Pain and Swelling after Percutaneous Endoscopic Gastrostomy Removal: An Unexpected Evolution.
Gastrostomy site metastization is considered an uncommon complication of percutaneous endoscopic gastrostomy (PEG) placement in patients with head and neck tumours, but it is important to consider this possibility when evaluating gastrostomy-related symptoms. The authors present the case of a 40-year-old male with excessive alcohol consumption and active smoking, diagnosed with a stage IV oropharyngeal squamous cell carcinoma. The patient developed a paraneoplastic demyelinating motor polyneuropathy that, associated with tumour mass effect, caused dysphagia with need for nasogastric tube feeding. Treatment with radiotherapy and then chemoradiotherapy was administered and a PEG was placed with the pull method. Cancer remission and resolution of polyneuropathy was achieved, so PEG was removed. Two weeks later, the patient presented with pain and swelling at the gastrostomy site suggesting a local abscess, with improvement after drainage and antibiotic therapy. After 1 month, there was a tumour mass at the gastrostomy site and an oropharyngeal cancer metastasis was diagnosed. The patient underwent surgical excision of abdominal wall metastasis and abdominal disease was controlled. Nevertheless, there was subsequent oropharyngeal neoplasia recurrence and the patient died 6 months later. This case raises the discussion about gastrostomy placement methods that could avoid gastrostomy site metastization, the possible differential diagnosis, and diagnostic workout. Surgical resection may allow metastatic disease control, but by primary disease evolution greatly affects prognosis.


Re-reconsidering Burt: beyond a reasonable doubt.
The Burt controversy has taken a number of strange twists and turns, leading many observers to conclude that he has been exonerated of the accusation that he fabricated his data on monozygotic twins reared apart. A comparison of his twin sample with that from other well documented studies, however, leaves little doubt that he committed fraud.


Genetic and environmental factors in alexithymia: a population-based study of 8,785 Danish twin pairs.
The role of genetic and environmental factors for developing alexithymia is still unclear, and the aim of this study was to examine these factors in a large population-based sample of twins. The Toronto Alexithymia Scale-20 (TAS-20) was included in a mail survey of 46,418 individuals born between 1931 and 1982 and registered with the Danish Twin Registry. The response rate was 75.3%. A total of 8,785 twin pairs, where both cotwins had completed all items of the TAS-20, were selected for this study. Analyses were conducted for total TAS-20 scores and the subscales of (1) difficulties in identifying feelings, (2) difficulties in describing feelings, and (3) externally oriented thinking. The phenotypes were analyzed both as categorical and continuous data. All measures of similarity suggested that genetic factors added to all facets of alexithymia. Structural equation modeling of the noncategorical data, an ACE model including additive genetic, shared environmental and nonshared environmental effects, provided the best fit for all three facets of alexithymia as well as total alexithymia scores, with heritabilities of 30-33% and the remaining variance being explained by shared (12-20%) and nonshared environmental effects (50-56%). The results from this large population-based sample suggest that genetic factors have a noticeable and similar impact on all facets of alexithymia. While the results suggested a moderate influence of shared environmental factors, our results are in concordance with the general finding that environmental influences on most psychological traits are primarily of the nonshared rather than the shared type.


Examining mobility, independence, motor function, participation, and parental stress in a school-aged Turkish cerebral palsy population: a cross-sectional study.
This study aimed to describe a school-aged Turkish cerebral palsy (CP) population in terms of gross motor function, mobility, independence, and participation, and to investigate parental stress. Mobility (Functional Mobility Scale (FMS)), independence (Barthel Index (BI)), motor function (Gross Motor Function Measurement (GMFM)), functional classification (Gross Motor Function Classification System (GMFCS)), participation (Pediatric Outcome Data Collection Instrument (PODCI)), and parents' stress (Parental Stress Scale (PSS)) of 100 school-aged children with CP aged 5-15 years old were evaluated. School-related difficulties and restrictions were also questioned. Of the 100 children with GMFCS levels I-V, almost half had independent mobility on level or all surfaces according to the FMS, with a relatively high GMFM score (72.8%), and above average BI (12 from 20), and PODCI Global Functioning (62.8%) scores. Strong-to-very strong correlations were determined between all test batteries. A mean score of 42.3 ± 9.92 out of 90 was obtained for parental stress with a weak correlation to the GMFCS and the child's mobility distance according to family (p < 0.05). Turkish school-aged children with CP displayed functional abilities that are above average besides experiencing restrictions in the school environment. Parents' view on the physical condition of the school varied depending on functional and mobility levels of their children.


Access to COVID-19 testing by individuals with housing insecurity during the early days of the COVID-19 pandemic in the United States: a scoping review.
The COVID-19 pandemic focused attention on healthcare disparities and inequities faced by individuals within marginalized and structurally disadvantaged groups in the United States. These individuals bore the heaviest burden across this pandemic as they faced increased risk of infection and difficulty in accessing testing and medical care. Individuals experiencing housing insecurity are a particularly vulnerable population given the additional barriers they face. In this scoping review, we identify some of the barriers this high-risk group experienced during the early days of the pandemic and assess novel solutions to overcome these barriers. A scoping review was performed following PRISMA-Sc guidelines looking for studies focusing on COVID-19 testing among individuals experiencing housing insecurity. Barriers as well as solutions to barriers were identified as applicable and summarized using qualitative methods, highlighting particular ways that proved effective in facilitating access to testing access and delivery. Ultimately, 42 studies were included in the scoping review, with 143 barriers grouped into four categories: lack of cultural understanding, systemic racism, and stigma; medical care cost, insurance, and logistics; immigration policies, language, and fear of deportation; and other. Out of these 42 studies, 30 of these studies also suggested solutions to address them. A paucity of studies have analyzed COVID-19 testing barriers among those experiencing housing insecurity, and this is even more pronounced in terms of solutions to address those barriers. Expanding resources and supporting investigators within this space is necessary to ensure equitable healthcare delivery.


Differential contribution of mesoaccumbens and mesohabenular dopamine to intracranial self-stimulation.
The contribution of mesoaccumbens dopamine transmission to intracranial self-stimulation is well-established. However, although the nucleus accumbens comprises two main subregions, the shell and the core, little is known of the contribution of each to this behaviour. Our first aim was to study the effects of d-amphetamine infusions into the shell and core in order to understand their relative importance to reward and operant responding. Our second aim was to examine the contribution of a lesser studied group of dopamine neurons, those within the mesohabenular pathway, to intracranial self-stimulation. Male Sprague-Dawley rats were implanted with bilateral cannulae in the nucleus accumbens shell, core or in the lateral habenula and a monopolar stimulation electrode in the posterior mesencephalon, a brain site that is sensitive to changes in dopamine transmission. Using curve-shift scaling, we measured the reward- and performance-enhancing effects of intra-accumbens (1-20 μg) and intra-habenular (10-40 μg) infusions of d-amphetamine or vehicle. Within the nucleus accumbens, the use of multiple doses and long test sessions allowed us to observe an interaction between drug effect and infusion site. We show, for the first time, differences in the minimal doses necessary to enhance rewarding effectiveness and operant responding, in the magnitude of these enhancements as well as in their duration. Conversely, regardless of dose, intra-habenular D-amphetamine did not alter rewarding effectiveness or operant rate, highlighting the differential contribution of mesoaccumbens and mesohabenular dopamine pathways to intracranial self-stimulation.


[Endoscopic treatment of infectious necrosis in severe acute pancreatitis].
Severe acute pancreatitis (SAP) is one of the most common acute and critical diseases. SAP is often accompanied by necrosis of the pancreas and surrounding tissues.When necrosis is co-infected, it often means high mortality. With the development of endoscopic technology, endoscopic intervention in the treatment of necrotizing pancreatitis has achieved good results, which has the advantages of minimal-invasiveness, effectiveness, and safety, and could significantly improve the prognosis of patients with SAP. This article aims to review the research progress of endoscopic treatment of necrotizing pancreatitis.


Spatial knowledge of geographical globes: evidence of vertical alignment effects.
This study investigated human spatial memory of geographical globes. In two experiments, participants studied locations presented on a three-dimensional globe. Subsequently, participants' knowledge of the locations was tested employing two types of pointing task. Directional judgments from imagined locations on the globe were performed either vertically through the ground (as if digging a straight tunnel between the locations) or horizontally along the surface of the globe (the shortest distance for an aircraft to fly to a given destination). In the vertical pointing task, judgments originating from imagined locations in the upper hemisphere were superior by comparison with those originating from imagined locations in the lower hemisphere. Performance in the horizontal pointing task was more variable, with a tendency for superior judgments originating from imagined locations in the lower hemisphere. The results provide evidence of a novel alignment effect involving vertical judgments.


[Historical review of the borderline personality disorder concept].
The concept of borderline syndrome is the subject of current debate because of its ambiguity and lack of homogeneity. Furthermore, the concept is rejected by many authors as a common category for atypical and non-specific disorders that cannot be classified elsewhere. The current use of the term borderline seems to be more a consequence of its historic use than its true clinical meaning. There is discrepancy on whether this term determines a level of severity, an organization of personality or a defined syndromic entity. In 1938, Stern was the first author to use the term borderline, and it was not introduced in the DSM III until 1980. This work makes a historical review of the use of the term borderline and also of those terms that have been used to define patients with the same characteristics. The different schools (psychoanalytic, biological, eclectic and biosocial) have different concepts on the term borderline. There is still no concise and exact definition for the diagnostic criteria of borderline and it is even possible the best term for this group of patients has still not been determined. It will be important to consider the contributions of the DSM V or ICD 11 in the next years.


Electronic Structure of Biotin Conformers Studied with SAC-CI and OVGF Methods.
In this work, the study was performed with 37 gas-phase conformers of biotin and two biologically active conformers of biotin in the ligand-receptor complexes with astavidin and streptavidin. The ionization energies and photoelectron spectra of conformers were calculated by two methods: the general-R symmetry-adapted cluster-configuration interaction (general-R-SAC-CI) method and the outer-valence Green's function (OVGF) method. The photoelectron spectrum of each conformer was calculated using basis set D95 (df,pd) for both methods. The simulated photoelectron spectra of free molecules and bioactive conformers calculated by the two methods were compared. Natural bonding orbital (NBO) calculations were also performed for the assignment of ionization bands of each conformer. NBO calculation indicated that the first to five ionization bands correspond to ionizations from orbitals localized in the two rings. The most important point about the ionization of all conformers is that the removal of an electron from the σ-bonding orbital (C-S) takes place above 10.0 eV.


Membrane defects accelerate outer membrane β-barrel protein folding.
Outer membrane β-barrel proteins spontaneously fold into lipid bilayers with rates of folding that are strongly influenced by the physical properties of the membrane. We show that folding is accelerated when the bilayer is at the phase transition temperature, because of the coexistence of lipid phase domains and the high degree of defects present at domain boundaries. These results are consistent with previous observations of faster folding into thin and highly curved membranes, which also contain a higher prevalence of defects. The importance of defects in β-barrel folding provides insight into the intrinsic folding process and the biological assembly pathway.


A novel approach to forecast dust concentration in open pit mines by integrating meteorological parameters and production intensity.
Mine dust pollution poses a hindrance to achieving green and climate-smart mining. This paper uses weather forecast data and mine production intensity data as model inputs to develop a novel model for forecasting daily dust concentration values in open pit mines by employing and integrating multiple machine learning techniques. The results show that the forecast model exhibits high accuracy, with a Pearson correlation coefficient exceeding 0.87. The PM2.5 forecast model performs best, followed by the total suspended particle and PM10 models. The inclusion of production intensity significantly enhances model performance. Total column water vapor exerts the most significant impact on the model's predictive performance, while the impacts of rock production and coal production are also notable. The proposed daily forecast model leverages production intensity data to predict future dust concentrations accurately. This tool offers valuable insights for optimizing mine design parameters, enabling informed decisions based on real-time forecasts. It effectively prevents severe pollution in the mining area while maximizing the use of natural meteorological conditions for effective dust removal and diffusion.


Acute pancreatitis: animal models and recent advances in basic research.
Acute pancreatitis (AP) is characterized by edema, acinar cell necrosis, hemorrhage, and severe inflammation of the pancreas. Patients with AP present with elevated blood and urine levels of pancreatic digestive enzymes, such as amylase and lipase. Severe AP may lead to systemic inflammatory response syndrome and multiorgan dysfunction syndrome, which account for the high mortality rate of AP. Although most (>80%) cases of AP are associated with gallstones and alcoholism, some are idiopathic. Although the pathogenesis of AP has not yet been elucidated, a common feature is the premature activation of trypsinogen within pancreatic tissues, which triggers autodigestion of the gland. Recent advances in basic research suggest that etiologic factors including cyclooxygenase-2, substance P, and angiotensin II may have novel roles in this disease. Basic research data obtained thus far have been based on animal models of AP ranging from mild edematous pancreatitis to severe necrotizing pancreatitis. In view of this, an adequate selection of experimental animal models is of paramount importance. Notwithstanding these animal models, it should be emphasized that none of these models mimic the clinical situation where varying degrees of severity usually occur. In this review, commonly used animal models of AP will be critically evaluated. A discussion of recent advances in our knowledge about AP risk factors is also included.


Sponge cell reactivity to various forms of silica.
Several sponge species incorporate a wide range of foreign material. Whether such material is actively selected by the sponge is controversial. Here we compare the available suspended matter and the sediment incorporated in the tissue of the demosponge Chondrosia reniformis. Field observations and laboratory experiments indicate that this species selects and incorporates only siliceous materials, in particular quartz particles and opal sponge spicules, avoiding carbonate particles. The reaction of ectosome cells of Chondrosia depends on the forms of silica: after settlement of crystalline quartz particles on the sponge surface, the pinacocytes contract uniformly, giving rise to a ruffled surface that remains throughout the incorporation of foreign material. In contrast, the opal spicules elicit a motile response in pinacocytes, which cover the spicules as a result. After incorporation, while the opal spicules remain unaltered within sponge tissue, the engulfed quartz particles are quickly etched, reduced in size, and released from the sponge. The etching of quartz particles by C. reniformis is produced by ascorbic acid, and is the first evidence of such activity from the animal kingdom. Ascorbic acid has been found to change the quartz surface features, which leads to an increased radical production and a consequent dissolution of quartz. This process does not occur on opal spicules.


Errors in estimates of peritoneal fluid volume.
Inherent limitations in the suitability of drainage volumes for monitoring intraperitoneal fluid volume have resulted in the frequent use of indicator dilution techniques, but little attention has been given to confirming the adequacy of the estimates that volume markers provide. In a series of experimental exchanges in rats, volume estimates were compared based on the dilution of blue dextran and hemoglobin with direct collections of surgically exposed intraperitoneal fluid. Significant systematic and random errors in the indicator dilution volume estimates were observed. The systematic errors appeared to be due to the rapid removal of a fixed amount of marker from peritoneal fluid, while the random errors were caused by the rapid appearance of a variable amount of endogenous chromogen. The behavior of the markers observed in this study was not consistent with the assumptions commonly used to analyze volume transport in peritoneal dialysis.


Early Combined Immunosuppression May Be More Effective for Reducing Complications in Isolated Colonic- vs Ileal-Dominant Crohn Disease.
We assessed whether differential efficacy of early combined immunosuppression (ECI) in comparison with conventional management (CM) is present in patients with Crohn disease (CD) according to disease location. In this posthoc analysis of the Randomized Evaluation of an Algorithm for Crohn's Treatment trial, the effect of ECI vs CM modified by disease location (isolated-colonic vs ileal-dominant) in terms of time to first complication (hospitalization, surgery, or disease-related complications-presence of a new abscess, fistula, or stricture; serious worsening of disease activity; extraintestinal manifestations) was analyzed using a marginal Cox proportional hazard model to account for cluster randomization. Factors adjusted included practice size, country, and other covariates selected in a backward logistic regression analysis with the first composition as outcome and P < 0.10. Of the 1969 patients with CD, 435 had isolated colonic CD (ECI n = 257, CM n = 178) and 1534 had ileal CD (ECI n = 817, CM n = 717). Over 24 months there was a significant differential impact for ECI vs CM for reducing the risk of a CD-related complication between patients with colonic CD and ileal CD (colonic CD hazard ratio [HR] = 0.51; 95% CI, 0.30-0.85 vs ileal CD HR = 0.79; 95% CI, 0.57-1.10; P = 0.033). No difference was identified between ECI vs CM for reducing the risk of surgery (colonic HR = 0.52 vs ileal HR = 0.74; P = 0.468) or hospitalization (colonic HR = 0.77 vs ileal HR = 0.83; P = 0.806). In this posthoc analysis of the Randomized Evaluation of an Algorithm for Crohn's Treatment trial, symptom-based ECI was associated with greater efficacy for reducing the risk of CD-related complications in patients with colonic disease location relative to ileal disease location.


Traumatic brain injuries in a well-defined population: epidemiological aspects and severity.
The aim was to describe epidemiological and medical aspects of 449 cases of traumatic brain injury (TBI) from a well-defined geographical area with a population of 137,000 inhabitants. An episode of disturbed consciousness was a prerequisite for inclusion in the study. The incidence of TBI was 354/100,000 inhabitants. Median age was 23 years, range 0-91 years; 55% were men and 45% were women; 33% children 0-14 years, 50% adults 15-64 years, and 17% elderly persons 65-91 years old. Severity classification was based on Glasgow Coma Scale (GCS) on arrival; mild TBI 97% (GCS 13-15), moderate 1% (GCS 9-12), and severe 2% (GCS 3-8). The most common injury events were falls (55%) and vehicle-related events (30%). The percentage of falls was high among children and elderly persons but among adults vehicle-related injury events were also prominent. At least 17% of all patients were under the influence of alcohol, especially adult male bicyclists. CT was performed on 163 cases (36%) revealing 34 cases with intracranial hemorrhage (ICH) which is 21% of the examined or 8% of all the injured. The rate of ICH increased with increasing age (from 3% among children to 17% among the elderly persons) and also increased with decreasing GCS from 6% in the group of mild TBI to 60% among those with severe TBI. Attention should be directed to acute management of mild TBI in order to detect potentially dangerous ICH as well as to preventive actions against falls and vehicle related accidents.


A minireview of analytical methods for the geographical origin analysis of teas (Camellia sinensis).
Chemical compositions in tea leaves are influenced by their growing surrounding, and the content of these components are related to the quality of teas. The determination of the concentration of chemical composition in teas will predict the ranking of teas and indicate the geographical origins. This overview concerns an investigation of analytical methods that are being used for the determination of the geographical origin of tea. The analytical approaches have been subdivided into three groups: spectroscopic techniques, chromatographic techniques, and other techniques. The advantages, drawbacks, and reported applications concerning geographical authenticity are discussed.


Plasma apolipoprotein A1 as a biomarker for Parkinson disease.
To identify plasma-based biomarkers for Parkinson disease (PD) risk. In a discovery cohort of 152 PD patients, plasma levels of 96 proteins were measured by multiplex immunoassay; proteins associated with age at PD onset were identified by linear regression. Findings from discovery screening were then assessed in a second cohort of 187 PD patients, using a different technique. Finally, in a third cohort of at-risk, asymptomatic individuals enrolled in the Parkinson's Associated Risk Study (PARS, n = 134), plasma levels of the top candidate biomarker were measured, and dopamine transporter (DAT) imaging was performed, to evaluate the association of plasma protein levels with dopaminergic system integrity. One of the best candidate protein biomarkers to emerge from discovery screening was apolipoprotein A1 (ApoA1; p = 0.001). Low levels of ApoA1 correlated with earlier PD onset, with a 26% decrease in risk of developing PD associated with each tertile increase in ApoA1 (Cox proportional hazards, p < 0.001, hazard ratio = 0.742). The association between plasma ApoA1 levels and age at PD onset was replicated in an independent cohort of PD patients (p < 0.001). Finally, in the PARS cohort of high-risk, asymptomatic subjects, lower plasma levels of ApoA1 were associated with greater putaminal DAT deficit (p = 0.037). Lower ApoA1 levels correlate with dopaminergic system vulnerability in symptomatic PD patients and in asymptomatic individuals with physiological reductions in dopamine transporter density consistent with prodromal PD. Plasma ApoA1 may be a new biomarker for PD risk.


Do people reduce compliance with COVID-19 guidelines following vaccination? A longitudinal analysis of matched UK adults.
COVID-19 vaccines do not confer immediate immunity and vaccinated individuals may still be at risk of transmitting the virus. Governments have not exempted vaccinated individuals from behavioural measures to reduce the spread of COVID-19, such as practising social distancing. However, vaccinated individuals may have reduced compliance with these measures, given lower perceived risks. We used monthly panel data from October 2020 to March 2021 in the UK COVID-19 Social Study to assess changes in compliance following vaccination. Compliance was measured with two items on compliance with guidelines in general and compliance with social distancing. We used matching to create comparable groups of individuals by month of vaccination (January, February or not vaccinated by February) and fixed effects regression to estimate changes in compliance over the study period. Compliance increased between October 2020 and March 2021, regardless of vaccination status or month of vaccination. There was no clear evidence that vaccinated individuals decreased compliance relative to those who were not yet vaccinated. There was little evidence that sample members vaccinated in January or February reduced compliance after receiving vaccination for COVID-19. Continued monitoring is required as younger individuals receive the vaccine, lockdown restrictions are lifted and individuals receive second doses of the vaccine.


Pathogenesis of late airway changes in long-term surviving lung allografts.
Late airway changes are frequently observed in long-term surviving rat lung allografts. In this present study, we investigate this problem using the mixed lymphocyte reaction, graft-versus-host assay (popliteal lymph node assay), skin grafting from the donor strain to the lung allograft recipient, and histology to evaluate this problem. The results show that spleen cells from recipient rats with long-term surviving lung allografts possessed alloreactivity in mixed lymphocyte reaction against both donor and third-party ACI antigens. Suppressor cell activity was not detected in spleen cells from these recipient rats. The popliteal lymph node assay showed that the response to recipient spleen cells was detectable but weaker than that of naive spleen cells from the same strain. Mean survival time of skin grafts from the donor strain to long-term allograft survivors was significantly longer than that between donor and recipient strains. Chest roentgenograms revealed opacification of long-term surviving lung allografts at 2 to 3 wk after skin transplantation that was coincident with the rejection of the skin grafts, and histologic examination of the lung allografts revealed changes compatible with acute rejection. We conclude that alloreactivity can be demonstrated in rats with long-term surviving lung allografts and suggest that late airway changes in these lungs are immunologically mediated.


A role for tumor necrosis factor-alpha in experimental Bacillus cereus endophthalmitis pathogenesis.
To determine the contribution of tumor necrosis factor-alpha (TNFalpha) in the pathogenesis of experimental Bacillus cereus endophthalmitis. Experimental B. cereus endophthalmitis was induced in wild-type control (B6.129F1) and age-matched homozygous TNFalpha knockout mice (TNFalpha(-/-), B6.129S6-Tnf(tm1Gk1)/J). At various times after infection, eyes were analyzed by electroretinography and were harvested for quantitation of bacteria, myeloperoxidase, proinflammatory cytokines and chemokines, and histologic analysis. B. cereus replicated more rapidly in the eyes of TNFalpha(-/-) mice than in the eyes of B6.129F1 mice. Retinal function decreased more rapidly in TNFalpha(-/-) mice than in B6.129F1 mice. Retinal layers were not as structurally intact at 6 and 12 hours after infection in TNFalpha(-/-) eyes as in B6.129F1 eyes. Histologic analysis suggested less polymorphonuclear leukocyte (PMN) infiltration into the vitreous of TNFalpha(-/-) mice than of B6.129F1 mice. B6.129F1 eyes also had greater myeloperoxidase concentrations than did eyes of TNFalpha(-/-) mice. In general, concentrations of proinflammatory cytokines and chemokines (IL-1beta, KC, IL-6, and MIP-1alpha) were greater in eyes of TNFalpha(-/-) mice than of B6.129F1 mice. TNFalpha is important to intraocular pathogen containment by PMNs during experimental B. cereus endophthalmitis. In the absence of TNFalpha, fewer PMNs migrated into the eye, facilitating faster bacterial replication and retinal function loss. Although greater concentrations of proinflammatory cytokines were synthesized in the absence of TNFalpha, the resultant inflammation was diminished, and an equally devastating course of infection occurred.


Enlarged Interlayer Spacing in Cobalt-Manganese Layered Double Hydroxide Guiding Transformation to Layered Structure for High Supercapacitance.
Cobalt-manganese layered double hydroxide (CoMn-LDH) has been known as a highly desired cathode material used with an alkaline electrolyte. However, the layered double hydroxide structure is unstable and changes almost instantly in alkaline solution due to the instability of a manganese(III) ion. Thus, it is important to investigate the true active phase for designing efficient electrode materials. In this work, the metal-organic framework is used as a templating precursor to derive CoMn-LDH from three different manganese solutions, namely, MnSO4, Mn(NO3)2, and MnCl2. Anions in the solutions participate in the derivation process and strongly affect the layer structure, phase transformation process, and charge storage properties of the resulting materials. CoMn-LDH synthesized from manganese sulfate solution exhibits the largest interlayer spacing of 1.08 nm, and more interestingly, the layered structure can well be retained in KOH solution, while the other two synthesized from manganese chloride and nitrate solutions transform into the spinel structure. As a cathode material, it delivers a high areal capacity of 582.07 mC/cm2 at 2 mA/cm2, which is about 100% higher than those of the other two samples. The present work explores the active phase of CoMn-LDH in the alkaline electrolyte and proposes a potential mechanism of the phase transformation, which provides insights into understanding and designing of the active electrode materials for stable and high-performing supercapacitors in an alkaline environment.


Analysis of small sample size studies using nonparametric bootstrap test with pooled resampling method.
Experimental studies in biomedical research frequently pose analytical problems related to small sample size. In such studies, there are conflicting findings regarding the choice of parametric and nonparametric analysis, especially with non-normal data. In such instances, some methodologists questioned the validity of parametric tests and suggested nonparametric tests. In contrast, other methodologists found nonparametric tests to be too conservative and less powerful and thus preferred using parametric tests. Some researchers have recommended using a bootstrap test; however, this method also has small sample size limitation. We used a pooled method in nonparametric bootstrap test that may overcome the problem related with small samples in hypothesis testing. The present study compared nonparametric bootstrap test with pooled resampling method corresponding to parametric, nonparametric, and permutation tests through extensive simulations under various conditions and using real data examples. The nonparametric pooled bootstrap t-test provided equal or greater power for comparing two means as compared with unpaired t-test, Welch t-test, Wilcoxon rank sum test, and permutation test while maintaining type I error probability for any conditions except for Cauchy and extreme variable lognormal distributions. In such cases, we suggest using an exact Wilcoxon rank sum test. Nonparametric bootstrap paired t-test also provided better performance than other alternatives. Nonparametric bootstrap test provided benefit over exact Kruskal-Wallis test. We suggest using nonparametric bootstrap test with pooled resampling method for comparing paired or unpaired means and for validating the one way analysis of variance test results for non-normal data in small sample size studies. Copyright © 2017 John Wiley & Sons, Ltd.


Update on Postnatal Steroids.
Antenatal steroid treatment to enhance fetal lung maturity and surfactant treatment to prevent or treat respiratory distress syndrome have been major advances in perinatal medicine in the past 40 years contributing to improved outcomes for preterm infants. Use of postnatal steroids to prevent or treat chronic lung disease in preterm infants has been less successful and associated with adverse neurodevelopmental outcomes. Although early (in the first week of life) postnatal steroid treatment facilitates earlier extubation and reduces the risk of chronic lung disease, it is associated with adverse effects, such as hyperglycemia, hypertension, gastrointestinal bleeding and perforation, hypertrophic cardiomyopathy, growth failure, and cerebral palsy, and cannot be recommended. Early treatment with hydrocortisone may also improve survival without chronic lung disease, but concerns remain about possible adverse effects such as gastrointestinal perforation and sepsis, particularly in very preterm infants. Early inhaled budesonide also reduces the incidence of chronic lung disease but there are concerns that this may occur at the expense of increased risk of death. More studies of early low-dose steroids with adequate long-term follow-up are needed before they can be recommended for the prevention of chronic lung disease. Late (after the first week of life) postnatal steroids may have a better benefit-to-harm ratio than early steroids. A Cochrane Review shows that late steroid treatment reduces chronic lung disease, the combination of death and chronic lung disease at both 28 days and 36 weeks' corrected age, and the need for later rescue dexamethasone. Adverse effects include hyperglycemia, hypertension, hypertrophic cardiomyopathy, and severe retinopathy of prematurity but without an increase in blindness. Long-term neurodevelopmental effects are not significantly increased by late postnatal steroid treatment. Current recommendations are that postnatal steroid treatment should be reserved for preterm infants who are ventilator-dependent after the first 7-14 days of life and any course should be low dose and of short duration to facilitate endotracheal extubation. Budesonide/surfactant mixtures show some promise as a means of reducing chronic lung disease in preterm infants with severe respiratory distress syndrome, but further larger studies with long-term follow-up are needed before this treatment can be recommended as a routine intervention.


Reliability of the electric pulp tester as an indicator of pulpal anesthesia in primary maxillary posterior teeth to assess the need for supplemental injections: An observational clinical study.
The primary maxillary molars occasionally remain sensitive during operative procedures even post the buccal supraperiosteal injection. This could be due to the widely flared palatal roots receiving accessory innervation from the palatal nerves. Identifying inadequate anesthesia upfront using the electric pulp test (EPT) would give vital information to the clinician on the need of a supplemental palatal injection. Aim: The aim of this study was to assess and evaluate the reliability of the EPT as an indicator of pulpal anesthesia in primary maxillary molars. Methodology: Fifty one primary maxillary molars were subjected to the EPT following a buccal supraperiosteal injection. During the operative procedure, the " Face Legs Activity Cry Consolability" (FLACC) scores were recorded. The outcome of the EPT was correlated with the results of the FLACC score using Pearson's Chi-square test. Results: The EPT results were correlated to the FLACC scores. Five out of the 10 primary maxillary second molars which responded to the EPT scored 0 on the FLACC scale. The remaining 5 teeth scored 1 on the FLACC scale. The P value was 0.056 which was not statistically significant. This infers that the EPT is not a reliable tool to assess the adequacy of pulpal anesthesia in primary maxillary second molars. Conclusion: From the results of the present study, it can be concluded that the EPT is not a reliable tool to be used as an indicator of pulpal anesthesia in primary maxillary molars.


Benchmarking RNA-seq differential expression analysis methods using spike-in and simulation data.
Benchmarking RNA-seq differential expression analysis methods using spike-in and simulated RNA-seq data has often yielded inconsistent results. The spike-in data, which were generated from the same bulk RNA sample, only represent technical variability, making the test results less reliable. We compared the performance of 12 differential expression analysis methods for RNA-seq data, including recent variants in widely used software packages, using both RNA spike-in and simulation data for negative binomial (NB) model. Performance of edgeR, DESeq2, and ROTS was particularly different between the two benchmark tests. Then, each method was tested under most extensive simulation conditions especially demonstrating the large impacts of proportion, dispersion, and balance of differentially expressed (DE) genes. DESeq2, a robust version of edgeR (edgeR.rb), voom with TMM normalization (voom.tmm) and sample weights (voom.sw) showed an overall good performance regardless of presence of outliers and proportion of DE genes. The performance of RNA-seq DE gene analysis methods substantially depended on the benchmark used. Based on the simulation results, suitable methods were suggested under various test conditions.


Cytotoxicity and genotoxicity of a low-shrinkage monomer and monoacylphosphine oxide photoinitiator: Comparative analyses of individual toxicity and combination effects in mixtures.
To compare cytotoxicity and genotoxicity of novel urethane-based monomer FIT-852 and monoacylphosphine oxide photoinitiator (Lucirin TPO) with conventional Bisphenol A-glycidyl-methacrylate (BisGMA) and triethylene glycol dimethacrylate (TEGDMA) monomers and camphorquinone (CQ)/amine photoinitiator system, respectively. Moreover, we quantified and analyzed the combinatorial effects of individual substances in resin-based mixtures concerning the nature of the combinatorial effects. Cytotoxic and genotoxic effects of BisGMA, FIT, TEGDMA, CQ, DMAEMA and TPO and their combined toxicity in four clinically relevant mixtures (FIT/TPO, FIT/CQ, BisGMA/TPO, BisGMA/CQ) were tested on human fetal lung fibroblasts MRC-5 using MTT and Comet assays. We assessed combination effects of monomers and photoinitiators on overall toxicity from the measured concentration-effect relationships. Combination index (CI) was calculated on the basis of the median-effect equation derived from the mass-action law principle. Individual substances showed decreasing cytotoxic effects in the following order: BisGMA>TPO>FIT>CQ>DMAEMA>TEGDMA. Experimental mixtures showed decreasing cytotoxic effects in the order BisGMA/TPO>BisGMA/CQ>FIT/CQ>FIT/TPO. FIT-based mixtures exhibited antagonistic cytotoxic effects between components while BisGMA-based mixtures demonstrated synergistic effects at ED50. TPO amplified both antagonistic and synergistic cytotoxic effects in mixtures. Pure substances showed genotoxicity in the following order: TPO>BisGMA>FIT>CQ>TEGDMA. We did not detect the genotoxic potential of DMAEMA. The rank of genotoxic concentrations of the mixtures was: BisGMA/TPO>BisGMA/CQ>FIT/CQ>FIT/TPO. Lower cytotoxicity and genotoxicity of FIT than BisGMA suggests its greater biocompatibility. Conversely, photoinitiator TPO was significantly more cytotoxic and genotoxic than both CQ and DMAEMA. CI values showed that components of FIT-based mixtures exhibit an antagonistic cytotoxic effect, while compontents of BisGMA-based mixtures show synergism.


Role of SATB2 in human pancreatic cancer: Implications in transformation and a promising biomarker.
SATB2 (special AT-rich binding protein-2), a transcription factor and chromatin modulator, regulates the expression of genes required for maintaining pluripotency and self-renewal. The molecular mechanisms by which human pancreatic normal ductal epithelial cells are transformed to cancer cells are not well understood. The main goal of the paper is to examine the molecular mechanisms by which SATB2 regulates transformation of human pancreatic normal ductal epithelial (HPNE) cells, and assess whether transformed HPNE cells gained the phenotypes of cancer stem cells (CSCs). The results demonstrate that SATB2 is highly expressed in pancreatic CSCs, primary tissues and cell lines, but not in HPNE cells. SATB2 induces cellular transformation, stemness and epithelial to mesenchymal transition in HPNE cells, and inhibition of its expression suppresses these activities. Overexpression of SATB2 in HPNE cells resulted in induction of stem cell markers (CD44, CD24 and CD133), and transcription factors (Oct4, Sox2 and Nanog). SATB2 can directly bind to promoters of Bcl-2, Bsp, Nanog, c-Myc, XIAP, Klf4 and Hoxa2, suggesting the role of SATB2 in pluripotency, cell survival and proliferation. SATB2-overexpressing HPNE cells (HPNE/SATB2) formed tumors in Balb C nude mice, whereas HPNE/Empty vector cells did not form any tumor. Since SATB2 is highly expressed in human pancreatic cancer tissues and cell lines, but not in HPNE cells and normal pancreatic tissue, it can drive pancreatic cancer growth and metastasis. Our findings suggest that SATB2 can induce dedifferentiation by inducing stemness and may have a role in pancreatic carcinogenesis, and can be used as a diagnostic biomarker.


Comparison of the genome-wide DNA methylation profiles between fast-growing and slow-growing broilers.
Growth traits are important in poultry production, however, little is known for its regulatory mechanism at epigenetic level. Therefore, in this study, we aim to compare DNA methylation profiles between fast- and slow-growing broilers in order to identify candidate genes for chicken growth. Methylated DNA immunoprecipitation-sequencing (MeDIP-seq) was used to investigate the genome-wide DNA methylation pattern in high and low tails of Recessive White Rock (WRR(h); WRR(l)) and that of Xinhua Chickens (XH(h); XH(l)) at 7 weeks of age. The results showed that the average methylation density was the lowest in CGIs followed by promoters. Within the gene body, the methylation density of introns was higher than that of UTRs and exons. Moreover, different methylation levels were observed in different repeat types with the highest in LINE/CR1. Methylated CGIs were prominently distributed in the intergenic regions and were enriched in the size ranging 200-300 bp. In total 13,294 methylated genes were found in four samples, including 4,085 differentially methylated genes of WRR(h) Vs. WRR(l), 5,599 of XH(h) Vs. XH(l), 4,204 of WRR(h) Vs. XH(h), as well as 7,301 of WRR(l) Vs. XH(l). Moreover, 132 differentially methylated genes related to growth and metabolism were observed in both inner contrasts (WRR(h) Vs. WRR(l) and XH(h) Vs. XH(l)), whereas 129 differentially methylated genes related to growth and metabolism were found in both across-breed contrasts (WRR(h) Vs. XH(h) and WRR(l) Vs. XH(l)). Further analysis showed that overall 75 genes exhibited altered DNA methylation in all four contrasts, which included some well-known growth factors of IGF1R, FGF12, FGF14, FGF18, FGFR2, and FGFR3. In addition, we validate the MeDIP-seq results by bisulfite sequencing in some regions. This study revealed the global DNA methylation pattern of chicken muscle, and identified candidate genes that potentially regulate muscle development at 7 weeks of age at methylation level.


Perturbations in polyamines and related enzymes following chlordecone-potentiated bromotrichloromethane hepatotoxicity.
The mechanism by which chlordecone (CD) amplifies the hepatotoxicity of halomethanes such as CCl4, CHCl3, and BrCCl3 has been a subject of intense study. Recent work has shown that suppression of hepatocellular regeneration leads to accelerated progression of liver injury leading to complete hepatic failure due to an unusual interaction between individually nontoxic low-dose combination of CD and CCl4. Since polyamines are involved in cell division, their levels reflect the extent to which there is suppression of hepatocellular regeneration during CD and CCl4 interaction. The present studies were designed to investigate the polyamine levels and associated enzymes in livers of rats treated with BrCCl3 alone or CD and BrCCl3 low-dose combination in order to confirm whether the sequence of events of hepatotoxicity is similar to that seen in CCl4 toxicity or that seen during CD and CCl4 interaction. The extent of liver toxicity in rats fed 10 ppm chlordecone (CD) for 15 days prior to the injection of a single low dose of BrCCl3 (15 microL/kg body weight) or after exposure to a high dose of BrCCl3 (80 microL/kg body weight) without CD pretreatment, was similar 6 and 24 hr later as assessed by plasma transaminase levels. There was also an increase in transaminase levels, in rats exposed to a single low dose of BrCCl3 alone (15 microL/kg body weight) but this increase was far below the high-dose exposure alone or the combination treatment. Hepatic levels of ornithine decarboxylase, S-adenosylmethionine decarboxylase, N1-acetylputrescine, N1-acetylspermidine, putrescine, spermidine, and spermine at the end of 24 hr increased after exposure to a low dose of BrCCl3 alone as compared to exposure to a high dose alone or the low-dose combination of CD and BrCCl3. Liver spermidine N1-acetyltransferase was elevated at 2, 6, and 24 hr after exposure to a high dose of BrCCl3 alone as compared to treatment with a low-dose combination of CD and BrCCl3 suggesting decreased synthesis of this enzyme, in spite of a greater need as seen from liver transaminase levels. In general, it was observed that there is significant elevation in some polyamines and related enzymes during toxicity of a low dose of BrCCl3 which seemed to stabilize within 24 hr. This was not observed with the other two groups of rats exposed either to BrCCl3 high dose alone or the low-dose combination of CD and BrCCl3.(ABSTRACT TRUNCATED AT 400 WORDS)


Amygdala-prefrontal disconnection in borderline personality disorder.
Abnormal fronto-amygdala circuitry has been implicated in impulsive aggression, a core symptom of borderline personality disorder (BPD). We examined relative glucose metabolic rate (rGMR) at rest and after m-CPP (meta-chloropiperazine) with (18)fluorodeoxyglucose (FDG) with positron emission tomography (PET) in 26 impulsive aggressive (IED)-BPD patients and 24 controls. Brain edges/amygdala were visually traced on MRI scans co-registered to PET scans; rGMR was obtained for ventral and dorsal regions of the amygdala and Brodmann areas within the prefrontal cortex (PFC). Correlation coefficients were calculated between rGMR for dorsal/ventral amygdala regions and PFC. Additionally, amygdala volumes and rGMR were examined in BPD and controls. Correlations PFC/amygdala Placebo: Controls showed significant positive correlations between right orbitofrontal (OFC) and ventral, but not dorsal, amygdala. Patients showed only weak correlations between amygdala and the anterior PFC, with no distinction between dorsal and ventral amygdala. Correlations PFC/amygdala: m-CPP response: Controls showed positive correlations between OFC and amygdala regions, whereas patients showed positive correlations between dorsolateral PFC and amygdala. Group differences between interregional correlational matrices were highly significant. Amygdala volume/metabolism: No group differences were found for amygdala volume, or metabolism in the placebo condition or in response to meta-chloropiperazine (m-CPP). We demonstrated a tight coupling of metabolic activity between right OFC and ventral amygdala in healthy subjects with dorsoventral differences in amygdala circuitry, not present in IED-BPD. We demonstrated no significant differences in amygdala volumes or metabolism between BPD patients and controls.


Prediction of metastable phase of the Sc-N system in the N-rich region under high pressure.
The prediction of the high-pressure structure of the ScNx system enriches the phase diagram of the Sc-N system: three metastable phase structures (P1̄-ScN8, P1-ScN9 and P1-ScN11) are proposed in the N-rich region. These structures have novel polymeric nitrogen structures, and enrich the structural types of polymeric nitrogen under pressure. Interestingly, the P1-ScN11 phase can be quenched to ambient conditions, and release energy at a relatively mild temperature of 800 K. The larger charge transfer plays an important role in the structural stability by inducing the Sc-N ionic bond interaction and N-N covalent bond interaction. The prominent energy properties of P1̄-ScN8, P1-ScN9 and P1-ScN11 make them potential candidates in the application of propellants and explosives.


ATP-sensitive potassium channels exhibit variance in the number of open channels below the limit predicted for identical and independent gating.
In small cells containing small numbers of ion channels, noise due to stochastic channel opening and closing can introduce a substantial level of variability into the cell's membrane potential. Negatively cooperative interactions that couple a channel's gating conformational change to the conformation of its neighbor(s) provide a potential mechanism for mitigating this variability, but such interactions have not previously been directly observed. Here we show that heterologously expressed ATP-sensitive potassium channels generate noise (i.e., variance in the number of open channels) below the level possible for identical and independent channels. Kinetic analysis with single-molecule resolution supports the interpretation that interchannel negative cooperativity (specifically, the presence of an open channel making a closed channel less likely to open) contributes to the decrease in noise. Functional coupling between channels may be important in modulating stochastic fluctuations in cellular signaling pathways.


Surface roughness of orthodontic wires via atomic force microscopy, laser specular reflectance, and profilometry.
The surface roughness of orthodontic archwires is an essential factor that determines the effectiveness of arch-guided tooth movement. Using the non-destructive techniques of atomic force microscopy (AFM) and of laser specular reflectance, the surface roughness of 11 nickel-titanium orthodontic wires, a stainless steel and a beta-titanium wire was measured. The results were compared with those obtained using surface profilometry. The smoothest wire, stainless steel, had an optical roughness of 0.10 micron, compared with 0.09 micron from AFM and 0.06 from profilometry. The surface roughness for the beta-titanium wire measured by all three methods was approximately 0.21 micron, while that of the NiTi wires ranged from 0.10 to 1.30 microns. As the surface roughness not only affects the effectiveness of sliding mechanics, but also the corrosion behaviour and the aesthetics of orthodontic components, the manufacturers of orthodontic wires should make an effort to improve the surface quality of their products.


Cued recall and the nature of the memory disorder in dementia.
The study investigated the retrieval deficit hypothesis of forgetting in senile dementia, using a cued recall technique. Memory for lists of words was tested with either no cues given at the time of recall, or alternatively by cueing the patient either with the word's first letter or its semantic category. Results do not support a retrieval deficit explanation of forgetting in dementia, but instead suggest the possibility of a processing deficit at the acquisition stage.


Nursing education: Key issues for the 21st century.
In this paper, I reflect on what can be learned by engaging in future thinking within our discipline, and what implications the results of that thinking may have for the development of nursing education. Recognizing the marvelous diversity of perspective within our discipline with regard to what will and ought to be our future mandate, it seems reasonable to search for some grounding in what might ensure that we enter that future wisely. We all know that change is a fundamental characteristic of all future projections, and yet that insight seems a weak justification for failure to plan. Nurse educators hold a particular obligation to ensure that they are preparing the professionals who will take that future forward. Although we have always recognized that they must nurse for today with an eye on tomorrow, it is inordinately difficult to come to some agreement on how we can best bridge that gap within our educational programs and strategies. Toward this end, I draw on lessons that can be drawn from our professional history as a rich and vibrant context to propose some key issues for that future theorizing.


The task of a statistical referee.
The results are presented of an audit of the statistical standard of papers published in The British Journal of Surgery. A number of deficiencies are highlighted, many of which stem from an over-emphasis on statistical significance at the expense of any assessment of the clinical relevance of research findings. The flaws in the design of published studies, and in particular the many instances of inadequate sample sizes, emphasize that statistical input should be sought at the beginning of a research project rather than at the end.


Failure of chronic exposure to nonthermal FM radio waves to mutate Drosophila.
A stock of Drosophila sc VI - YS/y ac oc ptg - YL/y ac oc ptg - YL/y sc S1 B In49 ct ns v sc8 that accumulated the recessive lethals on the X chromosome was exposed to a frequency of 98.5 MHz (wave length 3.35 m) and a field strength of 0.3 V/m. The flies were kept near the base of the 300-ft antenna of a 50,000 watt transmitter for 32 weeks. There was no significant difference in the percentage of lethals between the stock exposed to 4,020 hours of nonthermal FM radio waves and the controls.


miRNA-based therapies: strategies and delivery platforms for oligonucleotide and non-oligonucleotide agents.
The discovery of miRNAs as important regulatory agents for gene expression has expanded the therapeutic opportunities for oligonucleotides. In contrast to siRNA, miRNA-targeted therapy is able to influence not only a single gene, but entire cellular pathways or processes. It is possible to supplement downregulated or non-functional miRNAs by synthetic oligonucleotides, as well as alleviating effects caused by overexpression of malignant miRNAs through artificial antagonists, either oligonucleotides or small molecules. Chemical oligonucleotide modifications together with an efficient delivery system seem to be mandatory for successful therapeutic application. While miRNA-based therapy benefits from the decades of research spent on other therapeutic oligonucleotides, there are some specific challenges associated with miRNA therapy, mainly caused by the short target sequence. The current status and recent progress of miRNA-targeted therapeutics is described and future challenges and potential applications in treatment of cancer and viral infections are discussed.


Preventive effects of Laminaria japonica aqueous extract on the oxidative stress and xanthine oxidase activity in streptozotocin-induced diabetic rat liver.
Increasing evidence in both experimental and clinical studies suggests that oxidative stress plays a major role in the pathogenesis of diabetes mellitus type 1 and type 2. Xanthine oxidase (XO) has been proposed as one of the sources of free radical formation in diabetes. We therefore investigated the preventive effects of Laminaria japonica aqueous extract (LJE) on alterations in the activity of hepatic XO and oxidative stress in the streptozotocin-induced experimental diabetes. We found that lipid peroxide levels and xanthine oxidase activity were increased, whereas glutathione (GSH), GSH reductase and GSH peroxidase were decreased in the liver of streptozotocin-induced diabetic rats. Pretreatment with LJE of 100 mg/kg orally for 5 d significantly reduced blood glucose levels and hepatic lipid peroxidation in the diabetic rats. In addition, the content of glutathione was restored to the control level by LJE pretreatment. Furthermore, LJE significantly suppressed the increased activity of XO and type conversion of the xanthine dehydrogenase to XO in diabetic rat liver. The results suggest that Laminaria japonica would be of great value in preventing hyperglycemia in diabetes mellitus as a dietary supplement possibly, through its antioxidant activity.


Bleomycin-induced pulmonary fibrosis. Effects of steroid on lung collagen metabolism.
Using bleomycin-induced pulmonary fibrosis as a model, we have set out to study collagen metabolism in the fibrotic process. As was previously shown, intratracheal administration of bleomycin in the rat caused increased deposition and net synthesis of collagen in the lung. This was accompanied by marked increases in the tissue-free proline pool size and less dramatic increases in the pool's radioactivity when lung mince was pulsed with radioactive proline to measure the net collagen synthesis. Using a technique based on the quantitation of the rate of release of hydroxyproline-containing peptides when lung homogenates were incubated in calcium-containing buffer, lung collagenolytic activity was markedly diminished as a result of bleomycin treatment. Concomitant treatment with the steroid methylprednisolone did not affect significantly this decrease in lung collagenolytic activity. Such steroid treatment, however, prevented the increase in bleomycin-induced lung collagen deposition and partially suppressed total lung collagen synthesis, without affecting the net rate of lung collagen synthesis expressed per mg of DNA. Steroid treatment also inhibited the marked increase in tissue-free proline pool size and radioactivity caused by bleomycin. The mechanism of amelioration of the fibrotic response by the steroid is discussed.


Technical note. A design study of a bioelectric amplifier and improvement of its parameters.
A design study of a bioelectric amplifier that has better parameters than conventional designs is presented. The design allows the construction of bioelectric amplifiers with improved parameters in terms of noise, common mode rejection ratio, and input impedance. The voltage gain and bandwidth are easily adapted to a wide range of biomedical applications. The experimental results of the designed bioelectric amplifier are also included.


[Distribution characteristics and chemical pattern of cadmium in grasses planted in the cadmium contaminated soil].
In this paper, the distribution and chemical pattern of Cd in the grasses planted in Cd contaminated soil in western suburb of Shenyang were analyzed. The results showed that Cd was mainly distributed in the grass roots, and characteristics of Cd distribution in various grasses were different. Some grasses had resisting ability against Cd, some had strong capability of bio-accumulation for Cd. Results of different grasses extracted by different solvents showed that acid-soluble Cd in grasses was about 63.3% of total, and water-soluble and organic Cd were little, accounting for 0.7% and 0.4% of total respectively. Acid-soluble Cd was more active than the others during the transformation in the soil-plant system, while water-soluble Cd had certain regularity with the change of time and temperature, and organic Cd became more active with the increase of solvent polarity.


Research on classification method of high myopic maculopathy based on retinal fundus images and optimized ALFA-Mix active learning algorithm.
To conduct a classification study of high myopic maculopathy (HMM) using limited datasets, including tessellated fundus, diffuse chorioretinal atrophy, patchy chorioretinal atrophy, and macular atrophy, and minimize annotation costs, and to optimize the ALFA-Mix active learning algorithm and apply it to HMM classification. The optimized ALFA-Mix algorithm (ALFA-Mix+) was compared with five algorithms, including ALFA-Mix. Four models, including ResNet18, were established. Each algorithm was combined with four models for experiments on the HMM dataset. Each experiment consisted of 20 active learning rounds, with 100 images selected per round. The algorithm was evaluated by comparing the number of rounds in which ALFA-Mix+ outperformed other algorithms. Finally, this study employed six models, including EfficientFormer, to classify HMM. The best-performing model among these models was selected as the baseline model and combined with the ALFA-Mix+ algorithm to achieve satisfactory classification results with a small dataset. ALFA-Mix+ outperforms other algorithms with an average superiority of 16.6, 14.75, 16.8, and 16.7 rounds in terms of accuracy, sensitivity, specificity, and Kappa value, respectively. This study conducted experiments on classifying HMM using several advanced deep learning models with a complete training set of 4252 images. The EfficientFormer achieved the best results with an accuracy, sensitivity, specificity, and Kappa value of 0.8821, 0.8334, 0.9693, and 0.8339, respectively. Therefore, by combining ALFA-Mix+ with EfficientFormer, this study achieved results with an accuracy, sensitivity, specificity, and Kappa value of 0.8964, 0.8643, 0.9721, and 0.8537, respectively. The ALFA-Mix+ algorithm reduces the required samples without compromising accuracy. Compared to other algorithms, ALFA-Mix+ outperforms in more rounds of experiments. It effectively selects valuable samples compared to other algorithms. In HMM classification, combining ALFA-Mix+ with EfficientFormer enhances model performance, further demonstrating the effectiveness of ALFA-Mix+.


Meiotic behaviour of a new complex X-Y-autosome translocation and amplified heterochromatin in Jumnos ruckeri (Saunders) (Coleoptera, Scarabaeidae, Cetoniinae).
Species belonging to the Cetoniinae subfamily studied so far possess 20 chromosomes, including a small X and a punctiform Y: 20,Xyp in the males. In a series of species from the Goliathini tribe under study we found a very unusual karyotype, with 12 autosomes and large sex chromosomes (14,neoXY) in Jumnos ruckieri from Thailand. Applying various techniques including pachytene bivalent spreading, we showed that 40% (mitotic and meiotic prophases) to 60% (metaphases) of the karyotype length was composed of heterochromatin. Both sex chromosomes were NOR carriers. At pachynema they underwent a complete synapsis of their distal regions, indicating their autosomal origin. At contrast, their very uneven central regions remained separated, but associated with nucleolus material. This association persisted until diakinesis, forming a pseudo-chiasma between the neoX and the neoY, which were always in end-to-end association. Compared to free autosomes the autosomal parts of the neo-sex chromosomes had a significant lack of interstitial chiasmata, indicating a possible lack of recombination at their proximal regions. As in the cases of X-autosome translocations in mammals, autosomal and gonosomal parts of the neo-sex chromosomes were insulated by heterochromatin, which may be a necessary condition to avoid deleterious position effects, whatever the mechanisms of gene dosage compensation.


[The diagnosis and treatment of cholangiolithiasis after cholecystectomy].
Results of complex examination and treatment of 138 patients with postcholecystectomic cholangiolithiasis were analyzed. Residual cholangiolithiasis was diagnosed in 104 (75.4%), recurrent--in 34 (24.6%) patients. Differential-diagnostic symptoms of residual and recurrent cholangiolithiasis are specifiEd. Diagnostic and curative algorithm was developed, criteria of choice of curative (instrumental or surgical) methods were clarified. Mini-invasive surgeries (endoscopic papillosphincterotomy, suprapapillar choledochoduodenostomy, dissection of stenosed choledochoduodenoanastomosis, percutaneous transhepatic cholangiostomy, lithoextraction through external bile fistual, mechanical and laser lithotripsy, nasobiliar drainage) from different diapeutic approaches were performed in 137 (99.3%) patients. Diapeutic instrumental procedures were effective and final in 91.9% cases (in residual cholangiolithiasis--94.2%, in recurrent--82.4% cases). Lethality was 0.7%.


Resection of hepatic metastases from colorectal cancer.
We studied 141 patients who had resection of hepatic metastases from colorectal cancer, considering all such lesions removed between 1948 and 1982. The study involved extended observations of patients described previously. Also included were 21 patients who had wedge resections of small metastases done since 1976, who, therefore, did not qualify for analysis of major hepatic resections reported recently (1980 and 1983). The overall five-year survival rate was 25%, significantly higher than that of a group of historical controls who had resectable metastases that were not removed. The size and nature of our extended sample allowed identification of some determinants of favorable prognosis: Dukes' stage of the primary lesion, absence of extrahepatic metastases, and being female. Contrary to our earlier observations, this study justified removal of some multiple hepatic metastases.


Circulating Spexin Decreased and Negatively Correlated with Systemic Insulin Sensitivity and Pancreatic β Cell Function in Obese Children.
Spexin (SPX) is a novel peptide that has recently emerged as an important regulatory adipokine of obesity and related metabolic disease. Little is known about its role in children. The aim of the current study was to determine the potential role of SPX in obese children and explore its relationships with obesity-related markers, insulin sensitivity and pancreatic β cell function. We studied the levels of serum SPX in 40 obese and 32 normal weight pre-puberty children (mean age was 8.59 ± 1.82 and 8.15 ± 2.03 years in obesity and control groups respectively). We investigated the levels of body mass index, blood pressure, lipids, glucose, insulin, Homeostasis model assessment for insulin-resistant (HOMA-IR, HOMA for β-cell function [HOMA-β]), insulinogenic index and C-peptide index and analyzed their correlations with SPX levels. SPX levels were significantly decreased in obese children compared to controls. Moreover, serum SPX levels were lower in IR obese subjects in contrast with the non-IR obese subjects. Serum SPX concentrations correlated negatively and significantly with triglycerides, systolic blood pressure, diastolic blood pressure, fasting insulin level, HOMA-IR, insulinogenic index, and HOMA-β levels in obese children. In summary, serum SPX levels significantly decreased in obese children and negatively correlated with insulin resistance and pancreatic β cell function indicators. Therefore, SPX may play a protective role in the process of glucose homeostasis and is closely related to β cell function in obese children.


Changes in arterial distensibility produced by converting enzyme inhibitors in hypertensive humans.
Converting enzyme inhibitors enhance arterial compliance in hypertensive humans. The enhancement is due not only to an increase in arterial diameter and volume but also to an increase in arterial distensibility. The latter effect reflects the drug action on arterial smooth muscle tone rather than the lower stretch due to the blood pressure reduction. The improvement in the buffering function of large arteries in hypertensives may contribute to produce a more important decrease in systolic pressure and a better reversion of cardiac hypertrophy.


Gender-specific expression of ATP-binding cassette (Abc) transporters and cytoprotective genes in mouse choroid plexus.
The choroid plexus (CP) and blood-brain barrier (BBB) control the movement of several drugs and endogenous compounds between the brain and systemic circulation. The multidrug resistance associated protein (Mrp) efflux transporters form part of these barriers. Several Mrp transporters are positively regulated by the transcription factor nuclear factor erythroid-2-related factor (Nrf2) in liver. The Mrps, Nrf2 and Nrf2-dependent genes are cytoprotective and our aim was to examine basal gender differences in expression of Mrp transporters, Nrf2 and Nrf2-dependent genes (Nqo1 and Ho-1) in the brain-barriers. Previous studies have shown higher expression of Mrp1, Mrp2 and Mrp4 in female mouse liver and kidney. We hypothesized that similar renal/hepatic gender-specific patterns are present in the brain-barrier epithelia interfaces. qPCR and immunoblot analyses showed that Mrp4, Ho-1 and Nqo1 expression was higher in female CP. Mrp1, Mrp2 and Nrf2 expression in the CP had no gender pattern. Female Mrp1, Mrp2 and Mrp4 mouse brain expressions in remaining brain areas, excluding CP, were higher than male. Functional analysis of Mrp4 in CP revealed active accumulation of the Mrp4 model substrate fluo-cAMP. WT female CP had 10-fold higher accumulation in the vascular spaces than males and 60% higher than Mrp4-/- females. Probenecid blocked all transport. Methotrexate did as well except in Mrp4-/- females where it had no effect, suggesting compensatory induction of transport occurred in Mrp4-/-. Collectively, our findings indicate significant gender differences in expression of Mrp transporters and cytoprotective genes in the CP and BBB.


[A family with dominant-phenotype Beta-thalassemia].
We report a 43-year-old Japanese woman with microcytic and hypochromic anemia, who had been erroneously diagnosed as having iron deficiency anemia 20 years previously at the time of her first labor, and treated with iron and blood transfusion. At the present visit to our clinic, she was found to have an increased HbA2 level and prolonged glycerol lysis time. Genetic analysis of the beta-globin gene revealed deletion of 3 bases at codons 127/128 (CAG/GCT-->CCT). A genetic study of the patient's family showed that two of her four children possessed the same mutation. The patient had mild anemia, her first son had very mild anemia, and her second daughter had moderate anemia with hemolysis. These affected family members were diagnosed as having dominant-phenotype beta-thalassemia.


[Patients with variations of sex development : an example of interdisciplinary care].
The medical, psychological and social aspects of disorders of sex development (DSD) represent a challenge for the management of these patients. However, advances in our understanding of the etiology and genetics of this condition, novel surgical approaches and the growing influence of patient groups as well as wider recognition of ethical issues have helped improve the care of patients with a DSD. Importantly, a multidisciplinary approach involving specialists is crucial for understanding and treating such rare and complex cases. According to the recommendations of the Swiss National Ethical Commission, we shall use the term « Variation of Sex Development » rather than « Disorder of Sex Development » in this publication. This article addresses the care of DSD patients throughout development from the point of view of specialists in complementary fields.


Hypertrophy at ECG and its regression during treatment survey (HEART survey). Rationale, design and baseline characteristics of patients.
Left ventricular hypertrophy (LVH) detected at electrocardiography (ECG) is a predictor of an increased cardiovascular risk in essential hypertension. However, uncertainty remains concerning the reproducibility of ECG LVH and the prognostic relevance of its regression over time in hypertension. The aim of this study was to determine the prognostic value of baseline ECG LVH and its serial changes in a large cohort of hypertensive patients. The Hypertrophy at ECG and its Regression during Treatment Survey (HEART Survey) is a prospective observational study conducted in 66 Italian centers. Inclusion criteria are essential hypertension with ECG LVH defined by the Perugia score (Cornell voltage criteria and/or a typical left ventricular "strain" pattern and/or a Romhilt-Estes score > or = 5 points) in subjects aged 45-84 years. The treatment of hypertension and other risk factors accords with current guidelines and is individually tailored. ECG is recorded twice at entry and periodically repeated over a 4-year follow-up period. Expert readers (unaware of the clinical findings) classify ECG. The incidence of major cardiovascular events in relation to baseline ECG and its changes over time are assessed, together with the reproducibility in the two baseline recordings. Overall, 708 patients aged 64 +/- 9 years have been enrolled in centers from northern (27%), central (32%) and southern (41%) Italy. Their baseline characteristics are presented. Follow-up is ongoing. The HEART Survey will examine the prognostic value of baseline ECG LVH and of its regression over time in a wide population of hypertensive patients.


Noninvasive detection of acute renal allograft rejection by measurement of soluble Tim-3 in urine.
The purpose of the present study was to assess whether urinary soluble T-cell immunoglobulin and mucin domain-containing protein 3 (sTim-3) could be adopted as a novel non‑invasive biomarker for acute rejection (AR) following renal transplantation. A total of 156 patients were enrolled between January 2006 and December 2009, comprising 49 patients with biopsy‑proven AR, 58 patients with stable grafts and no abnormal histological findings (NO‑AR), 10 patients with subclinical rejection (SCR) in protocol biopsies, 10 patients with acute tubular necrosis (ATN) and 29 patients with chronic allograft nephropathy (CAN). Additionally, urine samples from 40 healthy individuals were also collected as controls. The urinary concentration of sTim‑3 was determined by ELISA in the 156 renal allograft recipients and 40 healthy controls. Compared with NO‑AR and healthy controls, patients with AR excreted urinary sTim‑3 at a significantly higher level (4,356±440.4, 95% CI: 3,473‑5,242 ng/mmol creatinine). Likewise, patients with ATN exhibited a significantly lower level of urinary sTim‑3 (2,060±217, 95% CI: 1,679‑2,680 ng/mmol creatinine) than patients with AR. The discriminatory value was measured by the area under the receiver operating characteristic curve (ROC), which had a value of 0.88 (95% CI: 0.809‑0.951), demonstrating that sTim‑3 was a suitable marker for the diagnosis of AR. At a cut-off point of 1,836 ng/mmol creatinine, the sensitivity was 89.8% and the specificity was 82.8% (P<0.001). Amongst the patients with AR, patients with steroid‑resistant acute rejection (n=31) had significantly higher urinary sTim‑3 concentrations than patients with steroid‑sensitive acute rejection (n=18; 5,548±613.5, 95%CI: 4,287‑6,809 ng/mmol creatinine vs. 2,653±391.7, 95% CI: 1,830‑3,476 ng/mmol creatinine; P=0.0002). No significant difference in urinary sTim‑3 was found between patients with AR and CAN (3,920±543.5, 95% CI: 3,473‑5,242 ng/mmol creatinine), and a significantly higher level of Tim‑3 was excreted by patients with CAN compared with patients with NO‑AR and healthy controls (P<0.001). The present study, therefore, suggests that urinary sTim‑3 may be used as a valuable non‑invasive biomarker for the detection of AR. In addition, urinary sTim‑3 levels were demonstrated to be associated with the response to anti‑rejection therapy. The results of the present study may provide support future research into the screening of novel immune suppressants.


Concentration, Source, and Total Health Risks of Cadmium in Multiple Media in Densely Populated Areas, China.
Cadmium (Cd) is a non-essential and harmful element to humans. Cadmium contamination is a serious issue for human health, especially in densely populated agroecology areas. In this study, the investigation of an agroecology area was conducted to gain insight into the relationship between Cd in wheat and soil and then evaluate the Cd total risk for human health. The soil samples and their matching wheat samples, underground water samples, and atmospheric deposition (air) samples were collected from a wheat-growing area in an agroecology plain. The cadmium concentration in the four types of media, in order, was air > soil > wheat > water. The mean concentration of the geoaccumulation index (Igeo) showed that the total Cd in soil (Cd-T) and Cdair reached a mild and moderate pollution level. The results of the correlation and principal component analysis (PCA) showed that the majority of Cdwheat originated from Cd-2 (exchangeable), Cd-4 (humic acid-bound), and Cd-7 (residual). Furthermore, the results of the stepwise multiple linear regression (SMLR) showed that three fractions were primarily controlled by Cd-T: clay, cation exchange capacity (CeC), and total organic carbon (TOC). In addition, the total cancer risk (CR) of Cd in multiple media was, in the order wheat > water > soil > air. It is noteworthy that the Cd content in underground water and wheat by the ingestion pathway posed cancer risks to the local residents and provided a comprehensive insight into multiple media environment management. Furthermore, it provides a very significant basic study for detailed research into the mobility and transformation for factions.


A new gaseous cavitation model in a tilting-pad journal bearing.
With the higher rotational speeds and loads in bearings, the gaseous cavitation becomes more and cannot be ignorable in the bearing designs. However, there is no enough research in non-equilibrium gaseous cavitation model. This paper builds a new gaseous cavitation model based on the Bunsen solubility and bubble dynamics. The equilibrium pressure is calculated by the Bunsen solubility based on the local pressure and its pressure difference with the local pressure decides the cavitation mass transfer rate in this new model for gaseous cavitation. A titling-pad journal bearing at 3000 rpm and under 299 kN load is chosen as the research object with this new model and an original equilibrium model applied. As for the minimum film thickness and bearing force balance, this new model performs in better accordance with the experiment than the equilibrium model. According to the multiphase distributions in the bearing film, the gaseous cavitation rate in this new model can simulate the non-equilibrium processes of dissolution and cavitation under the high rotational speed, which is close to the physical gaseous cavitation process. This new model is developed and applied successfully in tilting-pad journal bearings for simulating the non-equilibrium gaseous cavitation.


A method for induced-fit docking, scoring, and ranking of flexible ligands. Application to peptidic and pseudopeptidic beta-secretase (BACE 1) inhibitors.
Inhibition of beta-secretase (BACE 1) has recently been investigated as a promising therapeutic approach in the treatment of Alzheimer's disease, and a growing number of BACE 1 inhibitors and crystal structures of BACE 1/inhibitors complexes have been reported. We report herein a predictive computational method and its application to potential BACE 1 inhibitors. Using a training set of 50 known highly flexible inhibitors, we developed a docking method that accounts for the flexibility of both the protein and the inhibitors. Protein flexibility is accounted for using a specifically designed genetic algorithm. We next developed a scoring function consisting of force field evaluation of the inhibitor/protein interactions and two additional terms for hydrogen bonding and entropy change upon binding. Discarding three outliers from the training set, our protocol was found to perform well with an rmsd of 1.19 kcal/mol. Evaluation of the predictive power was next carried out by virtual screening of 80 synthetic compounds. The significant enrichment at the top of the ranking list in active compounds demonstrated the ability of the docking and scoring protocol to rank the compounds relative to their activities.


OPAL: Occlusion Pattern Aware Loss for Unsupervised Light Field Disparity Estimation.
Light field disparity estimation is an essential task in computer vision. Currently, supervised learning-based methods have achieved better performance than both unsupervised and optimization-based methods. However, the generalization capacity of supervised methods on real-world data, where no ground truth is available for training, remains limited. In this paper, we argue that unsupervised methods can achieve not only much stronger generalization capacity on real-world data but also more accurate disparity estimation results on synthetic datasets. To fulfill this goal, we present the Occlusion Pattern Aware Loss, named OPAL, which successfully extracts and encodes general occlusion patterns inherent in the light field for calculating the disparity loss. OPAL enables: i) accurate and robust disparity estimation by teaching the network how to handle occlusions effectively and ii) significantly reduced network parameters required for accurate and efficient estimation. We further propose an EPI transformer and a gradient-based refinement module for achieving more accurate and pixel-aligned disparity estimation results. Extensive experiments demonstrate our method not only significantly improves the accuracy compared with SOTA unsupervised methods, but also possesses stronger generalization capacity on real-world data compared with SOTA supervised methods. Last but not least, the network training and inference efficiency are much higher than existing learning-based methods. Our code will be made publicly available.


[Rofecoxib-related cutaneous vasculitis].
Drugs are at the origin of around 10% of the cases of vasculitis involving the small vessels. Recent cases report vasculitis related to the administration of nonsteroidal antiinflammatory selective inhibitors of cyclo-oxygenase 2. Vasculitis associated with ketoprofen appeared in a 76 year-old man: the symptoms disappeared when treatment stopped. A few weeks later, during treatment with rofecoxib, a relapse appeared, including purpura. The diagnosis of rofecoxib-induced cutaneous vasculitis was confirmed by regression of all symptoms when treatment stopped. Coxibs, like other nonsteroidal antiinflammatory drugs, may cause vasculitis, at an as-yet undetermined frequency.


Oral nicotinamide protects against ultraviolet radiation-induced immunosuppression in humans.
Cutaneous immunity, which is a key defence against the development of skin cancers, is suppressed by even small doses of ultraviolet (UV) radiation. Preventing this UV-induced immunosuppression may therefore reduce the incidence of skin cancer. Nicotinamide (vitamin B3) has immune-protective and cancer-preventive effects against UV radiation in mice, and we have shown previously that topical nicotinamide is immune protective in humans. Using the Mantoux model of skin immunity in healthy volunteers, we compared oral nicotinamide to placebo (both administered for 1 week) in a randomized, double-blinded, crossover design against the effects of solar-simulated ultraviolet (ssUV) radiation on delayed-type hypersensitivity to tuberculin purified protein derivative. Discrete areas of the back were irradiated with low doses of ssUV daily for three consecutive days. Immunosuppression, calculated as the difference in Mantoux-induced erythema of irradiated sites compared with unirradiated control sites, was determined in volunteers taking oral nicotinamide and placebo. Significant immunosuppression occurred in an UV dose-dependent manner in the presence of placebo. Oral nicotinamide, at doses of either 1500 or 500 mg daily, was well tolerated and significantly reduced UV immunosuppression with no immune effects in unirradiated skin. Oral nicotinamide is safe and inexpensive and looks promising as a chemopreventive supplement for reducing the immunosuppressive effects of sunlight.


Model-based evaluation of a new upgrading concept for N-removal.
Mathematical modelling is considered a time and cost-saving tool for evaluation of new wastewater treatment concepts. Modelling can help to bridge the gap between lab and full-scale application. Bio-augmentation can be used to obtain nitrification in activated sludge systems with a limited aerobic sludge retention time. In the present study the potential for augmenting the endogenous nitrifying population is evaluated. Implementing a nitrification reactor in the sludge return line fed with sludge liquor with a high ammonia concentration leads to augmentation of the native nitrifying population. Since the behaviour of nitrifiers is relatively well known, a choice was made to evaluate this new concept mainly based on mathematical modelling. As an example an existing treatment plant (WWTP Walcheren, The Netherlands) that needed to be upgraded was used. A mathematical model, based on the TUDP model and implemented in AQUASIM was developed and used to evaluate the potential of this bioaugmentation in the return sludge line. A comparison was made between bio-augmentation and extending the existing aeration basins and anoxic tanks. The results of both modified systems were compared to give a quantitative basis for evaluation of benefits gained from such a system. If the plant is upgraded by conventional extension it needs an increase in volume of about 225%; using a bioaugmentation in the return sludge line the total volume of the tanks needs to be expanded by only 75% (including the side stream tanks). Based on the modelling results a decision was made to implement the bioaugmentation concept at full scale without further pilot scale testing, thereby strongly decreasing the scale-up period for this process.


Live Cell Therapy as Potential Risk Factor for Q Fever.
During an outbreak of Q fever in Germany, we identified an infected sheep flock from which animals were routinely used as a source for life cell therapy (LCT), the injection of fetal cells or cell extracts from sheep into humans. Q fever developed in 7 LCT recipients from Canada, Germany, and the United States.


CT-measured pulmonary artery diameter as an independent predictor of pulmonary hypertension in cystic fibrosis.
The role of computed tomography (CT) scan, as a promising prognostic imaging modality in cystic fibrosis (CF), has been widely investigated, focusing on parenchymal abnormalities. The aim of the present study was to evaluate the diagnostic performance of thoracic vascular parameters on CT to detect pulmonary hypertension (PH). CF patients who contemporaneously underwent CT and echocardiography were retrospectively enrolled. Baseline characteristics in addition to pulmonary artery diameter (PAD) and pulmonary to aortic (PA/A) ratio were compared between cohorts with and without PH, based on the results of echocardiography separately in paediatric patients (< 18) and adults (≥ 18). Of a total 119 CF patients, 39 (32.8%) had PH (paediatric: 23/78, 29.5%, adult: 16/41, 39%). In paediatric CF patients, mean age, HCo3, PCo2, and pulmonary artery diameter (PAD) were significantly higher in the PH group compared to the non-PH group. Mean pulmo however, only PAD remained as the independent predictor of PH based on multivariate analysis (overall: 22.86 mm [±3.86] vs. 18.43 mm [±4.72], p = 0.005, paediatric patients: 22.63 mm [±4.4] vs. 17.10 mm [±4.64], p = 0.03). Using a cut off of 19.25 mm, the diagnostic performance of PAD to detect PH was found to be as follows: sensitivity = 82%, specificity = 70%, and accuracy = 73.1%. No significant difference was demonstrated in PAD between PH and non-PH groups in adults with CF (23.19 [±3.60] vs. 21.34 [±3.49], p = 0.7). In CF patients, PAD revealed an age-dependent performance to detect PH. PAD can be applied to predict pulmonary hypertension in paediatric CF patients and may be recommended to be routinely measured on follow-up chest CT scan in childhood CF.


Primary care gap: factors associated with persistent lack of primary care after hospitalisation.
Access to primary care in the USA is associated with decreased acute care utilisation and better health outcomes, yet millions of Americans lack a primary care provider (PCP). In our study, we report the risk factors for having no assigned PCP for hospitalised patients both at the time of discharge and over the course of the following year. We conducted a retrospective cohort study of 12 663 adult patients discharged from the medicine service at our academic inpatient hospital from 2017 to 2018. We compared the characteristics of patients with and without a PCP listed in the electronic health record at time of discharge. In a second analysis, for those patients without a PCP, we used subsequent encounters with our health system to compare characteristics of those who had a PCP assigned within 1 year after discharge with those who did not. At time of discharge, patients without a PCP were more likely to be younger, male, non-Asian and non-Black, to have Medicaid insurance or to be self-pay, to be experiencing homelessness and to have a substance use disorder diagnosis. During the year after discharge, the most significant risk factors for persistently lacking a PCP were non-private insurance status (Medicaid, Medicare, self-pay), experiencing homelessness and having a substance use disorder diagnosis. Our study demonstrates important risk factors for persistently lacking an assigned PCP in our urban patient population, including health insurance status, homelessness and substance use disorders. Targeted interventions are indicated to connect these high-risk individuals to primary care.


Oxidative stress induced by HIV-1 reverse transcriptase modulates the enzyme's performance in gene immunization.
HIV-1 infection induces chronic oxidative stress. The resultant neurotoxicity has been associated with Tat protein. Here, we for the first time describe the induction of oxidative stress by another HIV-1 protein, reverse transcriptase (RT). Expression of HIV-1 RT in human embryonic kidney cells generated potent production of the reactive oxygen species (ROS), detected by the fluorescence-based probes. Quantitative RT-PCR demonstrated that expression of RT in HEK293 cells induced a 10- to 15-fold increased transcription of the phase II detoxifying enzymes human quinone oxidoreductase (Nqo1) and heme oxygenase 1 (HO-1), indicating the induction of oxidative stress response. The capacity to induce oxidative stress and stress response appeared to be an intrinsic property of a vast variety of RTs: enzymatically active and inactivated, bearing mutations of drug resistance, following different routes of processing and presentation, expressed from viral or synthetic expression-optimized genes. The total ROS production induced by RT genes of the viral origin was found to be lower than that induced by the synthetic/expression-optimized or chimeric RT genes. However, the viral RT genes induced higher levels of ROS production and higher levels of HO-1 mRNA than the synthetic genes per unit of protein in the expressing cell. The capacity of RT genes to induce the oxidative stress and stress response was then correlated with their immunogenic performance. For this, RT genes were administered into BALB/c mice by intradermal injections followed by electroporation. Splenocytes of immunized mice were stimulated with the RT-derived and control antigens and antigen-specific proliferation was assessed by IFN-γ/IL-2 Fluorospot. RT variants generating high total ROS levels induced significantly stronger IFN-γ responses than the variants inducing lower total ROS, while high levels of ROS normalized per unit of protein in expressing cell were associated with a weak IFN-γ response. Poor gene immunogenicity was also associated with a high (per unit of protein) transcription of antioxidant response element (ARE) dependent phase II detoxifying enzyme genes, specifically HO-1. Thus, we have revealed a direct link between the propensity of the microbial proteins to induce oxidative stress and their immunogenicity.


Proteomics in myocardial diseases.
Recently, proteome analysis has been introduced to analyze differential protein expression and cellular protein composition in cardiovascular medicine. Proteins expressed by diseased hearts (myocardial proteomics) were first investigated over a decade ago using two-dimensional polyacrylamide gel electrophoresis (2D-PAGE). However, while 2D-PAGE is very successful for the abundant and moderately expressed proteins, it struggles to identify proteins expressed at low levels. However, the sensitivity of mass spectrometry has increased considerably during recent years, and technical progress widens the detection limits of mass-spectrometric analysis. Proteomics now allows us to examine global alterations in protein expression in the diseased hearts, and will provide new insights into the cellular mechanisms involved in cardiac dysfunction. This review will summarize the present knowledge about the use of proteome analysis in myocardial diseases.


Biotinylated-lipid bilayer coated mesoporous silica nanoparticles for improving the bioavailability and anti-leukaemia activity of Tanshinone IIA.
The oral bioavailability and anti-leukaemia activity of Tanshinone IIA (TanIIA) were enhanced by using biotinylated-lipid bilayer coated mesoporous silica nanoparticles (Bio-LB-MSNs) as a vehicle. The in vitro release of TanIIA from TanIIA@MSNs was significantly higher than that of the TanIIA powder (p < .05). The in vitro cellular uptake of TanIIA by Caco-2 was increased by loading drug into the Bio-LB-MSNs more than those of the compared nanovehicles without biotin modification. The apparent in situ permeability coefficient (Papp) of TanIIA@Bio-LB-MSNs showed nearly 2.5-, 1.6- and 1.3-fold improvement compared with the TanIIA powder, TanIIA@MSNs and TanIIA@LB-MSNs. Following oral administration of TanIIA@Bio-LB-MSNs in rats, the area under the plasma concentration-time curves (AUC) of TanIIA was 3.4-, 1.9- and 2.4-fold larger than those in the groups received a pure TanIIA powder, TanIIA@MSNs or TanIIA@LB-MSNs, indicating that drug bioavailability was enhanced by using MSNs as a vehicle, and further improved significantly through biotin modification. The in vitro anti-leukaemia activity of TanIIA was also enhanced after being loaded into nanoparticles and modification, with 50% inhibitive concentration (IC50) of NB4 cells at 6.5 μM for TanIIA@Bio-LB-MSN. In conclusion, Bio-LB-MSNs are a promising vehicle to improve the oral bioavailability and anti-leukaemia activity of the poorly water-soluble drug TanIIA.


Venous thromboembolism in patients hospitalised with COVID-19 in England.
The aim of this study was to detail the incidence of venous thromboembolism (VTE) in patients hospitalised with COVID-19 in England. This was an exploratory retrospective analysis of observational data from the Hospital Episode Statistics dataset for England. All patients aged ≥18 years in England with a diagnosis of COVID-19 who had a hospital stay that was completed between 1st March 2020 and 31st March 2021 were included. A recorded diagnosis of VTE during the index stay or during a subsequent admission in the six weeks following discharge was the primary outcome in the main analysis. In secondary analysis, VTE diagnosis was the primary exposure and in-hospital mortality the primary outcome. Over the 13 months, 374,244 unique patients had a diagnosis of COVID-19 during a hospital stay, of whom 17,346 (4.6%) had a recorded diagnosis of VTE. VTE was more commonly recorded in patients aged 40-79 years, males and in patients of Black ethnicity, even after adjusting for covariates. Recorded VTE diagnosis was associated with longer hospital stay and higher adjusted in-hospital mortality (odds ratio 1.35 (95% confidence interval 1.29 to 1.41)). VTE was a common complication of hospitalisation with COVID-19 in England. VTE was associated with both increased length of stay and mortality rate.


Semianalytic Monte Carlo radiative transfer model for oceanographic lidar systems.
A semianalytic Monte Carlo radiative transfer model (SALMON) has been developed which is particularly well-suited for addressing oceanographic lidar systems. SALMON is based on the method of expected values in which an analytical estimate is made of the probability of collection by a remote receiver of scattered or emitted photons at appropriate points in the stochastically constructed underwater photon trajectory. Sample results indicate that a substantial reduction in both variance and computer resources can be realized by using SALMON, as compared with more conventional Monte Carlo approaches, to study radiative transfer mechanisms associated with lidar systems.