Characterization of Müller glia and neuronal progenitors during adult zebrafish retinal regeneration.
The adult zebrafish retina exhibits a robust regenerative response following light-induced photoreceptor cell death. This response is initiated by the Müller glia proliferating in the inner nuclear layer (INL), which gives rise to neuronal progenitor cells that continue to divide and migrate to the outer nuclear layer (ONL), where they differentiate into rod and cone photoreceptors. We previously conducted a microarray analysis of retinal gene expression at 16, 31, 51, 68, and 96 h of constant intense-light treatment to identify genes and their corresponding proteins that may be involved in the generation and proliferation of the neuronal progenitor cells. We examined the expression of two candidate transcription factors, Pax6 and Ngn1, and one candidate transgene, olig2:EGFP, in the regenerating light-damaged retina. We compared the temporal and spatial expression patterns of these markers relative to PCNA (proliferating cell nuclear antigen), an established marker for proliferating cells in the zebrafish retina, and the Tg(gfap:EGFP) nt11 transgenic line that specifically labels Müller glial cells. We found that Müller glial cells dedifferentiate during regeneration, based on the loss of cell-specific markers such as GFAP (glial fibrillary acidic protein) and glutamine synthetase following their reentry into the cell cycle to produce neuronal progenitors. Pax6 expression was first detected in the proliferating neuronal progenitors by 51 h of constant light treatment, which is significantly after the Müller glia first reenter the cell cycle after 31h of light. This suggests that Pax6 expression increases in neuronal progenitors, rather than in the proliferating Müller glia. EGFP expression from the olig2 promoter was first detected by 68 h of constant light treatment in the dedifferentiated Müller glia, with Pax6 expressed in the closely associated proliferating neuronal progenitors migrating to the ONL. Both Pax6 and olig2 expression persisted until 3 days post-light treatment, when the neuronal progenitors begin differentiating into new rod and cone photoreceptors. Ngn1 protein expression was initially detected in proliferating neuronal progenitors at 68 h of light treatment. However, Ngn1 expression persisted in a subset of the INL nuclei until 17 days post-light treatment. Using the Tg(gfap:EGFP) nt11 transgenic line, Ngn1 was localized to the Müller glial nuclei that were reestablished following the regenerative response. These markers, therefore, can be used to identify different cell types at particular stages of retinal regeneration: neuronal progenitor formation, proliferation, and the reestablishment of the Müller glia cells. These markers will be important to further characterize the regeneration response in other retinal damage models and to elucidate the defects associated with mutants and morphants that disrupt the regeneration response.


Drug-induced cholestasis.
Recent progress in understanding the molecular mechanisms of bile formation and cholestasis have led to new insights into the pathogenesis of drug-induced cholestasis. This review summarizes their variable clinical presentations, examines the role of transport proteins in hepatic drug clearance and toxicity, and addresses the increasing importance of genetic determinants, as well as practical aspects of diagnosis and management.


Redescriptions of three tintinnid ciliates, Tintinnopsis tocantinensis, T. radix, and T. cylindrica (ciliophora, spirotrichea), from coastal waters off China.
In the present study the morphology and ciliary pattern of three marine tintinnid ciliates, namely Tintinnopsis tocantinensisKofoid and Campbell, 1929, Tintinnopsis radix (Imhof, 1886) Brandt, 1907, and Tintinnopsis cylindricaDaday, 1887, isolated from Chinese coastal waters off Shenzhen and Qingdao, respectively, were investigated using living observation and silver impregnation methods. Detailed ciliary patterns of T. tocantinensis and T. radix are reported here for the first time, comprising a ventral, dorsal, and posterior kinety as well as a right, left, and lateral ciliary field. Furthermore, based on previous and present investigations, redescriptions for all three species and improved diagnoses for T. tocantinensis and T. radix are supplied.


Discovery, structural determination, and putative processing of the precursor protein that produces the cyclic trypsin inhibitor sunflower trypsin inhibitor 1.
Backbone-cyclized proteins are becoming increasingly well known, although the mechanism by which they are processed from linear precursors is poorly understood. In this report the sequence and structure of the linear precursor of a cyclic trypsin inhibitor, sunflower trypsin inhibitor 1 (SFTI-1) from sunflower seeds, is described. The structure indicates that the major elements of the reactive site loop of SFTI-1 are present before processing. This may have importance for a protease-mediated cyclizing reaction as the rigidity of SFTI-1 may drive the equilibrium of the reaction catalyzed by proteolytic enzymes toward the formation of a peptide bond rather than the normal cleavage reaction. The occurrence of residues in the SFTI-1 precursor susceptible to cleavage by asparaginyl proteases strengthens theories that involve this enzyme in the processing of SFTI-1 and further implicates it in the processing of another family of plant cyclic proteins, the cyclotides. The precursor reported here also indicates that despite strong active site sequence homology, SFTI-1 has no other similarities with the Bowman-Birk trypsin inhibitors, presenting interesting evolutionary questions.


Structural models of mammalian mitochondrial transcription factor B2.
Mammalian mitochondrial DNA (mtDNA) encodes 13 core proteins of oxidative phosphorylation, 12S and 16S ribosomal RNAs, and 22 transfer RNAs. Mutations and deletions of mtDNA and/or nuclear genes encoding mitochondrial proteins have been implicated in a wide range of diseases. Thus, cell survival and health of the organism require some steady-state level of the mitochondrial genome and its expression. In mammalian systems, the mitochondrial transcription factor B2 (mtTFB2 or TFB2M) is indispensable for transcription initiation. TFB2M along with two other proteins, mitochondrial RNA polymerase (mtRNAP or POLRMT) and mitochondrial transcription factor A (mtTFA or TFAM), are key components of the core mitochondrial transcription apparatus. Structural information for POLRMT and TFAM from humans is available; however, there is no available structure for TFB2M. In the present study, three-dimensional structure of TFB2M from humans was modeled using a combination of homology modeling and small-angle X-ray scattering (SAXS). The TFB2M structural model adds substantively to our understanding of TFB2M function. An explanation for the low or absent RNA methyltransferase activity is provided. A putative nucleic acid-binding site is revealed. The amino and carboxy termini, while likely lacking defined secondary structure, appear to adopt compact, globular conformations, thus "capping" the ends of the protein. Finally, sites of interaction of TFB2M with other factors, protein and/or nucleic acid, are suggested by the identification of species-specific clusters on the surface of the protein.


Formation of Nepsilon-(succinyl)lysine in vivo: a novel marker for docosahexaenoic acid-derived protein modification.
Free radical-catalyzed peroxidation of docosahexaenoic acid (DHA, C22:6/omega-3) generates various lipid peroxidation products that covalently modify biomolecules such as proteins. Under a free radical-generating system, DHA significantly modified lysine residues in bovine serum albumin. Upon incubation of oxidized DHA with an amino-compound pyridoxamine or a lysine-containing peptide, N-propanoyl and N-succinyl adducts were determined to be the major modification products. The hydroperoxide levels in the oxidized DHA closely reflected the formation of the N(epsilon)-(succinyl)lysine (SUL) upon reaction with the peptide, indicating that the hydroperoxides of DHA represent a potential pathway for the formation of SUL. To detect the DHA-derived protein modification in vivo, we developed a monoclonal antibody (mAb2B12) specific to SUL and found that the antibody specifically reacts with the SUL moiety. The formation of SUL was then immunochemically demonstrated in the liver of mice fed with DHA followed by intraperitoneal injection of carbon tetrachloride (CCl(4)), a hepatic lipid peroxidation model. Immunoreactive materials with mAb2B12 were observed in the DHA + CCl(4) group, but were not significant in the control, DHA-alone, and CCl(4)-alone groups. These data suggest that the formation of DHA-derived adducts such as SUL may be implicated in the oxidative damage observed in DHA-enriched tissues.


Comparative effects of anti-inflammatory corticosteroids in human bone-derived osteoblast-like cells.
While effects of inhaled corticosteroids on serum markers of bone metabolism in normal and asthmatic subjects have been reported, there are little data on the direct effects of these corticosteroids on end-organs such as bone. The results presented here compare the effects of budesonide and its epimers (22S- and 22R-budesonide), fluticasone and dexamethasone on growth and differentiation of cultured human bone cells. Osteoblast-like cells were cultured from human foetal bone chips grown to confluence and used at first subculture. At concentrations of 10(-11)-10(-7) M each corticosteroid (CS) caused a dose-dependent decrease in [3H]thymidine incorporation into deoxyribonucleic acid (DNA), median effective concentration (EC50): fluticasone (0.06 nM) >22R (0.26 nM) >22S (0.4 nM) >budesonide (0.47 nM) >dexamethasone (1.5 nM). Each CS resulted in a dose-dependent increase in alkaline phosphatase activity, EC50: fluticasone (0.14 nM) >22R (0.2 nM)=22S (0.2 nM) >budesonide (0.4 nM) >dexamethasone (1.6 nM). The 1,25 dihydroxyvitamin D3 (1,25(OH)2D3)-stimulated osteocalcin production was decreased in the presence of each CS, EC50: fluticasone (0.02 nM) >22S (0.1 nM) >22R (0.2 nM) >budesonide (1.0 nM) >dexamethasone (1.8 nM). In human bone cells the potencies of fluticasone and budesonide in relation to dexamethasone are not dissimilar to those derived from human lymphocytes in vitro.


The relation among gonadal steroids, immunocompetence, body mass, and behavior in young black-headed gulls (Larus ridibundus).
We experimentally examined the effect of testosterone on the antibody response to a single immunization with sheep red blood cells in young black-headed gulls. This species performs a number of testosterone-mediated elaborate postural displays in social interactions and breeds in dense colonies in which there is a high likelihood of infectious diseases. In young chicks, only one-third were capable of responding to immunization. In the responding chicks, testosterone enhanced antibody titers. Even when antibody responsiveness was measured >1 mo after the termination of hormonal treatment, antibody responses were enhanced in birds treated with androgen but not estrogen. At 9 mo of age, all birds responded to immunization, but there was no effect of testosterone on antibody titers. In these juveniles, frequency of display behavior was negatively related to changes in body mass, which suggests that displaying is energetically costly. Despite decreased body mass, antibody titers were highest in birds that displayed more frequently. This suggests that displaying signals immunocompetence. The results are discussed in relation to the immunocompetence handicap hypothesis and to what is known of the influence of the bursa of Fabricius and social stress on antibody production.


Peripheral spatial vision: limits imposed by optics, photoreceptors, and receptor pooling.
We examined the contribution of optical and photoreceptor properties as well as receptor pooling to eccentricity-dependent variations in spatial vision by comparing the performance of ideal observers with that of human observers. We measured contrast sensitivity functions in human observers and calculated such functions in ideal observers for retinal eccentricities of 0-40 deg. Comparisons of human and ideal performance in a variety of tasks reveal that many aspects of the variation in spatial vision with eccentricity can be understood from an analysis of the discrimination information available at the retinal ganglion cells.


The clear liquid diet is no longer a necessity in the routine postoperative management of surgical patients.
The reinstitution of oral intake in patients who have undergone intra-abdominal surgery has traditionally progressed in a stepwise fashion. Various retrospective studies and anecdotal reports have suggested that a "regular" diet as the first postoperative meal is well tolerated. Although clear liquids are accepted as the standard first postoperative meal, there appears to be little scientific data to support their use. The current study was undertaken to determine whether there is any difference in tolerance to clear liquids versus a regular diet as the first postoperative oral intake. This study is not intended to suggest that clear liquid diets harm patients but to attempt to support our hypothesis that a regular diet as the first postoperative meal is not associated with and increased morbidity. A total of 241 patients undergoing abdominal operations were prospectively randomized to receive either routine clear liquids (N=135) or regular diet (N=106) as the first oral intake. They were followed for any symptoms or signs of dietary intolerance. The group receiving a regular diet was not found to have any statistically significant increase in dietary intolerance in comparison with the clear liquid group. Nutritional data collected in a subset of patients revealed a higher caloric intake in those assigned to a regular diet. These results suggest that the routine use of clear liquids as the initial postoperative diet may be unnecessary and nutritionally suboptimal when compared with a regular diet.


An Independent Risk of Gout on the Development of Deep Vein Thrombosis and Pulmonary Embolism: A Nationwide, Population-Based Cohort Study.
Previous studies indicated that gout is a risk factor of cardiovascular diseases. This study aimed to determine if patients with gout have an increased risk of deep vein thrombosis (DVT) or pulmonary embolism (PE).We used the Longitudinal Health Insurance Database, a subset of the national insurance claim dataset, which enrolled 1 million Taiwanese to identify 57,981 patients with gout and 115,961 reference subjects matched by sex, age, and entry date of diagnosis. The risk of DVT and PE was analyzed using the Cox proportional hazards model.In this Taiwanese dataset observed from 2000 to 2010, we found the incidence of DVT was 5.26 per 10 person-years in the gout cohort, which was twofold higher than the incidence of 2.63 per 10 person-years in the reference cohort. After adjusting for age, sex, and 9 comorbidities, the hazard ratio (HR) of developing DVT was 1.66 (95% confidence interval [CI] = 1.37-2.01). Among patients with gout, the youngest age group had the highest increase in the risk of developing DVT (HR [95% CI] = 2.04 [1.24-3.37] for ages 20 to 49 years, 1.80 [1.28-2.51] for ages 50 to 64 years, and 1.45 [1.11-1.91] for ages ≥65 years). The incidence of PE was about one-fifth that of DVT in gout patients, but the effect of gout on the risk was similar (HR [95% CI] = 1.53 [1.01-2.29]).Our analysis confirmed that gout increased the risk of DVT and PE. Further exploration is needed in the future.


Radiation-induced changes in DNA methylation and their relationship to chromosome aberrations in nuclear power plant workers.
We investigated the association between occupational radiation exposure and DNA methylation changes in nuclear power plant workers. We also evaluated whether radiation- induced DNA methylation alterations are associated with chromosome aberrations. The study population included 170 radiation-exposed workers and 30 controls. We measured global, long interspersed nuclear element-1 (LINE-1), and satellite 2 methylation levels in blood leukocyte DNA. The analysis of chromosome aberrations was performed on peripheral lymphocytes. Global DNA methylation levels were lower in radiation-exposed workers than in controls. The methylation levels were negatively associated with the recent 1.5-year radiation dose in a multiple linear regression model (β = - 0.0088, p ≤ 0.001); the levels increased proportionally with the total cumulative dose in radiation-exposed workers. LINE-1 methylation levels were higher in radiation-exposed workers than in controls and were significantly associated with the total cumulative radiation dose in a multiple linear regression model (β = - 0.031, p = 0.035). Global DNA methylation levels were also correlated with chromosome aberrations among workers. Workers with low global methylation levels had a higher frequency of chromosome aberrations than did subjects with high global methylation levels. Occupational exposure to low-dose radiation could affect DNA methylation levels, and the radiation-induced DNA methylation alterations may be associated with chromosome aberrations.


Upper airway and skin symptoms in allergic and non-allergic asthma: Results from the Swedish GA2LEN study.
Allergic and non-allergic asthma are viewed as separate entities, despite sharing similarities. The aims of this study were to determine differences in symptoms from the upper airways and the skin in allergic and non-allergic asthma. The secondary aims were to identify childhood risk factors and to compare quality of life in the two asthma groups. This cohort (age 17-76 years) consisted of 575 subjects with allergic or non-allergic asthma and 219 controls. The participants participated in an interview, spirometry, FeNO, skin prick test, and responded to the Mini Asthma Quality of Life Questionnaire. Self-reported allergic rhinitis was significantly more common in both allergic and non-allergic asthma (82.3 and 40.7%) groups compared with the controls. The prevalence of chronic rhinosinusitis (CRS) was similar in both asthma groups. Eczema was significantly more common in both asthmatic groups (72.3 and 59.8%) than controls (47.0%) (p < 0.001 and p = 0.012). Severe respiratory infection in childhood and parental allergy were risk factors for both allergic and non-allergic asthma groups. Quality of life was significantly lower in non-allergic than allergic asthma groups (p = 0.01). Concomitant symptoms from the upper airways and the skin were significantly more common in both allergic and non-allergic asthma. This indicates that non-allergic asthma has a systemic component with similarities to what is found in allergic asthma. There were similarities in the childhood risk factor pattern between the two types of asthma but asthma-related quality of life was lower in the non-allergic asthma group.


Translation, cultural adaptation and validation of a patient-reported experience measure for children.
There is no national, validated, generic patient-reported experience measure (PREM) for children under 15 years of age in Sweden. A recent cross-sectional study found no consensus in how children's voices are heard in paediatric health care, as well as a lack of validated questionnaires. The aim of this study is to translate, adapt and validate the six versions of the Children's and Young People's PREM for use in a Swedish health care context. An exploratory sequential mixed-method design including cognitive interviews and content validity index (CVI) was used. The interviews focused on evaluating children's understanding of the questionnaire, and the CVI was used to further adjust the relevance of the questionnaire. A convenience sample of 62 children participated in the cognitive interviews and an additional convenience sample of 42 children was included in the CVI testing. The children, aged 8-16 years, were attending routine visits at paediatric departments in a county hospital and a children's hospital in the mid-Sweden region between October 2020 and June 2022. The translation, adaptation and validation process identified several issues regarding the understanding of the questionnaire in a Swedish context. Adaptations were made based on issues related to context, wording and the structure of the questions. CVI testing resulted in the removal of 3-10 questions in each of the different versions of the questionnaire. The study has resulted in six face- and content-validated Swedish versions of the questionnaire ready for pilot testing. Although the versions of the original questionnaire were developed in collaboration with children in the United Kingdom, this did not mean that they could automatically be used in a Swedish health care context. This study confirms the importance of a rigorous process of adaptation and validation to ensure quality and applicability to children accessing health care in different countries. Children's views have guided the development of the original instrument and its adaptation to the Swedish health care context. Due to the strong patient involvement in the process of developing the Swedish versions of the questionnaire, the research group made a pragmatic decision to have no other patient contribution in the study.


A new skin-surface device for measuring the curvature and global and segmental ranges of motion of the spine: reliability of measurements and comparison with data reviewed from the literature.
There is an increasing awareness of the risks and dangers of exposure to radiation associated with repeated radiographic assessment of spinal curvature and spinal movements. As such, attempts are continuously being made to develop skin-surface devices for use in examining the progression and response to treatment of various spinal disorders. However, the reliability and validity of measurements recorded with such devices must be established before they can be recommended for use in the research or clinical environment. The aim of this study was to examine the reliability of measurements using a newly developed skin-surface device, the Spinal Mouse. Twenty healthy volunteers (mean age 41 +/- 12 years, nine males, 11 females) took part. On 2 separate days, spinal curvature was measured with the Spinal Mouse during standing, full flexion, and full extension (each three times by each of two examiners). Paired t-tests, intraclass correlation coefficients (ICC), and standard errors of measurement (SEM) with 95% confidence intervals were used to characterise between-day and interexaminer reliability for: standing sacral angle, lumbar lordosis, thoracic kyphosis, and ranges of motion (flexion, extension) of the thoracic spine, lumbar spine, hips, and trunk. The between-day reliability for segmental ranges of flexion was also determined for each motion segment from T1-2 to L5-S1. The majority of parameters measured for the 'global regions' (thoracic, lumbar, or hips) showed good between-day reliability. Depending on the parameter of interest, between-day ICCs ranged from 0.67 to 0.92 for examiner 1 (average 0.82) and 0.57 to 0.95 for examiner 2 (average 0.83); for 70% of the parameters measured, the ICCs were greater than 0.8 and generally highest for the lumbar spine and whole trunk measures. For lumbar spine range of flexion, the SEM was approximately 3 degrees. The ICCs were also good for the interexaminer comparisons, ranging from 0.62 to 0.93 on day 1 (average 0.81) and 0.70 to 0.94 on day 2 (average 0.86), although small systematic differences were sometimes observed in their mean values. The latter were still evident even if both examiners used the same skin markings. For segmental ranges of flexion, the ICCs varied between vertebral levels but overall were lower than for the global measures (average for all levels in all analyses, ICC 0.6). For each examiner, the average between-day SEM over all vertebral levels was approximately 2 degrees. For 'global' regions of the spine, the Spinal Mouse delivered consistently reliable values for standing curvatures and ranges of motion which compared well with those reported in the literature. This suggests that the device can be reliably implemented for in vivo studies of the sagittal profile and range of motion of the spine. As might be expected for the smaller angles being measured, the segmental ranges of flexion showed lower reliability. Their usefulness with regard to the interpretation of individual results and the detection of 'real change' on an individual basis thus remains questionable. Nonetheless, the group mean values showed few between-day differences, suggesting that the device may still be of use in providing clinically interesting data on segmental motion when examining groups of individuals with a given spinal pathology or undergoing some type of intervention.


An assessment of temporal, spatial and taxonomic trends in harmful algal toxin exposure in stranded marine mammals from the U.S. New England coast.
Despite a long-documented history of severe harmful algal blooms (HABs) in New England coastal waters, corresponding HAB-associated marine mammal mortality events in this region are far less frequent or severe relative to other regions where HABs are common. This long-term survey of the HAB toxins saxitoxin (STX) and domoic acid (DA) demonstrates significant and widespread exposure of these toxins in New England marine mammals, across multiple geographic, temporal and taxonomic groups. Overall, 19% of the 458 animals tested positive for one or more toxins, with 15% and 7% testing positive for STX and DA, respectively. 74% of the 23 different species analyzed demonstrated evidence of toxin exposure. STX was most prevalent in Maine coastal waters, most frequently detected in common dolphins (Delphinus delphis), and most often detected during July and October. DA was most prevalent in animals sampled in offshore locations and in bycaught animals, and most frequently detected in mysticetes, with humpback whales (Megaptera novaeangliae) testing positive at the highest rates. Feces and urine appeared to be the sample matrices most useful for determining the presence of toxins in an exposed animal, with feces samples having the highest concentrations of STX or DA. No relationship was found between the bloom season of toxin-producing phytoplankton and toxin detection rates, however STX was more likely to be present in July and October. No relationship between marine mammal dietary preference and frequency of toxin detection was observed. These findings are an important part of a framework for assessing future marine mammal morbidity and mortality events, as well as monitoring ecosystem health using marine mammals as sentinel organisms for predicting coastal ocean changes.


The peptide transport system Opt is involved in both nutrition and environmental sensing during growth of Lactococcus lactis in milk.
Lactococcus lactis is known to take up extracellular peptides via at least three distinct peptide transporters. The well-described oligopeptide transporter Opp alone is able to ensure the growth of L. lactis in milk, while the di- and tripeptide transporter DtpT is involved in a peptide-dependent signalling mechanism. The oligopeptide Opt transporter displays two peptide-binding proteins, OptA and OptS. We previously demonstrated that OptA-dependent transport is dedicated to nutritional peptides, as an optABCDF mutant (of a strain devoid of Opp) has an impaired capacity to grow in milk. Using isogenic peptide transport mutants, this study shows that biosynthesis of the Opt transporter is much less sensitive to downregulation that is dependent on extracellular peptides taken up by DtpT than is Opp biosynthesis; this peptide-dependent regulation relies on the transcriptional repressor CodY. We demonstrate the dual function of the Opt system; while OptA contributes to the bacterial nutrition during growth in milk, OptS is involved in the transport of signalling peptides derived from milk and controlling opp expression. So, these results shed new light on the peptide-dependent regulation relying on two peptide transporters with different specificities: DtpT and Opt (via OptS).


Integrated mapping of lymphatic filariasis and podoconiosis: lessons learnt from Ethiopia.
The World Health Organization (WHO), international donors and partners have emphasized the importance of integrated control of neglected tropical diseases (NTDs). Integrated mapping of NTDs is a first step for integrated planning of programmes, proper resource allocation and monitoring progress of control. Integrated mapping has several advantages over disease specific mapping by reducing costs and enabling co-endemic areas to be more precisely identified. We designed and conducted integrated mapping of lymphatic filariasis (LF) and podoconiosis in Ethiopia; here we present the methods, challenges and lessons learnt. Integrated mapping of 1315 communities across Ethiopia was accomplished within three months. Within these communities, 129,959 individuals provided blood samples that were tested for circulating Wuchereria bancrofti antigen using immunochromatographic card tests (ICT). Wb123 antibody tests were used to further establish exposure to LF in areas where at least one ICT positive individual was detected. A clinical algorithm was used to reliably diagnose podoconiosis by excluding other potential causes of lymphoedema of the lower limb. A total of 8110 individuals with leg swelling were interviewed and underwent physical examination. Smartphones linked to a central database were used to collect data, which facilitated real-time data entry and reduced costs compared to traditional paper-based data collection approach; their inbuilt Geographic Positioning System (GPS) function enabled simultaneous capture of geographical coordinates. The integrated approach led to efficient use of resources and rapid mapping of an enormous geographical area and was well received by survey staff and collaborators. Mobile based technology can be used for such large scale studies in resource constrained settings such as Ethiopia, with minimal challenges. This was the first integrated mapping of podoconiosis and LF globally. Integrated mapping of podoconiosis and LF is feasible and, if properly planned, can be quickly achieved at nationwide scale.


Heats of formation of xenon fluorides and the fluxionality of XeF(6) from high level electronic structure calculations.
Atomization energies at 0 K and heats of formation at 0 and 298 K are predicted for XeF(+), XeF(-), XeF(2), XeF(4), XeF(5)(-), and XeF(6) from coupled cluster theory (CCSD(T)) calculations with new correlation-consistent basis sets for Xe. To achieve near chemical accuracy (+/-1 kcal/mol), up to four corrections were added to the complete basis set binding energies based on frozen core coupled cluster theory energies: a correction for core-valence effects, a correction for scalar relativistic effects, a correction for first-order atomic spin-orbit effects, and in some cases, a second-order spin-orbit correction. Vibrational zero-point energies were computed at the coupled cluster level of theory. The structure of XeF(6) is difficult to obtain with the C(3)(v)() and O(h)() structures having essentially the same energy. The O(h)() structure is only 0.19 kcal/mol below the C(3)(v)() one at the CCSD(T)/CBS level using an approximate geometry for the C(3)(v)() structure. With an optimized C(3)(v)() geometry, the C(3)(v)() structure would probably become slightly lower in energy than the O(h)() one. The calculated heats of formation for the neutral XeF(n)() fluorides are less negative than the experimental values from the equilibrium measurements by 2.0, 7.7, and 12.2 kcal/mol for n = 2, 4, and 6, respectively. For the experimental values, derived from the photoionization measurements, this discrepancy becomes even larger, suggesting a need for a redetermination of the experimental values. Evidence is presented for the fluxionality of XeF(6) caused by the presence of a sterically active, free valence electron pair on Xe.


Evaluation of tools to prevent drug incompatibilities in paediatric and neonatal intensive care units.
Intravenous drug administration in neonatal (NICU) and paediatric intensive care units (PICU) is critical because of poor venous access, polymedication, fluid restriction and low infusion rate. Risk is further increased by inadequate information on the physicochemical compatibility of drugs. Eight decision-supporting tools were hence evaluated to improve the detection of drug incompatibilities in paediatric wards. NICU and PICU, University hospital. Eight tools (Thériaque 2007, Stabilis 3, Perfysi 2 databases; KIK 3.0 software; Neofax 2007 handbook; King 2008 Guide, CHUV 9.0, pH 2007 cross-tables) were assessed by two pharmacists using 40 drug pairs (20 incompatible; 20 compatible) frequently prescribed in PICUs and NICUs. Trissel's 14th Ed. handbook served as the gold standard. Four criteria were evaluated (each with a maximum of 250 points): accuracy (sensitivity, specificity, positive and negative predictive values), completeness (number of drug pairs documented), comprehensiveness (presence of 16 different items), and applicability (by combining the time needed by 7 pharmacists to classify 5 drug pairs, plus an evaluation of their design, usefulness, reliability and ergonomics, using visual analogy scales). The percentage of non-compliant answers (NCA) was calculated for both the performing pharmacists and the tools. Global score of drug incompatibilities (accuracy + completeness + comprehensiveness + applicability). Thériaque obtained the best global score (840/1000 points), followed by pH (807), CHUV (803), Perfysi (776), Neofax (678), King Guide (642), Stabilis (584) and KIK (523), respectively. The highest scores were reached by Thériaque for accuracy (234/250); Thériaque and pH for completeness (200/250); Thériaque and Perfysi for comprehensiveness (218/250); and pH for applicability (298/250). The range of pharmacists' NCAs was between 9% (4/45 NCAs) and 33% (15/45), whereas that for drug pairs was between 10% (6/63) and 30% (19/63). The range of NCAs for tools was between 6% (2/35, pH) and 49% (18/35, Perfysi). Thériaque proved outstanding as a drug-incompatibility tool. However, all resources showed some shortcomings. The large ranges of pharmacists' NCAs shows that such an assessment is subject to different interpretations. Standard operating procedures for drug-incompatibility assessment should be implemented in drug-information centres. Tools with low NCA percentage, such as the pH or CHUV tables, may be useful for nurses in ICUs.


Simultaneous onset of steroid resistant nephrotic syndrome and IDDM in two young children.
The cases are reported of two young children who developed insulin-dependent diabetes mellitus (IDDM) within 2 weeks of receiving a diagnosis of nephrotic syndrome. Neither patient responded to 8 weeks of daily prednisolone. The first patient presented at 2 years and 9 months of age. Her renal biopsy showed mesangial proliferation. The second child presented with steroid resistant nephrotic syndrome at 18 months of age and developed IDDM 2 weeks later. He achieved partial remission with cyclosporine therapy. His initial renal biopsy at 3 years of age showed minimal change disease and follow-up renal biopsy at 5 years of age showed early diabetic glomerulosclerosis. Tests for NPHS2 and WT1 genetic mutations were negative in both patients. To our knowledge this is the first report of steroid resistant nephrotic syndrome with almost simultaneous onset of IDDM in young children.


Prevalence and factors associated with female sterilization in Rwanda: evidence from the demographic and health survey data (2019-2020).
Female sterilization is a safe and effective surgical procedure of achieving contraception. There is disparity in the prevalence of female sterilization globally, with high income countries having higher rates than low- and middle-income countries. However, current evidence of the uptake of female sterilization in Rwanda is not known. We therefore evaluated the prevalence and factors associated with female sterilization among women of reproductive age in Rwanda. This was a secondary data analysis of 14,634 women of reproductive age (15-49) in Rwanda. The data utilized was from the Rwanda Demographic Health and Survey (RDHS) 2019/2020. The predictors of female sterilization were determined using multivariable binary logistic regression analysis. We found that the prevalence of female sterilization was 1.1% among women of reproductive age in Rwanda. Women older than 35 years had about 8 times higher chance of being sterilized as compared to younger women (aOR: 7.87, 95% CI: 4.77-12.99). Women living with their partners had higher odds of being sterilized as compared to never married women (aOR: 19.23, 95% CI: 4.57-80.82), while women from minority religion are more likely to be sterilized as compared to those of the catholic religion (aOR: 2.12, 95% CI: 1.03-4.37). Women from rich household had a higher chance to be sterilized as compared to their counterparts from poor households (aOR: 3.13, 95% CI: 1.94-5.03). Women from the Western region were more likely to accept sterilization compared to women from Kigali (aOR: 2.025, 95% CI: 1.17-3.49) and women who had more than 5 children had higher odds when compared to women who had 5 or less children (aOR: 1.49, 95% CI: 1.06-2.10). The overall prevalence of sterilization among Rwandan women of reproductive age was 1.1%, which was very low as compared to India (29%), China (14.1%) and United States of America (13.7%). The age, marital status, religion, household wealth quintile, region and children ever born were associated with the uptake of female sterilization among Rwandan women. Public awareness campaign on the advantages of female sterilization should be done to improve uptake.


Reconstitution of affinity-purified dopamine D2 receptor binding activities by specific lipids.
The role of lipids in maintaining ligand binding properties of affinity-purified bovine striatal dopamine D2 receptor was investigated in detail. The receptor, purified on a haloperidol-linked Sepharose CL6B affinity column, exhibited low [3H]spiroperidol binding unless reconstituted with soybean phospholipids. In order to understand the role of individual phospholipids in maintaining the receptor binding activity, the purified preparation was reconstituted separately with individual phospholipids and assayed for [3H]spiroperidol binding. Except for phosphatidylcholine and phosphatidylethanolamine, that respectively restored 30 and 20% binding as compared to that obtained with soybean lipids, reconstitution with other lipids had very little effect. When various combinations of phospholipids were used for reconstitution, a phosphatidylcholine and phosphatidylserine mixture seemed to almost fully restore the receptor binding. A mixture of phosphatidylcholine and phosphatidylethanolamine was as effective as phosphatidylcholine alone in reconstituting ligand binding; however, when phosphatidylserine was also included in the mixture, there was a pronounced increase in binding (about 2-fold compared to the soybean lipids and about 6-fold compared to the phosphatidylcholine-phosphatidylethanolamine mixture). Substitution of other phospholipids or cholesterol for phosphatidylserine in phosphatidylcholine and phosphatidylethanolamine mixture had little effect. Maximal reconstitution of [3H]spiroperidol binding was obtained with phosphatidylcholine, phosphatidylethanolamine and phosphatidylserine mixture (2:2:1, w/w) at a concentration of 0.5 mg/ml. The reconstituted receptor exhibited high affinity binding for [3H]spiroperidol which was comparable to that obtained with membrane or solubilized preparations. Various dopaminergic antagonists and agonists showed appropriate order of potency for the reconstituted receptor. The presently described reconstitution data suggest a role of specific phospholipids in preserving the binding properties of dopamine D2 receptor and should prove useful in studies on functional reconstitution of the receptor.


Oral disease profiles in chronic graft versus host disease.
At least half of patients with chronic graft-versus-host-disease (cGVHD), the leading cause of morbidity and non-relapse mortality after allogeneic stem cell transplantation, have oral manifestations: mucosal lesions, salivary dysfunction, and limited mouth-opening. cGVHD may manifest in a single organ or affect multiple organ systems, including the mouth, eyes, and the skin. The interrelationship of the 3 oral manifestations of cGVHD with each other and with the specific manifestations of extraoral cGVHD has not been studied. In this analysis, we explored, in a large group of patients with cGVHD, the potential associations between: (1) oral mucosal disease and erythematous skin disease, (2) salivary gland dysfunction and lacrimal gland dysfunction, and (3) limited mouth-opening and sclerotic skin cGVHD. Study participants, enrolled in a cGVHD Natural History Protocol (NCT00331968, n = 212), underwent an oral examination evaluating: (1) mucosal cGVHD [NIH Oral Mucosal Score (OMS)], (2) salivary dysfunction (saliva flow and xerostomia), and (3) maximum mouth-opening measurement. Parameters for dysfunction (OMS > 2, saliva flow ≤ 1 mL/5 min, mouth-opening ≤ 35 mm) were analyzed for association with skin cGVHD involvement (erythema and sclerosis, skin symptoms), lacrimal dysfunction (Schirmer's tear test, xerophthalmia), Lee cGVHD Symptom Scores, and NIH organ scores. Oral mucosal disease (31% prevalence) was associated with skin erythema (P < 0.001); salivary dysfunction (11% prevalence) was associated with lacrimal dysfunction (P = 0.010) and xerostomia with xerophthalmia (r = 0.32, P = 0.001); and limited mouth-opening (17% prevalence) was associated with skin sclerosis (P = 0.008) and skin symptoms (P = 0.001). There was no association found among these 3 oral cGVHD manifestations. This analysis supports the understanding of oral cGVHD as 3 distinct diseases: mucosal lesions, salivary gland dysfunction, and mouth sclerosis. Clear classification of oral cGVHD as 3 separate manifestations will improve clinical diagnosis, observational research data collection, and the definitions of outcome measures in clinical trials.


Structure and specificity of GATA proteins in Th2 development.
Development of Th2 subset of CD4+ T cells involves the interleukin-4 (IL-4)- and Stat6-dependent increase in GATA-3 expression during primary activation. Recently we reported that the phenotypic stability and factor independence of Th2 cells involves acquisition of an intracellular pathway that maintains GATA-3 expression. Evidence from retroviral expression studies implied that this pathway involved an autoactivation of GATA-3 expression, since Stat6-deficient T cells induced endogenous GATA-3 when infected with GATA-3-expressing retroviruses. That study left unresolved the issue of whether GATA-3 autoactivation was direct or indirect. Several other Th2-specific transcription factors have been described, including c-Maf and JunB. We therefore examined the ability of these other transcription factors to induce GATA-3 expression and promote Th2 development. Neither c-Maf nor JunB induced Th2 development in Stat6-deficient CD4+ T cells, in contrast to GATA-3. Consistent with this indication of a possible direct autoactivation pathway, we also observed that heterologous GATA family proteins GATA-1, GATA-2, and GATA-4 were also capable of inducing GATA-3 expression in developing Stat6-deficient T cells and promote Th2 development. Mutational analysis revealed evidence for two distinct mechanisms of GATA-3 action. IL-4 induction by GATA-3 required each of the functional domains to be present, whereas repression of gamma interferon could occur even when mutants of GATA-3 lacking the second transactivation domain, TA2, were expressed. The GATA-dependent induction of the GATA-3 but not the other GATA genes in T cells suggests that T-cell-specific cis elements within the GATA-3 locus likely cooperate with a general GATA recognition motif to allow GATA-3-dependent autoactivation.


Increased macrophage migration into adipose tissue in obese mice.
Macrophage-mediated inflammation is a key component of insulin resistance; however, the initial events of monocyte migration to become tissue macrophages remain poorly understood. We report a new method to quantitate in vivo macrophage tracking (i.e., blood monocytes from donor mice) labeled ex vivo with fluorescent PKH26 dye and injected into recipient mice. Labeled monocytes appear as adipose, liver, and splenic macrophages, peaking in 1-2 days. When CCR2 KO monocytes are injected into wild-type (WT) recipients, or WT monocytes given to MCP-1 KO recipients, adipose tissue macrophage (ATM) accumulation is reduced by ~40%, whereas hepatic macrophage content is decreased by ~80%. Using WT donor cells, ATM accumulation is several-fold greater in obese recipient mice compared with lean mice, regardless of the source of donor monocytes. After their appearance in adipose tissue, ATMs progressively polarize from the M2- to the M1-like state in obesity. In summary, the CCR2/MCP-1 system is a contributory factor to monocyte migration into adipose tissue and is the dominant signal controlling the appearance of recruited macrophages in the liver. Monocytes from obese mice are not programmed to become inflammatory ATMs but rather the increased proinflammatory ATM accumulation in obesity is in response to tissue signals.


Epimorphin deletion inhibits polyposis in the Apcmin/+ mouse model of colon carcinogenesis via decreased myofibroblast HGF secretion.
Interactions between the epithelium and surrounding mesenchyme/stroma play an important role in normal gut morphogenesis, the epithelial response to injury, and epithelial carcinogenesis. The tumor microenvironment, composed of stromal cells including myofibroblasts and immune cells, regulates tumor growth and the cancer stem cell niche. Deletion of epimorphin (Epim), a syntaxin family member expressed in myofibroblasts and macrophages, results in partial protection from colitis and from inflammation-induced colon cancer in mice. We sought to determine whether epimorphin deletion protects from polyposis in the Apcmin/+ mouse model of intestinal carcinogenesis. Epim-/- mice were crossed to Apcmin/+ mice; Apcmin/+ and Apcmin/+/Epim-/- mice were killed at 3 mo of age. Polyp numbers and sizes were quantified in small intestine and colon, and gene expression analyses for pathways relevant to epithelial carcinogenesis were performed. Primary myofibroblast cultures were isolated, and expression and secretion of selected growth factors from Apcmin/+ and Apcmin/+/Epim-/- myofibroblasts were examined by ELISA. Small bowel polyposis was significantly inhibited in Apcmin/+/Epim-/- compared with Apcmin/+ mice. Apcmin/+/Epim-/- compared with Apcmin/+ polyps and adjacent uninvolved intestinal mucosa had increased transforming growth factor-β (TGF-β) expression and signaling with increased P-Smad2/3 expression. Myofibroblasts isolated from Apcmin/+/Epim-/- vs. Apcmin/+ mice had markedly decreased hepatocyte growth factor (HGF) expression and secretion. We concluded that Epim deletion inhibits polyposis in Apcmin/+ mice, associated with increased mucosal TGF-β signaling and decreased myofibroblast HGF expression and secretion. Our data suggest that Epim deletion reduces tumorigenicity of the stromal microenvironment.


Asymmetrical localization of mRNAs in enterocytes of human jejunum.
Intracellular localization of specific mRNAs is known to be a mechanism for targeting proteins to specific sites within the cell. Previous studies from this laboratory have demonstrated co-localization of mRNAs and proteins for a number of genes in absorptive enterocytes of fetal rat intestine. The present study was undertaken to examine in human enterocytes the intracellular localization patterns of mRNAs for the microvillous membrane proteins lactase-phlorizin hydrolase (LPH), sucrase-isomaltase (SI), and intestinal alkaline phosphatase (IAP), and the cytoskeletal protein beta-actin. In sections of human jejunum, mRNAs were localized by in situ hybridization using digoxigenin-labeled anti-sense RNA probes. Both LPH and SI mRNAs were localized to the apical region of villous enterocytes, whereas IAP and beta-actin mRNAs were detected both apically and basally relative to the nucleus. Therefore, in contrast to LPH, SI, and beta-actin mRNAs, which co-localize with their encoded proteins, that of IAP is present in the basal region of the cell where IAP protein has not directly been demonstrated to be present. Absorptive enterocytes from humans possess the mechanisms for intracellular mRNA localization, but not all mRNAs co-localize with their encoded proteins.


Becoming a father is an emotional roller coaster - an analysis of first-time fathers' blogs.
To identify and describe the process of fatherhood during the partner's pregnancy among expectant, first-time fathers. Pregnancy seems to be a demanding period for expectant fathers, and this period is a part of their transition to fatherhood. Blogs can be seen as personal diaries and offer an alternative method of collecting data as they are an arena for sharing experiences and narratives. An explorative qualitative design. Blogs from the Internet by eleven first-time fathers living in Sweden were included in the study. Qualitative content analysis was used for the analysis of the blogs. A theme emerged expressing the latent content of the text: 'Becoming a father for the first time is an emotional roller coaster where the role of the expectant father is not obvious' and five different categories describing the manifest content: the pregnancy, a new life, to make the child real, preparations for the delivery and the arrival of the child, and a new role in life. The metaphor 'roller coaster' indicates the tension between different feelings about the men's future as fathers. They are searching for answers on how to be a good father. They feel excluded when they visit antenatal care centres and have difficulties finding out how to support their partner. This is an existential period when they understand themselves as adults and also miss relatives who have died. During pregnancy, the men start to communicate with their child, and this interaction gives a sense of reality and creates hope and joy about being a father. Staff involved in antenatal care can use the knowledge from this study when meeting with expectant fathers. Perspectives expressed in blogs may enhance the professionals' understanding that the transition process of fatherhood is complex.


Detection of Low Oxygen Microenvironments in a Murine Model of Invasive Pulmonary Aspergillosis Using Pimonidazole.
Infection tissue microenvironments are dynamic, complex, and play a critical role in host-microbe interaction outcomes. A crucial parameter of the infection site microenvironment is oxygen. Both host and microbial cell physiology is significantly impacted by the availability of oxygen. When oxygen tensions drop to levels that do not meet the metabolic demands of the cell, a hypoxia response ensues. In numerous host-microbe studies, it has now been observed that the host and microbial hypoxia response plays a critical role in disease outcomes. However, in most pathosystems, spatial and temporal oxygen dynamics throughout the infection remain ill defined. Here, we detail a protocol for detecting low oxygen environments in tissue in a murine model of invasive pulmonary aspergillosis. The protocol utilizes mice immune compromised with a high dose of steroid and challenged via the aerosol route with conidia of the major human fungal pathogen Aspergillus fumigatus. Qualitative analysis of oxygen levels at the site of infection in the murine lung is accomplished with pimonidazole-mediated adduct detection via immunohistochemistry. The protocol is adaptable to other host-microbe interaction models.


The influence of anesthetic choice, PaCO2, and other factors on osmotic blood-brain barrier disruption in rats with brain tumor xenografts.
Increasing the delivery of therapeutic drugs to the brain improves outcome for patients with brain tumors. Osmotic opening of the blood-brain barrier (BBB) can markedly increase drug delivery, but achieving consistent, good quality BBB disruption (BBBD) is essential. We evaluated four experiments compared with our standard isoflurane/O2 protocol to improve the quality and consistency of BBBD and drug delivery to brain tumor and normal brain in a rat model. Success of BBBD was assessed qualitatively with the large molecular weight marker Evans blue albumin and quantitatively by measuring delivery of the low molecular weight marker [3H]-methotrexate. With isoflurane/O2 anesthesia, the effects of two BBBD drugs of different osmolalities were evaluated at two different infusion rates and infusion durations. Arabinose was superior to saline (P = 0.006) in obtaining consistent Evans blue staining in 16 of 24 animals, and it significantly increased [3H]-methotrexate delivery compared with saline in the tumor (0.388 +/- 0.03 vs 0.135 +/-0.04; P = 0.0001), brain around the tumor (0.269 +/- 0.03 vs 0.035 +/- 0.03; P = 0.0001), brain distant to the tumor (0.445 +/- 0.05 vs 0.034 +/- 0.07; P = 0.001), and opposite hemisphere (0.024 +/- 0.00 vs 0.016 +/- 0.00; P = 0.0452). Forty seconds was better than 30 s (P = 0.0372) for drug delivery to the tumor. Under isoflurane/O2 anesthesia (n = 30), maintaining hypocarbia was better than hypercarbia (P = 0.025) for attaining good BBBD. A propofol/ N2O regimen was compared with the isoflurane/O2 regimen, altering blood pressure, heart rate, and PaCO2 as covariates (n = 48). Propofol/N2O was superior to isoflurane/O2 by both qualitative and quantitative measures (P < 0.0001). Neurotoxicity and neuropathology with the propofol/N2O regimen was evaluated, and none was found. These data support the use of propofol/N2O along with maintaining hypocarbia to optimize BBBD in animals with tumors. Propofol/N2O anesthesia may be better than isoflurane/O2 for optimizing osmotic blood-brain barrier disruption for delivery of chemotherapeutic drugs to brain tumor and normal brain.


Synchronous presentation of hepatoid alpha-fetoprotein-producing lung cancer and colorectal adenocarcinoma.
We describe the synchronous presentation of hepatoid adenocarcinoma of the lung and colorectal adenocarcinoma in a patient with elevated alpha-fetoprotein (AFP) serum levels. Our patient was treated after surgery with a conventional chemotherapy regimen including bevacizumab, an anti-vascular endothelial growth factor monoclonal antibody, which was demonstrated to improve the clinical results in the treatment of colorectal and lung cancer compared with chemotherapy alone, and is today approved both for colon and lung cancer. Besides the unconventional association of the two cancer types in our patient and the unsatisfactory clinical benefit obtained with the medical treatment administered, we report on the significance of AFP serum levels as a tumor marker in this peculiar situation. In our patient these levels, monitored from the first clinical symptoms through the last chemotherapy course, did not show any correlation with the response to treatment or with the patient's overall outcome. In particular, the serum marker remained essentially unchanged after the surgical removal of the lung mass and the subsequent chemotherapy.


The effect of vitamin D administration on inflammatory markers in patients with inflammatory bowel disease.
The exact relationship between vitamin D deficiency and inflammatory bowel disease (IBD) remains unclear. We evaluated the effect of vitamin D3 administration on inflammatory responses and disease severity in patients with IBD. We investigated the serum 25-hydroxyvitamin D3 [25-(OH)D] and C-reactive protein (CRP) levels and the partial Mayo score (PMS) in patients with IBD. Vitamin D3 was administered in patients with either vitamin D deficiency or insufficiency and CRP serum vitamin D levels and PMS were re-examined at 6 months of administration. In 88 patients with Crohn's disease (CD), a negative correlation was found between serum vitamin D and CRP. In 178 patients with ulcerative colitis (UC), serum vitamin D showed no association with CRP or PMS. Serum vitamin D increased from 11.08±3.63 to 22.69±6.11 ng/mL in 29 patients with CD and from 11.45±4.10 to 24.20±6.61 ng/mL in 41 patients with UC who received vitamin D3 treatment (P<0.001 and P<0.001, respectively). In patients with CD, median ΔCRP was -0.24 in the normalized vitamin D group and -0.11 in the non-normalized group (P=0.308). In patients with UC, median ΔCRP was -0.01 in the normalized vitamin D group and 0.06 in the non-normalized group (P=0.359). Although a negative correlation was found between serum vitamin D and CRP levels in patients with CD, administration of vitamin D did not improve the CRP level in patients with CD. In patients with UC, serum vitamin D level was unrelated to CRP or PMS.


Slippery Surface Based on Photoelectric Responsive Nanoporous Composites with Optimal Wettability Region for Droplets' Multifunctional Manipulation.
The development of responsive slippery surfaces is important because of the high demand for such materials in the fields of liquid manipulation on biochips, microfluidics, microreactions, and liquid-harvesting devices. Although great progress has been achieved, the effect of substrate wettability on slippery surfaces stability is overlooked by scientists. In addition, current responsive slippery surfaces generally function utilizing single external stimuli just for imprecisely controlling liquid motion, while advanced intelligences are always expected to be integrated into one smart interface material for widespread multifunctional applications. Therefore, designing slippery surfaces that collaboratively respond to complex external stimuli and possess sophisticated composite function for expanding applications from controlling droplets motion to patterned writing is urgently needed but remains a challenge. Here, a photoelectric cooperative-responsive slippery surface based on ZnO nanoporous composites is demonstrated. First, the effect of composite surface wettability on slippery surface stability is systematically researched and the optimum wettability region for fabricating stable slippery surfaces is determined. Furthermore, controllable droplet motion and patterned writing are realized on the same slippery surfaces under photoelectric cooperative stimuli, and the related response mechanism is also deeply studied. This kind of material has potential applications in biochips, microfluidics, in situ patterning, and water-harvesting systems.


A mechanical comparison of veterinary linear external fixation systems.
To compare the fixation rigidity of recently developed external fixation systems (EFSs) to that of the traditional Kirschner-Ehmer (KE) system. In vitro biomechanical study. Five different EFSs (KE, Secur-U, small SK carbon fiber, small SK titanium, large SK carbon fiber) were assembled into 7 frame geometries to stabilize Delrin plastic rods with a 1-cm gap. External skeletal fixation (ESF) constructs were tested in axial compression, torsion, medial-lateral bending, and cranial-caudal bending. Testing was conducted within the elastic range of each fixator. Mean stiffness in each mode was determined from the slope of the linear portion of the load-deformation curve. Comparison of stiffness values of each EFS within each loading mode and frame type was performed with 1-way analysis of variance (P <.05). Mean stiffness values were significantly higher for the large SK EFS in all frame types compared with KE but were equal in torsional stiffness in the double-bar type 1a frame. The small SK EFS with titanium connecting bar had greater stiffness than the KE in all modes for frame types Ia, Ia-accessory bar, and II-modified. No overall difference was detected between the KE EFS and the small SK with carbon fiber rod. The stiffness of the Secur-U type Ia frame with augmentation plate was significantly greater than the KE type Ia with accessory bar. The newer external fixation systems evaluated in this study provided fixation rigidity equal to or greater than that of the KE system. EFSs with increased frame rigidity should permit the use of less complex frame designs while providing fracture stability.


A good sugar, d-mannose, suppresses autoimmune diabetes.
It is well known that too much sugar uptake causes many health problems, including diabetes and obesity (Lustig et al. in Nature 482:27-29, 2012). However, a team of researchers led by Dr. Wanjun Chen of the National Institute of Dental and Craniofacial Research (NIDCR), National Institutes of Health (NIH), USA, have recently shown that d-mannose, a naturally occurring C-2 epimer of glucose is likely beneficial to human health. Their studies have revealed that supraphysiological levels of d-mannose that are safely achievable via drinking-water supplementation can be preventive and therapeutic to experimental autoimmune diabetes and asthmatic lung inflammation (Zhang et al. in Nat Med 23:1036-1045, 2017).


Ipilimumab-induced Guillain-Barré Syndrome Presenting as Dysautonomia: An Unusual Presentation of a Rare Complication of Immunotherapy.
Immune-related adverse events are common and well-documented in patients treated with ipilimumab, a cytotoxic T-lymphocyte antigen-4 monoclonal antibody approved for the treatment of metastatic and stage III melanoma. Neurological complications are rare, but widely variable and potentially devastating. Here, we discuss a case of a patient who was treated with a single dose of ipilimumab for resected stage III melanoma. She subsequently developed pandysautonomia that manifested as a tonically dilated pupil, gastrointestinal dysmotility, urinary retention, and profound orthostatic hypotension. Guillain-Barré syndrome was diagnosed on electromyography. She was treated with intravenous immunoglobulin, droxidopa, and supportive care, with prolonged but eventual recovery. Given the broadening use of ipilimumab in the treatment of advanced and metastatic melanoma, awareness and recognition of its profound immune-mediated adverse effects are essential.


Plasma inter-alpha-trypsin inhibitor-related urinary glycoprotein EDC1 inhibits the growth of a Burkitt's lymphoma cell line.
A homogeneous preparation of a urinary glycoprotein has been isolated from urine of patients with malignant melanoma and advanced adenocarcinomas of colon and lung. This molecule, Mr 30 kDa, is homologous to EDC1, a proteinase inhibitor antigenically related to plasma inter-alpha-trypsin inhibitor (IATI) originally isolated from the urine of a leukemic patient, E.D. The newly isolated EDC1 inhibits cellular proliferation of a Burkitt's lymphoma cell line, Raji, growing in serum-free medium supplemented with insulin, transferrin, selenium, and linoleic acid. This concentration-dependent inhibitory effect was monitored in terms of change in cell number and 3H-thymidine incorporation. The growth of cells treated with approximately 3.3 pmol EDC1/ml was 50% that of the control group by both assays. EDC1 was not cytotoxic to the cells because the EDC1-treated cells excluded trypan blue and resumed normal growth after removal of EDC1. In addition, EDC1 treatment of Raji cells prelabeled with 3H-labeled DNA did not release more radioactivity into the conditioned medium than the untreated labeled cells. EDC1 did not affect the growth of Hs2B2, a B-lymphoblast cell line, and Hs294T, a human malignant melanoma cell line. Equimolar and larger quantities of other proteinase inhibitors with inhibitory profiles similar to that of EDC1 (alpha-1 proteinase inhibitor, soybean trypsin inhibitor, lima bean trypsin inhibitor, and turkey ovomucoid) did not affect the growth of Raji cells. Raji cells have an absolute requirement of transferrin as a nutrient and require insulin to modulate the expression of transferrin receptors. The cells also synthesize interleukin-1 as an autocrine growth stimulator. EDC1 did not form a detectable complex with transferrin, insulin, or any autocrine factor synthesized by the cells.


Alcohol consumption in relation to aberrant DNA methylation in breast tumors.
The mechanism for the observed association of alcohol consumption breast cancer risk is not known; understanding that mechanism could improve understanding of breast carcinogenesis and optimize prevention strategies. Alcohol may impact breast malignancies or tumor progression by altering DNA methylation. We examined promoter methylation of three genes, the E-cadherin, p16, and retinoic acid-binding receptor-β2 (RAR-β2) genes in archived breast tumor tissues from participants in a population-based case-control study. Real time methylation-specific PCR was performed on 803 paraffin-embedded samples, and lifetime alcohol consumption was queried. Unordered polytomous and unconditional logistic regression were used to derive adjusted odds ratios (ORs) and 95% confidence intervals (CIs). RAR-β2 methylation was not associated with drinking. Among premenopausal women, alcohol consumption was also not associated with promoter methylation for E-cadherin and p16 genes. In case-case comparisons of postmenopausal breast cancer, compared with lifetime never drinkers, promoter methylation likelihood was increased for higher alcohol intake for E-cadherin (OR=2.39; 95% CI, 1.15-4.96), in particular for those with estrogen receptor-negative tumors (OR=4.13; 95% CI, 1.16-14.72), and decreased for p16 (OR=0.52; 95% CI, 0.29-0.92). There were indications that the association with p16 was stronger for drinking at younger ages. Methylation was also associated with drinking intensity independent of total consumption for both genes. We found alcohol consumption was associated with DNA methylation in postmenopausal breast tumors, suggesting that the association of alcohol and breast cancer may be related, at least in part, to altered methylation, and may differ by drinking pattern.


Cardiovascular and Cerebral Hemodynamics in Asymptomatic Healthy Subjects With/Without Abnormal Head-up Tilt Test Versus Recurrent Fainters.
The aim of this study was to compare hemodynamic and autonomic responses during head-up tilt test (HUTT) between healthy volunteers and patients with a history of fainting and confirmed vasovagal syncope. We hypothesize that the autonomic and hemodynamic physiologic responses remain intact during orthostatic stress in people without previous fainting and negative HUTT, but deteriorate similarly in patients with recurrent vasovagal syncope and in asymptomatic healthy subjects who develop a vasovagal response during HUTT. The study included 57 asymptomatic healthy volunteers (42% women, mean age 23.7 ± 3.6 years) categorized as negative HUTT (n = 41) and positive HUTT (n = 16). They were compared with 14 patients (50% women, mean age 24.2 ± 6.1 years) with previous spontaneous recurrent syncope and inducible vasovagal response during HUTT. Cerebral and cardiovascular hemodynamic variables were assessed noninvasively during the HUTT in each participant. In all patients with recurrent syncope, tilt was positive after a mean delay of 15.6 ± 8.6 minutes and did not differ from the time to syncope observed after 19.6 ± 6.9 minutes in asymptomatic healthy subjects with a positive test. A significant decrease throughout the tilting was observed in the blood pressure, peripheral resistances, cerebral blood flow, and vascular efferent sympathetic regulation in both groups of subjects with a positive test. This study shows that there are subjects, without a history of syncope, who have a positive HUTT with hemodynamic and autonomic responses alike to patients with confirmed vasovagal syncope, precluding them to be selected as controls in vasovagal syncope studies.


Binocular misalignments elicited by altered gravity provide evidence for nonlinear central compensation.
Increased ocular positioning misalignments upon exposure to altered gravity levels (g-levels) have been strongly correlated with space motion sickness (SMS) severity, possibly due to underlying otolith asymmetries uncompensated in novel gravitational environments. We investigated vertical and torsional ocular positioning misalignments elicited by the 0 and 1.8 g g-levels of parabolic flight and used these data to develop a computational model to describe how such misalignments might arise. Ocular misalignments were inferred through two perceptual nulling tasks: Vertical Alignment Nulling (VAN) and Torsional Alignment Nulling (TAN). All test subjects exhibited significant differences in ocular misalignments in the novel g-levels, which we postulate to be the result of healthy individuals with 1 g-tuned central compensatory mechanisms unadapted to the parabolic flight environment. Furthermore, the magnitude and direction of ocular misalignments in hypo-g and hyper-g, in comparison to 1 g, were nonlinear and nonmonotonic. Previous linear models of central compensation do not predict this. Here we show that a single model of the form a + bg (ε), where a, b, and ε are the model parameters and g is the current g-level, accounts for both the vertical and torsional ocular misalignment data observed inflight. Furthering our understanding of oculomotor control is critical for the development of interventions that promote adaptation in spaceflight (e.g., countermeasures for novel g-level exposure) and terrestrial (e.g., rehabilitation protocols for vestibular pathology) environments.


RES uptake of red blood cell stroma: time course of effects on phagocytic function and susceptibility to endotoxin shock.
Previous studies have demonstrated that the injection of red blood cell (RBC) stroma to simulate the reticuloendothelial system (RES) uptake of RBC debris following intravascular hemolysis causes an acute depression in RES phagocytic function and an increase in shock susceptibility. The present study evaluated the time course of these changes. Initial studies demonstrated that the uptake of iodinated RBC stroma was followed by a decrease in the amount of radioactivity present in the liver between 30 and 60 min after injection. This was associated with an increase in free label in the circulation, indicating an active deiodination of the stroma. Phagocytic function was depressed at 30 min after injection of RBC stroma, but had returned to control by 60 min. Susceptibility to endotoxin shock was increased when endotoxin was injected 30 min, 1 hr, 3 hr, or 6 hr but not 24 hr after the RBC stroma. The increased mortality with endotoxin shock was shown not to be due to depletion of complement by the RBC stroma. This study demonstrated that over the period of recovery of RES phagocytic function following the ingestion of RBC stroma there is metabolism (deiodination) of the particulate material. Additionally, susceptibility to endotoxin shock is increased for a longer period of time than the depression of phagocytic function.


Resetting the circadian clock in cultured Xenopus eyecups: regulation of retinal melatonin rhythms by light and D2 dopamine receptors.
A circadian oscillator is located within the eye of Xenopus laevis. This oscillator regulates retinal melatonin synthesis, stimulating it at night. The primary goal of the studies reported here was to define input pathways to this circadian oscillator as a step toward identification of circadian clock mechanisms. A flow-through superfusion culture system was developed to monitor circadian rhythms of melatonin release from individual eyecups. This system was used to determine the effects of light and dopaminergic agents on melatonin production and on the phase of the circadian oscillator. Six hour light pulses suppressed melatonin production and reset the phase of the free-running melatonin rhythm. Light pulses caused phase delays when applied during the early subjective night, phase advances when applied during the late subjective night, and no phase shift when applied during the subjective day. Dopamine receptor agonists mimicked light in suppressing melatonin release and resetting the phase of the circadian rhythm. The phase-response relationship for phase shifts induced by quinpirole, a D2 dopamine receptor agonist, was similar to that for phase shifts induced by light. Pharmacological analysis with selective catecholamine receptor agonists and antagonists indicated that there are pathways to the melatonin-generating system and the circadian oscillator that include D2 dopamine receptors. A D2 receptor antagonist, eticlopride, completely blocked the effects of dopamine on melatonin release and on circadian phase. However, eticlopride did not alter similar effects induced by light, indicating that dopamine-independent pathways exist for light input to these systems. The effects of light and quinpirole on melatonin release and circadian phase were not additive, indicating that the pathways converge. These pathways to the circadian oscillator in the retina present new avenues for pursuit of cellular circadian clock mechanisms.


Carboxylicivirga gen. nov. in the family Marinilabiliaceae with two novel species, Carboxylicivirga mesophila sp. nov. and Carboxylicivirga taeanensis sp. nov., and reclassification of Cytophaga fermentans as Saccharicrinis fermentans gen. nov., comb. nov.
Two facultatively anaerobic mesophilic bacteria, strains MEBiC 07026(T) and MEBiC 08903(T), were isolated from two different tidal flat sediments and both strains showed approximately 92.2 % 16S rRNA gene sequence similarity with [Cytophaga] fermentans DSM 9555(T). 16S rRNA gene sequence similarity between the two new isolates was 97.5 % but levels of DNA-DNA relatedness between the two were 31.3-31.8 %. Phylogenetic analysis revealed that the two isolates and [Cytophaga] fermentans DSM 9555(T) were affiliated with the family Marinilabiliaceae in the class Bacteroidia. The dominant fatty acids of strains MEBiC 07026(T), MEBiC 08903(T) and [Cytophaga] fermentans DSM 9555(T) were branched-type or hydroxylated C15 : 0, but [Cytophaga] fermentans DSM 9555(T) contained a higher proportion of anteiso-branched fatty acids. The two new isolates contained a markedly higher proportion of monounsaturated fatty acids than other members of the family Marinilabiliaceae. The major respiratory quinone of the strains was MK-7. Strains MEBiC07026(T) and MEBiC08903(T) utilized a wide range of carboxylic acids whereas [Cytophaga] fermentans DSM 9555(T) utilized carbohydrates rather than carboxylic acids. The DNA G+C content of the novel strains was about 44 mol% but that of [Cytophaga] fermentans DSM 9555(T) revealed from the genome sequence was 37.6 mol%. Based on evidence from this polyphasic taxonomic study, a novel genus, Carboxylicivirga gen. nov., is proposed in the family Marinilabiliaceae with two novel species, Carboxylicivirga mesophila sp. nov. with type strain MEBiC 07026(T) ( = KCCM 42978(T) = JCM 18290(T)) and Carboxylicivirga taeanensis sp. nov. with type strain MEBiC 08903(T) ( = KCCM 43024(T) = JCM 19490(T)). Additionally, [Cytophaga] fermentans DSM 9555(T) ( = ATCC 19072(T)) is reclassified as Saccharicrinis fermentans gen. nov., comb. nov.


Frozen quantum coherence.
We analyze under which dynamical conditions the coherence of an open quantum system is totally unaffected by noise. For a single qubit, specific measures of coherence are found to freeze under different conditions, with no general agreement between them. Conversely, for an N-qubit system with even N, we identify universal conditions in terms of initial states and local incoherent channels such that all bona fide distance-based coherence monotones are left invariant during the entire evolution. This finding also provides an insightful physical interpretation for the freezing phenomenon of quantum correlations beyond entanglement. We further obtain analytical results for distance-based measures of coherence in two-qubit states with maximally mixed marginals.


High Temperature-Induced m6A Epigenetic Changes Affect Early Porcine Embryonic Developmental Competence in Pigs.
N6-methyladenosine (m6A), the most prevalent modification in eukaryotic messenger RNA (mRNA), plays a key role in various developmental processes in mammals. Three proteins that affect RNA m6A modification have been identified: methyltransferases, demethylases, and m6A-binding proteins, known as "writer," "eraser," and "reader" proteins, respectively. However, changes in the m6A modification when early porcine embryos are exposed to stress remain unclear. In this study, we exposed porcine oocytes to a high temperature (HT, 41°C) for 10 h, after which the mature oocytes were parthenogenetically activated and cultured for 7 days to the blastocyst stage. HT significantly decreased the rates of the first polar body extrusion and blastocyst formation. Further detection of m6A modification found that HT can lead to increased expression levels of "reader," YTHDF2, and "writer," METTL3, and decreased expression levels of "eraser," FTO, resulting in an increased level of m6A modification in the embryos. Additionally, heat shock protein 70 (HSP70) is upregulated under HT conditions. Our study demonstrated that HT exposure alters m6A modification levels, which further affects early porcine embryonic development.


Yield of early postoperative computed tomography after frontal ventriculoperitoneal shunt placement.
Despite being widely used, ventriculoperitoneal (VP) shunt placement is a procedure often associated with complications and revision surgeries. Many neurosurgical centers routinely perform early postoperative cranial computer tomography (CT) to detect postoperative complications (e.g., catheter malposition, postoperative bleed, over-drainage). Because guidelines are lacking, our study aimed to evaluate the yield of early routine postoperative CT after shunt placement for adult hydrocephalus. We retrospectively reviewed 173 patients who underwent frontal VP shunting for various neurosurgical conditions. Radiological outcomes were proximal catheter malposition, and ventricular width in preoperative and postoperative imaging. Clinical outcomes included postoperative neurological outcome, revision surgery because of catheter malposition or other causes, mortality, and finally surgical, non-surgical, and overall morbidity. In only 3 (1.7%) patients did the early routine postoperative CT lead to revision surgery. Diagnostic ratios for CT finding 1 asymptomatic patient who eventually underwent revision surgery per total number to scan were 1:58 for shunt malposition, 1:86 for hygroma, and 1:173 for a cranial bleed. Five (2.9%) patients with clinically asymptomatic shunt malposition or hygroma underwent intervention based on early postoperative CT (diagnostic ratio 1:25). Shunt malposition occurred in no patient with normal pressure hydrocephalus and 2 (40%) patients with stroke. Lower preoperative Evans' Index was a statistically significant predictor for high-grade shunt malposition. We found a rather low yield for early routine postoperative cranial CT after frontal VP-shunt placement. Therefore, careful selection of patients who might benefit, considering the underlying disease and preoperative radiological findings, could reduce unnecessary costs and exposure to radiation.


A pyrrole-based natural small molecule mitigates HSP90 expression in MDA-MB-231 cells and inhibits tumor angiogenesis in mice by inactivating HSF-1.
Heat shock proteins (HSPs), molecular chaperones, are crucial for the cancer cells to facilitate proper functioning of various oncoproteins involved in cell survival, proliferation, migration, and tumor angiogenesis. Tumor cells are said to be "addicted" to HSPs. HSPs are overexpressed in many cancers due to upregulation of transcription factor Heat-shock factor 1 (HSF-1), the multifaceted master regulator of heat shock response. Therefore, pharmacological targeting of HSPs via HSF-1 is an effective strategy to treat malignant cancers like triple negative breast cancer. In the current study, we evaluated the efficacy of a pyrrole derivative [bis(2-ethylhexyl)1H-pyrrole-3,4-dicarboxylate], TCCP, purified from leaves of Tinospora cordifolia for its ability to suppress heat shock response and angiogenesis using MDA-MB-231 cells and the murine mammary carcinoma: Ehrlich ascites tumor model. HSP90 was downregulated by TCCP by inactivation of HSF-1 resulting in inhibition of tumor cell proliferation, VEGF-induced cell migration, and concomitant decrease in tumor burden and neo-angiogenesis in vivo. The mechanism of suppression of HSPs involves inactivation of PI3K/Akt and phosphorylation on serine 307 of HSF-1 by the activation of ERK1. HSF-1 and HSP90 and 70 localization and expression were ascertained by immunolocalization, immunoblotting, and qPCR experiments. The anti-angiogenic effect of TCCP was studied in vivo in tumor-bearing mice and ex vivo using rat corneal micro-pocket assay. All the results thus corroborate the logic behind inactivating HSF-1 using TCCP as an alternative approach for cancer therapy.


Longitudinal monitoring of mesoscopic cortical activity in a mouse model of microinfarcts reveals dissociations with behavioral and motor function.
Small vessel disease is characterized by sporadic obstruction of small vessels leading to neuronal cell death. These microinfarcts often escape detection by conventional magnetic resonance imaging and are identified only upon postmortem examination. Our work explores a brain-wide microinfarct model in awake head-fixed mice, where occlusions of small penetrating arterioles are reproduced by endovascular injection of fluorescent microspheres. Mesoscopic functional connectivity was mapped longitudinally in awake GCaMP6 mice using genetically encoded calcium indicators for transcranial wide-field calcium imaging. Microsphere occlusions were quantified and changes in cerebral blood flow were measured with laser speckle imaging. The neurodeficit score in microinfarct mice was significantly higher than in sham, indicating impairment in motor function. The novel object recognition test showed a reduction in the discrimination index in microinfarct mice compared to sham. Graph-theoretic analysis of functional connectivity did not reveal significant differences in functional connectivity between sham and microinfarct mice. While behavioral tasks revealed impairments following microinfarct induction, the absence of measurable functional alterations in cortical activity has a less straightforward interpretation. The behavioral alterations produced by this model are consistent with alterations observed in human patients suffering from microinfarcts and support the validity of microsphere injection as a microinfarct model.


[Analysis of hydrocarbon impurities in high purity isobutene by gas chromatography].
A capillary column HP-AlO2O3/S PLOT(50 m x 0.32 mm i.d. x 8 microm) has been used for the analysis of trace hydrocarbon impurities in high purity isobutene. The results showed that these hydrocarbon impurities could be well separated and with the liquid-phase sample injection valve the disproportionation of sample composition could be avoided. The results also show high accuracy and precision.


Dependence, misuse, and beliefs regarding use of hypnotics by elderly psychiatric patients taking zolpidem, estazolam, or flunitrazepam.
To examine the prevalence rates and correlates of dependence on, misuse of, and beliefs regarding use of hypnotics in elderly psychiatric patients with long-term use of zolpidem, estazolam, or flunitrazepam. A total of 139 psychiatric outpatients 65 or more years of age who used zolpidem, estazolam, or flunitrazepam for at least 3 months were studied. The levels of hypnotic dependence and beliefs regarding hypnotic use (necessity and concern) were assessed. Three patterns of hypnotic misuse in the past 1 month were also explored. The correlates of high dependence, misuse, and unfavorable attitude and high concern toward hypnotic use were examined using logistic regression analyses. A total of 28.8%, 7.9%, 12.2%, and 22.3% of participants reported high dependence on, misuse of, unfavorable attitude toward, and high concern toward hypnotic use, respectively. Males were more likely to report unfavorable attitude toward hypnotic use than females. Elders with significant depression were more likely to report high concern toward hypnotic use than those without significant depression. Elders with high concern toward hypnotic use were more likely to report high dependence on hypnotics than those with low concern. Elders with significant depression and taking zolpidem were more likely to misuse hypnotics than those without significant depression and taking estazolam or flunitrazepam, respectively. Clinicians should monitor the possibility of dependence on and misuse of hypnotics among elderly psychiatric patients who had the correlates identified in this study.


Progesterone alters global transcription profiles at environmental concentrations in brain and ovary of female zebrafish (Danio rerio).
Progesterone (P4) is a natural steroid hormone excreted by humans and animals. Noncomplete degradation in treatment plants result in levels in the ng/L range in surface waters. Very little is known of the effects on fish at such concentrations. Here we determine the global expression profile in the brain and ovary of female zebrafish exposed for 14 days to 3.5, 33 and 306 ng/L P4 to elucidate molecular effects. For validation selected transcripts were determined by RT-qPCR. In the brain, 54 and 255 transcripts were altered at 3.5 and 306 ng/L, respectively. Genes related to circadian rhythm (nr1d2b, per1b), cell cycle and reproduction (cdc20, ccnb1) were down-regulated. In the ovary, transcriptional changes occurred in 200, 84 and 196 genes at 3.5, 33 and 306 ng/L, respectively. The genes belong to different pathways including cardiac hypertrophy, cell cycle and its regulation. P4 slightly influenced oocyte maturation as revealed by histology of the ovaries. In the liver, vtg1 was down-regulated at all concentrations and VTG protein at 306 ng/L in the blood. The data show molecular effects and the modes of action of P4 at environmental concentrations. Ultimately they may translate to adverse effects on reproduction.


Psychogenic balance disorders: is it a new entity of psychogenic movement disorders?
The various reported psychogenic dyskinesias include tremor, dystonia, myoclonus, gait disorder, Parkinsonism, tics, and chorea. It is not easy to diagnose psychogenic movement disorders, especially in patients with underlying organic disease. We describe three patients with balance and/or posture abnormalities that occur when they stand up, start to move, or halt from walking, although their gaits are normal. One had an underlying unilateral frontal lobe lesion. All patients improved dramatically after receiving a placebo-injection or medication. These abnormal features differ from the previously reported features of astasia without abasia and of psychogenic gait disorders, including recumbent gait. We describe and discuss the patients' unique clinical characteristics.


The gestural repertoire of the wild bonobo (Pan paniscus): a mutually understood communication system.
In animal communication, signallers and recipients are typically different: each signal is given by one subset of individuals (members of the same age, sex, or social rank) and directed towards another. However, there is scope for signaller-recipient interchangeability in systems where most signals are potentially relevant to all age-sex groups, such as great ape gestural communication. In this study of wild bonobos (Pan paniscus), we aimed to discover whether their gestural communication is indeed a mutually understood communicative repertoire, in which all individuals can act as both signallers and recipients. While past studies have only examined the expressed repertoire, the set of gesture types that a signaller deploys, we also examined the understood repertoire, the set of gestures to which a recipient reacts in a way that satisfies the signaller. We found that most of the gestural repertoire was both expressed and understood by all age and sex groups, with few exceptions, suggesting that during their lifetimes all individuals may use and understand all gesture types. Indeed, as the number of overall gesture instances increased, so did the proportion of individuals estimated to both express and understand a gesture type. We compared the community repertoire of bonobos to that of chimpanzees, finding an 88 % overlap. Observed differences are consistent with sampling effects generated by the species' different social systems, and it is thus possible that the repertoire of gesture types available to Pan is determined biologically.


Loop-mediated isothermal amplification assay for detection of Histomonas meleagridis infection in chickens targeting the 18S rRNA sequences.
Histomonas meleagridis is the causative agent of histomonosis, a disease of gallinaceous fowl characterized by necrotic typhlitis, hepatitis, and high mortality. To develop a rapid and sensitive method for specific detection of H. meleagridis, an assay based on loop-mediated isothermal amplification (LAMP) targeting the 18S rRNA gene was established. The detection limit of the LAMP assay was 10 copies for standard plasmids containing an 18S rRNA gene fragment, which was superior to that of a classical PCR method. Specificity tests revealed that there was no cross-reaction with other protozoa such as Trichomonas gallinae, Blastocytis sp, Tetratrichomonas gallinarum, Plasmodium gallinaceum, Toxoplasma gondii, Eimeria tenella, Leucocytozoon caulleryi and Leucocytozoon sabrazesi. The assay was evaluated for its diagnostic utility using liver and caeca samples collected from suspected field cases, the detection rate was 100 and 97.92%, respectively. These results indicate that the LAMP assay may be a useful tool for rapid detection and identification of H. meleagridis in poultry.


Data on sex differences in one-year outcomes of out-of-hospital cardiac arrest patients without ST-segment elevation.
Sex differences in out-of-hospital cardiac arrest (OHCA) patients are increasingly recognized. Although it has been found that post-resuscitated women are less likely to have significant coronary artery disease (CAD) than men, data on follow-up in these patients are limited. Data for this data in brief article was obtained as a part of the randomized controlled Coronary Angiography after Cardiac Arrest without ST-segment elevation (COACT) trial. The data supplements the manuscript "Sex differences in out-of-hospital cardiac arrest patients without ST-segment elevation: A COACT trial substudy" were it was found that women were less likely to have significant CAD including chronic total occlusions, and had worse survival when CAD was present. The dataset presented in this paper describes sex differences on interventions, implantable-cardioverter defibrillator (ICD) shocks and hospitalizations due to heart failure during one-year follow-up in patients successfully resuscitated after OHCA. Data was derived through a telephone interview at one year with the patient or general practitioner. Patients in this randomized dataset reflects a homogenous study population, which can be valuable to further build on research regarding long-term sex differences and to further improve cardiac care.


[An update on amebiasis].
The description of Entamoeba dispar, and the recovery of Entamoeba moshkovskii from humans had a major impact in the epidemiology and clinical management of amebiasis. Infections range from asymptomatic colonization to hemorrhagic colitis and extra-intestinal diseases. Only a minority of amebiasis patients progress to the development of disease. Recent studies suggest that susceptibility to infection, and its outcome is influenced by the host, parasite genotype, and environment. The identification of Entamoeba histolytica is based on the detection of specific antigens by ELISA and DNA in stool and other clinical samples. Several diagnostic tests have been developed, including polymerase chain reaction, the technique of choice, for the detection and differentiation of E. histolytica, E. dispar, and E. moshkovskii. Combination of serologic tests with detection of the parasite DNA by PCR or antigen by ELISA offers the best approach to diagnosis. However, these techniques are impractical for clinical laboratories of developing countries. Clinicians must follow the guidelines of the World Health Organization to avoid unnecessary treatments. This review describes and discusses recent advances in amebiasis with emphasis in the clinical aspects and management of infection.


Severe hypercapnia causes reversible depression of aEEG background activity in neonates: an observational study.
Elevated carbon dioxide (CO2) blood levels have a depressant effect on the central nervous system and can lead to coma in adults. Less is known about the effect of CO2 on the neurological function of infants. To describe the effect of acute severe hypercapnia (PaCO2 >70 mm Hg) on amplitude-integrated electroencephalography (aEEG) and cerebral oxygenation in newborn infants. Observational study of full-term and preterm infants with acute severe hypercapnia (identified by arterial blood gas measurements), monitored with aEEG. Visual analysis of the aEEG was performed in all infants. In preterm infants <32 weeks postmenstrual age (PMA), analysis of two-channel EEG was performed. Mean spontaneous activity transients (SAT) rate (SATs/min), interval between SATs (ISI in seconds) and the ISI percentage (ISP) were calculated for 10-min periods before, during and after hypercapnia. Mean regional cerebral oxygen saturation (rScO2) and fractional tissue oxygen extraction (FTOE) measured with near-infrared spectroscopy were also calculated for these periods. Twenty-five infants (21 preterm, 4 full-term) comprising 32 episodes of acute severe hypercapnia were identified. Twenty-seven episodes were accompanied by a transient aEEG depression. Twenty-two episodes in 15 preterm infants <32 weeks PMA were quantitatively analysed. During hypercapnia, SAT rate decreased and ISI and ISP increased significantly. No significant change occurred in rScO2 or FTOE during hypercapnia. Profound depression of brain activity due to severe hypercapnia is also seen in infants. It can be recognised by an acute depression of the aEEG, without clinically detectable changes in cerebral oxygenation.


Are objective measures of physical capability related to accelerated epigenetic age? Findings from a British birth cohort.
Our aim was to investigate the association of epigenetic age and physical capability in later life. Having a higher epigenetic than chronological age (known as age acceleration (AA)) has been found to be associated with an increased rate of mortality. Similarly, physical capability has been proposed as a marker of ageing due to its consistent associations with mortality. The MRC National Survey of Health and Development (NSHD) cohort study. We used data from 790 women from the NSHD who had DNA methylation data available. Epigenetic age was calculated using buccal cell (n=790) and matched blood tissue (n=152) from 790 female NSHD participants. We investigated the association of AA at age 53 with changes in physical capability in women from ages 53 to 60-64. Regression models of change in each measure of physical capability on AA were conducted. Secondary analysis focused on the relationship between AA and smoking, alcohol, body mass index (BMI) and socioeconomic position. Three objective measures of physical capability were used: grip strength, standing balance time and chair rise speed. Epigenetic age was lower than chronological age (mean 53.4) for both blood (50.3) and buccal cells (42.8). AA from blood was associated with a greater decrease in grip strength from ages 53 to 60-64 (0.42 kg decrease per year of AA, 95% CI 0.03, 0.82 kg; p=0.03, n=152), but no associations were observed with standing balance time or chair rise speed. Current smoking and lower BMI were associated with lower epigenetic age from buccal cells. We found evidence that AA in blood is associated with a greater decrease in grip strength in British females aged between 53 and 60-64, but no association with standing balance time or chair rise speed was found.


Inspiratory and Expiratory Computed Tomography Imaging Clusters Reflect Functional Characteristics in Chronic Obstructive Pulmonary Disease.
Disease probability measure (DPM) is a useful voxel-wise imaging assessment of gas-trapping and emphysematous lesions in patients with chronic obstructive pulmonary disease (COPD). To elucidate the progression of COPD, we performed a cluster analysis using the following DPM parameters: normal (DPMNormal), gas-trapping (DPMGasTrap), and emphysematous lesions (DPMEmph). Our findings revealed the characteristics of each cluster and the 3-year disease progression using imaging parameters. Inspiratory and expiratory chest computed tomography (CT) images of 131 patients with COPD were examined, of which 84 were followed up for 3 years. The percentage of low attenuation volume (LAV%) and the square root of the wall area of a hypothetical airway with an internal perimeter of 10 mm (√Aaw at Pi10) were quantitatively measured using inspiratory chest CT. A hierarchical cluster analysis was performed using the DPM parameters at baseline. Five clusters were named according to the dominant DPM parameters: normal (NL), normal-GasTrap (NL-GT), GasTrap (GT), GasTrap-Emphysema (GT-EM), and Emphysema (EM). Women were predominantly diagnosed with GT. Forced expiratory volume in 1 s gradually decreased in the following order: NL, NL-GT, GT, GT-EM, and EM. DPMEmph correlated well with LAV%. Four clusters other than NL showed significantly higher values of √Aaw at Pi10 than NL; however, no significant differences were observed among them. In all clusters, DPMEmph increased after 3 years. DPMNormal only increased in the GT cluster. Clusters using DPM parameters may reflect the characteristics of COPD and help understand the pathophysiology of the disease.