 g/L at each timepoint) concentrations. Common reasons for treatment discontinuation were progressive disease in 34 (24%) patients and adverse events, unacceptable toxicity, or death in 24 (17%) patients. Major bleeding occurred in 13 (9%) patients (11 [8%] grade 3-4). Grade 3 or worse infections occurred in 43 (30%) patients, including pneumonia in 19 (13%) patients. In the extended analysis, 38 patients died, 18 as a result of adverse events (four pneumonia, three chronic lymphocytic leukaemia, two Richter's syndrome, two sepsis, and one each of acute myocardial infarction, septic shock, encephalopathy, general deterioration in physical health, abnormal hepatic function, myocardial infarction, and renal infarction). A high proportion of patients had an overall response to ibrutinib and the risk:benefit profile was favourable, providing further evidence for use of ibrutinib in the most difficult subset of patients with chronic lymphocytic leukaemia or small lymphocytic lymphoma. Ibrutinib represents a clinical advance in the treatment of patients with del17p chronic lymphocytic leukaemia and has been incorporated into treatment algorithms as a primary treatment for these patients. Pharmacyclics LLC, an AbbVie Company.


Within-Day Time-Varying Associations Between Behavioral Cognitions and Physical Activity in Adults.
This study used time-varying effect modeling to examine time-of-day differences in how behavioral cognitions predict subsequent physical activity (PA). Adults (N = 116) participated in three 4-day "bursts" of ecological momentary assessment (EMA). Participants were prompted with eight EMA questionnaires per day assessing behavioral cognitions (i.e., intentions, self-efficacy, outcome expectations) and wore an accelerometer during waking hours. Subsequent PA was operationalized as accelerometer-derived minutes of moderate- or vigorousintensity PA in the 2 hr following the EMA prompt. On weekdays, intentions positively predicted subsequent PA in the morning (9:25 a.m.-11:45 a.m.) and in the evening (8:15 p.m.-10:00 p.m.). Self-efficacy positively predicted subsequent PA on weekday evenings (7:35 p.m.-10:00 p.m.). Outcome expectations were unrelated to subsequent PA on weekdays. On weekend days, behavior cognitions and subsequent PA were unrelated regardless of time of day. This study identifies windows of opportunity and vulnerability for motivation-based PA interventions aiming to deliver intervention content within the context of adults' daily lives.


How Do Contexts Affect Physicians' Clinical Reasoning? A Narrative Review.
This article was migrated. The article was marked as recommended. Background Research about clinical reasoning has tended to focus on the individual, assessing their ability to perform clinical reasoning tasks. However, recent studies have noted that clinical reasoning varies with the clinical context. Objectives The purpose of this narrative review is to examine how the context can affect physicians clinical reasoning skills. Methods A narrative literature review was conducted by searching PubMed, PsycINFO and Embase via Ovid using the search terms clinical OR critical AND thinking OR judgement OR reasoning. Of 22,296 results found, 25 studies were found to be relevant to our review. Results Most studies focused on diagnostic skills. Contexts affecting clinical reasoning fell into three broad categories: patient, physician and environmental (the physical and social setting) factors. Patient contexts researched included factors both personal to the patient and their physical disease manifestations. Physician contexts included experience, age, exposure to similar diagnoses, incorrect diagnostic suggestion, emotions, and the use of reflection and checklists. Environmental contexts included time pressure, unfamiliarity with surroundings, dealing with uncertainty and high-stakes outcomes. The effect of applying more than one contextual factor increasing cognitive load, was explored. Conclusion This original review suggests that the context can affect a physician's clinical reasoning abilities. This review identifies areas for continued research, including which contexts have a negative or positive impact, and the effect of multiple contexts (cognitive loading) on clinical reasoning. Further empirical research is needed to investigate these areas in more depth and to establish how far these benefits have an impact in practice.


Recombinative reading derived from pseudoword instruction in a miniature linguistic system.
A miniature linguistic system was used to study acquisition of recombinative symbolic behavior. Three studies evaluated the teaching conditions of conditional discriminations with printed and spoken pseudowords that could potentially generate recombinative reading. Fifty-four college students across all studies learned to match 12 printed pseudowords to 12 spoken pseudowords. Some also matched pictures to the same spoken words. Each two-syllable pseudoword was formed by symbols from an arbitrarily created alphabet composed of four vowels and four consonants. Letters had univocal correspondence with phonemes. Recombinative receptive reading, comprehensive reading, and textual responding to pseudowords were periodically assessed. Experiment 1 (n = 20) showed that recombinative reading increased as the number of trained words composed of the same symbols increased. Experiment 2 (n = 14) showed that overtraining the same two words did not produce recombinative reading for most participants. Experiment 3 (n = 20), in which training with pictures was omitted, showed that elemental control by within-syllable units can develop even when the trained pseudowords are meaningless (not related to pictures). The present results support the utility of the miniature linguistic system methodology for identifying and controlling environmental determinants of rudimentary reading skills.


Shockwave based nonlinear optical manipulation in densely scattering opaque suspensions.
Optical manipulation of particulate-loaded, highly scattering (opaque) suspensions is considered impossible. Here we demonstrate theoretically and experimentally optical manipulation of the local properties of such opaque suspensions. We show that the optical forces exerted by multiply-scattered light give rise to dense shock fronts of particle concentration, propagating deep inside the opaque suspensions, where the optical field is completely diffuse. We exploit these waves to demonstrate a plethora of optofluidic manipulations, ranging from optical transport and concentration of large populations of nanoparticles, to light-induced 'writing' of concentrated spots in the suspensions and light-induced phase-transition from suspension to gel in localized volumes inside the fluids.


A review of professional liability cases affecting the practice of optometry.
In establishing the liability of optometrists for negligence the courts have applied the same standard of care that is imposed upon other health care professionals, holding that optometrists must employ the minimum degree of skill, care and learning that is ordinarily exhibited by members of the profession who are in good standing. The leading cases establishing this standard have involved glaucoma, retinal detachment, and intraocular tumors. Optometrists have also been held liable under product liability law for injuries caused by ophthalmic lenses, which illustrates the trend toward strict liability. Other cases have involved the doctrine of informed consent.


Assessing residents' operative skills for external ventricular drain placement and shunt surgery in pediatric neurosurgery.
OBJECTIVE The authors previously demonstrated the use of a validated Objective Structured Assessment of Technical Skills (OSATS) tool for evaluating residents' operative skills in pediatric neurosurgery. However, no benchmarks have been established for specific pediatric procedures despite an increased need for meaningful assessments that can either allow for early intervention for underperforming trainees or allow for proficient residents to progress to conducting operations independently with more passive supervision. This validated methodology and tool for assessment of operative skills for common pediatric neurosurgical procedures-external ventricular drain (EVD) placement and shunt surgery- was applied to establish its procedure-based feasibility and reliability, and to document the effect of repetition on achieving surgical skill proficiency in pediatric EVD placement and shunt surgery. METHODS A procedure-based technical skills assessment for EVD placements and shunt surgeries in pediatric neurosurgery was established through the use of task analysis. The authors enrolled all residents from 3 training programs (Baylor College of Medicine, Houston Methodist Hospital, and University of Texas-Medical Branch) who rotated through pediatric neurosurgery at Texas Children's Hospital over a 26-month period. For each EVD placement or shunt procedure performed with a resident, the faculty and resident (for self-assessment) completed an evaluation form (OSATS) based on a 5-point Likert scale with 7 categories. Data forms were then grouped according to faculty versus resident (self) assessment, length of pediatric neurosurgery rotation, postgraduate year level, and date of evaluation ("beginning of rotation," within 1 month of start date; "end of rotation," within 1 month of completion date; or "middle of rotation"). Descriptive statistical analyses were performed with the commercially available SPSS statistical software package. A p value < 0.05 was considered statistically significant. RESULTS Five attending evaluators (including 2 fellows who acted as attending surgeons) completed 260 evaluations. Twenty house staff completed 269 evaluations for self-assessment. Evaluations were completed in 562 EVD and shunt procedures before the surgeons left the operating room. There were statistically significant differences (p < 0.05) between overall attending (mean 4.3) and junior resident (self; mean 3.6) assessments, and between overall attending (mean 4.8) and senior resident (self; mean 4.6) assessment scores on general performance and technical skills. The learning curves produced for the residents demonstrate a stereotypical U- or V-shaped curve for acquiring skills, with a significant improvement in overall scores at the end of the rotation compared with the beginning. The improvement for junior residents (Δ score = 0.5; p = 0.002) was larger than for senior residents (Δ score = 0.2; p = 0.018). CONCLUSIONS The OSATS is an effective assessment tool as part of a comprehensive evaluation of neurosurgery residents' performance for specific pediatric procedures. The authors observed a U-shaped learning curve, contradicting the idea that developing one's surgical technique and learning a procedure represents a monotonic, cumulative process of repetitions and improvement.


Simultaneous mutually exclusive active tubercular posterior uveitis.
Ocular tuberculosis (TB) is a form of extra-pulmonary TB, which can involve almost any intraocular structure or ocular adnexa. Posterior uveitis, the commonest form of intraocular TB manifests as choroidal tubercles, choroidal tuberculoma, subretinal abscess, neuroretinitis, or serpiginous-like choroiditis. These forms of posterior tubercular lesions can be broadly classified into two groups based on their pathophysiology and morphology. One group of lesions is related to the direct invasion and reactivation of the bacilli in the choroidal tissue, whereas the other is a result of hypersensitivity reaction to the bacilli. Simultaneous bilateral active posterior uveitis with such varying morphology and pathophysiology in either eye of the same patient is an extremely rare presentation. We report a case with pulmonary TB on Anti-tubercular therapy (ATT), who presented to us with two mutually exclusive and distinctly different forms of tubercular posterior uveitis in either eye simultaneously. Both lesions were active at the time of presentation.


QTL mapping of rat blood pressure loci on RNO1 within a homologous region linked to human hypertension on HSA15.
Fine-mapping of regions linked to the inheritance of hypertension is accomplished by genetic dissection of blood pressure quantitative trait loci (BP QTLs) in rats. The goal of the current study was to further fine-map two genomic regions on rat chromosome 1 with opposing blood pressure effects (BP QTL1b1 and BP QTL1b1a), the homologous region of which on human chromosome 15 harbors BP QTLs. Two new substrains were constructed and studied from the previously reported BP QTL1b1, one having significantly lower systolic BP by 17 mmHg than that of the salt-sensitive (S) rat (P = 0.007). The new limits of BP QTL1b1 were between 134.09 Mb and 135.40 Mb with a 43% improvement from the previous 2.31 Mb to the current 1.31 Mb interval containing 4 protein-coding genes (Rgma, Chd2, Fam174b, and St8sia2), 2 predicted miRNAs, and 4 lncRNAs. One new substrain was constructed and studied from the previously reported BPQTL1b1a having a significantly higher systolic BP by 22 mmHg (P = 0.006) than that of the S rat. The new limits of BPQTL1b1a were between 133.53 Mb and 134.52 Mb with a 32% improvement from the previous1.45 Mb to the current 990.21 Kb interval containing 1 protein-coding gene, Mctp2, and a lncRNA. The congenic segments of these two BP QTLs overlapped between 134.09 Mb and 134.52 Mb. No exonic variants were detected in any of the genes. These findings reiterate complexity of genetic regulation of BP within QTL regions, where elements beyond protein-coding sequences could be factors in controlling BP.


Enhancing the role of physicians in the cost-effective use of pharmaceuticals.
The appropriate use of pharmaceuticals, like much else in medicine, is receiving increased public scrutiny. Health care practitioners are looking for ways to reduce costs without negatively influencing quality of care. This article reviews methods for physicians and pharmacists to work together to implement cost-effective prescribing practices and assess clinical outcomes. These methods include educational initiatives, administrative programs to restrict ordering practices, use of formularies and prescribing guidelines, financial incentives, and programs that support physician and pharmacist collaboration.


Comparative effectiveness of sodium-glucose co-transporter-2 inhibitors and dipeptidyl peptidase-4 inhibitors on liver function in patients with type 2 diabetes in Japan: A real-world data analysis.
To compare the effects of sodium-glucose co-transporter-2 inhibitors (SGLT2is) versus dipeptidyl peptidase-4 inhibitors (DPP4is) on liver function in patients with type 2 diabetes (T2D) in Japan. This was a Japanese retrospective cohort study using the RWD Database (1 January 2015 to 24 September 2021). Patients newly treated with an SGLT2i or a DPP4i were matched 1:4 (SGLT2i:DPP4i) using propensity score. The primary endpoint was the change from baseline to 1 year after the index date in alanine aminotransferase (ALT). Secondary endpoints included change from baseline in various laboratory test results, including the Fibrosis-4 (FIB-4) index, aspartate aminotransferase, gamma-glutamyl transpeptidase (GGT), albumin and HbA1c. Endpoints were compared between treatment groups using Welch's t-test in the full population and in subgroups stratified by baseline characteristics. Baseline characteristics of 955 and 3063 matched patients newly treated with an SGLT2i and a DPP4i, respectively, were well balanced. Patients receiving an SGLT2i had significantly greater reductions in ALT, FIB-4 index and GGT and a significantly greater increase in albumin than patients receiving a DPP4i. A significantly greater change from baseline in ALT was observed in the SGLT2i group than in the DPP4i group among subgroups with lower baseline FIB-4 index and HbA1c. In this study, improvements in various measures, including ALT, the FIB-4 index, GGT and albumin, were observed with SGLT2is compared with DPP4is, suggesting that SGLT2is may provide hepatoprotective benefits, including the prevention of liver fibrosis, in patients with T2D in Japan.


Lower LDL-cholesterol levels associated with increased inflammatory burden in patients with acute ST-segment elevation myocardial infarction.
Association of low-density lipoprotein cholesterol and highly sensitive C-reactive protein in ST-elevation myocardial infarction patients was assessed in this study. 591 consecutive patients who were hospitalized with a diagnosis of ST-elevation myocardial infarction were enrolled and assigned into tertiles according to their serum low-density lipoprotein cholesterol levels. Differences in highly sensitive C-reactive protein among low-density lipoprotein cholesterol tertiles and correlations between highly sensitive C-reactive protein and low-density lipoprotein cholesterol were assessed. Highly sensitive C-reactive protein levels differed significantly among the groups (p<0.001) and found to be highest in the low-density lipoprotein cholesterol tertile 1 and lowest in the low-density lipoprotein cholesterol tertile 3 (post-hoc p-values: tertile 1 vs. 2 <0.001; tertile 1 vs. 3 <0.001; tertile 2 vs. 3=0.019). There was a negative correlation between hs-CRP and both low-density lipoprotein cholesterol (r=-0.332, p<0.001) and total cholesterol (r=-0.326, p<0.001). There was also a negative correlation between highly sensitive C-reactive protein and high-density lipoprotein cholesterol, though the strength of this relationship was weak (r=-0.103, p=0.014). Lower low-density lipoprotein cholesterol levels are associated with higher inflammatory burden in patients with acute STEMI. Further studies are required to elucidate the significance of low-density lipoprotein cholesterol levels in ST-elevation myocardial infarction settings.


Coral larvae move toward reef sounds.
Free-swimming larvae of tropical corals go through a critical life-phase when they return from the open ocean to select a suitable settlement substrate. During the planktonic phase of their life cycle, the behaviours of small coral larvae (<1 mm) that influence settlement success are difficult to observe in situ and are therefore largely unknown. Here, we show that coral larvae respond to acoustic cues that may facilitate detection of habitat from large distances and from upcurrent of preferred settlement locations. Using in situ choice chambers, we found that settling coral larvae were attracted to reef sounds, produced mainly by fish and crustaceans, which we broadcast underwater using loudspeakers. Our discovery that coral larvae can detect and respond to sound is the first description of an auditory response in the invertebrate phylum Cnidaria, which includes jellyfish, anemones, and hydroids as well as corals. If, like settlement-stage reef fish and crustaceans, coral larvae use reef noise as a cue for orientation, the alleviation of noise pollution in the marine environment may gain further urgency.


A high-resolution gene expression map of the medial and lateral domains of the gynoecium of Arabidopsis.
Angiosperms are characterized by the formation of flowers, and in their inner floral whorl, one or various gynoecia are produced. These female reproductive structures are responsible for fruit and seed production, thus ensuring the reproductive competence of angiosperms. In Arabidopsis (Arabidopsis thaliana), the gynoecium is composed of two fused carpels with different tissues that need to develop and differentiate to form a mature gynoecium and thus the reproductive competence of Arabidopsis. For these reasons, they have become the object of study for floral and fruit development. However, due to the complexity of the gynoecium, specific spatio-temporal tissue expression patterns are still scarce. In this study, we used precise laser-assisted microdissection and high-throughput RNA sequencing to describe the transcriptional profiles of the medial and lateral domain tissues of the Arabidopsis gynoecium. We provide evidence that the method used is reliable and that, in addition to corroborating gene expression patterns of previously reported regulators of these tissues, we found genes whose expression dynamics point to being involved in cytokinin and auxin homeostasis and in cell cycle progression. Furthermore, based on differential gene expression analyses, we functionally characterized several genes and found that they are involved in gynoecium development. This resource is available via the Arabidopsis eFP browser and will serve the community in future studies on developmental and reproductive biology.


Analysis of early mesothelial cell responses to Staphylococcus epidermidis isolated from patients with peritoneal dialysis-associated peritonitis.
The major complication of peritoneal dialysis (PD) is the development of peritonitis, an infection within the abdominal cavity, primarily caused by bacteria. PD peritonitis is associated with significant morbidity, mortality and health care costs. Staphylococcus epidermidis is the most frequently isolated cause of PD-associated peritonitis. Mesothelial cells are integral to the host response to peritonitis, and subsequent clinical outcomes, yet the effects of infection on mesothelial cells are not well characterised. We systematically investigated the early mesothelial cell response to clinical and reference isolates of S. epidermidis using primary mesothelial cells and the mesothelial cell line Met-5A. Using an unbiased whole genome microarray, followed by a targeted panel of genes known to be involved in the human antibacterial response, we identified 38 differentially regulated genes (adj. p-value < 0.05) representing 35 canonical pathways after 1 hour exposure to S. epidermidis. The top 3 canonical pathways were TNFR2 signaling, IL-17A signaling, and TNFR1 signaling (adj. p-values of 0.0012, 0.0012 and 0.0019, respectively). Subsequent qPCR validation confirmed significant differences in gene expression in a number of genes not previously described in mesothelial cell responses to infection, with heterogeneity observed between clinical isolates of S. epidermidis, and between Met-5A and primary mesothelial cells. Heterogeneity between different S. epidermidis isolates suggests that specific virulence factors may play critical roles in influencing outcomes from peritonitis. This study provides new insights into early mesothelial cell responses to infection with S. epidermidis, and confirms the importance of validating findings in primary mesothelial cells.


For the assessment of intestinal permeability, size matters.
The purpose of this review is to demonstrate that an intestine leaky to small molecules can be impermeable to large antigenic molecules. The author proposes that the permeability of the epithelium to very small sugar molecules such as lactulose/mannitol-used for the past 50 years to gauge intestinal permeability-does not necessarily correlate with epithelial permeability to macromolecules. This article begins with the history and science behind the use of small sugars to measure permeability, a method developed in 1899. The lactulose/mannitol test may give useful information regarding the overall condition of the digestive tract; however, the author suggests that the test is not indicative of the transport of macromolecules such as bacterial toxins and food antigens, which have the capacity to damage the structure of the intestinal barrier and/or challenge the immune system. This article describes the various mechanisms and physiological transport pathways through which increased antigen uptake may result in immunological reactions to food antigens and bacterial lipopolysaccharides, resulting in the pathogenesis of disease. Finally, the article presents evidence indicating that increased intestinal, antigenic permeability plays a key role in the development of various inflammatory and autoimmune disorders. Therefore, more knowledge about the epithelium's permeability to large molecules undoubtedly contributes not only to early detection but also to secondary prevention of many inflammatory autoimmune, neuroimmune, and neurodegenerative disorders.


A solid-phase fluorescence sensor for measuring chemical species in water.
In this study, the first of its kind, a solid-phase fluorescence sensing platform was developed to quantify contaminants in water. ZnO quantum dots (QDs) were combined with molecularly imprinted polymers (MIPs) to form fluorescence sensing materials. Solid sensing layers were formed via a straightforward spin-coating method, which demonstrated a strong attachment to the sensor substrate while maintaining the integrity of the sensing materials. The developed sensing platform comprised a portable fluorescence detector to measure fluorescence intensity, instead of traditional fluorescence spectroscopy. The solid sensing platform was first tested with 2,4-dichlorophenoxyacetic acid (2,4-D), demonstrating high sensitivity (0.0233) and a very strong correlation (0.98) between the target molecule concentration and sensor signal. Further, the sensing platform was successfully adapted to measure a substance with a different molecular mass and chemical structure, the algae toxin microcystin-LR (MCLR); this demonstrated the sensor's versatility in quantifying target molecules. Tap water samples spiked with MCLR were also used to test the sensor's practical application. Finally, the working mechanism of the sensing platform was established, and the key information for using the sensor to measure various contaminants was determined. With its high performance, broad applicability, and ease of use, the developed platform provides a suitable basis for lab-on-chip image-based sensing devices for environmental monitoring.


Common writings of baby names in Japan, 1989-2003: Explanation of survey data.
Previous research on Japanese names has analyzed the surveys on baby names conducted by Meiji Yasuda Life Insurance Company. The company displayed the yearly top 10 common writings of baby names between 1989 and 2003. However, it was unclear how the surveys for those 15 years were conducted. The data are necessary to evaluate the usableness of the surveys and conduct empirical research. Therefore, I asked the company for further data about the surveys. The methods of the surveys were consistent not only between 1989 and 2003, but also consistent with those between 2004 and 2018. The analyses on the annual sample sizes by gender showed that the surveys between 1989 and 2003 are comparable to the surveys between 2004 and 2018. The company is unable to access the raw data of these surveys, which makes it impossible to provide results other than the top 10 most common writings.


[Clinical, diagnostic and pathogenetic aspects of reflux-associated cough].
Gastroesophageal reflux may be responsible for atypical extra-esophageal symptoms, such as chest pain, dyspnea, chronic cough, or hoarseness. Prospective studies of gastroesophageal reflux have indicated reflux as the cause for chronic cough in 10 to 20% of patients. The precise mechanism by which reflux causes cough remains uncertain, although the possibility that the cough is caused by stimulation of the esophageal mucosa receptors rather than aspiration is suggestive from some studies. Prolonged esophageal pH monitoring affords an opportunity to document objective gastroesophageal reflux. Furthermore, pH monitoring gives the opportunity to correlate temporally acid reflux events with the onset of certain symptoms.


Transumbilical approach for laparo-endoscopic single-site adrenalectomy: initial experience and short-term outcome.
To report our initial experience with transumbilical laparo-endoscopic single-site adrenalectomy for adrenal tumors by using a single port with a multichannel cannula and bent laparoscopic instrumentation. Between December 2009 and December 2010, 30 patients underwent transumbilical laparo-endoscopic single-site adrenalectomy at our hospital. The procedure was carried out for adrenal cortical adenoma in 17 patients, adrenal pheochromocytoma in seven patients and other types of tumors in six patients. A multichannel port, bent laparoscopic instruments and Opti4 laparoscopic electrodes were used in all patients. The intraperitoneal space was approached through the umbilicus. The multichannel port was placed through a 2-cm incision at the inner edge of the umbilicus. A 5-mm flexible laparoscope was introduced to maintain an adequate laparoscopic view, and surgical specimens were extracted using an Endocatch bag. All procedures were successfully completed, with only one incision through the umbilicus, and without conversion to a standard laparoscopic approach. Mean operative time was 120.1 ± 34.7 min. Tumor laterality and patient body mass index did not affect surgical morbidity. The initial 15 patients had a significantly longer mean pneumoperitoneum time (95.8 ± 37.5 min) than the last 15 patients (70.5 ± 18.7 min). Only one postoperative complication was observed (postoperative hematoma). A transumbilical approach for laparo-endoscopic single-site adrenalectomy is safe and feasible, and it results in superior cosmesis. Improvements in surgical devices might facilitate further development of this approach.


Numerical study of high-frequency oscillatory air flow and convective mixing in a CT-based human airway model.
High-frequency oscillatory ventilation (HFOV) is considered an efficient and safe respiratory technique to ventilate neonates and patients with acute respiratory distress syndrome. HFOV has very different characteristics from normal breathing physiology, with a much smaller tidal volume and a higher breathing frequency. In this study, the high-frequency oscillatory flow is studied using a computational fluid dynamics analysis in three different geometrical models with increasing complexity: a straight tube, a single-bifurcation tube model, and a computed tomography (CT)-based human airway model of up to seven generations. We aim to understand the counter-flow phenomenon at flow reversal and its role in convective mixing in these models using sinusoidal waveforms of different frequencies and Reynolds (Re) numbers. Mixing is quantified by the stretch rate analysis. In the straight-tube model, coaxial counter flow with opposing fluid streams is formed around flow reversal, agreeing with an analytical Womersley solution. However, counter flow yields no net convective mixing at end cycle. In the single-bifurcation model, counter flow at high Re is intervened with secondary vortices in the parent (child) branch at end expiration (inspiration), resulting in an irreversible mixing process. For the CT-based airway model three cases are considered, consisting of the normal breathing case, the high-frequency-normal-Re (HFNR) case, and the HFOV case. The counter-flow structure is more evident in the HFNR case than the HFOV case. The instantaneous and time-averaged stretch rates at the end of two breathing cycles and in the vicinity of flow reversal are computed. It is found that counter flow contributes about 20% to mixing in HFOV.


Clinical effectiveness of conventional influenza vaccination in asthmatic children.
Influenza immunization rates among young asthmatics remain unsatisfactory due to persistent concern about the impact of influenza and the benefits of the vaccine. We assessed the effectiveness of the conventional inactivated trivalent sub-unit influenza vaccine in reducing acute respiratory disease in asthmatic children. We conducted a two-season retrospective cohort study covering the 1995-6 and 1996-7 influenza outbreaks in 22 computerized primary care practices in The Netherlands. In total, 349 patients aged between 0 and 12 years meeting clinical asthma-criteria were included; 14 children were lost to follow-up in the second season. The occurrence of physician-diagnosed acute respiratory disease episodes including influenza-like illness, pneumonia. bronchitis, bronchiolitis, asthma exacerbation and acute otitis media in vaccinated and unvaccinated children were compared after adjustments for age, prior health care and medication use. The occurrence of acute respiratory disease in unvaccinated children was 28% and 24% in the 1995-6 and 1996-7 season, respectively, and was highest in children under 6 years of age (43%). The overall pooled clinical vaccine effectiveness was 27% (95% confidence interval -7 to 51%, P = 0.11) after adjustments. A statistically higher vaccine protectiveness of 55% (95% CI 20-75%, P = 0.01) was observed among asthmatics under 6 years of age compared with -5% in older children (95% CI -81 to 39%). The occurrence of acute respiratory disease among asthmatic children during influenza epidemics is very high, notably in the youngest. Influenza vaccination may reduce morbidity in asthmatic infants and pre-school children. However, larger, preferably experimental, studies are needed to establish the benefits of vaccination, notably in older asthmatic children.


Heme Oxygenase-1 Protects the Liver from Septic Injury by Modulating TLR4-Mediated Mitochondrial Quality Control in Mice.
Mitochondrial dysfunction is involved in the pathogenesis of sepsis-induced multiple organ dysfunction syndrome (MODS). Mitochondrial quality control (QC) is characterized by self-recovering mitochondrial damage through mitochondrial biogenesis, mitophagy, and fission/fusion. Heme oxygenase (HO)-1 acts as a signaling molecule to modulate inflammation. The present study elucidated the cytoprotective mechanisms of HO-1 in sepsis, particularly focusing on toll-like receptor (TLR)4-mediated mitochondrial QC. Mice were subjected to sepsis by cecal ligation and puncture (CLP). The mice were injected intraperitoneally with hemin (10 mg/kg) at 12 h before CLP or zinc protoporphyrin IX (ZnPP; 30 mg/kg) at 2 h before CLP. The serum and tissues were collected 6 h after CLP. Mortality, MODS, and proinflammatory cytokines increased in septic mice. These increases were augmented by ZnPP but attenuated by hemin. Hemin decreased mitochondrial lipid peroxidation and mitochondrial dysfunction. Hemin enhanced mitochondrial biogenesis, as indicated by increased levels of peroxisome proliferator-activated receptor-γ coactivator 1α, nuclear respiratory factor 1, and mitochondrial transcription factor A (TFAM). Hemin also enhanced mitophagy, as indicated by decreased PTEN-induced putative kinase 1 (PINK1) level and increased Parkin level. Hemin decreased fission-related protein, dynamin-related protein 1 (DRP1), and increased fusion-related protein, mitofusin 2. Hemin attenuated the increased TLR4 expression. TAK-242, a TLR4 antagonist, attenuated mortality, inflammatory response, and impaired mitochondrial QC. Our findings suggest that HO-1 attenuates septic injury by modulating TLR4-mediated mitochondrial QC.


Improvement in hepatic insulin sensitivity after Roux-en-Y gastric bypass in a rat model of obesity is partially mediated via hypothalamic insulin action.
Roux-en-Y gastric bypass (RYGB) surgery, an effective treatment for morbid obesity, commonly leads to near complete resolution of type 2 diabetes. The underlying mechanisms, however, remain unclear and factors other than weight loss alone may be involved. To determine whether increased hypothalamic insulin sensitivity after RYGB drives the rapid improvement in glucose metabolism, high-fat-fed rats received either an insulin receptor (IR) antisense vector or a control lentiviral vector that was microinjected into the ventromedial hypothalamus (VMH). Six weeks later, rats underwent RYGB or control gastrointestinal surgery. Four weeks after surgery, weight loss was comparable in RYGB and surgical controls. Nevertheless, only RYGB rats that received the control vector demonstrated both improved hepatic and peripheral insulin sensitivity. Insulin suppressed hepatic glucose production (HGP) by 50% (p < 0.05) with RYGB, whereas the effect of insulin on HGP was completely absent in VMH IR knockdown (IRkd) rats. By contrast, both RYGB groups displayed an identical twofold increase in insulin-stimulated peripheral glucose uptake. The animals that underwent control gastrointestinal surgery failed to show any improvement in either hepatic or peripheral insulin sensitivity; VMH IRkd did not influence the magnitude of insulin resistance. Our findings demonstrate that RYGB surgery in high-fat-fed obese rats enhances hepatic and peripheral insulin sensitivity independently of weight loss. The improved hepatic, but not the peripheral, response to insulin is mediated centrally at the level of the VMH. These data provide direct evidence that the metabolic benefits of RYGB surgery are not simply a consequence of weight loss but likely in part involve the central nervous system.


Stability and effects of some pesticides in soil.
The influence of 29 pesticides on CO(2) production and nitrification by soil microorganisms was determined. A few compounds were stable but without significant effect in soil (chlorinated hydrocarbons), some persisted and depressed respiration and nitrification (carbamates, cyclodienes, phenylureas, thiolcarbamates), and others displayed toxicity but were transformed by soil microorganisms (amides, anilides, organophosphates, phenylcarbamates, triazines). Some compounds of the last type induced an initial increase and subsequent decrease in CO(2) production by soil. No simple explanation of this effect is possible, but the results of studies of model systems having established activities suggest that in soil any one or a combination of the following mechanisms is responsible for the observed complex relation of CO(2) production to time: (i) a pesticide acts to uncouple oxidative phosphorylation in a manner analogous to 2,4-dinitrophenol; (ii) a pesticide lacking antimicrobial action is oxidized in part and transformed to a stable and toxic product; (iii) a pesticide that is selectively toxic inhibits CO(2) production by sensitive microorganisms but is subject to oxidation without detoxification by other members of the microbial population that are resistant to its initial action. Pesticide concentrations greatly in excess of those recommended for agricultural and home use were required to produce an effect, and supplementary organic matter (glucose) tended to reduce pesticide toxicity and increase the microbial degradation of pesticides in soil.


Reliable Identification of Endometrial Precancers Through Combined Pax2, β-Catenin, and Pten Immunohistochemistry.
The diagnosis of endometrial atypical hyperplasia/endometrioid intraepithelial neoplasia (AH/EIN) remains challenging and subjective in some cases, with variable histologic criteria and differences of opinion among gynecologic pathologists, potentially leading to under/overtreatment. There has been growing interest in the use of specific immunohistochemical markers as adjuncts in AH/EIN diagnosis. For example, the World Health Organization 2020 Classification specifies that loss of Pten, Pax2, or mismatch repair proteins are desirable diagnostic criteria. Other markers, most notably β-catenin and Arid1a, are also aberrantly expressed in some AH/EIN. However, the performance of some markers individually-and more importantly as a group-has not been rigorously explored, raising questions as to which marker(s) or combination(s) is the most effective in practice. Formalin-fixed paraffin-embedded tissue sections from AH/EIN cases (n=111) were analyzed by immunohistochemistry for 6 markers: Pax2, Pten, Mlh1, β-catenin, Arid1a, and p53. Aberrant expression was tabulated for each case and marker. An additional set of normal endometria (n=79) was also analyzed to define optimal diagnostic criteria for marker aberrance. The performance characteristics of each marker, the entire panel, and subsets thereof were quantitatively and statistically analyzed. In order of number of cases detected, the most frequently aberrant markers in AH/EIN were Pax2 (81.1% of cases), Pten (50.5%), β-catenin (47.7%), Arid1a (7.2%), Mlh1 (4.5%), and p53 (2.7%). The majority of cases showed aberrant expression of ≥2 markers. All 6 markers together identified 92.8% of cases. Arid1a, Mlh1, and p53 were robust and readily scored markers, but all cases showing aberrant expression of these 3 markers were also detected by Pax2, Pten, or β-catenin. A focused panel of only 3 markers (Pax2, Pten, and β-catenin) showed optimal performance characteristics as a diagnostic adjunct in the histopathologic diagnosis of AH/EIN. Use of this panel is practicable and robust, with at least 1 of the 3 markers being aberrant in 92.8% of AH/EIN.


Inhibition of influenza-virus-induced apoptosis in chorion cells of human fetal membranes by nordihydroguaiaretic Acid.
It has been postulated that the pathogenesis of influenza virus infection involves not only the virus-proliferation-mediated apoptotic cell death in infected cells, but also a direct reactive oxygen species (ROS)-induced cellular injury in the infected organs. We examined effects of an antioxidant, nordihydroguaiaretic acid (NDGA), on apoptosis induction and viral proliferation. Subsequently, the results were compared with those of pyrrolidine dithiocarbamate (PDTC), another antioxidant. The levels of ROS production were measured with 2',7'-dichlorofluorescein diacetate; apoptosis induction and viral proliferation were analyzed by DNA fragmentation and plaque-forming assays, respectively. The treatment of infected cells with NDGA inhibited ROS overproduction, apoptotic DNA fragmentation and virus proliferation. The maximum inhibition against DNA fragmentation (76%) was observed with 500 microM NDGA. The antiviral activity of NDGA against influenza virus was more potent than that of PDTC. The present study, therefore, suggests for the first time that NDGA, a known antioxidant reagent, inhibits the induction of apoptosis in human fetal membrane chorion cells infected with influenza virus through the more potent antiviral activity than that of PDTC.


[The coordination of the forensic medical service with the medical criminology subdivisions of internal affairs organs in the personal identification of unidentified corpses].
In order to improve the cooperation between medical criminology departments of the organs of home affairs and forensic medical service in personality identification of unidentified corpses, the authors propose amendments to the routine procedure regulated by documents of the Ministry of Home Affairs of the Russian Federation, for these documents are in need of serious correction and revision, so that they conform to the judicial legislation and other documents.


Drivers and Management Implications of Long-Term Cisco Oxythermal Habitat Decline in Lake Mendota, WI.
Cisco (Coregonus artedi) are an important indicator species for cold-water lake habitats in the Great Lakes region, and many populations have been extirpated at their southern range limit over the last century. Understanding the roles of climate and water quality in these extirpations should inform protection of cold-water fishes. Using the water temperature at the depth where dissolved oxygen falls to 3 mg L-1 (TDO3) as a metric, we investigated the roles of climate and water quality as drivers of habitat availability for cisco in Lake Mendota, WI, USA from 1976 to 2013. We find that summer (Jun-Aug) air temperatures, spring (Mar-May) phosphorus load, and spring inflow influence summer TDO3. Warm air temperatures lead to the greatest increases in TDO3, whereas reduced phosphorus loads can reduce TDO3, thus alleviating oxythermal stress. Under air temperatures expected under the A1B climate change scenario, a 25% reduction in phosphorus load would stabilize TDO3 at current levels, while a 75% reduction in phosphorus loading would be required to expand oxythermal habitat. Costs of these reductions are estimated to range from US$16.9 million (-25%) to US$155-167 million (-75%) over a 20-year period but may be feasible by expanding upon current watershed phosphorus reduction initiatives if sustained funding were available. Identifying targeted reductions will become increasingly important throughout the region as warmer temperatures and longer stratification reduces cool- and cold-water fish habitat in many Midwestern lakes under the expected future climate.


The limitations of point of care testing for pandemic influenza: what clinicians and public health professionals need to know.
As the world prepares for the next influenza pandemic, governments have made significant funding commitments to vaccine development and antiviral stockpiling. While these are essential components to pandemic response, rapid and accurate diagnostic testing remains an often neglected cornerstone of pandemic influenza preparedness. Clinicians and Public Health Practitioners need to understand the benefits and drawbacks of different influenza tests in both seasonal and pandemic settings. Culture has been the traditional gold standard for influenza diagnosis but requires from 1-10 days to generate a positive result, compared to nucleic acid detection methods such as real time reverse transcriptase polymerase chain reaction (RT-PCR). Although the currently available rapid antigen detection kits can generate results in less than 30 minutes, their sensitivity is suboptimal and they are not recommended for the detection of novel influenza viruses. Until point-of-care (POC) tests are improved, PILPN recommends that the best option for pandemic influenza preparation is the enhancement of nucleic acid-based testing capabilities across Canada.


The Swedish cause of death register.
Sweden has a long tradition of recording cause of death data. The Swedish cause of death register is a high quality virtually complete register of all deaths in Sweden since 1952. Although originally created for official statistics, it is a highly important data source for medical research since it can be linked to many other national registers, which contain data on social and health factors in the Swedish population. For the appropriate use of this register, it is fundamental to understand its origins and composition. In this paper we describe the origins and composition of the Swedish cause of death register, set out the key strengths and weaknesses of the register, and present the main causes of death across age groups and over time in Sweden. This paper provides a guide and reference to individuals and organisations interested in data from the Swedish cause of death register.


Neurobehavioral deficits and a progressive ictogenesis in the tetrodotoxin model of epileptic spasms.
Our goal was to determine whether animals with a history of epileptic spasms have learning and memory deficits. We also used continuous (24/7) long-term electroencephalographic (EEG) recordings to evaluate the evolution of epileptiform activity in the same animals over time. Object recognition memory and object location memory tests were undertaken, as well as a matching to place water maze test that evaluated working memory. A retrospective analysis was undertaken of long-term video/EEG recordings from rats with epileptic spasms. The frequency and duration of the ictal events of spasms were quantified. Rats with a history of epileptic spasms showed impairment on the three behavioral tests, and their scores on the object recognition memory and matching to place water maze tests indicated neocortical involvement in the observed impaired cognition. Analysis of EEG recordings unexpectedly showed that the ictal events of spasms and their accompanying behaviors progressively increased in duration over a 2-week period soon after onset, after which spasm duration plateaued. At the same time, spasm frequency remained unchanged. Soon after spasm onset, ictal events were variable in wave form but became more stereotyped as the syndrome evolved. Our EEG findings are the first to demonstrate progressive ictogenesis for epileptic spasms. Furthermore, in demonstrating cognitive deficits in the tetrodotoxin model, we have met a criterion for an animal model of West syndrome. Animal models will allow in-depth studies of spasm progression's potential role in cognitive regression and may elucidate why early treatment is considered essential for improved neurodevelopmental outcomes in children.


Discovery of a First-in-Class Small-Molecule Ligand for WDR91 Using DNA-Encoded Chemical Library Selection Followed by Machine Learning.
WD40 repeat-containing protein 91 (WDR91) regulates early-to-late endosome conversion and plays vital roles in endosome fusion, recycling, and transport. WDR91 was recently identified as a potential host factor for viral infection. We employed DNA-encoded chemical library (DEL) selection against the WDR domain of WDR91, followed by machine learning to predict ligands from the synthetically accessible Enamine REAL database. Screening of predicted compounds identified a WDR91 selective compound 1, with a KD of 6 ± 2 μM by surface plasmon resonance. The co-crystal structure confirmed the binding of 1 to the WDR91 side pocket, in proximity to cysteine 487, which led to the discovery of covalent analogues 18 and 19. The covalent adduct formation for 18 and 19 was confirmed by intact mass liquid chromatography-mass spectrometry. The discovery of 1, 18, and 19, accompanying structure-activity relationship, and the co-crystal structures provide valuable insights for designing potent and selective chemical tools against WDR91 to evaluate its therapeutic potential.


Spectral broadening of characteristic γ-ray emission peaks from 12C(3He,pγ)14N reactions in fusion plasmas.
The spectral broadening of characteristic γ-ray emission peaks from the reaction (12)C((3)He,pγ)(14)N was measured in D((3)He) plasmas of the JET tokamak with ion cyclotron resonance heating tuned to the fundamental harmonic of (3)He. Intensities and detailed spectral shapes of γ-ray emission peaks were successfully reproduced using a physics model combining the kinetics of the reacting ions with a detailed description of the nuclear reaction differential cross sections for populating the L1-L8 (14)N excitation levels yielding the observed γ-ray emission. The results provide a paradigm, which leverages knowledge from areas of physics outside traditional plasma physics, for the development of nuclear radiation based methods for understanding and controlling fusion burning plasmas.


Reported contact with child protection services among those reporting child physical and sexual abuse: results from a community survey.
This study uses results from a large community survey to examine the relationship between a history of child maltreatment and self-reports of contact with Child Protection Services (CPS). The Ontario Health Supplement was a province-wide, probability-based survey of household dwellings in the province of Ontario, Canada. A random sample of residents aged 15 and older participated in the Ontario Health Supplement (N=9953). A face-to-face interview included a question about contact with Child Protection Services (CPS), and the Child Maltreatment History Self-Report, a self-administered questionnaire, was used to assess history of child physical and sexual abuse. Only a very small percentage of respondents with a history of child abuse reported contact with CPS; 5.1% of those with a history of physical abuse, and 8.7% of those with a history of sexual abuse. Contact with CPS was associated with younger age of respondent for both types of abuse and female gender for physical abuse. In the case of sexual abuse, younger respondents whose parental employment classification was in the lower socioeconomic group were more likely to have contact with CPS. Interventions that target only those who come in contact with CPS will not reach most persons exposed to child abuse.


Why predictive indexes perform less well in validation studies. Is it magic or methods?
When prognostic indexes have been tested in a second population, they have often performed less well. Since this is believed to be inevitable, methodologic differences that may explain the discrepancies have been overlooked. Data from a prospective study of 232 patients undergoing noncardiac surgery were used to examine the effect of methodologic differences in assembly of population, postoperative surveillance, and the criteria for cardiac complications on the performance of Goldman's cardiac risk index. Our prospective population was used to simulate the methods used in Goldman's study and in three other studies using the risk index to demonstrate the potential impact of differences in population, surveillance, and outcome criteria for cardiac complications. If Goldman's detection and outcome criteria were employed and only the eligibility criteria used for assembly of the populations differed, the overall complication rates would be between 5.2% and 6.9%; and the complication rates for the different Goldman classes were similar. When both different detection strategies and different outcome criteria were used, however, important discrepancies in cardiac complication rates emerged. For example, complication rates in class 2 varied from 2% to 23%. In conclusion, important discrepancies in performance of prognostic indexes may arise from differences in surveillance strategies and definitions of outcome. With sufficient attention to methodologic consistency, the performance of predictive indexes may not inevitably deteriorate in subsequent studies.


Costs of providing a rheumatological service.
As a result of a management budgeting exercise, the costs of rheumatology services in two hospitals in the Northern Region have been calculated. These comprehensive and itemized charges were derived by an external group of accountants. The data for a 1-year period from April 1985 are presented. Differences in both mean out-patient-visit and in-patient bed-day charges between hospitals were found. Factors contributing to these differences are discussed. The major costs, particularly of in-patient care, are not directly controllable by the clinician. Mean costs per out-patient visit were 26.00 pounds and 36.90 pounds at the two hospitals. Costs for in-patient care per bed-day were 49.00 pounds and 70.71 pounds, respectively. The calculated total cost of the rheumatology service in Newcastle was approximately 1.00 pound per capita catchment population per annum.


Abilities of pulse pressure variations and stroke volume variations to predict fluid responsiveness in prone position during scoliosis surgery.
Pulse pressure variation (PPV) and stroke volume variation (SVV) are robust indicators of fluid responsiveness in mechanically ventilated supine patients. The aim of the study was to evaluate the ability of PPV and SVV to predict fluid responsiveness in mechanically ventilated patients in the prone position (PP) during scoliosis surgery. Thirty subjects were studied after the induction of anaesthesia in the supine position [before and after volume expansion (VE) with 500 ml of hetastarch 6%] and in PP (immediately after PP and before and after VE). PPV, SVV, cardiac output (CO), and static compliance of the respiratory system were recorded at each interval. Subjects were defined as responders (Rs) to VE if CO increased > or =15%. Three subjects were excluded. In the supine position, 16 subjects were Rs. PPV and SVV before VE were correlated with VE-induced changes in CO (r(2)=0.64, P<0.0001 and r(2)=0.56, P<0.0001, respectively). Fluid responsiveness was predicted by PPV >11% (sensitivity=88%, specificity=82%) and by SVV >9% (sensitivity=88%, specificity=91%). PP induced an increase in PPV and SVV (P<0.0001) and a decrease in the static compliance of the respiratory system (P<0.0001). In PP, 17 patients were Rs. PPV and SVV before VE were correlated with VE-induced changes in CO (r(2)=0.59, P<0.0001 and r(2)=0.55, P<0.0005, respectively). Fluid responsiveness was predicted in PP by PPV >15% (sensitivity=100%, specificity=80%) and by SVV >14% (sensitivity=94%, specificity=80%). PP induces a significant increase in PPV and SVV but does not alter their abilities to predict fluid responsiveness.


[Current approaches to the development of a system of automated diagnosis of osteochondrodysplasias in children].
On the basis of studying of data on 1469 patients there is proposed a methodology of development of a system of automated diagnosis of osteo-chondrodysplasia in children. It is based on registration of the course peculiarities, variety of clinical and genetic forms, inter- and intragroup similarity and progredient course of diseases of the type. At the first stage there have been made a complex analysis of formalized clinico-roentgenologic signs of osteo-chondrodysplasia with the aid of "Rbase-5000" program package. Osteo-chondrodysplasia course regularities, revealed in this way, were used further on in the process of an expert system development for their automated diagnosis.


Understanding the contribution of ascorbic acid to the pigment development in model white wine systems using liquid chromatography with diode array and mass spectrometry detection techniques.
The present study investigated the contribution of ascorbic acid to the formation of coloured species in model white wine systems containing (+)-catechin as the oxidisable phenolic substrate. Reactions were carried out in the presence or absence of ascorbic acid in model wine systems buffered with either tartaric acid or formic acid. High performance liquid chromatography with diode array detector (HPLC-DAD) or mass spectrometry (HPLC-MS) analyses demonstrated that glyoxylic acid-derived xanthylium pigments were the main coloured species produced in all samples except those containing just (+)-catechin and formic acid. Higher concentrations of these pigments were detected in the tartaric acid based model system containing both (+)-catechin and ascorbic acid than in the corresponding formic acid model system. The inability of formic acid to form an aldehyde, unlike the known oxidative formation of aldehydes from tartaric acid, contributes to the lower colour development in the formic acid model system. Significantly, these observations imply that ascorbic acid must break down to provide an aldehyde, or ketone, capable of reacting with (+)-catechin to generate the glyoxylic acid-derived xanthylium cations.


[Conservative therapy in rehabilitating patients with eye injuries].
The authors offer recommendations on the choice and use of optimal clinically tried drugs in ophthalmic traumatology with consideration for posttraumatic changes, doses, and mechanism of action. The recommendations are based on the clinical observations of 16,000 patients treated at department of ocular injuries, reconstructive surgery, and ocular prosthetics of Helmholtz Institute of Ocular Diseases in Moscow.


Effect of water temperature on exercise-induced maternal hyperthermia on fetal development in rats.
The objective of this study was to determine if water temperature influenced exercise-induced hyperthermia in swim-trained pregnant rats and the resulting fetal development. Pregnant Sprague-Dawley rats with 6 weeks pre-pregnancy training were exercised daily from day 1 to day 18 of gestation in water that was 34.6 +/- 0.4 degrees C (Cool Water Swimmers--CWS) or 37.6 +/- 0.1 degrees C (Warm Water Swimmers--WWS), for one hour/day. During this time period another group of pregnant rats was immersed to the neck in warm water (37.6 +/- 0.2 degrees C) (Warm Water Controls--WWC). On day 19 of gestation all animals were sacrificed and fetal development assessed. Maternal exercise in warm water elevated maternal body core temperature by 2.3 +/- 0.1 degrees C above resting values, with an increase in fetal abnormalities compared to the same exercise intensity in cool water. Fifty-eight percent of the abnormal fetuses and 60% of the resorption sites were found in the WWS group. Of the abnormalities determined, 65% were from the WWS group and 45% of these fetuses showed micrencephaly. Results suggest cool water may regulate maternal body temperature during swimming exercise and that swimming in warm water should be avoided during gestation because of potential teratogenic effects.


Protection against 17D yellow fever encephalitis in mice by passive transfer of monoclonal antibodies to the nonstructural glycoprotein gp48 and by active immunization with gp48.
The protective capacity of antiviral antibodies has generally been considered to depend on their interactions with structural components of the virion. Here we report protection against lethal 17D yellow fever virus (YF) encephalitis of mice by passive administration of nonneutralizing monoclonal antibodies to a 17D YF-specified nonstructural glycoprotein, gp48, and by active immunization with purified gp48. Among five anti-gp48 monoclonal antibodies tested, two with high titer complement-fixing (CF) activity were protective, whereas three antibodies with little or no CF activity were not. The ability of antibodies to protect correlated with their ability to promote complement-mediated cytolysis (CMC) of 51Cr-labeled 17D YF-infected mouse neuroblastoma (Neuro 2a) cells. Purified gp48, prepared from lysates of 17D YF-infected Vero cells by immunoaffinity chromatography, was shown to bear both YF type-specific and flavivirus group-reactive determinants in a solid phase radioimmunoassay. Immunization of mice with purified gp48 resulted in solid protection in the absence of detectable anti-virion antibody, measured by neutralization and radioimmunoprecipitation assays. The results are consistent with plasma membrane expression of gp48 and susceptibility of 17D YF-infected neural cells to CMC, a possible mechanism of host defense in 17D YF encephalitis. Protection provided by immunization with gp48, which bears a group-reactive determinant and is highly conserved among flaviviruses, may have implications in regard to flavivirus vaccine design.


[Nutrition physiology studies with formula diets: metabolism of multiple unsaturated fatty acids and prostaglandin biosynthesis in the human].
Linoleic and linolenic acids are precursors for the biosynthesis of prostaglandins (PG) and related compounds. In man augmented linoleic acid intake results in stimulation of PG-biosynthesis, for PG originating from the kidney a stimulation only is found for PGE2. Dietary linolenic acid inhibits PG biosynthesis to a tenfold lesser degree than eicosapentaenoic acid. Renal PGE2 is depressed by linolenic acid intake, while no effect is found for PGF2 alpha up to 8 energy% of linolenic acid supply. Linoleic and linolenic acids additionally display effects on fatty acid metabolism. In contrast to the results of in vitro studies the supply with the precursor linoleic acid results in a decrease of arachidonic acid in cholesterolesters of plasma and in HDL-lecithin, while the intake of linolenic acid is without effect. From these data it is concluded that in vivo the conversion of linoleic to arachidonic acid occurs preferentially to the analogous conversion of linolenic to eicosapentaenoic acid.


Therapy modifications in response to poorly controlled hypertension, dyslipidemia, and diabetes mellitus.
Poorly controlled cardiovascular risk factors are common. Evaluating whether physicians respond appropriately to poor risk factor control in patients may better reflect quality of care than measuring proportions of patients whose conditions are controlled. To evaluate therapy modifications in response to poor control of hypertension, dyslipidemia, or diabetes in a large clinical population. Retrospective cohort study within an 18-month period in 2002 to 2003. Kaiser Permanente of Northern California. 253,238 adult members with poor control of 1 or more of these conditions. The authors assessed the proportion of patients with poor control who experienced a change in pharmacotherapy within 6 months, and they defined "appropriate care" as a therapy modification or return to control without therapy modification within 6 months. A total of 64% of patients experienced modifications in therapy for poorly controlled systolic blood pressure, 71% for poorly controlled diastolic blood pressure, 56% for poorly controlled low-density lipoprotein cholesterol level, and 66% for poorly controlled hemoglobin A1c level. Most frequent modifications were increases in number of drug classes (from 70% to 84%) and increased dosage (from 15% to 40%). An additional 7% to 11% of those with poorly controlled blood pressure, but only 3% to 4% of those with elevated low-density lipoprotein cholesterol level or hemoglobin A1c level, returned to control without therapy modification. Patients with more than 1 of the 3 conditions, higher baseline values, and target organ damage were more likely to receive "appropriate care." Patient preferences and suboptimal adherence to therapy were not measured and may explain some failures to act. As an additional measure of the quality of care, measuring therapy modifications in response to poor control in a large population is feasible. Many patients with poorly controlled hypertension, dyslipidemia, or diabetes had their therapy modified and, thus, seemed to receive clinically "appropriate care" with this new quality measure.